Diisopropylethylamine → (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(2,2-difluoroethylamino)propyl isoquinolin-3-ylcarbamate

HRID 416430ノート

反応式

HRID 416430 の反応式
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12](=[O:32])[O:13][CH2:14][C@@H:15]([N:18]([CH3:31])[C:19]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=2[Cl:30])=[O:20])[CH2:16][NH2:17])[N:2]=1.FC(F)(F)S(O[CH2:39][CH:40]([F:42])[F:41])(=O)=O.CCN(C(C)C)C(C)C>C1COCC1>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12](=[O:32])[O:13][CH2:14][C@@H:15]([N:18]([CH3:31])[C:19]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=2[Cl:30])=[O:20])[CH2:16][NH:17][CH2:39][CH:40]([F:42])[F:41])[N:2]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 57947642(S)-3-amino-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)propyl isoquinolin-3-ylcarbamate

生成物 1

HCID 57947556(S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(2,2-difluoroethylamino)propyl isoquinolin-3-ylcarbamate収率 56.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of (S)-3-amino-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)propyl isoquinolin-3-ylcarbamate (200 mg, 0.44 mmol) in THF (2.0 mL) were added 2,2-difluoroethyl trifluoromethanesulfonate (94 mg, 0.44 mmol) and DIEA (0.15 mL, 0.88 mmol) at RT The reaction mixture was stirred at RT for 30 min. The solvent was removed. The resulting residue was dissolved in MeOH and mixture was purified on RP-HPLC using a mixture of acetonitrile and water to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(2,2-difluoroethylamino)propyl isoquinolin-3-ylcarbamate (130 mg, 56% for two steps). LRMS (M+H+) m/z 524.2.

後処理

  1. customThe solvent was removed
  2. dissolutionThe resulting residue was dissolved in MeOH
  3. custommixture was purified on RP-HPLC
  4. additiona mixture of acetonitrile and water

出典と根拠

ORDレコード
ord-01dc562fe03a4881878999ccb26d16b2
出典データセット
uspto-grants-2012_01
特許番号
US08088793B2

反応ノート

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