Azetidine → HCID 118006235, compound

HRID 926639Notes

Reaction equation

HRID 926639 reaction equation
[N:1]1([C:6]2[CH:39]=[CH:38][C:9]([CH2:10][C:11]3[C:12](Cl)=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17]([C:22]([C:30]3[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=3)([C:24]3[N:28]([CH3:29])[CH:27]=[N:26][CH:25]=3)[OH:23])=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.[NH:40]1[CH2:43][CH2:42][CH2:41]1>CN(C=O)C>[N:40]1([C:12]2[C:11]([CH2:10][C:9]3[CH:38]=[CH:39][C:6]([N:1]4[CH:5]=[CH:4][CH:3]=[N:2]4)=[CH:7][CH:8]=3)=[C:20]([Cl:21])[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:22]([C:30]4[CH:31]=[CH:32][C:33]([Cl:36])=[CH:34][CH:35]=4)([C:24]4[N:28]([CH3:29])[CH:27]=[N:26][CH:25]=4)[OH:23])[CH:18]=3)[N:13]=2)[CH2:43][CH2:42][CH2:41]1

Participants

4

Reactant 2

HCID 10422AzetidineHCID 74221327HCID 74221327, compound2×

Product 1

HCID 118006235HCID 118006235, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloroquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol (200 mg, 0.348 mmol, Intermediate 64), azetidine (199 mg, 3.48 mmol), and DMF (2 mL) were combined in a reaction tube, then sealed and heated to 100° C. and maintained at that temperature for 24 hours. The vessel was then cooled to room temperature and the solvent was removed by reduced pressure distillation. The residue was taken up into EtOAc, transferred to a separatory funnel and extracted twice with a saturated, aqueous NH4Cl solution. The organic phase was separated, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified via reverse phase chromatography using acetonitrile with ammonium hydroxide in water as eluent to provide the title compound. MS (ESI): mass calcd. for C33H28Cl2N6O, 594.2. m/z found, 595.3 [M+H]+. 1H NMR (600 MHz, CDCl3) δ ppm 8.03 (d, J=2.1 Hz, 1H), 7.86 (d, J=2.4 Hz, 1H), 7.70-7.67 (m, 2H), 7.61-7.56 (m, 2H), 7.45 (dd, J=8.8, 2.2 Hz, 1H), 7.32-7.27 (m, 4H), 7.24 (d, J=1.1 Hz, 1H), 7.20-7.14 (m, 2H), 6.43 (t, J=2.1 Hz, 1H), 6.33 (d, J=1.2 Hz, 1H), 4.30 (s, 2H), 4.14 (t, J=7.6 Hz, 4H), 3.35 (s, 3H), 2.27-2.17 (m, 2H).

Workup

  1. customsealed
  2. temperaturemaintained at that temperature for 24 hours
  3. temperatureThe vessel was then cooled to room temperature
  4. customthe solvent was removed by reduced pressure distillation
  5. customtransferred to a separatory funnel
  6. extractionextracted twice with a saturated, aqueous NH4Cl solution
  7. customThe organic phase was separated
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude material was purified via reverse phase chromatography

Sources & evidence

ORD record
ord-530e93b5ce9b4b248cb1b5f3135ab12f
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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