Morpholine → HCID 67247478, compound

HRID 2425756Notes

Reaction equation

HRID 2425756 reaction equation
[ClH:1].[CH:2]([N:5]1[C:14]2[C:9](=[C:10]([CH3:15])[CH:11]=[CH:12][CH:13]=2)[CH:8]=[C:7]([C:16]([NH:18][CH2:19][CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:30])[C:27]([OH:29])=O)[CH2:22][CH2:21]2)=[O:17])[C:6]1=[O:31])([CH3:4])[CH3:3].[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(=O)([O-])O.[Na+]>ClCCl>[ClH:1].[CH:2]([N:5]1[C:14]2[C:9](=[C:10]([CH3:15])[CH:11]=[CH:12][CH:13]=2)[CH:8]=[C:7]([C:16]([NH:18][CH2:19][CH:20]2[CH2:21][CH2:22][N:23]([CH:26]([CH3:30])[C:27]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[O:29])[CH2:24][CH2:25]2)=[O:17])[C:6]1=[O:31])([CH3:4])[CH3:3]

Participants

7

Reactant 5

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67246126HCID 67246126, compound

Product 1

HCID 67247478HCID 67247478, compoundYield 94.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 2-[4-({[(1-isopropyl-5-methyl-2-oxo-1,2-dihydroquinolin-3-yl)carbonyl]amino}methyl)piperidin-1-yl]propanoic acid hydrochloride (243 mg, 0.54 mmol, step 2), morpholine (52 mg, 0.60 mmol), and diisopropylethylamine (0.19 mL, 1.08 mmol) in dichloromethane (15 mL) was added HBTU (226 mg, 0.60 mmol) at 0° C., and the mixture was stirred at 0° C. for 1 h and at room temperature for 3 h. Then, the resulting mixture was poured onto saturated aqueous sodium hydrogen carbonate (100 mL), and the aqueous layer was extracted with dichloromethane (100 mL×3). The combined organic layer was dried over magnesium sulfate, and concentrated in vacuo. The residue was chromatographed on a column of silica gel eluting with ammonia/methanol/dichloromethane (0.1:1:30) to give 265 mg of the title compound as salt free form. This was treated with 10% hydrogen chloride in methanol (5 mL), and the solvent removed in vacuo to give 194 mg (69%) of the title compound as a yellow amorphous.

Workup

  1. extractionthe aqueous layer was extracted with dichloromethane (100 mL×3)
  2. dry with materialThe combined organic layer was dried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was chromatographed on a column of silica gel eluting with ammonia/methanol/dichloromethane (0.1:1:30)

Sources & evidence

ORD record
ord-261ad46a6ad847d7830b184be4ffb0e6
Source dataset
uspto-grants-2011_06
Patent number
US07964727B2

Reaction notes

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