(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

Reaction equation

HRID 38515 reaction equation
[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]

Participants

6

Reactant 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

Product 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)phosphonateYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-be2e8afd5eaf4df0898f1e52458c7562
Source dataset
uspto-grants-2013_09
Patent number
US08524722B2

Linked notes

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