Methanol → HCID 178483068, compound

HRID 1984888Notes

Reaction equation

HRID 1984888 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH2:12][C@H:13]2[CH2:18][CH2:17][C@H:16]([CH2:19][NH:20][C:21]3[N:30]=[C:29]([N:31]([CH3:33])[CH3:32])[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]=3)[CH2:15][CH2:14]2)(=[O:10])=[O:9])=[C:4]([O:34][C:35]([F:38])([F:37])[F:36])[CH:3]=1.CO.C([O-])([O-])=O.[K+].[K+].[C:47]1(B(O)O)[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:32][N:31]([CH3:33])[C:29]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=[C:21]([NH:20][CH2:19][C@H:16]2[CH2:17][CH2:18][C@H:13]([CH2:12][NH:11][S:8]([C:5]3[CH:6]=[CH:7][C:2]([C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)=[CH:3][C:4]=3[O:34][C:35]([F:38])([F:37])[F:36])(=[O:10])=[O:9])[CH2:14][CH2:15]2)[N:30]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 178483067HCID 178483067, compound

Product 1

HCID 178483068HCID 178483068, compoundYield 63.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of trans-4-bromo-N-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-cyclohexylmethyl}-2-trifluoromethoxy-benzenesulfonamide obtained in step H of example 1 (122 mg, 0.198 mmol) in toluene (2.7 mL) were added MeOH (0.9 mL), 2 M aqueous K2CO3 (0.9 mL), phenylboronic acid (29.0 mg, 0.237 mmol), and tetrakis(triphenylphosphine)palladium (23.0 mg, 0.02 mmol). The reaction mixture was stirred at 130° C. for 10 hr. The mixture was poured into water, and the aqueous layer was extracted with CHCl3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated, and purified by flash chromatography H-silica gel, 25% EtOAc in hexane and silica gel, 9% MeOH in CHCl3) to give trans-3-trifluoromethoxy-biphenyl-4-sulfonic acid {4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-cyclohexylmethyl}-amide (77 mg, 0.125 mmol) as a white solid.

Workup

  1. extractionthe aqueous layer was extracted with CHCl3 (three times)
  2. dry with materialThe combined organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by flash chromatography H-silica gel, 25% EtOAc in hexane and silica gel, 9% MeOH in CHCl3)

Sources & evidence

ORD record
ord-474ddbe2405840b4914c1bdf0765e47a
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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