Hydrochloric Acid → HCID 76281462, compound

HRID 1480228Notes

Reaction equation

HRID 1480228 reaction equation
[C:1]([C:3]([NH:9][C:10]([C:12]1[CH:17]=[C:16]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])[C:15]([CH:24]2[CH2:26][CH2:25]2)=[CH:14][N:13]=1)=[O:11])([CH3:8])[CH2:4][CH:5]1[CH2:7][CH2:6]1)#[N:2].[Cl-].[NH4+].[N-:29]=[N+:30]=[N-:31].[Na+].N([O-])=O.[Na+].Cl>CN(C=O)C.C(OCC)(=O)C>[CH:24]1([C:15]2[C:16]([O:18][CH2:19][C:20]([F:23])([F:21])[F:22])=[CH:17][C:12]([C:10]([NH:9][C:3]([CH3:8])([C:1]3[N:29]=[N:30][NH:31][N:2]=3)[CH2:4][CH:5]3[CH2:6][CH2:7]3)=[O:11])=[N:13][CH:14]=2)[CH2:25][CH2:26]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 33557Sodium Azide2×HCID 23668193Sodium NitriteHCID 90203688HCID 90203688, compound

Product 1

HCID 76281462HCID 76281462, compoundYield 71.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
120 °C

Procedure

To a solution of N-(1-cyano-2-cyclopropyl-1-methyl-ethyl)-5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridine-2-carboxamide (example 150a, 300 mg, 817 μmol) in DMF (4 ml) under an argon atmosphere was added ammonium chloride (218 mg, 4.08 mmol), sodium azide (265 mg, 4.08 mmol). The reaction mixture was stirred at 120° C. under microwave radiation for 45 minutes. After cooling, the reaction mixture was poured into a mixture of ice water (12 mL) and ethyl acetate (4 mL). To the bi-phasic mixture was added sodium nitrite (231 mg, 3.35 mmol) (to decompose the excess of sodium azide), followed by a slow addition of a 4M aqueous solution of hydrochloric acid (until pH=2) under ice cooling. The bi-phasic mixture was then stirred at room temperature for 10 minutes, then diluted with more ethyl acetate and poured into a separatory funnel. After extraction the organic phase was collected and washed with water and brine. The organic phase was dried over sodium sulfate and evaporated down to dryness to yield the title compound (239 mg, 71%) as a crude solid which was used without any purification. MS (ESI, m/z): 411.5 (M+H+).

Workup

  1. temperatureAfter cooling
  2. stirringThe bi-phasic mixture was then stirred at room temperature for 10 minutes
  3. additionpoured into a separatory funnel
  4. extractionAfter extraction the organic phase
  5. customwas collected
  6. washwashed with water and brine
  7. dry with materialThe organic phase was dried over sodium sulfate
  8. customevaporated down to dryness

Sources & evidence

ORD record
ord-4c54a78d25e34b3791a736e81242b215
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

Loading…