Trifluoroacetic acid → 4-amino-N-(1-(4-chlorophenyl)-2-(1H-imidazol-2-yl)ethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide

HRID 423013Notes

Reaction equation

HRID 423013 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([NH:41][C:42]([C:44]2([NH:59]C(=O)OC(C)(C)C)[CH2:49][CH2:48][N:47]([C:50]3[C:51]4[CH:58]=[CH:57][NH:56][C:52]=4[N:53]=[CH:54][N:55]=3)[CH2:46][CH2:45]2)=[O:43])[CH2:16][C:17]2[N:18](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH:19]=[CH:20][N:21]=2)=[CH:11][CH:10]=1>O.CO>[NH2:59][C:44]1([C:42]([NH:41][CH:15]([C:12]2[CH:11]=[CH:10][C:9]([Cl:8])=[CH:14][CH:13]=2)[CH2:16][C:17]2[NH:21][CH:20]=[CH:19][N:18]=2)=[O:43])[CH2:49][CH2:48][N:47]([C:50]2[C:51]3[CH:58]=[CH:57][NH:56][C:52]=3[N:53]=[CH:54][N:55]=2)[CH2:46][CH2:45]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57750358tert-butyl 4-(1-(4-chlorophenyl)-2-(1-trityl-1H-imidazol-2-yl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate2×

Product 1

HCID 577503834-amino-N-(1-(4-chlorophenyl)-2-(1H-imidazol-2-yl)ethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamideYield 73.6%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 887MethanolSolvent

Procedure

Trifluoroacetic acid (5 mL, 64.90 mmol) was added to tert-butyl 4-(1-(4-chlorophenyl)-2-(1-trityl-1H-imidazol-2-yl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (Intermediate 89) (310 mg, 0.38 mmol) at room temperature and the resulting solution stirred for 30 minutes. Water (5-6 drops) was then added and stirring continued for a further 30 minutes. The resulting solution was diluted with methanol and applied to a 10 g SCX column which was then eluted with MeOH followed by 2N NH3 (in MeOH). Product-containing fractions were combined and concentrated by evaporation then triturated with MeCN/DMF (1:1) to give a pale yellow ppt. The precipitate was collected by filtration, washed with MeCN and dried under vacuum to afford 4-amino-N-(1-(4-chlorophenyl)-2-(1H-imidazol-2-yl)ethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (130 mg, 72.8%) as a cream solid.

Workup

  1. stirringstirring
  2. waitcontinued for a further 30 minutes
  3. washwas then eluted with MeOH
  4. concentrationconcentrated by evaporation
  5. customthen triturated with MeCN/DMF (1:1)
  6. customto give a pale yellow ppt
  7. filtrationThe precipitate was collected by filtration
  8. washwashed with MeCN
  9. customdried under vacuum

Sources & evidence

ORD record
ord-54278c4ff0414c36848794f46c7b8187
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

Loading…