Dimethylamine → HCID 86723455, compound

HRID 2201216Notes

Reaction equation

HRID 2201216 reaction equation
CS(OS(C)(=O)=O)(=O)=O.[Cl:10][C:11]1[O:15][C:14]([CH:16]2[C:21]3=[C:22]4[N:34]([CH3:35])[C:33](=[O:36])[N:32]([CH3:37])[C:31](=[O:38])[C:23]4=[C:24]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[N:20]3[CH2:19][CH:18]([CH2:39]O)[S:17]2)=[CH:13][CH:12]=1.[N:41]1[C:46](C)=CC=C[C:42]=1C.CNC>C(Cl)Cl>[Cl:10][C:11]1[O:15][C:14]([C@@H:16]2[C:21]3=[C:22]4[N:34]([CH3:35])[C:33](=[O:36])[N:32]([CH3:37])[C:31](=[O:38])[C:23]4=[C:24]([C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)[N:20]3[CH2:19][C@H:18]([CH2:39][N:41]([CH3:46])[CH3:42])[S:17]2)=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 79372,6-LutidineHCID 81560Methanesulfonic anhydrideHCID 77106011HCID 77106011, compound

Product 1

HCID 86723455HCID 86723455, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonic anhydride (60.9 mg, 0.35 mmol) was added to a solution of 10-(5-chlorofuran-2-yl)-8-(hydroxymethyl)-1,3-dimethyl-5-phenyl-7,8-dihydro-1H-pyrimido[4′,5′:3,4]pyrrolo[2,1-c][1,4]thiazine-2,4(3H,10H)-dione (Example 12.0) (160 mg, 0.35 mmol) and 2,6-lutidine (0.041 ml, 0.35 mmol) in DCM (16 ml) at 0°. The mixture was stirred at room temperature for 2 hours. The mixture was evaporated under vacuum and the residue redissolved in THF (6 ml). Dimethylamine solution (2M in THF, 6 ml, 12.0 mmol) was added and mixture stirred at room temperature for 1 h, at 35° C. for 16 hours, at 55° C. for 6 hours, again at room temperature for 3 days, then at 55° C. for 4 hours, and finally heated under microwave irradiation at 80° C. for 20 mins. The mixture was evaporated under vacuum. The residue was redissolved in DCM and methanol and loaded onto an Isolute™SCX-2 cartridge. The column was first rinsed with methanol/DCM (1:1, 50 ml) then eluted with 3.5 M NH3/methanol (50 ml). The basic eluent was evaporated under vacuum to afford the title compounds as a mixture of diastereomers

Workup

  1. customThe mixture was evaporated under vacuum
  2. dissolutionthe residue redissolved in THF (6 ml)
  3. stirringmixture stirred at room temperature for 1 h, at 35° C. for 16 hours, at 55° C. for 6 hours, again at room temperature for 3 days
  4. waitat 55° C. for 4 hours
  5. temperaturefinally heated under microwave irradiation at 80° C. for 20 mins
  6. customThe mixture was evaporated under vacuum
  7. dissolutionThe residue was redissolved in DCM
  8. washThe column was first rinsed with methanol/DCM (1:1, 50 ml)
  9. washthen eluted with 3.5 M NH3/methanol (50 ml)
  10. customThe basic eluent was evaporated under vacuum

Sources & evidence

ORD record
ord-dd19f90f7e554448a0b17bd183e10c94
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

Loading…