Hydrochloric Acid → (S)-2-{[(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}-pentanoic acid tert-butyl ester

HRID 2242430노트

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HRID 2242430 반응식
CO[C:3]([C@@H:5]1[CH2:9][C@H:8]([O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[C:13]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:12]=2)[CH2:7][C@H:6]1[C:29](=[O:42])[NH:30][C@H:31]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:32][CH2:33][CH3:34])=[O:4].[Li+].[OH-].Cl.C(OC(=O)[NH:52][C@H:53]([C:58](=[O:71])[NH:59][C@@H:60]([CH:65]1[CH2:70][CH2:69][CH2:68][CH2:67][CH2:66]1)[C:61](=[O:64])[NH:62][CH3:63])[C:54]([CH3:57])([CH3:56])[CH3:55])(C)(C)C.CN(C(ON1N=NC2C=CC=NC1=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>O1CCOCC1.O.CN(C=O)C>[C:38]([O:37][C:35](=[O:36])[C@@H:31]([NH:30][C:29]([C@@H:6]1[CH2:7][C@@H:8]([O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[C:13]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:12]=2)[CH2:9][C@H:5]1[C:3](=[O:4])[NH:52][C@H:53]([C:58](=[O:71])[NH:59][C@@H:60]([CH:65]1[CH2:66][CH2:67][CH2:68][CH2:69][CH2:70]1)[C:61](=[O:64])[NH:62][CH3:63])[C:54]([CH3:56])([CH3:57])[CH3:55])=[O:42])[CH2:32][CH2:33][CH3:34])([CH3:40])([CH3:41])[CH3:39]

참가 물질

9

반응물 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 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 59204183(1R,2R,4R)-2-((S)-1-tert-Butoxycarbonyl-butylcarbamoyl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarboxylic acid methyl ester

생성물 1

HCID 59204189(S)-2-{[(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}-pentanoic acid tert-butyl ester수율 81%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 218864351,4-Dioxane--water (1/1)용매

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온도
0 °C

실험 절차

Compound 43 (38 mg, 0.066 mmol) was dissolved in dioxane/water 1:1 (4 mL) and the solution was cooled to 0° C. and 1 M LiOH (132 ul, 0.132 mmol) was added. The temperature was raised to room temperature and the solution was stirred for 2 hours after which it was neutralized by addition of 1M HCl and evaporated and coevaporated with toluene. The residue and deprotected amine 38 (1.1 eq) was dissolved in DMF and coupled using the standard HATU coupling conditions as in the synthesis of compound 34. The crude product was extracted with EtOAc, washed with brine, dried, filtered and concentrated. Purification with HPLC (MeOH/water 9:1+0.2% TEA) provided compound 44 (44 mg, 81%) as a colorless solid.

후처리

  1. temperatureThe temperature was raised to room temperature
  2. customevaporated
  3. extractionThe crude product was extracted with EtOAc
  4. washwashed with brine
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification with HPLC (MeOH/water 9:1+0.2% TEA)

출처 및 근거

ORD 기록
ord-13e3031341644732949a319c87fbb654
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07671032B2

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