N,N-二异丙基乙胺 → (S)-6-(((3-Fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)-methyl)carbamoyl)nicotinic Acid

HRID 509365

反应方程式

HRID 509365 反应方程式
C[O:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]([C:11]([OH:13])=O)=[N:9][CH:10]=1)=[O:4].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.[F:48][C:49]1[C:50]([C@H:55]([C:57]2[CH:62]=[CH:61][C:60]([C:63]([F:66])([F:65])[F:64])=[CH:59][CH:58]=2)[NH2:56])=[N:51][CH:52]=[CH:53][CH:54]=1.Cl.FC(F)(F)C1C=CC([C@@H](C2C(C(F)(F)F)=CC=CN=2)N)=CC=1>C(Cl)Cl>[F:48][C:49]1[C:50]([C@@H:55]([NH:56][C:11]([C:8]2[CH:7]=[CH:6][C:5]([C:3]([OH:2])=[O:4])=[CH:10][N:9]=2)=[O:13])[C:57]2[CH:62]=[CH:61][C:60]([C:63]([F:66])([F:64])[F:65])=[CH:59][CH:58]=2)=[N:51][CH:52]=[CH:53][CH:54]=1

参与物

7

反应物 5

HCID 81531N,N-二异丙基乙胺HCID 3149925-(甲氧羰基)-2-吡啶羧酸HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71144279(S)-(3-Fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)methanamine HydrochlorideHCID 86687962(S)-(4-(Trifluoromethyl)phenyl)(3-(trifluoromethyl)pyridin-2-yl)methanamine Hydrochloride

产物 1

HCID 71144036(S)-6-(((3-Fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)-methyl)carbamoyl)nicotinic Acid

试剂、催化剂与溶剂 1

HCID 6344二氯甲烷溶剂

实验过程

To a solution of 5-(methoxycarbonyl)picolinic acid (101 mg, 0.558 mmol) in DCM (4 mL) was added HATU (217 mg, 0.571 mmol) and DIPEA (0.20 mL, 1.148 mmol). After stirring for 30 min at rt, the reaction was treated with (S)-(3-fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)methanamine hydrochloride (Intermediate 2) (125 mg, 0.364 mmol). After 16 h, the reaction was concentrated in vacuo and then taken up in THF (3 mL), MeOH (1 mL), and 1M LiOH (1 mL). The resulting mixture was stirred at rt for 2 h. The reaction mixture was concentrated in vacuo, acidified with 1N HCl and extracted with EtOAc (3×5 mL). The combined EtOAc layers were concentrated in vacuo and chromatographed through a Redi-Sep® pre-packed silica gel column (4 g), eluting with 0% to 100% EtOAc in hexane, to provide the title compound as an off-white solid. 1H NMR (CDCl3: CD3OD, 300 MHz) δ ppm 9.21 (d, J=1.5 Hz, 1H), 8.47 (d, J=4.7 Hz, 1H), 8.39 (dd, J=8.0, 1.9 Hz, 1H), 8.14 (d, J=8.0 Hz, 1H), 7.56 (d, J=8.5 Hz, 2H), 7.50 (d, J=8.6 Hz, 2H), 7.42 (t, J=9.5 Hz, 1H), 7.27-7.32 (m, 1H), 6.63 (s, 1H). MS (ESI pos. ion) m/z: 419.9 (M+H).

后处理

  1. waitAfter 16 h
  2. concentrationthe reaction was concentrated in vacuo
  3. stirringThe resulting mixture was stirred at rt for 2 h
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. extractionextracted with EtOAc (3×5 mL)
  6. concentrationThe combined EtOAc layers were concentrated in vacuo
  7. customchromatographed through a Redi-Sep® pre-packed silica gel column (4 g)
  8. washeluting with 0% to 100% EtOAc in hexane

来源与证据

ORD记录
ord-4a70336f844d40399c0d1505b2d88d1b
来源数据集
uspto-grants-2015_08
专利号
US09096527B2

关联笔记

加载中…