Diisopropylethylamine → HCID 89904540, compound

HRID 923844Notes

Reaction equation

HRID 923844 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][CH:25]([OH:28])[CH2:24]1.CCN(C(C)C)C(C)C>CC(O)C>[Br:1][C:2]1[C:3]([N:23]2[CH2:27][CH2:26][CH:25]([OH:28])[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

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 982104-HydroxypyrrolidineHCID 867025955-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 89904540HCID 89904540, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
140 °C

Procedure

5-Bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 12.2, 1 g, 2.53 mmol) and (Rac.)-pyrrolidin-3-ol (264 mg, 3.03 mmol) and DIPEA (883 μL, 5.06 mmol), in iPrOH (4213 μL) were added a MW vial and heated at 140° C. for 30 min. The RM was evaporated to dryness under reduced pressure, treated with 0.5 M HCl (10 mL) and EtOAc (20 mL) and extracted with EtOAc. The combined extracts were washed with water, dried over MgSO4 and evaporated to dryness under reduced pressure. Trituration of the residue in cyclohexane and filtration of the solid afforded the title compound as an off-white solid. UPLC-MS (condition 1) tR=2.63 min, m/z=445.9-447.9 [M+H]+, m/z=444.0-446.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.80-2.02 (m, 2H) 3.58 (d, J=11.49 Hz, 1H) 3.67-3.79 (m, 1H) 3.82-3.93 (m, 2H) 4.32-4.40 (m, 1H) 4.98 (br. s, 1H) 7.36 (d, J=8.56 Hz, 2H) 7.86 (d, J=9.05 Hz, 2H) 8.35 (d, J=1.96 Hz, 1H) 8.69 (d, J=1.96 Hz, 1H) 10.23 (s, 1H).

Workup

  1. customThe RM was evaporated to dryness under reduced pressure
  2. additiontreated with 0.5 M HCl (10 mL) and EtOAc (20 mL)
  3. extractionextracted with EtOAc
  4. washThe combined extracts were washed with water
  5. dry with materialdried over MgSO4
  6. customevaporated to dryness under reduced pressure
  7. filtrationTrituration of the residue in cyclohexane and filtration of the solid

Sources & evidence

ORD record
ord-b9ebead2e24f4ce7879390d2d9fd0e0c
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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