(R)-3-Pyrrolidinol → (R)-N-(4-(Chlorodifluoromethoxy)phenyl)-5-(4-fluoro-1H-pyrazol-5-yl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide

HRID 73788Notes

Reaction equation

HRID 73788 reaction equation
Cl[C:2]1[C:21]([C:22]2[NH:26][N:25]=[CH:24][C:23]=2[F:27])=[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.[NH:28]1[CH2:32][CH2:31][C@@H:30]([OH:33])[CH2:29]1>CCCCCCC.CCO.CO>[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[NH:26][N:25]=[CH:24][C:23]=3[F:27])[C:2]([N:28]3[CH2:32][CH2:31][C@@H:30]([OH:33])[CH2:29]3)=[N:3][CH:4]=2)=[CH:10][CH:11]=1

Participants

4

Reactant 2

HCID 2759337(R)-3-PyrrolidinolHCID 867026256-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(4-fluoro-1H-pyrazol-5-yl)nicotinamide

Product 1

HCID 72545600(R)-N-(4-(Chlorodifluoromethoxy)phenyl)-5-(4-fluoro-1H-pyrazol-5-yl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide

Reagents, catalysts & solvents 1

HCID 22386818heptane EtOH MeOHSolvent

Procedure

The title compound was prepared in an analogous fashion to that described in Example 5 using 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(4-fluoro-1H-pyrazol-5-yl)nicotinamide (Stage 25.1) and (R)-pyrrolidin-3-ol to afford a white powder. HPLC (Condition 4) tR=4.89 min, HPLC Chiral (CHIRALCEL® OD-H, 250×4.6 mm, eluent:n-heptane/EtOH/MeOH (85:10:5), 1 mL/min, UV 210 nm) tR=9.34 min, UPLC-MS (Condition 3) tR=0.96 min, m/z=468.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.67-1.92 (m, 2H) 3.00 (d, J=11.73 Hz, 1H) 3.19-3.33 (m, 2H) 3.43 (m, J=7.00 Hz, 1H) 4.22 (br. s, 1H) 4.87 (br. s, 1H) 7.31 (d, J=8.60 Hz, 2H) 7.85 (d, J=8.99 Hz, 2H) 7.90-8.10 (m, 2H) 8.77 (br. s, 1H) 10.18 (s, 1H) 12.83-13.19 (m, 1H).

Workup

  1. customto afford a white powder

Sources & evidence

ORD record
ord-a236e71902b046f7be57a8e01162ea30
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

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