Trifluoroacetic acid → HCID 11478104, compound

HRID 987520Notes

Reaction equation

HRID 987520 reaction equation
C(OC([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:16]=2)[N:11]([C:25](=[O:46])[CH2:26][C:27]2[CH:32]=[CH:31][C:30]([NH:33][C:34]([NH:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[CH3:43])=[O:35])=[C:29]([O:44][CH3:45])[CH:28]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.[OH-].[Na+]>ClCCl>[CH3:45][O:44][C:29]1[CH:28]=[C:27]([CH2:26][C:25]([N:11]2[C:12]3[C:17](=[CH:16][C:15]([CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:14][CH:13]=3)[NH:8][CH2:9][CH2:10]2)=[O:46])[CH:32]=[CH:31][C:30]=1[NH:33][C:34]([NH:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[CH3:43])=[O:35]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 14798Sodium HydroxideHCID 11239055HCID 11239055, compound

Product 1

HCID 11478104HCID 11478104, compoundYield 67.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 7-(-2-ethoxycarbonyl-ethyl)-4-{[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetyl}-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester (0.3 g, Reference Example 2) in dichloromethane (3 ml), at 0° C., was treated dropwise with trifluoroacetic acid (0.5 ml). After stirring for 2 hours at 0° C. a further portion of trifluoroacetic acid (0.5 ml) was added and stirring was continued for a further hour at 10° C. The reaction mixture was poured on crushed ice (50 ml), the pH of this mixture was adjusted to 8 by dropwise addition of sodium hydroxide (20 ml, 1N) and then the mixture was extracted twice with dichloromethane (25 ml). The combined organic extracts were washed twice with water (5 ml), then dried over magnesium sulphate and then evaporated under reduced pressure (2.7 kPa) at 40° C. The resulting white foamy solid (235 mg) was subjected to flash chromatography on silica (0.040-0.063 mm) eluting with a mixture of dichloromethane and methanol (99:1, v/v) to give the title compound (170 mg) as a white foamy solid. 1H NMR, 300 Hz, (CD3)2SO: δ1.2 (t, 3H); 2.3 (s, 3H); 2.6 (t, 2H); 2.8 (t, 2H); 3.25 (m, 2H); 3.7 (t, 2H); 3.85 (s, 2H); 3.9 (s, 3H); 4.1 (q, 2H); 5.8 (broad s, 1H); 6.4 (dd, J=8 Hz and 1.5 Hz, 1H); 6.5 (d, J=1.5 Hz, 1H); 6.7 (dd, J=8 Hz and 1.5 Hz, 1H); 6.85 (d, J=1.5 Hz, 1H); 7 (ddd, J=8, 8 and 1.5 Hz, 1H); 7.2 (m, 3H); 7.7 (broad d, J=8 Hz, 1H); 8 (d, J=8 Hz, 1H); 8.25 (s, 1H); 8.35 (s, 1H). MS (CI, NH3): MNH4+ 548, MH+ 531.

Workup

  1. additionwas added
  2. waitwas continued for a further hour at 10° C
  3. additionThe reaction mixture was poured
  4. extractionthe mixture was extracted twice with dichloromethane (25 ml)
  5. washThe combined organic extracts were washed twice with water (5 ml)
  6. dry with materialdried over magnesium sulphate
  7. customevaporated under reduced pressure (2.7 kPa) at 40° C
  8. washeluting with a mixture of dichloromethane and methanol (99:1

Sources & evidence

ORD record
ord-a3f1373487dc4d8ca0fc3d353170656b
Source dataset
uspto-grants-2003_10
Patent number
US06632814B1

Reaction notes

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