Hydrochloric Acid → HCID 178492174, compound

HRID 1621456Notes

Reaction equation

HRID 1621456 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:15])=[CH:12][N:11]=2)=[CH:5][CH:4]=1.[BH4-].[Na+].C(Cl)Cl.Cl>CO>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[N:11]=[CH:12][C:13]([CH2:14][OH:15])=[CH:16][C:17]=2[C:18]2[N:26]=[C:25]([CH3:27])[N:24]=[C:23]3[C:19]=2[N:20]=[CH:21][NH:22]3)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 4311764Sodium borohydride2×HCID 59548351HCID 59548351, compound

Product 1

HCID 178492174HCID 178492174, compoundYield 71.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

6-(6-Methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)nicotinaldehyde (157 mg, 0.352 mmol) was dissolved in methanol (5.0 mL) and sodium borohydride (21.6 mg, 0.571 mmol) was added. The reaction was stirred at room temperature for 75 minutes, and then more NaBH4 (26 mg, 0.69 mmol) was added, along with DCM (3 mL). After 40 more minutes, 5N aqueous HCl (0.50 mL, 2.5 mmol) was added, along with a MeOH rinse (about 1 mL), and stirring was continued at room temperature overnight. Then, the reaction was diluted with water (20 mL), and the suspension was filtered. The filtration was sluggish, so the filtrate was discarded, and the solid was collected, and the unfiltered material was extracted with 10:1 DCM/MeOH. These organic extracts were combined with the solid that was collected, while the aqueous suspension was again filtered. The solid from this filtration was combined with the solid and organic extracts collected earlier. The resultant solution was concentrated, treated with EtOAc, and filtered. The solid was washed with EtOAc and MeOH, but the solid was not 95% pure by HPLC, so the filtrate and solid were collected, concentrated, treated with DCM, and filtered again. The solid was washed with DCM. The product was still not 95% pure by HPLC, so the filtrate and solid were again collected, concentrated, and this time purified on HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min) to give (6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9H-purin-6-yl)pyridin-3-yl)methanol (91.1 mg, 71% yield). MS (ESI pos. ion) m/z 364 (M+H)+. 1H NMR (d6-DMSO, 400 MHz) δ 12.62 (s, 1H), 9.79 (s, 1H), 8.62 (s, 1H), 8.54 (s, 1H), 8.24 (s, 1H), 8.17 (d, J=8.41 Hz, 1H), 6.86 (d, J=8.61 Hz, 1H), 4.52 (s, 2H), 3.85 (s, 3H), 2.86 (s, 3H).

Workup

  1. washrinse (about 1 mL)
  2. stirringstirring
  3. waitwas continued at room temperature overnight
  4. additionThen, the reaction was diluted with water (20 mL)
  5. filtrationthe suspension was filtered
  6. filtrationThe filtration
  7. customthe solid was collected
  8. extractionthe unfiltered material was extracted with 10:1 DCM/MeOH
  9. customthat was collected, while the aqueous suspension
  10. filtrationwas again filtered
  11. filtrationThe solid from this filtration
  12. customcollected earlier
  13. concentrationThe resultant solution was concentrated
  14. additiontreated with EtOAc
  15. filtrationfiltered
  16. washThe solid was washed with EtOAc and MeOH
  17. customso the filtrate and solid were collected
  18. concentrationconcentrated
  19. additiontreated with DCM
  20. filtrationfiltered again
  21. washThe solid was washed with DCM
  22. customso the filtrate and solid were again collected
  23. concentrationconcentrated
  24. customthis time purified on HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min)

Sources & evidence

ORD record
ord-4e2fe813882146539f0a65abc66b8039
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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