Triphenylphosphine → 4-(2-Chloro-5-methoxyanilino)-5,7-di-(3-morpholinopropoxy)quinazoline

HRID 1826268Notes

Reaction equation

HRID 1826268 reaction equation
N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[Cl:17][C:18]1[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][C:19]=1[NH:20][C:21]1[C:30]2[C:25](=[CH:26][C:27]([OH:41])=[CH:28][C:29]=2[O:31][CH2:32][CH2:33][CH2:34][N:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)[N:24]=[CH:23][N:22]=1.O[CH2:49][CH2:50][CH2:51][N:52]1[CH2:57][CH2:56][O:55][CH2:54][CH2:53]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Cl:17][C:18]1[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][C:19]=1[NH:20][C:21]1[C:30]2[C:25](=[CH:26][C:27]([O:41][CH2:49][CH2:50][CH2:51][N:52]3[CH2:57][CH2:56][O:55][CH2:54][CH2:53]3)=[CH:28][C:29]=2[O:31][CH2:32][CH2:33][CH2:34][N:35]2[CH2:36][CH2:37][O:38][CH2:39][CH2:40]2)[N:24]=[CH:23][N:22]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 1995763-Morpholino-1-propanolHCID 1358309164-(2-Chloro-5-methoxyanilino)-7-hydroxy-5-(3-morpholinopropoxy)quinazoline

Product 1

HCID 98728724-(2-Chloro-5-methoxyanilino)-5,7-di-(3-morpholinopropoxy)quinazolineYield 31.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Di-tert-butyl azodicarboxylate (0.035 g) was added dropwise to a stirred mixture of 4-(2-chloro-5-methoxyanilino)-7-hydroxy-5-(3-morpholinopropoxy)quinazoline (0.045 g), 4-(3-hydroxypropyl)morpholine (0.016 g), triphenylphosphine (0.04 g) and methylene chloride (1 ml). The reaction mixture was stirred at ambient temperature for 10 minutes. The mixture was evaporated and the residue was purified by column chromatography on silica using a 9:10:1 mixture of methylene chloride, ethyl acetate and a saturated methanolic ammonia solution as eluent. The material so obtained was triturated under diethyl ether. The resultant solid was isolated, washed with diethyl ether and dried under vacuum to give the title compound (0.018 g); NMR Spectrum: (DMSOd6 and CF3COOD) 2.2–2.4 (m, 4H), 3.15 (m, 4H), 3.35 (m, 4H), 3.5 (m, 4H), 3.7 (m, 4H), 3.8 (s, 3H), 4.02 (t, 4H), 4.35 (t, 2H), 4.6 (t, 2H), 6.95 (s, 1H), 7.03 (s, 1H), 7.05 (m, 1H), 7.5 (s, 1H), 7.6 (d, 1H), 8.88 (s, 1H); Mass Spectrum: M+H+ 572 and 574.

Workup

  1. customThe mixture was evaporated
  2. customthe residue was purified by column chromatography on silica using
  3. additiona 9:10:1 mixture of methylene chloride, ethyl acetate
  4. customThe material so obtained
  5. customwas triturated under diethyl ether
  6. customThe resultant solid was isolated
  7. washwashed with diethyl ether
  8. customdried under vacuum

Sources & evidence

ORD record
ord-5fd67275086c413b8be0584de6cfe5a3
Source dataset
uspto-grants-2006_05
Patent number
US07049438B2

Reaction notes

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