Phosphorus oxychloride → HCID 11751183, compound

HRID 2354168Notes

Reaction equation

HRID 2354168 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][C:7]1[CH:15]=[CH:14][C:10]([C:11](O)=[O:12])=[CH:9][C:8]=1[N:16]1[C:25](=[O:26])[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([N:27]3[CH2:32][CH2:31][N:30]([CH:33]([CH3:35])[CH3:34])[CH2:29][CH2:28]3)[CH:23]=2)[N:18]=[CH:17]1.Cl.C[C:38]1([NH2:41])[CH2:40][CH2:39]1>N1C=CC=CC=1>[CH:38]1([NH:41][C:11](=[O:12])[C:10]2[CH:14]=[CH:15][C:7]([CH3:6])=[C:8]([N:16]3[C:25](=[O:26])[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([N:27]5[CH2:32][CH2:31][N:30]([CH:33]([CH3:34])[CH3:35])[CH2:29][CH2:28]5)[CH:23]=4)[N:18]=[CH:17]3)[CH:9]=2)[CH2:40][CH2:39]1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 12953687(1-Methylcyclopropyl)amine hydrochlorideHCID 66918923HCID 66918923, compound

Product 1

HCID 11751183HCID 11751183, compoundYield 39.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
120 °C

Procedure

Phosphorus oxychloride (0.11 ml) was added to a mixture of 4-methyl-3-[6-(4-isopropylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid (0.30 g), 1-methylcyclopropylamine hydrochloride (0.13 g) and pyridine (5 ml) and the resultant was heated to 120° C. for 5 minutes in a microwave (Personal Chemistry Emrys Optimizer with 300 W magnetron). The mixture was evaporated. The residue was partitioned between ethyl acetate and saturated NaHCO3 solution. The organic phase was dried (magnesium sulphate) and evaporated and the residue purified by column chromatography on a silica column using initially methylene chloride and then a 9:1 mixture of methylene chloride and methanol as eluent. There was thus obtained the title compound (0.13 g); NMR Spectrum: (CDCl3) 0.76 (m, 4H), 1.09 (d, 6H), 2.20 (s, 3H), 2.20 (s, 3H), 2.72 (in, 5H), 3.35 (m, 4H), 6.61 (s, 1H), 7.43 (m, 2H), 7.66 (m, 3H), 7.78 (m, 2H); Mass Spectrum: M+H+ 460.

Workup

  1. customThe mixture was evaporated
  2. customThe residue was partitioned between ethyl acetate and saturated NaHCO3 solution
  3. dry with materialThe organic phase was dried (magnesium sulphate)
  4. customevaporated
  5. customthe residue purified by column chromatography on a silica column
  6. additiona 9:1 mixture of methylene chloride and methanol as eluent

Sources & evidence

ORD record
ord-fceeaf0858324decb03a93a424795ba0
Source dataset
uspto-grants-2010_07
Patent number
US07750154B2

Reaction notes

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