1-Hydroxybenzotriazole → 4-benzyloxy-N-[2,2-diethoxy-2-(2-isobutyl-6-methyl-pyridin-4-yl)-ethyl]-3-ethyl-5-methyl-benzamide

HRID 2040830Notes

Reaction equation

HRID 2040830 reaction equation
[CH2:1]([O:8][C:9]1[C:17]([CH3:18])=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][C:10]=1[CH2:19][CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.Cl.[CH2:54]([O:56][C:57]([O:71][CH2:72][CH3:73])([C:60]1[CH:65]=[C:64]([CH3:66])[N:63]=[C:62]([CH2:67][CH:68]([CH3:70])[CH3:69])[CH:61]=1)[CH2:58][NH2:59])[CH3:55]>CN(C=O)C.CC(=O)OCC>[CH2:1]([O:8][C:9]1[C:17]([CH3:18])=[CH:16][C:12]([C:13]([NH:59][CH2:58][C:57]([O:71][CH2:72][CH3:73])([O:56][CH2:54][CH3:55])[C:60]2[CH:65]=[C:64]([CH3:66])[N:63]=[C:62]([CH2:67][CH:68]([CH3:69])[CH3:70])[CH:61]=2)=[O:15])=[CH:11][C:10]=1[CH2:19][CH3:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 757711-Hydroxybenzotriazole2×HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 594979194-Benzyloxy-3-ethyl-5-methyl-benzoic acidHCID 670269622,2-Diethoxy-2-(2-isobutyl-6-methyl-pyridin-4-yl)-ethylamine dihydrochloride

Product 1

HCID 685531514-benzyloxy-N-[2,2-diethoxy-2-(2-isobutyl-6-methyl-pyridin-4-yl)-ethyl]-3-ethyl-5-methyl-benzamideYield 60.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-benzyloxy-3-ethyl-5-methylbenzoic acid (115 mg, 0.425 mmol) in DMF (1.5 mL), EDC HCl (46 mg, 0.467 mmol) followed by HOBT (63 mg, 0.467 mmol) is added. The mixture is stirred at rt for 15 min before DIPEA (219 mg, 1.70 mmol) and a solution of 2,2-diethoxy-2-(2-isobutyl-6-methyl-pyridin-4-yl)-ethylamine dihydrochloride (150 mg, 0.425 mmol) in DMF (0.5 mL) is added. The mixture is stirred at rt for 4.5 h before another portion of EDC HCl (20 mg) and HOBT (30 mg) is added. Stirring is continued at rt for 16 h. The mixture is diluted with EA (30 mL), washed with sat. aq. NaHCO3 solution (15 mL), water (15 mL) and brine (15 mL), dried over Na2SO4, filtered and concentrated. The crude product is purified on prep. TLC with heptane:EA 1:1 to give 4-benzyloxy-N-[2,2-diethoxy-2-(2-isobutyl-6-methyl-pyridin-4-yl)-ethyl]-3-ethyl-5-methyl-benzamide (137 mg) as a pale yellow wax; LC-MS: tR=1.13, [M+1]+=533.15.

Workup

  1. additionis added
  2. additionis added
  3. washwashed with sat. aq. NaHCO3 solution (15 mL), water (15 mL) and brine (15 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified on prep

Sources & evidence

ORD record
ord-7bb0d3968d0d4ad7b1e78ddf434371a0
Source dataset
uspto-grants-2013_11
Patent number
US08580824B2

Reaction notes

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