Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][C:9]2[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=2[N:7]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=2)[S:6]1(=[O:23])=[O:22].[CH3:24][NH2:25].Cl>>[ClH:1].[CH3:24][NH:25][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][C:9]2[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=2[N:7]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=2)[S:6]1(=[O:23])=[O:22]
Reactant: CN
Reactant: Cc1cccc(N2c3ccccc3CN(CCCCl)S2(=O)=O)c1
Agent: Cl
Product: CNCCCN1Cc2ccccc2N(c2cccc(C)c2)S1(=O)=O

Procedure:
In an analogous manner to Example 1, step 8, 3-(3-chloropropyl)-1-(3-methylphenyl)-3,4-dihydro-1H-2,1,3-benzothiadiazine 2,2-dioxide (21 mg) was reacted with methylamine and then treated with HCl to provide N-methyl-3-[1-(3-methylphenyl)-2,2-dioxido-1,4-dihydro-3H-2,1,3-benzo thiadiazin-3-yl]propan-1-amine hydrochloride (18 mg):
Reaction SMILES: [ClH:1].CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[N:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH2:29][CH2:30][N:31]([CH2:45][C:46]2[CH:51]=[CH:50][N:49]=[CH:48][CH:47]=2)[CH2:32][CH2:33][CH2:34][O:35][C:36]2[CH:44]=[CH:43][C:39]([C:40](O)=[O:41])=[CH:38][CH:37]=2)[CH:24]=1.Cl.[CH2:53]([NH2:55])[CH3:54].[OH-].[Na+].C(OC(=O)C)C.Cl>C(OCC)(=O)C.C(N(CC)CC)C.CN(C=O)C>[ClH:1].[ClH:1].[ClH:1].[CH2:53]([NH:55][C:40](=[O:41])[C:39]1[CH:38]=[CH:37][C:36]([O:35][CH2:34][CH2:33][CH2:32][N:31]([CH2:30][CH2:29][C:25]2[CH:24]=[N:23][CH:28]=[CH:27][CH:26]=2)[CH2:45][C:46]2[CH:47]=[CH:48][N:49]=[CH:50][CH:51]=2)=[CH:44][CH:43]=1)[CH3:54]
Reactant: CCN
Reactant: O=C(O)c1ccc(OCCCN(CCc2cccnc2)Cc2ccncc2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CCNC(=O)c1ccc(OCCCN(CCc2cccnc2)Cc2ccncc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.7 %

Procedure:
1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (WSC)(95 mg), and 1-hydroxy benzotriazole (HOBt)(66 mg) were added to a DMF solution (4 ml) of 4-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}benzoic acid (149 mg), ethyl amine hydrochloride (38 mg), and triethylamine (0.08 ml). The mixture was stirred at room temperature overnight. The reaction mixture was added to ice water. A 1N-sodium hydroxide aqueous solution was added thereto, followed by extraction using ethyl acetate. The organic layer was washed with water and then was dried with anhydrous sodium sulfate, followed by condensation under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1→4:1). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution (0.16 ml) was added to an ethyl acetate solution of the residue. The precipitated insoluble matter was separated, washed with ethyl acetate, and dried to give the title compound (80 mg) as a white powder.
Reaction SMILES: C1([CH2:6][C:7](Cl)=[O:8])CCCC1.[N:10]1[CH:11]=[CH:12][N:13]2[CH:18]=[CH:17][C:16]([CH2:19][NH:20][C:21]([C:23]3[S:24][C:25]([C:28]4[CH2:29][CH2:30][NH:31][CH2:32][CH:33]=4)=[CH:26][CH:27]=3)=[O:22])=[CH:15][C:14]=12.NC1C=CC(C(OC)=O)=CC=1>>[C:7]([N:31]1[CH2:30][CH:29]=[C:28]([C:25]2[S:24][C:23]([C:21]([NH:20][CH2:19][C:16]3[CH:17]=[CH:18][N:13]4[CH:12]=[CH:11][N:10]=[C:14]4[CH:15]=3)=[O:22])=[CH:27][CH:26]=2)[CH2:33][CH2:32]1)(=[O:8])[CH3:6]
Reactant: O=C(Cl)CC1CCCC1
Reactant: O=C(NCc1ccn2ccnc2c1)c1ccc(C2=CCNCC2)s1
Agent: COC(=O)c1ccc(N)cc1
Product: CC(=O)N1CC=C(c2ccc(C(=O)NCc3ccn4ccnc4c3)s2)CC1

Procedure:
The title compound was prepared as described in Example 52A, substituting acetyl chloride for 2-cyclopentylacetyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.13-9.06 (m, 1H), 8.48 (d, J=7.0 Hz, 1H), 7.88 (s, 1H), 7.72 (d, J=3.9 Hz, 1H), 7.51 (d, J=1.2 Hz, 1H), 7.38 (s, 1H), 7.15 (t, J=4.2 Hz, 1H), 6.83 (dd, J=7.0, 1.6 Hz, 1H), 6.28-6.21 (m, 1H), 4.46 (d, J=5.9 Hz, 2H), 4.15-4.04 (m, 2H), 3.61 (dt, J=11.3, 5.6 Hz, 2H), 2.63-2.35 (m, 2H), 2.07-1.99 (m, 3H); MS (ESI)(+)) m/e 381 (M+H)+.
Reaction SMILES: C([N:14]1[CH2:17][C:16]([NH:19][C:20]2[CH:21]=[C:22]3[C:31](=[CH:32][C:33]=2[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:30][CH2:29][C:28]2[N:23]3[CH:24]([CH3:41])[C:25](=[O:40])[NH:26][N:27]=2)([CH3:18])[CH2:15]1)(C1C=CC=CC=1)C1C=CC=CC=1>C1COCC1.CO.Cl.[OH-].[OH-].[Pd+2]>[CH3:41][CH:24]1[N:23]2[C:28]([CH2:29][O:30][C:31]3[C:22]2=[CH:21][C:20]([NH:19][C:16]2([CH3:18])[CH2:17][NH:14][CH2:15]2)=[C:33]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:32]=3)=[N:27][NH:26][C:25]1=[O:40]
Reactant: CC1C(=O)NN=C2COc3cc(-c4ccccc4)c(NC4(C)CN(C(c5ccccc5)c5ccccc5)C4)cc3N21
Agent: [Pd+2]
Agent: Cl
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CC1C(=O)NN=C2COc3cc(-c4ccccc4)c(NC4(C)CNC4)cc3N21
Temperature: 50 °C
Yield: 139.8 %

Procedure:
To a solution of 6-(1-benzhydryl-3-methyl-azetidin-3-ylamino)-4-methyl-7-phenyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Example #79, Step C, 0.10 g, 0.18 mmol) in THF (20 mL), MeOH (20 mL) and aqueous HCl (12N, 0.3 mL) was added Pd(OH)2/C (10%, 0.02 g, 0.014 mmol) and the solution was heated at 50° C. under an atmosphere of H2 (55 psi) for 4 h. The reaction mixture was cooled to ambient temperature and filtered. The filtrate was evaporated in vacuo to give 4-methyl-6-(3-methyl-azetidin-3-ylamino)-7-phenyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.095 g, 57% pure, 82%), which was used in the next step directly without further purification. LC/MS (Table 1, Method 2) Rt=0.890 min; MS m/z: 378 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[N:6][C:5]2[CH2:8][CH2:9][NH:10][CH2:11][C:4]=2[C:3]=1[CH3:12].C([O-])(=O)/C=C\C([O-])=O.[F:21][C:22]1[CH:30]=[CH:29][CH:28]=[CH:27][C:23]=1[C:24](Cl)=[O:25]>>[Cl:1][C:2]1[N:7]=[N:6][C:5]2[CH2:8][CH2:9][N:10]([C:24](=[O:25])[C:23]3[CH:27]=[CH:28][CH:29]=[CH:30][C:22]=3[F:21])[CH2:11][C:4]=2[C:3]=1[CH3:12]
Reactant: O=C(Cl)c1ccccc1F
Reactant: Cc1c(Cl)nnc2c1CNCC2
Agent: O=C([O-])/C=C\C(=O)[O-]
Product: Cc1c(Cl)nnc2c1CN(C(=O)c1ccccc1F)CC2

Procedure:
A suspension of 14.4 g of 6-carbethoxy-5,6,7,8-tetrahydro-4-methyl-3(2H)pyrido[4,3-c]pyridazinone in 100 cc of concentrated hydrochloric acid is heated to the boil at reflux for 20 hours while stirring. The resulting 5,6,7,8-tetrahydro-4-methyl-3(2H)pyrido[4,3-c]pyridazinone is isolated (M.P. of the hydrochloride 344° to 348°) and is converted in a manner analogous to that described in Example 1(e) into 3-chloro-5,6,7,8-tetrahydro-4-methylpyrido[4,3-c]pyridazine (M.P. of the maleate: 170° to 173°), this is reacted with o-fluorobenzoyl chloride, whereby 3-chloro-6-(o-fluorobenzoyl)-5,6,7,8-tetrahydro-4-methylpyrido[4,3-c]pyridazine is obtained (M.P. 151°-153°).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6](S(C)=O)[C:5]([C:11]#[N:12])=[C:4]([N:13]2[CH:17]=[CH:16][CH:15]=[N:14]2)[N:3]=1.[CH3:18][C:19]1[C:20]([CH2:25][OH:26])=[N:21][CH:22]=[CH:23][CH:24]=1.C1CCN2C(=NCCC2)CC1>COCCOC>[NH2:1][C:2]1[N:7]=[C:6]([O:26][CH2:25][C:20]2[C:19]([CH3:18])=[CH:24][CH:23]=[CH:22][N:21]=2)[C:5]([C:11]#[N:12])=[C:4]([N:13]2[CH:17]=[CH:16][CH:15]=[N:14]2)[N:3]=1
Reactant: CS(=O)c1nc(N)nc(-n2cccn2)c1C#N
Reactant: Cc1cccnc1CO
Solvent: COCCOC
Solvent: C1CCC2=NCCCN2CC1
Product: Cc1cccnc1COc1nc(N)nc(-n2cccn2)c1C#N

Procedure:
From 2-amino-4-methanesulfinyl-6-pyrazol-1-yl-pyrimidine-5-carbonitrile, 3-methyl-2-pyridinemethanol and DBU in DME. ES-MS m/e (%): 308 (M+H+, 100).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[C:4]([F:21])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([CH2:19][CH3:20])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.[Cl:22][C:23]1[N:24]=[CH:25][N:26](COCC[Si](C)(C)C)[C:27]=1[C:28](O)=[O:29].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[Cl:22][C:23]1[N:24]=[CH:25][NH:26][C:27]=1[C:28]([NH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[C:5]([O:10][C:11]2[CH:18]=[C:17]([CH2:19][CH3:20])[CH:16]=[C:13]([C:14]#[N:15])[CH:12]=2)[C:4]=1[F:21])=[O:29]
Reactant: CCc1cc(C#N)cc(Oc2c(Cl)ccc(CN)c2F)c1
Reactant: C[Si](C)(C)CCOCn1cnc(Cl)c1C(=O)O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CCc1cc(C#N)cc(Oc2c(Cl)ccc(CNC(=O)c3[nH]cnc3Cl)c2F)c1
Yield: 26.5 %

Procedure:
3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-ethylbenzonitrile (0.055 g, 0.181 mmol), 4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid (0.050 g, 0.181 mmol) and DIPEA (0.063 mL, 0.361 mmol) were combined in THF (2 mL) and treated with HATU (0.076 g, 0.199 mmol) at 25° C. overnight with stirring. The reaction mixture was concentrated to dryness, dissolved in DCM, washed with water, dried over MgSO4, filtered and concentrated to dryness. The residue was dissolved in DCM (2.5 mL) and treated with TFA (2.5 mL) at 25° C. for 3 days. The reaction mixture was concentrated to dryness, dissolved in DCM, washed with saturated aqueous NaHCO3, dried over MgSO4, filtered and concentrated to dryness. The resultant solid was recrystallized from boiling IPA, cooled in an ice bath and filtered to give 4-chloro-N-({4-chloro-3-[(3-cyano-5-ethylphenyl)oxy]-2-fluorophenyl}methyl)-1H-imidazole-5-carboxamide (0.021 g, 0.048 mmol, 26.8% yield) as a white solid. The mother liquor was concentrated to dryness and purified on an XTerra™ C-18 column eluted with 5 to 75% CH3CN/H2O (0.2% NH4OH buffer). Appropriate fractions were combined, concentrated to dryness, chased twice with ethanol and twice with toluene to remove residual water to give additional 4-chloro-N-({4-chloro-3-[(3-cyano-5-ethylphenyl)oxy]-2-fluorophenyl}methyl)-1H-imidazole-5-carboxamide (0.043 g, 0.099 mmol, 54.9% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.19 (br. s., 1H), 8.30 (br. s., 1H), 7.76 (s, 1H), 7.43-7.54 (m, 2H), 7.29-7.42 (m, 1H), 7.18 (m, 2H), 4.53 (d, J=5.22 Hz, 2H), 2.64 (q, J=7.23 Hz, 2H), 1.15 (t, J=7.48 Hz, 3H). LC-MS (ES−) m/z 431.16, 433.15 [M−1]. LC-MS (ES+) m/z 433.08, 435.07 [M+H].
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH2:33][NH:32][C:31](=[O:34])[C:4]=2[C:5]([NH:23][C:24]2[CH:25]=[C:26]([CH3:30])[CH:27]=[CH:28][CH:29]=2)=[N:6][C:7]=1[NH:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]1[NH:15]C(=O)OC(C)(C)C.[F:35][C:36]([F:41])([F:40])[C:37]([OH:39])=[O:38]>C(Cl)Cl>[C:37]([OH:39])([C:36]([F:41])([F:40])[F:35])=[O:38].[NH2:15][C@H:10]1[CH2:11][CH2:12][CH2:13][CH2:14][C@H:9]1[NH:8][C:7]1[N:6]=[C:5]([NH:23][C:24]2[CH:25]=[C:26]([CH3:30])[CH:27]=[CH:28][CH:29]=2)[C:4]2[C:31](=[O:34])[NH:32][CH2:33][C:3]=2[C:2]=1[Cl:1]
Reactant: Cc1cccc(Nc2nc(N[C@@H]3CCCC[C@@H]3NC(=O)OC(C)(C)C)c(Cl)c3c2C(=O)NC3)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1cccc(Nc2nc(N[C@@H]3CCCC[C@@H]3N)c(Cl)c3c2C(=O)NC3)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 61.9 %

Procedure:
To a solution of tert-butyl (1S,2R)-2-(7-chloro-3-oxo-4-(m-tolylamino)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (20 mg, 0.041 mmol) in DCM (0.8 mL) was added trifluoroacetic acid (0.31 mL). The reaction mixture was stirred at RT for 1 h, then concentrated to a brown residue which was diluted in MeOH (2 mL) and purified via preparative HPLC to give a TFA salt of the title compound as a fluffy white solid (12.3 mg, 61.9%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.85 (s, 1H), 8.36 (s, 1H), 7.83 (br s, 3H), 7.39-7.57 (m, 2H), 7.12-7.32 (m, 1H), 6.84 (d, J=7.6 Hz, 1H), 6.22 (d, J=6.8 Hz, 1H), 4.19-4.43 (m, 3H), 3.71 (br s, 1H), 2.32 (s, 3H), 1.37-1.99 (m, 8H). [M+H] calc'd for C20H24ClN5O, 386. found, 386.
Reaction SMILES: [F:1][C:2]1[C:7]([C:8]2[NH:12][CH:11]=[C:10]([CH2:13][N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[H-].[Na+].C1OCCOCCOCCOCCOC1.[O:40]1[C:44]([C:45]2[S:49][C:48]([S:50](Cl)(=[O:52])=[O:51])=[CH:47][CH:46]=2)=[CH:43][CH:42]=[N:41]1>O1CCCC1.C(=O)([O-])O.[Na+]>[F:1][C:2]1[C:7]([C:8]2[N:12]([S:50]([C:48]3[S:49][C:45]([C:44]4[O:40][N:41]=[CH:42][CH:43]=4)=[CH:46][CH:47]=3)(=[O:51])=[O:52])[CH:11]=[C:10]([CH2:13][N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:18])([CH3:19])[CH3:20])[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: O=S(=O)(Cl)c1ccc(-c2ccno2)s1
Reactant: CN(Cc1c[nH]c(-c2cccnc2F)c1)C(=O)OC(C)(C)C
Agent: C1COCCOCCOCCOCCO1
Agent: O=C([O-])O
Agent: [H-]
Solvent: C1CCOC1
Product: CN(Cc1cc(-c2cccnc2F)n(S(=O)(=O)c2ccc(-c3ccno3)s2)c1)C(=O)OC(C)(C)C
Reaction time: 0.33 h
Yield: 23.6 %

Procedure:
To a solution of tert-butyl {[5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamate (200 mg) in tetrahydrofuran (10 mL) was added sodium hydride (60% in oil, 53 mg) under ice-cooling, and the mixture was stirred for 20 min. After stirring, 15-crown-5 (290 mg) was added. 5-Isoxazol-5-ylthiophene-2-sulfonyl chloride (246 mg) was added and the mixture was further stirred under ice-cooling for 1 hr. The reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=1:1) to give the title compound as a colorless oil (yield 80 mg, 24%).
Reaction SMILES: C[O:2][C:3](=[O:24])[C:4]1[C:9]([N+:10]([O-:12])=[O:11])=[CH:8][CH:7]=[CH:6][C:5]=1[NH:13][CH2:14][CH2:15][NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].[OH-].[Li+]>C1COCC1.O.C(OCC)(=O)C>[C:20]([O:19][C:17]([NH:16][CH2:15][CH2:14][NH:13][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([N+:10]([O-:12])=[O:11])[C:4]=1[C:3]([OH:24])=[O:2])=[O:18])([CH3:23])([CH3:21])[CH3:22]
Reactant: COC(=O)c1c(NCCNC(=O)OC(C)(C)C)cccc1[N+](=O)[O-]
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)NCCNc1cccc([N+](=O)[O-])c1C(=O)O
Temperature: 50 °C
Yield: 95.8 %

Procedure:
To a solution of 2-(2-tert-butoxycarbonylaminoethylamino)-6-nitro-benzoic acid methylester (0.26 g, 0.00077 mol) in THF-water (3:1, 20 mL) under nitrogen was added lithium hydroxide (0.14 g, 0.00326 mol) as a solid in one portion. The reaction mixture was heated at 50° C. for 5 h then cooled to room temperature overnight. The mixture was diluted with ethyl acetate (10 mL) and washed with 10% aqueous HCl, water, and brine. The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo to a yellow oil which was purified by ISCO chromatography on silica gel using 15-50% ethyl acetate-hexane to give product as a pale yellow oil 2-(2-tert-butoxycarbonylaminoethylamino)-6-nitro-benzoic acid (0.24 g, 96%). 1H NMR (400 MHz, CDCl3) δ 11.8 (s, 1H), 7.57 (t, 1H, J=7.8 Hz), 7.05 (d, 1H, J=7.8 Hz), 6.81 (d, 1H, J=7.8 Hz), 6.73 (s, 1H), 4.5 (s, 1H), 3.47 (m, 2H), 3.19 (m, 2H), 1.47 (s, 9H); MS (m/e) 326 (M+1).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[C:26]([F:29])([F:28])[F:27])[CH2:9]/[C:10](/[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([CH3:19])[CH:14]=2)=[N:11]\[OH:12])=[CH:4][CH:3]=1.[CH3:30][S:31]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)(=[O:33])=[O:32]>>[CH3:30][S:31]([N:34]1[CH2:39][CH2:38][N:37]([C:2]2[CH:7]=[CH:6][C:5]([CH:8]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:29])([F:28])[F:27])[CH2:9]/[C:10](/[C:13]3[CH:18]=[CH:17][N:16]=[C:15]([CH3:19])[CH:14]=3)=[N:11]\[OH:12])=[CH:4][CH:3]=2)[CH2:36][CH2:35]1)(=[O:33])=[O:32]
Reactant: Cc1cc(/C(CC(c2ccc(Br)cc2)c2ccccc2C(F)(F)F)=N/O)ccn1
Reactant: CS(=O)(=O)N1CCNCC1
Product: Cc1cc(/C(CC(c2ccc(N3CCN(S(C)(=O)=O)CC3)cc2)c2ccccc2C(F)(F)F)=N/O)ccn1

Procedure:
In analogy to example 39, from (E)-3-(4-bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-(2-trifluoromethyl-phenyl)-propan-1-one oxime (example 132) and 1-methanesulfonyl-piperazine (CAS RN: [55276-43-2]) was prepared the title compound as a yellow foam, MS (ESI+): m/z=547.3 ([M+H]+).
Reaction SMILES: [CH2:1]([C@@](C)(O)C(O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:14]([OH:19])(=[O:18])[C@H:15]([CH3:17])[OH:16].C(N(CC1C=CC=CC=1)C(=NC(C)C)O)(C)C>C1COCC1>[C:14]([O:19][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)(=[O:18])[CH:15]([CH3:17])[OH:16]
Reactant: C[C@H](O)C(=O)O
Reactant: C[C@@](O)(Cc1ccccc1)C(=O)O
Agent: CC(C)N=C(O)N(Cc1ccccc1)C(C)C
Solvent: C1CCOC1
Product: CC(O)C(=O)OCc1ccccc1
Temperature: -15 °C
Reaction time: 0.17 h
Yield: 95 %

Procedure:
Construction of Benzyl-L-lactic Acid. L-Lactic acid (9 g, 100 mmol) is added to N,N'-diisopropylbenzylisourea (23.3 g, 100 mmol) with stirring. The mixture becomes very viscous within 10 min and is stirred intermittently for 1 h. The volume is then increased to 200 mL with THF, and the mixture stirred for 48 h at room temperature. After cooling the mixture to -15° C., the diisopropylurea is removed by filtration and the THF is evaporated under reduced pressure. The resulting thick oil is pumped under high vacuum for 24 h to give benzyl lactate (17.4 g, 95%) which may be used without further purification.