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

HRID 422982Notes

Reaction equation

HRID 422982 reaction equation
CCN(C(C)C)C(C)C.[NH2:10][C:11]1([C:17]([NH:19][CH:20]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)[CH2:21][CH2:22][CH2:23][OH:24])=[O:18])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.Cl[C:33]1[C:34]2[CH:41]=[CH:40][NH:39][C:35]=2[N:36]=[CH:37][N:38]=1>C(O)C>[NH2:10][C:11]1([C:17]([NH:19][CH:20]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)[CH2:21][CH2:22][CH2:23][OH:24])=[O:18])[CH2:16][CH2:15][N:14]([C:33]2[C:34]3[CH:41]=[CH:40][NH:39][C:35]=3[N:36]=[CH:37][N:38]=2)[CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 53566827H-Pyrrolo(2,3-d)pyrimidine, 4-chloro-HCID 577502714-amino-N-(1-(4-chlorophenyl)-4-hydroxybutyl)piperidine-4-carboxamide2×

Product 1

HCID 426021754-amino-N-(1-(4-chlorophenyl)-4-hydroxybutyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamideYield 63.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
65 °C

Procedure

DIPEA (2.85 mL, 16.0 mmol) was added to 4-amino-N-(1-(4-chlorophenyl)-4-hydroxybutyl)piperidine-4-carboxamide (Intermediate 72) (1.04 g, 3.19 mmol) and 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (0.490 g, 3.19 mmol) in ethanol (15.96 mL) at 25° C. The resulting solution was stirred at 65° C. overnight. The crude product was analysed by LCMS and evaporated to dryness. The crude solid was then purified by ion exchange chromatography, using an SCX-2 column. The product was eluted from the column using 20% 7N ammonia in methanol/DCM. The crude mixture was then re-purified by flash silica chromatography (eluent 0-10% 7N ammonia/MeOH in DCM) and pure fractions 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 (63.9%) (racemate) as a fine white solid. The racemate was chirally resolved by supercritical flow chromatography (SFC) to afford the pure enantiomers in yields of 272 mg (19%) and 245 mg (17%) respectively. The NMR spectra for both enantiomers were identical.

Workup

  1. customevaporated to dryness
  2. customThe crude solid was then purified by ion exchange chromatography
  3. washThe product was eluted from the column
  4. customThe crude mixture was then re-purified by flash silica chromatography (eluent 0-10% 7N ammonia/MeOH in DCM) and pure fractions
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-149666eb82754250a96b763cf582c18d
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

Loading…