Hydrochloric Acid → Fluoren-9-ylmethyl (3r)-3-(n-{(1r)-1-[(4-chlorophenyl)methyl]-2-[4-(2-nitrophenyl)piperazinyl]-2-oxoethyl}carbamoyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

HRID 228078Notes

Reaction equation

HRID 228078 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:27]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]([O-:26])=[O:25])[CH2:14][CH2:13]2)=[O:11])=[CH:4][CH:3]=1.Cl.[CH2:36]1[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH2:39][N:38]([C:46]([O:48][CH2:49][CH:50]2[C:62]3[C:57](=[CH:58][CH:59]=[CH:60][CH:61]=3)[C:56]3[C:51]2=[CH:52][CH:53]=[CH:54][CH:55]=3)=[O:47])[C@H:37]1[C:63]([OH:65])=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:27][C:63]([C@H:37]2[CH2:36][C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[CH2:39][N:38]2[C:46]([O:48][CH2:49][CH:50]2[C:62]3[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=3[C:56]3[C:51]2=[CH:52][CH:53]=[CH:54][CH:55]=3)=[O:47])=[O:65])[C:10]([N:12]2[CH2:13][CH2:14][N:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N+:24]([O-:26])=[O:25])[CH2:16][CH2:17]2)=[O:11])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 181649HOAtHCID 978342(3R)-2-(((9H-fluoren-9-yl)methoxy)carbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidHCID 10236463N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide methyliodideHCID 21060087n-{(1r)-1-[(4-Chlorophenyl)methyl]-2-[4-(2-nitrophenyl)piperazinyl]-2-oxoethyl}(tert-butoxy)-carboxamide

Product 1

HCID 58714293Fluoren-9-ylmethyl (3r)-3-(n-{(1r)-1-[(4-chlorophenyl)methyl]-2-[4-(2-nitrophenyl)piperazinyl]-2-oxoethyl}carbamoyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

N-{(1R)-1-[(4-Chlorophenyl)methyl]-2-[4-(2-nitrophenyl)piperazinyl]-2-oxoethyl}(tert-butoxy)-carboxamide (1.4 g, 2.8 mmol) was treated with satd HCl in EtOAc as described in Preparation XVI. The resulting crude material was diluted with EtOAc and washed with satd NaHCO3 soln. The organic layer was separated, dried over Na2SO4, filtered and concentrated in vacuo. This sample (1.05 g, 2.50 mmol), was coupled to N-Fmoc-D-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (1.1 g, 2.7 mmol) (Peptech), by the procedure for Preparation XIX using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (Aldrich) (1.6 g, 5.5 mmol) and HOAT (370 mg, 2.7 mmol). The crude compound was obtained in a quantitative yield (2.2 g). MS (ESI, pos. ion) m/z: 770 (M+H), (ESI, neg. ion) m/z: 768 (M−H). Calc'd for C44H40ClN5O6: 769.27.

Workup

  1. washwashed with satd NaHCO3 soln
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-db8458baa3884752801f47db608b1123
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

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