Diisopropylethylamine → N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-propyl-1,2-benzisoxazole-5-carboxamide

HRID 14252노트

반응식

HRID 14252 반응식
[CH2:1]([C:4]1[C:8]2[CH:9]=[C:10]([C:13]([OH:15])=O)[CH:11]=[CH:12][C:7]=2[O:6][N:5]=1)[CH2:2][CH3:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[NH2:49][C@@H:50]([CH2:64][C:65]1[CH:70]=[C:69]([F:71])[CH:68]=[C:67]([F:72])[CH:66]=1)[C@H:51]([OH:63])[CH2:52][NH:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[C:57]([CH2:61][CH3:62])[CH:56]=1>C(Cl)Cl>[F:71][C:69]1[CH:70]=[C:65]([CH:66]=[C:67]([F:72])[CH:68]=1)[CH2:64][C@H:50]([NH:49][C:13]([C:10]1[CH:11]=[CH:12][C:7]2[O:6][N:5]=[C:4]([CH2:1][CH2:2][CH3:3])[C:8]=2[CH:9]=1)=[O:15])[C@H:51]([OH:63])[CH2:52][NH:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[C:57]([CH2:61][CH3:62])[CH:56]=1

참가 물질

6

반응물 4

HCID 81531Diisopropylethylamine2회HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210858433-Propyl-1,2-benzisoxazole-5-carboxylic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

생성물 1

HCID 57508098N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-propyl-1,2-benzisoxazole-5-carboxamide수율 19.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a stirred solution of 3-propyl-1,2-benzisoxazole-5-carboxylic acid (70 mg, 0.3 mmol) and HATU (130 mg, 0.3 mmol) in methylene chloride (5 mL) was added N,N-diisopropylethylamine (110 μL, 0.6 mmol). In a separate flask, N,N-diisopropylethylamine (110 μL, 0.6 mmol) was added to (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (EXA xxx)(140 mg, 0.3 mmol) in methylene chloride (2 mL). This solution was added to the above solution containing the acid and the resulting reaction mixture was stirred at room temperature for 18 h. The reaction mixture was partitioned between methylene chloride and water. The organic layer was washed with water, dried (sodium sulfate), filtered, and concentrated under reduced pressure to afford a crude oil. Purification by flash column chromatography (silica, gradient 97:3 to 94:6 methylene chloride/methanol) provided N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-propyl-1,2-benzisoxazole-5-carboxamide (30 mg). ESI-MS m/z 522 [M+H]+

후처리

  1. additionThis solution was added to the above solution
  2. additioncontaining the acid
  3. customthe resulting reaction mixture
  4. customThe reaction mixture was partitioned between methylene chloride and water
  5. washThe organic layer was washed with water
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto afford a crude oil
  10. customPurification by flash column chromatography (silica, gradient 97:3 to 94:6 methylene chloride/methanol)

출처 및 근거

ORD 기록
ord-a322266aa392493f9410ea6daa5cd517
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727997B2

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