Triphenylphosphine → 6-(3-(4-Acetylpiperazin-1-yl)propoxy)-4-(4-fluoroindol-5-yloxy)-7-methoxyquinazoline

HRID 916411Notes

Reaction equation

HRID 916411 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[F:13][C:14]1[C:22]([O:23][C:24]2[C:33]3[C:28](=[CH:29][C:30]([O:35][CH3:36])=[C:31]([OH:34])[CH:32]=3)[N:27]=[CH:26][N:25]=2)=[CH:21][CH:20]=[C:19]2[C:15]=1[CH:16]=[CH:17][NH:18]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:56]([N:59]1[CH2:64][CH2:63][N:62]([CH2:65][CH2:66][CH2:67]O)[CH2:61][CH2:60]1)(=[O:58])[CH3:57]>C(Cl)Cl>[C:56]([N:59]1[CH2:64][CH2:63][N:62]([CH2:65][CH2:66][CH2:67][O:34][C:31]2[CH:32]=[C:33]3[C:28](=[CH:29][C:30]=2[O:35][CH3:36])[N:27]=[CH:26][N:25]=[C:24]3[O:23][C:22]2[C:14]([F:13])=[C:15]3[C:19](=[CH:20][CH:21]=2)[NH:18][CH:17]=[CH:16]3)[CH2:61][CH2:60]1)(=[O:58])[CH3:57]

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 114467711-(4-(3-Hydroxypropyl)piperazin-1-yl)ethan-1-one2×HCID 589602194-[(4-fluoro-1H-indol-5-yl)oxy]-6-hydroxy-7-methoxyquinazoline

Product 1

HCID 101958126-(3-(4-Acetylpiperazin-1-yl)propoxy)-4-(4-fluoroindol-5-yloxy)-7-methoxyquinazolineYield 19%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (117 μl, 0.738 mmol) was added dropwise to a solution of 4-(4-fluoroindol-5-yloxy)-6-hydroxy-7-methoxyquinazoline (0.2 g, 0.615 mmol), triphenylphosphine (0.242 g, 0.92 mmol) and 3-(4-acetylpiperazin-1-yl)propan-1-ol (0.137 g, 0.738 mmol), (prepared as described for the starting material in Example 1 or Example 7), in methylene chloride (5 ml). After stirring at ambient temperature for 1 hour, triphenylphosphine (0.032 g), 3-(4-acetylpiperazin-1-yl)propan-1-ol (0.022 g) and diethyl azodicarboxylate (20 μl) were added. The mixture was stirred for 1 hour at ambient temperature and evaporated under vacuum. The residue was purified by column chromatography, eluting with increasingly polar mixtures of methylene chloride and ethyl acetate followed by methylene chloride and methanol. The fractions containing the expected product were combined and evaporated. The residue was repurified by preparative LC/MS eluting with increasingly polar mixtures of acetonitrile and water (containing 1% acetic acid). The fractions containing the expected product were combined and evaporated. The residue was triturated under diethyl ether and pentane and the residue was filtered, washed with diethyl ether and dried under vacuum to give 6-(3-(4-acetylpiperazin-1-yl)propoxy)-4-(4-fluoroindol-5-yloxy)-7-methoxyquinazoline (0.057 g, 19%).

Workup

  1. custom(prepared
  2. stirringThe mixture was stirred for 1 hour at ambient temperature
  3. customevaporated under vacuum
  4. customThe residue was purified by column chromatography
  5. washeluting
  6. temperaturewith increasingly polar mixtures of methylene chloride and ethyl acetate
  7. additionThe fractions containing the expected product
  8. customevaporated
  9. customThe residue was repurified by preparative LC/MS
  10. washeluting
  11. temperaturewith increasingly polar mixtures of acetonitrile and water (containing 1% acetic acid)
  12. additionThe fractions containing the expected product
  13. customevaporated
  14. customThe residue was triturated under diethyl ether
  15. filtrationpentane and the residue was filtered
  16. washwashed with diethyl ether
  17. customdried under vacuum

Sources & evidence

ORD record
ord-d6574ef5cdb44bef93ca2726a41eb729
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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