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

HRID 73745

반응식

HRID 73745 반응식
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]

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 3776Isopropanol용매HCID 8857Ethyl Acetate용매

반응 조건

온도
140 °C

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-fc2b0494a808430399dc0d072e9b685e
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08829195B2

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