7-Amino-1,1-dimethyl-1,2,4,5-tetrahydrobenzo[c]azepin-3-one → 2-(2-(3-(3-amino-3-oxopropyl)-4-(prop-1-en-2-yl)phenylamino)-5-chloropyrimidin-4-ylamino)-3-fluoro-N-methylbenzamide

HRID 1688117ノート

反応式

HRID 1688117 の反応式
[NH2:1][C:2]1[CH:15]=[CH:14][C:5]2[C:6]([CH3:13])([CH3:12])[NH:7][C:8](=[O:11])[CH2:9][CH2:10][C:4]=2[CH:3]=1.Cl[C:17]1[N:22]=[C:21]([NH:23][C:24]2[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:25]=2[C:26]([NH:28][CH3:29])=[O:27])[C:20]([Cl:35])=[CH:19][N:18]=1>Cl.O1CCOCC1.CC(O)C>[NH2:7][C:8](=[O:11])[CH2:9][CH2:10][C:4]1[CH:3]=[C:2]([NH:1][C:17]2[N:22]=[C:21]([NH:23][C:24]3[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:25]=3[C:26]([NH:28][CH3:29])=[O:27])[C:20]([Cl:35])=[CH:19][N:18]=2)[CH:15]=[CH:14][C:5]=1[C:6]([CH3:13])=[CH2:12]

参加物

5

反応物 2

HCID 672644267-Amino-1,1-dimethyl-1,2,4,5-tetrahydrobenzo[c]azepin-3-oneHCID 717421912-(2,5-Dichloropyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide

生成物 1

HCID 672643982-(2-(3-(3-amino-3-oxopropyl)-4-(prop-1-en-2-yl)phenylamino)-5-chloropyrimidin-4-ylamino)-3-fluoro-N-methylbenzamide

試薬・触媒・溶媒 2

HCID 204431481,4-Dioxane hydrochloride触媒HCID 3776Isopropanol溶媒

反応条件

温度
120 °C

実験手順

A mixture of 7-amino-1,1-dimethyl-1,2,4,5-tetrahydrobenzo[c]azepin-3-one (40 mg), 2-(2,5-dichloropyrimidin-4-ylamino)-3-fluoro-N-methylbenzamide (50 mg), and 2 drops of 4 N HCl/dioxane in IPA (3 mL) were microwave-heated at 120° C. for 1.5 hours. The mixture was concentrated to afford crude 2-(2-(3-(3-amino-3-oxopropyl)-4-(prop-1-en-2-yl)phenylamino)-5-chloropyrimidin-4-ylamino)-3-fluoro-N-methylbenzamide. The crude mixture was stirred for 4 hours in TFA and concentrated. Purification by semi-preparative HPLC provided 2-(5-chloro-2-(1,1-dimethyl-3-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-ylamino)pyrimidin-4-ylamino)-3-fluoro-N-methylbenzamide (45.7 mg) as a TFA salt: 1H NMR (300 MHz, CD3OD) δ 8.3 (s, 1H), 7.7-7.5 (m, 3H), 7.65 (s, 1H, slowly exchanging NH), 7.4 (d, 1H), 7.32 (d, 1H), 7.28 (dd, 1H), 3.0 (m, 2H), 3.0 (s, 3H), 2.7 (m, 2H), 1.8 (s, 6H).

後処理

  1. concentrationThe mixture was concentrated

出典と根拠

ORDレコード
ord-0cd97495e40742ff999713f7f6a57cd5
出典データセット
uspto-grants-2012_04
特許番号
US08148391B2

反応ノート

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