4-Methylmorpholine → HCID 9997310, compound

HRID 1376123Notes

Reaction equation

HRID 1376123 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH:7][C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]=2[C:17]([OH:19])=[O:18])=[CH:3][CH:2]=1.[C:20]([O:25][CH3:26])(=[O:24])[C@H:21]([CH3:23])O.CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CCOCC.CC#N.CN(C=O)C>[CH3:26][O:25][C:20]([C@@H:21]([O:18][C:17]([C:9]1[NH:10][C:11]2[C:16]([C:8]=1[NH:7][C:4]1[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=1)=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:19])[CH3:23])=[O:24]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 94386methyl (S)-lactateHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 101989283-(pyridin-4-ylamino)-1H-indole-2-carboxylic Acid

Product 1

HCID 9997310HCID 9997310, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

Stir at 0° C. a mixture of 3-(4-pyridinylamino)-1H-indole-2-carboxylic acid (3.0 g, 12 mmol), methyl (S)-(−)-lactate (2.3 mL, 24 mmol), 4-methylmorpholine (2.6 mL,24 mmol) and DMF (50.0 mL). Add benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP, 5.32 g, 12 mmol) in one portion and stir at ambient temperature overnight. Add brine (50 mL) and extract with ethyl acetate (3×200 mL). Concentrate under vacuum to an oil. Chromatograph over silica gel (5 g) and elute with dichloromethane, EtOAC, and MeOH. Concentrate like fractions under vacuum to an oil. Treat the oil with HCl in ether (10 mL) add additional ether (50 mL) and concentrate under vacuum to an oil. Treat the oil with 5% aqueous NaHCO3 and extract with EtOAc. Dry the extract over Na2SO4, filter and concentrate to an oil. Scratch the oil with a glass rod in the presence of ether to obtain a sticky solid. Add CH3CN and then ether and obtain of the title compound as a yellow solid, 140 mg: MS 340(M+H), Rt=2.73 min. (95/5/0.1 (A) 5/95/0.1 (B) Water/CAN/Formic Acid YMC ODS-A 2×50 mm 1 mL/min Gradient Composition: 100% A for 0.1 min Linear Gradient to 100% B at 2 min Hold until 3.5 min.)

Workup

  1. extractionAdd brine (50 mL) and extract with ethyl acetate (3×200 mL)
  2. concentrationConcentrate under vacuum to an oil
  3. washChromatograph over silica gel (5 g) and elute with dichloromethane, EtOAC, and MeOH
  4. concentrationConcentrate like fractions under vacuum to an oil
  5. additionTreat the oil with HCl in ether (10 mL)
  6. additionadd additional ether (50 mL)
  7. concentrationconcentrate under vacuum to an oil
  8. additionTreat the oil with 5% aqueous NaHCO3
  9. extractionextract with EtOAc
  10. customDry the
  11. extractionextract over Na2SO4
  12. filtrationfilter
  13. concentrationconcentrate to an oil
  14. customto obtain a sticky solid

Sources & evidence

ORD record
ord-6dd8d2f433e54ad89b0680e8d9d8dc3c
Source dataset
uspto-grants-2007_01
Patent number
US07169925B2

Reaction notes

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