1,2-Dichloroethane → Azetidine-3-carboxylic acid [2-[2-ethyl-4-(1-methylcarbamoyl-2-naphthalen-2-yl-ethyl)-piperazin-1-yl]-1-(4-fluorobenzyl)-2-oxo-ethyl]-amide trifluoro-acetate

HRID 720191Notes

Reaction equation

HRID 720191 reaction equation
C(OC([N:8]1[CH2:11][CH:10]([C:12](=[O:49])[NH:13][CH:14]([CH2:41][C:42]2[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=2)[C:15]([N:17]2[CH2:22][CH2:21][N:20]([CH:23]([C:35](=[O:38])[NH:36][CH3:37])[CH2:24][C:25]3[CH:34]=[CH:33][C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH:26]=3)[CH2:19][CH:18]2[CH2:39][CH3:40])=[O:16])[CH2:9]1)=O)(C)(C)C.ClCCCl.C(Cl)Cl.[C:57]([OH:63])([C:59]([F:62])([F:61])[F:60])=[O:58].O>>[F:60][C:59]([F:62])([F:61])[C:57]([OH:63])=[O:58].[CH2:39]([CH:18]1[CH2:19][N:20]([CH:23]([C:35](=[O:38])[NH:36][CH3:37])[CH2:24][C:25]2[CH:34]=[CH:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=2)[CH2:21][CH2:22][N:17]1[C:15](=[O:16])[CH:14]([NH:13][C:12]([CH:10]1[CH2:11][NH:8][CH2:9]1)=[O:49])[CH2:41][C:42]1[CH:43]=[CH:44][C:45]([F:48])=[CH:46][CH:47]=1)[CH3:40]

Participants

4

Reactant 3

HCID 111,2-DichloroethaneHCID 18672661TFA dichloromethane waterHCID 695879793-[2-[2-Ethyl-4-(1-methylcarbamoyl-2-naphthalen-2-ylethyl)-piperazin-1-yl]-1-(4-fluorobenzyl)-2-oxo-ethylcarbamoyl]-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 69746596Azetidine-3-carboxylic acid [2-[2-ethyl-4-(1-methylcarbamoyl-2-naphthalen-2-yl-ethyl)-piperazin-1-yl]-1-(4-fluorobenzyl)-2-oxo-ethyl]-amide trifluoro-acetate

Procedure

3-[2-[2-ethyl-4-(1-methylcarbamoyl-2-naphthalen-2-ylethyl)-piperazin-1-yl]-1-(4-fluorobenzyl)-2-oxo-ethylcarbamoyl]-azetidine-1-carboxylic acid tert-butyl ester is dissolved in DCM/TFA/H2O (2/1/0.1) (10 mL) and stirred at room temperature for 1 hour. 1,2-dichloroethane (10 mL) is added, the solvent removed in vacuo to give a residue which is purified by preparative HPLC to afford 300 mg of the desired product. 1H NMR (CDCl3, 300 MHz, δ): 7.71–7.64 (m, 3H), 7.55–7.54 (m, 1H), 7.40–7.31 (m, 2H), 7.26–7.13 (m,3H), 6.97–6.87 (m, 3), 5.00 (t, J=7.7 Hz, 1H), 4.46 (br s, 0.5H), 4.32 (d, J=13.8 Hz, 0.5H), 4.08–3.86 (m, 6H), 3.68–3.63 (m, 0.5H), 3.60–3.49 (m, 1.5H), 3.47–3.41 (m, 0.5H), 3.25–3.00 (m, 2H), 3.14–3.03 (m, 3H), 2.98–2.65 (m, 5.5H), 2.54–2.35 (m, 3H), 1.77–1.56 (m, 1.5H), 1.55–1.36 (m, 0.5), 0.69–0.58 (m, 3H); 13C NMR, (CDCl3, 75 MHz) δ 175.0, 173.0, 172.0, 166.0, 163.0, 135.4, 134.1, 133.0, 132.9, 132.8, 132.7, 129.7, 129.5, 129.4, 129.0, 128.9, 128.8, 128.7, 127.7, 127.6, 127.3, 127.1, 117.1, 116.8, 116.5, 71.3, 71.2, 56.8, 53.9, 53.4, 52.2, 52.0, 51.9, 50.7, 50.3, 50.1, 50.0, 49.1, 41.6, 39.7, 38.4, 37.0, 35.7, 26.4, 24.0, 23.4, 11.1; HRFAB(positive) m/e 574.317945 calculated for C33H40FN5O3 (M+H)+, Found 574.319344.

Workup

  1. customthe solvent removed in vacuo
  2. customto give a residue which
  3. customis purified by preparative HPLC

Sources & evidence

ORD record
ord-0520884de83848d1a4e04b558b30a7cc
Source dataset
uspto-grants-2006_11
Patent number
US07132539B2

Reaction notes

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