Diisopropylethylamine → (R)-2-(N-(1-(tert-butoxycarbonyl)piperidin-3-yl)-4-(pyrazolo[1,5-a]pyrimidin-3-yl)benzamido)-3-methylpyridine 1-oxide

HRID 588386Notes

Reaction equation

HRID 588386 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:14][C:15]2[C:20]([CH3:21])=[CH:19][CH:18]=[CH:17][N+:16]=2[O-:22])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:23]1[N:27]2[CH:28]=[CH:29][CH:30]=[N:31][C:26]2=[C:25]([C:32]2[CH:40]=[CH:39][C:35]([C:36](O)=[O:37])=[CH:34][CH:33]=2)[CH:24]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([N:14]([C:15]2[C:20]([CH3:21])=[CH:19][CH:18]=[CH:17][N+:16]=2[O-:22])[C:36](=[O:37])[C:35]2[CH:34]=[CH:33][C:32]([C:25]3[CH:24]=[N:23][N:27]4[CH:28]=[CH:29][CH:30]=[N:31][C:26]=34)=[CH:40][CH:39]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1176527814-(Pyrazolo[1,5-a]pyrimidin-3-yl)benzoic acidHCID 178426682HCID 178426682, compound

Product 1

HCID 117652714(R)-2-(N-(1-(tert-butoxycarbonyl)piperidin-3-yl)-4-(pyrazolo[1,5-a]pyrimidin-3-yl)benzamido)-3-methylpyridine 1-oxide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of Preparation 14 (R)-2-(1-(tert-butoxycarbonyl)piperidin-3-ylamino)-3-methylpyridine 1-oxide (540 mg, 1.76 mmol) and Preparation 19 4-(pyrazolo[1,5-a]pyrimidin-3-yl)benzoic acid (420 mg, 1.76 mmol) in DMF (10 mL) was added HATU (803 mg, 2.11 mmol) at 30° C. The reaction was stirred at room temperature for 30 min. Diisopropylethyl amine (682 mg, 5.28 mmol) was then added at 0° C. dropwise. The reaction was stirred at 30° C. for 2 h. The resulting mixture poured into water then extracted with EtOAc (3×30 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel chromatography to deliver the title compound (760 mg, 82%) as a brown oil.

Workup

  1. stirringThe reaction was stirred at 30° C. for 2 h
  2. extractionthen extracted with EtOAc (3×30 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-240ddfe133d041baa097b4340d50a6a2
Source dataset
uspto-grants-2016_01
Patent number
US09227956B2

Reaction notes

Loading…