Ethyl isocyanatoacetate → HCID 24830239, compound

HRID 2410044Notes

Reaction equation

HRID 2410044 reaction equation
[CH:1]1([N:7]2[C:12]([OH:13])=[C:11]([C:14]([NH:16][CH2:17][C:18]([OH:20])=[O:19])=[O:15])[C:10](=[O:21])[N:9]([CH:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)[C:8]2=[O:27])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N(CC(OCC)=O)=C=O.C1(N2C(=O)CC(=O)N(C3CCCC3)C2=O)CCCCC1.C(N(C(C)C)CC)(C)C>ClCCl>[CH:1]1([N:7]2[C:12](=[O:13])[C:11]([C:14]([NH:16][CH2:17][C:18]([OH:20])=[O:19])=[O:15])=[C:10]([OH:21])[N:9]([CH:22]3[CH2:23][CH2:24][CH2:25][CH2:26]3)[C:8]2=[O:27])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 76283Ethyl isocyanatoacetateHCID 81531DiisopropylethylamineHCID 68635820HCID 68635820, compoundHCID 178525898HCID 178525898, compound

Product 1

HCID 24830239HCID 24830239, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-[(1-Cyclohexyl-3-cyclopentyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine. Ethyl isocyanatoacetate (8.33 mL, 74.3 mmoles) was added to a mixture of 1-cyclohexyl-3-cyclopentyl-2,4,6(1H,3H,5H)-pyrimidinetrione (18.8 g, 67.54 mmoles) and diisopropylethylamine (23.53 mL, 135.08 mmoles) in dichloromethane (800 mL) and stirred for 2 hours. Reaction mixture from a prior run (approx 25% scale) was added. The combined reaction mixture was washed with 2 molar hydrochloric acid (2×1.0 L) and evaporated. The residue was dissolved in ethanol (200 mL) and treated with 3.0 molar sodium hydroxide (100 mL). The mixture was stirred for 2 hours. Ethyl acetate (500 mL) was added and the mixture acidified with 6 molar hydrochloric acid (200 mL), water (500 mL) was added and the layers separated. The aqueous layer was extracted with ethyl acetate (500 mL) and the organic solution was washed with 1 molar hydrochloric acid. The organic solution was dried and evaporated to a solid residue which recrystallized from acetic acid (300 mL) to afford the title compound (15.5 g, 49%). Mp 222-224° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.08 (s, 1H), 10.17 (t, J=5.43 Hz, 1 H), 5.08-5.33 (m, 1 H), 4.63 (t, J=12.25 Hz, 1 H), 4.12 (d, J=5.81 Hz, 2 H), 2.18-2.36 (m, 2 H), 1.93-2.06 (m, 2 H), 1.69-1.91 (m, 6 H), 1.46-1.68 (m, 5 H), 1.28 (q, J=12.88 Hz, 2 H), 1.12 (q, J=13.05 Hz, 1 H).

Workup

  1. customReaction mixture from a prior run (approx 25% scale)
  2. additionwas added
  3. customThe combined reaction mixture
  4. washwas washed with 2 molar hydrochloric acid (2×1.0 L)
  5. customevaporated
  6. dissolutionThe residue was dissolved in ethanol (200 mL)
  7. additiontreated with 3.0 molar sodium hydroxide (100 mL)
  8. stirringThe mixture was stirred for 2 hours
  9. additionEthyl acetate (500 mL) was added
  10. additionwas added
  11. customthe layers separated
  12. extractionThe aqueous layer was extracted with ethyl acetate (500 mL)
  13. washthe organic solution was washed with 1 molar hydrochloric acid
  14. customThe organic solution was dried
  15. customevaporated to a solid residue which
  16. customrecrystallized from acetic acid (300 mL)

Sources & evidence

ORD record
ord-def871f2dee344a68f7d532f5818af16
Source dataset
uspto-grants-2014_08
Patent number
US08815884B2

Reaction notes

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