Acetic Acid → 1,1-Dimethylethyl N-(5-bromo-1,2-dihydro-1-methyl-2-oxo-3-pyridinyl)-N-[5-[(ethylamino)methyl]-2-pyridinyl]carbamate

HRID 2069732Notes

Reaction equation

HRID 2069732 reaction equation
[C:1]([O:5][C:6](=[O:25])[N:7]([C:16]1[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=[C:20]([Br:22])[CH:21]=1)[C:8]1[CH:13]=[CH:12][C:11]([CH:14]=O)=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:26]([NH2:28])[CH3:27].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>C1COCC1.C(Cl)Cl>[C:1]([O:5][C:6](=[O:25])[N:7]([C:16]1[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=[C:20]([Br:22])[CH:21]=1)[C:8]1[CH:13]=[CH:12][C:11]([CH2:14][NH:28][CH2:26][CH3:27])=[CH:10][N:9]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6341Ethylamine2×HCID 5049666Sodium triacetoxyborohydrideHCID 59473778HCID 59473778, compound

Product 1

HCID 594737951,1-Dimethylethyl N-(5-bromo-1,2-dihydro-1-methyl-2-oxo-3-pyridinyl)-N-[5-[(ethylamino)methyl]-2-pyridinyl]carbamateYield 63.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

(5-bromo-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-(5-formyl-pyridin-2-yl)-carbamic acid tert-butyl ester (500 mg, 1.22 mmol), ethanamine (6.12 ml of a 2.0 M solution in THF), sodium triacetoxyborohydride (649 mg, 3.06 mmol), and acetic acid (147 mg, 2.45 mmol) were added to a 20 ml microwave vial. The vial was capped and heated in a sand bath at 40 degrees centigrade overnight. TLC and LCMS analysis showed the reaction to be incomplete. Another 6 ml of ethanamine was added to the vial and the reaction was heated again at 40 degrees centigrade overnight. The reaction was diluted with DCM and washed with saturated aqueous sodium bicarbonate, dried and concentrated. The crude product was purified by flash chromatography using 10% methanol in DCM to give 340 mg (63.5%) of (5-bromo-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-(5-ethylaminomethyl-pyridin-2-yl)-carbamic acid tert-butyl ester.

Workup

  1. customThe vial was capped
  2. temperatureheated in a sand bath at 40 degrees centigrade overnight
  3. customthe reaction
  4. temperaturewas heated again at 40 degrees centigrade overnight
  5. washwashed with saturated aqueous sodium bicarbonate
  6. customdried
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-c8c9b80daec24229afadd48048f85cdb
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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