Dichloromethane → HCID 86621216、化合物

HRID 1673140ノート

反応式

HRID 1673140 の反応式
[NH2:1][CH:2]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[Cl:30])[C:3]1[S:7][C:6]([NH:8][C:9]([C:11]2([C:14]3[CH:22]=[CH:21][C:17]4[O:18][CH2:19][O:20][C:16]=4[CH:15]=3)[CH2:13][CH2:12]2)=[O:10])=[N:5][C:4]=1[CH3:23].[Si:31]([O:38][C@H:39]([CH2:43]Cl)[CH2:40][CH:41]=O)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32].[BH4-].[Na+].C(Cl)Cl>CO.O>[O:18]1[C:17]2[CH:21]=[CH:22][C:14]([C:11]3([C:9]([NH:8][C:6]4[S:7][C:3]([CH:2]([N:1]5[CH2:41][CH2:40][C@H:39]([O:38][Si:31]([C:34]([CH3:36])([CH3:35])[CH3:37])([CH3:32])[CH3:33])[CH2:43]5)[C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=5[Cl:30])=[C:4]([CH3:23])[N:5]=4)=[O:10])[CH2:13][CH2:12]3)=[CH:15][C:16]=2[O:20][CH2:19]1

参加物

7

反応物 4

HCID 6344DichloromethaneHCID 4311764Sodium borohydrideHCID 13963152HCID 13963152、化合物HCID 76672719N-(5-(amino(2-chlorophenyl)methyl)-4-methylthiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

生成物 1

HCID 86621216HCID 86621216、化合物

試薬・触媒・溶媒 2

HCID 887Methanol溶媒2 回HCID 962Water溶媒

実験手順

To a solution of N-(5-(amino(2-chlorophenyl)methyl)-4-methylthiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (Isomer A) (450 mg, 1.02 mmol) in MeOH (5 mL) was added (S)-3-(tert-butyldimethylsilyloxy)-4-chlorobutanal (289 mg, 1.22 mmol). The reaction mixture was stirred at room temperature for 20 min before NaBH4 (58 mg, 1.53 mmol) was added. Stirring was continued at room temperature for 3 h. After approximately 1 h some precipitate/gum started to form in the reaction solution so MeOH (5 mL) and CH2Cl2 (2 mL) were added to keep everything in solution. The reaction was diluted with H2O and extracted with EtOAc. The combined organic layers was washed with brine, dried over MgSO4 and concentrated. The residue was adsorbed onto silica gel and purified by column chromatography (0-25% EtOAc/hexanes) to afford 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-(((S)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)(2-chlorophenyl)methyl)-4-methylthiazol-2-yl)cyclopropanecarboxamide (Isomer A) as a pale yellow solid (470 mg, 74%). 1H NMR (400 MHz, CDCl3) δ 8.40 (s, 1H), 7.83 (dd, J=8.1, 1.6 Hz, 1H), 7.28-7.25 (m, 2H), 7.13 (m, 1H), 6.88-6.83 (m, 2H), 6.79 (d, J=7.9 Hz, 1H), 6.00 (s, 2H), 5.08 (s, 1H), 4.33 (m, 1H), 2.94 (dd, J=9.9, 6.3 Hz, 1H), 2.67 (td, J=8.3, 3.4 Hz, 1H), 2.53 (q, J=8.4 Hz, 1H), 2.37 (s, 3H), 2.17 (dd, J=9.9, 4.7 Hz, 1H), 2.00 (m, 1H), 1.74-1.61 (m, 3H), 1.17 (m, 2H), 0.86 (m, 9H), 0.01 (s, 3H), −0.01 (s, 3H); HPLC ret. time 3.45 min, 10-99% CH3CN, 5 min run; ESI-MS 626.5 m/z (MH+).

後処理

  1. additionwas added
  2. waitAfter approximately 1 h some precipitate/gum started
  3. additionwere added
  4. extractionextracted with EtOAc
  5. washThe combined organic layers was washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. custompurified by column chromatography (0-25% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-778652db69bb4ec49b4f9f584b3b599c
出典データセット
uspto-grants-2011_08
特許番号
US07999113B2

反応ノート

読み込み中…