Triethylamine → 4-Chloro-1-[2-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-4-methoxy-phenyl]-5-methyl-1H-pyrazole-3-carboxylic acid dibutylamide

HRID 2274580Notes

Reaction equation

HRID 2274580 reaction equation
[Cl:1][C:2]1[C:3]([C:19](=[O:29])[N:20]([CH2:25][CH2:26][CH2:27][CH3:28])[CH2:21][CH2:22][CH2:23][CH3:24])=[N:4][N:5]([C:8]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:9]=2[C:10](O)=[O:11])[C:6]=1[CH3:7].[CH2:30]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:33][C@@H:32]([CH2:40][OH:41])[NH:31]1.C(N=C=NCCCN(C)C)C.OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C>ClCCl>[CH2:25]([N:20]([CH2:21][CH2:22][CH2:23][CH3:24])[C:19]([C:3]1[C:2]([Cl:1])=[C:6]([CH3:7])[N:5]([C:8]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:9]=2[C:10]([N:31]2[C@H:32]([CH2:40][OH:41])[CH2:33][C:34]3[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:30]2)=[O:11])[N:4]=1)=[O:29])[CH2:26][CH2:27][CH3:28]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 776757[(3S)-1,2,3,4-Tetrahydroisoquinolin-3-yl]methanolHCID 896470572-(4-Chloro-3-dibutylcarbamoyl-5-methyl-pyrazol-1-yl)-5-methoxy-benzoic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 716177154-Chloro-1-[2-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-4-methoxy-phenyl]-5-methyl-1H-pyrazole-3-carboxylic acid dibutylamideYield 4.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-(4-chloro-3-dibutylcarbamoyl-5-methyl-pyrazol-1-yl)-5-methoxy-benzoic acid (0.35 g, 0.82 mmol) and (S)-(1,2,3,4-tetrahydroisoquinolin-3-yl)methanol (0.13 g, 0.82 mmol) in dichloromethane (8 mL) under nitrogen atmosphere was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.16 g, 0.82 mmol) and hydroxybenzotriazole (0.13 g, 0.82 mmol). The mixture was stirred at ambient temperature for 5 minutes. Triethylamine (0.34 mL, 2.5 mmol) was added to the mixture. The reaction was stirred for 60 hours at ambient temperature. The mixture was washed with water and purified by eluting through a silica gel column with a 10 to 100% ethyl acetate/heptane gradient to afford the title compound (21 mg, 4.5% yield). MS (ESI) [m/e, (M+H)+]=567.3. 1H NMR (400 MHz, chloroform-d) δ ppm 6.75-7.36 (m, 7H), 4.13-5.41 (m, 4H), 3.80-3.96 (m, 3H), 2.51-3.71 (m, 8H), 2.17-2.32 (m, 3H), 1.48-1.68 (m, 4H), 1.19-1.44 (m, 4H), 0.70-0.97 (m, 6H).

Workup

  1. stirringThe reaction was stirred for 60 hours at ambient temperature
  2. washThe mixture was washed with water
  3. custompurified
  4. washby eluting through a silica gel column with a 10 to 100% ethyl acetate/heptane gradient

Sources & evidence

ORD record
ord-ccaeeef5148340069d803e69499e46a4
Source dataset
uspto-grants-2015_09
Patent number
US09126980B2

Reaction notes

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