Hydrochloric Acid → Cxd-101

HRID 222404Notes

Reaction equation

HRID 222404 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([CH2:7][N:8]2[CH2:13][CH2:12][CH:11]([C:14]3[CH:36]=[CH:35][C:17]([C:18]([NH:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[NH:27]C(=O)OC(C)(C)C)=[O:19])=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)[C:4]([CH3:37])=[N:3]1.O.Cl.[OH-].[Na+]>CO>[NH2:27][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[NH:20][C:18](=[O:19])[C:17]1[CH:35]=[CH:36][C:14]([CH:11]2[CH2:10][CH2:9][N:8]([CH2:7][C:5]3[C:4]([CH3:37])=[N:3][N:2]([CH3:1])[CH:6]=3)[CH2:13][CH2:12]2)=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 59830877tert-Butyl (2-{[4-(1-{1,3-dimethyl-1H-pyrazol-4-ylmethyl}piperidin-4-yl)benzoyl]amino}phenyl)carbamate

Product 1

HCID 16225380Cxd-101Yield 86%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

tert-Butyl (2-{[4-(1-{1,3-dimethyl-1H-pyrazol-4-ylmethyl}piperidin-4-yl)benzoyl]amino}phenyl)carbamate (Method 6 below; 92.3 g, 183.3 mmol) was slurried in methanol (754 ml) and water (141 ml) and cooled to 0-5° C. Concentrated hydrochloric acid was added maintaining the temperature below 20° C. The reaction mixture was stirred for 20 hours at ambient temperature. The reaction was cooled to 0-5° C. and aqueous sodium hydroxide solution added maintaining the temperature at below 20° C. until a pH of 12-14 is obtained. The reaction mixture was heated to reflux temperature for 30 minutes before cooling to 20° C. over about 4 hours. The product was collected by filtration and washed with aqueous methanol before being dried in vacuo at 45° C. to constant weight to give the title compound (63.3 g 86%).

Workup

  1. temperaturemaintaining the temperature below 20° C
  2. temperatureThe reaction was cooled to 0-5° C.
  3. temperaturemaintaining the temperature at below 20° C. until a pH of 12-14
  4. customis obtained
  5. temperatureThe reaction mixture was heated
  6. temperatureto reflux temperature for 30 minutes
  7. temperaturebefore cooling to 20° C. over about 4 hours
  8. filtrationThe product was collected by filtration
  9. washwashed with aqueous methanol
  10. custombefore being dried in vacuo at 45° C. to constant weight

Sources & evidence

ORD record
ord-104bdb28c8d64b368fbb474a5d00fe27
Source dataset
uspto-grants-2012_06
Patent number
US08207202B2

Reaction notes

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