Diisopropylethylamine → 4-(5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine

HRID 241191ノート

反応式

HRID 241191 の反応式
Cl.[CH3:2][C:3]1([CH3:21])[C:7]([CH3:9])([CH3:8])[O:6][B:5]([C:10]2[CH:11]=[CH:12][C:13]3[O:19][CH2:18][CH2:17][NH:16][CH2:15][C:14]=3[CH:20]=2)[O:4]1.CCN(C(C)C)C(C)C.Cl[C:32]1[C:37]([CH2:38][C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=2)=[C:36]([CH3:46])[N:35]=[CH:34][N:33]=1>CN1C(=O)CCC1>[F:45][C:42]1[CH:41]=[CH:40][C:39]([CH2:38][C:37]2[C:32]([N:16]3[CH2:15][C:14]4[CH:20]=[C:10]([B:5]5[O:4][C:3]([CH3:21])([CH3:2])[C:7]([CH3:8])([CH3:9])[O:6]5)[CH:11]=[CH:12][C:13]=4[O:19][CH2:18][CH2:17]3)=[N:33][CH:34]=[N:35][C:36]=2[CH3:46])=[CH:44][CH:43]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 668206297-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine hydrochlorideHCID 866478404-Chloro-5-(4-fluorobenzyl)-6-methylpyrimidine

生成物 1

HCID 668205164-(5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine収率 79.5%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
120 °C

実験手順

To a solution of 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine hydrochloride (1.4 g, 4.5 mmol) and DIPEA (6.4 mL, 37 mmol) in NMP (24 mL) was added and 4-chloro-5-(4-fluorobenzyl)-6-methylpyrimidine (reagent preparation 5) (1.7 g, 7.3 mmol). The resulting mixture was heated (120° C.) for 12 h and then partitioned between ethyl acetate (100 mL) and 1N aqueous hydrochloric acid (50 mL). The organic layer was washed with additional 1N aqueous hydrochloric acid (50 mL), brine (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated. Column chromatography on silica (0-30% ethyl acetate/hexanes) provided 4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine (1.7 g, 47% yield) as a white foam. MS (EI) for C27H31BFN3O3: 476 (MH+).

後処理

  1. custompartitioned between ethyl acetate (100 mL) and 1N aqueous hydrochloric acid (50 mL)
  2. washThe organic layer was washed with additional 1N aqueous hydrochloric acid (50 mL), brine (50 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-f958011dc0a54628b1a6f1fdec9bd212
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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