1,2-Dichloroethane → N1-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(4-methyl-1,3-oxazol-2-yl)-N3,N3-dipropylisophthalamide

HRID 349076ノート

反応式

HRID 349076 の反応式
[CH2:1]([N:4]([CH2:22][CH2:23][CH3:24])[C:5]([C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([C:16]2[O:17][CH:18]=[C:19]([CH3:21])[N:20]=2)[CH:15]=1)[C:10](O)=[O:11])=[O:6])[CH2:2][CH3:3].Cl.Cl.[NH2:27][C@@H:28]([CH2:42][C:43]1[CH:48]=[C:47]([F:49])[CH:46]=[C:45]([F:50])[CH:44]=1)[C@H:29]([OH:41])[CH2:30][NH:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([CH2:39][CH3:40])[CH:34]=1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)CCl>CN(C)C=O.O>[F:50][C:45]1[CH:44]=[C:43]([CH:48]=[C:47]([F:49])[CH:46]=1)[CH2:42][C@H:28]([NH:27][C:10](=[O:11])[C:9]1[CH:13]=[C:14]([C:16]2[O:17][CH:18]=[C:19]([CH3:21])[N:20]=2)[CH:15]=[C:7]([C:5]([N:4]([CH2:22][CH2:23][CH3:24])[CH2:1][CH2:2][CH3:3])=[O:6])[CH:8]=1)[C@H:29]([OH:41])[CH2:30][NH:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([CH2:39][CH3:40])[CH:34]=1

参加物

8

反応物 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 210857873-[(Dipropylamino)carbonyl]-5-(4-methyl-1,3-oxazol-2-yl)benzoic acidHCID 57487281(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

生成物 1

HCID 58802778N1-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(4-methyl-1,3-oxazol-2-yl)-N3,N3-dipropylisophthalamide収率 26.9%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A solution of 3-[(dipropylamino)carbonyl]-5-(4-methyl-1,3-oxazol-2-yl)benzoic acid (77.5 mg, 0.23 mmol), (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride (96 mg, 0.23 mmol), HOBt (32 mg, 0.23 mmol), and N-methylmorpholine (83 μL, 0.75 mmol) was stirred in dimethylformamide (2 mL) for 15 min. EDC (73 mg, 0.42 mmol) was added and the reaction mixture was stirred overnight. The reaction mixture was diluted with water, and extracted with ethyl acetate (3×25 mL). The organic layer was washed with 1 N hydrochloric acid (25 mL), saturated sodium bicarbonate (25 mL), saturated sodium chloride, dried (sodium sulfate), and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:9 methanol/chloroform) provided N1-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(4-methyl-1,3-oxazol-2-yl)-N 3,N3-dipropylisophthalamide (40 mg): 1H NMR (300 MHz, CDCl3) δ 8.20 (br s, 1H, —NH), 8.17 (s, 1H), 8.05 (s, 1H), 7.52 (s, 1H), 7.38 (s, 1H), 7.24–7.08 (m, 5H), 7.02 (d, J=8 Hz, 2H), 6.61 (t, J=8 Hz, 1H), 4.27 (br s, 1H), 3.93 (d, J=4 Hz, 1H), 3.85 (s, 2H), 3.54 (br s, 2H), 3.43 (br s, 2H), 2.84 (d, J=5 Hz, 2H), 2.63 (q, J=8 Hz, 2H), 2.18 (s, 3H), 1.74 (t, J=5 Hz, 2H), 1.41 (d, J=7 Hz, 2H), 1.22 (t, J=8 Hz, 3H), 1.03 (t, J=7 Hz, 3H), 0.64 (t, J=7 Hz, 3H); ESI MS m/z 647 [M+H]+

後処理

  1. extractionextracted with ethyl acetate (3×25 mL)
  2. washThe organic layer was washed with 1 N hydrochloric acid (25 mL), saturated sodium bicarbonate (25 mL), saturated sodium chloride
  3. dry with materialdried (sodium sulfate)
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (silica, 1:9 methanol/chloroform)

出典と根拠

ORDレコード
ord-286f5411d21446c3a7fbee6b9f7c34f3
出典データセット
uspto-grants-2007_02
特許番号
US07176242B2

反応ノート

読み込み中…