Diisopropylethylamine → 2-((3S,4S)-3-(Dimethylamino)-4-hydroxypyrrolidin-1-yl)-5'-fluoro-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

HRID 924109Notes

Reaction equation

HRID 924109 reaction equation
Cl[C:2]1[C:7]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([F:14])[CH:13]=2)=[CH:6][C:5]([C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=2)=[O:16])=[CH:4][N:3]=1.CCN(C(C)C)C(C)C.[CH3:38][N:39]([CH3:46])[C@H:40]1[CH2:44][NH:43][CH2:42][C@@H:41]1[OH:45]>CC(O)C>[CH3:38][N:39]([CH3:46])[C@@H:40]1[C@@H:41]([OH:45])[CH2:42][N:43]([C:2]2[C:7]([C:8]3[CH:9]=[N:10][CH:11]=[C:12]([F:14])[CH:13]=3)=[CH:6][C:5]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]([F:27])([F:28])[F:26])=[CH:20][CH:19]=3)=[O:16])=[CH:4][N:3]=2)[CH2:44]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 45791186(3S,4S)-4-(dimethylamino)pyrrolidin-3-olHCID 722015862-Chloro-5'-fluoro-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

Product 1

HCID 1181951082-((3S,4S)-3-(Dimethylamino)-4-hydroxypyrrolidin-1-yl)-5'-fluoro-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
110 °C

Procedure

2-Chloro-5′-fluoro-N-(4-(trifluoromethoxy)phenyl)-[3,3′-bipyridine]-5-carboxamide (Stage 236.1, 60 mg, 0.137 mmol) and DIPEA (0.167 mL, 0.959 mmol) were added to a vial containing iPrOH (1 mL). (3S,4S)-4-(dimethylamino)pyrrolidin-3-ol (50 mg, 0.246 mmol) was added. The mixture was stirred at 110° C. for 16 h. The solvent was evaporated off under reduced pressure and the residue was purified by preparative SFC (Column DEAP, from 15% to 20% in 6 min) to afford the title product as a beige foam. HPLC (Condition 10) tR=5.93 min, UPLC-MS (Condition 3) tR=0.81 min, m/z=506.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.14 (s, 6H) 2.52-2.58 (m, 1H) 2.88 (dd, J=11.14, 5.28 Hz, 1H) 3.21 (dd, J=11.34, 5.86 Hz, 1H) 3.28 (dd, J=10.56, 5.86 Hz, 1H) 3.44 (dd, J=11.34, 7.00 Hz, 1H) 4.07 (quin, J=5.28 Hz, 1H) 5.07 (d, J=5.08 Hz, 1H) 7.35 (d, J=9.38 Hz, 2H) 7.85 (d, J=9.38 Hz, 3H) 8.09 (d, J=2.35 Hz, 1H) 8.52 (s, 1H) 8.61 (d, J=2.35 Hz, 1H) 8.78 (d, J=2.35 Hz, 1H) 10.19 (s, 1H).

Workup

  1. customThe solvent was evaporated off under reduced pressure
  2. customthe residue was purified by preparative SFC (Column DEAP, from 15% to 20% in 6 min)

Sources & evidence

ORD record
ord-424c4b5829f249ff90fc2ed4987e1d25
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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