Diisopropylcarbodiimide → (S)-2-(1-methyl-3-phenyl-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-6-ylamino)-N-(1-phenylethyl)acetamide

HRID 402482Notes

Reaction equation

HRID 402482 reaction equation
[CH3:1][N:2]1[C:6]2=[N:7][C:8]([NH: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@H:46]([NH2:53])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>C1COCC1>[CH3:1][N:2]1[C:6]2=[N:7][C:8]([NH:15][CH2:16][C:17]([NH:53][C@H:46]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[CH3:45])=[O:18])=[CH:9][C:10]([C:11]([F:12])([F:13])[F:14])=[C:5]2[C:4]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:3]1

Participants

6

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 758181-Phenethylamine, (-)-HCID 672095372-(1-methyl-3-phenyl-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-6-ylamino)acetic acid

Product 1

HCID 70817059(S)-2-(1-methyl-3-phenyl-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-6-ylamino)-N-(1-phenylethyl)acetamideYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(1-methyl-3-phenyl-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-6-ylamino) acetic acid (0.035 g, 0.095 mmol), DIC (0.018 g, 0.143 mmol) and HOBt (0.020 g, 0.143 mmol) in THF (5 ml) was stirred at rt for 10 min. (S)-(−)-α-methyl benzyl amine (0.013 g, 0.104 mmol) was added to the reaction mixture dropwise at rt and stirring was continued for 16 h. The reaction mixture was poured into ice cold water and the precipitated product was collected by filtration and dried under vacuum. The crude product was purified by preparative HPLC using acetonitrile/water as mobile phase to yield the title compound as a white solid (0.018 g, 42%). [1H-NMR (CDCl3, 300 MHz) δ 7.52-7.38 (m, 4H), 7.32-7.21 (m, 6H), 6.66 (s, 1H), 6.39 (d, 1H), 5.51 (t, 1H), 5.30-5.15 (m, 1H), 4.20 (dd, 2H), 3.95 (s, 3H), 1.52 (d, 3H); HPLC RtA=5.294 (98%) min; LCMS RtA=1.682 min; [M+H]+=454.1]

Workup

  1. additionwas added to the reaction mixture dropwise at rt
  2. additionThe reaction mixture was poured into ice cold water
  3. filtrationthe precipitated product was collected by filtration
  4. customdried under vacuum
  5. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-82df30bf38bb487aae0e63a966ee0375
Source dataset
uspto-grants-2014_06
Patent number
US08742106B2

Reaction notes

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