Acrylamide → Cinacalcet

HRID 1928709Notes

Reaction equation

HRID 1928709 reaction equation
C(N)(=O)C=C.Br[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=1.[C:17]1([C@H:27]([NH:29][C:30](=[O:33])[CH:31]=[CH2:32])[CH3:28])[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][CH:18]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:28][C@@H:27]([NH:29][CH2:30][CH2:31][CH2:32][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=1)[C:17]1[CH:18]=[CH:19][CH:20]=[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:26]=12.[C:17]1([C@H:27]([NH:29][C:30](=[O:33])/[CH:31]=[CH:32]/[C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=2)[CH3:28])[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][CH:18]=1

Participants

9

Reactant 5

HCID 6579AcrylamideHCID 8471TriethylamineHCID 9817Benzene, 1-bromo-3-(trifluoromethyl)-2×HCID 80271Tri-o-tolylphosphineHCID 57710597HCID 57710597, compound

Product 2

HCID 156419CinacalcetHCID 24854937HCID 24854937, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Procedure

Cinacalcet was synthesized by reacting the acrylamide with 1-bromo-3-(trifluoromethyl)benzene using metal catalyzed cross-coupling conditions. In one embodiment, N—((R)-1-naphthalen-1-yl-ethyl)-acrylamide (1.0 equiv.; 0.44 mmol; 100 mg), palladium (II) acetate (5 mol %; 4.9 mg), tri-o-tolylphosphine (0.1 equiv.; 0.44 mmol; 13.4 mg) were suspended in acetonitrile (25 mL). To this suspension was added 1-bromo-3-(trifluoromethyl)benzene (1.0 equiv.; 0.44 mmol; 99 mg) and triethylamine (30 equiv.; 13.2 mmol; 1.8 mL) via syringe. The reaction was heated at reflux for 16 hours to afford (E)-N—((R)-1-Naphthalen-1-yl-ethyl)-3-(3-trifluoromethyl-phenyl)-acrylamide as the product. Solution yield: 79%. Confirmed identity by RRT and LC/MS (M+1): 370.4.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 16 hours

Sources & evidence

ORD record
ord-e2c385b665e64c1f9879a0c09e3d5944
Source dataset
uspto-grants-2012_05
Patent number
US08183415B2

Reaction notes

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