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Isopropylamine → (2R)-7-(2-hydroxy-3-(isopropylamino)propoxy)4-(indol-5-yloxy)-6-methoxyquinazoline

HRID 454300
Notes
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Reaction equation

HRID 454300 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.[CH:28]([NH2:31])([CH3:30])[CH3:29]>C1COCC1>[OH:26][C@H:25]([CH2:27][NH:31][CH:28]([CH3:30])[CH3:29])[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 6363IsopropylamineHCID 53976813HCID 53976813, compound

Product 1

HCID 57138584(2R)-7-(2-hydroxy-3-(isopropylamino)propoxy)4-(indol-5-yloxy)-6-methoxyquinazolineYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of (2R)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (100 mg, 0.28 mmol), (prepared as described for the starting material in Example 292), and isopropylamine (1.0 ml) in THF (10 ml) was stirred at 75° C. for 18 hours under an atmosphere of nitrogen and then allowed to cool to ambient temperature. The mixture was filtered and the filtrate evaporated in vacuo. The residue was purified by silica gel chromatography, gradient elution with dichloromethane/methanolic ammonia (7M) (100/0 to 90/10) to give (2R)-7-(2-hydroxy-3-(isopropylamino)propoxy)-4-(indol-5-yloxy)-6-methoxyquinazoline (82 mg, 68%).

Workup

  1. custom(prepared
  2. temperatureto cool to ambient temperature
  3. filtrationThe mixture was filtered
  4. customthe filtrate evaporated in vacuo
  5. customThe residue was purified by silica gel chromatography, gradient elution with dichloromethane/methanolic ammonia (7M) (100/0 to 90/10)

Sources & evidence

ORD record
ord-f0c3688df4be4fce9a570f3c65ab1cd0
Source dataset
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08492560B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes