Diisopropylethylamine → (S)-5-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide

HRID 73745

反応式

HRID 73745 の反応式
CCN(C(C)C)C(C)C.[Br:10][C:11]1[C:12](Cl)=[N:13][CH:14]=[C:15]([CH:30]=1)[C:16]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:26]([Cl:29])([F:28])[F:27])=[CH:21][CH:20]=1)=[O:17].[NH:32]1[CH2:36][CH2:35][C@H:34]([OH:37])[CH2:33]1>CC(O)C.CCOC(C)=O>[Br:10][C:11]1[C:12]([N:32]2[CH2:36][CH2:35][C@H:34]([OH:37])[CH2:33]2)=[N:13][CH:14]=[C:15]([CH:30]=1)[C:16]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:26]([Cl:29])([F:28])[F:27])=[CH:21][CH:20]=1)=[O:17]

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 2733874(3S)-pyrrolidin-3-olHCID 725460895-bromo-6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)nicotinamide

生成物 1

HCID 86702602(S)-5-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide

試薬・触媒・溶媒 2

HCID 3776Isopropanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
140 °C

実験手順

DIPEA (190 μL, 1.1 mmol) was added to a solution of 5-bromo-6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)nicotinamide (Stage 9.3, 206 mg, 0.5 mmol) and (S)-pyrrolidin-3-ol (52.3 mg, 0.6 mmol) in iPrOH (500 μL) in a vial, which was sealed and heated at 140° C. for 1 h. After cooling at RT, the RM was dissolved in EtOAc, washed with 0.5 M aq. HCl and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (RediSep® Silica gel column, n-heptane/EtOAc from 20 to 100% EtOAc) to afford the title compound as a white crystalline powder. HPLC (Condition 4) tR=5.59 min, UPLC-MS (Condition 3) tR=1.17 min, m/z=462.0/464.1 [M+H]+.

後処理

  1. customwas sealed
  2. temperatureAfter cooling at RT
  3. washwashed with 0.5 M aq. HCl and brine
  4. dry with materialdried over Na2SO4
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give the crude product which
  7. customwas purified by flash chromatography (RediSep® Silica gel column, n-heptane/EtOAc from 20 to 100% EtOAc)

出典と根拠

ORDレコード
ord-fc2b0494a808430399dc0d072e9b685e
出典データセット
uspto-grants-2014_09
特許番号
US08829195B2

関連ノート

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