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

HRID 422982노트

반응식

HRID 422982 반응식
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

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 53566827H-Pyrrolo(2,3-d)pyrimidine, 4-chloro-HCID 577502714-amino-N-(1-(4-chlorophenyl)-4-hydroxybutyl)piperidine-4-carboxamide2회

생성물 1

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

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
65 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-149666eb82754250a96b763cf582c18d
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101623B2

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