Cesium carbonate → HCID 86608821, compound

HRID 2055586Notes

Reaction equation

HRID 2055586 reaction equation
[F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[C@H:17]([NH:19][C:20]([C:22]1([NH:25][C:26](=[O:31])[C:27]([F:30])([F:29])[F:28])[CH2:24][CH2:23]1)=[O:21])[CH3:18].Br[C:33]1[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:34]=1[NH2:35].C(=O)([O-])[O-].[Cs+].[Cs+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)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]>[NH2:35][C:34]1[C:36]([F:40])=[CH:37][CH:38]=[CH:39][C:33]=1[C:6]1[CH:5]=[CH:4][C:3]([C@H:17]([NH:19][C:20]([C:22]2([NH:25][C:26](=[O:31])[C:27]([F:30])([F:29])[F:28])[CH2:24][CH2:23]2)=[O:21])[CH3:18])=[C:2]([F:1])[CH:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 27829402-Bromo-6-fluoroanilineHCID 86608822HCID 86608822, compound

Product 1

HCID 86608821HCID 86608821, compound

Reagents, catalysts & solvents 2

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

Procedure

N-{(1R)-1-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl}-1-[(trifluoroacetyl)amino]cyclopropanecarboxamide (1.50 g, 3.377 mmol), 2-bromo-6-flouroaniline (401 ul, 3.545 mmol), tris(dibenzylideneacetone)dipalladium (309 mg, 0.338 mmol), cesium carbonate (1.10 g, 3.377 mmol) and 1.65M tri-t-butylphosphine in dioxane (491 ul, 0.810 mmol) were suspended in dioxane (15 ml), degassed with Argon purge and heated to 90 C for 15 minutes. After this time, the mixture was filtered through a Gelman Acrodisc and the filter was washed with EtOAc (10 ml) and methanol (20 ml). The combined filtrates were concentrated in vacuo and the residue purified by column chromatography eluting with a 0-100% EtAOc/CH2Cl2 gradient to give N-[(1R)-1-(2′-amino-3,3′-difluoro-1,1′-biphenyl-4-yl)ethyl]-1-[(trifluoroacetyl)amino]cyclopropanecarboxamide. Low resolution mass spectrometry: (M+H+)=428.2. 1H NMR (400 MHz, (CD3)2SO) δ 9.79 (s, 1H), 8.28 (d, 1H, J=7.6 Hz), 7.48 (t, 1H, J=8.2 Hz), 7.19-7.26 (m, 2H), 7.02-7.09 (m, 1H), 6.89 (d, 1H, J=7.6 Hz), 6.61-6.68 (m, 1H), 5.22-5.29 (m, 1H), 1.45-1.57 (m, 2H), 1.42 (d, 3H, J=7.1 Hz) and 0.93-1.08 (m, 2H) ppm.

Workup

  1. customdegassed with Argon
  2. custompurge
  3. temperatureheated to 90 C for 15 minutes
  4. filtrationAfter this time, the mixture was filtered through a Gelman Acrodisc
  5. washthe filter was washed with EtOAc (10 ml) and methanol (20 ml)
  6. concentrationThe combined filtrates were concentrated in vacuo
  7. customthe residue purified by column chromatography
  8. washeluting with a 0-100% EtAOc/CH2Cl2 gradient

Sources & evidence

ORD record
ord-67563d237203491ba09439ab872a5c42
Source dataset
uspto-grants-2008_02
Patent number
US07332499B2

Reaction notes

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