HCID 66781783, compound → HCID 66782133, compound

HRID 554731Notes

Reaction equation

HRID 554731 reaction equation
[CH2:1]([NH:8][C:9](=[O:51])[NH:10][CH:11]([CH3:50])[CH2:12][C:13]([NH:15][CH:16]([C:29](=[O:49])[N:30]([CH2:41][CH:42](OCC)OCC)[CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[C:36]2[C:40]=1[NH:39][N:38]=[CH:37]2)[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24]C(C)(C)C)=[CH:20][CH:19]=1)=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)=O>[CH2:1]([NH:8][C:9]([N:10]1[CH:11]([CH3:50])[CH2:12][C:13](=[O:14])[N:15]2[CH:16]([CH2:17][C:18]3[CH:19]=[CH:20][C:21]([OH:24])=[CH:22][CH:23]=3)[C:29](=[O:49])[N:30]([CH2:31][C:32]3[CH:33]=[CH:34][CH:35]=[C:36]4[C:40]=3[NH:39][N:38]=[CH:37]4)[CH2:41][CH:42]12)=[O:51])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 1

HCID 66781783HCID 66781783, compound

Product 1

HCID 66782133HCID 66782133, compoundYield 33.7%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

A solution of crude 3-(3-Benzyl-ureido)-N-{2-(4-tert-butoxy-phenyl)-1-[(2,2-diethoxy-ethyl)-(1H-indazol-7-ylmethyl)-carbamoyl]-ethyl}-butyramide (3.46 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 6-(4-Hydroxy-benzyl)-8-(1H-indazol-7-ylmethyl)-2-methyl-4,7-dioxo-hexahydro-pyrazino[1,2-a]pyrimidine-1-carboxylic acid benzylamide (0.923 g, 3 step yield: 29%). 1H NMR (CDCl3, 300 MHz) δ 8.30 (s, 1H), 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), 4.55 (m, 1H), 4.5˜4.25 (m, 4H), 3.5˜3.3 (m, 2H), 3.25˜3.1 (m, 2H), 2.2 (t, J=7.2, 2H) 1.45 (m, 3H) MS ESI 553 (M+H), 575 (M+Na).

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-3669cd7ad4fd48dca2a354bf12314a3d
Source dataset
uspto-grants-2011_11
Patent number
US08049008B2

Reaction notes

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