Potassium Carbonate → 2-(2-Cyclopropyl-8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-5-yl)-isonicotinonitrile

HRID 1848335Notes

Reaction equation

HRID 1848335 reaction equation
[CH:1]1([C:4]2[N:17]=[C:7]3[C:8]([O:15][CH3:16])=[CH:9][CH:10]=[C:11](B(O)O)[N:6]3[N:5]=2)[CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].Br[C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][N:32]=1)[C:28]#[N:29]>COCCOC.[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:1]1([C:4]2[N:17]=[C:7]3[C:8]([O:15][CH3:16])=[CH:9][CH:10]=[C:11]([C:25]4[CH:26]=[C:27]([CH:30]=[CH:31][N:32]=4)[C:28]#[N:29])[N:6]3[N:5]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 117355442-Bromo-4-cyanopyridineHCID 58074662(2-Cyclopropyl-8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-5-yl)boronic acid

Product 1

HCID 468306322-(2-Cyclopropyl-8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-5-yl)-isonicotinonitrile

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

In a screw cap vial (2-cyclopropyl-8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-5-yl)boronic acid, compound 303, (26 mg, 0.1 mmol) was dissolved in DME (0.6 mL) and 1 M K2CO3 (0.2 mL) under argon. 2-Bromo-isonicotinonitrile (18 mg, 0.1 mmol) and Pd(PPh3)4 (6 mg, 0.005 mmol) were added. The suspension was shaken at 80° C. for 17 h after which brine was added, and the aqueous phase was extracted with DCM (×3). The combined organic phases were dried, filtered and concentrated. The crude product was purified by flash chromatography, eluent TBME:heptane 4:1->9:1. This afforded the title compound as a solid 1H NMR (300 MHz, DMSO) δ 9.23-9.09 (m, 1H), 9.00 (dd, J=4.9, 0.8 Hz, 1H), 7.95 (dd, J=4.9, 1.5 Hz, 1H), 7.90 (d, J=8.3 Hz, 1H), 7.24 (d, J=8.4 Hz, 1H), 4.03 (s, 3H), 2.29 (tt, J=8.1, 5.0 Hz, 1H), 1.18-0.87 (m, 4H).

Workup

  1. additionwas added
  2. extractionthe aqueous phase was extracted with DCM (×3)
  3. customThe combined organic phases were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography, eluent TBME:heptane 4:1->9:1

Sources & evidence

ORD record
ord-1311d054ce174ccfbe05bfeefb60295b
Source dataset
uspto-grants-2015_02
Patent number
US08952162B2

Reaction notes

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