Cesium carbonate → HCID 11693265, compound

HRID 2055581Notes

Reaction equation

HRID 2055581 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[C@H:8]([NH:10][C:11]([C:13]1([NH:16][C:17](=[O:22])[C:18]([F:21])([F:20])[F:19])[CH2:15][CH2:14]1)=[O:12])[CH3:9].C(=O)([O-])[O-].[Cs+].[Cs+].[F:32][C:33]([F:54])([F:53])[S:34]([O:37][C:38]1[C:43]([O:44][S:45]([C:48]([F:51])([F:50])[F:49])(=[O:47])=[O:46])=[CH:42][CH:41]=[CH:40][C:39]=1Cl)(=[O:36])=[O:35].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCOCC1.CO.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:50][C:48]([F:49])([F:51])[S:45]([O:44][C:43]1[C:38]([O:37][S:34]([C:33]([F:32])([F:53])[F:54])(=[O:35])=[O:36])=[C:39]([C:4]2[CH:5]=[CH:6][C:7]([C@H:8]([NH:10][C:11]([C:13]3([NH:16][C:17](=[O:22])[C:18]([F:21])([F:20])[F:19])[CH2:15][CH2:14]3)=[O:12])[CH3:9])=[C:2]([F:1])[CH:3]=2)[CH:40]=[CH:41][CH:42]=1)(=[O:47])=[O:46]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 86608819HCID 86608819, compoundHCID 86608820HCID 86608820, compound

Product 1

HCID 11693265HCID 11693265, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
85 °C

Procedure

3-Fluoro-4-{-(1R)-1-[({1-[(trifluoroacetyl)amino]cyclopropyl}carbonyl)amino]ethyl}-phenylboronic acid (0.050 g, 0.138 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.013 g, 0.014 mmol), and cesium carbonate (0.054 g, 0.166 mmol) were added to a flame-dried flask under argon. 2-chloro-6-{[(trifluoromethyl)sulfonyl]oxy}phenyl trifluoromethanesulfonate (0.068 g, 1.66 mmol) as a solution in dioxane (0.33M) and tri-tert-butyl phosphine (0.007 g, 0.035 mmol) as a solution in dioxane (1.65M) were added to the solids and heated at 85° C. After 1.5 hours the reaction was diluted with methanol, filtered and purified by reverse phase chromatography using a gradient from 95/5H2O/CH3CN to 5/95H2O/CH3CN. The product was lyophilized to yield the title compound as a solid. High resolution mass spectrometry: C22H16F10N2O8S2 requires: 691.0261, found: 691.0275. 1H NMR (400 MHz, (CD3)2SO) δ 9.80 (s, 1H), 8.32 (d, J=7.4 Hz, 1H), 7.86-7.92 (m, 1H), 7.76-7.81 (m, 2H), 7.53 (t, J=7.9 Hz, 1H), 7.37 (dd, J=11 Hz, J=1.7 Hz, 1H), 7.33 (dd, J=7.9 Hz, J=1.7 Hz, 1H), 5.24 (qn, J=7.4 Hz, 1H), 1.41 (d, J=7.4 Hz, 3H), 1.30-1.37 (m, 2H), 0.92-1.08 (m, 2H).

Workup

  1. filtrationfiltered
  2. custompurified by reverse phase chromatography

Sources & evidence

ORD record
ord-42eb51c0877e417d8a104b43a70116cf
Source dataset
uspto-grants-2008_02
Patent number
US07332499B2

Reaction notes

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