Cesium carbonate → Tert-butyl 7-(4-(5-chloropyridin-2-ylcarbamoyl)phenoxy)-6-cyanochroman-4-carboxylate

HRID 1626389Notes

Reaction equation

[C:1]([C:4]1[CH:29]=[CH:28][C:7]([O:8][C:9]2[CH:18]=[C:17]3[C:12]([CH:13]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14][CH2:15][O:16]3)=[CH:11][C:10]=2[C:26]#[N:27])=[CH:6][CH:5]=1)(=[O:3])[NH2:2].Cl[C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][N:32]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:37][C:34]1[CH:35]=[CH:36][C:31]([NH:2][C:1]([C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]3[CH:18]=[C:17]4[C:12]([CH:13]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:14][CH2:15][O:16]4)=[CH:11][C:10]=3[C:26]#[N:27])=[CH:28][CH:29]=2)=[O:3])=[N:32][CH:33]=1

Participants

Conditions

Temperature: 80 °C

Procedure

tert-Butyl 7-(4-carbamoylphenoxy)-6-cyanochroman-4-carboxylate (30 mg, 0.076 mmol), 2,5-dichloropyridine (12 mg, 0.084 mmol), XPHOS (7.3 mg, 0.015 mmol), palladium (II) acetate (1.7 mg, 0.0076 mmol) and cesium carbonate (62 mg, 0.19 mmol) were diluted with dioxane (600 μL) in a 1 mL vial. The reaction was purged with argon for 3 minutes, capped and heated at 80° C. for 12 hours. The reaction was cooled and loaded directly onto a biotage 25 column and eluted with 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes to yield tert-butyl 7-(4-(5-chloropyridin-2-ylcarbamoyl)phenoxy)-6-cyanochroman-4-carboxylate (5 mg, 0.0099 mmol, 13% yield).

Workup

customThe reaction was purged with argon for 3 minutes
customcapped
temperatureThe reaction was cooled
washeluted with 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-73182cd5232a453a982e1900512da314
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785445B2

Reaction notes

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