Diisopropyl Ether → HCID 89907938、化合物

HRID 525776ノート

反応式

HRID 525776 の反応式
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

参加物

6

反応物 4

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

生成物 1

HCID 89907938HCID 89907938、化合物

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
130 °C

実験手順

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).

後処理

  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))

出典と根拠

ORDレコード
ord-95032601864046468870384312d1090c
出典データセット
uspto-grants-2016_05
特許番号
US09340537B2

反応ノート

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