Cesium carbonate → N-(4-(4-Fluoro-2-methoxyphenyl)pyridin-2-yl)piperidine-4-carboxamide

HRID 1896237Notes

Reaction equation

HRID 1896237 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]([CH:17]3[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]3)=[O:16])[CH:9]=2)=[C:4]([O:30][CH3:31])[CH:3]=1.C(C1CCN(C(OC(C)(C)C)=O)CC1)(=O)N.ClC1C=C(C2C=CC(F)=CC=2OC)C=CN=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.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>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[O:16])[CH:9]=2)=[C:4]([O:30][CH3:31])[CH:3]=1

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27356461-(tert-Butoxycarbonyl)piperidine-4-carboxamideHCID 584326092-Chloro-4-(4-fluoro-2-methoxyphenyl)pyridineHCID 67382653Tert-butyl 4-(4-(4-fluoro-2-methoxyphenyl)pyridin-2-ylcarbamoyl)piperidine-1-carboxylate

Product 1

HCID 53379794N-(4-(4-Fluoro-2-methoxyphenyl)pyridin-2-yl)piperidine-4-carboxamideYield 23.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

The Boc-protected precursor of Example 3 tert-butyl 4-(4-(4-fluoro-2-methoxyphenyl)pyridin-2-ylcarbamoyl)piperidine-1-carboxylate was synthesized according to Method B starting from the above obtained compound tert-butyl 4-carbamoylpiperidine-1-carboxylate (100 mg, 0.44 mmol), 2-chloro-4-(4-fluoro-2-methoxy-phenyl)pyridine (94 mg, 0.4 mmol), Cs2CO3 (184 mg, 0.56 mmol), xantphos (13 mg, 23 μmol) and Tetrakis(triphenylphosphine)palladium (0) (9 mg, 8 μmol) in 1,4-dioxane (10 ml) at 125° C. for 3 h, and was purified after usual workup by column chromatography using DCM, petroleum ether, MeOH to afford the product in a yield of 23.5% as colorless oil. 1H-NMR (400 MHz, CDCl3): δ=8.34 (s, 1H), 8.25 (d, 1H), 8.00 (s, 1H), 7.70-7.65 (m, 1H), 7.48-7.42 (m, 1H), 7.35-7.32 (m, 1H), 7.22 (d, 1H), 6.76-6.70 (m, 2H), 4.17 (s, 2H), 3.83 (s, 3H), 2.82 (t, 2H), 2.45-2.40 (m, 1H), 1.93-1.90 (m, 2H), 1.79-1.70 (m, 2H), 1.46 (s, 9H), 0.88-0.86 (m, 4H), MS (m/z): 430.2 (M+H+).

Workup

  1. customwas synthesized
  2. customwas purified after usual workup by column chromatography
  3. customto afford the product in a yield of 23.5% as colorless oil

Sources & evidence

ORD record
ord-6377d3434771478a846a676abd0e6dd4
Source dataset
uspto-grants-2013_08
Patent number
US08518948B2

Reaction notes

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