Methylamine → {1-(4-Fluoro-benzyl)2-[2-methoxymethyl-4-(1-methylcarbamoyl-2-naphthalen-2-yl-ethyl)-piperazin-1-yl]-2oxo-ethyl}-carbamic acid tert-butyl ester

HRID 720203Notes

Reaction equation

HRID 720203 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:36][C:37]1[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=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]([OH:21])=O)[CH2:14][CH:13]1[CH2:33][O:34][CH3:35])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C[N:47]([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)[CH2:46]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]([CH2:36][C:37]1[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=1)[C:10]([N:12]1[CH2:17][CH2:16][N:15]([CH:18]([C:19](=[O:21])[NH:47][CH3:46])[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][O:34][CH3:35])=[O:11])([CH3:3])([CH3:2])[CH3:4]

Participants

9

Reactant 5

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 2724699PyBOPHCID 219016992-{4-[2-Tert-butoxycarbonylamino-3-(4-fluorophenyl)-propionyl]-3-methoxymethyl-piperazine-1-yl}-3-naphthalen-2-yl-propionic acid

Product 1

HCID 69587995{1-(4-Fluoro-benzyl)2-[2-methoxymethyl-4-(1-methylcarbamoyl-2-naphthalen-2-yl-ethyl)-piperazin-1-yl]-2oxo-ethyl}-carbamic acid tert-butyl esterYield 100%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a cold solution of 2-{4-[2-tert-butoxycarbonylamino-3-(4-fluorophenyl)-propionyl]-3-methoxymethyl-piperazine-1-yl}-3-naphthalen-2-yl-propionic acid, 64, (2.7 g, 4.3 mmol) and PyBOP (2.9 g, 5.6 mmol) in anhydrous dichloromethane (15 mL) is added 2M methyl amine solution in THF (4.4 mL, 8.8 mmol) and triethyl amine (1.5 mL, 10.7 mmol). The reaction mixture is placed in a refrigerator overnight. EtOAc (50 mL) and water (200 mL) are added, and the organic layer is separated. The aqueous layer is extracted with EtOAc (3×100 mL). All organic layers are combined and washed with brine (100 mL), and dried over Na2SO4. The solution is concentrated in vacuo to afford 2.6 g (100% yield) of the desired product. 1H NMR (CDCl3, δ): 7.62–7.50 (m, 3H), 7.45 (s, 1H), 7.35–7.12 (m, 3H), 7.05–6.92 (m, 2H), 6.82–6.70 (m, 2H), 5.45 (dd, J=20.5, 8.2 Hz, 0.5H), 4.75–4.45 (m, 1H), 4.05 (d, J=12.3 Hz, 0.5H), 3.5–3.20 (m, 1H), 3.20–3.08 (m, 1H), 3.08–2.98 (m, 1H), 2.92 (s, 8H), 2.84–2.64 (m, 2H), 2.55 (br s, 2H), 2.40–1.85 (m, 1H), 1.6 (s, 7H), 1.22 (d, J=6.6 Hz, 7H); 13C NMR, δ 171.6, 171.4, 171.2, 170.2, 163.5, 160.3, 154.9, 137.3,137.2, 132.6, 132.3, 132.1, 131.2, 127.6, 127.5, 126.0, 125.4, 115.4, 115.1, 114.9, 79.5, 79.3, 70.2, 69.6, 69.3, 58.9, 58.8, 53.3, 51.2, 49.8, 49.6, 48.7, 48.3, 46.3, 42.9, 39.8, 38.9, 38.6, 33.6, 28.3, 26.5, 26.4, 25.8, 25.7.

Workup

  1. customis placed in a refrigerator overnight
  2. customthe organic layer is separated
  3. extractionThe aqueous layer is extracted with EtOAc (3×100 mL)
  4. washwashed with brine (100 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationThe solution is concentrated in vacuo

Sources & evidence

ORD record
ord-dee257db478240cc839e7b6af7e511d8
Source dataset
uspto-grants-2006_11
Patent number
US07132539B2

Reaction notes

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