1,2-Dichloroethane → N3-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4'-methoxy-N5,N5-dipropyl[1,1'-biphenyl]-3,5-dicarboxamide hydrochloride

HRID 348827노트

반응식

HRID 348827 반응식
[CH2:1]([N:4]([CH2:24][CH2:25][CH3:26])[C:5]([C:7]1[CH:8]=[C:9]([C:21]([OH:23])=O)[CH:10]=[C:11]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH:12]=1)=[O:6])[CH2:2][CH3:3].FC(F)(F)C(O)=O.[NH2:34][C@@H:35]([CH2:49][C:50]1[CH:55]=[C:54](F)[CH:53]=[C:52](F)[CH:51]=1)[C@H:36]([OH:48])[CH2:37][NH:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([O:46][CH3:47])[CH:41]=1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)C[Cl:77]>C(Cl)Cl.CN(C)C=O>[ClH:77].[CH2:49]([C@H:35]([NH:34][C:21]([C:9]1[CH:10]=[C:11]([C:13]2[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)[CH:12]=[C:7]([C:5]([N:4]([CH2:24][CH2:25][CH3:26])[CH2:1][CH2:2][CH3:3])=[O:6])[CH:8]=1)=[O:23])[C@H:36]([OH:48])[CH2:37][NH:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([O:46][CH3:47])[CH:41]=1)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1

참가 물질

8

반응물 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 21085976HCID 21085976, 화합물HCID 69869154(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol Trifluoroacetate

생성물 1

HCID 68608068N3-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4'-methoxy-N5,N5-dipropyl[1,1'-biphenyl]-3,5-dicarboxamide hydrochloride

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

A mixture of 5-[(dipropylamino)carbonyl]-4′-methoxy[1,1′-biphenyl]-3-carboxylic acid (IX–L, step 1, 316 mg, 0.89 mmol), (2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanol dihydrochloride (VIII, 332 mg, 0.89 mmol), HOBt (181 mg, 1.34 mmol), and N-methylmorpholine (0.37 g, 3.56 mmol) in methylene chloride (8 mL) and dimethylformamide (2 mL) is stirred at 20–25 degrees for 15 minutes EDC (257 mg, 1.34 mmol) is added and the reaction mixture is stirred for 4.5 hours. The reaction mixture is partitioned between methylene chloride and water. The organic phase is washed with hydrochloric acid (1N), water, and saline, dried (magnesium sulfate), and concentrated. The concentrate is dissolved in a minimum of methanol, treated with hydrochloric acid (3 mL of a 1.0 M mixture in ether, 3 mmol), and stirred for 10 minutes. More ether is added to precipitate the rest of the product. The precipitate is collected by filtration and dried in the vacuum oven at 50 degrees C. to give the title compound, mp=205–209 degrees C.; IR (ATR): 2964 and 1649 cm−1; APCI-MS (m/z) [M+H]+=638.

후처리

  1. additionis added
  2. customThe reaction mixture is partitioned between methylene chloride and water
  3. washThe organic phase is washed with hydrochloric acid (1N), water, and saline
  4. dry with materialdried (magnesium sulfate)
  5. concentrationconcentrated
  6. dissolutionThe concentrate is dissolved in a minimum of methanol
  7. additiontreated with hydrochloric acid (3 mL of a 1.0 M mixture in ether, 3 mmol), and
  8. stirringstirred for 10 minutes
  9. additionMore ether is added
  10. customto precipitate the rest of the product
  11. filtrationThe precipitate is collected by filtration
  12. customdried in the vacuum oven at 50 degrees C

출처 및 근거

ORD 기록
ord-c0fb6ba791c94c3eaa11f59b997d86e5
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07176242B2

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