4-Methylmorpholine → HCID 12988761, compound

HRID 2083939Notes

Reaction equation

HRID 2083939 reaction equation
[NH2:1][C:2]1[C:3](=[O:21])[N:4]([CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:5](=[O:15])[N:6]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:7]=1.CN1CCOCC1.[CH2:29]([S:36](Cl)(=[O:38])=[O:37])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>O1CCCC1.CN(C)C=O.C(OCC)(=O)C>[CH2:8]([N:6]1[CH:7]=[C:2]([NH:1][S:36]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)(=[O:38])=[O:37])[C:3](=[O:21])[N:4]([CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:5]1=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 3

HCID 79724-MethylmorpholineHCID 74740Phenylmethanesulfonyl chlorideHCID 12988760HCID 12988760, compound

Product 1

HCID 12988761HCID 12988761, compoundYield 74%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

EX-1C) A solution of 5-amino-1-Benzyl-3-methoxycarbonylmethyl-2,4(1H,3H) pyrimidinedione (EX-1B; 3.12 g, 10.77 mmol) in 18.0 mL of tetrahydrofuran and dimethylformamide (1:1, 0.62M) was added N-methyl morpholine (3.60 mL, 32.74 mmol) in one portion at room temperature. The resulting mixture was cooled to 0° C. in an ice bath and was allowed to stir for 15 minutes. A solution of benzylsulfonyl chloride (2.26 g, 11.86 mmol) in 18.0 mL tetrahydrofuran was added drop wise over a 30 minute period. After the addition was complete the reaction was stirred for 3 hours at 0° C. The reaction mixture was diluted with ethyl acetate (250.0 mL) and washed with 1N HCl ((2×50 mL), saturated NaHCO3 (2×50 mL), and brine (2×50 mL). The organic solution was dried (MgSO4), filtered and concentrated. Trituration with ethyl acetate and hexanes gave pure 1-Benzyl-3-methoxycarbonylmethyl-5-[[(phenylmethyl)sulfonyl]amino]-2,4(1H,3H)pyrimidinedione (EX-1C) in 74% yield as a white solid: 1H NMR (300 MHz, DMSO) δ 9.16 (s, 1H), 8.02 (s, 1H), 7.43-7.37 (m, 10H), 5.01 (s, 2H), 4.65 (s, 2H), 4.45 (s, 2H), 3.69 (s, 3H); HRMS (ES) calcd for C21 H22N3O6S 444.1229, found 444.1242.

Workup

  1. additionAfter the addition
  2. stirringwas stirred for 3 hours at 0° C
  3. washwashed with 1N HCl ((2×50 mL), saturated NaHCO3 (2×50 mL), and brine (2×50 mL)
  4. dry with materialThe organic solution was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-5c47bccc69704734a411607e825ab87c
Source dataset
uspto-grants-2004_04
Patent number
US06716838B1

Reaction notes

Loading…