Cesium carbonate → HCID 118522632, compound

HRID 529743Notes

Reaction equation

HRID 529743 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:33][CH:34]([F:36])[F:35])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[C:17]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][NH:10][N:9]=2)[CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:43]([O:47][C:48](=[O:51])[CH2:49]Br)([CH3:46])([CH3:45])[CH3:44]>CN(C=O)C.O>[C:43]([O:47][C:48](=[O:51])[CH2:49][N:10]1[CH:11]=[C:12]([NH:13][C:14]([C:16]2[C:17]([NH:25][C:26]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:32])=[N:18][N:19]3[CH:24]=[CH:23][CH:22]=[N:21][C:20]=23)=[O:15])[C:8]([C:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[O:33][CH:34]([F:36])[F:35])=[N:9]1)([CH3:46])([CH3:45])[CH3:44]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 79177tert-Butyl bromoacetateHCID 178453004HCID 178453004, compound

Product 1

HCID 118522632HCID 118522632, compoundYield 74.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of tert-butyl (3-((3-(5-chloro-2-(difluoromethoxy)phenyl)-1H-pyrazol-4-yl)carbamoyl)pyrazolo[1,5-a]pyrimidin-2-yl)carbamate (1.0 g, 1.92 mmol) in DMF (10 mL) was treated with cesium carbonate (0.69 g, 2.12 mmol) and tert-butyl-bromoacetate (0.43 g, 2.12 mmol) and was left to stir at room temperature for 2.5 hours. The reaction mixture was diluted with water and the resultant precipitate was collected by filtration. The resultant solid was purified by flash chromatography on silica eluting with 0-70% EtOAc in cyclohexane. Appropriate fractions were combined and evaporated to afford [4-[(2-tert-butoxycarbonylamino-pyrazolo[1,5-a]pyrimidine-3-carbonyl)-amino]-3-(5-chloro-2-difluoromethoxy-phenyl)-pyrazol-1-yl]-acetic acid tert-butyl ester as a white solid (0.91 g, 74%). LCMS (Method 3) [M+H]+=633.9, RT=4.46 min. 1H NMR (400 MHz, CDCl3) δ: (ppm) 9.78 (s, 1H), 9.70 (s, 1H), 8.76 (dd, 1H, J=1.8, 6.8 Hz), 8.47 (dd, 1H, J=1.8, 4.3 Hz), 8.34 (s, 1H), 7.69 (d, 1H, J=2.5 Hz), 7.41 (dd, 1H, J=2.7, 8.7 Hz), 7.28 (d, 1H, J=8.8 Hz), 6.92 (dd, 1H, J=4.4, 6.9 Hz), 6.47 (t, 1H, J=74.0 Hz), 4.85 (s, 2H), 1.56 (s, 9H), 1.49 (s, 9H).

Workup

  1. waitwas left
  2. filtrationthe resultant precipitate was collected by filtration
  3. customThe resultant solid was purified by flash chromatography on silica eluting with 0-70% EtOAc in cyclohexane
  4. customevaporated

Sources & evidence

ORD record
ord-f85f2816c20b4eceb84e0850226a5825
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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