Ethyl isocyanatoacetate → HCID 24832003, compound

HRID 2410032Notes

Reaction equation

HRID 2410032 reaction equation
[CH:1]1([N:7]2[C:12](=[O:13])[CH2:11][C:10](=[O:14])[N:9]([CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[C:8]2=[O:21])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(C(C)C)CC)(C)C.[N:31]([CH2:34][C:35]([O:37]CC)=[O:36])=[C:32]=[O:33]>ClCCl>[CH:1]1([N:7]2[C:12](=[O:13])[C:11]([C:32]([NH:31][CH2:34][C:35]([OH:37])=[O:36])=[O:33])=[C:10]([OH:14])[N:9]([CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[C:8]2=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 76283Ethyl isocyanatoacetateHCID 81531DiisopropylethylamineHCID 68635825HCID 68635825, compound

Product 1

HCID 24832003HCID 24832003, compoundYield 47.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-{[3-Cyclohexyl-6-hydroxy-2,4-dioxo-1-(tetrahydro-2H-pyran-4-yl)-1-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine. 1-Cyclohexyl-3-(tetrahydro-2H-pyran-4-yl)-2,4,6(1H,3H,5H)-pyrimidinetrione (900 mg, 3.06 mmoles) and diisopropylethylamine (1.06 mL, 6.12 mmoles) were stirred together in dry dichloromethane (50 mL) and treated with ethyl isocyanatoacetate (360 uL, 3.21 mmoles). The mixture was stirred for under argon overnight, washed twice with 1 molar hydrochloric acid, dried and evaporated. The residue was dissolved in ethanol (15 mL) and treated with 1 molar sodium hydroxide solution (2.0 mL) and 6 molar sodium hydroxide solution (2.0 mL) and stirred for 4 hours. The mixture was partitioned between ethyl acetate and 1 molar hydrochloric acid, the organic solution washed with 1 molar hydrochloric acid, dried and evaporated to a solid. The solid was triturated with diethyl ether, collected, washed with a small amount of diethyl ether and hexane to afford the title compound (570 mg, 47%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.10 (br. s, 1 H), 10.19 (t, J=5.56 Hz, 1 H), 4.83-4.94 (m, 1 H), 4.63 (t, J=11.49 Hz, 1 H), 4.13 (d, J=5.81 Hz, 2 H), 3.93 (dd, J=11.12, 4.04 Hz, 2 H), 3.30-3.37 (m, 2 H), 2.56 (m, 2 H), 2.21-2.33 (m, 2 H), 1.79 (d, J=12.88 Hz, 2 H), 1.61 (s, 3 H), 1.52 (d, J=10.61 Hz, 2 H), 1.28 (q, J=12.97 Hz, 2 H), 1.11-1.18 (m, 1 H).

Workup

  1. washwashed twice with 1 molar hydrochloric acid
  2. customdried
  3. customevaporated
  4. dissolutionThe residue was dissolved in ethanol (15 mL)
  5. additiontreated with 1 molar sodium hydroxide solution (2.0 mL) and 6 molar sodium hydroxide solution (2.0 mL)
  6. stirringstirred for 4 hours
  7. customThe mixture was partitioned between ethyl acetate and 1 molar hydrochloric acid
  8. washthe organic solution washed with 1 molar hydrochloric acid
  9. customdried
  10. customevaporated to a solid
  11. customThe solid was triturated with diethyl ether
  12. customcollected
  13. washwashed with a small amount of diethyl ether and hexane

Sources & evidence

ORD record
ord-f4c6c4fb58314e6fa2276775f510c74f
Source dataset
uspto-grants-2014_08
Patent number
US08815884B2

Reaction notes

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