Ammonium Chloride → (S)-N6-(5-Cyclopropyl-1H-pyrazol-3-yl)-N2-(1-(4-fluorophenyl)ethyl)pyridine-2,3,6-triamine

HRID 75881Notes

Reaction equation

HRID 75881 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[N:15]=[C:14]([NH:16][C@H:17]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)[CH3:18])[C:13]([N+:26]([O-])=O)=[CH:12][CH:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.[Cl-].[NH4+].C([O-])(=O)C.[NH4+]>CO.C1COCC1.[Zn]>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[N:15]=[C:14]([NH:16][C@H:17]([C:19]4[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=4)[CH3:18])[C:13]([NH2:26])=[CH:12][CH:11]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 517165Ammonium AcetateHCID 68522604(S)-N6-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-(1-(4-fluorophenyl)ethyl)-3-nitropyridine-2,6-diamine

Product 1

HCID 68521442(S)-N6-(5-Cyclopropyl-1H-pyrazol-3-yl)-N2-(1-(4-fluorophenyl)ethyl)pyridine-2,3,6-triamine

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To a suspension of (S)—N6-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-(1-(4-fluorophenyl)ethyl)-3-nitropyridine-2,6-diamine (Example 26; 0.40 g, 1.05 mmol) and zinc dust (0.342 g, 5.23 mmol) in MeOH-THF (1:1, 16 ml) was slowly added a saturated aqueous ammonium chloride solution (2.5 ml). The mixture was stirred at 25° C. for 1 hr, then treated with saturated ammonium acetate solution (4 ml). The resulting mixture was stirred for another 30 min. The Zn dust was removed by filtration and the cake was washed with EtOAc (20 ml). The organic layer was separated, washed with brine (10 ml), and dried over Na2SO4. Removal of the solvent gave the title compound at quantitative yield. 1H NMR (400 MHz) δ 11.5 (br, 1H), 7.98 (br, 1H), 7.43 (m, 2H), 7.07 (m, 2H), 6.67 (d, J=8 Hz, 1H), 6.09 (s, 1H), 5.63-5.70 (m, 2H), 5.19 (m, 1H), 4.04 (br, 2H), 1.77 (m, 1H), 1.46 (d, J=6.8 Hz, 3H), 0.85 (m, 2H), 0.59 (m, 2H). MS: Calcd.: 352. Found: [M+H]+ 353.

Workup

  1. stirringThe resulting mixture was stirred for another 30 min
  2. customThe Zn dust was removed by filtration
  3. washthe cake was washed with EtOAc (20 ml)
  4. customThe organic layer was separated
  5. washwashed with brine (10 ml)
  6. dry with materialdried over Na2SO4
  7. customRemoval of the solvent

Sources & evidence

ORD record
ord-f046fec09bec4a8eb678af6a9ef23063
Source dataset
uspto-grants-2014_09
Patent number
US08835465B2

Reaction notes

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