Phosphorus oxychloride → tert-Butyl 4-chloro-5,6-dihydropyrido(4',3':4,5)thieno(2,3-d)pyrimidine-7(8H)-carboxylate

HRID 1887409Notes

Reaction equation

HRID 1887409 reaction equation
P(Cl)(Cl)([Cl:3])=O.[C:6]([O:10][C:11]([N:13]1[CH2:25][C:24]2[S:23][C:22]3[N:21]=[CH:20][NH:19][C:18](=O)[C:17]=3[C:16]=2[CH2:15][CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7]>C(N(CC)CC)C>[C:6]([O:10][C:11]([N:13]1[CH2:25][C:24]2[S:23][C:22]3[N:21]=[CH:20][N:19]=[C:18]([Cl:3])[C:17]=3[C:16]=2[CH2:15][CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 49788562tert-Butyl 4-oxo-3,5,6,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-7(4H)-carboxylate

Product 1

HCID 49788563tert-Butyl 4-chloro-5,6-dihydropyrido(4',3':4,5)thieno(2,3-d)pyrimidine-7(8H)-carboxylateYield 89%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of phosphorous oxychloride (30 mL) was added triethylamine (30 mL) over 15 mins at 0° C. under argon. 4-oxo-3,5,6,8-tetrahydro-4H-9-thia-1,3,7-triaza-fluorene-7-carboxylic acid tert-butyl ester (4.20 g, 14 mmol) was then added to the flask. The reaction mixture was stirred at 0° C. for 30 mins then heated at 65° C. for 2 h. The reaction mixture was cooled to rt before concentrated in vacuo. The residue was coevaporated with toluene (2×200 mL). DCM (50 mL) was added to the solid residue and the reaction mixture was quenched with ice/saturated aqueous NaHCO3. The resulting mixture was extracted with DCM (3×100 mL). The combined organic layers was dried over sodium sulfate, filtered and concentrated in vacuo to yield 4.08 g (12.5 mmol, 89%) of a light yellow solid. 1H-NMR (CD2Cl2-d2) δ 8.74 (s, 1H), 4.74 (s, 2H), 3.78 (t, 2H), 3.19 (t, 2H), 1.49 (s, 9H); LCMS RT=3.53 min, [M+H]+=326.0.

Workup

  1. temperaturethen heated at 65° C. for 2 h
  2. temperatureThe reaction mixture was cooled to rt
  3. concentrationbefore concentrated in vacuo
  4. additionDCM (50 mL) was added to the solid residue
  5. customthe reaction mixture was quenched with ice/saturated aqueous NaHCO3
  6. extractionThe resulting mixture was extracted with DCM (3×100 mL)
  7. dry with materialThe combined organic layers was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ec9ca65b62304d758ec101dd85de5027
Source dataset
uspto-grants-2013_08
Patent number
US08501755B2

Reaction notes

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