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1-Hydroxybenzotriazole → 4-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3,4-dihydro-2H-1,4-benzoxazine-6-carboxamide

HRID 349010
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HRID 349010 반응식
[CH2:1]([N:5]1[C:10]2[CH:11]=[C:12]([C:15]([OH:17])=O)[CH:13]=[CH:14][C:9]=2[O:8][CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl.Cl.[NH2:63][C@@H:64]([CH2:78][C:79]1[CH:84]=[C:83]([F:85])[CH:82]=[C:81]([F:86])[CH:80]=1)[C@H:65]([OH:77])[CH2:66][NH:67][CH2:68][C:69]1[CH:74]=[CH:73][CH:72]=[C:71]([CH2:75][CH3:76])[CH:70]=1>C(Cl)Cl>[CH2:1]([N:5]1[C:10]2[CH:11]=[C:12]([C:15]([NH:63][C@@H:64]([CH2:78][C:79]3[CH:80]=[C:81]([F:86])[CH:82]=[C:83]([F:85])[CH:84]=3)[C@H:65]([OH:77])[CH2:66][NH:67][CH2:68][C:69]3[CH:74]=[CH:73][CH:72]=[C:71]([CH2:75][CH3:76])[CH:70]=3)=[O:17])[CH:13]=[CH:14][C:9]=2[O:8][CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4]
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참가 물질

7

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2회HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210859294-Butyl-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acidHCID 57487281(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

생성물

1
HCID 575126124-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3,4-dihydro-2H-1,4-benzoxazine-6-carboxamide수율 17.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

실험 절차

A solution of 4-Butyl-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid (43 mg), HATU (104 mg), HOBt (37 mg), and diisopropylethylamine (47 μL) was stirred in methylene chloride (1.0 mL) for 15 min. A solution of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride (62 mg) and diisopropylethylamine (47 μL) in methylene chloride (1.0 mL) was added and the reaction mixture was stirred overnight. The mixture was diluted with methylene chloride, washed with 1 N hydrochloric acid (15 mL), saturated sodium bicarbonate (15 mL), and brine, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:9 methanol/chloroform) provided 15 mg of the title compound: APCI MS m/z 552 [M+H]+.

후처리

  1. washwashed with 1 N hydrochloric acid (15 mL), saturated sodium bicarbonate (15 mL), and brine
  2. dry with materialdried (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-22698eddb8a74bfaa43515fbbe389777
출처 데이터셋
uspto-grants-2007_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07176242B2

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