Phenylacetyl chloride → 2-(4-(Morpholine-4-carbonyl)phenylamino)-6-(4-(2-phenylacetyl)piperazin-1-yl)nicotinamide

HRID 2044047Notes

Reaction equation

HRID 2044047 reaction equation
[N:1]1([C:7]([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[N:24]=[C:23]([N:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)[CH:22]=[CH:21][C:17]=3[C:18]([NH2:20])=[O:19])=[CH:11][CH:10]=2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.CCN(CC)CC.[C:38]1([CH2:44][C:45](Cl)=[O:46])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C1COCC1.C(Cl)Cl>[N:1]1([C:7]([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[N:24]=[C:23]([N:25]4[CH2:30][CH2:29][N:28]([C:45](=[O:46])[CH2:44][C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)[CH2:27][CH2:26]4)[CH:22]=[CH:21][C:17]=3[C:18]([NH2:20])=[O:19])=[CH:11][CH:10]=2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 7679Phenylacetyl chlorideHCID 8471TriethylamineHCID 498463872-(4-(Morpholine-4-carbonyl)phenylamino)-6-(piperazin-1-yl)nicotinamide

Product 1

HCID 574896042-(4-(Morpholine-4-carbonyl)phenylamino)-6-(4-(2-phenylacetyl)piperazin-1-yl)nicotinamideYield 38.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 2-(4-(morpholine-4-carbonyl)phenylamino)-6-(piperazin-1-yl)nicotinamide (28 mg, 0.068 mmol) and Et3N (0.019 mL, 0.136 mmol) in THF (2 mL) and CH2Cl2 (2.000 mL) was added 2-phenylacetyl chloride (10.55 mg, 0.068 mmol). The reaction mixture was stirred at rt for 10 min, diluted with CH2Cl2, washed with satd NaHCO3, separated, and concentrated. The residue was purified by prep-HPLC. The product containing fractions were collected, basified with 1N NaOH, extracted with CH2Cl2, separated, and concentrated to give 14 mg of 2-(4-(morpholine-4-carbonyl)phenylamino)-6-(4-(2-phenylacetyl)piperazin-1-yl)nicotinamide as a white solid. LCMS: (M+H)+=529.40. 1H NMR (400 MHz, CDCl3) δ ppm 11.17 (1H, s), 7.63 (2H, d, J=8.56 Hz), 7.55 (1H, d, J=8.81 Hz), 7.35-7.40 (2H, m), 7.31-7.35 (2H, m), 7.23-7.31 (3H, m), 5.99 (1H, d, J=8.81 Hz), 5.59 (2H, s), 3.50-3.81 (18H, m).

Workup

  1. washwashed with satd NaHCO3
  2. customseparated
  3. concentrationconcentrated
  4. customThe residue was purified by prep-HPLC
  5. additionThe product containing fractions
  6. customwere collected
  7. extractionextracted with CH2Cl2
  8. customseparated
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-210c26547d5145648cc0aee66acf8bd9
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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