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Pyrrolidine → (2R)-7-(2-hydroxy-3-(pyrrolidin-1-yl)propoxy)-4-(indol-5-yloxy)-6-methoxyquinazoline

HRID 1791808
Notes
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Reaction equation

HRID 1791808 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C:11]3[C:20]4[C:15](=[CH:16][C:17]([O:23][CH2:24][C@H:25]5[CH2:27][O:26]5)=[C:18]([O:21][CH3:22])[CH:19]=4)[N:14]=[CH:13][N:12]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[NH:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1>CN(C=O)C>[OH:26][C@H:25]([CH2:27][N:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1)[CH2:24][O:23][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([O:10][C:6]3[CH:5]=[C:4]4[C:9](=[CH:8][CH:7]=3)[NH:1][CH:2]=[CH:3]4)=[N:12][CH:13]=[N:14]2)=[CH:19][C:18]=1[O:21][CH3:22]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 53976813HCID 53976813, compound

Product 1

HCID 54265542(2R)-7-(2-hydroxy-3-(pyrrolidin-1-yl)propoxy)-4-(indol-5-yloxy)-6-methoxyquinazolineYield 90.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of (2R)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (300 mg, 0.83 mmol), and pyrrolidine (176 mg, 2.48 mmol) in DMF (5 ml) was stirred at 75° C. for 3 hours under an atmosphere of nitrogen and allowed to cool to ambient temperature. The solvents were removed in vacuo and the residue purified on silica gel, gradient elution with dichloromethane, dichloromethane/methanol (95/5), dichloromethane/methanolic ammonia (7M) (98/2 to 90/10), to give (2R)-7-(2-hydroxy-3-(pyrrolidin-1-yl)propoxy)-4-(indol-5-yloxy)-6-methoxyquinazoline (326 mg, 87%).

Workup

  1. temperatureto cool to ambient temperature
  2. customThe solvents were removed in vacuo
  3. customthe residue purified on silica gel, gradient elution with dichloromethane, dichloromethane/methanol (95/5), dichloromethane/methanolic ammonia (7M) (98/2 to 90/10)

Sources & evidence

ORD record
ord-e3241eccbfb14974b801d4e0361b08ed
Source dataset
uspto-grants-2006_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07074800B1

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes