Potassium Carbonate → [4-(4-Chloro-3-dibutylcarbamoyl-5-methyl-pyrazol-1-yl)-3-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-phenoxy]-acetic acid ethyl ester

HRID 2274606Notes

Reaction equation

HRID 2274606 reaction equation
[CH2:1]([N:5]([CH2:36][CH2:37][CH2:38][CH3:39])[C:6]([C:8]1[C:12]([Cl:13])=[C:11]([CH3:14])[N:10]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:16]=2[C:22]([N:24]2[C@H:33]([CH2:34][OH:35])[CH2:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH2:25]2)=[O:23])[N:9]=1)=[O:7])[CH2:2][CH2:3][CH3:4].I[CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:45]([O:44][C:42](=[O:43])[CH2:41][O:21][C:18]1[CH:19]=[CH:20][C:15]([N:10]2[C:11]([CH3:14])=[C:12]([Cl:13])[C:8]([C:6](=[O:7])[N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[CH2:36][CH2:37][CH2:38][CH3:39])=[N:9]2)=[C:16]([C:22]([N:24]2[C@H:33]([CH2:34][OH:35])[CH2:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH2:25]2)=[O:23])[CH:17]=1)[CH3:46]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12183Ethyl iodoacetateHCID 716174794-Chloro-1-[4-hydroxy-2-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-phenyl]-5-methyl-1H-pyrazole-3-carboxylic acid dibutylamide2×

Product 1

HCID 71617712[4-(4-Chloro-3-dibutylcarbamoyl-5-methyl-pyrazol-1-yl)-3-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-phenoxy]-acetic acid ethyl esterYield 7.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-chloro-1-[4-hydroxy-2-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-phenyl]-5-methyl-1H-pyrazole-3-carboxylic acid dibutylamide (intermediate D, 170 mg, 0.31 mmol), ethyl 2-iodoacetate (99 mg, 0.46 mmol), potassium carbonate (13 mg, 0.092 mmol), and triethylamime (0.085 mL, 0.62 mmol) was stirred in acetonitrile (3 mL) at ambient temperature for 12 hours. The solvent was removed in vacuo. The crude material was purified by eluting through a silica gel column with a 10 to 100% ethyl acetate/heptane gradient to afford the title compound (15 mg, 7.6% yield). MS (ESI) [m/e, (M+H)+]=639.3. 1H NMR (400 MHz, chloroform-d) δ ppm 6.73-7.39 (m, 7H), 2.51-5.41 (m, 17H), 2.16-2.41 (m, 3H), 0.68-1.70 (m, 16H).

Workup

  1. customThe solvent was removed in vacuo
  2. customThe crude material was purified
  3. washby eluting through a silica gel column with a 10 to 100% ethyl acetate/heptane gradient

Sources & evidence

ORD record
ord-07bd9014d51d4079a1df67c291ce7449
Source dataset
uspto-grants-2015_09
Patent number
US09126979B2

Reaction notes

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