Diisopropyl Ether → HCID 89907938, compound

HRID 525776Notes

Reaction equation

HRID 525776 reaction equation
Cl[C:2]1[C:21]([C:22]2[NH:26][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.[NH2:27][CH2:28][CH:29]([OH:33])[CH2:30][CH2:31][OH:32].CCN(C(C)C)C(C)C.O(C(C)C)C(C)C>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]([NH:27][CH2:28][CH:29]([OH:33])[CH2:30][CH2:31][OH:32])=[N:3][CH:4]=2)=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 7914Diisopropyl EtherHCID 81531DiisopropylethylamineHCID 143256114-Aminobutane-1,3-diolHCID 722015896-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide

Product 1

HCID 89907938HCID 89907938, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
130 °C

Procedure

6-Chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide (Stage 48.1, 500 mg, 1.253 mmol), 4-aminobutane-1,3-diol (Stage 97.1, 152 mg, 1.447 mmol), DIPEA (0.667 mL, 3.82 mmol) and iPrOH (2 mL) were added to a MW vial, which was sealed, flushed with argon and stirred at 130° C. for 20 h. The RM was diluted with EtOAc and washed with water and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue which was treated with iPr2O and the resulting solid was filtered off and purified by flash chromatography (Silica gel column, 40 g, DCM/DCM-MeOH (9:1)) to afford the title compound as a white solid. UPLC-MS (Condition 8) tR=0.94 min, m/z=468 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1H NMR (400 MHz, DMSO-d6) δ ppm 1.46-1.74 (m, 2H) 3.44-3.58 (m, 3H) 3.64-3.72 (m, 1H) 3.77-3.90 (m, 1H) 4.40 (t, J=5.07 Hz, 1H) 4.82 (d, J=5.38 Hz, 1H) 6.96 (t, J=1.96 Hz, 1H) 7.36 (d, J=8.93 Hz, 2H) 7.83-7.99 (m, 3H) 8.41 (d, J=2.32 Hz, 1H) 8.65 (d, J=2.20 Hz, 1H) 9.04 (s, 1H) 10.21 (s, 1H) 13.21 (s, 1H).

Workup

  1. customwas sealed
  2. customflushed with argon
  3. additionThe RM was diluted with EtOAc
  4. washwashed with water and brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent was evaporated off under reduced pressure
  7. customto give a residue which
  8. filtrationthe resulting solid was filtered off
  9. custompurified by flash chromatography (Silica gel column, 40 g, DCM/DCM-MeOH (9:1))

Sources & evidence

ORD record
ord-95032601864046468870384312d1090c
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

Loading…