Hydrochloric Acid → HCID 69073036, compound

HRID 228122Notes

Reaction equation

HRID 228122 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:24]C(OC(C)(C)C)=O)[C:10](=[O:23])[N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)=[CH:4][CH:3]=1.Cl.CCN(C(C)C)C(C)C.[N:42]1([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:51][C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH2:44][C@H:43]1[C:52]([OH:54])=O.CCN=C=NCCCN(C)C.CI.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:24][C:52]([C@@H:43]2[CH2:44][C:45]3[C:50](=[CH:49][CH:48]=[CH:47][CH:46]=3)[CH2:51][N:42]2[C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])=[O:54])[C:10](=[O:23])[N:11]2[CH2:12][CH2:13][N:14]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH2:15][CH2:16]2)=[CH:4][CH:3]=1

Participants

9

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 21060092HCID 21060092, compound

Product 1

HCID 69073036HCID 69073036, compoundYield 31.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To N-{(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-(4-phenylpiperazinyl)ethyl}(tert-butoxy)carboxamide (Step 1) (573 mg, 1.30 mmol) in 50 mL round bottomed flask equipped with magnetic stirring was added 25 mL of EtOAc satd with HCl, and the reaction mixture was stirred for 1 h. The resulting solid was filtered and washed with hexane. The solid was dried further in vacuo and then added to a 50 mL round bottomed flask equipped with magnetic stirring. DMF (10 mL), DIEA (110 μl, 0.631 mmol) (Aldrich), Boc-L-Tic-OH (90 mg, 0.68 mmol) (Peptech), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (396 mg, 1.33 mmol), and HOAT (90 mg, 0.661 mmol) were added to the reaction flask. The resulting solution was stirred 2 h then worked up as in Preparation XIX. The resulting crude was purified by flash chromatography (SiO2, 1:1, hexane-EtOAc) to afford tert-butyl 3-(N-{(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-(4-phenylpiperazinyl)ethyl}carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (130 mg). MS (ESI, pos. ion) m/z: 603 (M+H), (ESI, neg. ion) m/z: 601 (M−H). Calc'd for C34H39ClN4O4: 603.15.

Workup

  1. stirringthe reaction mixture was stirred for 1 h
  2. filtrationThe resulting solid was filtered
  3. washwashed with hexane
  4. customThe solid was dried further in vacuo
  5. additionadded to a 50 mL round bottomed flask
  6. customequipped with magnetic stirring
  7. stirringThe resulting solution was stirred 2 h
  8. customThe resulting crude was purified by flash chromatography (SiO2, 1:1, hexane-EtOAc)

Sources & evidence

ORD record
ord-721981368d3a463ebb04fe6fb312aa81
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

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