Diisopropyl Ether → HCID 89907938, 화합물

HRID 525776노트

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HRID 525776 반응식
Cl[C:2]1[C:21]([C:22]2[NH:26][N:25]=[CH:24][CH:23]=2)=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([Cl:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1.[NH2:27][CH2:28][CH:29]([OH:33])[CH2:30][CH2:31][OH:32].CCN(C(C)C)C(C)C.O(C(C)C)C(C)C>CC(O)C>[Cl:19][C:16]([F:18])([F:17])[O:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][C:6](=[O:7])[C:5]2[CH:20]=[C:21]([C:22]3[NH:26][N:25]=[CH:24][CH:23]=3)[C:2]([NH:27][CH2:28][CH:29]([OH:33])[CH2:30][CH2:31][OH:32])=[N:3][CH:4]=2)=[CH:10][CH:11]=1

참가 물질

6

반응물 4

HCID 7914Diisopropyl EtherHCID 81531DiisopropylethylamineHCID 143256114-Aminobutane-1,3-diolHCID 722015896-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide

생성물 1

HCID 89907938HCID 89907938, 화합물

시약·촉매·용매 1

HCID 3776Isopropanol용매

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온도
130 °C

실험 절차

6-Chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide (Stage 48.1, 500 mg, 1.253 mmol), 4-aminobutane-1,3-diol (Stage 97.1, 152 mg, 1.447 mmol), DIPEA (0.667 mL, 3.82 mmol) and iPrOH (2 mL) were added to a MW vial, which was sealed, flushed with argon and stirred at 130° C. for 20 h. The RM was diluted with EtOAc and washed with water and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue which was treated with iPr2O and the resulting solid was filtered off and purified by flash chromatography (Silica gel column, 40 g, DCM/DCM-MeOH (9:1)) to afford the title compound as a white solid. UPLC-MS (Condition 8) tR=0.94 min, m/z=468 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1H NMR (400 MHz, DMSO-d6) δ ppm 1.46-1.74 (m, 2H) 3.44-3.58 (m, 3H) 3.64-3.72 (m, 1H) 3.77-3.90 (m, 1H) 4.40 (t, J=5.07 Hz, 1H) 4.82 (d, J=5.38 Hz, 1H) 6.96 (t, J=1.96 Hz, 1H) 7.36 (d, J=8.93 Hz, 2H) 7.83-7.99 (m, 3H) 8.41 (d, J=2.32 Hz, 1H) 8.65 (d, J=2.20 Hz, 1H) 9.04 (s, 1H) 10.21 (s, 1H) 13.21 (s, 1H).

후처리

  1. customwas sealed
  2. customflushed with argon
  3. additionThe RM was diluted with EtOAc
  4. washwashed with water and brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent was evaporated off under reduced pressure
  7. customto give a residue which
  8. filtrationthe resulting solid was filtered off
  9. custompurified by flash chromatography (Silica gel column, 40 g, DCM/DCM-MeOH (9:1))

출처 및 근거

ORD 기록
ord-95032601864046468870384312d1090c
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340537B2

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