Hydrochloric Acid → HCID 178492172, compound

HRID 1621550Notes

Reaction equation

HRID 1621550 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[C:17]([C:18]3[N:26]=[C:25]([CH3:27])[N:24]=[C:23]4[C:19]=3[N:20]=[CH:21][N:22]4C3CCCCO3)=[CH:16][C:13]([CH:14]=O)=[CH:12][N:11]=2)=[CH:5][CH:4]=1.[C:34]([NH2:38])([CH3:37])([CH3:36])[CH3:35].[BH4-].[Na+].Cl.C(O)(C(F)(F)F)=O>C(Cl)Cl.C(O)C.CO.C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C>[C:34]([NH:38][CH2:14][C:13]1[CH:16]=[C:17]([C:18]2[N:26]=[C:25]([CH3:27])[N:24]=[C:23]3[C:19]=2[N:20]=[CH:21][NH:22]3)[C:10]([NH:9][C:6]2[CH:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[N:11][CH:12]=1)([CH3:37])([CH3:36])[CH3:35]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 6385Tert-ButylamineHCID 6422Trifluoroacetic acidHCID 4311764Sodium borohydrideHCID 59548351HCID 59548351, compound

Product 1

HCID 178492172HCID 178492172, compoundYield 54.8%

Reagents, catalysts & solvents 4

HCID 178460666HCID 178460666, compoundCatalystHCID 702EthanolSolventHCID 887MethanolSolvent3×HCID 6344DichloromethaneSolvent2×

Procedure

6-(6-Methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)nicotinaldehyde (99.5 mg, 0.223 mmol) was suspended in CH2Cl2 (1.5 mL) and ethanol (1.5 mL), and tert-butylamine (0.075 mL, 0.71 mmol) and tetraisopropoxytitanium (0.20 mL, 0.68 mmol) were added. The reaction was stirred under nitrogen at room temperature for 20 min, and then was fitted with a reflux condenser and put in a preheated oil bath (about 50° C.) and stirred for 90 min. Then, the reaction was cooled to room temperature and sodium borohydride (28.7 mg, 0.759 mmol) and MeOH (1.0 mL) were added. The reaction was stirred at room temperature for 45 minutes, and then more MeOH and 5N HCl (0.50 mL) were added, and stirring was continued overnight at room temperature. Then, the reaction was diluted with DCM and MeOH and filtered through a Celite® (diatomaceous earth) pad, which was washed with DCM, MeOH, and a 1:1 mixture of these 2 solvents. The filtrate was concentrated and diluted with DCM and MeOH and filtered through another Celite® (diatomaceous earth) pad, which was washed with DCM and MeOH. The filtrate was concentrated and purified by prep HPLC to give 5-((tert-butylamino)methyl)-N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-amine (51.1 mg, 98.3% purity, 43% yield) as a TFA salt. 1H NMR (d6-DMSO, 400 MHz) δ 12.74 (br s, 1H), 9.81 (br s, 1H), 8.70 (s, 1H), 8.65 (br s, 2H), 8.59 (d, J=2.74 Hz, 1H), 8.42 (d, J=2.35 Hz, 1H), 8.14 (dd, J=8.80 Hz, 2.74 Hz, 1H), 6.89 (d, J=8.80 Hz, 1H), 4.18 (br s, 2H), 3.86 (s, 3H), 2.87 (s, 3H), 1.39 (s, 9H). m/z (ESI, +ve ion) 419 (M+H)+.

Workup

  1. customwas fitted with a reflux condenser
  2. customput in a preheated oil bath
  3. stirring(about 50° C.) and stirred for 90 min
  4. temperatureThen, the reaction was cooled to room temperature
  5. stirringThe reaction was stirred at room temperature for 45 minutes
  6. stirringstirring
  7. waitwas continued overnight at room temperature
  8. filtrationfiltered through a Celite® (diatomaceous earth) pad, which
  9. washwas washed with DCM, MeOH
  10. additiona 1:1 mixture of these 2 solvents
  11. concentrationThe filtrate was concentrated
  12. additiondiluted with DCM and MeOH
  13. filtrationfiltered through another Celite® (diatomaceous earth) pad, which
  14. washwas washed with DCM and MeOH
  15. concentrationThe filtrate was concentrated
  16. custompurified by prep HPLC

Sources & evidence

ORD record
ord-a901247ca48649c79d92189efd163965
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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