Dimethylamine, hydrochloride → Ammonia methanol

HRID 1875697Notes

Reaction equation

HRID 1875697 reaction equation
C[N:2](C)C=C[C:5](C1C=NC(Cl)=CC=1)=[O:6].OC(C(F)(F)F)=O.CC1C=C(NC(N)=N)C=C[C:28]=1[N:29]1C[C@@H]2C[C@H:30]1CN2C.C([O-])([O-])=O.[K+].[K+].Cl[C:48]1[N:53]=[CH:52][C:51]([C:54]2[CH:59]=[CH:58][N:57]=[C:56]([NH:60][C:61]3[CH:66]=[CH:65][C:64]([N:67]4[CH2:72][C@@H:71]5[CH2:73][C@H:68]4[CH2:69][N:70]5[CH3:74])=[C:63]([CH3:75])[CH:62]=3)[N:55]=2)=[CH:50][CH:49]=1.N(C)C.Cl>C(O)(C)C>[NH3:2].[CH3:5][OH:6].[CH3:28][N:29]([C:48]1[N:53]=[CH:52][C:51]([C:54]2[CH:59]=[CH:58][N:57]=[C:56]([NH:60][C:61]3[CH:66]=[CH:65][C:64]([N:67]4[CH2:72][C@@H:71]5[CH2:73][C@H:68]4[CH2:69][N:70]5[CH3:74])=[C:63]([CH3:75])[CH:62]=3)[N:55]=2)=[CH:50][CH:49]=1)[CH3:30]

Participants

8

Reactant 5

HCID 10473Dimethylamine, hydrochlorideHCID 11430Potassium CarbonateHCID 54299500HCID 54299500, compoundHCID 86635010HCID 86635010, compoundHCID 178428591HCID 178428591, compound

Product 2

HCID 21705897Ammonia methanolYield 1%HCID 44176650HCID 44176650, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
100 °C

Procedure

Alternatively, a heterogeneous mixture of 3-(3-(dimethylamino)prop-2-en-1-onyl)-6-chloropyridine (0.063 g, 0.75 mmol) and [3-methyl-4-((1S,4S)-2-methyl-2,5-diazabicyclo[2.2.1]heptan-5-yl)phenyl]guanidine TFA salt (0.110 g, 0.75 mmol) with K2CO3 (0.051 g, 2.25 mmol) in isopropanol (1 mL) was shaken in a sealed tube at 100° C. in for 24 h. The formation of 4-(6-(chloro)pyridin-3-yl)-N-(3-methyl-4-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)pyrimidin-2-amine was confirmed by LCMS. To this reaction vial 40% of aqueous solution of Me2NH.HCl solution (1 mL) was added and then heated in a sealed tube for 3 h at 100° C. The resulting reaction mixture was purified by column chromatography (silica gel; CH2Cl2 then 1% 2N NH3/MeOH in CH2Cl2) to afford 4-(6-(N,N-dimethylamino)pyridin-3-yl)-N-(3-methyl-4-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)pyrimidin-2-amine, compound #1; LCMS: purity: 99%; MS (m/e): 416 (MH+).

Workup

  1. temperatureheated in a sealed tube for 3 h at 100° C
  2. customThe resulting reaction mixture
  3. customwas purified by column chromatography (silica gel

Sources & evidence

ORD record
ord-3048dc1ea2c34d6080990f2b855dd58d
Source dataset
uspto-grants-2012_11
Patent number
US08309566B2

Reaction notes

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