Diisopropylethylamine → HCID 178463529, compound

HRID 409020Notes

Reaction equation

HRID 409020 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:12]=[C:11]2[S:13][CH:14]=[CH:15][C:10]2=[CH:9][C:8]=1[CH:16]([NH2:18])[CH3:17].Cl[C:20]1[N:28]=[CH:27][N:26]=[C:25]2[C:21]=1[NH:22][CH:23]=[N:24]2.C(N(C(C)C)CC)(C)C>C(O)CCC>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:12]=[C:11]2[S:13][CH:14]=[CH:15][C:10]2=[CH:9][C:8]=1[CH:16]([NH:18][C:20]1[N:28]=[CH:27][N:26]=[C:25]2[C:21]=1[N:22]=[CH:23][NH:24]2)[CH3:17]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 53592776-ChloropurineHCID 66632471HCID 66632471, compound

Product 1

HCID 178463529HCID 178463529, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
110 °C

Procedure

To a reaction flask containing 1-(6-(pyridin-2-yl)thieno[2,3-b]pyridin-5-yl)ethanamine (134 mg, 0.525 mmol), 6-chloropurine (97 mg, 0.63 mmol, 1.2 eq) and diisopropylethylamine (137 μL, 0.79 mmol, 1.5 eq) was added 5 mL of n-butanol. The reaction was heated to 110° C. for 24 h, then cooled to rt and concentrated in vacuo. The residue was dissolved in ethyl acetate (˜50 mL) with heat and sonication, then washed with 5 mL water and 5 mL brine. The organic layer was dried over MgSO4, filtered, and concentrated. Purification by column chromatography using 0-80% gradient of (90:9:1 DCM:MeOH:NH4OH) in dichloromethane afforded racemic N-(1-(6-(pyridin-2-yl)thieno[2,3-b]pyridin-5-yl)ethyl)-9H-purin-6-amine. The room temperature NMR spectrum in CDCl3 exists as a roughly 3:1 mixture of isomers. 1H NMR (400 MHz, CDCl3) δ 8.80 (br d, J=4.3 Hz, 0.75 H), 8.73 (br d, J=3.1 Hz, 0.25 H), 8.55 (s, 0.25 H), 8.36-8.26 (series of m, 1.75 H), 8.15-8.03 (series of m, 1.5 H), 7.93 (br s, 0.75 H), 7.88 (m, 1.4 H), 7.56 (m, 0.5 H), 7.55 (d, J=5.9 Hz, 0.75 H), 7.37 (dd, J=6.6, 5.1 Hz, 0.75 H), 7.26 (d, J=5.9 Hz, 0.75 H), 7.20 (d, J=5.9 Hz, 0.25 H), 6.65 (m, 0.25 H), 6.35 (m, 0.25 H), 6.15 (br s, 0.75 H), 1.55 (d, J=7.0 Hz, 2.25 H), 1.35 (d, J=6.3 Hz, 0.75 H) ppm. LC/MS (M+1, found=374.0). Chiral SFC separation of the racemate afforded the individual enantiomers, (S)—N-(1-(6-(pyridin-2-yl)thieno[2,3-b]pyridin-5-yl)ethyl)-9H-purin-6-amine and (R)—N-(1-(6-(pyridin-2-yl)thieno[2,3-b]pyridin-5-yl)ethyl)-9H-purin-6-amine.

Workup

  1. temperaturecooled to rt
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in ethyl acetate (˜50 mL)
  4. temperaturewith heat
  5. customsonication
  6. washwashed with 5 mL water and 5 mL brine
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by column chromatography

Sources & evidence

ORD record
ord-7e14805bc26c4c19a132ac70008cb307
Source dataset
uspto-grants-2014_06
Patent number
US08759371B2

Reaction notes

Loading…