4-Methylmorpholine → HCID 54767965, compound

HRID 1925905Notes

Reaction equation

HRID 1925905 reaction equation
[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]3[CH2:17][C:18]4[C:19]([O:27][CH3:28])=[CH:20][CH:21]=[C:22]([O:25][CH3:26])[C:23]=4[O:24][C:14]=3[C:13]2=[O:29])[C:9](O)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN1CCOCC1.F[P-](F)(F)(F)(F)F.[N:44]1(OC(N(C)C)=[N+](C)C)[C:48]2[N:49]=[CH:50][CH:51]=[CH:52][C:47]=2N=N1.NC1C=CC=CN=1>O1CCCC1.O>[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]3[CH2:17][C:18]4[C:19]([O:27][CH3:28])=[CH:20][CH:21]=[C:22]([O:25][CH3:26])[C:23]=4[O:24][C:14]=3[C:13]2=[O:29])[C:9]([NH:44][C:48]2[CH:47]=[CH:52][CH:51]=[CH:50][N:49]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 104392-AminopyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67521190HCID 67521190, compound

Product 1

HCID 54767965HCID 54767965, compoundYield 17.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

A solution of (S)-3-cyclohexyl-2-(5,8-dimethoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-propionic acid (100 mg, 0.24 mmol), in tetrahydrofuran (5 mL) was treated with N-methylmorpholine (70 mg, 0.56 mmol), 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate (HATU) (212 mg, 0.56 mmol) and commercially available 2-aminopyridine (25 mg, 0.26 mmol). The mixture was heated in a sealed tube was heated for 16 hours at 90° C. The reaction mixture was diluted with water and extracted with ethyl acetate (3×). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue, upon silica gel flash chromatography using hexane-ethyl acetate gradient elution, afforded (S)-3-cyclohexyl-2-(5,8-dimethoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-N-pyridin-2-yl-propionamide (19 mg, 17.8%), as a white solid. 1H NMR (DMSO-d6) δ: 10.83 (br. s., 1H), 8.34 (br. s., 1H), 8.00 (d, J=7.8 Hz, 1H), 7.77 (br. s., 1H), 7.12 (br. s., 1H), 6.92 (d, J=8.8 Hz, 1H), 6.67 (d, J=8.8 Hz, 1H), 5.09 (br. s., 1H), 4.39 (d, J=18.6 Hz, 1H), 4.02 (d, J=19.1 Hz, 1H), 3.76 (s, 6H), 3.55 (br. s., 2H), 1.50-1.89 (m, 7H), 0.87-1.28 (m, 6H).

Workup

  1. temperatureThe mixture was heated in a sealed tube
  2. extractionextracted with ethyl acetate (3×)
  3. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. washhexane-ethyl acetate gradient elution

Sources & evidence

ORD record
ord-1c1fdd9d0d03446680ed78bae18aeb28
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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