Dimethyl Sulfoxide → 2-((2-(4-(1H-indazol-5-ylamino)-2-[(3-phenyl)phenyl)-7-methoxyquinazolin-6-yloxy) ethyl)(methyl)amino)-N,N-dimethylacetamide

HRID 61623Notes

Reaction equation

HRID 61623 reaction equation
ClC[CH2:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[O:15][CH3:16])[N:11]=[C:10]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:18]=1)[N:9]=[C:8]2[NH:29][C:30]1[CH:31]=[C:32]2[C:36](=[CH:37][CH:38]=1)[N:35](C(OC(C)(C)C)=O)[N:34]=[CH:33]2.[CH3:46][N:47]([CH3:53])[C:48](=[O:52])[CH2:49][NH:50][CH3:51].[CH3:54]S(C)=O>>[NH:35]1[C:36]2[C:32](=[CH:31][C:30]([NH:29][C:8]3[C:7]4[C:12](=[CH:13][C:14]([O:15][CH3:16])=[C:5]([O:4][CH2:3][CH2:51][N:50]([CH3:54])[CH2:49][C:48]([N:47]([CH3:53])[CH3:46])=[O:52])[CH:6]=4)[N:11]=[C:10]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[CH:18]=4)[N:9]=3)=[CH:38][CH:37]=2)[CH:33]=[N:34]1

Participants

4

Reactant 3

HCID 679Dimethyl SulfoxideHCID 2063713N,N-dimethyl-2-(methylamino)acetamideHCID 59361996tert-butyl 5-(6-(2-chloroethoxy)-2-[(3-phenyl)phenyl)-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate

Product 1

HCID 497796792-((2-(4-(1H-indazol-5-ylamino)-2-[(3-phenyl)phenyl)-7-methoxyquinazolin-6-yloxy) ethyl)(methyl)amino)-N,N-dimethylacetamideYield 74%

Conditions

Temperature
85 °C

Procedure

To a mixture of tert-butyl 5-(6-(2-chloroethoxy)-2-[(3-phenyl)phenyl)-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate (0.25 g, 0.40 mmole) in DMSO (2 mL) was added N,N-dimethyl-2-(methylamino)acetamide (0.232 g, 2.00 mmole) and the reaction was stirred at 85° C. for 4 h. The mixture was poured onto ice-water and the crude product was filtered. The product was then dissolved in a mixture of CH2Cl2 and CH3OH and the solution was concentrated in vacuo. The residue was purified via preparative TLC (SiO2, 10% CH2Cl2/CH3OH). To the product was added TFA (4 mL) and the reaction was stirred at RT for 2 h. The solution was concentrated in vacuo and the residue was triturated with ether, filtered and dried under vacuum to give 2-((2-(4-(1H-indazol-5-ylamino)-2-[(3-phenyl)phenyl)-7-methoxyquinazolin-6-yloxy)ethyl)(methyl)amino)-N,N-dimethylacetamide (0.178 g, 0.30 mmole, 74%). MS 602.6 (M+1). HPLC retention time 5.24 mins.

Workup

  1. additionThe mixture was poured onto ice-water
  2. filtrationthe crude product was filtered
  3. dissolutionThe product was then dissolved in a mixture of CH2Cl2 and CH3OH
  4. concentrationthe solution was concentrated in vacuo
  5. customThe residue was purified via preparative TLC (SiO2, 10% CH2Cl2/CH3OH)
  6. additionTo the product was added TFA (4 mL)
  7. stirringthe reaction was stirred at RT for 2 h
  8. concentrationThe solution was concentrated in vacuo
  9. customthe residue was triturated with ether
  10. filtrationfiltered
  11. customdried under vacuum

Sources & evidence

ORD record
ord-7ce5a62d8f1c4f30bef3b83038ddb588
Source dataset
uspto-grants-2016_09
Patent number
US09440961B2

Reaction notes

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