6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide → 6-(cis-3-(Aminomethyl)-4-hydroxypyrrolidin-1-yl)-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide

HRID 525759노트

반응식

HRID 525759 반응식
Cl[C:2]1[C:21]([C:22]2[NH:26][N:25]=[CH:24][CH:23]=2)=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([Cl:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1.Cl.Cl.[NH2:29][CH2:30][C@H:31]1[CH2:35][NH:34][CH2:33][C@H:32]1[OH:36]>C(Cl)Cl.CCCCCC>[NH2:29][CH2:30][C@H:31]1[C@@H:32]([OH:36])[CH2:33][N:34]([C:2]2[C:21]([C:22]3[NH:26][N:25]=[CH:24][CH:23]=3)=[CH:20][C:5]([C:6]([NH:8][C:9]3[CH:10]=[CH:11][C:12]([O:15][C:16]([Cl:19])([F:18])[F:17])=[CH:13][CH:14]=3)=[O:7])=[CH:4][N:3]=2)[CH2:35]1

참가 물질

4

반응물 2

HCID 722015896-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamideHCID 89906931cis-4-(Aminomethyl)pyrrolidin-3-ol dihydrochloride

생성물 1

HCID 899080066-(cis-3-(Aminomethyl)-4-hydroxypyrrolidin-1-yl)-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide

시약·촉매·용매 1

HCID 21226440Methylenechloride Hexane용매

실험 절차

The title compound was prepared in an analogous fashion to that described in Example 48 using 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide (Stage 48.1) and cis-4-(aminomethyl)pyrrolidin-3-ol dihydrochloride (Stage 80.1). The crude product was purified by preparative HPLC (Condition 10). Fractions containing product were combined, treated with sat. aq. Na2CO3 and the MeCN was evaporated off under reduced pressure to give an aq. residue which was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue was suspended in DCM/n-hexane, filtered and dried to afford the title product as a beige solid. HPLC (Condition 7) tR=5.38 min, UPLC-MS (Condition 3) tR=0.78 min, m/z=479 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.85-2.05 (m, 1H) 2.38-2.86 (m, 2H) 2.88-3.06 (m, 1H) 3.08-3.23 (m, 1H) 3.24-3.37 (m, 2H) 3.91-4.18 (m, 1H) 6.33-6.42 (m, 1H) 7.32 (d, J=8.60 Hz, 2H) 7.68-7.91 (m, J=9.00 Hz, 3H) 7.97-8.06 (m, 1H) 8.68-8.78 (m, 1H) 10.20 (s, 1H) 12.94 (br. s, 1H).

후처리

  1. customThe title compound was prepared in an analogous fashion to
  2. customThe crude product was purified by preparative HPLC (Condition 10)
  3. additionFractions containing product
  4. additiontreated with sat. aq. Na2CO3
  5. customthe MeCN was evaporated off under reduced pressure
  6. customto give an aq. residue which
  7. extractionwas extracted with EtOAc
  8. washThe combined extracts were washed with brine
  9. dry with materialdried over Na2SO4
  10. customthe solvent was evaporated off under reduced pressure
  11. customto give a residue
  12. filtrationfiltered
  13. customdried

출처 및 근거

ORD 기록
ord-e8b186e889bf4356a52602282ad5c7bd
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340537B2

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