Hydrochloric Acid → 5-bromo-6-(pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 923887Notes

Reaction equation

HRID 923887 reaction equation
[Br: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].[NH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1.CCN(C(C)C)C(C)C.Cl>CC(O)C>[Br:1][C:2]1[C:3]([N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]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 313Hydrochloric AcidHCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 867025955-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 899068675-bromo-6-(pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

5-Bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 12.2, 1 g, 2.53 mmol) and pyrrolidine (0.544 g, 5.06 mmol) were suspended in iPrOH (2.53 mL), and DIPEA (1.325 mL, 7.58 mmol) was added. The RM was subjected to MW irradiation at 140° C. for 1 hr. The RM was treated with 0.5 M HCl (40 mL) and extracted with EtOAc. The combined extracts were sequentially washed with 0.5 M HCl (40 mL) and brine, dried over Na2SO4 and evaporated to dryness under reduced pressure. Crystallization from a cyclohexane/EtOAc mixture yielded the title compound as an off-white solid. UPLC-MS (Condition 3) tR=1.34 min, m/z=430.1/432.1 [M+H]+, m/z=428.3/430.3 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.76-2.01 (m, 4H) 3.60-3.80 (m, 4H) 7.33 (d, J=8.20 Hz, 2H) 7.72-7.91 (m, 2H) 8.32 (d, J=1.95 Hz, 1H) 8.66 (d, J=1.95 Hz, 1H) 10.20 (s, 1H).

Workup

  1. customThe RM was subjected to MW irradiation at 140° C. for 1 hr
  2. extractionextracted with EtOAc
  3. washThe combined extracts were sequentially washed with 0.5 M HCl (40 mL) and brine
  4. dry with materialdried over Na2SO4
  5. customevaporated to dryness under reduced pressure
  6. customCrystallization from a cyclohexane/EtOAc mixture

Sources & evidence

ORD record
ord-1ecdc2172a2543d0b730d5f164968d70
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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