Thionyl Chloride → 7-[(2E)-4-Chlorobut-2-enoyl]-N-(3,4-dichlorophenyl)-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amine

HRID 38546

Reaction equation

HRID 38546 reaction equation
Br[CH2:2]/[CH:3]=[CH:4]/[C:5]([OH:7])=O.S(Cl)([Cl:10])=O.[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:22]3[C:29]4[CH2:30][CH2:31][NH:32][CH2:33][C:28]=4[S:27][C:23]=3[N:24]=[CH:25][N:26]=2)[CH:16]=[CH:17][C:18]=1[Cl:19].CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:10][CH2:2]/[CH:3]=[CH:4]/[C:5]([N:32]1[CH2:31][CH2:30][C:29]2[C:22]3[C:21]([NH:20][C:15]4[CH:16]=[CH:17][C:18]([Cl:19])=[C:13]([Cl:12])[CH:14]=4)=[N:26][CH:25]=[N:24][C:23]=3[S:27][C:28]=2[CH2:33]1)=[O:7]

Participants

6

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 64364114-Bromocrotonic acidHCID 58116912(3,4-Dichloro-phenyl)-(5,6,7,8-tetrahydro-9-thia-1,3,7-triaza-fluoren-4-yl)-amine

Product 1

HCID 581168067-[(2E)-4-Chlorobut-2-enoyl]-N-(3,4-dichlorophenyl)-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amineYield 58.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2E)-4-Bromobut-2-enoic acid (1.33 g, 6.83 mmol) was dissolved in petroleum ether (25 mL). Thionylchloride (2.65 mL, 36.6 mmol) was added, and the mixture was heated to reflux for 4 h. The mixture was then concentrated in vacuo. Toluene was added and again removed in vacuo. The residue was dissolved in dichloromethane (14 mL). This solution was added to a solution of N-(3,4-dichlorophenyl)-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4-amine from Example 15A (2.00 g, 5.69 mmol) and DIPEA (1.25 g, 9.68 mmol) in DMF (20 mL) at −10° C. The mixture was warmed to rt and stirred overnight. The precipitate was collected by suction filtration and washed with water to yield 1.52 g of a solid, which was used in the next step without further purification or separation.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 4 h
  3. concentrationThe mixture was then concentrated in vacuo
  4. additionToluene was added
  5. customagain removed in vacuo
  6. dissolutionThe residue was dissolved in dichloromethane (14 mL)
  7. filtrationThe precipitate was collected by suction filtration
  8. washwashed with water

Sources & evidence

ORD record
ord-fccfc73a97bd4aea90a59c399293f87b
Source dataset
uspto-grants-2013_09
Patent number
US08524722B2

Linked notes

Loading…