Triethylamine → HCID 118214748, compound

HRID 2205608Notes

Reaction equation

HRID 2205608 reaction equation
[NH2:1][C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]#[N:10])=[C:4]([CH3:11])[N:3]=1.[NH2:12][C@H:13]([C:15]1[N:20]=[C:19]2[CH:21]=[CH:22][N:23]([CH3:24])[C:18]2=[CH:17][C:16]=1[N:25]1[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[C@H:27]([CH3:38])[CH2:26]1)[CH3:14].C(N(CC)CC)C>CS(C)=O>[NH2:1][C:2]1[N:7]=[C:6]([NH:12][C@H:13]([C:15]2[N:20]=[C:19]3[CH:21]=[CH:22][N:23]([CH3:24])[C:18]3=[CH:17][C:16]=2[N:25]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[C@H:27]([CH3:38])[CH2:26]2)[CH3:14])[C:5]([C:9]#[N:10])=[C:4]([CH3:11])[N:3]=1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 754124462-Amino-4-chloro-6-methyl-5-pyrimidinecarbonitrile2×HCID 118214747HCID 118214747, compound

Product 1

HCID 118214748HCID 118214748, compoundYield 84.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

To a 50 mL pear flask were added 2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile (30.5 mg, 0.181 mmol) and tert-butyl (R)-4-(5-((S)-1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-2-methylpiperazine-1-carboxylate (45 mg, 0.120 mmol) in DMSO (0.60 mL). Triethylamine (84 μL, 0.60 mmol) was added, and the mixture was stirred at 80° C. for 2 hours. Additional triethylamine (84 μL, 0.602 mmol) and 2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile (10 mg, 0.060 mmol) were added and the mixture was heated for another 3 hours at 80° C. The cooled mixture was partitioned between saturated NaHCO3 and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over MgSO4, filtered, and concentrated. The residue was purified by liquid chromatography (SiO2, 25-100% EtOAc/heptanes gradient) to give the title compound as a white solid (51 mg, 84%). 1H NMR (400 MHz, CDCl3) δ ppm 1.48-1.52 (m, 12H), 1.54 (d, J=6.82 Hz, 3H), 2.39 (s, 3H), 2.79-2.86 (m, 1H), 2.89-3.09 (m, 3H), 3.35 (br s, 1H), 3.78 (s, 3H), 4.05 (d, J=9.85 Hz, 1H), 4.34 (br s, 1H), 5.27 (br s, 1H), 5.94 (quin, J=6.76 Hz, 1H), 6.66 (d, J=3.28 Hz, 1H), 7.24 (d, J=3.28 Hz, 1H), 7.31 (d, J=7.83 Hz, 1H), 7.40 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C26H35N9O2, 506. found 506.

Workup

  1. temperaturethe mixture was heated for another 3 hours at 80° C
  2. customThe cooled mixture was partitioned between saturated NaHCO3 and ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by liquid chromatography (SiO2, 25-100% EtOAc/heptanes gradient)

Sources & evidence

ORD record
ord-8423612d58134d84a1d335a6c49045e9
Source dataset
uspto-grants-2016_06
Patent number
US09371321B2

Reaction notes

Loading…