Methylamine → {1-(4-Chlorobenzyl)-2-[2-ethyl-4-(1-methylcarbamo yl-2-naphthalen-2-yl-ethyl)-piperazin-1-yl]-2-oxo-ethyl]-carbamic acid tert-butyl ester

HRID 720185Notes

Reaction equation

HRID 720185 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:35][C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=1)[C:10]([N:12]1[CH2:17][CH2:16][N:15]([CH:18]([CH2:22][C:23]2[CH:32]=[CH:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:24]=2)[C:19](O)=[O:20])[CH2:14][CH:13]1[CH2:33][CH3:34])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C[N:46]([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)[CH2:45]C1.F[P-](F)(F)(F)(F)F.CN.C1COCC1.C(N(CC)CC)C>ClCCl.O.CCOC(C)=O>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([CH2:35][C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=1)[C:10]([N:12]1[CH2:17][CH2:16][N:15]([CH:18]([C:19](=[O:20])[NH:46][CH3:45])[CH2:22][C:23]2[CH:32]=[CH:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:24]=2)[CH2:14][CH:13]1[CH2:33][CH3:34])=[O:11])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 5

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 2724699PyBOPHCID 219015732-{4-[2-Tert-butoxycarbonylamino-3-(4-chlorophenyl)-propionyl]-3-ethyl-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid

Product 1

HCID 72406545{1-(4-Chlorobenzyl)-2-[2-ethyl-4-(1-methylcarbamo yl-2-naphthalen-2-yl-ethyl)-piperazin-1-yl]-2-oxo-ethyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a cold solution of 2-{4-[2-tert-butoxycarbonylamino-3-(4-chlorophenyl)-propionyl]-3-ethyl-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid, 43, (1.0 g, 1.6 mmol) and PyBOP (1.1 g, 2.0 mmol) in anhydrous dichloromethane (10 mL) are added 2 M methyl amine solution in THF (0.9 mL, 1.6 mmol) and triethyl amine (0.6 mL, 3.9 mmol). The reaction mixture is placed in a refrigerator overnight. EtOAc (50 mL) and water (100 mL) are added, the organic layer is decanted and the aqueous layer is extracted with EtOAc (3×75 mL). All organic layers are combined and washed with brine (100 mL), dried over Na2SO4, concentrated in vacuo and purified over silica (EtOAc/Hexane, 1:1) to provide 1.0 g (quantitative yield) of the desired product. 1H NMR (CDCl3, 300 MHz): δ 7.72–7.50 (m, 4H), 7.29–7.14 (m, 4H), 7.10–7.04 (m, 2H), 7.00–6.97 (m, 3H), 5.60–5.51 (m, 1H), 4.73–4.66 (m, 1H), 4.30–4.11 (m, 1H), 3.45–3.26 (m, 2H), 3.15–3.05 (m, 1H), 2.86–2.79 (m, 3H), 2.75–2.59 (m, 5H), 2.56–2.47 (m, 1H), 2.43–2.29 (m, 1H), 2.05–2.01 (m,1H), 1.61 (s, 9H), 0.64–0.54 (m, 2); 13C NMR, (CDCl3, 75 MHz): δ 171.9, 170.3, 170.0, 155.0, 137.4, 137.2 135.3, 135.1, 133.6, 132.8, 132.2, 131.2, 131.1, 131.0, 128.7, 128.6, 128.4, 127.9, 127.8, 127.6, 127.5, 126.4, 126.0, 125.4, 124.7, 118.6, 110.4, 79.6, 69.9, 55.4, 50.9, 50.2, 46.4, 39.8, 37.9, 32.0, 32.6, 28.4, 26.5, 26.1, 23.0, 22.0, 10.6, 10.0.

Workup

  1. customis placed in a refrigerator overnight
  2. customthe organic layer is decanted
  3. extractionthe aqueous layer is extracted with EtOAc (3×75 mL)
  4. washwashed with brine (100 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. custompurified over silica (EtOAc/Hexane, 1:1)

Sources & evidence

ORD record
ord-628987eaee094f739c20482c77bb69a5
Source dataset
uspto-grants-2006_11
Patent number
US07132539B2

Reaction notes

Loading…