Hydrochloric Acid → (S)-3-((S)-1-Cyclopentyloxycarbonyl-3-methyl-butylcarbamoyl)-7-nitro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

HRID 2360648Notes

Reaction equation

HRID 2360648 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:17]([C:18](O)=[O:19])[CH2:16][C:15]2[C:10](=[CH:11][C:12]([N+:21]([O-:23])=[O:22])=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.[CH:34]1([O:39][C:40](=[O:47])[C@H:41]([CH2:43][CH:44]([CH3:46])[CH3:45])[NH2:42])[CH2:38][CH2:37][CH2:36][CH2:35]1.C(N(CC)CC)C.CCN=C=NCCCN(C)C.Cl.Cl>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C@H:17]([C:18](=[O:19])[NH:42][C@H:41]([C:40]([O:39][CH:34]2[CH2:35][CH2:36][CH2:37][CH2:38]2)=[O:47])[CH2:43][CH:44]([CH3:46])[CH3:45])[CH2:16][C:15]2[C:10](=[CH:11][C:12]([N+:21]([O-:23])=[O:22])=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 53718217(S)-cyclopentyl 2-amino-4-methylpentanoateHCID 67052655(S)-2-(tert-butoxycarbonyl)-7-nitro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

Product 1

HCID 57971746(S)-3-((S)-1-Cyclopentyloxycarbonyl-3-methyl-butylcarbamoyl)-7-nitro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl esterYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(S)-7-Nitro-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid-2-tert-butyl ester (2.5 g, 7.76 mmol) was dissolved in DCM (100 ml). HOBt (1.16 g, 8.53 mmol) was added, L-leucine cyclopentyl ester (3.19 g, 8.53 mmol) was added followed by triethylamine (2.38 ml, 17.1 mmol). EDCl.HCl (1.46 g, 8.5 mmol) was added and the reaction stirred at room temperature for 16 h. To the reaction was added DCM (100 ml) and the organic layer washed with water (3×300 ml), dried with Na2SO4 and the solvent removed in vacuo. The crude product was purified by chromatography (EtOAc:heptane 1:2→EtOAc) to give the required product 3.14 g (82% yield), LCMS purity 100%, m/z 504 [M++H]+

Workup

  1. washthe organic layer washed with water (3×300 ml)
  2. dry with materialdried with Na2SO4
  3. customthe solvent removed in vacuo
  4. customThe crude product was purified by chromatography (EtOAc:heptane 1:2→EtOAc)

Sources & evidence

ORD record
ord-08b16f1ff09441d0b057194bf47256c2
Source dataset
uspto-grants-2014_04
Patent number
US08686032B2

Reaction notes

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