Ethanol → N-[(1S)-1-(5-Fluoropyrimidin-2-yl)ethyl]-9-(5-isopropoxy-1H-pyrazol-3-yl)-9H-purin-2-amine

HRID 450406Notes

Reaction equation

HRID 450406 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]([C@@H:8]([NH:10][C:11]2[N:16]=[C:15]([NH:17][C:18]3[CH:22]=[C:21]([O:23][CH:24]([CH3:26])[CH3:25])[NH:20][N:19]=3)[C:14]([N+:27]([O-])=O)=[CH:13][N:12]=2)[CH3:9])=[N:6][CH:7]=1.[CH2:30](O)C.C(O)(=O)C.C(N)=N.C(OCC)(=O)C>[Cl-].[Na+].O.[Pd]>[F:1][C:2]1[CH:3]=[N:4][C:5]([C@@H:8]([NH:10][C:11]2[N:16]=[C:15]3[C:14]([N:27]=[CH:30][N:17]3[C:18]3[CH:22]=[C:21]([O:23][CH:24]([CH3:26])[CH3:25])[NH:20][N:19]=3)=[CH:13][N:12]=2)[CH3:9])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 8857Ethyl AcetateHCID 160693Formamidine acetateHCID 178458663N2-[(1S)-1-(5-Fluoropyrimidin-2-yl)ethyl]-N4-(5-isopropoxy-1H-pyrazol-3-yl)-5-nitropyrimidine-2,4-diamine2×

Product 1

HCID 178458595N-[(1S)-1-(5-Fluoropyrimidin-2-yl)ethyl]-9-(5-isopropoxy-1H-pyrazol-3-yl)-9H-purin-2-amine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 57417360Sodium chloride; waterSolvent

Procedure

N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-isopropoxy-1H-pyrazol-3-yl)-5-nitropyrimidine-2,4-diamine (Intermediate 32, 0.2 g) was dissolved into ethanol (20 mL) with Pd—C (40 mg) and a hydrogen inlet. The mixture was stirred at room temperature until no starting material was detected with TLC or LCMS. Formamidine acetate (0.5 g) was added to the filtrate after the filtration of resulting mixture. The mixture was stirred at 85° C. for 4 hours. Ethyl acetate (40 mL) was added into the resulting mixture, and brine (10 mL×3) was used to wash the organic layer. The organic layer was dried and concentrated. The resulting residue was separated by silica gel column (Ethyl acetate/MeOH) to afford 0.08 g desired product. MS (electrospray): 384 (M+1) for C17H18FN9O. 1H NMR (300 MHz, CD3OD) δ ppm 8.70 (s, 2H) 8.60 (s, 1H) 8.40 (s, 1H) 6.20 (s, 1H) 5.30 (m, 1H) 4.60 (m, 1H) 1.60 (d, 3H) 1.50 (d, 6H).

Workup

  1. filtrationafter the filtration
  2. customof resulting mixture
  3. stirringThe mixture was stirred at 85° C. for 4 hours
  4. washto wash the organic layer
  5. customThe organic layer was dried
  6. concentrationconcentrated
  7. customThe resulting residue was separated by silica gel column (Ethyl acetate/MeOH)

Sources & evidence

ORD record
ord-284fe3b023f54f61aec4b1abc2907378
Source dataset
uspto-grants-2013_07
Patent number
US08486966B2

Reaction notes

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