Hydrochloric Acid → (1-Benzyl-1H-indazol-5-yl)-(6-(1-methylpyrrol-2-yl)-quinazolin-4-yl)-amine hydrochloride

HRID 2306743Notes

Reaction equation

HRID 2306743 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[Sn](CCCC)(CCCC)CCCC.[ClH:20].[CH2:21]([N:28]1[C:36]2[C:31](=[CH:32][C:33]([NH:37][C:38]3[C:47]4[C:42](=[CH:43][CH:44]=[C:45](I)[CH:46]=4)[N:41]=[CH:40][N:39]=3)=[CH:34][CH:35]=2)[CH:30]=[N:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(N(CC)CC)C.Cl>O1CCOCC1.CCOC(C)=O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[ClH:20].[CH2:21]([N:28]1[C:36]2[C:31](=[CH:32][C:33]([NH:37][C:38]3[C:47]4[C:42](=[CH:43][CH:44]=[C:45]([C:3]5[N:2]([CH3:1])[CH:6]=[CH:5][CH:4]=5)[CH:46]=4)[N:41]=[CH:40][N:39]=3)=[CH:34][CH:35]=2)[CH:30]=[N:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27693971-methyl-2-(tributylstannyl)-1H-pyrroleHCID 21952130(1-Benzylindazol-5-yl)-(6-iodoquinazolin-4-yl)-amine hydrochloride

Product 1

HCID 22609846(1-Benzyl-1H-indazol-5-yl)-(6-(1-methylpyrrol-2-yl)-quinazolin-4-yl)-amine hydrochlorideYield 29%

Reagents, catalysts & solvents 3

HCID 10974057(Butane-1,4-diyl)bis(diphenylphosphane)--dichloropalladium (1/1)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A stirred solution of 1-methyl-2-(tri-n-butylstannyl)pyrrole (prepared as described in H. M. R. Hoffmann et al. Synthesis, 1996, 164) (1.07 g, 2.89 mmol), (1-benzylindazol-5-yl)-(6-iodoquinazolin-4-yl)-amine hydrochloride (1.0 g, 1.95 mmol), triethylamine (0.4 ml , 0.29 g, 2.87 mmol) and 1,4-bis(diphenylphosphino)-butane palladium (II) chloride (0.1 g, catalytic) in dioxane (10 ml) was heated to reflux under a nitrogen atmosphere for 18 hours. The mixture was concentrated in vacuo and purified by silica gel chromatography, eluting with 2:1 i-hexane/EtOAc. Concentration of the appropriate fractions gave a yellow solid which was dissolved in EtOAc and treated with a solution of HCl in dioxane. The precipitate was collected by filtration, washed with EtOAc and dried at 60C in vacuo to give the product as a green-yellow solid (0.26 g, 0.557 mmol, 29%); δH [2H6]DMSO 11.95 (1H, s), 8.86-8.96 (2H, m), 8.18-8.27 (2H, m), 8.07 (1H, s), 7.99 (1H, d), 7.83 (1H, d), 7.65 (1H, dd), 7.22-7.40 (5H, m), 7.01 (1H, t), 6.49 (1H, dd), 6.19 (1H, t), 5.71 (2H, s), 3.82 (3H, s); m/z (M+1+) 431.

Workup

  1. temperatureto reflux under a nitrogen atmosphere for 18 hours
  2. concentrationThe mixture was concentrated in vacuo
  3. custompurified by silica gel chromatography
  4. washeluting with 2:1 i-hexane/EtOAc
  5. customConcentration of the appropriate fractions gave a yellow solid which
  6. filtrationThe precipitate was collected by filtration
  7. washwashed with EtOAc
  8. dry with materialdried at 60C in vacuo

Sources & evidence

ORD record
ord-5eb0ff85316d42e28932114ccf64ed3d
Source dataset
uspto-grants-2004_12
Patent number
US06828320B2

Reaction notes

Loading…