Triethylamine → (R)-phenyl 1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino)pyridin-2-yl)piperidin-3-ylcarbamate

HRID 2044043Notes

Reaction equation

HRID 2044043 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](Cl)(=[O:47])[O:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>C(Cl)Cl>[C:12]([C:11]1[CH:15]=[CH:16][C:8]([N:4]2[CH2:5][CH2:6][CH2:7][C@@H:2]([NH:1][C:39](=[O:47])[O:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH2:3]2)=[N:9][C:10]=1[NH:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)=[O:25])=[CH:22][CH:23]=1)(=[O:13])[NH2:14]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 49846316(R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

Product 1

HCID 66832742(R)-phenyl 1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino)pyridin-2-yl)piperidin-3-ylcarbamateYield 51.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of (R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide (140 mg, 0.330 mmol) and Et3N (0.069 mL, 0.495 mmol) in CH2Cl2 (3 mL) was added phenyl carbonochloridate (51.6 mg, 0.330 mmol) at 0° C. and stirred for 10 min. The reaction mixture was quenched with satd. NaHCO3, extracted with CH2Cl2, separated, and concentrated. The residue was purified (ISCO, 100% ethyl acetate, 12 g silica gel column) to obtained 93 mg of (R)-phenyl 1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino)pyridin-2-yl)piperidin-3-ylcarbamate as a white solid. LCMS: (M+H)+=545.31. 1H NMR (400 MHz, CDCl3) δ ppm 11.20 (1H, s), 7.69 (2H, d, J=8.79 Hz), 7.50 (1H, d, J=8.79 Hz), 7.31-7.39 (4H, m, J=7.91, 7.91 Hz), 7.19 (1H, t, J=7.47 Hz), 7.08 (2H, d, J=7.47 Hz), 6.10 (1H, d, J=8.79 Hz), 5.64 (1H, s), 5.35 (1H, d, J=7.47 Hz), 5.30 (1H, s), 4.03 (1H, dd, J=12.96, 2.86 Hz), 3.78-3.91 (1H, m), 3.64 (7H, s), 3.38-3.53 (2H, m), 1.98-2.12 (1H, m), 1.76-1.87 (1H, m), 1.63-1.76 (1H, m), 1.19-1.34 (1H, m).

Workup

  1. customThe reaction mixture was quenched with satd
  2. extractionNaHCO3, extracted with CH2Cl2
  3. customseparated
  4. concentrationconcentrated
  5. customThe residue was purified (ISCO, 100% ethyl acetate, 12 g silica gel column)

Sources & evidence

ORD record
ord-000d5813891245038403f4c47969aa29
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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