4-(Methylsulfonyl)benzyl Bromide → (R)-2-chloro-5-(4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

HRID 1631707Notes

Reaction equation

HRID 1631707 reaction equation
[CH3:1][S:2]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9]Br)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[Cl:13][C:14]1[N:23]=[CH:22][C:21]2[NH:20][CH2:19][C@@H:18]3[CH2:24][O:25][CH2:26][CH2:27][N:17]3[C:16]=2[N:15]=1.CC(C)([O-])C.[K+]>CS(C)=O.CCOC(C)=O.O>[Cl:13][C:14]1[N:23]=[CH:22][C:21]2[N:20]([CH2:9][C:8]3[CH:11]=[CH:12][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:6][CH:7]=3)[CH2:19][C@@H:18]3[CH2:24][O:25][CH2:26][CH2:27][N:17]3[C:16]=2[N:15]=1

Participants

7

Reactant 3

HCID 27335814-(Methylsulfonyl)benzyl BromideHCID 23665647Potassium tert-butoxideHCID 86670088(R)-2-chloro-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

Product 1

HCID 86670093(R)-2-chloro-5-(4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridineYield 32.1%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Methylsulphonylbenzyl bromide (121 mg, 0.485 mmol) was added to a mixture of (R)-2-chloro-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine (PREPARATION x3, 100 mg, 0.441 mmol) and potassium tert-butoxide (59.4 mg, 0.529 mmol) in DMSO (2206 μL) at room temperature. The resultant mixture was stirred overnight at room temperature and subsequently diluted with EtOAc and water. The mixture was extracted twice with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, eluting with 0-10% MeOH/CHCl3 gradient) to afford the title compound as an off-white solid (55.9 mg, 32%).

Workup

  1. extractionThe mixture was extracted twice with EtOAc
  2. washThe combined extracts were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (SiO2, eluting with 0-10% MeOH/CHCl3 gradient)

Sources & evidence

ORD record
ord-a18568e81cd44fb280f17ca70a89c430
Source dataset
uspto-grants-2014_07
Patent number
US08791107B2

Reaction notes

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