Water → HCID 18008933、化合物

HRID 987534ノート

反応式

HRID 987534 の反応式
Br[CH2:2][CH2:3][C:4](Br)=[O:5].[CH2:7]([O:9][C:10](=[O:45])[CH2:11][CH2:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]([C:23](=[O:44])[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]([NH:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[CH3:41])=[O:33])=[C:27]([O:42][CH3:43])[CH:26]=1)[CH2:18][CH2:17][NH:16]2)[CH3:8].C(N(CC)CC)C.O>O1CCCC1>[C:4]([N:16]1[C:15]2[C:20](=[CH:21][CH:22]=[C:13]([CH2:12][CH2:11][C:10]([O:9][CH2:7][CH3:8])=[O:45])[CH:14]=2)[N:19]([C:23](=[O:44])[CH2:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:32]([NH:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[CH3:41])=[O:33])=[C:27]([O:42][CH3:43])[CH:26]=2)[CH2:18][CH2:17]1)(=[O:5])[CH:3]=[CH2:2]

参加物

6

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 10998423Bromopropionylbromide2 回HCID 11478104HCID 11478104、化合物

生成物 1

HCID 18008933HCID 18008933、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

3-Bromo propionyl bromide (262 μl) was added to a stirred suspension of 3-(1-{[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetyl}-1,2,3,4-tetrahydro-quinoxalin-6-yl)-propionic acid ethyl ester (0.229 g, Reference Example 1) and triethylamine (680 μl) in tetrahydrofuran (10 ml) cooled to 0° C. under argon atmosphere. After stirring at 0° C. for 1 hour then at 20° C. overnight the mixture was treated with 3-bromo propionyl bromide (90 μl) and stirring was continued for 2 hours at 21° C. The reaction mixture was treated with water (25 ml) and after stirring for 15 minutes at 20° C. the mixture was extracted three times with ethyl acetate (25 ml). The combined extracts were washed with saturated aqueous sodium bicarbonate (10 ml), then washed four times with water (10 ml), then dried over magnesium sulfate and then evaporated to dryness under reduced pressure (40° C., 40 mbar). The residue (1.7 g) was subjected to flash chromatography on silica (50 g, 0.040-0.063 mm particle size) eluting with a mixture of cyclohexane and ethyl acetate (1:1, v/v) to give the title compound as a yellow foam (550 mg). TLC: RF=30/72, silica, eluting with a mixture of dichloromethane and methanol (9:1, v/v). 1H NMR [400 MHz, (CD3)2SO, at a temperature of 373° K.]: δ1.20 (t, J=7 Hz, 3H); 2.28 (s,, 3H); 2.64 (t, J=7.5 Hz, 2H); 2.91 (t, J=7.5 Hz, 2H); 3.81 (s, 3H); 3.84 (s, 2H); 3.87 (m, 2H); 3.93 (m, 2H); 4.11 (q, J=7 Hz, 2H); 5.68 (dd, J=10.5 and 2 Hz, 1H); 6.21 (dd, J=17 and 2 Hz, 1H); 6.38 (dd, J=17 and 10.5 Hz, 1H); 6.58 (broad d, J=8 Hz, 1H); 6.75 (broad s, 1H); 6.99 (broad t, J=7.5 Hz, 1H); from 7.10 to 7.25 (m, 4H); 7.57 (d, J=8.5 Hz, 1H); 7.69 (broad d, J=8 Hz, 1H); 7.92 (d, J=8.5 Hz, 1H); 8.18 (broad s, 1H); 8.28 (broad s, 1H). MS (EI): 584 (M+).

後処理

  1. stirringstirring
  2. waitwas continued for 2 hours at 21° C
  3. stirringafter stirring for 15 minutes at 20° C. the mixture
  4. extractionwas extracted three times with ethyl acetate (25 ml)
  5. washThe combined extracts were washed with saturated aqueous sodium bicarbonate (10 ml)
  6. washwashed four times with water (10 ml)
  7. dry with materialdried over magnesium sulfate
  8. customevaporated to dryness under reduced pressure (40° C., 40 mbar)
  9. washeluting with a mixture of cyclohexane and ethyl acetate (1:1

出典と根拠

ORDレコード
ord-7bb38e3139e14fc0acdf73467a1d74da
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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