Methanesulfonic Acid → 1207830-72-5

HRID 655111Notes

Reaction equation

HRID 655111 reaction equation
S(O)(=O)(=O)C.[Si]([O:13][CH:14]1[CH2:17][N:16]([CH2:18][C@H:19]([O:30][C:31]2[N:36]=[CH:35][N:34]=[C:33]3[N:37]([C:40]4[C:45]([Cl:46])=[CH:44][CH:43]=[CH:42][C:41]=4[Cl:47])[N:38]=[CH:39][C:32]=23)[C:20]([NH:22][C:23]2[CH:28]=[N:27][C:26]([CH3:29])=[CH:25][N:24]=2)=[O:21])[CH2:15]1)(C(C)(C)C)(C)C.C1COCC1.CS(O)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>O.COC(C)(C)C>[Cl:46][C:45]1[CH:44]=[CH:43][CH:42]=[C:41]([Cl:47])[C:40]=1[N:37]1[C:33]2[N:34]=[CH:35][N:36]=[C:31]([O:30][C@@H:19]([CH2:18][N:16]3[CH2:17][CH:14]([OH:13])[CH2:15]3)[C:20]([NH:22][C:23]3[CH:28]=[N:27][C:26]([CH3:29])=[CH:25][N:24]=3)=[O:21])[C:32]=2[CH:39]=[N:38]1

Participants

7

Reactant 4

HCID 6395Methanesulfonic AcidHCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 86646431HCID 86646431, compound

Product 1

HCID 461755201207830-72-5

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Procedure

A mixture of (S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-(1-(2,6-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyrazin-2-yl)propanamide mesylate (16.5 g), THF (50.00 mL), water (20.0 mL) and methanesulfonic acid (2.62 g) was stirred for 19 hours at ambient temperature. tert-Butyl methyl ether (40.0 mL) was added followed by the dropwise addition of a solution of potassium carbonate (3.77 g) in water (20.0 mL) over 20 mins with stirring. The aqueous phase was removed and the organic phase was washed with water (20.0 mL) then evaporated under reduced pressure at 50° C. THF (80 mL) was added to the residue and then removed by evaporation under reduced pressure. This process was repeated. THF (20.0 mL) was added to the residue followed by tert-butyl methyl ether (60.0 ml). The mixture was filtered then stirred whilst cyclohexane (50.0 mL) was added dropwise. The solid was collected by filtration and washed with a mixture tert-butyl methyl ether (50.0 mL) and cyclohexane (50.0 mL) and dried to give (2S)-2-[1-(2,6-dichlorophenyl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-3-(3-hydroxyazetidin-1-yl)-N-(5-methylpyrazin-2-yl)propanamide in an overall yield for steps a) and b) of 69%.

Workup

  1. stirringwith stirring
  2. customThe aqueous phase was removed
  3. washthe organic phase was washed with water (20.0 mL)
  4. customthen evaporated under reduced pressure at 50° C
  5. additionTHF (80 mL) was added to the residue
  6. customremoved by evaporation under reduced pressure
  7. additionTHF (20.0 mL) was added to the residue
  8. filtrationThe mixture was filtered
  9. stirringthen stirred whilst cyclohexane (50.0 mL)
  10. additionwas added dropwise
  11. filtrationThe solid was collected by filtration
  12. washwashed with a mixture tert-butyl methyl ether (50.0 mL) and cyclohexane (50.0 mL)
  13. customdried

Sources & evidence

ORD record
ord-fb52844b8e3742368a075c0296d19b21
Source dataset
uspto-grants-2011_12
Patent number
US08071585B2

Reaction notes

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