Ammonium → (R)-5-(4,5-Dihydro-1H-imidazol-2-yl)-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 525738노트

반응식

HRID 525738 반응식
[C:1]([C:3]1[C:4]([N:23]2[CH2:27][CH2:26][C@@H:25]([OH:28])[CH2:24]2)=[N:5][CH:6]=[C:7]([CH:22]=1)[C:8]([NH:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]([F:21])([F:20])[F:19])=[CH:13][CH:12]=1)=[O:9])#[N:2].OS([O-])=O.[Na+].[CH2:34](N)[CH2:35][NH2:36].[NH4+]>CCOC(C)=O>[NH:2]1[CH2:34][CH2:35][N:36]=[C:1]1[C:3]1[C:4]([N:23]2[CH2:27][CH2:26][C@@H:25]([OH:28])[CH2:24]2)=[N:5][CH:6]=[C:7]([CH:22]=1)[C:8]([NH:10][C:11]1[CH:12]=[CH:13][C:14]([O:17][C:18]([F:19])([F:20])[F:21])=[CH:15][CH:16]=1)=[O:9]

참가 물질

6

반응물 4

HCID 223AmmoniumHCID 3301EthylenediamineHCID 23665763Sodium BisulfiteHCID 89907102(R)-5-cyano-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

생성물 1

HCID 89907994(R)-5-(4,5-Dihydro-1H-imidazol-2-yl)-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

A stirred mixture of (R)-5-cyano-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 70.2, 1 g, 2.55 mmol), NaHSO3 (0.953 g, 15.3 mmol) and ethylenediamine (7.66 g, 1.27 mmol) was treated dropwise with 40% aq. ammonium silfide (4.34 mL, 25.5 mmol) and heated at 100° C. for 18 h. The cooled mixture was treated with EtOAc, washed with sat. aq. NaHCO3 and brine, was dried over anhydrous Na2SO4 and the solvent was evaporated off under reduced pressure. The crude product was purified by flash chromatography (RediSep® Silica gel column, DCM/(5% aq. NH3 in MeOH) from 0 to 40% (5% aq. NH3 in MeOH)) to afford the product as a pale-yellow solid. HPLC (Condition 4) tR=3.89 min, UPLC-MS (Condition 8) tR=0.72 min, m/z=436.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.67-1.98 (m, 3H) 3.40-3.75 (m, 8H) 4.30 (br. s, 1H) 4.91 (br. s, 1H) 7.31 (d, J=8.60 Hz, 2H) 7.78-7.91 (m, 2H) 8.06 (d, J=2.35 Hz, 1H) 8.71 (d, J=2.35 Hz, 1H) 10.17 (s, 1H).

후처리

  1. washwashed with sat. aq. NaHCO3 and brine
  2. dry with materialwas dried over anhydrous Na2SO4
  3. customthe solvent was evaporated off under reduced pressure
  4. customThe crude product was purified by flash chromatography (RediSep® Silica gel column, DCM/(5% aq. NH3 in MeOH) from 0 to 40% (5% aq. NH3 in MeOH))

출처 및 근거

ORD 기록
ord-a8875911c93b463a90af15bc332da7be
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340537B2

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