Diisopropylethylamine → Capivasertib

HRID 422985ノート

反応式

HRID 422985 の反応式
C(N(C(C)C)C(C)C)C.[NH2:10][C:11]1([C:17]([NH:19][C@H:20]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[CH2:21][CH2:22][OH:23])=[O:18])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.Cl[C:32]1[C:33]2[CH:40]=[CH:39][NH:38][C:34]=2[N:35]=[CH:36][N:37]=1>C(O)CCC.CCOC(C)=O>[NH2:10][C:11]1([C:17]([NH:19][C@H:20]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[CH2:21][CH2:22][OH:23])=[O:18])[CH2:16][CH2:15][N:14]([C:32]2[C:33]3[CH:40]=[CH:39][NH:38][C:34]=3[N:35]=[CH:36][N:37]=2)[CH2:13][CH2:12]1

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 53566827H-Pyrrolo(2,3-d)pyrimidine, 4-chloro-HCID 57750388(S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)piperidine-4-carboxamide2 回

生成物 1

HCID 25227436Capivasertib収率 61.2%

試薬・触媒・溶媒 2

HCID 2631-Butanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

N-Ethyldiisopropylamine (1.676 ml, 9.62 mmol) was added to (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)piperidine-4-carboxamide (Intermediate 49) (1 g, 3.21 mmol) and 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (0.493 g, 3.21 mmol) in butan-1-ol (15 ml). The resulting solution was stirred at 60° C. for 18 hours. The reaction mixture was diluted with EtOAc (50 mL), and washed sequentially with water (25 mL) and saturated brine (25 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 6% MeOH with ammonia in DCM. Pure fractions were evaporated to dryness to afford (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (842 mg) as a white foam. (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide was stirred in ethyl acetate (7 mL) for 18 hours. The solid was collected by filtration, washed with a small amount of ethyl acetate and vacuum oven dried at 55° C. for 18 hours to afford (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (0.585 g, 42.5%) as a white solid. m/z (ES+) (M+H)+=429; HPLC tR=1.60 min.

後処理

  1. washwashed sequentially with water (25 mL) and saturated brine (25 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 6% MeOH with ammonia in DCM
  7. customPure fractions were evaporated to dryness

出典と根拠

ORDレコード
ord-de61dd75e6324ddaaa93b336f9cd25d0
出典データセット
uspto-grants-2012_01
特許番号
US08101623B2

反応ノート

読み込み中…