Propylphosphonic acid → 2-(1-Cyclopropyl-3-trifluoromethyl-1H-pyrazol-4-yl)-N-[5-(7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-pyridin-3-yl]-acetamide

HRID 82121Notes

Reaction equation

HRID 82121 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:18]3[CH:17]=[N:16][CH:15]=[N:14][C:13]=3[N:12]([CH:19]([CH3:21])[CH3:20])[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.[CH:22]1([N:25]2[CH:29]=[C:28]([CH2:30][C:31](O)=[O:32])[C:27]([C:34]([F:37])([F:36])[F:35])=[N:26]2)[CH2:24][CH2:23]1.CCCP(O)(O)=O>C1COCC1>[CH:22]1([N:25]2[CH:29]=[C:28]([CH2:30][C:31]([NH:1][C:2]3[CH:7]=[N:6][CH:5]=[C:4]([C:8]([C:10]4[C:18]5[CH:17]=[N:16][CH:15]=[N:14][C:13]=5[N:12]([CH:19]([CH3:21])[CH3:20])[CH:11]=4)=[O:9])[CH:3]=3)=[O:32])[C:27]([C:34]([F:37])([F:36])[F:35])=[N:26]2)[CH2:24][CH2:23]1

Participants

5

Reactant 3

HCID 204484Propylphosphonic acidHCID 70817456(5-aminopyridin-3-yl)(7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)methanoneHCID 708178072-(1-Cyclopropyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)acetic acid

Product 1

HCID 708175882-(1-Cyclopropyl-3-trifluoromethyl-1H-pyrazol-4-yl)-N-[5-(7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-pyridin-3-yl]-acetamideYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (5-Amino-pyridin-3-yl)-(7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methanone (Preparation 95, 50 mg, 0.17 mmol), (1-Cyclopropyl-3-trifluoromethyl-1H-pyrazol-4-yl)-acetic acid (Preparation 148, 47.1 mg, 0.21 mmol) and TEA (0.08 mL, 0.62 mmol) in THF (1 mL), 1-propylphosphonic acid cyclic anhydride (50% solution in EtOAc, 0.26 mL, 0.44 mmol) was added and the mixture was stirred at room temperature for 18 hours. The reaction mixture was evaporated under reduced pressure and the residue partitioned between water and EtOAc. The organic layer was washed with saturated sodium bicarbonate solution, dried (Na2SO4) and evaporated in vacuo. Purification by column chromatography on silica gel (EtOAc) gave the title compound as a white solid in 77% yield, 68 mg.

Workup

  1. customThe reaction mixture was evaporated under reduced pressure
  2. customthe residue partitioned between water and EtOAc
  3. washThe organic layer was washed with saturated sodium bicarbonate solution
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo
  6. customPurification by column chromatography on silica gel (EtOAc)

Sources & evidence

ORD record
ord-20e22034dce046a29d5e0c658987b22e
Source dataset
uspto-grants-2014_09
Patent number
US08846698B2

Reaction notes

Loading…