1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-Benzyl-4-isopropoxy-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide

HRID 1643699Notes

Reaction equation

HRID 1643699 reaction equation
[CH2:1]([CH:8]1[CH2:12][C:11]2[C:13]([O:20][CH:21]([CH3:23])[CH3:22])=[CH:14][C:15]([C:17]([OH:19])=O)=[CH:16][C:10]=2[O:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24][N:25]1[CH:29]=[CH:28][C:27]([NH2:30])=[N:26]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl>[CH3:24][N:25]1[CH:29]=[CH:28][C:27]([NH:30][C:17]([C:15]2[CH:14]=[C:13]([O:20][CH:21]([CH3:22])[CH3:23])[C:11]3[CH2:12][CH:8]([CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[O:9][C:10]=3[CH:16]=2)=[O:19])=[N:26]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 1372541-Methyl-3-aminopyrazoleHCID 59560120HCID 59560120, compound

Product 1

HCID 595604632-Benzyl-4-isopropoxy-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amideYield 16%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-benzyl-4-isopropoxy-2,3-dihydro-benzofuran-6-carboxylic acid (220j) (0.5 g, 1.6 mmol) in CH2Cl2 (15 mL) were added 1-methyl-1H-pyrazol-3-ylamine (0.16 g, 1.7 mmol), EDCI (0.46 g, 2.4 mmol), HOBt (0.32 g, 2.4 mmol) and N-methylmorphiline (0.81 g, 8 mmol) sequentially. The mixture was stirred at room temperature overnight. The reaction solution was washed with water (5 mL), aq. HCl (1 N, 5 mL) and sat. NaHCO3. The organic phase was dried over Na2SO4 and concentrated to give a yellow oil. The crude oil was purified by prep. HPLC to give the product as a white solid (98.6 mg, 16% yield, TFA salt). 1H NMR (400 MHz, CDCl3): δ 10.71 (s, 1H), 7.58 (s, 1H), 7.30-7.48 (m, 5H), 7.01˜7.19 (d, 2H), 6.57 (s, 1H), 5.08 (d, 1H), 4.74 (m, 1H), 3.74 (s, 3H), 2.66 (d, 2H), 2.17 (m, 1H), 1.96 (m, 1H), 1.28 (d, 6H).

Workup

  1. washThe reaction solution was washed with water (5 mL), aq. HCl (1 N, 5 mL) and sat. NaHCO3
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated
  4. customto give a yellow oil
  5. customThe crude oil was purified by prep

Sources & evidence

ORD record
ord-7c24fa8d89c443728c91e1f931b9f10a
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

Loading…