N-methyl-2-pyrrolidone → HCID 86724223, compound

HRID 571999Notes

Reaction equation

HRID 571999 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([C:9]#[N:10])=[C:4]([NH:11][C@H:12]([C:14]2[N:23]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)[C:22](=[O:31])[C:21]3[C:16](=[C:17](I)[CH:18]=[C:19]([F:32])[CH:20]=3)[N:15]=2)[CH3:13])[N:3]=1.[CH3:34][N:35]1C(=O)CCC1>>[NH2:1][C:2]1[N:3]=[C:4]([NH:11][C@H:12]([C:14]2[N:23]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)[C:22](=[O:31])[C:21]3[C:16](=[C:17]([C:34]#[N:35])[CH:18]=[C:19]([F:32])[CH:20]=3)[N:15]=2)[CH3:13])[C:5]([C:9]#[N:10])=[C:6]([NH2:8])[N:7]=1

Participants

3

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 86724224HCID 86724224, compound

Product 1

HCID 86724223HCID 86724223, compound

Procedure

To a solution of (S)-2,4-diamino-6-((1-(6-fluoro-3-(3-fluorophenyl)-8-iodo-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile (560 mg, 1.0 mmol) in NMP (4 mL) was added cuprous cyanide (2.0 mmol, 180 mg) and tetrakis(triphenylphosphine)Pd(0) (0.10 mmol, 120 mg). The mixture was irradiated in microwave reactor at 150° C. for one hour. Purification by flash chromatography (40 g flash silica, 30% EtOAc/Hexanes to 20% MeOH/EtOAc), followed by HPLC eluting with 5%-95% water/acetonitrile (0.1% v/v trifluoroacetic acid) provided (S)-2-(1-((2,6-diamino-5-cyanopyrimidin-4-yl)amino)ethyl)-6-fluoro-3-(3-fluorophenyl)-4-oxo-3,4-dihydroquinazoline-8-carbonitrile as a white solid. 1H NMR (400 MHz, DMSO) δ 8.55 (dd, J=2.8, 8.4 Hz, 1H), 8.20 (dd, J=3.2, 8.0 Hz, 1H), 7.88-7.17 (m, 5H), 5.07 (m, 1H), 1.44 (d, J=6.8 Hz, 3H). ES/MS 460.1 (M+H+);

Workup

  1. customThe mixture was irradiated in microwave reactor at 150° C. for one hour
  2. customPurification by flash chromatography (40 g flash silica, 30% EtOAc/Hexanes to 20% MeOH/EtOAc)
  3. washeluting with 5%-95% water/acetonitrile (0.1% v/v trifluoroacetic acid)

Sources & evidence

ORD record
ord-bc60e7798fb34981a1869d898f267148
Source dataset
uspto-grants-2015_05
Patent number
US09029384B2

Reaction notes

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