Hydrochloric Acid → HCID 71617596, compound

HRID 2274610Notes

Reaction equation

HRID 2274610 reaction equation
[CH2:1]([N:5]([CH2:35][CH2:36][CH2:37][CH3:38])[C:6]([C:8]1[CH:12]=[C:11]([CH3:13])[N:10]([C:14]2[CH:19]=[C:18]([OH:20])[CH:17]=[CH:16][C:15]=2[C:21]([N:23]2[C@H:32]([CH2:33][OH:34])[CH2:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:24]2)=[O:22])[N:9]=1)=[O:7])[CH2:2][CH2:3][CH3:4].CC(C)([O-])C.[K+].Cl[CH2:46][C:47]([O:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)=[O:48].Cl>O1CCCC1.C(OCC)(=O)C>[CH2:50]([O:49][C:47](=[O:48])[CH2:46][O:20][C:18]1[CH:17]=[CH:16][C:15]([C:21]([N:23]2[C@H:32]([CH2:33][OH:34])[CH2:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:24]2)=[O:22])=[C:14]([N:10]2[C:11]([CH3:13])=[CH:12][C:8]([C:6](=[O:7])[N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[CH2:35][CH2:36][CH2:37][CH3:38])=[N:9]2)[CH:19]=1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8786Acetic acid, 2-chloro-, phenylmethyl esterHCID 23665647Potassium tert-butoxideHCID 71617481HCID 71617481, compound2×

Product 1

HCID 71617596HCID 71617596, compoundYield 3.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1-[5-hydroxy-2-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-phenyl]-5-methyl-1H-pyrazole-3-carboxylic acid dibutylamide (intermediate E, 29 mg, 0.056 mmol) and potassium tert-butoxide (0.062 mL, 1M, 0.062 mmol) in tetrahydrofuran (0.5 mL) was stirred at ambient temperature for 10 minutes. Benzyl 2-chloroacetate (0.010 mL, 0.067 mmol) was added and the mixture was stirred at ambient temperature for 2 hours. Ethyl acetate and aqueous HCl solution was added until the pH was about 7. The organic layer was eluted through a short pad of silica gel column and the crude material was purified by HPLC and prep TLC to afford the title compound (1.3 mg, 3.5% yield). MS (ESI) [m/e, (M+H)+]=667.3. 1H NMR (400 MHz, chloroform-d) δ ppm 6.74-7.70 (m, 12H), 6.15-6.31 (m, 1H), 3.94-5.36 (m, 8H), 2.56-3.71 (m, 6H), 2.09-2.35 (m, 3H), 0.65-1.70 (m, 14H).

Workup

  1. washThe organic layer was eluted through a short pad of silica gel column
  2. customthe crude material was purified by HPLC

Sources & evidence

ORD record
ord-2ddcf927afb34d12b1cd2537f06378dd
Source dataset
uspto-grants-2015_09
Patent number
US09126979B2

Reaction notes

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