Chloroform → 3-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylamino}-propan-1-ol

HRID 1876177Notes

Reaction equation

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

Participants

Conditions

Temperature: 115 °C

Procedure

A mixture of (2-chloro-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine hydrochloride (88 mg, 0.26 mmol) and 3-amino-propan-1-ol (62 μL, 0.82 mmol) in n-BuOH (2 mL) was heated at 115° C. for 29 h then concd in vacuo. Chloroform (5 mL) was added and this washed with satd NaHCO3 (1×2 mL); then dried (MgSO4), filtered through silica with a wash of 100:10:1 CHCl3:MeOH:concd NH4OH, concd then purified by MPLC (amine column (Isco 60-2203-201)/0-100% i-PrOH in CHCl3) yielding the title compound as a pale yellow oil (70 mg; 79%). 1H NMR (CDCl3) δ 7.43 (m, 1H), 7.38 (m, 1H), 7.12 (m, 2H), 6.92 (m, 2H), 6.80 (m, 1H), 6.69 (m, 1H), 3.84 (s, 3H), 3.78-3.66 (m, 4H), 3.52 (s(br), 3H), 1.81 (m, 2H); LC-MS (ESI+; 339 ([M+H]+)).

Workup

washthis washed with satd NaHCO3 (1×2 mL)
dry with materialthen dried (MgSO4)
filtrationfiltered through silica with
washa wash of 100:10:1 CHCl3
customMeOH:concd NH4OH, concd then purified by MPLC (amine column (Isco 60-2203-201)/0-100% i-PrOH in CHCl3)

Sources & evidence

ORD record: ord-5c929d3744464737a4e3679ac9c3fcc6
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08309562B2

Reaction notes

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