Hydrochloric Acid → 2-[5-Chloro-2-(1-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-5-piperidin-1-yl-benzamide

HRID 1687150ノート

反応式

HRID 1687150 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:14][C:10]=2[C:11]([NH2:13])=[O:12])[C:5]([Cl:24])=[CH:4][N:3]=1.[NH2:25][C:26]1[CH:38]=[CH:37][C:29]2[N:30]([CH3:36])[C:31](=[O:35])[CH2:32][CH2:33][CH2:34][C:28]=2[CH:27]=1.Cl>COC(O)C.O1CCOCC1>[Cl:24][C:5]1[C:6]([NH:8][C:9]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:14][C:10]=2[C:11]([NH2:13])=[O:12])=[N:7][C:2]([NH:25][C:26]2[CH:38]=[CH:37][C:29]3[N:30]([CH3:36])[C:31](=[O:35])[CH2:32][CH2:33][CH2:34][C:28]=3[CH:27]=2)=[N:3][CH:4]=1

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 197602587-Amino-1-methyl-1,3,4,5-tetrahydro-benzo[B]azepin-2-oneHCID 866338852-(2,5-Dichloro-pyrimidin-4-ylamino)-5-piperidin-1-yl-benzamide

生成物 1

HCID 668299562-[5-Chloro-2-(1-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-5-piperidin-1-yl-benzamide収率 21.1%

試薬・触媒・溶媒 2

HCID 312751,4-Dioxane溶媒HCID 30156371-Methoxyethanol溶媒

反応条件

温度
120 °C

実験手順

2-(2,5-dichloro-pyrimidin-4-ylamino)-5-piperidin-1-yl-benzamide (50.1 mg, 0.137 mmol) and 7-amino-1-methyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (28.7 mg, 0.151 mmol) were slurried in methoxyethanol (2.0 mL) prior to adding ˜0.2 mL of 4N HCl in dioxane. This mixture was heated at 120° C. for 2 h. After quenching with saturated aqueous NaHCO3 solution (2 mL), the resulting precipitate was collected by filtration, successively washed water (5×2 mL) and ether (2×1 mL) to afford product (15 mg, 21%) as a yellow powder that had the following properties: mp: 295-297° C.; LC/MS (ESI+): 520 (M+H); 1H-NMR (DMSO-d6, 400 MHz): δ 11.20 (s, 1H), 9.45 (s, 1H), 8.42 (d, J=8.0, 1H), 8.28 (s, 1H), 8.15 (s, 1H), 7.65 (m, 2H), 7.52 (d, J=8.9, 1H), 7.30 (s, 1H), 7.20 (d, J=8.6, 1H), 7.05 (d, J=9.4, 1H), 3.20 (s, 3H), 3.18 (m, 4H), 2.65-2.20 (series of m, 6H), 1.65 (m, 4H), 1.55 (m, 2H).

後処理

  1. customAfter quenching with saturated aqueous NaHCO3 solution (2 mL)
  2. filtrationthe resulting precipitate was collected by filtration, successively washed water (5×2 mL) and ether (2×1 mL)

出典と根拠

ORDレコード
ord-cde7ff94001d4d7888981e40a87f5014
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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