4-(Methylsulfonyl)benzyl Bromide → HCID 60197661, compound

HRID 1631767Notes

Reaction equation

HRID 1631767 reaction equation
[N:1]1[C:10]2[N:9]3[CH2:11][CH2:12][O:13][CH2:14][CH:8]3[CH2:7][NH:6][C:5]=2[CH:4]=[N:3][C:2]=1[C:15]1[CH:16]=[N:17][C:18]([NH2:21])=[N:19][CH:20]=1.CC(C)([O-])C.[Na+].Br[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([S:36]([CH3:39])(=[O:38])=[O:37])=[CH:32][CH:31]=1>CS(C)=O>[CH3:39][S:36]([C:33]1[CH:34]=[CH:35][C:30]([CH2:29][N:6]2[CH2:7][CH:8]3[CH2:14][O:13][CH2:12][CH2:11][N:9]3[C:10]3[N:1]=[C:2]([C:15]4[CH:16]=[N:17][C:18]([NH2:21])=[N:19][CH:20]=4)[N:3]=[CH:4][C:5]2=3)=[CH:31][CH:32]=1)(=[O:37])=[O:38]

Participants

5

Reactant 3

HCID 27335814-(Methylsulfonyl)benzyl BromideHCID 23676156Sodium t-butoxideHCID 60197659HCID 60197659, compound

Product 1

HCID 60197661HCID 60197661, compoundYield 4.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 5-(5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridin-2-yl)pyrimidin-2-amine (EXAMPLE 1, 70.2 mg, 0.246 mmol) in DMSO (1.2 mL) was added sodium tert-butoxide (28.4 mg, 0.295 mmol). The resulting mixture was stirred at room temperature for 5 minutes after which 1-(bromomethyl)-4-(methylsulfonyl)benzene (0.5 mL, 0.271 mmol) was added dropwise. The resulting brown solution was stirred at room temperature for 2 hours. The reaction mixture was quenched with aqueous saturated NH4Cl, diluted with ethyl acetate, and washed with aqueous saturated NH4Cl (3×10 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The product was purified by LC/MS and the pure fractions were combined and lyophilized to give a yellow solid (4.6 mg, 4%). The product's regiochemistry was confirmed by 2D NOESY. 1H NMR (400 MHz, DMSO-d6) δ 3.16-3.25 (m, 7H), 3.44-3.46 (m, 1H), 3.53-3.57 (m, 1H), 3.80-3.97 (m, 1H), 3.98-4.03 (m, 1H), 4.65 (s, 2H), 4.76-4.80 (d, 1H), 7.37 (s, 1H), 7.42 (br s, 2H), 7.61-7.63 (d, J=8.0 Hz, 2H) 7.91-7.93 (d, J=8.0 Hz, 2H), 9.00 (s, 2H). ESI-MS m/z [M+H]+ calc'd for C21H23N7O3S, 454.16. found 454.4.

Workup

  1. additionwas added dropwise
  2. customThe reaction mixture was quenched with aqueous saturated NH4Cl
  3. additiondiluted with ethyl acetate
  4. washwashed with aqueous saturated NH4Cl (3×10 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe product was purified by LC/MS

Sources & evidence

ORD record
ord-ef6935c6126e42ecb7d7c29c5738e5b0
Source dataset
uspto-grants-2014_07
Patent number
US08791107B2

Reaction notes

Loading…