Triphenylphosphine → 4-(2-Methylindol-5-yloxy)-7-(3-(pyrrolidin-yl)propoxy)quinazoline

HRID 454083Notes

Reaction equation

HRID 454083 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[OH:15][C:16]1[CH:25]=[C:24]2[C:19]([C:20]([O:26][C:27]3[CH:28]=[C:29]4[C:33](=[CH:34][CH:35]=3)[NH:32][C:31]([CH3:36])=[CH:30]4)=[N:21][CH:22]=[N:23]2)=[CH:18][CH:17]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:56]1([CH2:61][CH2:62][CH2:63]O)[CH2:60][CH2:59][CH2:58][CH2:57]1>C(Cl)Cl>[CH3:36][C:31]1[NH:32][C:33]2[C:29]([CH:30]=1)=[CH:28][C:27]([O:26][C:20]1[C:19]3[C:24](=[CH:25][C:16]([O:15][CH2:63][CH2:62][CH2:61][N:56]4[CH2:60][CH2:59][CH2:58][CH2:57]4)=[CH:17][CH:18]=3)[N:23]=[CH:22][N:21]=1)=[CH:35][CH:34]=2

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 2093421-PyrrolidinepropanolHCID 1357631147-Hydroxy-4-(2-methylindol-5-yloxy)quinazoline

Product 1

HCID 220308234-(2-Methylindol-5-yloxy)-7-(3-(pyrrolidin-yl)propoxy)quinazolineYield 35.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diisopropyl azodicarboxylate (146 mg, 0.72 mmol) was added to a solution of 7-hydroxy-4-(2-methylindol-5-yloxy)quinazoline (100 mg, 0.34 mmol), triphenyl phosphine (189 mg, 0.72 mol), and 3-pyrrolidinopropan-1-ol (89 mg, 0.686 mmol), (J. Org. Chem. 1988, 53, 3164), in methylene chloride (2.5 ml). After stirring overnight at ambient temperature, the solid was filtered. The filtrate was purified by column chromatography eluting with ethyl acetate/methylene chloride (1/1) followed by ethyl acetate/methylene chloride/methanol (4/5/1), methylene chloride/methanol (9/1) and 3N ammonia in methanol/methylene chloride (1/9). After removal of the solvent, the residue was triturated with ether, filtered, and dried under vacuum to give 4-(2-methylindol-5-yloxy)-7-(3-(pyrrolidin-yl)propoxy)quinazoline (49 mg, 35%).

Workup

  1. filtrationthe solid was filtered
  2. customThe filtrate was purified by column chromatography
  3. washeluting with ethyl acetate/methylene chloride (1/1)
  4. customAfter removal of the solvent
  5. customthe residue was triturated with ether
  6. filtrationfiltered
  7. customdried under vacuum

Sources & evidence

ORD record
ord-e98edf82ec354b419fca0bd04427b408
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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