Triphenylphosphine → 6-(3-(4-Acetylpiperazin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline

HRID 916367Notes

Reaction equation

HRID 916367 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]=[C:17]([CH3:37])[NH:18]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:57]([N:60]1[CH2:65][CH2:64][N:63]([CH2:66][CH2:67][CH2:68]O)[CH2:62][CH2:61]1)(=[O:59])[CH3:58]>C(Cl)Cl>[C:57]([N:60]1[CH2:65][CH2:64][N:63]([CH2:66][CH2:67][CH2:68][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][C:17]([CH3:37])=[CH:16]3)[CH2:62][CH2:61]1)(=[O:59])[CH3:58]

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 112677704-(4-Fluoro-2-methylindol-5-yloxy)-6-hydroxy-7-methoxyquinazolineHCID 114467711-(4-(3-Hydroxypropyl)piperazin-1-yl)ethan-1-one

Product 1

HCID 101745406-(3-(4-Acetylpiperazin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazolineYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (0.178 g, 1.02 mmol) was added to a solution of 4-(4-fluoro-2-methylindol-5-yloxy)-6-hydroxy-7-methoxyquinazoline (0.267 g, 0.787 mmol), triphenylphosphine (0.31 g, 1.188 mmol) and 3-(4-acetylpiperazin-1yl)propan-1-ol (0.176 g, 0.945 mmol) in methylene chloride (10 ml). After stirring for 15 minutes at ambient temperature, further triphenylphosphine (0.062 mg, 0.236 mmol) and diethyl azodicarboxylate (0.041 mg, 0.3 mmol) were added. After stirring for 1 hour at ambient temperature, the mixture was poured onto a column of silica and eluted with increasingly polar mixtures of ethyl acetate and methylene chloride followed by methylene chloride and methanol. The fractions containing the expected product were combined and evaporated. The residue was triturated under diethyl ether and the solid was filtered, washed with ether and dried under vacuum to give 6-(3-(4-acetylpiperazin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline 0.210 g, 60%).

Workup

  1. stirringAfter stirring for 1 hour at ambient temperature
  2. additionthe mixture was poured onto a column of silica
  3. washeluted
  4. temperaturewith increasingly polar mixtures of ethyl acetate and methylene chloride
  5. additionThe fractions containing the expected product
  6. customevaporated
  7. customThe residue was triturated under diethyl ether
  8. filtrationthe solid was filtered
  9. washwashed with ether
  10. customdried under vacuum

Sources & evidence

ORD record
ord-161198c0962642c29d01470c981c78de
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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