Hydrochloric Acid → HCID 178492168, compound

HRID 1811965Notes

Reaction equation

HRID 1811965 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.[NH2:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1.[BH4-].[Na+].Cl.C(O)(C(F)(F)F)=O>C(Cl)Cl.CCO.CO.C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C>[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][NH:22]4)=[CH:16][C:13]([CH2:14][NH:34][CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=3)=[CH:12][N:11]=2)=[CH:5][CH:4]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 195092-PyridinemethanamineHCID 4311764Sodium borohydrideHCID 59548351HCID 59548351, compound

Product 1

HCID 178492168HCID 178492168, compoundYield 69.2%

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 (73.8 mg, 0.166 mmol) was suspended in CH2Cl2 (1.5 mL) and EtOH (1.5 mL), and 2-(aminomethyl)pyridine (0.050 mL, 0.49 mmol) and tetraisopropoxytitanium (0.15 ml, 0.51 mmol) were added via syringe. The reaction was stirred under nitrogen at room temperature for 90 min, and then sodium borohydride (26.3 mg, 0.695 mmol) and MeOH (1.0 mL) were added, and stirring was continued. After 70 min, more MeOH and 5 N aqueous HCl (0.50 mL) were added, and stirring was continued overnight. The suspension was diluted with DCM and MeOH and filtered through a Celite® (diatomaceous earth) pad, which was washed with DCM and MeOH. The filtrate was concentrated, treated with DMSO and TFA, and purified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 28 min using a total flow rate of 100 mL/min) to give N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-5-((pyridin-2-ylmethylamino)methyl)pyridin-2-amine (52.1 mg, 55% yield) as a TFA salt. 1H NMR (d6-DMSO, 400 MHz) δ 12.69 (br s, 1H), 9.81 (br s, 1H), 9.46 (br s, 2H), 8.68 (s, 1H), 8.66 (d, J=4.30 Hz, 1H), 8.56 (d, J=2.74 Hz, 1H), 8.41 (d, J=2.35 Hz, 1H), 8.14 (dd, J=9.00 Hz, 2.74 Hz, 1H), 7.89 (dt, J=7.73 Hz, 1.76 Hz, 1H), 7.51 (d, J=7.82 Hz, 1H), 7.46-7.41 (m, 1H), 6.88 (d, J=8.80 Hz, 1H), 4.41 (s, 2H), 4.29 (s, 2H), 3.85 (s, 3H), 2.86 (s, 3H). m/z (ESI, pos. ion) 454 (M+H)+.

Workup

  1. stirringstirring
  2. waitAfter 70 min
  3. stirringstirring
  4. waitwas continued overnight
  5. filtrationfiltered through a Celite® (diatomaceous earth) pad, which
  6. washwas washed with DCM and MeOH
  7. concentrationThe filtrate was concentrated
  8. additiontreated with DMSO and TFA
  9. custompurified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 28 min

Sources & evidence

ORD record
ord-fe8aff5b8117463a97edf204722c5c01
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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