Hydrochloric Acid → HCID 178492230, compound

HRID 1811869Notes

Reaction equation

HRID 1811869 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.[CH3:34][O:35][C:36]1[CH:42]=[CH:41][C:39]([NH2:40])=[CH:38][CH:37]=1.[BH4-].[Na+].Cl>CCO.C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C.O.CO.C(Cl)Cl>[CH3:34][O:35][C:36]1[CH:42]=[CH:41][C:39]([NH:40][CH2:14][C:13]2[CH:16]=[C:17]([C:18]3[N:26]=[C:25]([CH3:27])[N:24]=[C:23]4[C:19]=3[N:20]=[CH:21][NH:22]4)[C:10]([NH:9][C:6]3[CH:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)=[N:11][CH:12]=2)=[CH:38][CH:37]=1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 7732P-AnisidineHCID 4311764Sodium borohydrideHCID 59548351HCID 59548351, compound

Product 1

HCID 178492230HCID 178492230, compoundYield 76%

Reagents, catalysts & solvents 5

HCID 178460666HCID 178460666, compoundCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)nicotinaldehyde (187.1 mg, 0.4200 mmol) was suspended in EtOH (3.8 mL) and tetraisopropoxytitanium (Fluka, Buchs, Switzerland, 0.25 mL, 0.84 mmol) and 4-methoxyaniline (Aldrich, St. Louis, Mo., 81.9 mg, 0.665 mmol) were added. DCM (2 mL) was added about 15 minutes later, and the reaction was stirred under nitrogen at room temperature overnight. Then, sodium borohydride (36 mg, 0.95 mmol) was added along with DCM (3 mL), and stirring was continued at room temperature, resulting in precipitation. After stirring for 1 hour, the suspension was treated with MeOH (1.5 mL) and 5 N HCl (0.60 mL). Stirring was continued at room temperature overnight. Then, the reaction was treated with water (20 mL) and filtered, and the solid was washed with water. The solid and unfiltered material were combined, concentrated, and treated with MeOH, and filtered. The filtration was sluggish, so instead the suspension was concentrated, treated with TFA and DMSO, and filtered with DCM and MeOH. This filtration was also sluggish, so the suspension was filtered instead through a Celite® (diatomaceous earth) pad. The filtrate was concentrated, but could not be filtered for HPLC purification despite treatment with DMSO, TFA, MeOH, and DCM. So, this solution was concentrated, and the fine suspension was filtered through a Celite® (diatomaceous earth) pad. This filtrate was purified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min) to give 5-((4-methoxyphenylamino)methyl)-N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-amine (149.4 mg, 76% yield). MS (ESI pos. ion) m/z 469 (M+H)+. 1H NMR (d6-DMSO, 400 MHz) δ 12.60 (s, 1H), 9.72 (s, 1H), 8.62 (s, 1H), 8.53 (d, J=2.54 Hz, 1H), 8.27 (s, 1H), 8.14 (dd, J=9.10 Hz, 2.45 Hz, 1H), 7.22 (s, 1H), 7.09 (s, 1H), 6.97 (s, 2H), 6.90-6.80 (m 3H), 4.38 (s, 2H), 3.85 (s, 3H), 3.67 (s, 3H), 2.85 (s, 3H).

Workup

  1. stirringstirring
  2. customwas continued at room temperature
  3. customresulting in precipitation
  4. stirringAfter stirring for 1 hour
  5. stirringStirring
  6. waitwas continued at room temperature overnight
  7. filtrationfiltered
  8. washthe solid was washed with water
  9. concentrationconcentrated
  10. additiontreated with MeOH
  11. filtrationfiltered
  12. filtrationThe filtration
  13. concentrationso instead the suspension was concentrated
  14. additiontreated with TFA and DMSO
  15. filtrationfiltered with DCM and MeOH
  16. filtrationThis filtration
  17. filtrationso the suspension was filtered instead through a Celite® (diatomaceous earth) pad
  18. concentrationThe filtrate was concentrated
  19. filtrationcould not be filtered for HPLC purification despite treatment with DMSO, TFA, MeOH, and DCM
  20. concentrationSo, this solution was concentrated
  21. filtrationthe fine suspension was filtered through a Celite® (diatomaceous earth) pad
  22. customThis filtrate was purified by prep 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-246d7ae5f60d41e3ba7aa61a87b7d745
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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