Dimethyl Sulfoxide → tert-Butyl [(1S,2R)-2-({6-carbamoyl-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl]amino)cyclohexyl}carbamate

HRID 1504852Notes

Reaction equation

HRID 1504852 reaction equation
[C:1]([C:3]1[N:8]=[CH:7][C:6]([NH:9][C@@H:10]2[CH2:15][CH2:14][CH2:13][CH2:12][C@@H:11]2[NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:5][C:4]=1[NH:24][C:25]1[CH:30]=[C:29]([CH3:31])[CH:28]=[C:27]([CH3:32])[N:26]=1)#[N:2].CS(C)=[O:35].[OH-].[Na+].OO>O>[C:1]([C:3]1[N:8]=[CH:7][C:6]([NH:9][C@@H:10]2[CH2:15][CH2:14][CH2:13][CH2:12][C@@H:11]2[NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:5][C:4]=1[NH:24][C:25]1[CH:30]=[C:29]([CH3:31])[CH:28]=[C:27]([CH3:32])[N:26]=1)(=[O:35])[NH2:2]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 86731720tert-butyl [(1S,2R)-2-({6-cyano-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl}amino)cyclohexyl]carbamate

Product 1

HCID 86731721tert-Butyl [(1S,2R)-2-({6-carbamoyl-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl]amino)cyclohexyl}carbamate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a flask were added tert-butyl [(1S,2R)-2-({6-cyano-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl}amino)cyclohexyl]carbamate (18.9 g, 43.3 mmol) and DMSO (380 mL). The resulting mixture was cooled in an ice bath. To the reaction mixture was added sodium hydroxide (6.0 M in water, 21.7 mL, 130 mmol) followed by the slow addition of hydrogen peroxide (35% solution in water, 7.96 mL, 91 mmol). The addition was performed at such a rate to maintain the internal reaction temperature between 25° C. and 30° C. After 20 minutes, the reaction mixture was slowly diluted with water (500 mL). After 30 minutes, the mixture was filtered, and the collected solids were washed with water and then dried overnight under a nitrogen bag. The collected solids were suspended in ethyl acetate (500 mL) and the resulting slurry was seeded with a previously processed batch of tert-butyl [(1S,2R)-2-({6-carbamoyl-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl}amino)cyclohexyl]carbamate. After 1 hour, the mixture was diluted with hexanes (150 mL), filtered, washed with hexanes, and dried in a nitrogen bag to afford tert-butyl [(1S,2R)-2-({6-carbamoyl-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl}amino)cyclohexyl]carbamate. MS ESI calc'd. for C24H35N6O3 [M+H]+ 455. found 455. 1H NMR (600 MHz, DMSO-d6) δ 11.68 (s, 1H), 8.51 (d, J=1.8 Hz, 1H), 7.81 (d, J=3.0 Hz, 1H), 7.55 (d, J=1.8 Hz, 1H), 7.21 (s, 1H), 6.54-6.50 (m, 2H), 6.40 (s, 1H), 6.05 (d, J=6.0 Hz, 1H), 3.81 (s, 1H), 3.54 (s, 1H), 2.34 (s, 3H), 2.17 (s, 3H), 1.82-1.76 (m, 1H), 1.72-1.64 (m, 1H), 1.60-1.42 (m, 4H), 1.36-1.28 (m, 1H), 1.27 (s, 9), 1.10-1.06 (m, 1H).

Workup

  1. temperatureThe resulting mixture was cooled in an ice bath
  2. additionThe addition
  3. temperatureto maintain the internal reaction temperature between 25° C. and 30° C
  4. waitAfter 30 minutes
  5. filtrationthe mixture was filtered
  6. washthe collected solids were washed with water
  7. customdried overnight under a nitrogen bag
  8. waitAfter 1 hour
  9. additionthe mixture was diluted with hexanes (150 mL)
  10. filtrationfiltered
  11. washwashed with hexanes
  12. customdried in a nitrogen bag

Sources & evidence

ORD record
ord-80fdc3f7e72e4819b2ccf1792fd1a908
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

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