Diisopropylethylamine → [4-(4-Tert-butylamino-quinazolin-2-ylamino)-cyclohexyl]-carbamic acid tert-butyl ester

HRID 1984947Notes

Reaction equation

[C:1]([O:5][C:6](=[O:15])[NH:7][C@H:8]1[CH2:13][CH2:12][C@@H:11]([NH2:14])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:16]([NH:20][C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:24]=[C:23](Cl)[N:22]=1)([CH3:19])([CH3:18])[CH3:17].C(N(C(C)C)CC)(C)C>CC(O)C>[C:1]([O:5][C:6](=[O:15])[NH:7][CH:8]1[CH2:9][CH2:10][CH:11]([NH:14][C:23]2[N:22]=[C:21]([NH:20][C:16]([CH3:19])([CH3:18])[CH3:17])[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[N:24]=2)[CH2:12][CH2:13]1)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 170 °C

Procedure

To a suspension of cis-(4-amino-cyclohexyl)-carbamic acid tert-butyl ester (122 mg, 0.57 mmol) in 2-propanol (2 mL) were added tert-butyl-(2-chloro-quinazolin-4-yl)-amine (100 mg, 0.42 mmol) and diisopropylethylamine (180 μL, 1 mmol) and the mixture was heated at 170° C. for 1 hr using a Smith Microwave Synthesizer. The resulting solution was concentrated and purified by column chromatography (silica gel, 3% MeOH in CH2Cl2) to give [4-(4-tert-butylamino-quinazolin-2-ylamino)-cyclohexyl]-carbamic acid tert-butyl ester (112 mg, 65%) as a yellow solid. To a suspension of cis-[4-(4-tert-butylamino-quinazolin-2-ylamino)-cyclohexyl]-carbamic acid tert-butyl ester (95 mg, 0.23 mmol) in CH2Cl2 (3 mL) was added trifluoroacetic acid (2 mL) dropwise. The reaction mixture was stirred at ambient temperature for 2 hr. The solution was concentrated, alkalized with saturated aqueous NaHCO3 and 1 M aqueous sodium hydroxide (pH=9), and the aqueous layer was extracted with CH2Cl2 (three times). The combined organic layer was dried over MgSO4, filtered, and concentrated. The solid was collected by filtration to give cis-N2-(4-amino-cyclohexyl)-N-tert-butyl-quinazoline-2,4-diamine (44.6 mg, 53%) as a yellow solid.

Workup

concentrationThe resulting solution was concentrated
custompurified by column chromatography (silica gel, 3% MeOH in CH2Cl2)

Sources & evidence

ORD record: ord-4abad255a2e54ebc9a326fccca87a0ec
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07544690B2

Reaction notes

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