Diisopropylethylamine → HCID 25206289, 화합물

HRID 387626노트

반응식

HRID 387626 반응식
Cl.[NH2:2][C@@H:3]([CH2:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([F:29])[CH:23]=1)[C@H:4]([OH:20])[CH2:5][NH:6][C:7]1([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)[CH2:9][CH2:8]1.[O:30]=[C:31]1[C:40]2[CH:39]=[CH:38][CH:37]=[C:36]([C:41](O)=[O:42])[C:35]=2[CH2:34][CH2:33][N:32]1[CH:44]([CH2:48][CH2:49][CH3:50])[CH2:45][CH2:46][CH3:47].OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>ClCCl.O>[F:29][C:24]1[CH:23]=[C:22]([CH:27]=[C:26]([F:28])[CH:25]=1)[CH2:21][C@H:3]([NH:2][C:41]([C:36]1[C:35]2[CH2:34][CH2:33][N:32]([CH:44]([CH2:48][CH2:49][CH3:50])[CH2:45][CH2:46][CH3:47])[C:31](=[O:30])[C:40]=2[CH:39]=[CH:38][CH:37]=1)=[O:42])[C@H:4]([OH:20])[CH2:5][NH:6][C:7]1([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:17])([F:18])[F:19])[CH:11]=2)[CH2:9][CH2:8]1

참가 물질

8

반응물 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68470583HCID 68470583, 화합물HCID 86643873HCID 86643873, 화합물HCID 178418300HCID 178418300, 화합물

생성물 1

HCID 25206289HCID 25206289, 화합물

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

Poured into a suspension of 150 mg of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)butan-2-ol hydrochloride (2:1), 101 mg of 1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid, 4 mg of hydroxybenzotriazole and 76 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 6 cm3 of dichloromethane is 0.217 cm3 of N,N-diisopropylethylamine at a temperature close to 20° C. The solution is kept stirring for 24 h at a temperature close to 20° C. 15 cm3 of water are added to the reaction medium. The organic phase is washed with 5 cm3 of a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated using a rotary evaporator under reduced pressure (5 kPa). The product obtained is purified by flash chromatography over silica (column: 15 g; particle size: 120-40 μm, spherical; flow rate: 10 cm3/min; eluent: 100% ethyl acetate). After concentrating the fractions under reduced pressure, 140 mg of N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]-cyclopropyl}amino)propyl]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide are obtained in the form of a colorless oil.

후처리

  1. customclose to 20° C
  2. customclose to 20° C
  3. washThe organic phase is washed with 5 cm3 of a saturated aqueous solution of sodium chloride
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customa rotary evaporator under reduced pressure (5 kPa)
  7. customThe product obtained
  8. customis purified by flash chromatography over silica (column: 15 g; particle size: 120-40 μm, spherical; flow rate: 10 cm3/min; eluent: 100% ethyl acetate)
  9. concentrationAfter concentrating the fractions under reduced pressure, 140 mg of N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]-cyclopropyl}amino)propyl]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide
  10. customare obtained in the form of a colorless oil

출처 및 근거

ORD 기록
ord-ce7fa733b4d346089206bdf62c72ece8
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08372864B2

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