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

HRID 2169608Notes

Reaction equation

HRID 2169608 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, 7 H), 3.44-3.46 (m, 1 H), 3.53-3.57 (m, 1 H), 3.80-3.97 (m, 1 H), 3.98-4.03 (m, 1 H), 4.65 (s, 2 H), 4.76-4.80 (d, 1 H), 7.37 (s, 1 H), 7.42 (br s, 2 H), 7.61-7.63 (d, J=8.0 Hz, 2 H) 7.91-7.93 (d, J=8.0 Hz, 2 H), 9.00 (s, 2 H). 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-49298626dc9e4230be9d781c69948cce
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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