4-Methylmorpholine → HCID 178448521, compound

HRID 468640Notes

Reaction equation

HRID 468640 reaction equation
CN1CCOCC1.[F:8][C:9]1[C:10]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH2:34][C@H:35]3[CH2:40][CH2:39][C@H:38]([O:41][CH:42]4[CH2:47][CH2:46][CH2:45][CH2:44][O:43]4)[CH2:37][CH2:36]3)=[CH:29][CH:28]=2)=[CH:11][C:12](=[O:26])[N:13]([CH2:15][CH2:16][C@@:17]([CH3:25])([S:21]([CH3:24])(=[O:23])=[O:22])[C:18](O)=[O:19])[CH:14]=1.ClC1N=C(OC)N=C(OC)N=1.[O:59]1[CH2:64][CH2:63][CH2:62][CH2:61][CH:60]1[O:65][NH2:66]>CC1CCCO1.O>[F:8][C:9]1[C:10]([C:27]2[CH:28]=[CH:29][C:30]([O:33][CH2:34][C@H:35]3[CH2:40][CH2:39][C@H:38]([O:41][CH:42]4[CH2:47][CH2:46][CH2:45][CH2:44][O:43]4)[CH2:37][CH2:36]3)=[CH:31][CH:32]=2)=[CH:11][C:12](=[O:26])[N:13]([CH2:15][CH2:16][C@@:17]([CH3:25])([S:21]([CH3:24])(=[O:23])=[O:22])[C:18]([NH:66][O:65][CH:60]2[CH2:61][CH2:62][CH2:63][CH2:64][O:59]2)=[O:19])[CH:14]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 178448522HCID 178448522, compound

Product 1

HCID 178448521HCID 178448521, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 73012-MethyltetrahydrofuranSolvent

Procedure

N-Methyl morpholine (340 uL, 3.09 mmol) was added to a suspension of (2R)-4-[5-fluoro-2-oxo-4-(4-{[trans-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methoxy}-phenyl)pyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoic acid (1.28 g, 2.21 mmol), 2-chloro-4,6-dimethoxy-1,3,5-triazine (510 mg, 2.87 mmol) in 2-methyltetrahydrofuran (30 mL) and the reaction was stirred for 1 h at rt. O-(Tetrahydro-2H-pyran-2-yl)hydroxylamine (61 mg, 0.52 mmol) was added, and the reaction was stirred overnight at rt. Water (50 mL) was added, and the mixture was extracted with EtOAc (3×150 mL). The combined organic phases were dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude material was purified via flash chromatography using an eluent of EtOAc in n-heptane (75-100%) to afford the title compound as a light brown residue (700 mg, 46%). MS (LCMS) m/z 677.4 (M+1).

Workup

  1. stirringthe reaction was stirred overnight at rt
  2. extractionthe mixture was extracted with EtOAc (3×150 mL)
  3. dry with materialThe combined organic phases were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified via flash chromatography

Sources & evidence

ORD record
ord-bdfc5ed945bb43c3bb32c9789fc41c00
Source dataset
uspto-grants-2014_01
Patent number
US08624034B2

Reaction notes

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