Diisopropylethylamine → HCID 178461953, compound

HRID 243411Notes

Reaction equation

HRID 243411 reaction equation
Cl.Cl.[NH2:3][C@H:4]([C:6]1[N:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)[C:8]2[C:14]([C:15]#[N:16])=[C:13]([F:17])[CH:12]=[CH:11][C:9]=2[N:10]=1)[CH3:5].Cl[C:25]1[N:33]=[CH:32][N:31]=[C:30]2[C:26]=1[N:27]=[CH:28][N:29]2C1CCCCO1.CCN(C(C)C)C(C)C>CC(O)C>[F:17][C:13]1[CH:12]=[CH:11][C:9]2[N:10]=[C:6]([C@@H:4]([NH:3][C:25]3[N:33]=[CH:32][N:31]=[C:30]4[C:26]=3[N:27]=[CH:28][NH:29]4)[CH3:5])[N:7]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[C:8]=2[C:14]=1[C:15]#[N:16]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 681570552-((S)-1-Aminoethyl)-5-fluoro-3-pyridin-2-yl-3H-benzoimidazole-4-carbonitrile dihydrochloride

Product 1

HCID 178461953HCID 178461953, compoundYield 61.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2-((S)-1-aminoethyl)-5-fluoro-3-pyridin-2-yl-3H-benzoimidazole-4-carbonitrile dihydrochloride (250 mg, 0.71 mmol) in IPA (7 mL) was added 6-chloro-9-(tetrahydro-pyran-2-yl)-9H-purine (220 mg, 0.92 mmol) and DIPEA (361 μL, 2.1 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=2.86 min, [M+H]+=484. The product was dissolved HCl in methanol (5 mL, 2.5M) and the reaction stirred at RT for 2 h. 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 290 as a white solid (174 mg, 51%) 1H NMR 400 MHz (DMSO-d6): δ 12.57 (1H, br s), 8.53-8.50 (1H, m), 8.04 (1H, dd, J=9.0, 4.72 Hz), 8.00 (1H, s), 7.96-7.88 (1H, m), 7.74 (1H, d, J=8.0 Hz), 7.47 (1H, dd, J=7.2, 4.9 Hz), 7.43-7.34 (1H, m), 7.30 (1H, dd, J=10.3, 9.2 Hz), 5.71 (1H, br s), 1.62 (3H, d, J=7.0 Hz). LCMS (Method K): RT=2.88 min, [M+H]+=400

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-c869299a0c2f49f9a7227f360bc3402e
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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