Sodium hydride → 2-(3-(5-chloro-2-methoxyphenyl)-4-(pyrazolo[1,5-a]pyrimidine-3-carboxamido)-1H-pyrazol-1-yl)-2-fluoroacetic acid

HRID 1466609Notes

Reaction equation

HRID 1466609 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[C:24]4[N:23]=[CH:22]N=CC=4NN=3)=[O:15])=[CH:11][NH:10][N:9]=2)[CH:7]=1.[H-].[Na+].Br[CH:30]([F:36])[C:31]([O:33]CC)=[O:32]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:11]=[N:10][N:9]4[CH:8]=[CH:6][CH:22]=[N:23][C:24]=34)=[O:15])=[CH:11][N:10]([CH:30]([F:36])[C:31]([OH:33])=[O:32])[N:9]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2733407Acetic acid, 2-bromo-2-fluoro-, ethyl esterHCID 178490636HCID 178490636, compound

Product 1

HCID 866683822-(3-(5-chloro-2-methoxyphenyl)-4-(pyrazolo[1,5-a]pyrimidine-3-carboxamido)-1H-pyrazol-1-yl)-2-fluoroacetic acidYield 59.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To N-(3-(5-chloro-2-methoxyphenyl)-1H-pyrazol-4-yl)pyrazolo pyrimidine-3-carboxamide (37.1 mg, 0.10 mmol) in 1.5 DMF was added sodium hydride (10 mg, 0.40 mmol) and the mixture stirred for 5 min at which time ethyl bromofluoroacetate (37 mg, 0.20 mmol) was added. The mixture was stirred overnight, then purified by reverse phase HPLC and lyophilized to afford 13.3 mg (30%) of 2-(3-(5-chloro-2-methoxyphenyl)-4-(pyrazolo[1,5-a]pyrimidine-3-carboxamido)-1H-pyrazol-1-yl)-2-fluoroacetic acid as a colorless solid. LCMS (ESI) m+H=445.1. 1H NMR (400 MHz, DMSO) δ 9.71 (s, 1H), 9.33 (d, J=7.0 Hz, 1H), 8.76-8.71 (m, 1H), 8.66 (d, J=8.3 Hz, 1H), 8.38 (s, 1H), 7.58-7.20 (m, 5H), 5.98 (d, J=56.5 Hz, 1H), 3.84 (s, 3H).

Workup

  1. additionwas added
  2. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-6c62fcbec1e84b9c991a350a394bd089
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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