Hydrochloric Acid → (S)-N-((1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-yl)pyrrolidine-2-carboxamide

HRID 13154

반응식

HRID 13154 반응식
[O:1]1[CH2:6][CH2:5][O:4][C:3]2[CH:7]=[C:8]([C@@H:11]([O:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[N:21]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[N:20]=[CH:19]4)[C@@H:12]([NH2:14])[CH3:13])[CH:9]=[CH:10][C:2]1=2.C(OC([N:39]1[CH2:43][CH2:42][CH2:41][C@H:40]1[C:44](O)=[O:45])=O)(C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl>CN1C(=O)CCC1.O.CCOC(C)=O.CC(O)C>[O:1]1[CH2:6][CH2:5][O:4][C:3]2[CH:7]=[C:8]([C@@H:11]([O:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[N:21]([C:25]3[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=3)[N:20]=[CH:19]4)[C@@H:12]([NH:14][C:44]([C@@H:40]3[CH2:41][CH2:42][CH2:43][NH:39]3)=[O:45])[CH3:13])[CH:9]=[CH:10][C:2]1=2

참가 물질

10

반응물 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59339888(1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-amine

생성물 1

HCID 58201640(S)-N-((1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-yl)pyrrolidine-2-carboxamide

시약·촉매·용매 4

HCID 962Water용매HCID 3776Isopropanol용매HCID 8857Ethyl Acetate용매HCID 13387N-methyl-2-pyrrolidone용매2회

실험 절차

(1R,28)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-amine (19a) (102 mg, 0.24 mmol) dissolved in NMP (1 mL) was added to a solution of (S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (77 mg, 0.36 mmol), HATU (150 mg, 0.39 mmol) and DIPEA (170 μl, 0.97 mmol) in NMP (2 mL). The mixture was stirred at r.t. for 1 h. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2×10 mL), the organic solution was washed with brine, dried (Na2SO4), filtered and evaporated to give an oily residue. The obtained material was dissolved in EtOAc (20 mL) and treated with 5-6N HCl in 2-Propanol (5 mL), the solution was stirred at +40° C. for 1 h. Solvents was removed by evaporation. The crude material was purified by HPLC, relevant fractions was freezedried to give the title compound as a colourless solid. Yield 21 mg (16%)

후처리

  1. extractionextracted with EtOAc (2×10 mL)
  2. washthe organic solution was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto give an oily residue
  7. stirringthe solution was stirred at +40° C. for 1 h
  8. customSolvents was removed by evaporation
  9. customThe crude material was purified by HPLC, relevant fractions
  10. customwas freezedried

출처 및 근거

ORD 기록
ord-ec1002f98a714fadb721ddd260d57ac2
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07728030B2

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