Diisopropylcarbodiimide → (S)-N-(1-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl)-2-(1-methyl-3-phenyl-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-6-yloxy)acetamide

HRID 402469Notes

Reaction equation

HRID 402469 reaction equation
[CH3:1][N:2]1[C:6]2=[N:7][C:8]([O:15][CH2:16][C:17](O)=[O:18])=[CH:9][C:10]([C:11]([F:14])([F:13])[F:12])=[C:5]2[C:4]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:3]1.CC(C)N=C=NC(C)C.C1C=CC2N(O)N=NC=2C=1.[CH3:45][C:46]1[C:50]([CH:51]([NH2:53])[CH3:52])=[C:49]([CH3:54])[NH:48][N:47]=1>CN(C=O)C>[CH3:45][C:46]1[C:50]([C@@H:51]([NH:53][C:17](=[O:18])[CH2:16][O:15][C:8]2[N:7]=[C:6]3[N:2]([CH3:1])[N:3]=[C:4]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:5]3=[C:10]([C:11]([F:14])([F:13])[F:12])[CH:9]=2)[CH3:52])=[C:49]([CH3:54])[NH:48][N:47]=1

Participants

6

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 31363771-(3,5-dimethyl-1H-pyrazol-4-yl)ethanamineHCID 67209383(1-Methyl-3-phenyl-4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridin-6-yloxy)-acetic acid

Product 1

HCID 70817239(S)-N-(1-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl)-2-(1-methyl-3-phenyl-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-6-yloxy)acetamideYield 9.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (1-Methyl-3-phenyl-4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridin-6-yloxy)-acetic acid (1.35 g, 3.843 mmol), DIC (727 mg, 5.769 mmol) and HOBt (674 mg, 4.996 mmol) in DMF (15 ml) was stirred at rt for 15 min. 1-(3,5-dimethyl-1H-pyrazole-4-yl)ethanamine (642 mg, 4.612 mmol) was added to the solution at rt and stirring was continued overnight at rt. After completion of the reaction, ice-cold water was added to the reaction mixture and the mixture was stirred for 10 min. The precipitate was collected by filtration and dried under vacuum. The racemic mixture was subjected to chiral preparative chromatographic separation to yield the enantiomeric pure title compound (165 mg) and the R enantiomer (165 mg, see example 1.62). [1H-NMR (CDCl3, 300 MHz) δ 7.62-7.48 (m, 5H), 6.99 (s, 1H), 6.55 (d, 1H), 5.33-4.92 (m, 3H), 4.1 (s, 3H), 2.25 (s, 6H), 1.55 (d, 3H); HPLC RtE=6.194 min. (98%); LCMS RtA=1.382, [M+H]+=473.1; Mp=145-147° C.]

Workup

  1. customAfter completion of the reaction, ice-cold water
  2. additionwas added to the reaction mixture
  3. stirringthe mixture was stirred for 10 min
  4. filtrationThe precipitate was collected by filtration
  5. customdried under vacuum
  6. customThe racemic mixture was subjected to chiral preparative chromatographic separation

Sources & evidence

ORD record
ord-0fdb5d4755a54ceeb8540600a00ead2f
Source dataset
uspto-grants-2014_06
Patent number
US08742106B2

Reaction notes

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