Trifluoroacetic acid → HCID 11478104、化合物

HRID 987520ノート

反応式

HRID 987520 の反応式
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]

参加物

5

反応物 3

HCID 6422Trifluoroacetic acid2 回HCID 14798Sodium HydroxideHCID 11239055HCID 11239055、化合物

生成物 1

HCID 11478104HCID 11478104、化合物収率 67.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-a3f1373487dc4d8ca0fc3d353170656b
出典データセット
uspto-grants-2003_10
特許番号
US06632814B1

反応ノート

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