Acetic Acid → 6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-[4-(4-methyl-piperazin-1-yl)-butyl]-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

HRID 216450

反応式

HRID 216450 の反応式
[CH:1]1([CH2:4][O:5][NH:6][C:7]([C:9]2[C:22]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([Br:30])=[CH:26][C:25]=3[CH3:31])=[C:21]([F:32])[C:12]3[N:13]=[CH:14][N:15]([CH2:16][CH2:17][CH2:18][CH:19]=O)[C:11]=3[CH:10]=2)=[O:8])[CH2:3][CH2:2]1.[CH3:33][N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C[N+](C)(C)C>CC#N.C(OCC)(=O)C>[CH:1]1([CH2:4][O:5][NH:6][C:7]([C:9]2[C:22]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([Br:30])=[CH:26][C:25]=3[CH3:31])=[C:21]([F:32])[C:12]3[N:13]=[CH:14][N:15]([CH2:16][CH2:17][CH2:18][CH2:19][N:37]4[CH2:38][CH2:39][N:34]([CH3:33])[CH2:35][CH2:36]4)[C:11]=3[CH:10]=2)=[O:8])[CH2:2][CH2:3]1

参加物

7

反応物 4

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 13696215Tetramethylammonium Triacetoxyborohydride (>90%)HCID 866171186-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-(4-oxo-butyl)-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

生成物 1

HCID 111808016-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-[4-(4-methyl-piperazin-1-yl)-butyl]-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide収率 69%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-(4-oxo-butyl)-3H benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide 11n (15 mg, 0.030 mmol) is dissolved in MeCN (500 μL) and methylpiperazine (10 μl, 0.089 mmol) is added followed by AcOH (5 μL, 0.089 mmol). After 5 minutes, tetramethylammonium triacetoxyborohydride (12 mg, 0.045 mmol) is added. After 5 minutes, the reaction mixture is diluted with ethyl acetate and washed with NaHCO3 and brine. The organic layer is dried (Na2SO4) and concentrated under reduced pressure to give 12 mg (69%) of pure desired product as a white solid. MS APCI (−) m/z 587, 585 (M−1 Br pattern) detected; 1H NMR (400 MHz, CDCl3) δ 7.99 (s, 1H), 7.98 (s, 1H), 7.30 (d, 1H), 7.08 (dd, 1H), 6.30 (d, 1H), 6.1 (broad singlet, 1H), 4.26 (t, 2H), 3.64 (d, 2H), 3.37 (s, 1H), 2.45 (broad, 8H), 2.41 (s, 3H), 2.38 (t, 2H), 2.28 (s, 3H), 1.95 (quin, 2H), 1.55 (quin, 2H), 0.98 (m, 1H), 0.50 (qt, 2H), 0.22 (qt, 2H).

後処理

  1. waitAfter 5 minutes
  2. washwashed with NaHCO3 and brine
  3. dry with materialThe organic layer is dried (Na2SO4)
  4. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-a11ba821e1f4444dbc54283bc4374862
出典データセット
uspto-grants-2012_06
特許番号
US08193229B2

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