Triethylamine → HCID 67191334, compound

HRID 2355509Notes

Reaction equation

HRID 2355509 reaction equation
C(N(CC)CC)C.Br[C:9]1[CH:10]=[C:11]([C@:15]([C@@H:23]2[CH2:28][CH2:27][CH2:26][N:25]([C:29]([NH:31][C@H:32]([CH2:40][N:41]([CH3:51])[C:42]([O:44][CH2:45][CH2:46][Si:47]([CH3:50])([CH3:49])[CH3:48])=[O:43])[CH2:33][CH:34]3[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)=[O:30])[CH2:24]2)([OH:22])[CH2:16][CH2:17][CH2:18][CH2:19][O:20][CH3:21])[CH:12]=[CH:13][CH:14]=1.[C]=O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].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.CN(C=O)C.CO>[CH:34]1([CH2:33][C@H:32]([NH:31][C:29]([N:25]2[CH2:26][CH2:27][CH2:28][C@@H:23]([C@@:15]([C:11]3[CH:10]=[C:9]([CH:14]=[CH:13][CH:12]=3)[C:42]([O:44][CH3:45])=[O:43])([OH:22])[CH2:16][CH2:17][CH2:18][CH2:19][O:20][CH3:21])[CH2:24]2)=[O:30])[CH2:40][N:41]([CH3:51])[C:42]([O:44][CH2:45][CH2:46][Si:47]([CH3:48])([CH3:50])[CH3:49])=[O:43])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 67191587HCID 67191587, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 67191334HCID 67191334, compoundYield 53.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 21901440N,N-dimethylformamide methanolSolvent

Conditions

Temperature
70 °C

Procedure

Triethylamine (50 μL) was added to a stirred suspension of (3R)-3-((S)-1-(3-bromophenyl)-1-hydroxy-5-methoxypentyl)-N—((S)-1-cyclohexyl-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamide (21.0 mg, 0.03 mmol), Pd(dppf)Cl2 (5 mg) and Pd(PPh3)4 (5 mg) in 4:1 DMF/MeOH (2 mL). A carbon monoxide atmosphere was established in the reaction vessel and the mixture was stirred at 70° C. overnight. After cooling to ambient temperature, the mixture was extracted with EtOAc (2×5 mL) and the combined organic layers were washed with 1 N aq HCl (2×1 mL) and concentrated. The residue was purified by preparative HPLC to give methyl 3-((S)-1-((R)-1-((S)-1-cyclohexyl-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-ylcarbamoyl)-piperidin-3-yl)-1-hydroxy-5-methoxypentyl)benzoate (5.4 mg, 27%). MS m/z 698 (M+Na+).

Workup

  1. temperatureAfter cooling to ambient temperature
  2. extractionthe mixture was extracted with EtOAc (2×5 mL)
  3. washthe combined organic layers were washed with 1 N aq HCl (2×1 mL)
  4. concentrationconcentrated
  5. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-7cd3ba01995e487687af0d2448fe591c
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

Loading…