Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → tert-Butyl N-[(tert-butoxy)carbonyl]-N-(6-{[(2R)-7-(cyclopropylsulfanyl)-14-hydroxy-4,17,20-trimethyl-3,12-dioxo-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10 (21),16,19-hexaen-2-yl]amino}-4-fluoroisoquinolin-1-yl)carbamate

HRID 708816노트

반응식

HRID 708816 반응식
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:28][C:29]1[CH:30]=[CH:31][C:32]([S:83][CH:84]2[CH2:86][CH2:85]2)=[C:33]([CH2:35][N:36]([CH3:82])[C:37]([CH:39]([NH:55][C:56]2[CH:57]=[C:58]3[C:63](=[CH:64][CH:65]=2)[C:62]([N:66]([C:74]([O:76][C:77]([CH3:80])([CH3:79])[CH3:78])=[O:75])[C:67]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])=[O:68])=[N:61][CH:60]=[C:59]3[F:81])[C:40]2[CH:45]=[C:44]([CH3:46])[C:43]([CH2:47][CH:48]([OH:53])[CH2:49][C:50]([OH:52])=O)=[C:42]([CH3:54])[CH:41]=2)=[O:38])[CH:34]=1>CN(C1C=CN=CC=1)C.ClCCl.CN(C=O)C>[C:77]([O:76][C:74]([N:66]([C:62]1[C:63]2[C:58](=[CH:57][C:56]([NH:55][C@H:39]3[C:37](=[O:38])[N:36]([CH3:82])[CH2:35][C:33]4[CH:34]=[C:29]([CH:30]=[CH:31][C:32]=4[S:83][CH:84]4[CH2:85][CH2:86]4)[NH:28][C:50](=[O:52])[CH2:49][CH:48]([OH:53])[CH2:47][C:43]4[C:42]([CH3:54])=[CH:41][C:40]3=[CH:45][C:44]=4[CH3:46])=[CH:65][CH:64]=2)[C:59]([F:81])=[CH:60][N:61]=1)[C:67](=[O:68])[O:69][C:70]([CH3:71])([CH3:72])[CH3:73])=[O:75])([CH3:78])([CH3:79])[CH3:80]

참가 물질

6

반응물 2

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 1180928014-{4-[({[5-Amino-2-(cyclopropylsulfanyl)phenyl]methyl}(methyl)carbamoyl)[(1-{bis[(tert-butoxy)carbonyl]amino}-4-fluoroisoquinolin-6-yl)amino]methyl]-2,6-dimethylphenyl}-3-hydroxybutanoic acid

생성물 1

HCID 118098686tert-Butyl N-[(tert-butoxy)carbonyl]-N-(6-{[(2R)-7-(cyclopropylsulfanyl)-14-hydroxy-4,17,20-trimethyl-3,12-dioxo-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10 (21),16,19-hexaen-2-yl]amino}-4-fluoroisoquinolin-1-yl)carbamate수율 32.6%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회

실험 절차

To a solution of BOP (234 mg, 0.529 mmol), TEA (0.074 mL, 0.529 mmol) and DMAP (129 mg, 1.058 mmol) in dichloromethane (10 mL) and DMF (10 mL) was added 2E in dichloromethane (10 mL) via a syringe pump over 10.0 h. The reaction was continued at rt for 4 h, quenched by water and extracted by EtOAc (×3). The combined organics were washed by brine, dried with Na2SO4 and concentrated. The crude product was purified by flash chromatography (loading in chloroform, 0% to 100% ethyl acetate in hexane over 10 min using a 4 g silica gel cartridge) to give a mixture of diastereoisomers (92 mg, 43% yield). The diastereoisomers were separated to give 2F (30 mg, 0.037 mmol, 32.6% yield) using a R,R-Welko-O 1 column (21.1 mm×250 mm, 10 micron, Regis Technologies, Inc.). MS (ESI) m/z: 814.7 (M+H)+.

후처리

  1. customquenched by water
  2. extractionextracted by EtOAc (×3)
  3. washThe combined organics were washed by brine
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography (loading in chloroform
  7. wait0% to 100% ethyl acetate in hexane over 10 min using
  8. customa 4 g silica gel cartridge) to give
  9. additiona mixture of diastereoisomers (92 mg, 43% yield)
  10. customThe diastereoisomers were separated

출처 및 근거

ORD 기록
ord-8920ab6ed5a841ef8b4361aa3c6bce93
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09174974B2

반응 노트

불러오는 중…