Hydrochloric Acid → HCID 118045017, compound

HRID 525762Notes

Reaction equation

HRID 525762 reaction equation
Cl[C:2]1[C:21]([C:22]2[N:26](C3CCCCO3)[N:25]=[CH:24][CH:23]=2)=[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:33]1[CH2:38][CH2:37][CH:36]([OH:39])[CH2:35][CH2:34]1.CCN(C(C)C)C(C)C.Cl.C([O-])(O)=O.[Na+]>CO.CC(O)C>[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][CH:23]=3)[C:2]([N:33]3[CH2:38][CH2:37][CH:36]([OH:39])[CH2:35][CH2:34]3)=[N:3][CH:4]=2)=[CH:10][CH:11]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 79341Piperidin-4-olHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 867026376-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide

Product 1

HCID 118045017HCID 118045017, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3776IsopropanolSolvent

Procedure

A mixture of 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide (Stage 48.2, 80 mg, 0.166 mmol), piperidin-4-ol (33.5 mg, 0.331 mmol), DIPEA (0.116 mL, 0.662 mmol) and iPrOH (0.331 mL) was added to a vial, which was sealed and subjected to MW irradiation at 140° C. for 1 h. Aq. 37% HCl (202 μL, 2.46 mmol) and MeOH (1 mL) was added and the mixture was stirred at RT. The RM was treated with sat. aq. NaHCO3 and extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by preparative SFC (Column DEAP, from 21% to 26% in 10 min.) to afford the title product as a white solid. UPLC-MS (Condition 3) tR=0.95 min, m/z=464.1 [M+H]+, m/z=508.0 [M+formic acid-H]−; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.33-1.49 (m, 2H) 1.73 (d, J=10.27 Hz, 2H) 2.87 (t, J=10.51 Hz, 2H) 3.50 (d, J=13.08 Hz, 2H) 3.62 (dd, J=8.19, 4.16 Hz, 1H) 4.67 (d, J=4.03 Hz, 1H) 6.54-6.70 (m, 1H) 7.34 (d, J=8.80 Hz, 2H) 7.77 (m, J=1.22 Hz, 2H) 7.88 (d, J=9.05 Hz, 2H) 8.27 (m, J=2.08 Hz, 1H) 8.69-8.78 (m, 1H) 10.31-10.44 (m, 1H) 12.96-13.21 (m, 1H).

Workup

  1. additionwas added to a vial, which
  2. customwas sealed
  3. customsubjected to MW irradiation at 140° C. for 1 h
  4. extractionextracted with EtOAc
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. customthe solvent was evaporated off under reduced pressure
  8. customto give the crude product which
  9. customwas purified by preparative SFC (Column DEAP, from 21% to 26% in 10 min.)

Sources & evidence

ORD record
ord-1b706a05d2b6487eb11483702072a339
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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