Trifluoroacetic acid → HCID 67599809, compound

HRID 1616073Notes

Reaction equation

HRID 1616073 reaction equation
FC1C=C2C(=CC=1)N=C(C(NC(=O)OC(C)(C)C)C)C(C1C=CC=CN=1)=C2C1C(C)=CC=CN=1.FC(F)(F)C(O)=O.NC1C(C#N)=C(Cl)N=CN=1.C(N(C(C)C)CC)(C)C.[NH2:61][C:62]1[C:67]([C:68]#[N:69])=[C:66]([NH:70][C@H:71]([C:73]2[C:82]([C:83]3[CH:88]=[CH:87][CH:86]=[CH:85][N:84]=3)=[C:81]([C:89]3[C:94]([CH3:95])=[CH:93][CH:92]=[CH:91][N:90]=3)[C:80]3[C:75](=[CH:76][CH:77]=[C:78]([F:96])[CH:79]=3)[N:74]=2)[CH3:72])[N:65]=[CH:64][N:63]=1>C(Cl)Cl>[NH2:61][C:62]1[C:67]([C:68]#[N:69])=[C:66]([NH:70][CH:71]([C:73]2[C:82]([C:83]3[CH:88]=[CH:87][CH:86]=[CH:85][N:84]=3)=[C:81]([C:89]3[C:94]([CH3:95])=[CH:93][CH:92]=[CH:91][N:90]=3)[C:80]3[C:75](=[CH:76][CH:77]=[C:78]([F:96])[CH:79]=3)[N:74]=2)[CH3:72])[N:65]=[CH:64][N:63]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 122782624-Amino-6-chloropyrimidine-5-carbonitrile2×HCID 67599683Tert-butyl 1-(6-fluoro-4-(3-methylpyridin-2-yl)-3-(pyridin-2-yl)quinolin-2-yl)ethylcarbamateHCID 86695297(S)-4-amino-6-(1-(6-fluoro-4-(3-methylpyridin-2-yl)-3-(pyridin-2-yl)quinolin-2-yl)ethylamino)pyrimidine-5-carbonitrile

Product 1

HCID 67599809HCID 67599809, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 1-(6-fluoro-4-(3-methylpyridin-2-yl)-3-(pyridin-2-yl)-quinolin-2-yl)ethylcarbamate (0.23 g, 0.50 mmol) in DCM (5 mL) was added trifluoroacetic acid (0.97 mL, 12.5 mmol) and the resulting solution was stirred at room temperature for one hour. The solution was concentrated under reduced pressure then diluted with 1-butanol (2.5 mL) followed by the addition of 4-amino-6-chloropyrimidine-5-carbonitrile (0.082 g, 0.53 mmol) and diisopropylethylamine (0.26 mL, 1.51 mmol) and 4-amino-6-chloropyrimidine-5-carbonitrile (0.082 g, 0.53 mmol). The solution was stirred at 120° C. for 3 h then purification was attempted by silica gel column chromatography eluting with 0-100% (1:10:90 NH4OH:MeOH:DCM) in DCM). The resulting crude solid was repurified by silica gel column chromatography eluting with a gradient of 0-7% MeOH in DCM to afford a mixture of (R) and (S)-4-amino-6-(1-(6-fluoro-4-(3-methylpyridin-2-yl)-3-(pyridin-2-yl)quinolin-2-yl)ethylamino)pyrimidine-5-carbonitrile as a yellow glass: LC-MS (ESI) m/z 477.2 [M+H]+.

Workup

  1. concentrationThe solution was concentrated under reduced pressure
  2. additionthen diluted with 1-butanol (2.5 mL)
  3. stirringThe solution was stirred at 120° C. for 3 h
  4. custompurification
  5. washeluting with 0-100% (1:10:90 NH4OH:MeOH:DCM) in DCM)
  6. customThe resulting crude solid was repurified by silica gel column chromatography
  7. washeluting with a gradient of 0-7% MeOH in DCM
  8. customto afford

Sources & evidence

ORD record
ord-b8c010a4164646608db6b56b12124474
Source dataset
uspto-grants-2014_07
Patent number
US08765768B2

Reaction notes

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