Hydrochloric Acid → 2-[(1-Methyl-1H-indazol-5-yl)oxy]-3-pyridinemethanamine

HRID 1715563Notes

Reaction equation

HRID 1715563 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([O:11][C:12]3[N:19]=[CH:18][CH:17]=[CH:16][C:13]=3[C:14]#[N:15])=[CH:8][CH:9]=2)[CH:4]=[N:3]1.Cl>CO.[OH-].[OH-].[Pd+2]>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([O:11][C:12]3[C:13]([CH2:14][NH2:15])=[CH:16][CH:17]=[CH:18][N:19]=3)=[CH:8][CH:9]=2)[CH:4]=[N:3]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 574187422-(1-Methyl-1H-indazol-5-yloxy)-nicotinonitrile

Product 1

HCID 674103932-[(1-Methyl-1H-indazol-5-yl)oxy]-3-pyridinemethanamineYield 35%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

2-(1-Methyl-1H-indazol-5-yloxy)-nicotinonitrile (3n) (0.132 g, 0.528 mmol) was suspended in MeOH (6 mL). Pd(OH)2 (0.060 mg, 0.427 mmol) was added under a nitrogen atmosphere followed by concentrated aqueous HCl (0.6 mL). The system was purged with H2 gas and the reaction stirred at room temperature for 3 hours under an H2(g) atmosphere. The reaction mixture was filtered through a pad of celite, washed through with MeOH. The organics were concentrated under reduced pressure to afford the crude product, which was purified by flash column chromatography (MeOH/Et3N/EtOAc) to provide the desired product (4n) (0.047 g, 35% yield). 1H NMR (400 mHz, CD3OD) δ 7.96 (s, 1H), 7.90 (d, J=4.7 Hz, 1H), 7.82 (d, J=7.0 Hz, 1H), 7.56 (d, J=9.4 Hz, 1H), 7.46 (d, J=2.3 Hz, 1H), 7.23-7.21 (m, 1H), 7.09-7.06 (m, 1H), 4.07 (s, 3H), 3.95 (s, 2H).

Workup

  1. customThe system was purged with H2 gas
  2. filtrationThe reaction mixture was filtered through a pad of celite
  3. washwashed through with MeOH
  4. concentrationThe organics were concentrated under reduced pressure
  5. customto afford the crude product, which
  6. customwas purified by flash column chromatography (MeOH/Et3N/EtOAc)

Sources & evidence

ORD record
ord-2ae0f2ffe9d04d6091f5701910946f86
Source dataset
uspto-grants-2010_09
Patent number
US07799782B2

Reaction notes

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