4-Methylmorpholine → HCID 54767968, compound

HRID 1925909Notes

Reaction equation

HRID 1925909 reaction equation
[CH3:1][O:2][C:3]1[C:24]2[O:23][C:10]3[C:11](=[O:22])[N:12]([C@@H:14]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:15]([OH:17])=O)[CH2:13][C:9]=3[CH2:8][C:7]=2[C:6]([O:25][CH3:26])=[CH:5][CH:4]=1.CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[NH2:58][C:59]1[CH:64]=[CH:63][C:62]([Cl:65])=[CH:61][N:60]=1>O1CCCC1.O>[Cl:65][C:62]1[CH:63]=[CH:64][C:59]([NH:58][C:15](=[O:17])[C@@H:14]([N:12]2[CH2:13][C:9]3[CH2:8][C:7]4[C:6]([O:25][CH3:26])=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[C:24]=4[O:23][C:10]=3[C:11]2=[O:22])[CH2:18][CH:19]([CH3:21])[CH3:20])=[N:60][CH:61]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 661742-Amino-5-chloropyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67520997HCID 67520997, compound

Product 1

HCID 54767968HCID 54767968, compoundYield 18.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

A solution of (S)-2-(5,8-dimethoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid (100 mg, 0.24 mmol), in tetrahydrofuran (10 mL) was treated with N-methylmorpholine (760 mg, 0.69 mmol), 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate (HATU) (263 mg, 0.69 mmol) and commercially available 2-amino-5-chloropyridine (42 mg, 0.33 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)-2-(5,8-dimethoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid (5-chloro-pyridin-2-yl)-amide (21 mg, 16.2%), as an off white solid. 1H NMR (DMSO-d6) δ: 11.09 (br. s., 1H), 8.40 (br. s., 1H), 8.05 (d, J=8.8 Hz, 1H), 7.90 (d, J=8.8 Hz, 1H), 6.91 (d, J=8.8 Hz, 1H), 6.66 (d, J=8.8 Hz, 1H), 5.05 (br. s., 1H), 4.38 (d, J=19.1 Hz, 1H), 4.03 (d, J=18.6 Hz, 1H), 3.76 (s, 6H), 3.55 (br. s., 2H), 1.82 (br. s., 1H), 1.67 (br. s., 1H), 1.45 (br. s., 1H), 0.93 (t, J=6.1 Hz, 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-7700f5f7870a4a68bcb871771afb04b2
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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