Sodium Carbonate → HCID 58169815, compound

HRID 1696053Notes

Reaction equation

HRID 1696053 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]([F:16])([F:15])[CH3:14])[C:7](=[O:17])[C:6]3([CH3:22])[CH2:18][O:19][CH2:20][CH2:21][N:5]3[C:4]=2[N:3]=1.[CH:23]1([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33](B3OC(C)(C)C(C)(C)O3)=[CH:32][CH:31]=2)=[O:28])[CH2:25][CH2:24]1.C(=O)([O-])[O-].[Na+].[Na+]>CC1CCCO1>[CH:23]1([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([C:2]3[N:11]=[CH:10][C:9]4[N:8]([CH2:12][C:13]([F:16])([F:15])[CH3:14])[C:7](=[O:17])[C:6]5([CH3:22])[CH2:18][O:19][CH2:20][CH2:21][N:5]5[C:4]=4[N:3]=3)=[CH:32][CH:31]=2)=[O:28])[CH2:25][CH2:24]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 44119149N-Cyclopropyl-N'-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureaHCID 781653442-chloro-5-(2,2-difluoropropyl)-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

Product 1

HCID 58169815HCID 58169815, compound

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

2-Chloro-5-(2,2-difluoropropyl)-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (707 mg, 2.125 mmol) and 1-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (770 mg, 2.55 mmol) where combined in methyltetrahydrofuran (10 mL) and aqueous sodium carbonate (2 M) (2.2 mL). The reaction mixture was heated in a 50° C. oil bath and then 1,1-bis(di-tert-butylphosphino)ferrocene palladium dichloride (38 mg) was added. The reaction mixture was then placed in an 80° C. oil bath. After about 1 hour the oil bath was reduced to 74° C. After about 4 hours some solvent had evaporated, 6 mL de-gassed methyltetrahydrofuran was added and decreased the oil bath temperature to 70° C. After about 6 hours, solvent had again evaporated, 6 mL de-gassed methyltetrahydrofuran was added. After another hour, 1,1-bis(di-tert-butylphosphino)ferrocene palladium dichloride (9 mg) was added and heating continued at 70° C. for 3 hours, then cooled to room temperature and allowed to stir overnight. The reaction mixture was then diluted with 4 mL 1:1 methyltetrahydrofuran/water, stir for 15 minutes, the solids were collected by filtration, the filter cake washed with 2×3 mL portions of 1:5 water/methyltetrahydrofuran, air-dried for 1 hour, then under vacuum for 1 hour to give the title compound.

Workup

  1. customwas then placed in an 80° C.
  2. customAfter about 4 hours some solvent had evaporated
  3. custom6 mL de-gassed methyltetrahydrofuran
  4. additionwas added
  5. customto 70° C
  6. waitAfter about 6 hours
  7. customsolvent had again evaporated
  8. custom6 mL de-gassed methyltetrahydrofuran
  9. additionwas added
  10. waitAfter another hour
  11. addition1,1-bis(di-tert-butylphosphino)ferrocene palladium dichloride (9 mg) was added
  12. temperatureheating
  13. waitcontinued at 70° C. for 3 hours
  14. temperaturecooled to room temperature
  15. additionThe reaction mixture was then diluted with 4 mL 1:1 methyltetrahydrofuran/water
  16. stirringstir for 15 minutes
  17. filtrationthe solids were collected by filtration
  18. washthe filter cake washed with 2×3 mL portions of 1:5 water/methyltetrahydrofuran
  19. customair-dried for 1 hour

Sources & evidence

ORD record
ord-a76614f932d64d12bc39d4beafe0840d
Source dataset
uspto-grants-2012_04
Patent number
US08163755B2

Reaction notes

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