Hydrochloric Acid → HCID 178492177, compound

HRID 1811883Notes

Reaction equation

HRID 1811883 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:17]2[N:25]=[C:24]([CH3:26])[N:23]=[C:22]3[C:18]=2[N:19]=[CH:20][N:21]3C2CCCCO2)[C:5]([NH:8][C:9]2[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)=[N:6][CH:7]=1.[NH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.Cl>C1COCC1.C([O-])(O)=O.[Na+].CO.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:16][O:15][C:12]1[N:11]=[CH:10][C:9]([NH:8][C:5]2[C:4]([C:17]3[N:25]=[C:24]([CH3:26])[N:23]=[C:22]4[C:18]=3[N:19]=[CH:20][NH:21]4)=[CH:3][C:2]([NH:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[CH:7][N:6]=2)=[CH:14][CH:13]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 6115AnilineHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 23676156Sodium t-butoxideHCID 595484095-chloro-N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-amine

Product 1

HCID 178492177HCID 178492177, compoundYield 96%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 5-chloro-N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-amine (0.200 g, 0.443 mmol) and aniline (0.161 mL, 1.770 mmol) (Fluka, Buchs, Switzerland) in THF (10 mL) was treated with sodium tert-butoxide (0.128 g, 1.328 mmol) and 2-di-t-butylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (0.030 g). The mixture was deoxygenated and treated with Pd2(dba)3 (0.041 g, 0.044 mmol) under N2. The flask was fitted with a reflux condenser, then placed into a pre-heated bath at 80° C. and stirred overnight. The reaction mixture was diluted with saturated aqueous NaHCO3 (15 mL) and extracted with CH2Cl2 (2×25 mL). The combined organic extracts were washed with NaHCO3 (20 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give a tan oil. A glass microwave reaction vessel was charged with the crude oil and 1 N aqueous HCl (1.5 mL) in THF (2.5 mL). The reaction mixture was stirred and heated in a Discover model microwave reactor (CEM, Matthews, N.C.) at 100° C. for 8 min (100 watts, Powermax feature on). The mixture was diluted with methanol and then concentrated. The mixture was triturated with acetonitrile and allowed to stir 5 minutes. The precipitate was collected by filtration and washed with diethyl ether (3×25 mL). This gave N2-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-N5-phenylpyridine-2,5-diamine (0.180 g, 0.424 mmol, 96% yield) as a tan solid. MS (ESI pos. ion) m/z 425 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 9.85 (s, 1H); 8.52 (s, 1H); 8.41 (s, 1H); 7.87 (s, 1H); 7.52 (d, J=7.43 Hz, 2H); 7.39 (d, J=7.43 Hz, 1H); 7.21-7.29 (m, 2H); 7.10 (s, 2H); 7.00 (d, 1H); 6.88 (s, 1H); 3.98 (s, 3H); 2.83 (s, 3H).

Workup

  1. customThe mixture was deoxygenated
  2. customThe flask was fitted with a reflux condenser
  3. customplaced into a pre-heated bath at 80° C.
  4. extractionextracted with CH2Cl2 (2×25 mL)
  5. washThe combined organic extracts were washed with NaHCO3 (20 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationThe solution was filtered
  8. concentrationconcentrated in vacuo
  9. customto give a tan oil
  10. customA glass microwave reaction vessel
  11. stirringThe reaction mixture was stirred
  12. concentrationconcentrated
  13. customThe mixture was triturated with acetonitrile
  14. stirringto stir 5 minutes
  15. filtrationThe precipitate was collected by filtration
  16. washwashed with diethyl ether (3×25 mL)

Sources & evidence

ORD record
ord-95bc26846dd14289a772d743f87cba9c
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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