Ammonium formate → HCID 90410008, compound

HRID 626600Notes

Reaction equation

HRID 626600 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([NH:16][C:17]2[CH:22]=[C:21]([O:23][C:24]3[CH:25]=[N:26][C:27]([N+:30]([O-])=O)=[CH:28][CH:29]=3)[CH:20]=[CH:19][N:18]=2)=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])=O.[NH4+]>CO.C1COCC1.[Zn]>[NH2:30][C:27]1[N:26]=[CH:25][C:24]([O:23][C:21]2[CH:20]=[CH:19][N:18]=[C:17]([NH:16][C:14]([N:11]3[CH2:10][CH2:9][N:8]([CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[CH2:13][CH2:12]3)=[O:15])[CH:22]=2)=[CH:29][CH:28]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 90410005HCID 90410005, compound

Product 1

HCID 90410008HCID 90410008, compoundYield 66.4%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a stirring solution of 4-benzyl-N-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)piperazine-1-carboxamide (0.574 g, 1.321 mmol) in MeOH/THF (1:1, 30 mL) at RT was sequentially added ammonium formate (0.833 g, 13.21 mmol) and zinc powder (0.864 g, 13.21 mmol). The resulting suspension was stirred briskly at RT. After 75 min, the reaction was filtered through diatomaceous earth, rinsing with THF. The combined filtrates were concentrated and purified by silica gel chromatography (0-10% MeOH/DCM) to afford N-(4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)-4-benzylpiperazine-1-carboxamide (0.355 g, 64%) as a brittle pink foam. 1H NMR (400 MHz, DMSO-d6): δ 9.13 (s, 1H), 8.05 (d, J=5.7 Hz, 1H), 7.75 (d, J=2.9 Hz, 1H), 7.30-7.29 (m, 5H), 7.24-7.23 (m, 2H), 6.52 (dd, J=5.7, 2.4 Hz, 1H), 6.49 (d, J=8.9 Hz, 1H), 5.99 (s, 2H), 3.46 (s, 2H), 3.40 (t, J=4.7 Hz, 4H), 2.31 (t, J=4.7 Hz, 4H); MS (ESI) m/z: 405.2 (M+H+).

Workup

  1. customat RT
  2. filtrationthe reaction was filtered through diatomaceous earth
  3. washrinsing with THF
  4. concentrationThe combined filtrates were concentrated
  5. custompurified by silica gel chromatography (0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-70ad46ce7b8a4824a9dc07fa546d2a7a
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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