Diisopropylethylamine → HCID 178461074, compound

HRID 1984889Notes

Reaction equation

HRID 1984889 reaction equation
[NH2:1][CH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([CH2:9][NH:10][C:11]2[N:20]=[C:19]([N:21]([CH3:23])[CH3:22])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=2)[CH2:5][CH2:4]1.C(N(C(C)C)CC)(C)C.[CH3:33][CH:34]([S:36](Cl)(=[O:38])=[O:37])[CH3:35]>C(Cl)Cl>[CH3:22][N:21]([CH3:23])[C:19]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=[C:11]([NH:10][CH2:9][C@H:6]2[CH2:7][CH2:8][C@H:3]([CH2:2][NH:1][S:36]([CH:34]([CH3:35])[CH3:33])(=[O:38])=[O:37])[CH2:4][CH2:5]2)[N:20]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 824082-Propanesulfonyl chlorideHCID 178483061HCID 178483061, compound

Product 1

HCID 178461074HCID 178461074, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
4 °C

Procedure

To a suspension of trans-N2-(4-aminomethyl-cyclohexylmethyl)-N4,N4-dimethyl-quinazoline-2,4-diamine obtained in step A of example 15 (227 mg, 0.72 mmol) in CH2Cl2 (4 mL) was added diisopropylethylamine (263 μL, 1.51 mmol). The mixture was cooled at 4° C. and a solution of 2-propanesulfonyl chloride (108 mg, 0.76 mmol) in CH2Cl2 (1 mL) was added below 5° C. The reaction mixture was stirred at ambient temperature for 12 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, 66% EtOAc in hexane) to give trans-propane-2-sulfonic acid {4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-cyclohexylmethyl}-amide (135 mg, 45%) as a pale yellow solid.

Workup

  1. customThe reaction was quenched with saturated aqueous NaHCO3 The aqueous layer
  2. extractionwas extracted with CHCl3 (three times)
  3. dry with materialThe combined organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash chromatography (NH-silica gel, 66% EtOAc in hexane)

Sources & evidence

ORD record
ord-970946cb288b4da19d58d01f05373adb
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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