Diisopropylethylamine → 6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-pent-4-enyl-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

HRID 216447

反応式

HRID 216447 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:24]([OH:26])=O)=[CH:11][C:12]3[N:16]([CH2:17][CH2:18][CH2:19][CH:20]=[CH2:21])[CH:15]=[N:14][C:13]=3[C:22]=2[F:23])=[C:4]([CH3:27])[CH:3]=1.CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=[CH:58][CH:59]=[CH:60][C:55]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl.C1([N:74](C)[OH:75])CC1>C1COCC1.C(Cl)Cl.C(OCC)(=O)C>[CH:59]1([CH2:58][O:75][NH:74][C:24]([C:10]2[C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=3[CH3:27])=[C:22]([F:23])[C:13]3[N:14]=[CH:15][N:16]([CH2:17][CH2:18][CH2:19][CH:20]=[CH2:21])[C:12]=3[CH:11]=2)=[O:26])[CH2:60][CH2:55]1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 211142136-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-pent-4-enyl-3H-benzoimidazole-5-carboxylic acidHCID 21114231Cyclopropyl methyl hydroxylamine hydrochloride

生成物 1

HCID 588906146-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-pent-4-enyl-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide収率 70%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 21919333Tetrahydrofurane dichloromethane溶媒

実験手順

6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-pent-4-enyl-3H-benzoimidazole-5-carboxylic acid 10d (0.390 g, 0.902 mmol) is dissolved in 1:1 THF/methylene chloride (6 mL) and Hunig's base (0.346 mL, 1.985 mmol) is added followed by PyBOP (0.563 g, 1.083 mmol). After 10 minutes, cyclopropyl methyl hydroxylamine hydrochloride (0.134 g, 1.083 mmol) is added. After 16 hours, the reaction mixture is diluted with ethyl acetate and washed with 0.1 N HCl, saturated NaHCO3, and brine. The organic layer is dried (Na2SO4) and concentrated under reduced pressure. The crude yellow residue is purified by FCC eluted with ethyl acetate to give 0.315 g (70%) pure desired product as a yellow solid: MS APCI (+) m/z 503, 501 (M+1 Br pattern) detected.

後処理

  1. additionis added
  2. waitAfter 16 hours
  3. washwashed with 0.1 N HCl, saturated NaHCO3, and brine
  4. dry with materialThe organic layer is dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe crude yellow residue is purified by FCC
  7. washeluted with ethyl acetate

出典と根拠

ORDレコード
ord-8d53df655d4c4b28869f68b35f770c39
出典データセット
uspto-grants-2012_06
特許番号
US08193229B2

関連ノート

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