(3R,4R)-4-fluoropyrrolidin-3-ol → N-(4-(Chlorodifluoromethoxy)phenyl)-6-(trans-3-fluoro-4-hydroxypyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)nicotinamide

HRID 525750Notes

Reaction equation

HRID 525750 reaction equation
Cl[C:2]1[C:21]([C:22]2[N:26](C3CCCCO3)[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.[F:33][C@@H:34]1[CH2:38][NH:37][CH2:36][C@H:35]1[OH:39]>>[Cl:19][C:16]([F:17])([F:18])[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[NH:26][N:25]=[CH:24][CH:23]=3)[C:2]([N:37]3[CH2:36][C@@H:35]([OH:39])[C@H:34]([F:33])[CH2:38]3)=[N:3][CH:4]=2)=[CH:10][CH:11]=1

Participants

3

Reactant 2

HCID 72207824(3R,4R)-4-fluoropyrrolidin-3-olHCID 867026376-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide

Product 1

HCID 89907402N-(4-(Chlorodifluoromethoxy)phenyl)-6-(trans-3-fluoro-4-hydroxypyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)nicotinamide

Procedure

The title compound was prepared in an analogous fashion to that described in Example 33 using 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide (Stage 48.2) and trans-4-fluoropyrrolidin-3-ol to afford an amorphous white powder. HPLC (Condition 4) tR=5.21 min, UPLC-MS (Condition 3) tR=0.99 min, m/z=468.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.06 (d, J=12.12 Hz, 1H) 3.33-3.49 (m, 2H) 3.53-3.76 (m, 1H) 4.15 (br. s, 1H) 4.77-5.02 (m, 1H) 5.36-5.50 (m, 1H) 6.41 (br. s, 1H) 7.31 (d, J=8.60 Hz, 2H) 7.79-7.91 (m, 3H) 8.06 (d, J=1.96 Hz, 1H) 8.73 (br. s, 1H) 10.21 (s, 1H) 12.90-13.21 (m, 1H).

Workup

  1. customto afford an amorphous white powder

Sources & evidence

ORD record
ord-375fffff06e34befb602861d262fcbe5
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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