Pyrrolidine → HCID 54274489, compound

HRID 454303Notes

Reaction equation

HRID 454303 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][C@H:15]1[CH2:17][O:16]1)[N:9]=[CH:8][N:7]=[C:6]2[O:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][C:23]([CH3:28])=[CH:22]2.[NH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1>C1COCC1>[OH:16][C@H:15]([CH2:17][N:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1)[CH2:14][O:13][C:12]1[CH:11]=[C:10]2[C:5]([C:6]([O:18][C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[NH:24][C:23]([CH3:28])=[CH:22]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:2][CH3:1]

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 53955805HCID 53955805, compound

Product 1

HCID 54274489HCID 54274489, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of the (2R)-6-methoxy-4-(2-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (250 mg, 0.66 mmol), (prepared as described for the starting material in Example 269), and pyrrolidine (1.5 ml) in THF (10 ml) was stirred at 75° C. for 3 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 using gradient elution with dichloromethane/methanolic ammonia (7M) (100/0 to 90/10) to give (2R)-7-(2-hydroxy-3-(pyrrolidin-1-yl)propoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (165 mg, 55%).

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
  6. washelution with dichloromethane/methanolic ammonia (7M) (100/0 to 90/10)

Sources & evidence

ORD record
ord-e3bb57cdcc0a41dd96022f9cf5def7b7
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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