Acetic Acid → (1R,2S)-2-(4-chlorophenyl)-1'-(2-(4-isopropylpiperazin-1-yl)ethyl)spiro[cyclopropane-1,3'-indolin]-2'-one

HRID 1805327ノート

反応式

HRID 1805327 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[C@:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([CH2:19][CH:20]=O)[C:11]3=[O:22])[CH2:9]2)=[CH:4][CH:3]=1.[CH:23]([N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)([CH3:25])[CH3:24].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@@:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([CH2:19][CH2:20][N:29]4[CH2:30][CH2:31][N:26]([CH:23]([CH3:25])[CH3:24])[CH2:27][CH2:28]4)[C:11]3=[O:22])[CH2:9]2)=[CH:4][CH:3]=1

参加物

6

反応物 4

HCID 176Acetic AcidHCID 780131-IsopropylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 58305328(1S,2R)-2-(2-(4-chlorophenyl)-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)acetaldehyde

生成物 1

HCID 58305276(1R,2S)-2-(4-chlorophenyl)-1'-(2-(4-isopropylpiperazin-1-yl)ethyl)spiro[cyclopropane-1,3'-indolin]-2'-one収率 82.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A mixture of (1R,2S) and (1S,2R)-2-(2-(4-chlorophenyl)-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)acetaldehyde (0.1 mmol), (1-Isopropyl)piperazine (0.15 mmol) and acetic acid (catalytic amount) in DCM (2 ml) was stirred for 20 minutes at room temperature. The mixture was cooled to 0° C. and NaBH(OAc)3 (2 mmol) was added carefully. The mixture was warmed to room temperature and stirred for 14 hours at room temperature. The mixture was concentrated under reduced pressure and dissolved in DMF. Purification by preparative HPLC gave the title product as colorless oil (35 mg). LC/MS m/e calcd. for C25H30ClN3O: 423, observed (M+H)+: 424.1 1HNMR (400 MHz, MeOD-d4) δppm 1.37 (d, J=6.57 Hz, 6 H) 2.18 (dd, J=8.46, 5.94 Hz, 2 H) 2.46-2.64 (m, 1H) 2.85 (d, J=3.54 Hz, 2 H) 3.22 (s, 2 H) 3.50 (d, J=6.57 Hz, 2 H) 3.90-4.27 (m, 2 H) 6.09 (d, J=7.58 Hz, 1H) 6.76 (s, 1 H) 7.10 (d, J=7.83 Hz, 1 H) 7.16-7.25 (m, 3 H) 7.33 (d, J=8.59 Hz, 2 H).

後処理

  1. temperatureThe mixture was cooled to 0° C.
  2. temperatureThe mixture was warmed to room temperature
  3. stirringstirred for 14 hours at room temperature
  4. concentrationThe mixture was concentrated under reduced pressure
  5. dissolutiondissolved in DMF
  6. customPurification by preparative HPLC

出典と根拠

ORDレコード
ord-ee205c3da47c43fbb058c4a10cc602fb
出典データセット
uspto-grants-2013_01
特許番号
US08354443B2

反応ノート

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