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Sodium borohydride → 1-(Benzo[d][1,3]dioxol-5-yl)-N-(5-((S)-((R)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)(2-chloro-4-fluorophenyl)methyl)thiazol-2-yl)cyclopropanecarboxamide

HRID 1855237
ノート
印刷プレビュー

反応式

HRID 1855237 の反応式
[NH2:1][C@@H:2]([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=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][CH:4]=1.[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+]>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]([C@@H: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:23]5[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=5[Cl:30])=[CH:4][N:5]=4)=[O:10])[CH2:12][CH2:13]3)=[CH:15][C:16]=2[O:20][CH2:19]1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 4311764Sodium borohydrideHCID 13963153(R)-3-(tert-butyldimethylsilyloxy)-4-chlorobutanalHCID 59757103(S)-N-(5-(Amino(2-chloro-4-fluorophenyl)methyl)thiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

生成物 1

HCID 597571341-(Benzo[d][1,3]dioxol-5-yl)-N-(5-((S)-((R)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)(2-chloro-4-fluorophenyl)methyl)thiazol-2-yl)cyclopropanecarboxamide収率 59%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 962Water溶媒

実験手順

To a solution of (S)-N-(5-(amino(2-chloro-4-fluorophenyl)methyl)thiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (1.2 mmol) in MeOH (10 mL) was added (R)-3-(tert-butyldimethylsilyloxy)-4-chlorobutanal (341 mg, 1.4 mmol). The reaction mixture was stirred at room temperature for 5 min. Then NaBH4 (68 mg, 1.8 mmol) was added and stirring was continued at room temperature for 1 h. The reaction was diluted with H2O and extracted with EtOAc. The combined organic layers were washed with brine and dried over MgSO4. After the removal of solvent, the residue was purified by column chromatography (10-20% EtOAc/Hexane) to afford 1-(Benzo[d][1,3]dioxol-5-yl)-N-(5-((S)—((R)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)(2-chloro-4-fluorophenyl)methyl)thiazol-2-yl)cyclopropanecarboxamide (446 mg, 59% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.45 (s, 1H), 7.79 (dd, J=8.6, 6.3 Hz, 1H), 7.25 (d, J=6.4 Hz, 1H), 7.01-6.94 (m, 2H), 6.85 (td, J=8.3, 1.7 Hz, 2H), 6.78 (d, J=7.9 Hz, 1H), 5.99 (s, 2H), 4.99 (s, 1H), 4.35-4.30 (m, 1H), 2.77 (dd, J=9.9, 6.2 Hz, 1H), 2.51-2.48 (m, 2H), 2.36 (dd, J=9.9, 4.3 Hz, 1H), 2.06-2.01 (m, 1H), 1.71-1.65 (m, 3H), 1.18 (t, J=3.0 Hz, 2H), 0.85 (s, 9H), −0.01 (d, J=7.3 Hz, 6H); HPLC ret. time 3.59 min, 10-99% CH3CN, 5 min run; ESI-MS 630.6 m/z (MH+).

後処理

  1. stirringstirring
  2. waitwas continued at room temperature for 1 h
  3. extractionextracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. customAfter the removal of solvent
  7. customthe residue was purified by column chromatography (10-20% EtOAc/Hexane)

出典と根拠

ORDレコード
ord-dc25b2505ef64d599f17c99d024ef049
出典データセット
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08962856B2

反応ノート

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