Triethylamine → 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-{[methoxy-(2-methoxy-acetyl)-amino]-methyl}-benzamide

HRID 2038642

반응식

HRID 2038642 반응식
[CH3:1][O:2][CH2:3][C:4]([OH:6])=O.ON1C(=O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[F:31][C:32]1[C:33]([NH:50][C:51]2[CH:56]=[CH:55][C:54]([I:57])=[CH:53][C:52]=2[F:58])=[C:34]([CH:42]=[C:43]([CH2:46][NH:47][O:48][CH3:49])[C:44]=1[F:45])[C:35]([NH:37][O:38][CH2:39][CH2:40][OH:41])=[O:36].C(N(CC)CC)C>C(Cl)Cl.C1COCC1.C(OCC)(=O)C>[F:31][C:32]1[C:33]([NH:50][C:51]2[CH:56]=[CH:55][C:54]([I:57])=[CH:53][C:52]=2[F:58])=[C:34]([CH:42]=[C:43]([CH2:46][N:47]([O:48][CH3:49])[C:4](=[O:6])[CH2:3][O:2][CH3:1])[C:44]=1[F:45])[C:35]([NH:37][O:38][CH2:39][CH2:40][OH:41])=[O:36]

참가 물질

9

반응물 5

HCID 8471TriethylamineHCID 12251Methoxyacetic AcidHCID 730263-hydroxy-1,2,3-benzotriazin-4(3H)-oneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 115335813,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(methoxyamino-methyl)-benzamide

생성물 1

HCID 115705873,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-{[methoxy-(2-methoxy-acetyl)-amino]-methyl}-benzamide수율 34%

시약·촉매·용매 3

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of methoxyacetic acid (9.0 μL, 0.12 mmol) in methylene chloride (1 ml) were added 3-hydroxy-4-oxo-3,4-dihydro-1,2,3-benzotriazine (18.9 mg, 0.12 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (22.5 mg, 0.12 mmol), and the mixture was stirred for 3 hours. This solution was added dropwise to a solution of 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(methoxyamino-methyl)-benzamide (50.0 mg, 0.10 mmol) obtained in Example 15 in THF (3 ml), and triethylamine (40.9 μl, 0.29 mmol) was added thereto. The mixture was stirred for 15 hours. The reaction mixture was diluted with ethyl acetate (45 ml), and washed with saturated aqueous ammonium chloride (20 ml), and then with saturated brine (2×20 ml). The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resultant residue was purified by preparative TLC (CH2Cl2/MeOH (10:1)) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-{[methoxy-(2-methoxy-acetyl)-amino]-methyl}-benzamide (Compound F-6, 19.1 mg, 34%) as a colorless oil.

후처리

  1. additionwas added
  2. stirringThe mixture was stirred for 15 hours
  3. washwashed with saturated aqueous ammonium chloride (20 ml)
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resultant residue was purified by preparative TLC (CH2Cl2/MeOH (10:1))

출처 및 근거

ORD 기록
ord-fd43d396a3c04dadb8bb7319b43e6822
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575391B2

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