Potassium Carbonate → Acetamide, N-3-pyridinyl- (9CI)

HRID 2369426Notes

Reaction equation

HRID 2369426 reaction equation
C(=O)([O-])[O-].[K+].[K+].Cl[CH2:8][C:9]([NH:11][C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)=[O:10]>CN(C=O)C>[N:14]1[CH:15]=[CH:16][CH:17]=[C:12]([NH:11][C:9](=[O:10])[CH3:8])[CH:13]=1

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 50864572-chloro-N-(pyridin-3-yl)acetamide

Product 1

HCID 79978Acetamide, N-3-pyridinyl- (9CI)Yield 102.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 7 (200 mg, 0.33 mmol, 1.00 equiv, 50%) in DMF (5 mL) was added potassium carbonate (91.1 mg, 0.66 mmol, 2.00 equiv) and 2-chloro-N-(pyridin-3-yl)acetamide (85.5 mg, 0.50 mmol, 1.50 equiv) at room temperature under nitrogen. The resulting solution was stirred overnight at ambient temperature. The solids were filtered out and the filtrate was concentrated under vacuum. The crude product (150 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% NH4HCO3 and CH3CN (10.0% CH3CN up to 58.0% in 12 min); UV detection at 254/220 nm; Flow rate: 20 mL/mim. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give 2-(((1r,4r)-4-(6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)amino)cyclohexyl)(methyl)amino)-N-(pyridin-3-yl)acetamide (70 mg) as a white solid. LC-MS (ES, m/z): 437 (M+H+); NMR (400 MHz, DMSO): δ 9.86 (s, 1H), 8.83 (s, 1H), 8.27 (d, 1H), 8.25 (s, 1H), 8.11 (d, 1H), 7.35 (dd, 1H), 5.98 (d, 1H), 4.05-4.15 (m, 1H), 3.31 (s, 2H), 3.07 (t, 2H), 2.92 (t, 2H), 2.38-2.45 (m, 3H), 2.33 (s, 3H), 1.99-2.01 (m, 2H), 1.89-1.92 (m, 2H), 1.40-1.51 (m, 4H).

Workup

  1. filtrationThe solids were filtered out
  2. concentrationthe filtrate was concentrated under vacuum
  3. customThe crude product (150 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU)
  4. waitmobile phase, water with 0.05% NH4HCO3 and CH3CN (10.0% CH3CN up to 58.0% in 12 min)
  5. customThe product-containing fractions were collected
  6. custompartially evaporated
  7. customto remove water and CH3CN under reduced pressure
  8. waitThe residue was lyophilized overnight

Sources & evidence

ORD record
ord-fd525e8019ca42a2804cc5425dd2408f
Source dataset
uspto-grants-2014_04
Patent number
US08703941B2

Reaction notes

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