(Diethoxyphosphinyl)acetic acid → Diethyl(2-{4-[(3-chloro-4-fluorophenyl)amino]-5,8-dihydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-7(6H)-yl}-2-oxoethyl)phosphonate

HRID 38515

반응식

HRID 38515 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[C:18]4[CH2:19][CH2:20][NH:21][CH2:22][C:17]=4[S:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8].[CH2:23]([O:25][P:26]([CH2:31][C:32](O)=[O:33])([O:28][CH2:29][CH3:30])=[O:27])[CH3:24].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[CH2:29]([O:28][P:26]([CH2:31][C:32]([N:21]1[CH2:20][CH2:19][C:18]2[C:11]3[C:10]([NH:9][C:4]4[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=4)=[N:15][CH:14]=[N:13][C:12]=3[S:16][C:17]=2[CH2:22]1)=[O:33])(=[O:27])[O:25][CH2:23][CH3:24])[CH3:30]

참가 물질

6

반응물 4

HCID 36704(Diethoxyphosphinyl)acetic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 58116889(3-Chloro-4-fluoro-phenyl)-(5,6,7,8-tetrahydro-9-thia-1,3,7-triaza-fluoren-4-yl)-amine

생성물 1

HCID 58116908Diethyl(2-{4-[(3-chloro-4-fluorophenyl)amino]-5,8-dihydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-7(6H)-yl}-2-oxoethyl)phosphonate수율 94%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

N-(3-Chloro-4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4-amine from Example 12A (3.00 g, 8.96 mmol) and (diethoxyphosphoryl)acetic acid (2.46 g, 12.5 mmol) were dissolved in DMF (60 mL). DIPEA (3.47 g, 26.9 mmol) and TBTU (4.32 g, 13.4 mmol) were added, and the reaction was stirred overnight at rt. Subsequently, the mixture was concentrated in vacuo, and the residue was dissolved in ethyl acetate. The solution was extracted with 1 M aqueous sodium hydroxide solution, dried over sodium sulfate, and the solvent was removed in vacuo. The residue was triturated with tert-butyl methyl ether. The precipitate was collected by suction filtration to yield 4.31 g (94%) of the title compound as white crystals.

후처리

  1. concentrationSubsequently, the mixture was concentrated in vacuo
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. extractionThe solution was extracted with 1 M aqueous sodium hydroxide solution
  4. dry with materialdried over sodium sulfate
  5. customthe solvent was removed in vacuo
  6. customThe residue was triturated with tert-butyl methyl ether
  7. filtrationThe precipitate was collected by suction filtration

출처 및 근거

ORD 기록
ord-be2e8afd5eaf4df0898f1e52458c7562
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524722B2

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