Benzenesulfonyl chloride → (R)-2-(4-(morpholine-4-carbonyl)phenylamino)-6-(3-(phenylsulfonamido)piperidin-1-yl)nicotinamide

HRID 2044045Notes

Reaction equation

HRID 2044045 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[C:10]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[O:25])=[CH:20][CH:19]=3)[N:9]=2)[CH2:3]1.CCN(CC)CC.[C:39]1([S:45](Cl)(=[O:47])=[O:46])[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C1COCC1.C(Cl)Cl>[N:26]1([C:24]([C:21]2[CH:20]=[CH:19][C:18]([NH:17][C:10]3[N:9]=[C:8]([N:4]4[CH2:5][CH2:6][CH2:7][C@@H:2]([NH:1][S:45]([C:39]5[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=5)(=[O:47])=[O:46])[CH2:3]4)[CH:16]=[CH:15][C:11]=3[C:12]([NH2:14])=[O:13])=[CH:23][CH:22]=2)=[O:25])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1

Participants

6

Reactant 3

HCID 7369Benzenesulfonyl chlorideHCID 8471TriethylamineHCID 49846316(R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

Product 1

HCID 66832987(R)-2-(4-(morpholine-4-carbonyl)phenylamino)-6-(3-(phenylsulfonamido)piperidin-1-yl)nicotinamideYield 74.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide (30 mg, 0.071 mmol) and Et3N (0.049 mL, 0.353 mmol) in THF (2 mL) was added benzenesulfonyl chloride (18.72 mg, 0.106 mmol). The solution was stirred at rt for 10 min. The reaction mixture was diluted with CH2Cl2, washed with satd NaHCO3, separated, and concentrated. The residue was purified (ISCO, 5% NH4OH/MeOH/CH2Cl2, 40 g silica gel column) to obtain 30 mg of (R)-2-(4-(morpholine-4-carbonyl)phenylamino)-6-(3-(phenylsulfonamido)piperidin-1-yl)nicotinamide as a light yellow solid. LCMS: (M+H)+=465.40. 1H NMR (400 MHz, CDCl3) δ ppm 11.13 (1H, s), 7.84-7.90 (2 H, m), 7.58-7.63 (2H, m), 7.54-7.57 (1H, m), 7.44-7.52 (3H, m), 7.33 (2H, d, J=8.56 Hz), 5.99 (1H, d, J=8.81 Hz), 5.71-5.87 (2H, m), 3.85 (1H, d, J=10.83 Hz), 3.38-3.79 (12H, m), 1.67-1.79 (2H, m), 1.44-1.57 (2H, m).

Workup

  1. washwashed with satd NaHCO3
  2. customseparated
  3. concentrationconcentrated
  4. customThe residue was purified (ISCO, 5% NH4OH/MeOH/CH2Cl2, 40 g silica gel column)

Sources & evidence

ORD record
ord-6b90ec3565f549a08ec8c10bff359bc8
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

Loading…