Diisopropylethylamine → (R)-5-chloro-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 923856Notes

Reaction equation

HRID 923856 reaction equation
[Cl:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].ClC1[C:25](Cl)=[N:26][CH:27]=[C:28](C=1)[C:29]([OH:31])=O.N1CC[C@@H](O)C1.CCN(C(C)C)C(C)C>CC(O)C>[Cl:1][C:2]1[C:3]([N:26]2[CH2:27][CH2:28][C@@H:29]([OH:31])[CH2:25]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2479875,6-Dichloronicotinic acidHCID 2759337(R)-3-PyrrolidinolHCID 81946485,6-dichloro-N-[4-(trifluoromethoxy)phenyl]pyridine-3-carboxamide

Product 1

HCID 89907107(R)-5-chloro-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 5,6-dichloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (prepared from 5,6-dichloronicotinic acid in an analogous fashion to that described in Stage 12.2, 1.5 g, 4.27 mmol), (R)-pyrrolidin-3-ol (447 mg, 5.13 mmol), iPrOH (10 mL) and DIPEA (1.104 g, 8.54 mmol) were subjected to MW irradiation at 140° C. for 60 min. The RM was quenched with water (100 mL) and extracted with EtOAc (3×100 mL). The combined organic extracts were washed with brine (100 mL), dried over MgSO4, filtered and the filtrate was evaporated off under reduced pressure to afford the title compound as a beige powder. 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.85-1.97 (m, 2H) 3.59 (d, J=12 Hz, 1H) 3.7-3.8 (m, 1H) 3.8-3.95 (m, 2H) 4.35-4.40 (m, 1H) 5.00 (s, 1H) 7.35 (d, J=2 Hz, 2H) 7.86 (d, J=2 Hz, 2H) 8.17 (s, 1H) 8.66 (s, 1H) 10.22 (s, 1H).

Workup

  1. customwere subjected to MW irradiation at 140° C. for 60 min
  2. customThe RM was quenched with water (100 mL)
  3. extractionextracted with EtOAc (3×100 mL)
  4. washThe combined organic extracts were washed with brine (100 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe filtrate was evaporated off under reduced pressure

Sources & evidence

ORD record
ord-ce7270f269a94c6787f607fdf3fcdd38
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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