Lithium Hydroxide → 10-{4-[5-({4,5-Dimethyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl]-3-(hydroxymethyl)pyridin-2-yl}-4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one

HRID 593133Notes

Reaction equation

HRID 593133 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:32]2[CH2:43][CH2:42][N:41]3[C:34](=[CH:35][C:36]4[CH2:37][C:38]([CH3:45])([CH3:44])[CH2:39][C:40]=43)[C:33]2=[O:46])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:29]=[C:22]3[CH:23]([CH3:28])[N:24]([CH3:27])[CH2:25][CH2:26][N:21]3[N:20]=2)[C:15](=[O:30])[N:14]([CH3:31])[CH:13]=1)(=O)C.[OH-].[Li+].C(O)(C)C.C1COCC1>O>[CH3:28][CH:23]1[N:24]([CH3:27])[CH2:25][CH2:26][N:21]2[N:20]=[C:19]([NH:18][C:16]3[C:15](=[O:30])[N:14]([CH3:31])[CH:13]=[C:12]([C:11]4[CH:10]=[CH:9][N:8]=[C:7]([N:32]5[CH2:43][CH2:42][N:41]6[C:34](=[CH:35][C:36]7[CH2:37][C:38]([CH3:44])([CH3:45])[CH2:39][C:40]=76)[C:33]5=[O:46])[C:6]=4[CH2:5][OH:4])[CH:17]=3)[CH:29]=[C:22]12

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 22597222Tetrahydrofuran 2-propanolHCID 86684568{4-[5-({4,5-Dimethyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl]-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl}methyl Acetate

Product 1

HCID 8668456910-{4-[5-({4,5-Dimethyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl]-3-(hydroxymethyl)pyridin-2-yl}-4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-oneYield 48.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with 318a (200 mg, 1.0 eq., 0.32 mmol), lithium hydroxide (38 mg, 5.0 eq., 1.60 mmol), i-propanol/THF (8/8 mL), and water (2 mL). The mixture was stirred at room temperature for 1 h and concentrated under reduced pressure. The residue was added partitioned between water and dichloromethane. The combined organic layer was concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford racemic mixture 318b as a yellow solid (91 mg, 43%).

Workup

  1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was added
  4. custompartitioned between water and dichloromethane
  5. concentrationThe combined organic layer was concentrated under reduced pressure
  6. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-1179735fb4e74ed98a5090d30fc575a8
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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