Methanol → N-(3-Chloro-4-fluorophenyl)-7-[(2E)-3-(1-methylpiperidin-2-yl)prop-2-enoyl]-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amine

HRID 38598Notes

Reaction equation

HRID 38598 reaction equation
C(OP([CH2:9][C:10]([N:12]1[CH2:33][CH2:32][C:15]2[C:16]3[C:21]([NH:22][C:23]4[CH:28]=[CH:27][C:26]([F:29])=[C:25]([Cl:30])[CH:24]=4)=[N:20][CH:19]=[N:18][C:17]=3[S:31][C:14]=2[CH2:13]1)=[O:11])(=O)OCC)C.[H-].[Na+].CO.[CH2:38]1[CH2:42]O[CH2:40][CH2:39]1>>[Cl:30][C:25]1[CH:24]=[C:23]([NH:22][C:21]2[C:16]3[C:15]4[CH2:32][CH2:33][N:12]([C:10](=[O:11])/[CH:9]=[CH:9]/[CH:10]5[CH2:42][CH2:38][CH2:39][CH2:40][N:12]5[CH3:13])[CH2:13][C:14]=4[S:31][C:17]=3[N:18]=[CH:19][N:20]=2)[CH:28]=[CH:27][C:26]=1[F:29]

Participants

5

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 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)phosphonate

Product 1

HCID 58117000N-(3-Chloro-4-fluorophenyl)-7-[(2E)-3-(1-methylpiperidin-2-yl)prop-2-enoyl]-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amineYield 24%

Conditions

Temperature
-78 °C

Procedure

In a separate flask, 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 from Example 13A (400 mg, 0.78 mmol) was dissolved in THF (1.0 mL). The solution was cooled to −78° C., and sodium hydride (60% in mineral oil, 31 mg, 0.78 mmol) was added. The mixture was stirred for 15 min, then solution A was added slowly. The mixture was slowly warmed to rt and stirred overnight. Methanol was added, and the solvents were removed in vacuo. The residue was purified by preparative HPLC to yield 90 mg (24%) of the title compound.

Workup

  1. temperatureThe mixture was slowly warmed to rt
  2. stirringstirred overnight
  3. customthe solvents were removed in vacuo
  4. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-327b830f672143a1b377bbac723ed663
Source dataset
uspto-grants-2013_09
Patent number
US08524722B2

Reaction notes

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