Hydrochloric Acid → HCID 131730541, compound

HRID 1972037Notes

Reaction equation

HRID 1972037 reaction equation
[ClH:1].Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:30][CH:31]2[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[C:17]([NH:19][C:20](=O)[CH3:21])[CH:18]=1)[CH2:4][CH2:5][CH3:6].[Cl:38]CC[CH2:41][S:42](Cl)(=[O:44])=[O:43].CCN(C(C)C)C(C)C.[H-].[Na+].Cl>C(Cl)Cl.CN(C1C=CN=CC=1)C.O.CCOC(C)=O.CCOCC>[ClH:38].[ClH:1].[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:30][CH:31]2[CH2:32][CH2:33][N:34]([CH3:37])[CH2:35][CH2:36]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:23][CH:24]2[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]2)=[C:17]([N:19]2[CH2:20][CH2:21][CH2:41][S:42]2(=[O:44])=[O:43])[CH:18]=1)[CH2:4][CH2:5][CH3:6]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 154103-Chloropropanesulphonyl chlorideHCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 67373992HCID 67373992, compound

Product 1

HCID 131730541HCID 131730541, compoundYield 28.4%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 22728543Water ethylacetateSolvent

Procedure

To a solution of 5-[3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-phenylamine (Example 62, 0.2 mmol, 88 mg) in dry DCM (1.0 mL) was added 3-chloropropanesulfonyl chloride (0.4 mmol, 71 mg), DIEA (0.4 mmol, 70 μL), and DMAP (10 mg). And the mixture was stirred at room temperature for 1 hour then condensed. It was then diluted with water/EtOAc. The solvent was removed in vacuo and dried under vacuum over night. The residue was dissolved in dry THF (1.0 mL) at 0° C., NaH (60% dispersion in mineral oil, 0.8 mmol, 32 mg) was added and the mixture was heated at 50° C. for 4 hours. It was then poured into ice-water and extracted with ethyl acetate. The organic layers combined, condensed and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH) to give a colorless sticky solid, which was dissolved in DCM (1.0 mL), 2N HCl in ether (1.0 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (35 mg). LCMS: m/z 544 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.70 and 7.81 (1H, s), 7.01-7.12 (3H, m), 5.37-5.56 (1H, m), 4.52-4.58 (1H, m), 3.21-3.69 (8H, m), 3.06-3.13 (2H, m), 2.93 (3H, s), 1.92-2.59 (8H, m), 1.27-1.82 (12H, m), 0.80 (3H, t).

Workup

  1. customcondensed
  2. customThe solvent was removed in vacuo
  3. customdried under vacuum over night
  4. dissolutionThe residue was dissolved in dry THF (1.0 mL) at 0° C.
  5. temperaturethe mixture was heated at 50° C. for 4 hours
  6. extractionextracted with ethyl acetate
  7. customcondensed
  8. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH)
  9. customto give a colorless sticky solid, which
  10. waitkept at room temperature for 10 min
  11. customcondensed
  12. customtriturated with hexanes

Sources & evidence

ORD record
ord-a7ae968738a34169867c9c477ea4c428
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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