Water → HCID 59843064, compound

HRID 1878786Notes

Reaction equation

HRID 1878786 reaction equation
[N:1]([CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][C:14](=[O:32])[N:15]([CH2:17][CH2:18][O:19][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=[CH:22][CH:21]=3)[N:16]=2)=[CH:7][C:6]=1[Cl:33])=[N+]=[N-].O.O.O.O.O.O.O.O.O.O.[S-2].[Na+].[Na+]>C1COCC1.CO>[NH2:1][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][C:14](=[O:32])[N:15]([CH2:17][CH2:18][O:19][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=[CH:22][CH:21]=3)[N:16]=2)=[CH:7][C:6]=1[Cl:33]

Participants

6

Reactant 3

HCID 962WaterHCID 73972Sodium sulfide nonahydrateHCID 59843032HCID 59843032, compound

Product 1

HCID 59843064HCID 59843064, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 6-(4-(azidomethyl)-3-chlorophenyl)-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2H)-one (400 mg, 864 μmol) in THF (8 mL), MeOH (1 mL), and water (1 mL) was added sodium sulfide, nonahydrate (540 mg, 6913 μmol) and stirred overnight at 40° C. The reaction was then partitioned between DCM and 5% NaHCO3. The organic layer was dried over MgSO4, concentrated, then purified on silica (40 g) eluting with 0>6% of NH3 in MeOH (2 M)/DCM. The product was further purified on RP-HPLC eluting with ACN/water (0.1% TFA). Desired fractions concentrated under reduced pressure then residue partitioned between DCM and NaOH (1 M). The organic was then dried over MgSO4 and concentrated under reduced pressure to provide a white solid. MS (ESI pos. ion) m/z: 437 (MH+); calc'd for C23H21ClN4O3: 436. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.91 (s, 3 H) 3.99 (s, 2 H) 4.65 (t, J=5.38 Hz, 2 H) 4.80 (t, J=5.28 Hz, 2 H) 6.67 (d, J=5.48 Hz, 1 H) 6.98-7.09 (m, 2 H) 7.32 (d, J=2.35 Hz, 1 H) 7.48 (d, J=8.02 Hz, 1 H) 7.58 (dd, J=8.02, 1.76 Hz, 1 H) 7.64 (d, J=9.78 Hz, 1 H) 7.79 (d, J=1.76 Hz, 1 H) 8.02 (d, J=9.19 Hz, 1 H) 8.64 (d, J=5.28 Hz, 1 H)

Workup

  1. customThe reaction was then partitioned between DCM and 5% NaHCO3
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated
  4. custompurified on silica (40 g)
  5. washeluting with 0>6% of NH3 in MeOH (2 M)/DCM
  6. customThe product was further purified on RP-HPLC
  7. washeluting with ACN/water (0.1% TFA)
  8. concentrationfractions concentrated under reduced pressure
  9. customresidue partitioned between DCM and NaOH (1 M)
  10. dry with materialThe organic was then dried over MgSO4
  11. concentrationconcentrated under reduced pressure
  12. customto provide a white solid

Sources & evidence

ORD record
ord-850d52afa7354a01be0ecd0e73977bfb
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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