Cesium carbonate → HCID 136387314, compound

HRID 718184Notes

Reaction equation

HRID 718184 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([N:16]3[C:20](=[O:21])[NH:19][C:18]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)=[N:17]3)=[N:13][C:14]=2[CH3:15])[CH:5]=[CH:4][N:3]=1.[CH:29]1([C:32]([NH2:34])=[O:33])[CH2:31][CH2:30]1.C([O-])([O-])=O.[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:28][C:25]1[CH:26]=[CH:27][C:22]([C:18]2[NH:19][C:20](=[O:21])[N:16]([C:12]3[N:13]=[C:14]([CH3:15])[C:9]([O:8][C:6]4[CH:5]=[CH:4][N:3]=[C:2]([NH:34][C:32]([CH:29]5[CH2:31][CH2:30]5)=[O:33])[CH:7]=4)=[CH:10][CH:11]=3)[N:17]=2)=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 80376CyclopropanecarboxamideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 136641693HCID 136641693, compound

Product 1

HCID 136387314HCID 136387314, compoundYield 25.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of Example A8 (0.250 g, 0.628 mmol), cyclopropane carboxamide (0.100 g, 1.175 mmol), Cs2CO3 (0.400 g, 1.228 mmol) and X-Phos (0.012 g, 0.025 mmol) in dioxane (20 mL) was purged with argon for 5 minutes. To the reaction mixture was added Pd2(dba)3 (0.012 g, 0.013 mmol) and the mixture wass heated in a reclosable sealed tube (100 mL) at 110° C. for 8 h. The solids from the reaction mixture was filtered and washed with DCM and THF. The filtrate was evaporated and the residue subjected to chromatography using (0-100% EtOAc/DCM) to provide N-(4-((6-(3-(4-fluorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methylpyridin-3-yl)oxy)pyridin-2-yl)cyclopropanecarboxamide (0.072 g, 24%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.73 (s, 1H), 10.89 (s, 1H), 8.21 (d, J=5.7 Hz, 1H), 7.98-7.93 (m, 3H), 7.75 (d, J=8.8 Hz, 1H), 7.59 (d, J=2.4 Hz, 1H), 7.40 (t, J=8.8 Hz, 2H), 6.71 (dd, J=5.7, 2.4 Hz, 1H), 2.33 (s, 3H), 1.95 (t, J=6.1 Hz, 1H), 0.75 (d, J=6.2 Hz, 4H), MS (ESI) m/z: 447.2 (M+H+).

Workup

  1. filtrationThe solids from the reaction mixture was filtered
  2. washwashed with DCM and THF
  3. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-0438594e3cb2473396df93ad847193f2
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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