Hydrochloric Acid → 7-[5-Chloro-4-(2-methylcarbamoyl-phenylamino)-pyrimidin-2-ylamino]-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid dimethylamide

HRID 1687133ノート

反応式

HRID 1687133 の反応式
[CH3:1][N:2]([CH3:17])[C:3]([N:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[C:13]([NH2:16])[CH:14]=[CH:15][C:8]=2[CH2:7][CH2:6]1)=[O:4].Cl[C:19]1[N:24]=[C:23]([NH:25][C:26]2[CH:35]=[CH:34][CH:33]=[CH:32][C:27]=2[C:28]([NH:30][CH3:31])=[O:29])[C:22]([Cl:36])=[CH:21][N:20]=1.Cl.O1CCOCC1>CC(O)C>[CH3:1][N:2]([CH3:17])[C:3]([N:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[C:13]([NH:16][C:19]3[N:24]=[C:23]([NH:25][C:26]4[CH:35]=[CH:34][CH:33]=[CH:32][C:27]=4[C:28](=[O:29])[NH:30][CH3:31])[C:22]([Cl:36])=[CH:21][N:20]=3)[CH:14]=[CH:15][C:8]=2[CH2:7][CH2:6]1)=[O:4]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamideHCID 672642137-Amino-1,2,4,5-tetrahydro-benzo[d]azepin-3-carboxylic acid dimethylamide

生成物 1

HCID 668296317-[5-Chloro-4-(2-methylcarbamoyl-phenylamino)-pyrimidin-2-ylamino]-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid dimethylamide収率 81%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
120 °C

実験手順

7-Amino-1,2,4,5-tetrahydro-benzo[d]azepin-3-carboxylic acid dimethylamide (80 mg, 0.343 mmol, 1.0 eq) and 2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (112 mg, 0.378 mmol, 1.1 eq) were dissolved in IPA (3 mL). 4.0 M HCl in dioxane (94.5 μL, 0.378 mmol, 1.1 eq) was added and the reaction was heated at 120° C. in a microwave for 10 minutes. The reaction was then concentrated under reduced pressure and the residue was taken up in CH2Cl2 (20 mL) and washed with sat. NaHCO3 (20 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by basic alumina chromatography using a gradient of 0-10% MeOH/CH2Cl2 as the eluting solvent to obtain 7-[5-chloro-4-(2-methylcarbamoyl-phenylamino)-pyrimidin-2-ylamino]-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid dimethylamide as a yellow foam (137 mg, 81%). LCMS (m/e) 494 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 11.08 (s, 1H), 8.66 (d, 1H, J=8.4 Hz), 8.11 (s, 1H), 7.51 (d, 1H, J=7.8 Hz), 7.50-7.40 (m, 1H), 7.40 (s, 1H), 7.30-7.25 (m, 1H), 7.14-7.02 (m, 2H), 6.93 (s, 1H), 6.32-6.21 (m, 1H), 3.46-3.38 (m, 4H), 3.05 (d, 3H, J=4.8 Hz), 2.98-2.90 (m, 4H), 2.87 (s, 3H), 2.86 (s, 3H).

後処理

  1. concentrationThe reaction was then concentrated under reduced pressure
  2. washwashed with sat. NaHCO3 (20 mL)
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by basic alumina chromatography

出典と根拠

ORDレコード
ord-729a445211564f6abfe7b9b3d99120d0
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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