4-Methylmorpholine → HCID 68524191, compound

HRID 1178893Notes

Reaction equation

HRID 1178893 reaction equation
[I-].[C:2]([NH:5][CH:6]([C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[CH:16]1[CH2:22][CH:21]2[NH:23][CH:18]([CH2:19][CH2:20]2)[CH2:17]1)[CH2:7][CH3:8])(=[O:4])[CH3:3].[C:24]([N:28]1[CH2:33][CH2:32][C@@H:31]([C:34](O)=[O:35])[C@H:30]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=2[F:44])[CH2:29]1)([CH3:27])([CH3:26])[CH3:25].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.ON1C2N=CC=CC=2N=N1.CN1CCOCC1>ClCCl>[Cl-:15].[C:2]([NH:5][CH:6]([C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[CH:16]1[CH2:22][CH:21]2[N:23]([C:34]([C@@H:31]3[CH2:32][CH2:33][NH+:28]([C:24]([CH3:27])([CH3:25])[CH3:26])[CH2:29][C@H:30]3[C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=3[F:44])=[O:35])[CH:18]([CH2:19][CH2:20]2)[CH2:17]1)[CH2:7][CH3:8])(=[O:4])[CH3:3]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 181649HOAtHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58780621HCID 58780621, compoundHCID 86607398HCID 86607398, compound

Product 1

HCID 68524191HCID 68524191, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-{2-[1-(acetylamino)propyl]-4-chlorophenyl}-8-azabicyclo[3.2.1]octane iodide (2-10) (46.8 mg, 0.115 mmol) in dichloromethane (2.0 mL) was added (3R,4R)-1-tert-butyl-3-(2,4-difluorophenyl)piperidine-4-carboxylic acid (1-12) (34.0 mg, 0.115 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′,-tetramethyluronium hexafluorophosphat (HATU, 52.1 mg, 0.138 mmol), 1-hydroxyl-7-azabenzotriazole (HOAT, 19.0 mg, 0.138 mmol), and NMM (35.0 g, 0.345 mmol). The mixture was stirred at room temperature overnight and quenched with a saturated aqueous solution of NaHCO3, extracted with dichloromethane (3×20 mL). The extracts were washed with brine, and dried over anhydrous MgSO4, and concentrated. Purification of the crude residue by prep-TLC (developed with 10% methanol/methylenechloride as mobile phase and separation of isomers by high-pressure liquid chromatography (gradient elution; 15%-95% acetonitrile/water as eluent) and addition of a solution of 1 N HCl solution in ether afforded (2-12) as a white solid (m/z (ES) 600 (MH+)).

Workup

  1. customquenched with a saturated aqueous solution of NaHCO3
  2. extractionextracted with dichloromethane (3×20 mL)
  3. washThe extracts were washed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated
  6. customPurification of the crude residue by prep-TLC (
  7. customdeveloped with 10% methanol/methylenechloride as mobile phase and separation of isomers by high-pressure liquid chromatography (gradient elution; 15%-95% acetonitrile/water as eluent) and addition of a solution of 1 N HCl solution in ether

Sources & evidence

ORD record
ord-d36a004b54714ac48dba0eaf7688a56f
Source dataset
uspto-grants-2007_10
Patent number
US07276520B2

Reaction notes

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