Tetrahydrofuran → HCID 178494339, compound

HRID 1791822Notes

Reaction equation

HRID 1791822 reaction equation
CO[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.C1C[O:37][CH2:36]C1>>[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:37][CH3:36])([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)[NH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 31268PyrrolidineHCID 53955805HCID 53955805, compound

Product 1

HCID 178494339HCID 178494339, compoundYield 55%

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)4-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-d59e72f577ec45aea447fd0ab95b016b
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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