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

HRID 423016Notes

Reaction equation

HRID 423016 reaction equation
C(O)(C(F)(F)F)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([NH:22][C:23]([C:25]2([NH:40]C(=O)OC(C)(C)C)[CH2:30][CH2:29][N:28]([C:31]3[C:32]4[CH:39]=[CH:38][NH:37][C:33]=4[N:34]=[CH:35][N:36]=3)[CH2:27][CH2:26]2)=[O:24])[CH2:16][C:17]([N:19]([CH3:21])[CH3:20])=[O:18])=[CH:11][CH:10]=1>ClCCl>[NH2:40][C:25]1([C:23]([NH:22][CH:15]([C:12]2[CH:13]=[CH:14][C:9]([Cl:8])=[CH:10][CH:11]=2)[CH2:16][C:17]([N:19]([CH3:20])[CH3:21])=[O:18])=[O:24])[CH2:26][CH2:27][N:28]([C:31]2[C:32]3[CH:39]=[CH:38][NH:37][C:33]=3[N:34]=[CH:35][N:36]=2)[CH2:29][CH2:30]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57750350tert-butyl 4-(1-(4-chlorophenyl)-3-(dimethylamino)-3-oxopropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate2×

Product 1

HCID 577504204-amino-N-(1-(4-chlorophenyl)-3-(dimethylamino)-3-oxopropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamideYield 65.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (1.0 mL) was added to a suspension of tert-butyl 4-(1-(4-chlorophenyl)-3-(dimethylamino)-3-oxopropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (Intermediate 98) (770 mg, 0.24 mmol) in dichloromethane (10 mL) under argon. The resulting solution was stirred at room temperature for one night. The solvents were removed in vacuo and the reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions were evaporated to dryness to afford 4-amino-N-(1-(4-chlorophenyl)-3-(dimethylamino)-3-oxopropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (74.0 mg, 64.8%) as a white powder.

Workup

  1. customThe solvents were removed in vacuo
  2. customthe reaction mixture was purified by preparative HPLC
  3. customThe fractions were evaporated to dryness

Sources & evidence

ORD record
ord-923811c89c23482b97a7d535159c22c7
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

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