3,3-Difluoropyrrolidine hydrochloride → N-(4-(Chlorodifluoromethoxy)phenyl)-6-(3,3-difluoropyrrolidin-1-yl)-5-(pyrimidin-5-yl)nicotinamide

HRID 924124Notes

Reaction equation

HRID 924124 reaction equation
Cl[C:2]1[C:21]([C:22]2[CH:23]=[N:24][CH:25]=[N:26][CH:27]=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.[F:29][C:30]1([F:35])[CH2:34][CH2:33][NH:32][CH2:31]1>>[Cl:19][C:16]([F:18])([F:17])[O:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][C:6](=[O:7])[C:5]2[CH:20]=[C:21]([C:22]3[CH:23]=[N:24][CH:25]=[N:26][CH:27]=3)[C:2]([N:32]3[CH2:33][CH2:34][C:30]([F:35])([F:29])[CH2:31]3)=[N:3][CH:4]=2)=[CH:10][CH:11]=1

Participants

3

Reactant 2

HCID 249034823,3-Difluoropyrrolidine hydrochlorideHCID 899064746-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(pyrimidin-5-yl)nicotinamide

Product 1

HCID 89908340N-(4-(Chlorodifluoromethoxy)phenyl)-6-(3,3-difluoropyrrolidin-1-yl)-5-(pyrimidin-5-yl)nicotinamide

Procedure

The title compound was prepared in an analogous fashion to that described in Example 224 using 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(pyrimidin-5-yl)nicotinamide (Stage 247.1) and 3,3-difluoropyrrolidine hydrochloride (no extraction with citric acid). After purification by flash chromatography on Silica gel, the residue was suspended in iPr2O (10 mL) and stirred for 30 min. Crystals were filtrated off, washed with iPr2O (10 mL) and dried to afford the title product as a white solid. HPLC (Condition 10) tR=7.198 min, UPLC-MS (Condition 3) tR=1.12 min, m/z=482 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.39 (spt, J=7.14 Hz, 2H) 3.37 (t, J=7.23 Hz, 2H) 3.62 (t, J=12.90 Hz, 2H) 7.36 (d, J=8.21 Hz, 2H) 7.87 (d, J=8.99 Hz, 2H) 8.15 (s, 1H) 8.82 (s, 1H) 8.94 (s, 2H) 9.23 (s, 1H) 10.28 (s, 1H).

Workup

  1. customThe title compound was prepared in an analogous fashion to
  2. extractionno extraction with citric acid)
  3. customAfter purification by flash chromatography on Silica gel
  4. filtrationCrystals were filtrated off
  5. washwashed with iPr2O (10 mL)
  6. customdried

Sources & evidence

ORD record
ord-9a29af192be447168ce34618c100a2c1
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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