Sodium Chloride → tert-Butyl 4-chloro-5,6,7,9-tetrahydro-8H-pyrimido[5',4':4,5]thieno[2,3-c]azepine-8-carboxylate

HRID 38561Notes

Reaction equation

HRID 38561 reaction equation
S1(CCCC1)(=O)=O.P(Cl)(Cl)(Cl)=O.O=[C:14]1[C:19]2[C:20]3[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22][C:21]=3[S:34][C:18]=2[N:17]=[CH:16][NH:15]1.[Cl-:35].[Na+]>C1(C)C=CC=CC=1.C(N(CC)CC)C>[Cl:35][C:14]1[C:19]2[C:20]3[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22][C:21]=3[S:34][C:18]=2[N:17]=[CH:16][N:15]=1

Participants

7

Reactant 4

HCID 5234Sodium ChlorideHCID 24813Phosphorus oxychlorideHCID 31347SulfolaneHCID 58116854tert-butyl 4-oxo-3,4,5,6,7,9-hexahydro-8H-pyrimido[5',4':4,5]thieno[2,3-c]azepine-8-carboxylate

Product 1

HCID 58116846tert-Butyl 4-chloro-5,6,7,9-tetrahydro-8H-pyrimido[5',4':4,5]thieno[2,3-c]azepine-8-carboxylateYield 80%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8471TriethylamineSolvent2×

Procedure

To sulfolane (20 mL) was added phosphoryl chloride (7.40 g, 48.3 mmol). Triethylamine (4.88 g, 48.3 mmol) was added dropwise, and the mixture was stirred for 30 min at rt. Subsequently, tert-butyl 4-oxo-3,4,5,6,7,9-hexahydro-8H-pyrimido[5′,4′:4,5]thieno[2,3-c]azepine-8-carboxylate from Example 78A (5.17 g, 16.1 mmol) was added, and the reaction mixture was heated for 2 h to 65° C. The mixture was then cooled to rt, and triethylamine (7.0 mL) was added. It was diluted with toluene and cooled to 0° C. Half-saturated aqueous sodium chloride solution was added, and the mixture was stirred for 20 min. The organic layer was separated, washed with water and dried over sodium sulfate, and the solvent was removed in vacuo. The residue was triturated with tert-butyl methyl ether, and the precipitate was collected by suction filtration to yield 4.40 g (80%) of the title compound.

Workup

  1. temperaturethe reaction mixture was heated for 2 h to 65° C
  2. temperatureThe mixture was then cooled to rt
  3. temperaturecooled to 0° C
  4. stirringthe mixture was stirred for 20 min
  5. customThe organic layer was separated
  6. washwashed with water
  7. dry with materialdried over sodium sulfate
  8. customthe solvent was removed in vacuo
  9. customThe residue was triturated with tert-butyl methyl ether
  10. filtrationthe precipitate was collected by suction filtration

Sources & evidence

ORD record
ord-9d68340b394b4e61a0942047bfa41ecc
Source dataset
uspto-grants-2013_09
Patent number
US08524722B2

Reaction notes

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