Ethyl Acetate → HCID 59242079, compound

HRID 1876230Notes

Reaction equation

HRID 1876230 reaction equation
Cl.Cl[CH2:3][C:4]1[N:13]=[C:12]([N:14]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[CH3:15])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=1.C([O-])([O-])=O.[Cs+].[Cs+].[NH2:30][CH2:31][CH2:32][CH2:33][OH:34].CCOC(C)=O>CN(C=O)C>[CH3:23][O:22][C:19]1[CH:20]=[CH:21][C:16]([N:14]([CH3:15])[C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[C:4]([CH2:3][NH:30][CH2:31][CH2:32][CH2:33][OH:34])[N:13]=2)=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 90863-Amino-1-propanolHCID 10796Cesium carbonateHCID 68515345HCID 68515345, compound

Product 1

HCID 59242079HCID 59242079, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (2-chloromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine hydrochloride (100 mg, 0.286 mmol), Cs2CO3 (201 mg, 0.617 mmol) and 3-amino-propan-1-ol (44 μL, 0.58 mmol) in DMF (1 mL) was heated at 80° C. After 18 h, EtOAc (12 mL) was added and this was washed with water (2×2 mL) and satd NaCl (2×2 mL). The soln was dried (MgSO4), filtered through a plug of silica with a wash of 100:10:1 chloroform:methanol:concd NH4OH then purified by preparative TLC (SiO2/200:10:1 chloroform:2-propanol:concd NH4OH). A band was removed from this preparative TLC plate and further purified by preparative TLC (SiO2/100:10:1 chloroform:methanol:concd NH4OH) yielding the title compound as a yellow oil. The bis(hydrochloride) salt was formed by adding then evaporating a soln of HCl in i-PrOH, giving an off-white solid. 1H NMR (DMSO-d6) δ 7.84 (m, 1H), 7.78 (m, 1H), 7.35 (m, 2H), 7.25 (m, 1H), 7.09 (m, 2H), 6.90 (m, 1H), 4.91 (t(br), 2H), 3.82 (s, 3H), 3.68 (s, 3H), 3.56 (t, J=6.2 Hz, 2H), 3.24 (m, 2H), 1.91 (m, 2H); LC-MS (ESI+; 353 ([M+H]+)).

Workup

  1. washthis was washed with water (2×2 mL) and satd NaCl (2×2 mL)
  2. dry with materialThe soln was dried (MgSO4)
  3. filtrationfiltered through a plug of silica with
  4. washa wash of 100:10:1 chloroform
  5. custommethanol:concd NH4OH then purified by preparative TLC (SiO2/200:10:1 chloroform:2-propanol:concd NH4OH)
  6. customA band was removed from this preparative TLC plate
  7. customfurther purified by preparative TLC (SiO2/100:10:1 chloroform:methanol:concd NH4OH)

Sources & evidence

ORD record
ord-7a0e9bf283fd49a4a580f380f83637c9
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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