Ethanol → N-Cyclopropyl-3-fluoro-5-(2-{[1-(hydroxymethyl)cyclopropyl]methyl}-1-oxo-4-{[(3R)-piperidin-3-ylmethyl]sulfanyl}-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamide

HRID 906467Notes

Reaction equation

HRID 906467 reaction equation
[Si]([O:8][CH2:9][C:10]1([CH2:13][N:14]2[CH:23]=[C:22]([S:24][CH2:25][C@@H:26]3[CH2:31][CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27]3)[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([C:39]4[CH:44]=[C:43]([C:45](=[O:50])[NH:46][CH:47]5[CH2:49][CH2:48]5)[CH:42]=[C:41]([F:51])[C:40]=4[CH3:52])[CH:20]=3)[C:15]2=[O:53])[CH2:12][CH2:11]1)(C(C)(C)C)(C)C.C(O)C>Cl.O1CCOCC1>[CH:47]1([NH:46][C:45](=[O:50])[C:43]2[CH:44]=[C:39]([C:19]3[CH:20]=[C:21]4[C:16](=[CH:17][CH:18]=3)[C:15](=[O:53])[N:14]([CH2:13][C:10]3([CH2:9][OH:8])[CH2:12][CH2:11]3)[CH:23]=[C:22]4[S:24][CH2:25][C@@H:26]3[CH2:31][CH2:30][CH2:29][NH:28][CH2:27]3)[C:40]([CH3:52])=[C:41]([F:51])[CH:42]=2)[CH2:49][CH2:48]1

Participants

5

Reactant 2

HCID 702EthanolHCID 86640977tert-Butyl (3R)-3-{[(2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)-cyclopropyl]methyl}-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl)sulfanyl]methyl}piperidine-1-carboxylate

Product 1

HCID 59285263N-Cyclopropyl-3-fluoro-5-(2-{[1-(hydroxymethyl)cyclopropyl]methyl}-1-oxo-4-{[(3R)-piperidin-3-ylmethyl]sulfanyl}-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamideYield 79.6%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of tert-Butyl (3R)-3-{[(2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)-cyclopropyl]methyl}-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl)sulfanyl]methyl}piperidine-1-carboxylate (Example 63e, 110 mg) in 4N HCl in dioxane (1 mL) and ethanol (3 mL) was stirred for 20 h before being concentrated in vacuo. The residue was dissolved in methanol (2 mL) and loaded onto a 10 g SCX cartridge. The impurities were washed through with methanol (50 mL) and discarded. The product was eluted with 1N methanolic ammonia (50 mL) and evaporated in vacuo to afford the title product (63 mg) as a white solid.

Workup

  1. concentrationbefore being concentrated in vacuo
  2. dissolutionThe residue was dissolved in methanol (2 mL)
  3. washThe impurities were washed through with methanol (50 mL)
  4. washThe product was eluted with 1N methanolic ammonia (50 mL)
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-335724508f954a4592058f30a0fbd791
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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