Dichloromethane → HCID 178491073, compound

HRID 1621458Notes

Reaction equation

HRID 1621458 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:37]=[C:38]([CH:40]=[CH:41][CH:42]=1)[NH2:39].C(Cl)Cl.[BH4-].[Na+]>C(O)C.C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C.CO>[CH3:34][O:35][C:36]1[CH:37]=[C:38]([NH:39][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:40]=[CH:41][CH:42]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 108243-Methoxyaniline2×HCID 4311764Sodium borohydrideHCID 59548351HCID 59548351, compound

Product 1

HCID 178491073HCID 178491073, compoundYield 81%

Reagents, catalysts & solvents 3

HCID 178460666HCID 178460666, compoundCatalystHCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

6-(6-Methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)nicotinaldehyde (191.7 mg, 0.4303 mmol) was suspended in ethanol (4.0 mL) and tetraisopropoxytitanium (0.26 mL, 0.878 mmol) and 3-methoxyaniline (0.080 mL, 0.716 mmol) were added. The reaction was stirred under nitrogen at room temperature overnight, and then more DCM (about 3 mL) was added, along with more Ti(OiPr4) (0.13 mL, 0.44 mmol) and 3-methoxyaniline (0.050 mL, 0.45 mmol). Stirring was continued overnight, and then sodium borohydride (32.3 mg, 0.854 mmol) was added, along with MeOH (1 mL). The reaction was stirred at room temperature for 35 minutes and then quenched with 5N HCl (0.60 mL), which was added dropwise. Stirring was continued at room temperature over the weekend. Then, the suspension was diluted with DCM and MeOH and filtered through a pad of Celite® (diatomaceous earth). The Celite® (diatomaceous earth) pad was washed with DCM and MeOH, and the filtrate was concentrated, treated with water, and filtered again through a fritted filter (no Celite® (diatomaceous earth)). The solid was washed with water, collected, and dried under high vacuum in a water bath at 50° C., and then at room temperature overnight, to give 5-((3-methoxyphenylamino)methyl)-N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-amine (162.8 mg, 81% yield). MS (ESI pos. ion) m/z 469 (M+H)+. 1H NMR (d6-DMSO, 400 MHz) δ 12.53 (s, 1H), 9.74 (s, 1H), 8.62 (s, 1H), 8.51 (d, J=2.54 Hz, 1H), 8.27 (d, J=2.15 Hz, 1H), 8.13 (dd, J=8.80 Hz, 2.74 Hz, 1H), 7.00 (t, J=8.12 Hz, 1H), 6.87 (d, J=8.80 Hz, 1H), 6.38-6.17 (m, 3H), 4.29 (s, 2H), 3.85 (s, 3H), 3.66 (s, 3H), 2.84 (s, 3H).

Workup

  1. stirringStirring
  2. waitwas continued overnight
  3. stirringThe reaction was stirred at room temperature for 35 minutes
  4. customquenched with 5N HCl (0.60 mL), which
  5. additionwas added dropwise
  6. stirringStirring
  7. customwas continued at room temperature over the weekend
  8. additionThen, the suspension was diluted with DCM and MeOH
  9. filtrationfiltered through a pad of Celite® (diatomaceous earth)
  10. washThe Celite® (diatomaceous earth) pad was washed with DCM and MeOH
  11. concentrationthe filtrate was concentrated
  12. additiontreated with water
  13. filtrationfiltered again through a fritted filter (no Celite® (diatomaceous earth))
  14. washThe solid was washed with water
  15. customcollected
  16. customdried under high vacuum in a water bath at 50° C.

Sources & evidence

ORD record
ord-c238311d82fa4324a4f00a585078ad8d
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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