Dimethylamine → HCID 67298303, compound

HRID 1520325Notes

Reaction equation

HRID 1520325 reaction equation
CS(O[CH2:6][CH2:7][CH2:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[C:14]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1)[N:13]=[C:12]2[NH:25][C:26]1[CH:31]=[CH:30][C:29]([F:32])=[C:28]([Cl:33])[CH:27]=1)(=O)=O.[NH:34]([CH3:36])[CH3:35]>CO>[ClH:33].[ClH:33].[Cl:33][C:28]1[CH:27]=[C:26]([NH:25][C:12]2[C:11]3[C:16](=[CH:17][CH:18]=[C:9]([CH2:8][CH2:7][CH2:6][N:34]([CH3:36])[CH3:35])[CH:10]=3)[N:15]=[C:14]([C:19]3[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=3)[N:13]=2)[CH:31]=[CH:30][C:29]=1[F:32]

Participants

4

Reactant 2

HCID 674DimethylamineHCID 86677071HCID 86677071, compound

Product 1

HCID 67298303HCID 67298303, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
150 °C

Procedure

(This method is representative of method G4 and G5. These two methods can be implemented in a similar way except for substitution of the appropriate solvent and temperature) A solution of 3.-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)propyl methanesulfonate (40 mg, 82 mmol) and 40% Me2NH aqueous (1 mL) in methanol (2 mL) was placed in a microwave reaction vial. The mixture was heated under microwave irradiation conditions at 150° C. for 30 minutes after which the solvent was removed in vacuo. The crude product was obtained, which was purified by column chromatography on basic silica gel (eluted with ethyl acetate/methanol 1:0→5:1). The HCl salt generated by 4 M HCl in dioxane was crystallized from 2-propanol to give 10 mg of N-(3-chloro-4-fluorophenyl)-6-(3-(dimethylamino)propyl)-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride as pale brown powder (24%). LCMS m/z=436 (M+1) (Method C) (retention time=1.68 min). 1H NMR (300 MHz, DMSO) δ 10.59 (s, 1H), 10.18 (s, 1H), 9.51 (s, 1H), 8.98-8.76 (m, 2H), 8.65 (s, 1H), 8.26 (dd, J=6.8, 2.6 Hz, 1H), 8.05-7.74 (m, 4H), 7.54 (t, J=9.1 Hz, 1H), 3.19-3.03 (m, 2H), 2.97-2.83 (m, 2H), 2.78 (s, 3H), 2.77 (s, 3H), 2.16 (s, 2H).

Workup

  1. customwas removed in vacuo
  2. customThe crude product was obtained
  3. customwhich was purified by column chromatography on basic silica gel (eluted with ethyl acetate/methanol 1:0→5:1)
  4. customwas crystallized from 2-propanol

Sources & evidence

ORD record
ord-9f956bc16fb24d2a8d04615e41640ba6
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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