Formic Acid → HCID 66782167, compound

HRID 1096535Notes

Reaction equation

HRID 1096535 reaction equation
C(OC1[CH:11]=[CH:10][C:9]([CH2:12][CH:13]([NH:36][C:37](=[O:54])[CH2:38][CH:39]([NH:43][C:44]([NH:46][CH2:47][C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)=[O:45])[CH2:40][CH:41]=[CH2:42])[C:14](=[O:35])[N:15]([CH2:27][CH:28](OCC)OCC)[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[C:18]=2[O:25][CH3:26])=[CH:8][CH:7]=1)(C)(C)C.[CH:55]([OH:57])=O>>[CH2:47]([NH:46][C:44]([N:43]1[CH:39]([CH2:40][CH:41]=[CH2:42])[CH2:38][C:37](=[O:54])[N:36]2[CH:13]([CH2:12][C:9]3[CH:8]=[CH:7][C:55]([OH:57])=[CH:11][CH:10]=3)[C:14](=[O:35])[N:15]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[C:18]=3[O:25][CH3:26])[CH2:27][CH:28]12)=[O:45])[C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=1

Participants

3

Reactant 2

HCID 284Formic AcidHCID 66781852HCID 66781852, compound

Product 1

HCID 66782167HCID 66782167, compoundYield 38%

Procedure

A solution of crude 3-(3-Benzyl-ureido)-hex-5-enoic acid {2-(4-tert-butoxy-phenyl)-1-[(2,2,-diethoxy-ethyl)-(2,3-dimethoxy-benzyl)-carbamoyl]-ethyl}-amide (3.7 g, 4.95 mmol) in formic acid (100 mL) was stirred at room temperature for 13 h. The solvent was removed under reduced pressure and then diluted with EtOAc, washed with water and brine. The organic layer was dried with Na2SO4 and concentrated in vacuo. The residue was purified by chromatography and recrystallized on ethyl acetate and hexane to give the 2-Allyl-8-(2,3-dimethoxy-benzyl)-6-(4-hydroxy-benzyl)-4,7-dioxo-hexahydro-pyrazino[1,2-a]pyrimidine-1-carboxylic benzylamide (1.3 g, 3 step yield: 38%). 1H NMR (CDCl3, 300 MHz) δ 7.4˜7.26 (m, 3H), 7.2 (d, J=7.01, 2H), 6.98 (t, J=8.0, 1H), 6.85 (m, 3H), 6.8 (t, J=7.0, 1H), 6.5 (d, J=8.76, 2H), 5.6 (m, 1H), 5.25 (t, J=4.7, 1H), 5.05 (d, J=10.75, 1H), 5.0 (d, J=18.54, 1H), 4.87 (d, J=14.51, 1H), 4.55 (m, 1H), 4.5˜4.25 (m, 4H, OH), 3.82 (s, 3H), 3.66 (s, 3H), 3.5˜3.3 (m, 2H), 3.25˜3.1 (m, 2H), 2.6˜2.4 (m, 2H), 2.2 (t, J=7.2, 2H) MS ESI 599.32 (M+H), 621.38 (M+Na), 637.19 (M+K)

Workup

  1. customThe solvent was removed under reduced pressure
  2. additiondiluted with EtOAc
  3. washwashed with water and brine
  4. dry with materialThe organic layer was dried with Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography
  7. customrecrystallized on ethyl acetate and hexane

Sources & evidence

ORD record
ord-a4b9081897444698b560b51bd844ece5
Source dataset
uspto-grants-2012_03
Patent number
US08138337B2

Reaction notes

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