Triphenylphosphine → 4-(Indol-5-yloxy)-6-methoxy-7-(2-morpholinoethoxy)quinazoline

HRID 454250Notes

Reaction equation

[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][CH:17]=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:22][CH3:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:44][CH2:45][N:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl>[NH:18]1[C:19]2[C:15](=[CH:14][C:13]([O:12][C:6]3[C:5]4[C:10](=[CH:11][C:2]([O:1][CH2:44][CH2:45][N:46]5[CH2:51][CH2:50][O:49][CH2:48][CH2:47]5)=[C:3]([O:22][CH3:23])[CH:4]=4)[N:9]=[CH:8][N:7]=3)=[CH:21][CH:20]=2)[CH:16]=[CH:17]1

Participants

Conditions

Temperature: 10 °C

Procedure

To a solution of 7-hydroxy-4-(indol-5-yloxy)-6-methoxyquinazoline (183 mg, 0.6 mmol), (prepared as described for the starting material in Example 107), triphenylphosphine (235 mg, 0.89 mmol) and 4-(2-hydroxyethyl)morpholine (93 mg, 0.72 mmol) in methylene chloride (4 ml) cooled at 10° C. was added diethyl azodicarboxylate (140 μl, 0.89 mmol). After stirring at ambient temperature for 3 hours, the mixture was left overnight at 5° C. The mixture was poured onto a column of silica and eluted with methylene chloride followed by methanol/methylene chloride (2/98) followed by 3N ammonia methanol/methylene chloride (2/98). The fractions containing the expected products were combined and evaporated to give 4-(indol-5-yloxy)-6-methoxy-7-(2-morpholinoethoxy)quinazoline (137 mg, 55%).

Workup

waitthe mixture was left overnight at 5° C
additionThe mixture was poured onto a column of silica
washeluted with methylene chloride
additionThe fractions containing the expected products
customevaporated

Sources & evidence

ORD record: ord-d0fb863ee2254f1fa1275c8fec31ea27
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08492560B2

Reaction notes

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