HCID 66781900, compound → HCID 66782414, compound

HRID 554728Notes

Reaction equation

HRID 554728 reaction equation
C([O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH:13]([NH:35][C:36](=[O:53])[CH2:37][CH:38]([NH:42][C:43]([NH:45][CH2:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)=[O:44])[CH2:39][CH:40]=[CH2:41])[C:14](=[O:34])[N:15]([CH2:26][CH:27](OCC)OCC)[CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[C:21]3[C:25]=2[NH:24][N:23]=[CH:22]3)=[CH:8][CH:7]=1)(C)(C)C>C(O)=O>[CH2:46]([NH:45][C:43]([N:42]1[CH:38]([CH2:39][CH:40]=[CH2:41])[CH2:37][C:36](=[O:53])[N:35]2[CH:13]([CH2:12][C:9]3[CH:10]=[CH:11][C:6]([OH:5])=[CH:7][CH:8]=3)[C:14](=[O:34])[N:15]([CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[NH:24][N:23]=[CH:22]4)[CH2:26][CH:27]12)=[O:44])[C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1

Participants

3

Reactant 1

HCID 66781900HCID 66781900, compound

Product 1

HCID 66782414HCID 66782414, compoundYield 34.9%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

A solution of crude 3-(3-Benzyl-ureido)-hex-5-enoic acid {2-(4-tert-butoxy-phenyl)-1-[(2,2-diethoxy-ethyl)-(1H-indazol-7-ylmethyl)-carbamoyl]-ethyl}-amide (3.60 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-6-(4-hydroxy-benzyl)-8-(1H-indazol-7-ylmethyl)-4,7-dioxo-hexahydro-pyrazino[1,2-a]pyrimidine-1-carboxylic acid benzylamide (1.0 g, 3 step yield: 30%), 1H NMR (CDCl3, 300 MHz) δ 8.20 (s, 1H), 7.4-7.26 (m, 3H), 7.2 (d, J=7.01, 2H), 6.98 (t, J=8.0, 1H), 6.80 (m, 3H), 6.75 (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), 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 579 (M+H), 601 (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-587ec6271898404e9f38a30d32c2e486
Source dataset
uspto-grants-2011_11
Patent number
US08049008B2

Reaction notes

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