Dimethyl Sulfate → HCID 22676827, compound

HRID 1006272Notes

Reaction equation

HRID 1006272 reaction equation
[H-].[Na+].[C:3]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([NH:22][C:23]([CH:25]4[CH2:27][CH2:26]4)=[O:24])[CH:20]=3)[N:15]([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=3)[C:14]=2[C:37]([OH:39])=O)=[CH:9][CH:8]=1)([CH3:6])([CH3:5])[CH3:4].COS([O:45][CH3:46])(=O)=O.O1CCC[CH2:48]1>>[C:3]([C:7]1[CH:8]=[CH:9][C:10]([C:13]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([N:22]([C:23]([CH:25]4[CH2:27][CH2:26]4)=[O:24])[CH3:48])[CH:20]=3)[N:15]([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=3)[C:14]=2[C:37]([O:45][CH3:46])=[O:39])=[CH:11][CH:12]=1)([CH3:4])([CH3:5])[CH3:6]

Participants

5

Reactant 4

HCID 6497Dimethyl SulfateHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 10300399HCID 10300399, compound

Product 1

HCID 22676827HCID 22676827, compoundYield 90%

Conditions

Temperature
0 °C

Procedure

Sodium hydride (192 mg, 0.800 mmol) was added to a cooled (0° C.) and stirred solution of 3-(4-tert-butylphenyl)-5-[(cyclopropylcarbonyl)amino]-1-(3-methoxybenzyl)-1H-indole-2-carboxylic acid (Example 167, 94.5 mg, 0.190 mmol) in tetrahydrofuran (5 mL). The cold bath was removed and stirring was continued for 1 h. Dimethylsulfate (0.75 mL, 101 mg, 0.80 mmol) was added and the reaction was stirred for an additional 2 h. The reaction was quenched with water (50 mL) and then extracted with ethyl acetate (3×30 mL). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. Flash chromatography of the residue over silica gel using 40% ethyl acetate/hexane afforded 894 mg (90%) of the desired product. The product had: 1H NMR (300 MHz, CDCl3) δ 7.38-7.50 (m, 3 H), 7.28-7.36 (m, 3 H), 7.11-7.24 (m, 2 H), 6.59-6.76 (m, 3 H), 5.70 (s, 2 H), 3.90 (s, 3 H), 3.69 (s, 3 H) 3.21 (s, 3 H), 1.34 (s, 9 H), 1.15-1.35 (m, 1 H), 0.87-0.97 (m, 2 H), 0.48-0.58 (m, 2 H); mass spectroscopy gave MH+=525.3 (calc'd exact mass for C33H36N2O4=524.27).

Workup

  1. customThe cold bath was removed
  2. stirringthe reaction was stirred for an additional 2 h
  3. customThe reaction was quenched with water (50 mL)
  4. extractionextracted with ethyl acetate (3×30 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-db3b13a054b54129a8aa9de676e622b2
Source dataset
uspto-grants-2004_09
Patent number
US06787651B2

Reaction notes

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