Triethylamine → ethyl (E)-7-[2-[5-(2,4-diamino-pyrimidin-5-ylmethyl)-2,3-dimethoxy-phenyl]-vinyl]-1-cyclopropyl-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylate

HRID 963434

反応式

HRID 963434 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:15]=[C:16](I)[C:17]=1[O:18][CH3:19])[CH2:6][C:7]1[C:8]([NH2:14])=[N:9][C:10]([NH2:13])=[N:11][CH:12]=1.[CH:21]1([N:24]2[C:33]3[C:28](=[CH:29][C:30]([F:37])=[C:31]([CH:35]=[CH2:36])[C:32]=3[F:34])[C:27](=[O:38])[C:26]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:25]2)[CH2:23][CH2:22]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[NH2:13][C:10]1[N:9]=[C:8]([NH2:14])[C:7]([CH2:6][C:5]2[CH:4]=[C:3]([O:2][CH3:1])[C:17]([O:18][CH3:19])=[C:16](/[CH:36]=[CH:35]/[C:31]3[C:32]([F:34])=[C:33]4[C:28]([C:27](=[O:38])[C:26]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:25][N:24]4[CH:21]4[CH2:23][CH2:22]4)=[CH:29][C:30]=3[F:37])[CH:15]=2)=[CH:12][N:11]=1

参加物

8

反応物 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 111010945-(3,4-Dimethoxy-5-iodo-benzyl)pyrimidine-2,4-diamineHCID 15636884Ethyl 1-cyclopropyl-6,8-difluoro-7-vinyl-4-oxo-1,4-dihydro-quinoline-3-carboxylate

生成物 1

HCID 86752726ethyl (E)-7-[2-[5-(2,4-diamino-pyrimidin-5-ylmethyl)-2,3-dimethoxy-phenyl]-vinyl]-1-cyclopropyl-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylate収率 49%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 193 mg of 5-(3,4-dimethoxy-5-iodo-benzyl)-pyrimidine-2,4-diamine, 224 mg of ethyl 1-cyclopropyl-6,8-difluoro-7-vinyl-4-oxo-1,4-dihydro-quinoline-3-carboxylate (J. Heterocyclic Chem., 28, 1581 (1991)), 26 mg of triphenylphosphine, 0.084 ml of triethylamine and 11.2 mg of palladium acetate in 2 ml of dimethylformamide is heated at 100° for 5 hrs. The reaction mixture is cooled to room temperature, poured into 50 ml of water and extracted twice with 25 ml of ethyl acetate each time. The organic phases are washed twice with 25 ml of 2N aqueous hydrochloric acid each time. The hydrochloric acid phases are made basic with sodium bicarbonate and extracted three times with 25 ml of methylene chloride each time. The combined organic phases are washed with 25 ml of water, dried over magnesium sulphate and concentrated. The crude product is recrystallized from methylene chloride/diethyl ether. 140 mg (49%) of ethyl (E)-7-[2-[5-(2,4-diamino-pyrimidin-5-ylmethyl)-2,3-dimethoxy-phenyl]-vinyl]-1-cyclopropyl-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylate are obtained as a yellowish solid. Mass spectrum (ISP): 578 (M++H, 100%).

後処理

  1. temperatureis heated at 100° for 5 hrs
  2. extractionextracted twice with 25 ml of ethyl acetate each time
  3. washThe organic phases are washed twice with 25 ml of 2N aqueous hydrochloric acid each time
  4. extractionextracted three times with 25 ml of methylene chloride each time
  5. washThe combined organic phases are washed with 25 ml of water
  6. dry with materialdried over magnesium sulphate
  7. concentrationconcentrated
  8. customThe crude product is recrystallized from methylene chloride/diethyl ether

出典と根拠

ORDレコード
ord-66fbcdabaca74c33a36ae53c009e6c5b
出典データセット
uspto-grants-1998_06
特許番号
US05763450

関連ノート

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