Hydrochloric Acid → Tert-butyl 3-{n-[(1r)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[methyl(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carbamoyl}-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

HRID 228097Notes

Reaction equation

HRID 228097 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:30]C(OC(C)(C)C)=O)[C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N:24]([CH3:29])[S:25]([CH3:28])(=[O:27])=[O:26])[CH2:14][CH2:13]2)=[O:11])=[CH:4][CH:3]=1.Cl.CCN(C(C)C)C(C)C.[N:48]1([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:57][C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH2:50][C@H:49]1[C:58]([OH:60])=O.CCN=C=NCCCN(C)C.CI.C1C=NC2N(O)N=NC=2C=1>CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:30][C:58]([CH:49]2[CH2:50][C:51]3[C:56](=[CH:55][CH:54]=[CH:53][CH:52]=3)[CH2:57][N:48]2[C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])=[O:60])[C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N:24]([CH3:29])[S:25]([CH3:28])(=[O:26])=[O:27])[CH2:14][CH2:13]2)=[O:11])=[CH:4][CH:3]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 664088(3S)-2-((tert-butoxy)carbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidHCID 10236463N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide methyliodideHCID 21060076n-[(1r)-1-[(4-Chlorophenyl)methyl]-2-(4-{2-[methyl-(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-(tert-butoxy)carboxamide

Product 1

HCID 69075194Tert-butyl 3-{n-[(1r)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[methyl(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carbamoyl}-1,2,3,4-tetrahydroisoquinoline-2-carboxylateYield 52%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

N-[(1R)-1-[(4-Chlorophenyl)methyl]-2-(4-{2-[methyl-(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-(tert-butoxy)carboxamide (Step 2) (327 mg, 0.593 mmol) was stirred with 25 mL of HCl satd EtOAc. The resulting crude material was diluted with EtOAc and washed with a satd NaHCO3 soln. The organic layer was separated, dried over Na2SO4, filtered and concentrated in vacuo. This material was treated with DIEA (115 μl, 0.660 mmol), Boc-L-Tic-OH (167 mg, 0.602 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (500 mg, 1.68 mmol), and HOAT (99 mg, 0.727 mmol) according to the procedure for preparation XIX. The crude was purified by flash chromatography (SiO2, 10% EtOAc in CH2Cl2) and concentrated in vacuo to yield tert-butyl 3-{N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[methyl(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carbamoyl}-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (219 mg). MS (ESI, pos. ion) m/z: 710 (M+H), (ESI, neg. ion) m/z: 708 (M−H). Calc'd for C36H44ClN5O6S: 710.28.

Workup

  1. washwashed with a satd NaHCO3 soln
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude was purified by flash chromatography (SiO2, 10% EtOAc in CH2Cl2)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-848b8b8f377a4575b979f7063cd87329
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

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