Hydrochloric Acid → 6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-amine

HRID 241195ノート

反応式

HRID 241195 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24]([C:27]5[CH:28]=[C:29]6[NH:35][C:34]([NH:36]C(=O)OC)=[N:33][C:30]6=[N:31][CH:32]=5)[CH:25]=[CH:26][C:20]=4[O:19][CH2:18][CH2:17]3)=[N:11][CH:12]=[N:13][C:14]=2[CH3:15])=[CH:4][CH:3]=1.Cl>CO.[OH-].[K+]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24]([C:27]5[CH:28]=[C:29]6[NH:35][C:34]([NH2:36])=[N:33][C:30]6=[N:31][CH:32]=5)[CH:25]=[CH:26][C:20]=4[O:19][CH2:18][CH2:17]3)=[N:11][CH:12]=[N:13][C:14]=2[CH3:15])=[CH:4][CH:3]=1

参加物

5

反応物 2

HCID 313Hydrochloric AcidHCID 59586590methyl[6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate

生成物 1

HCID 595861736-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-amine収率 67%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 14797Potassium Hydroxide溶媒

反応条件

温度
65 °C

実験手順

A mixture of methyl [6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate (15 mg, 0.028 mmol) in methanol and 2 M aqueous potassium hydroxide (1:1, 2 mL) was stirred at 65° C. for 18 hours. The reaction mixture was cooled, adjusted to pH 10 with 2 N hydrochloric acid, concentrated, diluted with ethyl acetate (10 mL), washed with brine solution (5 mL), dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative reverse phase HPLC to give 6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-amine (8.9 mg, 67% yield). 1H NMR (400 MHz, DMSO-D6): 8.46 (1H), 8.02 (br, 1H), 7.47 (d, 1H), 7.39 (dd, 1H), 7.10 to 6.96 (m, 5H), 7.75 (br, 1H), 4.53 (s, 2H), 4.30 (m, 2H), 4.00 (s, 2H), 3.89 (m, 2H), 2.22 (s, 3H), MS (EI) for C27H24FN7O: 428 (MH+).

後処理

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated
  3. additiondiluted with ethyl acetate (10 mL)
  4. washwashed with brine solution (5 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by preparative reverse phase HPLC

出典と根拠

ORDレコード
ord-dac38d1aaaf9413ea67fd156210765ac
出典データセット
uspto-grants-2014_02
特許番号
US08648066B2

反応ノート

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