4'-Amino-5'-methoxy-N,2'-dimethylbiphenyl-4-carboxamide → Methyl 2-(5-chloro-2-(5-methoxy-2-methyl-4'-(methylcarbamoyl)biphenyl-4-ylamino)pyrimidin-4-ylamino)benzoate

HRID 2091955ノート

反応式

HRID 2091955 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([O:13][CH3:14])=[O:12])[C:5]([Cl:19])=[CH:4][N:3]=1.[NH2:20][C:21]1[C:26]([O:27][CH3:28])=[CH:25][C:24]([C:29]2[CH:34]=[CH:33][C:32]([C:35]([NH:37][CH3:38])=[O:36])=[CH:31][CH:30]=2)=[C:23]([CH3:39])[CH:22]=1>CC(O)C.Cl>[Cl:19][C:5]1[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([O:13][CH3:14])=[O:12])=[N:7][C:2]([NH:20][C:21]2[C:26]([O:27][CH3:28])=[CH:25][C:24]([C:29]3[CH:34]=[CH:33][C:32]([C:35](=[O:36])[NH:37][CH3:38])=[CH:31][CH:30]=3)=[C:23]([CH3:39])[CH:22]=2)=[N:3][CH:4]=1

参加物

5

反応物 2

HCID 595867914'-Amino-5'-methoxy-N,2'-dimethylbiphenyl-4-carboxamide2 回HCID 86647794Methyl 2-((2,5-dichloropyrimidin-4-yl)amino)benzoate

生成物 1

HCID 68512573Methyl 2-(5-chloro-2-(5-methoxy-2-methyl-4'-(methylcarbamoyl)biphenyl-4-ylamino)pyrimidin-4-ylamino)benzoate

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid触媒HCID 3776Isopropanol溶媒

反応条件

温度
120 °C

実験手順

A mixture of methyl 2-(2,5-dichloropyrimidin-4-ylamino)benzoate (Step 1, 50 mg, 0.16 mmol) and 4′-amino-5′-methoxy-N,2′-dimethylbiphenyl-4-carboxamide (Intermediate 31, 46 mg, 0.16 mmol) in 2-propanol is treated with conc. aqueous HCl (4 drops). The mixture is sealed and heated in a microwave at 120° C. for 20 min. The mixture is concentrated, and the residue is partitioned between ethyl acetate and sodium carbonate aqueous solution. The organic layer is concentrated to afford crude methyl 2-(5-chloro-2-(5-methoxy-2-methyl-4′-(methylcarbamoyl)biphenyl-4-ylamino)pyrimidin-4-ylamino)benzoate as a brown solid. The obtained crude product is treated with neat cyclopropylamine (0.5 mL). The mixture is heated in a sealed tube at 110° C. overnight. The mixture is concentrated and the residue is applied to RP-HPLC for purification to afford the 4′-(5-chloro-4-(2-(cyclopropylcarbamoyl)phenylamino) pyrimidin-2-ylamino)-5′-methoxy-N,2′-dimethylbiphenyl-4-carboxamide as a white solid. 1H NMR (400 MHz, CD3OD) δ 8.75 (m, 1H), 8.49 (m, 1H), 8.15 (s, 1H), 7.91 (d, 2h0, 7.73-7.71 (m, 1H), 7.60 (m, 1H), 7.46 (d, 2H), 7.30-7.26 (m, 1H), 6.98 (s, 1H), 3.88 (s, 3H), 2.96 (s. 3H), 2.90-2.86 (m, 1H), 2.15 (s, 3H), 0.86-0.83 (m, 2H), 0.67-0.65 (m, 2H); ESMS m/z 557.2 (M+H+).

後処理

  1. customThe mixture is sealed
  2. concentrationThe mixture is concentrated
  3. customthe residue is partitioned between ethyl acetate and sodium carbonate aqueous solution
  4. concentrationThe organic layer is concentrated

出典と根拠

ORDレコード
ord-45d3eb3b15624197bb2ea26c42fd1534
出典データセット
uspto-grants-2013_05
特許番号
US08440681B2

反応ノート

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