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

HRID 422982ノート

反応式

HRID 422982 の反応式
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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
65 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-149666eb82754250a96b763cf582c18d
出典データセット
uspto-grants-2012_01
特許番号
US08101623B2

反応ノート

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