Morpholine → (R)-N-(1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino) pyridin-2-yl)piperidin-3-yl)morpholine-4-carboxamide

HRID 2044044Notes

Reaction equation

HRID 2044044 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]([N:25]2[CH2:30][CH2:29][CH2:28][C@@H:27]([NH:31][C:32](=[O:40])OC3C=CC=CC=3)[CH2:26]2)=[N:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[O:18])=[CH:13][CH:12]=1)(=[O:3])[NH2:2].[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1.CCN(CC)CC>C(Cl)Cl>[C:1]([C:4]1[CH:5]=[CH:6][C:7]([N:25]2[CH2:30][CH2:29][CH2:28][C@@H:27]([NH:31][C:32]([N:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)=[O:40])[CH2:26]2)=[N:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[O:18])=[CH:13][CH:12]=1)(=[O:3])[NH2:2]

Participants

5

Reactant 3

HCID 8083MorpholineHCID 8471TriethylamineHCID 66832742(R)-phenyl 1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino)pyridin-2-yl)piperidin-3-ylcarbamate

Product 1

HCID 66832164(R)-N-(1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino) pyridin-2-yl)piperidin-3-yl)morpholine-4-carboxamideYield 45.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of (R)-phenyl 1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino)pyridin-2-yl)piperidin-3-ylcarbamate (30 mg, 0.055 mmol), morpholine (7.20 mg, 0.083 mmol), and Et3N (0.012 mL, 0.083 mmol) in CH2Cl2 (2 mL) was heated at 50° C. overnight. The reaction mixture was diluted with CH2Cl2, washed with satd. NaHCO3 and water, and concentrated. The residue was purified by prep-HPLC and the product containing fractions were collected, neutralized with saturated NaHCO3, extracted with CH2Cl2, separated, and concentrated to obtain 13.5 mg of (R)—N-(1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino) pyridin-2-yl)piperidin-3-yl)morpholine-4-carboxamide as a light yellow solid as free base.

Workup

  1. washwashed with satd
  2. concentrationNaHCO3 and water, and concentrated
  3. customThe residue was purified by prep-HPLC and the product
  4. additioncontaining fractions
  5. customwere collected
  6. extractionextracted with CH2Cl2
  7. customseparated
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-ccf29cba99d84db195b68fdfe79540cf
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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