Trifluoroacetic acid → (1R,2S)-1-{[(1R,2R,4S)-2-{(S)-1-[((S)-Cyclohexyl-methylcarbamoyl-methyl)-carbamoyl]-2,2-dimethyl-propylcarbamoyl}-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester

HRID 2242425노트

반응식

HRID 2242425 반응식
C(O[C:6]([C@@H:8]1[CH2:12][C@H:11]([O:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=3)[N:17]=[C:16]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:15]=2)[CH2:10][C@H:9]1[C:32](=[O:44])[NH:33][C@:34]1([C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH2:36][C@H:35]1[CH:37]=[CH2:38])=[O:7])(C)(C)C.C([SiH]([CH2:50][CH3:51])CC)C.C(O)(C(F)(F)F)=O.C(OC(=O)[NH:65][C@H:66]([C:71](=[O:84])[NH:72][C@@H:73](C1CCCCC1)[C:74](=[O:77])[NH:75][CH3:76])[C:67]([CH3:70])([CH3:69])[CH3:68])(C)(C)C.CN(C(ON1N=N[C:96]2[CH:97]=[CH:98]C=N[C:95]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(OC([C@@H]1C[C@@H](O)C[C@H]1C(=O)N[C@]1(C(OCC)=O)C[C@H]1C=C)=O)(C)(C)C>C(Cl)Cl>[CH2:42]([O:41][C:39]([C@@:34]1([NH:33][C:32]([C@@H:9]2[CH2:10][C@@H:11]([O:13][C:14]3[C:23]4[C:18](=[CH:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=4)[N:17]=[C:16]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH:15]=3)[CH2:12][C@H:8]2[C:6](=[O:7])[NH:65][C@H:66]([C:71](=[O:84])[NH:72][C@@H:73]([CH:51]2[CH2:50][CH2:98][CH2:97][CH2:96][CH2:95]2)[C:74](=[O:77])[NH:75][CH3:76])[C:67]([CH3:69])([CH3:70])[CH3:68])=[O:44])[CH2:36][C@H:35]1[CH:37]=[CH2:38])=[O:40])[CH3:43]

참가 물질

8

반응물 6

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57892933{(S)-1-[((S)-Cyclohexyl-methylcarbamoyl-methyl)-carbamoyl]-2,2-dimethyl-propyl}-carbamic acid tert-butyl esterHCID 59165438(1R,2R,4S)-2-((1R,2S)-1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl) 4-hydroxy-cyclopentanecarboxylic acid tert-butyl esterHCID 59204175(1R,2R,4R)-2-((1R,2S)-1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarboxylic acid tert-butyl ester2회

생성물 1

HCID 59204178(1R,2S)-1-{[(1R,2R,4S)-2-{(S)-1-[((S)-Cyclohexyl-methylcarbamoyl-methyl)-carbamoyl]-2,2-dimethyl-propylcarbamoyl}-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester수율 74%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of compound 35 (30 mg, 0.050 mmol) in methylene chloride (1.5 mL) were added triethylsilane (21 □L, 0.132 mmol) and TFA (1.5 mL). The mixture was stirred for 2 h at room temperature and was then evaporated and coevaporated with toluene. The amine 38 (1.3 eq) was deprotected in the same manner as compound 35 and was then coupled to deprotected compound 35 using the same HATU coupling conditions as in the synthesis of 34. The crude product was extracted with EtOAc, washed with brine, dried, filtered and concentrated. Purification using HPLC (MeOH/water 9:1+0.2% triethylamine) provided compound 39 (30 mg, 74%) as a colorless solid.

후처리

  1. customwas then evaporated
  2. extractionThe crude product was extracted with EtOAc
  3. washwashed with brine
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification

출처 및 근거

ORD 기록
ord-3d7bd8536cd844a1893f40922ebdb776
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07671032B2

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