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

반응식

HRID 963434 반응식
[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

참가 물질

8

반응물 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

생성물 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-carboxylate수율 49%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-66fbcdabaca74c33a36ae53c009e6c5b
출처 데이터셋
uspto-grants-1998_06
특허 번호
US05763450

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