Water → HCID 18008963, compound

HRID 987530Notes

Reaction equation

HRID 987530 reaction equation
[C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:10]([O:12][C:13](=[O:49])[CH2:14][CH:15]([C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[N:23]([C:27](=[O:48])[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([NH:35][C:36]([NH:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[CH3:45])=[O:37])=[C:31]([O:46][CH3:47])[CH:30]=1)[CH2:22][CH2:21][NH:20]2)[CH3:16])[CH3:11].C(N(CC)CC)C.O>O1CCCC1>[CH2:10]([O:12][C:13](=[O:49])[CH2:14][CH:15]([C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[N:23]([C:27](=[O:48])[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([NH:35][C:36]([NH:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[CH3:45])=[O:37])=[C:31]([O:46][CH3:47])[CH:30]=1)[CH2:22][CH2:21][N:20]2[C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH3:16])[CH3:11]

Participants

6

Reactant 4

HCID 962WaterHCID 7412Benzoyl chloride2×HCID 8471TriethylamineHCID 18008930HCID 18008930, compound

Product 1

HCID 18008963HCID 18008963, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Benzoyl chloride (22 μl) was added to a stirred mixture of 3-(1-{[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetyl}-1,2,3,4-tetrahydro-quinoxalin-6-yl)-butyric acid ethyl ester (0.110 g, Reference Example 17) and triethylamine (87.8 μl) in tetrahydrofuran (10 ml) cooled to 0° C. under an argon atmosphere. The mixture was stirred for 1 hour at 0° C., then allowed to warm to 20° C., then stirred at this temperature for 2 hours and then treated with a further aliquot of benzoyl chloride (11 μl). After stirring overnight the reaction mixture was treated with water (20 ml) then extracted three times with ethyl acetate (25 ml). The combined extracts were dried over magnesium sulfate then evaporated (40° C., 40 mbar). The crude residue (147 mg) was subjected to flash chromatography on silica (20 g, 0.040-0.063 mm particle size) eluting with a mixture of dichloromethane and methanol (99:1, v/v) to give the title compound as a white foam (132 mg). TLC: RF 13/56 (cyclohexane:ethyl acetate, 9:1, v/v). 1H NMR [400 HMz, (CD3)2SO, at a temperature of 383° K.]: δ0.96 (d, J=7 Hz, 3H); 1.16 (t, J=7 Hz, 3H); 2.24 (d, J=7.5 Hz, 2H); 2.28 (s, 3H); 2.93 (m, 1H); 3.83 (s, 3H); 3.94 (m, 2H); 3.96 (s, 21H); 4.02 (m, 2H); 4.04 (q, J=7 Hz, 2H); 6.63 (broad s ,1H); 6.76 (broad d, J=8 Hz, 1H); 6.90 (broad s, 1H); 6.99 (m, 2H); from 7.10 to 7.20 (m, 4H); 7.34 (broad t, J=7.5 Hz, 2H); 7.41 (broad t, J=7.5 Hz, 1H); 7.57 (d, J=8 Hz, 1H); 7.67 (broad d, J=8 Hz, 1H); 8.02 (d, J=8.5 Hz, 1H); 8.16 (broad s, 1H); 8.24 (broad s, 1H). MS (EI): 648 (M+).

Workup

  1. temperatureto warm to 20° C.
  2. stirringstirred at this temperature for 2 hours
  3. stirringAfter stirring overnight the reaction mixture
  4. extractionthen extracted three times with ethyl acetate (25 ml)
  5. dry with materialThe combined extracts were dried over magnesium sulfate
  6. customthen evaporated (40° C., 40 mbar)
  7. washeluting with a mixture of dichloromethane and methanol (99:1

Sources & evidence

ORD record
ord-a93da1c377924ff687281a2c5df1f503
Source dataset
uspto-grants-2003_10
Patent number
US06632814B1

Reaction notes

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