Diisopropylethylamine → 1-butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-1,2,3,4-tetrahydroquinoline-7-carboxamide

HRID 349034노트

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HRID 349034 반응식
[CH2:1]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]([OH:17])=O)[CH:13]=2)[CH2:8][CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[NH2:51][C@@H:52]([CH2:66][C:67]1[CH:72]=[C:71]([F:73])[CH:70]=[C:69]([F:74])[CH:68]=1)[C@H:53]([OH:65])[CH2:54][NH:55][CH2:56][C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([CH2:63][CH3:64])[CH:58]=1>C(Cl)Cl>[CH2:1]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]([NH:51][C@@H:52]([CH2:66][C:67]3[CH:68]=[C:69]([F:74])[CH:70]=[C:71]([F:73])[CH:72]=3)[C@H:53]([OH:65])[CH2:54][NH:55][CH2:56][C:57]3[CH:62]=[CH:61][CH:60]=[C:59]([CH2:63][CH3:64])[CH:58]=3)=[O:17])[CH:13]=2)[CH2:8][CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4]

참가 물질

6

반응물 4

HCID 81531Diisopropylethylamine2회HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210851651-Butyl-1,2,3,4-tetrahydroquinoline-7-carboxylic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

생성물 1

HCID 575121101-butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-1,2,3,4-tetrahydroquinoline-7-carboxamide수율 41.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

실험 절차

A solution of 1-butyl-1,2,3,4-tetrahydroquinoline-7-carboxylic acid (134 mg, 0.57 mmol), HBTU (327 mg, 0.86 mmol), and diisopropylethylamine (150 μL, 0.86 mmol) was stirred in methylene chloride (3.0 mL) for 15 min. A solution of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (EXAMPLE SP-272) (234 mg, 0.57 mmol) and diisopropylethylamine (150 μL, 0.86 mmol) in methylene chloride (3.0 mL) was added and the reaction mixture was stirred overnight. The reaction mixture was diluted with methylene chloride, washed with 1 N hydrochloric acid (10 mL), saturated sodium bicarbonate (10 mL), and brine. The organic layer was then dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:9 methanol/chloroform) provided 1-butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-1,2,3,4-tetrahydroquinoline-7-carboxamide (130 mg): ESI MS m/z 550 [M+H]+

후처리

  1. washwashed with 1 N hydrochloric acid (10 mL), saturated sodium bicarbonate (10 mL), and brine
  2. dry with materialThe organic layer was then dried (magnesium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (silica, 1:9 methanol/chloroform)

출처 및 근거

ORD 기록
ord-7ee1948f2c8542e3ba4dbe648ed4617a
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07176242B2

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