Diisopropylethylamine → HCID 178429742, compound

HRID 243409Notes

Reaction equation

HRID 243409 reaction equation
Cl.Cl.[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH2:14])[CH3:13])[N:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[C:8]=2[C:21]=1[CH3:22].Cl[C:24]1[N:32]=[CH:31][N:30]=[C:29]2[C:25]=1[N:26]=[CH:27][N:28]2C1CCCCO1.CCN(C(C)C)C(C)C>CC(O)C>[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH:14][C:24]3[N:32]=[CH:31][N:30]=[C:29]4[C:25]=3[N:26]=[CH:27][NH:28]4)[CH3:13])[N:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[C:8]=2[C:21]=1[CH3:22]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157079(S)-1-(6-Fluoro-7-methyl-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride

Product 1

HCID 178429742HCID 178429742, compoundYield 51.5%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (S)-1-(6-fluoro-7-methyl-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (300 mg, 0.87 mmol) in IPA (10 mL) was added 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (271 mg, 1.14 mmol) and DIPEA (448 μL, 2.62 mmol) and the reaction mixture heated at 90° C. for 16 h. The reaction mixture was concentrated in vacuo and the resultant residue subjected to flash chromatography (SiO2, eluting with 0-10% methanol in EtOAc). LCMS (Method C): RT=2.81 min, [M+H]+=473. The product was dissolved HCl in methanol (5 mL, 2.5M) and the reaction stirred at RT for 30 min. The reaction mixture was concentrated in vacuo and the resultant residue loaded onto an SCX 2 cartridge, washed with methanol then eluted with ammonia in methanol (2M). The eluent was concentrated in vacuo and the residue triturated with diethyl ether to give 288 as a white solid (174 mg, 51%) 1H NMR 400 MHz δ (DMSO-d6 80° C.): 8.55-8.49 (1H, m), 8.01 (1H, s), 7.89 (1H, td, J=7.7, 1.9 Hz), 7.65 (1H, d, J=7.6 Hz), 7.49 (1H, dd, J=8.7, 4.7 Hz), 7.46 (1H, ddd, J=7.6, 4.9, 0.9 Hz), 7.17 (1H, br s), 7.02 (1H, dd, J=10.6, 9.0 Hz), 5.57 (1H, br s), 1.66 (3H, s), 1.55 (3H, d, J=6.8 Hz). LCMS (Method K): RT=3.01 min, [M+H]+=389

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. washthe resultant residue subjected to flash chromatography (SiO2, eluting with 0-10% methanol in EtOAc)
  3. dissolutionThe product was dissolved HCl in methanol (5 mL, 2.5M)
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. washwashed with methanol
  6. washthen eluted with ammonia in methanol (2M)
  7. concentrationThe eluent was concentrated in vacuo
  8. customthe residue triturated with diethyl ether

Sources & evidence

ORD record
ord-75c6fa1302a94b63a235e6b860fa7203
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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