4-Methylmorpholine → HCID 136128652, compound

HRID 2165728Notes

Reaction equation

HRID 2165728 reaction equation
[NH2:1][C:2]1[NH:3][C:4](=[O:33])[C:5]([CH2:9][CH2:10][CH2:11][CH2:12][N:13]([S:23]([C:26]2[CH:32]=[CH:31][C:29]([CH3:30])=[CH:28][CH:27]=2)(=[O:25])=[O:24])[C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=2)=[C:6]([NH2:8])[N:7]=1.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.Cl.[NH2:60][C@H:61]([C:69]([O:71][CH2:72][CH3:73])=[O:70])[CH2:62][CH2:63][C:64]([O:66][CH2:67][CH3:68])=[O:65].CN1CCOCC1>ClCCl.CN(C)C=O.C(O)(=O)C>[NH2:1][C:2]1[NH:3][C:4](=[O:33])[C:5]([CH2:9][CH2:10][CH2:11][CH2:12][N:13]([S:23]([C:26]2[CH:27]=[CH:28][C:29]([CH3:30])=[CH:31][CH:32]=2)(=[O:25])=[O:24])[C:14]2[CH:15]=[CH:16][C:17]([C:18]([NH:60][C@H:61]([C:69]([O:71][CH2:72][CH3:73])=[O:70])[CH2:62][CH2:63][C:64]([O:66][CH2:67][CH3:68])=[O:65])=[O:20])=[CH:21][CH:22]=2)=[C:6]([NH2:8])[N:7]=1

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 10868Dicyclohexylcarbodiimide2×HCID 73960Glutamic acid diethyl ester hydrochlorideHCID 757711-HydroxybenzotriazoleHCID 136404504HCID 136404504, compound

Product 1

HCID 136128652HCID 136128652, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent4×HCID 6344DichloromethaneSolvent3×

Procedure

To a stirred mixture of 1.00 g (0.00209 mol) of 4-[[4-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)butyl]tosylamino]benzoic acid.0.13 acetic acid in 6 mL of dry dichloromethane and 6 mL of dry dimethylformamide under nitrogen was added 0.433 g (0.00313 mol) of 1-hydroxybenzotriazole. After 17 min, to the mixture was added 0.646 g (0.00313 mol) of 1,3-dicyclohexylcarbodiimide and then 6 mL more dry dimethylformamide and 6 mL more dry dichloromethane. After 1 h 6 min, to the mixture was added a cloudy solution of 0.750 g (0.00313 mol) of diethyl glutamate hydrochloride and 0.633 g (0.00626 mol) of 4-methylmorpholine in 6 mL of dry dichloromethane and 6 mL of dry dimethylformamide. The mixture was stirred under nitrogen for 59 h 20 min, and to it was added 0.431 g (0.00209 mol) of 1,3-dicyclohexylcarbodiimide. The mixture was stirred for 17 h 15 min and was concentrated under vacuum at 33° C. to a residue to which was added 25 mL of methanol. Undissolved white solid was collected by suction filtration, and the filtrate was purified by a flash chromatography column consisting of 175 g of Silica Gel 60 with 8:1 ethyl acetate/methanol as the eluting solvent. Major fractions containing product were combined and concentrated under vacuum to an off-white solid; yield, 0.74 g (~50%): NMR (Me2SOd6) δ 1.14 (t, 3H), 1.17 (t, 3H), 1.2-1.4 (m, 4H), 1.9-2.2 (m, 4H), 2.37 (s, 3H) 2.4 (t, 2H), 3.55 (t, 2H), 4.03 (q, 2H), 4.10 (q, 2H), 4.41 (m, 1H), 5.58 (br s, 2H), 5.85 (br s, 2H), 7.15 (d, 2H), 7.3-7.5 (AA'BB', 4H), 7.81 (d, 2H), 8.75 (d, 1H), 9.68 (br s, 1H), 0.12 mol of dimethylformamide, 0.1 mol of an impurity containing a CONHCH moiety.

Workup

  1. waitAfter 1 h 6 min
  2. stirringThe mixture was stirred for 17 h 15 min
  3. concentrationwas concentrated under vacuum at 33° C. to a residue to which
  4. additionwas added 25 mL of methanol
  5. filtrationwas collected by suction filtration
  6. customthe filtrate was purified by a flash chromatography column
  7. additionMajor fractions containing product
  8. concentrationconcentrated under vacuum to an off-white solid
  9. customyield

Sources & evidence

ORD record
ord-2941c90347654a3084fabd053ccdb8dc
Source dataset
uspto-grants-1990_07
Patent number
US04940713

Reaction notes

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