Potassium Carbonate → 1,1-dimethylethyl (2S)-4-({5-[3-(aminomethyl)phenyl]-2-thienyl)methyl)-2-methyl-1-piperazinecarboxylate

HRID 2080332Notes

Reaction equation

HRID 2080332 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6](B(O)O)[CH:7]=[CH:8][CH:9]=1.Br[C:14]1[S:18][C:17]([CH2:19][N:20]2[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@@H:22]([CH3:33])[CH2:21]2)=[CH:16][CH:15]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.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>[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]([C:14]2[S:18][C:17]([CH2:19][N:20]3[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@@H:22]([CH3:33])[CH2:21]3)=[CH:16][CH:15]=2)[CH:7]=[CH:8][CH:9]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 16427085Boronic acid, B-(3-(aminomethyl)phenyl)-, hydrochloride (1:1)HCID 577367111,1-dimethylethyl (2S)-4-[(5-bromo-2-thienyl)methyl]-2-methyl-1-piperazinecarboxylate

Product 1

HCID 577367081,1-dimethylethyl (2S)-4-({5-[3-(aminomethyl)phenyl]-2-thienyl)methyl)-2-methyl-1-piperazinecarboxylateYield 42%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

To the solution of [3-(aminomethyl)phenyl]boronic acid hydrochloride (325 mg, 1.2 mmol) in dioxane/H2O (10 mL/3.3 mL) was added 1,1-dimethylethyl (2S)-4-[(5-bromo-2-thienyl)methyl]-2-methyl-1-piperazinecarboxylate (450 mg, 1.2 mmol), K2CO3 (828 mg, 6.0 mmol) and Pd(PPh3)4 (70 mg, 0.06 mmol). The resulting solution was irradiated in a microwave reactor at 150° C. for 20 minutes and diluted with EtOAc (5 mL). The organic layer was collected and the aqueous layer was extracted by EtOAc (2×5 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by Gilson HPLC, eluting with acetonitrile/water/0.1% TFA (10/90 to 90/10, v/v, over 12 min), to give the title compound (200 mg, 42%). LC/MS: m/z, 402 (M+H), 1.24 min.

Workup

  1. customThe resulting solution was irradiated in a microwave reactor at 150° C. for 20 minutes
  2. customThe organic layer was collected
  3. extractionthe aqueous layer was extracted by EtOAc (2×5 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by Gilson HPLC
  8. washeluting with acetonitrile/water/0.1% TFA (10/90 to 90/10

Sources & evidence

ORD record
ord-22ca46b7b3a948febddd73d9039c0208
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

Loading…