Tributylphosphine → HCID 22624924, compound

HRID 1384683Notes

Reaction equation

HRID 1384683 reaction equation
N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[Cl:19][C:20]1[CH:39]=[CH:38][C:23]([NH:24][C:25]2[C:34]3[C:29](=[CH:30][C:31]([OH:37])=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][N:26]=2)=[C:22]([F:40])[CH:21]=1.O[CH2:42][C:43]1[CH:48]=[CH:47][N:46]=[C:45]([N:49]([CH3:51])[CH3:50])[CH:44]=1.C(P(CCCC)CCCC)CCC>C(Cl)Cl>[ClH:19].[Cl:19][C:20]1[CH:39]=[CH:38][C:23]([NH:24][C:25]2[C:34]3[C:29](=[CH:30][C:31]([O:37][CH2:42][C:43]4[CH:48]=[CH:47][N:46]=[C:45]([N:49]([CH3:51])[CH3:50])[CH:44]=4)=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][N:26]=2)=[C:22]([F:40])[CH:21]=1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 22625066[2-(dimethylamino)-4-pyridinyl]methanol(SALTDATA: HCl)HCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22624924HCID 22624924, compoundYield 62.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1,1′-(azodicarbonyl)dipiperidine (1.68 g, 6 mmol) was added in portions to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (640 mg, 2 mmol), 4-hydroxymethyl-2-(dimethylamino)pyridine (426 mg, 2.8 mmol) and tributylphosphine (1.6 ml, 6 mmol) in methylene chloride (50 ml) at 0° C. The mixture was allowed to warm to ambient temperature over 2 hours, the insolubles were removed by filtration and the filtrate was washed with water and brine, dried (Na2SO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (100:0 increasing to 95:5). The purified product was dissolved in acetone/methanol and a 1M solution of ethereal hydrogen chloride was added. The resulting precipitate was collected by filtration and dried to give 4-(4-chloro-2-fluoroanilino)-7-(2-(dimethylamino)pyrid-4-yl)methoxy-6-methoxyquinazoline hydrochloride (305 mg, 30%). m.p. 290° C. 1H NMR Spectrum (DMSOd6) 3.05(s, 6H); 4.05(s, 3H); 5.45(s, 2H); 6.95(d, 1H); 7.35(s, 1H); 7.42(dd, 1H); 7.56(t, 2H); 7.62(dd, 1H); 8.00(d, 1H); 8.55(s, 1H), 9.80(s, 1H); 11.95(br s, 1H) MS-ESI: 454 [MH]+

Workup

  1. customthe insolubles were removed by filtration
  2. washthe filtrate was washed with water and brine
  3. dry with materialdried (Na2SO4)
  4. customthe solvent removed by evaporation
  5. customThe residue was purified by column chromatography
  6. washeluting with methylene chloride/methanol (100:0 increasing to 95:5)
  7. dissolutionThe purified product was dissolved in acetone/methanol
  8. additiona 1M solution of ethereal hydrogen chloride was added
  9. filtrationThe resulting precipitate was collected by filtration
  10. customdried

Sources & evidence

ORD record
ord-28c2203e36c94f98abffc9135d8bee90
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

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