Isopropyl isocyanate → (R)-6-(3-(3-isopropylureido) piperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

HRID 2044040Notes

Reaction equation

HRID 2044040 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.[N:32]([CH:35]([CH3:37])[CH3:36])=[C:33]=[O:34]>C1COCC1.C(Cl)Cl>[CH:35]([NH:32][C:33](=[O:34])[NH: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:19]=[CH:20][C:21]([C:24]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[O:25])=[CH:22][CH:23]=3)[N:9]=2)[CH2:3]1)([CH3:37])[CH3:36]

Participants

5

Reactant 2

HCID 61277Isopropyl isocyanateHCID 49846316(R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

Product 1

HCID 66832452(R)-6-(3-(3-isopropylureido) piperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamideYield 72.3%

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 (35 mg, 0.082 mmol) in THF (2 mL) was added 2-isocyanatopropane (14.03 mg, 0.165 mmol) and 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 obtained 30.2 mg of (R)-6-(3-(3-isopropylureido) piperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide as a light yellow solid.

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-e5b601ee74004b25b3d69c86dced6751
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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