Hydrochloric Acid → (S)-4-amino-6-((1-(7-fluoro-2-(2-(methylsulfonyl)phenyl)quinolin-3-yl)ethyl)-amino)pyrimidine-5-carbonitrile

HRID 75363Notes

Reaction equation

HRID 75363 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C@@H:22]([NH:24]C(=O)OC(C)(C)C)[CH3:23])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[S:18]([CH3:21])(=[O:20])=[O:19])=[N:9]2)=[CH:4][CH:3]=1.Cl.FC1C=C2C(C=C([C@@H](N)C)C(C3C=CC=CC=3S(C)(=O)=O)=N2)=CC=1.[NH2:57][C:58]1[C:63]([C:64]#[N:65])=[C:62](Cl)[N:61]=[CH:60][N:59]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:57][C:58]1[C:63]([C:64]#[N:65])=[C:62]([NH:24][C@H:22]([C:7]2[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[S:18]([CH3:21])(=[O:20])=[O:19])=[N:9][C:10]3[C:5]([CH:6]=2)=[CH:4][CH:3]=[C:2]([F:1])[CH:11]=3)[CH3:23])[N:61]=[CH:60][N:59]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 122782624-Amino-6-chloropyrimidine-5-carbonitrileHCID 57707808(S)-tert-butyl (1-(7-fluoro-2-(2-(methylsulfonyl)phenyl)quinolin-3-yl)-ethyl)carbamateHCID 86698503(1S)-1-(7-fluoro-2-(2-(methylsulfonyl)phenyl)-quinolin-3-yl)ethanamine

Product 1

HCID 71765914(S)-4-amino-6-((1-(7-fluoro-2-(2-(methylsulfonyl)phenyl)quinolin-3-yl)ethyl)-amino)pyrimidine-5-carbonitrileYield 5.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To (S)-tert-butyl (1-(7-fluoro-2-(2-(methylsulfonyl)phenyl)quinolin-3-yl)ethyl)-carbamate (440 mg, 1.0 mmol) was added HCl, 4M (1 mL). The resulting mixture was stirred at rt for 1 h. Solvent was removed and the crude (S)-1-(7-fluoro-2-(2-(methylsulfonyl)phenyl)quinolin-3-yl)ethanamine was used without further workup. A solution of (1S)-1-(7-fluoro-2-(2-(methylsulfonyl)phenyl)-quinolin-3-yl)ethanamine (100 mg, 290 mmol), 4-amino-6-chloropyrimidine-5-carbonitrile (45 mg, 290 μmol) and DIEA (101 μl, 581 mol) in DMF (4 mL) was heated to 100° C. overnight. Solvent was removed under reduce pressure and purified via preparatory. TLC using 3% of MeOH/DCM to afford a white powder of (S)-4-amino-6-((1-(7-fluoro-2-(2-(methylsulfonyl)phenyl)quinolin-3-yl)ethyl)-amino)pyrimidine-5-carbonitrile (6.9 mg, 5.1%). 1H NMR (500 MHz, CD3OD) δ ppm 1.51 (d, J=7.09 Hz, 3H) 3.17 (s, 3H) 5.43 (d, J=6.85 Hz, 1H) 7.48 (d, J=2.45 Hz, 1H) 7.60-7.63 (m, 1H) 7.66-7.69 (m, 2H) 7.73 (d, J=1.47 Hz, 1H) 7.81 (s, 1H) 8.07 (dd, J=9.05, 6.11 Hz, 1H) 8.13-8.17 (m, 1H) 8.49 (s, 1H). Mass Spectrum (ESI) m/e=463 (M+1).

Workup

  1. customSolvent was removed
  2. customSolvent was removed
  3. custompurified via preparatory

Sources & evidence

ORD record
ord-52a79a0644b04323a16c4dc679eb38b5
Source dataset
uspto-grants-2014_09
Patent number
US08835432B2

Reaction notes

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