Hydrochloric Acid → tert-butyl 3-(2-(4-(4-cyano-1-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylate

HRID 517982Notes

Reaction equation

HRID 517982 reaction equation
[NH2:1][C:2]1[C:3]([NH:34][CH3:35])=[CH:4][C:5]([C:10]2[CH:29]=[CH:28][C:13]([O:14][CH2:15][CH2:16][CH:17]3[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:18]3)=[C:12]([C:30]([F:33])([F:32])[F:31])[CH:11]=2)=[N:6][C:7]=1[C:8]#[N:9].Cl.[N:37]([O-])=O.[Na+]>CN1C(=O)CCC1.O.CCOC(C)=O>[C:8]([C:7]1[C:2]2[N:1]=[N:37][N:34]([CH3:35])[C:3]=2[CH:4]=[C:5]([C:10]2[CH:29]=[CH:28][C:13]([O:14][CH2:15][CH2:16][CH:17]3[CH2:18][N:19]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:20]3)=[C:12]([C:30]([F:33])([F:31])[F:32])[CH:11]=2)[N:6]=1)#[N:9]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 23668193Sodium NitriteHCID 67294695Tert-butyl 3-(2-(4-(5-amino-6-cyano-4-(methylamino)pyridin-2-yl)-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylate

Product 1

HCID 67294315tert-butyl 3-(2-(4-(4-cyano-1-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylateYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

tert-Butyl 3-(2-(4-(5-amino-6-cyano-4-(methylamino)pyridin-2-yl)-2-(trifluoro-methyl)phenoxy)ethyl)azetidine-1-carboxylate (100 mg) was dissolved in NMP (1000 μl) and hydrochloric acid (1M, 407 μl) added. A solution of sodium nitrite (20 mg) in water (150 μl) was added at room temperature and the reaction stirred for 1 hour. The reaction mixture was diluted with EtOAc (30 ml) and washed with water (3×20 ml) and brine (20 ml). Organics were dried over sodium sulphate and solvent evaporated under reduced pressure to yield crude product as a brown oil. Purification by flash chromatography (DCM to 2% MeOH in DCM mobile phase, 10 g silica column) afforded product tert-butyl 3-(2-(4-(4-cyano-1-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylate (84% yield).

Workup

  1. washwashed with water (3×20 ml) and brine (20 ml)
  2. dry with materialOrganics were dried over sodium sulphate and solvent
  3. customevaporated under reduced pressure
  4. customto yield crude product as a brown oil
  5. customPurification by flash chromatography (DCM to 2% MeOH in DCM mobile phase, 10 g silica column)

Sources & evidence

ORD record
ord-6c45e281c4694692a2de592c8c18dbe7
Source dataset
uspto-grants-2015_08
Patent number
US09115126B2

Reaction notes

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