Dimethylamine → HCID 49779624, compound

HRID 61621Notes

Reaction equation

HRID 61621 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][NH:47][CH3:48].[CH3:49]S(C)=O>>[CH3:46][N:47]([CH3:49])[CH2:48][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:24]=[CH:25][CH:26]=[CH:27][CH:28]=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)[NH:35][N:34]=[CH:33]2

Participants

4

Reactant 3

HCID 674DimethylamineHCID 679Dimethyl SulfoxideHCID 59361996tert-butyl 5-(6-(2-chloroethoxy)-2-[(3-phenyl)phenyl)-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate

Product 1

HCID 49779624HCID 49779624, compoundYield 45%

Conditions

Temperature
85 °C

Procedure

A solution 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 (3 mL) was cooled to 0° C. To this was added dimethylamine gas (bubbled into solution for 15 minutes) and the reaction was slowly heated to 85° C. and stirred for 2 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 crude product was added TFA (5 mL) and the reaction was stirred at RT for 1 h. The solution was concentrated in vacuo and the residue was triturated with ether, filtered and dried under vacuum to give 6-(2-(dimethylamino)ethoxy)-N-(1H-indazol-5-yl)-7-methoxy-2-(3-(phenyl)phenyl)quinazolin-4-amine (0.096 g, 0.18 mmole, 45% over 2 steps). MS 531 (M+1). HPLC retention time 5.18 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 crude product was added TFA (5 mL)
  7. stirringthe reaction was stirred at RT for 1 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-7f65d108a7a347c396e1f5d4711d9859
Source dataset
uspto-grants-2016_09
Patent number
US09440961B2

Reaction notes

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