1H-Pyrazole-3-carboxylic acid, 4-bromo-, methyl ester CAS#: 81190-89-8; ChemWhat Code: 1188593

IdentificationPhysical DataSpectra
Route of Synthesis (ROS)Safety and HazardsOther Data

Identification

Product Name1H-Pyrazole-3-carboxylic acid, 4-bromo-, methyl ester
IUPAC Namemethyl 4-bromo-1H-pyrazole-5-carboxylate
Molecular Structure1H-Pyrazole-3-carboxylic-acid-4-bromo-methyl-ester-CAS-81190-89-8
CAS Registry Number 81190-89-8
MDL NumberMFCD00466326
Synonymsmethyl 4-bromo-1H-pyrazole-3-carboxylate
81190-89-8
DTXSID50385177
DTXCID50336200
640-582-9
methyl 4-bromo-1H-pyrazole-5-carboxylate
190263-20-8
4-Bromo-1H-pyrazole-3-carboxylic acid methyl ester
1639902-31-0
methyl 4-bromopyrazole-3-carboxylate
MFCD00619124
1H-Pyrazole-3-carboxylic acid, 4-bromo-, methyl ester
MFCD00466326
4-bromopyrazole-3-carboxylic acid methyl ester
SCHEMBL13726965
SCHEMBL15519155
KWQDACZQHJCUNK-UHFFFAOYSA-N
ALBB-010454
BCP23475
BBL013079
methyl 4-bromopyrazole-5-carboxylate
SBB022111
STK315331
AKOS000310357
AKOS003744357
AB06264
CS-W019707
FS-2160
SY030486
DB-075744
ST45137494
EN300-138289
O11931
AH-034/11365123
SR-01000390601
SR-01000390601-1
1H-Pyrazole-3-carboxylic acid,4-bromo-,methyl ester
1H-PYRAZOLE-5-CARBOXYLIC ACID, 4-BROMO-, METHYL ESTER
Molecular FormulaC5H5BrN2O2
Molecular Weight205.01
InChIInChI=1S/C5H5BrN2O2/c1-10-5(9)4-3(6)2-7-8-4/h2H,1H3,(H,7,8)
InChI KeyKWQDACZQHJCUNK-UHFFFAOYSA-N 
SMILESCOC(=O)C1=C(C=NN1)Br
Patent Information
Patent IDTitlePublication Date
US2013/165464HETEROARYLS AND USES THEREOF2013

Physical Data

AppearanceWhite powder

Spectra

Description (NMR Spectroscopy)Nucleus (NMR Spectroscopy)Solvents (NMR Spectroscopy)
Chemical shifts, Spectrum13Cchloroform-d1

Route of Synthesis (ROS)

Route of Synthesis (ROS) of 1H-Pyrazole-3-carboxylic acid, 4-bromo-, methyl ester CAS 81190-89-8
Route of Synthesis (ROS) of 1H-Pyrazole-3-carboxylic acid, 4-bromo-, methyl ester CAS 81190-89-8
ConditionsYield
Stage #1: methyl 4-bromo-1H-pyrazole-3-carboxylate With sodium hydride In tetrahydrofuran at 0℃; for 0.166667h;
Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In tetrahydrofuran at 20℃;

Experimental Procedure
Intermediate 4A. Methyl 4-bromo-1-((2-(trimethylsiliyl)ethoxy)methyl)-1H-pyrazole-3carboxylate
To a suspension of methyl 4-brorno-1H-pyrazole-3-carboxylate (2.45 g, 11.9 rnmol) in THF (120 rnL) at () °C, was added 60% Nal-I (0.621 g, 15.5 mrnol) portionwise.The reaction was stirred at 0 °C for 10 mm, then 2-(trirnethylsilyi)ethoxymethyl chloride (254 mL, 14.34 mrnoi) was added dropwise. The suspension was warmed slowly to rt overnight. Then, it was cooled down to 0 °C, MeOH was added and the solvents were removed in vacuo. The residue was diluted with EtOAc and sat. Nal-ICOs. The aqqueous layer was extracted 2x with EtOAc. The organic layer was washed with brine, dried overMgSO4 and concentrated. Purification by flash chromatography (80 g column, 0-50% E:tOAc in Hexanes) afforded intermediate 4A as a colorless oil (3.17 g, 87%). ‘H NMR (400 MHz. CFILOROFORM-d) d 7.73 (s, IH), 5.48 (s, 2H), 3.97 (s, 3H), 3.63 – 3.56 (iii. 2H). 093 (t, .J=8.3 Hz, 2H). 000 (s. 9H). LCMS [M + H] = 337.0,
87%
Stage #1: methyl 4-bromo-1H-pyrazole-3-carboxylate With sodium hydride In tetrahydrofuran at 0℃; for 0.5h;
Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In tetrahydrofuran at 0℃; for 5h;

Experimental Procedure
To a solution of methyl 4-bromo-1H-pyrazole-3-carboxylate (10.0 g, 48.8 mmol) in THF (150.00 mL) was added NaH (2.341 g, 58.5 mmol) portion wise at 0 °C. The reaction mixture was stirred for 30 min, then SEM-Cl (10.38 mL, 58.5 mmol) was added. The reaction mixture was stirred at 0 °C for 5 h. The reaction was quenched with water (30 mL). The reaction mixture separated into two layers, and the aqueous layer was extracted with EtOAc (2 X 50 mL). The combined organic extracts were dried (Na2SO4) and concentrated to yield crude compound. The crude compound was purified by ISCO using 120 g silica column, the compound was eluted in 20% EA in hexanes, the fractions were collected and concentrated to afford methyl 4-bromo-1-((2- (trimethylsilyl)ethoxy)methyl)-1H-pyrazole-3-carboxylate (13.95 g, 41.6 mmol, 85 % yield) as an oil. LCMS Retention time: 1.63 min [A], MS (E+) m/z: 337.1 [M+2H].
85%
Stage #1: methyl 4-bromo-1H-pyrazole-3-carboxylate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Inert atmosphere;
Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In tetrahydrofuran; mineral oil at 20℃;

Experimental Procedure
3 Method C3: SEM Protection of Pyrazoles Illustrative Example 4-Bromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazole-3-carboxylic acid methyl ester
General procedure: The pyrazole (1 eq) is dissolved in dry THF at 0° C. After addition of NaH (1.5 eq), the mixture is stirred at 0° C. under Natmosphere for 30 min. Next, SEM-C1 (1.5 eq) is slowly added and the resulting mixture is stirred at room temperature overnight. Subsequently, the mixture is quenched with water and extracted with EtOAc. The organic phase is isolated, dried over Na2SO4, filtered and evaporated to give a residue that is used as such. The pyrazole (Int 4, 2 g, 9.76 mmol) is dissolved in dry THF (20 mL) at 0° C. After addition of NaH (60 w %, 584 mg, 14.6 mmol), the mixture is stirred at 0° C. under Natmosphere for 30 min. Next, SEM-C1 (2.58 mL, 14.6 mmol) is slowly added and the resulting mixture is stirred at room temperature overnight. Subsequently, the mixture is quenched with water and extracted with EtOAc. The organic phase is isolated, dried over Na2SO4, filtered and evaporated to give a residue that is used as such.

Safety and Hazards

Pictogram(s)exclamation-mark
SignalWarning
GHS Hazard StatementsH302 (66.7%): Harmful if swallowed [Warning Acute toxicity, oral]
H312 (33.3%): Harmful in contact with skin [Warning Acute toxicity, dermal]
H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]
H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]
H332 (66.7%): Harmful if inhaled [Warning Acute toxicity, inhalation]
H335 (100%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]
Precautionary Statement CodesP261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501

Other Data

TransportationUnder the room temperature and away from light
HS Code
StorageUnder the room temperature and away from light
Shelf Life2 years
Market Price
Druglikeness
Lipinski rules component
Molecular Weight205.011
logP1.828
HBA4
HBD1
Matching Lipinski Rules4
Veber rules component
Polar Surface Area (PSA)54.98
Rotatable Bond (RotB)2
Matching Veber Rules2

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