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

HRID 2274608Notes

Reaction equation

HRID 2274608 reaction equation
[Cl:1][C:2]1[C:3]([C:33](=[O:43])[N:34]([CH2:39][CH2:40][CH2:41][CH3:42])[CH2:35][CH2:36][CH2:37][CH3:38])=[N:4][N:5]([C:8]2[CH:18]=[CH:17][C:11]([O:12][CH2:13][C:14](O)=[O:15])=[CH:10][C:9]=2[C:19]([N:21]2[C@H:30]([CH2:31][OH:32])[CH2:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:22]2)=[O:20])[C:6]=1[CH3:7].[NH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.C(N=C=NCCCN(C)C)C.OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C>ClCCl>[CH2:35]([N:34]([CH2:39][CH2:40][CH2:41][CH3:42])[C:33]([C:3]1[C:2]([Cl:1])=[C:6]([CH3:7])[N:5]([C:8]2[CH:18]=[CH:17][C:11]([O:12][CH2:13][C:14](=[O:15])[NH:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)=[CH:10][C:9]=2[C:19]([N:21]2[C@H:30]([CH2:31][OH:32])[CH2:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:22]2)=[O:20])[N:4]=1)=[O:43])[CH2:36][CH2:37][CH3:38]

Participants

7

Reactant 5

HCID 6115AnilineHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 71617713[4-(4-Chloro-3-dibutylcarbamoyl-5-methyl-pyrazol-1-yl)-3-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-phenoxy]-acetic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 716177144-Chloro-1-[2-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-4-phenylcarbamoylmethoxy-phenyl]-5-methyl-1H-pyrazole-3-carboxylic acid dibutylamideYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of [4-(4-chloro-3-dibutylcarbamoyl-5-methyl-pyrazol-1-yl)-3-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-phenoxy]-acetic acid (15 mg, 0.025 mmol) and aniline (3.4 uL, 0.037 mmol) in dichloromethane (0.2 mL) under nitrogen atmosphere was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (7.1 mg, 0.037 mmol) and hydroxybenzotriazole (5.6 mg, 0.037 mmol). The mixture was stirred at ambient temperature for 5 minutes. Triethylamine (10 uL, 0.074 mmol) was added to the mixture. The reaction was stirred for 12 hours. After eluting through a short pad of silica gel column, the crude material was purified by HPLC to afford the title compound (8 mg, 50% yield). MS (ESI) [m/e, (M+H)+]=686.3. 1H NMR (400 MHz, chloroform-d) δ ppm 6.82-7.69 (m, 12H), 4.13-5.38 (m, 5H), 2.38-3.75 (m, 8H), 2.15-2.32 (m, 3H), 1.12-1.70 (m, 8H), 0.66-0.99 (m, 6H).

Workup

  1. stirringThe reaction was stirred for 12 hours
  2. washAfter eluting through a short pad of silica gel column
  3. customthe crude material was purified by HPLC

Sources & evidence

ORD record
ord-d19b30be4d2647f0a3710b9126cc7402
Source dataset
uspto-grants-2015_09
Patent number
US09126979B2

Reaction notes

Loading…