(E)-N'-(3-cyano-6-isopropylpyridin-2-yl)-N,N-dimethylformimidamide → {4-[4-(5-Bromo-pyridin-2-ylcarbamoyl)-2-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-phenylsulfanyl]-phenyl}-carbamic acid 9H-fluoren-9-ylmethyl ester

HRID 605061ノート

反応式

HRID 605061 の反応式
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:42])[NH:17][C:18]3[CH:23]=[CH:22][C:21]([S:24][C:25]4[CH:30]=[CH:29][C:28]([C:31](=[O:40])[NH:32][C:33]5[CH:38]=[CH:37][C:36]([Br:39])=[CH:35][N:34]=5)=[CH:27][C:26]=4[NH2:41])=[CH:20][CH:19]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C([C:45]1[C:46]([N:54]=[CH:55][N:56]([CH3:58])C)=[N:47][C:48]([CH:51]([CH3:53])[CH3:52])=[CH:49][CH:50]=1)#N>C(O)(=O)C>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:42])[NH:17][C:18]3[CH:19]=[CH:20][C:21]([S:24][C:25]4[CH:30]=[CH:29][C:28]([C:31](=[O:40])[NH:32][C:33]5[CH:38]=[CH:37][C:36]([Br:39])=[CH:35][N:34]=5)=[CH:27][C:26]=4[NH:41][C:58]4[C:45]5[CH:50]=[CH:49][C:48]([CH:51]([CH3:52])[CH3:53])=[N:47][C:46]=5[N:54]=[CH:55][N:56]=4)=[CH:22][CH:23]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

参加物

4

反応物 2

HCID 66808369(E)-N'-(3-cyano-6-isopropylpyridin-2-yl)-N,N-dimethylformimidamideHCID 67040714{4-[2-Amino-4-(5-bromo-pyridin-2-ylcarbamoyl)-phenylsulfanyl]-phenyl}-carbamic acid 9H-fluoren-9-ylmethyl ester

生成物 1

HCID 67040609{4-[4-(5-Bromo-pyridin-2-ylcarbamoyl)-2-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-phenylsulfanyl]-phenyl}-carbamic acid 9H-fluoren-9-ylmethyl ester収率 58.2%

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

反応条件

温度
150 °C

実験手順

A mixture of the product from Example 17D (23.9 g, 37.4 mmol) and N′-(3-cyano-6-isopropyl-pyridin-2-yl)-N,N-dimethyl-formamidine (9.71 g, 44.9 mmol, 1.2 eq) in 450 mL of glacial acetic acid was heated in an oil bath at 150° C. for 2 h and then cooled to room temperature. The reaction mixture was evaporated in vacuo and the residue was dissolved in approximately 70 mL of dichloromethane. This material was purified by silica gel chromatography using a Biotage Flash 75M cartridge, eluting first with 1:4 ethyl acetate/dichloromethane followed by 98:2 dichloromethane/methanol. The resulting product triturated with dichloromethane and filtered to provide the title compound as a white solid (17.6 g, 58%).

後処理

  1. temperaturecooled to room temperature
  2. customThe reaction mixture was evaporated in vacuo
  3. dissolutionthe residue was dissolved in approximately 70 mL of dichloromethane
  4. customThis material was purified by silica gel chromatography
  5. washeluting first with 1:4 ethyl acetate/dichloromethane
  6. customThe resulting product triturated with dichloromethane
  7. filtrationfiltered

出典と根拠

ORDレコード
ord-2fa67cb2020146cb9cc6dbc01988a0b8
出典データセット
uspto-grants-2011_03
特許番号
US07910595B2

反応ノート

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