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

HRID 422981Notes

Reaction equation

HRID 422981 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([NH:20][C:21]([C:23]2([NH:38]C(=O)OC(C)(C)C)[CH2:28][CH2:27][N:26]([C:29]3[C:30]4[CH:37]=[CH:36][NH:35][C:31]=4[N:32]=[CH:33][N:34]=3)[CH2:25][CH2:24]2)=[O:22])[CH2:16][CH2:17][CH2:18][OH:19])=[CH:11][CH:10]=1>CO>[NH2:38][C:23]1([C:21]([NH:20][CH:15]([C:12]2[CH:11]=[CH:10][C:9]([Cl:8])=[CH:14][CH:13]=2)[CH2:16][CH2:17][CH2:18][OH:19])=[O:22])[CH2:24][CH2:25][N:26]([C:29]2[C:30]3[CH:37]=[CH:36][NH:35][C:31]=3[N:32]=[CH:33][N:34]=2)[CH2:27][CH2:28]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57750349tert-butyl 4-(1-(4-chlorophenyl)-4-hydroxybutylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate2×

Product 1

HCID 426021754-amino-N-(1-(4-chlorophenyl)-4-hydroxybutyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamideYield 50.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Trifluoroacetic acid (2 ml, 25.96 mmol) was added to tert-butyl 4-(1-(4-chlorophenyl)-4-hydroxybutylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (Intermediate 17) (140 mg, 0.26 mmol) at 20° C. and the resulting solution stirred for 1 hour. The solution was then diluted with methanol, applied to a 10 g SCX column and eluted with methanol followed by 2N NH3/MeOH. Fractions containing product were combined, concentrated by evaporation and purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5 μm silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 4-amino-N-(1-(4-chlorophenyl)-4-hydroxybutyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (58.0 mg, 50.8%) as a colourless solid.

Workup

  1. washeluted with methanol
  2. additionFractions containing product
  3. concentrationconcentrated by evaporation
  4. custompurified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5 μm silica, 19 mm diameter, 100 mm length)
  5. additionFractions containing the desired compound
  6. customwere evaporated to dryness

Sources & evidence

ORD record
ord-34cb9dcffeab47e9b8f5806693cf0d0a
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

Loading…