Potassium Carbonate → HCID 67135670, compound

HRID 1896639Notes

Reaction equation

HRID 1896639 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:19]([NH2:20])=[CH:18][C:17]([Cl:21])=[C:16](Br)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].BrN1[C:28](=O)[CH2:27][CH2:26]C1=O.C1(B(O)O)CC1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.C(OCC)(=O)C.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>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:19]([NH2:20])=[CH:18][C:17]([Cl:21])=[C:16]([CH:26]3[CH2:27][CH2:28]3)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 67184N-bromobutanimideHCID 2760897Cyclopropylboronic acidHCID 86654220HCID 86654220, compound

Product 1

HCID 67135670HCID 67135670, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-amino-5-chloro-6-bromo-3′,4′,5′,6′-tetrahydro-2′H-[2,4]bipyridinyl-1′-carboxylic acid tert-butyl ester (0.59 g, prepared following procedures described in Example 5 with N-bromosuccinimide instead of N-chlorosuccinimide in Step C), cyclopropyl boronic acid (0.086 g), tetrakis(triphenylphosphine)palladium (0.094 g), potassium carbonate (0.14 g) in 1,2-dimethoxyethane (5 ml) and water (0.2 ml) was irradiated in a microwave at 150° C. for 20 minutes. The reaction mixture was cooled to ambient temperature, diluted with ethyl acetate, washed with aqueous sodium hydrogen carbonate (saturated), water then brine. The organic layer was dried over sodium sulfate and the solvent removed in vacuo. The residue was purified by chromatography on silica gel (eluent: dichloromethane/ethyl acetate 9:1) to afford 3-amino-5-chloro-6-cyclopropyl-3′,4′,5′,6′-tetrahydro-2′H-[2,4]bipyridinyl-1′-carboxylic acid tert-butyl ester (0.30 g) as a yellow solid. MS (ES+) 491/493 (MH+); 1H NMR (400 MHz, CDCl3) 1.0-1.1 (m, 4H), 1.45 (s, 9H), 1.60 (m, 1H), 1.70 (m, 2H), 1.85 (m, 2H), 2.50 (m, 1H), 2.80 (m, 2H), 4.20 (m, 2H), 7.65 (d, 1H), 7.75 (s, 1H), 7.80 (s, 1H), 7.9 (m, 1H), 8.60 (d, 1H).

Workup

  1. customwas irradiated in a microwave at 150° C. for 20 minutes
  2. washwashed with aqueous sodium hydrogen carbonate (saturated), water
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. customthe solvent removed in vacuo
  5. customThe residue was purified by chromatography on silica gel (eluent: dichloromethane/ethyl acetate 9:1)

Sources & evidence

ORD record
ord-c499c0de49be4378993a4c2e1b1b0167
Source dataset
uspto-grants-2013_08
Patent number
US08518971B2

Reaction notes

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