1,4-Dioxa-8-azaspiro(4.5)decane → HCID 10218231, compound

HRID 916486Notes

Reaction equation

HRID 916486 reaction equation
[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][C@H:26]4[CH2:28][O:27]4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:29])[NH:6]2.[O:30]1[C:34]2([CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)[O:33][CH2:32][CH2:31]1>CN(C=O)C>[O:30]1[C:34]2([CH2:39][CH2:38][N:37]([CH2:28][C@@H:26]([OH:27])[CH2:25][O:24][C:18]3[CH:17]=[C:16]4[C:21]([C:12]([O:11][C:10]5[C:2]([F:1])=[C:3]6[C:7](=[CH:8][CH:9]=5)[NH:6][C:5]([CH3:29])=[CH:4]6)=[N:13][CH:14]=[N:15]4)=[CH:20][C:19]=3[O:22][CH3:23])[CH2:36][CH2:35]2)[O:33][CH2:32][CH2:31]1

Participants

4

Reactant 2

HCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 58960243HCID 58960243, compound

Product 1

HCID 10218231HCID 10218231, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[(2R)-oxiran-2-ylmethoxy]quinazoline (200 mg, 0.506 mmol), (prepared as described for the starting material in Example 48), and 1,4-dioxa-8-azaspiro[4.5]decane (195 μl, 1.52 mmol) in DMF (3 ml) was stirred at 70° C. under argon for 3 hours. The volatiles were removed under vacuum and the residue was purified by column chromatography eluting with methylene chloride/methanol (95/5 followed by 90/10). The fractions containing the expected product were combined and evaporated to dryness. The residue was triturated with diethyl ether, filtered and dried under vacuum to give 7-{(2R)-3-[(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)]-2-hydroxypropoxy}-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline (190 mg, 70%).

Workup

  1. custom(prepared
  2. customThe volatiles were removed under vacuum
  3. customthe residue was purified by column chromatography
  4. washeluting with methylene chloride/methanol (95/5 followed by 90/10)
  5. additionThe fractions containing the expected product
  6. customevaporated to dryness
  7. customThe residue was triturated with diethyl ether
  8. filtrationfiltered
  9. customdried under vacuum

Sources & evidence

ORD record
ord-7e258eb51b464644921c13db7cfef6e3
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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