Diisopropyl Ether → HCID 89907876, compound

HRID 525699Notes

Reaction equation

HRID 525699 reaction equation
CCN(C(C)C)C(C)C.Cl[C:11]1[C:30]([C:31]2[NH:35][N:34]=[CH:33][CH:32]=2)=[CH:29][C:14]([C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=2)=[O:16])=[CH:13][N:12]=1.[CH3:36][N:37]([CH3:42])[CH:38]1[CH2:41][NH:40][CH2:39]1.O(C(C)C)C(C)C>CCOC(C)=O>[CH3:36][N:37]([CH3:42])[CH:38]1[CH2:41][N:40]([C:11]2[C:30]([C:31]3[NH:35][N:34]=[CH:33][CH:32]=3)=[CH:29][C:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:26])[F:27])=[CH:20][CH:19]=3)=[O:16])=[CH:13][N:12]=2)[CH2:39]1

Participants

6

Reactant 4

HCID 7914Diisopropyl EtherHCID 81531DiisopropylethylamineHCID 10351656N,N-dimethylazetidin-3-amineHCID 89907281HCID 89907281, compound

Product 1

HCID 89907876HCID 89907876, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

DIPEA (0.182 mL, 1.043 mmol) was added to 6-chloro-5-(1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 38.1, 70 mg, 0.174 mmol), N,N-dimethylazetidin-3-amine (60.1 mg, 0.348 mmol) and iPr2O (1 mL) in a vial, which was sealed and the RM was stirred at 110° C. for 5 h. After cooling to RT, the RM was dissolved in EtOAc, washed with brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a crude product which was purified by preparative HPLC (Condition 10). Fractions containing product were combined, treated with sat. aq. Na2CO3 and the MeCN was evaporated off under reduced pressure. The aq. phase was extracted with DCM (2×20 mL) and the combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the title compound as white crystals. HPLC (Condition 7) tR=5.627 min, UPLC-MS (Condition 3) tR=0.75 min, m/z=447.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.01 (s, 6H) 2.90-3.05 (m, 1H) 3.49-3.62 (m, 2H) 3.70-3.87 (m, 2H) 6.36-6.51 (m, 1H) 7.34 (d, J=8.99 Hz, 2H) 7.80-7.92 (m, J=8.60 Hz, 3H) 8.08 (d, J=2.35 Hz, 1H) 8.69-8.79 (m, J=2.30 Hz, 1H) 10.24 (s, 1H) 12.90-13.21 (m, 1H).

Workup

  1. customwas sealed
  2. temperatureAfter cooling to RT
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give a crude product which
  7. customwas purified by preparative HPLC (Condition 10)
  8. additionFractions containing product
  9. additiontreated with sat. aq. Na2CO3
  10. customthe MeCN was evaporated off under reduced pressure
  11. extractionThe aq. phase was extracted with DCM (2×20 mL)
  12. dry with materialthe combined extracts were dried over Na2SO4
  13. customthe solvent was evaporated off under reduced pressure

Sources & evidence

ORD record
ord-789d78e5c8544517b3be0028c53e8cd6
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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