Hydrochloric Acid → HCID 178492171, compound

HRID 1621551Notes

Reaction equation

HRID 1621551 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.[CH:34]([NH2:37])([CH3:36])[CH3:35].[BH4-].[Na+].Cl.C(O)(C(F)(F)F)=O>C(O)C.C(Cl)Cl.CO.C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C>[CH:34]([NH:37][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)([CH3:36])[CH3:35]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 6363IsopropylamineHCID 6422Trifluoroacetic acidHCID 4311764Sodium borohydrideHCID 59548351HCID 59548351, compound

Product 1

HCID 178492171HCID 178492171, compoundYield 96.8%

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 (90.6 mg, 0.203 mmol) was suspended in ethanol (1.2 mL) and DCM (1.2 mL), and isopropylamine (0.060 mL, 0.70 mmol) and tetraisopropoxytitanium (0.20 mL, 0.68 mmol) were added. The reaction was stirred at room temperature for 75 min, and then sodium borohydride (26.8 mg, 0.708 mmol) was added, along with MeOH (1 mL), and stirring was continued at room temperature. After 2 h, more MeOH and 5N 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 and purified by prep HPLC to give 5-((isopropylamino)methyl)-N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-amine (79.5 mg, 97.1% purity, 76% yield) as a TFA salt. 1H NMR (d6-DMSO, 400 MHz) δ 12.71 (br s, 1H), 9.80 (br s, 1H), 8.69 (s, 1H), 8.65 (br s, 2H), 8.58 (d, J=2.74 Hz, 1H), 8.42 (d, J=2.15 Hz, 1H), 8.14 (dd, J=9.00 Hz, 2.74 Hz, 1H), 6.89 (d, J=9.00 Hz, 1H), 4.24-4.18 (m, 2H), 3.86 (s, 3H), 3.48-3.38 (m, 1H), 2.87 (s, 3H), 1.31 (d, J=6.46 Hz, 6H). m/z (ESI, +ve ion) 405 (M+H)+.

Workup

  1. stirringstirring
  2. customwas continued at room temperature
  3. waitAfter 2 h
  4. stirringstirring
  5. waitwas continued overnight
  6. filtrationfiltered through a Celite® (diatomaceous earth) pad, which
  7. washwas washed with DCM and MeOH
  8. concentrationThe filtrate was concentrated
  9. custompurified by prep HPLC

Sources & evidence

ORD record
ord-65efa59669a94d7687bfd478b51c93a0
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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