Triphenylphosphine → tert-Butyl 4-[(4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazolin-7-yloxy)methyl]piperidine-1-carboxylate

HRID 2068060Notes

Reaction equation

HRID 2068060 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[F:15][C:16]1[C:24]([O:25][C:26]2[C:35]3[C:30](=[CH:31][C:32]([OH:38])=[C:33]([O:36][CH3:37])[CH:34]=3)[N:29]=[CH:28][N:27]=2)=[CH:23][CH:22]=[C:21]2[C:17]=1[CH:18]=[C:19]([CH3:39])[NH:20]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:59]([O:63][C:64]([N:66]1[CH2:71][CH2:70][CH:69]([CH2:72]O)[CH2:68][CH2:67]1)=[O:65])([CH3:62])([CH3:61])[CH3:60]>C(Cl)Cl>[F:15][C:16]1[C:24]([O:25][C:26]2[C:35]3[C:30](=[CH:31][C:32]([O:38][CH2:72][CH:69]4[CH2:70][CH2:71][N:66]([C:64]([O:63][C:59]([CH3:60])([CH3:62])[CH3:61])=[O:65])[CH2:67][CH2:68]4)=[C:33]([O:36][CH3:37])[CH:34]=3)[N:29]=[CH:28][N:27]=2)=[CH:23][CH:22]=[C:21]2[C:17]=1[CH:18]=[C:19]([CH3:39])[NH:20]2

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate2×HCID 1355308324-((4-Fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-ol

Product 1

HCID 67019228tert-Butyl 4-[(4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazolin-7-yloxy)methyl]piperidine-1-carboxylateYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diisopropyl azodicarboxylate (139 μl, 0.71 mmol) was added to a mixture of 4-(4-fluoro-2-methylindol-5-yloxy)-7-hydroxy-6-methoxyquinazoline (200 mg, 0.59 mmol), (prepared as described for the starting material in Example 7), triphenylphosphine (186 mg, 0.71 mmol) and 1-(tert-butoxycarbonyl)-4-hydroxymethylpiperidine, (also known as tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate), (152 mg, 0.71 mmol) in methylene chloride (3 ml), cooled in an ice/water bath. The mixture was allowed to warm to ambient temperature and was stirred overnight. The mixture was concentrated under reduced pressure and the residue purified by column chromatography, eluting with 1% methanol/methylene chloride and 0.1% triethylamine to give tert-butyl 4-[(4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazolin-7-yloxy)methyl]piperidine-1-carboxylate (293 mg containing 13.5 mol % triphenylphospine oxide, 86%).

Workup

  1. custom(prepared
  2. temperaturecooled in an ice/water bath
  3. concentrationThe mixture was concentrated under reduced pressure
  4. customthe residue purified by column chromatography
  5. washeluting with 1% methanol/methylene chloride and 0.1% triethylamine

Sources & evidence

ORD record
ord-0b672036109e4e639ad24f7e32fabb07
Source dataset
uspto-grants-2012_10
Patent number
US08293902B2

Reaction notes

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