Sodium Hydroxide → 5-(4-{5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)[1,3]thiazolo[5,4-b]pyridin-2-amine

HRID 241168ノート

反応式

HRID 241168 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[N:32]=[C:31]6[S:33][C:34]([NH:36]C(=O)C7C=CC=CC=7)=[N:35][C:30]6=[CH:29][CH:28]=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.[OH-].[Na+]>S(=O)(=O)(O)O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24]([C:27]5[N:32]=[C:31]6[S:33][C:34]([NH2:36])=[N:35][C:30]6=[CH:29][CH:28]=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:6][CH:7]=1

参加物

4

反応物 2

HCID 14798Sodium HydroxideHCID 86647850N-[5-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl]benzamide

生成物 1

HCID 573892595-(4-{5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)[1,3]thiazolo[5,4-b]pyridin-2-amine収率 37.2%

試薬・触媒・溶媒 1

HCID 1118Sulfuric Acid溶媒

実験手順

A solution of N-[5-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl]benzamide (84 mg, 0.14 mmol) in 70% aqueous sulfuric acid (2 mL) was heated to reflux for thirty minutes. On cooling to room temperature the pH of the mixture was adjusted to ˜5 by the addition of 50% aqueous sodium hydroxide. Concentration and purification by preparative reverse phase HPLC (0.1% aqueous ammonium acetate-acetonitrile) provided 5-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)[1,3]thiazolo[5,4-b]pyridin-2-amine (26 mg, 37%). 1H NMR (400 MHz, d6-DMSO): 8.44 (d, 1H), 8.36 (s, 1H), 8.08 (d, 1H), 8.01 (br s, 2H), 7.52 (dd, 1H), 7.16-7.10 (m, 4H), 7.00 (d, 1H), 6.90 (d, 1H), 4.48 (s, 2H), 4.28 (m, 2H), 3.96 (s, 2H), 3.76 (m, 2H), 2.14 (s, 3H). MS (EI) for C27H23FN6OS: 499 (MH+).

後処理

  1. temperatureto reflux for thirty minutes
  2. concentrationConcentration and purification by preparative reverse phase HPLC (0.1% aqueous ammonium acetate-acetonitrile)

出典と根拠

ORDレコード
ord-3166b971772c4438b57281e794b0cc1e
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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