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 525759ノート

反応式

HRID 525759 の反応式
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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 21226440Methylenechloride Hexane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-e8b186e889bf4356a52602282ad5c7bd
出典データセット
uspto-grants-2016_05
特許番号
US09340537B2

反応ノート

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