Hydrochloric Acid → HCID 178483069, compound

HRID 1984883Notes

Reaction equation

HRID 1984883 reaction equation
C(OC(=O)[NH:7][CH2:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([CH2:15][NH:16][C:17]2[N:26]=[C:25]([N:27]([CH3:29])[CH3:28])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=2)[CH2:11][CH2:10]1)(C)(C)C.Cl.N1C=CC=CC=1.[F:38][C:39]([F:52])([F:51])[O:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[S:47](Cl)(=[O:49])=[O:48]>CCOC(C)=O.C(Cl)Cl>[CH3:28][N:27]([CH3:29])[C:25]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]=[C:17]([NH:16][CH2:15][C@H:12]2[CH2:11][CH2:10][C@H:9]([CH2:8][NH:7][S:47]([C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=3[O:40][C:39]([F:38])([F:51])[F:52])(=[O:49])=[O:48])[CH2:14][CH2:13]2)[N:26]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 27772152-(Trifluoromethoxy)benzene-1-sulfonyl chlorideHCID 178483065HCID 178483065, compound

Product 1

HCID 178483069HCID 178483069, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a suspension of trans-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]cyclohexylmethyl}-carbamic acid tert-butyl ester obtained in step G of example 1 (500 mg, 1.21 mmol) in EtOAc (8 mL) was added 4 M hydrogen chloride in EtOAc (7 mL). The mixture was stirred at ambient temperature for 40 min and concentrated to give a white solid. To a suspension of the solid in CH2Cl2 (7 mL) was added pyridine (215 μL, 2.66 mmol). The mixture was cooled at 4° C. and a solution of 2-trifluoromethoxy-benzenesulfonyl chloride (331 mg, 1.27 mmol) in CH2Cl2 (2 mL) was added below 5° C. The reaction mixture was stirred at 4° C. for 2 hr. The reaction was quenched with saturated aqueous NaHCO3 The aqueous layer was extracted with CHCl3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated, and purified by flash chromatography (NH-silica gel, 20% EtOAc in hexane) to give trans-N-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-cyclohexylmethyl}-2-trifluoromethoxy-benzenesulfonamide (231 mg, 36%) as a pale yellow solid.

Workup

  1. concentrationconcentrated
  2. customto give a white solid
  3. temperatureThe mixture was cooled at 4° C.
  4. stirringThe reaction mixture was stirred at 4° C. for 2 hr
  5. customThe reaction was quenched with saturated aqueous NaHCO3 The aqueous layer
  6. extractionwas extracted with CHCl3 (three times)
  7. dry with materialThe combined organic layer was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by flash chromatography (NH-silica gel, 20% EtOAc in hexane)

Sources & evidence

ORD record
ord-6294e5dcc07e43f384657075c3dda742
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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