Tetrabutylammonium Fluoride → 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-((2-chlorophenyl)((S)-3-hydroxypyrrolidin-1-yl)methyl)-4-methylthiazol-2-yl)cyclopropanecarboxamide

HRID 1673141ノート

反応式

HRID 1673141 の反応式
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[S:17][C:18]([CH:22]([N:30]5[CH2:34][CH2:33][C@H:32]([O:35][Si](C(C)(C)C)(C)C)[CH2:31]5)[C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=5[Cl:29])=[C:19]([CH3:21])[N:20]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[S:17][C:18]([CH:22]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=5[Cl:29])[N:30]5[CH2:34][CH2:33][C@H:32]([OH:35])[CH2:31]5)=[C:19]([CH3:21])[N:20]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1

参加物

3

反応物 2

HCID 2724141Tetrabutylammonium FluorideHCID 86621216HCID 86621216、化合物

生成物 1

HCID 866212171-(benzo[d][1,3]dioxol-5-yl)-N-(5-((2-chlorophenyl)((S)-3-hydroxypyrrolidin-1-yl)methyl)-4-methylthiazol-2-yl)cyclopropanecarboxamide

実験手順

A mixture of 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) (400 mg, 0.64 mmol) and TBAF (1M in THF, 3.84 mL, 3.84 mmol) was stirred at room temperature for 5 h. The reaction was partitioned between H2O and EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated. The residue was adsorbed onto silica gel and purified by column chromatography (25-75% EtOAc/hexanes) to afford 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-((2-chlorophenyl)((S)-3-hydroxypyrrolidin-1-yl)methyl)-4-methylthiazol-2-yl)cyclopropanecarboxamide (Isomer A) as a pale yellow solid (245 mg, 75%, >99% de). 1H NMR (400 MHz, CDCl3) δ 8.41 (s, 1H), 7.85 (dd, J=8.1, 1.7 Hz, 1H), 7.29-7.26 (m, 2H), 7.14 (m, 1H), 6.88-6.84 (m, 2H), 6.79 (d, J=7.9 Hz, 1H), 6.00 (s, 2H), 5.07 (s, 1H), 4.30 (m, 1H), 2.79 (td, J=8.6, 5.8 Hz, 1H), 2.63-2.56 (m, 2H), 2.36 (s, 3H), 2.29 (td, J=9.0, 5.9 Hz, 1H), 2.15 (m, 1H), 1.85 (d, J=7.9 Hz, 1H), 1.78-1.65 (m, 3H), 1.18 (m, 2H); HPLC ret. time 2.70 min, 10-99% CH3CN, 5 min run; ESI-MS 512.5 m/z (MH+).

後処理

  1. customThe reaction was partitioned between H2O and EtOAc
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. custompurified by column chromatography (25-75% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-62240725125c4384aab8152b2be02a64
出典データセット
uspto-grants-2011_08
特許番号
US07999113B2

反応ノート

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