4-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline → N-[5-chloro-7-(3-methoxyprop-1-ynyl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

HRID 1785089Notes

Reaction equation

HRID 1785089 reaction equation
C[Si](C)(C)N[Si](C)(C)C.[Na].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([O:24][CH2:25][CH2:26][CH2:27][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[C:19]([O:22][CH3:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1.[Cl:34][C:35]1[CH:43]=[C:42]([C:44]#[C:45][CH2:46][O:47][CH3:48])[C:38]2[O:39][CH2:40][O:41][C:37]=2[C:36]=1[NH2:49]>CC(N(C)C)=O>[Cl:34][C:35]1[CH:43]=[C:42]([C:44]#[C:45][CH2:46][O:47][CH3:48])[C:38]2[O:39][CH2:40][O:41][C:37]=2[C:36]=1[NH:49][C:12]1[C:21]2[C:16](=[CH:17][C:18]([O:24][CH2:25][CH2:26][CH2:27][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[C:19]([O:22][CH3:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1

Participants

5

Reactant 3

HCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolineHCID 210827165-Chloro-7-(3-methoxyprop-1-ynyl)-1,3-benzodioxol-4-amineHCID 45051731Sodium hexamethyidisilazane

Product 1

HCID 9958962N-[5-chloro-7-(3-methoxyprop-1-ynyl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amineYield 72.2%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hexamethyldisilazane (1M solution in THF; 1.0 ml) was added to a mixture of 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (0.16 g) and 5-chloro-7-(3-methoxyprop-1-ynyl)-1,3-benzodioxol-4-amine (0.12 g) in DMA (5 ml) that was cooled to 0° C. The resultant mixture was stirred and allowed to warm to ambient temperature for 2 hours. The reaction mixture was reduced in vacuo and partitioned between ethylacetate and water. The organic layers were washed with water and brine and the product was purified column chromatography on silica using a gradient of 0-10% methanol/methylene chloride as eluent. The resultant yellow gum was dissolved in minimal methylene chloride, diluted with diethyl ether and precipitated as an HCl salt by the addition of 1.0M ethereal HCl. The resultant solid was centrifuged and washed with diethyl ether (3 times) and dried to give the title compound as a yellow solid (185 mg); NMR Spectrum: (DMSOd6+CD3CO2D at 100° C.) 2.33-2.40 (m, 2H), 3.30-3.40 (m, 9H), 3.93-3.98 (m, 4H), 4.03 (s, 3H), 4.38-4.41 (m, 4H), 6.19 (s, 2H), 7.15 (s, 1H), 7.41 (s, 1H), 8.16 (s, 1H), 8.66 (s, 1H); Mass Spectrum: M+H+ 541.5.

Workup

  1. temperatureto warm to ambient temperature for 2 hours
  2. custompartitioned between ethylacetate and water
  3. washThe organic layers were washed with water and brine
  4. customthe product was purified column chromatography on silica using a gradient of 0-10% methanol/methylene chloride as eluent
  5. dissolutionThe resultant yellow gum was dissolved in minimal methylene chloride
  6. additiondiluted with diethyl ether
  7. customprecipitated as an HCl salt by the addition of 1.0M ethereal HCl
  8. washwashed with diethyl ether (3 times)
  9. customdried

Sources & evidence

ORD record
ord-977e051cf17b49c0acda6249e6ba60e5
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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