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 2169545Notes

Reaction equation

HRID 2169545 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%). 1H NMR (400 MHz, DMSO-d6) δ 2.94-3.06 (m, 1 H), 3.08-3.29 (m, 5 H), 3.35-3.52 (m, 2 H), 3.67-3.76 (m, 1 H), 3.86-4.01 (m, 2 H), 4.25 (dd, J=13.64, 1.77 Hz, 1 H), 4.55 (s, 2 H), 7.30 (s, 1 H), 7.57 (d, J=8.34 Hz, 2 H), 7.87-7.92 (m, 2 H). ESI-MS m/z [M+H]+ calc'd for C17H19ClN4O3S, 395.09; found 395.2.

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-ea484703e99149ab8edab3be406fc2c7
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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