(3S)-pyrrolidin-3-ol → (S)-N-(4-(Chlorodifluoromethoxy)phenyl)-5-(4-fluoro-1H-pyrazol-5-yl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide

HRID 73810Notes

Reaction equation

HRID 73810 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 2733874(3S)-pyrrolidin-3-olHCID 867026256-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(4-fluoro-1H-pyrazol-5-yl)nicotinamide

Product 1

HCID 72545851(S)-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 (S)-3-pyrrolidinol to afford a white solid. HPLC (Condition 5) tR=5.69 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=12.62 min, UPLC-MS (Condition 6) tR=0.97 min, m/z=468.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.71-1.81 (m, 1H) 1.81-1.92 (m, 1H) 3.02 (d, J=11.34 Hz, 1H) 3.24-3.37 (m, 2H) 3.40-3.49 (m, 1H) 4.23 (br. s, 1H) 4.89 (br. s, 1H) 7.32 (d, J=9.4 Hz, 2H) 7.76-7.98 (m, J=9.00 Hz, 3H) 8.03 (d, J=2.35 Hz, 1H) 8.79 (d, J=2.35 Hz, 1H) 10.20 (br. s, 1H) 12.99 (br. s, 1H).

Workup

  1. customto afford a white solid

Sources & evidence

ORD record
ord-e2979971eb054882a108d11f2e2f8768
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

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