Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][N:10]2[C:14]([CH3:15])=[C:13]([C:16]([OH:18])=O)[N:12]=[N:11]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[NH2:19][C:20]1[S:21][C:22]2[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[CH:25][C:23]=2[N:24]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][N:10]2[C:14]([CH3:15])=[C:13]([C:16]([NH:19][C:20]3[S:21][C:22]4[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[CH:25][C:23]=4[N:24]=3)=[O:18])[N:12]=[N:11]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: COc1ccc2nc(N)sc2c1
Reactant: Cc1c(C(=O)O)nnn1Cc1ccc(Cl)c(Cl)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc2nc(NC(=O)c3nnn(Cc4ccc(Cl)c(Cl)c4)c3C)sc2c1
Temperature: 45 °C
Reaction time: 72 h
Yield: 9.6 %

Procedure:
A mixture of 1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxylic acid (Intermediate 4) (0.1 g, 0.35 mmol), 2-amino-6-methoxybenzothiazole (0.062 g, 0.35 mmol), HATU (0.082 g, 0.45 mmol) and DIPEA (85 μL, 0.45 mmol) in DMF (5 mL) was stirred at 45° C. for 3 days. The solvent was evaporated and the residue was washed with water and extracted with DCM. The organic phase was dried over sodium sulphate, filtered and concentrated in vacuo. The residue was purified by flash chromatography eluting with DCM/MeOH (99/1) to give after trituration in diisopropyl ether, the title compound as a white solid (15 mg, 10%). HRMS calculated for C19H15Cl2N5O2S (M+H)+ 448.0402, found: 448.0403, Rt: 3.31 min. MP: 225° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][C:9]1([CH3:15])[CH3:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:16](=O)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:10][C:9]1([CH3:15])[CH3:14])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCNCC1(C)C
Reactant: O=Cc1ccccc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: CC(C)(C)OC(=O)N1CCN(Cc2ccccc2)CC1(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
To a solution of 2.20 g of 2,2-dimethyl-piperazine-1-carboxylic acid tert-butyl ester in 50 ml DCM was added 1.15 ml of benzaldehyde, followed by the addition of 2.61 g of sodium triacetoxyborohydride in small portions. The reaction was stirred at r.t. overnight. To the reaction was then added water. The layers were separated and the organic layer was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. 3.30 g (100%) of the title compound were obtained and used without further purification.
Reaction SMILES: CO[C:3]1[C:7](OC)=[N:6][S:5](=[O:11])(=[O:10])[N:4]=1.[NH:12]([C:16]1[S:20][N:19]=[C:18]([CH2:21][S:22][CH2:23][CH2:24][NH2:25])[N:17]=1)[C:13]([NH2:15])=[NH:14].[CH3:26][NH2:27]>>[NH:12]([C:16]1[S:20][N:19]=[C:18]([CH2:21][S:22][CH2:23][CH2:24][NH:25][C:3]2[C:7]([NH:27][CH3:26])=[N:6][S:5](=[O:11])(=[O:10])[N:4]=2)[N:17]=1)[C:13]([NH2:15])=[NH:14]
Reactant: COC1=NS(=O)(=O)N=C1OC
Reactant: CN
Reactant: N=C(N)Nc1nc(CSCCN)ns1
Product: CNC1=NS(=O)(=O)N=C1NCCSCc1nsc(NC(=N)N)n1

Procedure:
When a methanolic solution of 3,4-dimethoxy-1,2,5-thiadiazole 1,1-dioxide is successively treated with an equimolar amount of 2-[(5-guanidino-1,2,4-thiadiazol-3-yl)methylthio]ethylamine [prepared according to the procedure described in published European Patent Application 6679] and excess methylamine, the title compound is thereby produced.
Reaction SMILES: Cl[CH2:2][C@@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C@H:8]1[CH2:13][CH2:12][C@@H:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1.[N-:22]=[N+:23]=[N-:24].[Na+].C(OCC)(=O)C>CS(C)=O>[N:22]([CH2:2][C@@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C@H:8]1[CH2:13][CH2:12][C@@H:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[N+:23]=[N-:24]
Reactant: [N-]=[N+]=[N-]
Reactant: Fc1ccc(C[C@H]2CC[C@@H](N3CCC[C@H]3CCl)CC2)cc1
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: [N-]=[N+]=NC[C@@H]1CCCN1[C@H]1CC[C@@H](Cc2ccc(F)cc2)CC1
Temperature: 50 °C

Procedure:
To a stirring solution of (2S)-2-(chloromethyl)-1-[cis-4-(4-fluorobenzyl)cyclohexyl]pyrrolidine in 2 ml of DMSO (Aldrich) at 25° C. under N2 was added sodium azide (28 mg, 2.90 mmol, Aldrich). The reaction was heated at 50° C. for 16 hours. Worked up by adding ethyl acetate then rinsing 5 times with H2O. The organic was dried over magnesium sulfate, and concentrated in vacuo to obtain 45 mg of an amber oil as product. MS (ESI) detects 317 (M+H).
Reaction SMILES: [F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:13]([OH:28])[C:14]([NH:17][C:18](=[O:27])OCC2C=CC=CC=2)([CH3:16])[CH3:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[H-].[Na+].Br[CH2:34][C:35]1[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][C:36]=1[C:45]1[CH:46]=[C:47]([C:53]2[CH:58]=[CH:57][C:56]([C:59]([O:61]C)=[O:60])=[CH:55][C:54]=2[CH3:63])[CH:48]=[CH:49][C:50]=1[O:51][CH3:52]>C1COCC1>[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:13]2[O:28][C:18](=[O:27])[N:17]([CH2:34][C:35]3[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][C:36]=3[C:45]3[CH:46]=[C:47]([C:53]4[CH:58]=[CH:57][C:56]([C:59]([OH:61])=[O:60])=[CH:55][C:54]=4[CH3:63])[CH:48]=[CH:49][C:50]=3[O:51][CH3:52])[C:14]2([CH3:16])[CH3:15])[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=1
Reactant: COC(=O)c1ccc(-c2ccc(OC)c(-c3ccc(C(F)(F)F)cc3CBr)c2)c(C)c1
Reactant: CC(C)(NC(=O)OCc1ccccc1)C(O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccc(-c2ccc(C(=O)O)cc2C)cc1-c1ccc(C(F)(F)F)cc1CN1C(=O)OC(c2cc(C(F)(F)F)cc(C(F)(F)F)c2)C1(C)C
Reaction time: 72 h

Procedure:
To a solution of benzyl {2-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-1,1-dimethylethyl}carbamate (65 mg, 0.149 mmol) in THF (1.5 mL) was added NaH (13 mg, 0.542 mmol) and methyl 2″-(bromomethyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (91.1 mg, 0.185 mmol). The reaction was stirred for 72 hours, and then additional NaH (36.2 mg, 1.51 mmol) was added. After 6 more hours at room temperature, the reaction was quenched with saturated NH4Cl solution (10 mL) and diluted with EtOAc (20 mL). The aqueous layer was extracted with EtOAc (20 mL), and the combined organic extracts were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification of the residue by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA) afforded 2″-({5-[3,5-bis(trifluoromethyl)phenyl]-4,4-dimethyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid. LCMS=726.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, rotamers present) a 8.03-8.02 (m, 1H), 7.80-7.96 (m, 1H), 7.89 (s, 1H), 7.79-7.76 (m, 2H), 7.62-7.59 (m, 1H), 7.42-7.31 (m, 3H), 7.22-7.08 (m, 3H), 5.26-5.28 (m, 1H), 4.81 (d, J=16.6 Hz), 4.44-4.42 (m, 1H), 4.02 (d, J=16.6 Hz), 3.85 (s, 3H), 2.37-2.35 (m, 3H), 1.24 (s), 1.06 (s), 0.56-0.54 (m, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][CH:4]=1.[N+:11]([C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17](Cl)=[O:18])([O-:13])=[O:12].[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[C:17]([C:16]1[CH:20]=[CH:21][CH:22]=[C:14]([N+:11]([O-:13])=[O:12])[CH:15]=1)=[O:18]
Reactant: O=C(Cl)c1cccc([N+](=O)[O-])c1
Reactant: COc1ccc(OC)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: COc1ccc(OC)c(C(=O)c2cccc([N+](=O)[O-])c2)c1
Temperature: 0 °C
Reaction time: 8 h
Yield: 81.6 %

Procedure:
In 1.6 l of methylene chloride was dissolved 280 g of p-dimethoxybenzene and 372 g of m-nitrobenzoyl chloride. In this solution 300 g of aluminum chloride was added with stirring. After being allowed to stand overnight, the mixture was poured into ice water and the organic liquid phase was separated. After the methylene chloride was removed by distillation, the residual product was recrystallized from ethanol to obtain 470 g of pale yellow crystals of the subject compound which had a melting point of 98° C.
Reaction SMILES: [C:1]([C:3]1[N:4]=[C:5]([C:8]2[CH:17]=[C:16]([O:18][C@H:19]3[CH2:43][CH2:42][C@H:22]4[C:23](=[O:41])[N:24]([CH3:40])[CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[CH:30][C@@H:31]5[CH2:36][C@@:32]5([C:37]([OH:39])=O)[NH:33][C:34](=[O:35])[C@@H:21]4[CH2:20]3)[C:15]3[C:10](=[C:11]([CH3:46])[C:12]([O:44][CH3:45])=[CH:13][CH:14]=3)[N:9]=2)[S:6][CH:7]=1)#[CH:2].[CH3:47]CN=C=NCCCN(C)C.C[NH:59][S:60]([CH:63]1[CH2:65][CH2:64]1)(=[O:62])=[O:61].C1CCN2C(=NCCC2)CC1>C(Cl)Cl>[C:1]([C:3]1[N:4]=[C:5]([C:8]2[CH:17]=[C:16]([O:18][C@H:19]3[CH2:43][CH2:42][C@H:22]4[C:23](=[O:41])[N:24]([CH3:40])[CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[CH:30][C@@H:31]5[CH2:36][C@@:32]5([C:37]([NH:59][S:60]([C:63]5([CH3:47])[CH2:65][CH2:64]5)(=[O:62])=[O:61])=[O:39])[NH:33][C:34](=[O:35])[C@@H:21]4[CH2:20]3)[C:15]3[C:10](=[C:11]([CH3:46])[C:12]([O:44][CH3:45])=[CH:13][CH:14]=3)[N:9]=2)[S:6][CH:7]=1)#[CH:2]
Reactant: CCN=C=NCCCN(C)C
Reactant: C#Cc1csc(-c2cc(O[C@H]3CC[C@H]4C(=O)N(C)CCCCC=C[C@@H]5C[C@@]5(C(=O)O)NC(=O)[C@@H]4C3)c3ccc(OC)c(C)c3n2)n1
Reactant: CNS(=O)(=O)C1CC1
Agent: C#Cc1csc(-c2cc(O[C@H]3CC[C@H]4C(=O)N(C)CCCC/C=C\[C@@H]5C[C@@]5(C(=O)NS(=O)(=O)C5(C)CC5)NC(=O)[C@@H]4C3)c3ccc(OC)c(C)c3n2)n1
Agent: C#Cc1csc(-c2cc(O[C@H]3CC[C@H]4C(=O)N(C)CCCC/C=C\[C@@H]5C[C@@]5(C(=O)O)NC(=O)[C@@H]4C3)c3ccc(OC)c(C)c3n2)n1
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Product: C#Cc1csc(-c2cc(O[C@H]3CC[C@H]4C(=O)N(C)CCCCC=C[C@@H]5C[C@@]5(C(=O)NS(=O)(=O)C5(C)CC5)NC(=O)[C@@H]4C3)c3ccc(OC)c(C)c3n2)n1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To compound 46 (0.00003 mmol) in DCM (2 mL) under nitrogen was added EDCI (0.000062 mmol). The reaction mixture was stirred at room temperature for 2 hrs. Methyl-cyclopropylsulfonamide (0.00012 mmol) and DBU (0.00012 mmol) were then added and the reaction was stirred at room temperature for 16 hrs. DCM was then added, the mixture was washed with water and brine. Solvent was evaporated and the crude material was purified by silica gel chromatography (DCM/MeOH) to yield compound 52 as a white solid. MS (ESI, EI+): m/z=760 (MH+).
Reaction SMILES: S(Cl)(Cl)=O.[O:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:19]=[CH:18][C:14]([C:15]([OH:17])=[O:16])=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.[CH3:20]O>>[CH3:20][O:16][C:15](=[O:17])[C:14]1[CH:13]=[CH:12][C:11]([N:8]2[CH2:7][CH2:6][O:5][CH2:10][CH2:9]2)=[CH:19][CH:18]=1
Reactant: O=C(O)c1ccc(N2CCOCC2)cc1
Reactant: CO
Solvent: O=S(Cl)Cl
Product: COC(=O)c1ccc(N2CCOCC2)cc1

Procedure:
Under ice cooling, thionyl chloride (436 μL) was added dropwise to methanol (10 mL). 4-Morpholinobenzoic acid (207 mg) was added thereto, and the resultant mixture was heated under reflux for 1.5 hours. The solvent was distilled away under reduced pressure. Methylene chloride and water were added to the residue for partitioning the mixture. The organic layer was dried over sodium sulfate anhydrate. The solvent was distilled away under reduced pressure, whereby the title compound was obtained.
Reaction SMILES: [I:1][C:2]#[C:3][CH2:4][O:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[CH:8][C:7]=1[O:14][CH3:15].[F:16][C:17]([F:29])([F:28])[C:18]1[CH:19]=[C:20]([CH:25]=[CH:26][CH:27]=1)[CH2:21][N:22]=[N+:23]=[N-:24]>>[I:1][C:2]1[N:22]([CH2:21][C:20]2[CH:25]=[CH:26][CH:27]=[C:18]([C:17]([F:16])([F:29])[F:28])[CH:19]=2)[N:23]=[N:24][C:3]=1[CH2:4][O:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[CH:8][C:7]=1[O:14][CH3:15]
Reactant: COc1cc(C=O)ccc1OCC#CI
Reactant: [N-]=[N+]=NCc1cccc(C(F)(F)F)c1
Product: COc1cc(C=O)ccc1OCc1nnn(Cc2cccc(C(F)(F)F)c2)c1I

Procedure:
Synthesized from 4-(3-iodoprop-2-ynyloxy)-3-methoxybenzaldehyde and 3-trifluoromethyl-benzylazide using general procedure; 0.398 g, 0.769 mmol, 97%; mp=130-134° C. (dec.); IR (υ[cm−1]) 3123, 1702, 1689, 1588, 1506, 1329, 1262, 1133, 1123, 994, 792; 1H NMR (600 MHz, CDCl3) δ=9.83 (s, 1H), 7.59 (d, J=7.6, 1H), 7.56 (s, 1H), 7.47 (t, J=7.7, 1H), 7.41 (dd, J=15.8, 6.7, 2H), 7.39 (s, 1H), 7.21 (d, J=8.1, 1H), 5.62 (s, 2H), 5.27 (s, 2H), 3.88 (s, 3H); 13C NMR (151 MHz, CDCl3) δ=191.2, 153.1, 150.5, 147.5, 135.0, 131.6, 131.6 (q, J=32.7), 131.1, 129.9, 126.7, 125.9 (q, J=3.6), 125.1 (q, J=3.7), 123.9 (q, J=272.4), 113.5, 109.7, 81.2, 62.9, 56.3, 54.0; HRMS (ESI-TOF) (m/z): [M+H]+ calcd for C19H16F3IN3O3, 518.0183; found 518.0186.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][N:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([OH:13])=[O:12].O.ON1C2C=CC=C[C:19]=2N=N1.[NH2:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1>CN(C=O)C>[CH2:3]([CH2:2][C:11]([O:13][CH3:19])=[O:12])[CH3:4].[N:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[CH2:26][NH:25][C:11]([C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[N:7][CH:6]=2)[N:1]=1)=[O:13]
Reactant: O=C(O)c1ccc2cnccc2n1
Reactant: NCc1ccccn1
Reactant: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Product: CCCC(=O)OC
Product: O=C(NCc1ccccn1)c1ccc2cnccc2n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 5 %
Yield: 207.5 %

Procedure:
To a stirring mixture of 2-[1,6]naphthyridinecarboxylic acid (50 mg, 0.287 mmol) in anhydrous DMF (1.0 mL) at room temperature was added sequentially 1-hydroxybenzotriazole hydrate (42.7 mg, 0.316 mmol), 2-(aminomethyl)pyridine (45.3 μL, 0.431 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarboiimide hydrochloride (61.8 mg, 0.316 mmol). The resulting mixture was allowed to stir at room temperature overnight and it was found to be clear. The solvent was removed under 5 vacuum. Flash column chromatography of the residue (50% hexane/ethyl acetate to 5% methanol I ethyl acetate) afforded the desired product as a light brown solid (78.7 mg, 99%): m.p. 123-125° C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8]3=[C:9]([CH2:11][CH2:12][N:7]3[C@H:6]3[CH2:13][CH2:14][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][C@@H:5]23)[CH:10]=1.[CH3:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1B(O)O>>[CH3:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:2]1[CH:3]=[C:4]2[C:8]3=[C:9]([CH2:11][CH2:12][N:7]3[C@H:6]3[CH2:13][CH2:14][N:15]([C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[CH2:16][C@@H:5]23)[CH:10]=1
Reactant: Cc1ccccc1B(O)O
Reactant: CC(C)(C)OC(=O)N1CC[C@H]2[C@@H](C1)c1cc(Br)cc3c1N2CC3
Product: Cc1ccccc1-c1cc2c3c(c1)[C@@H]1CN(C(=O)OC(C)(C)C)CC[C@@H]1N3CC2

Procedure:
The title compound was prepared by the method of Example 89 step C from tert-butyl(6aS,10aR)-2-bromo-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)carboxylate (189 mg, 0.5 mmol) and 2-methylphenylboronic acid (136 mg, 1.0 mmol) to afford after chromatographic purification the title compound (90 mg, 46%). 1H NMR (CDCl3, 300 MHz) δ 7.11–7.18 (m,4H), 6.82 (s, 1H), 6.77 (s, 1H), 3.86–4.30 (m, 2H), 3.58–3.64 (m, 1H), 2.76–3.42 (m, 7H), 2.20 (s, 3H), 1.70–1.85 (m, 2H), 1.40 (s, 9H) ppm. MS-ApCI: 391 [M+H+].
Reaction SMILES: [H-].[Na+].C1COCC1.[O:8]=[C:9]1[CH:15]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:14][S:13][CH2:12][CH2:11][NH:10]1.[CH2:24]([O:28][C:29]1[CH:36]=[CH:35][C:32]([CH2:33]Br)=[CH:31][CH:30]=1)[CH2:25][CH2:26][CH3:27]>O.CCOC(C)=O>[CH2:24]([O:28][C:29]1[CH:30]=[CH:31][C:32]([CH2:33][N:10]2[C:9](=[O:8])[CH:15]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:20])([CH3:22])[CH3:21])[CH2:14][S:13][CH2:12][CH2:11]2)=[CH:35][CH:36]=1)[CH2:25][CH2:26][CH3:27]
Reactant: CCCCOc1ccc(CBr)cc1
Reactant: CC(C)(C)OC(=O)NC1CSCCNC1=O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: CCCCOc1ccc(CN2CCSCC(NC(=O)OC(C)(C)C)C2=O)cc1
Yield: 156.7 %

Procedure:
81 mg of sodium hydride as a 60% suspension in oil (2.03 mmol) are introduced at room temperature into a 25 ml round-bottomed flask, with stirring and under an argon atmosphere, containing 20 ml of THF and 500 mg of 26 (2.03 mmol). The medium is stirred for 1 hour and 1.1 g (2.34 mmol) of 4-butoxybenzyl bromide are then added. The medium is stirred for 16 hours, 20 ml of EtOAc and 20 ml of water are added to the reaction medium and, after separation of the phases by settling, the organic phase is washed with 10 ml of water. The organic phase is dried, filtered and then evaporated to dryness to give 1.3 g of crude product, which product is chromatographed on a silica cartridge (25 g) with a 90/10 heptane/EtOAc mixture. 420 mg of product 39 are recovered (yield=53%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][OH:10])=[C:4]([O:11][CH3:12])[CH:3]=1.C(N(CC)CC)C.[CH3:20][S:21](Cl)(=[O:23])=[O:22]>ClCCl.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][O:10][S:21]([CH3:20])(=[O:23])=[O:22])=[C:4]([O:11][CH3:12])[CH:3]=1
Reactant: CS(=O)(=O)Cl
Reactant: COc1cc(F)ccc1CCO
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: COc1cc(F)ccc1CCOS(C)(=O)=O
Temperature: 0 °C
Reaction time: 1 h
Yield: 94.1 %

Procedure:
To a solution of 5.1 g (29.97 mmol) of 2-(4-Fluoro-2-methoxy-phenyl)-ethanol in 30 ml of anhydrous dichloromethane was added at 0° C. 6.26 ml (44.95 mmol) of triethylamine and 3.5 ml (44.95 mmol) of methanesulfonyl chloride. The resulting mixture was stirred at 0° C. for 1 h. The mixture was then diluted with water and dichloromethane and extracted with dichloromethane. Organic layer was dried and evaporated to give 7 g(100%) of methanesulfonic acid 2-(4-fluoro-2-methoxy-phenyl)-ethyl ester.
Reaction SMILES: [CH3:1][C:2]([CH3:34])([CH3:33])[C:3]([C:5]1[C:6]([CH3:32])=[C:7]([C:17]([N:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:20][CH2:21][C:22]([O:24]C)=[O:23])=[O:18])[N:8]2[C:13]=1[CH:12]=[C:11]([CH:14]([CH3:16])[CH3:15])[CH:10]=[CH:9]2)=[O:4].[OH-].[Na+].CC(O)=O>O1CCOCC1.O>[CH3:34][C:2]([CH3:1])([CH3:33])[C:3]([C:5]1[C:6]([CH3:32])=[C:7]([C:17]([N:19]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[O:18])[N:8]2[C:13]=1[CH:12]=[C:11]([CH:14]([CH3:16])[CH3:15])[CH:10]=[CH:9]2)=[O:4]
Reactant: COC(=O)CCN(C(=O)c1c(C)c(C(=O)C(C)(C)C)c2cc(C(C)C)ccn12)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Solvent: CC(=O)O
Product: Cc1c(C(=O)C(C)(C)C)c2cc(C(C)C)ccn2c1C(=O)N(CCC(=O)O)c1ccccc1
Temperature: 23 °C
Reaction time: 2 h
Yield: 72 %

Procedure:
To a stirred solution of methyl N-{[1-(2,2-dimethylpropanoyl)-2-methyl-7-(propan-2-yl)indolizin-3-yl]carbonyl}-N-phenyl-beta-alaninate (60 mg, 0.13 mmol) in 1,4-dioxane (5 mL) and water (1 mL) is added 10M aqueous NaOH (50 μL). The mixture is stirred at 23° C. for 2 h then acidified with HOAc, diluted water (5 mL), extracted with CH2Cl2, dried with MgSO4, filtered, and concentrated in vacuo to afford the title compound (42 mg, 72%).
Reaction SMILES: [CH2:1]1[S:6](=[O:8])(=[O:7])[O:5][CH2:4][CH2:3][CH2:2]1.[NH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C(O)C>[NH:9]([CH2:4][CH2:3][CH2:2][CH2:1][S:6]([OH:5])(=[O:8])=[O:7])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=S1(=O)CCCCO1
Reactant: Nc1ccccc1
Solvent: CCO
Product: O=S(=O)(O)CCCCNc1ccccc1
Temperature: 25 °C
Yield: 92 %

Procedure:
A solution of butanesultone (27.2 g, 0.2 mol) and aniline (46.5 g, 0.5 mol) in ethanol is heated under reflux for 4 hr. and cooled to room temperature to precipitate a white solid. The precipitates are filtered and recrystallized in ethanol to obtain 4-anilino-1-butanesulfonic acid (42.2 g, 90%) as white crystals. 4-Anilino-1-butanesulfonic acid (10 g) is dissolved in water and neutralized by sodium hydroxide. The neutral solution is concentrated under reduced pressure to give white solids. The solids are crystallized in methanol-chloroform to obtain 4-anilino-1-butanesulfonic acid sodium salt (10.0 g, 92%) as white crystals.
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][C:4]([O-:7])=[CH:3][CH:2]=1.[Na+].[CH3:9][C:10]([CH3:12])=O>>[C:4]1([OH:7])[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1.[C:4]1([CH:10]([CH3:12])[CH3:9])[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1
Reactant: CC(C)=O
Reactant: [O-]c1ccccc1
Agent: [Na+]
Product: CC(C)c1ccccc1
Product: Oc1ccccc1

Procedure:
One of the more specific embodiments of the '150 invention is a method for treating a reaction mixture resulting from the sulfuric acid cleavage of cumene hydroperoxide comprising the steps of (a) effecting the neutralization of the reaction mixture with sodium phenate, and forming a reaction mixture comprising phenol, acetone, cumene and a sodium sulfate salt of neutralization; (b) processing an initially salt-free aqueous stream in counter current contact with the neutralized sodium sulfate-containing reaction mixture at a temperature of from about 95° to about 120° F. and at a pH of from about 2 to about 6; (c) progressively saturating the resulting aqueous phase with the sodium sulfate and salting-out the organic acid cleavage products contained therein whereby the aqueous phase is recovered containing substantially all of the sodium sulfate and substantially free of organic products.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]CC)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O[C@@H]1[C@@H](OC(=O)C)[C@H](OC(=O)C)[C@@H](COC(=O)C)O[C@H]1[N-]C(NC(OC(C)(C)C)=O)CCCCCCCCCCC)(=O)C>CCCCCC.C(OCC)(=O)C>[OH:11][CH2:10][CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: CCCCCCCCCCCCC(NC(=O)OC(C)(C)C)C(=O)O
Agent: CCCCCCCCCCCC([N-][C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O)NC(=O)OC(C)(C)C
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CCCCCCCCCCC(CO)NC(=O)OC(C)(C)C
Yield: 87 %

Procedure:
Procedure as for 44 (using 40 in place of 41). RF=0.50 hexane:ethyl acetate 4:1 (v/v); yield 87%; 1H NMR δ 3.65-3.48 (m, 3H, αCH, CH2), 1.43 (s, 9H, 3×Boc CH3), 1.24 (m, 18H, 9CH2), 0.86 (t, 3H, CH3); FAB MS C17H35NO3 (301.46) m/z (%) 302 [M+H]+ (15), 324 [M+Na]+ (5), 434 [M+Cs]+ (10), 202 [M−Boc+H]+ (95).
Reaction SMILES: CCN(C(C)C)C(C)C.[Cl:10][C:11]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:12]=1[C:13]([OH:15])=O.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.[O:43]=[C:44]([N:62]1[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1)[CH2:45][NH:46][C:47](=[O:61])[C:48]1[CH:53]=[CH:52][C:51]([O:54][C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)=[CH:50][CH:49]=1>CN(C=O)C.O>[Cl:10][C:11]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:12]=1[C:13]([N:65]1[CH2:66][CH2:67][N:62]([C:44](=[O:43])[CH2:45][NH:46][C:47](=[O:61])[C:48]2[CH:49]=[CH:50][C:51]([O:54][C:55]3[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=3)=[CH:52][CH:53]=2)[CH2:63][CH2:64]1)=[O:15]
Reactant: O=C(O)c1cc(Cl)ccc1Cl
Reactant: O=C(NCC(=O)N1CCNCC1)c1ccc(Oc2ccccc2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(NCC(=O)N1CCN(C(=O)c2cc(Cl)ccc2Cl)CC1)c1ccc(Oc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 55 %

Procedure:
DIPEA (0.11 mL, 0.64 mmol) was added drop wise to 2,5-dichlorobenzoic acid (48 mg, 0.26 mmol) in DMF (5 mL). EDCI (102 mg, 0.53 mmol) and HOBT (34 mg, 0.26 mmol) were added consecutively. After 10 mins, N-(2-Oxo-2-piperazin-1-yl-ethyl)-4-phenoxy-benzamide hydrochloride (80 mg, 0.21 mmol) was added and the resulting mixture was stirred at room temperature overnight. Water was then added, and the product was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. Purification using column chromatography (silica gel of mesh size of 60-120 using 60:40 EtOAc:Hexane as eluent) afforded N-{2-[4-(2,5-Dichloro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-4-phenoxy-benzamide in 55% yield LC-MS purity: 99%, 1H NMR (DMSO-D6): δ 8.5 (t, 1H), 7.9 (d, 2H), 7.6 (t, 3H), 7.5 (t, 2H), 7.2 (t, 1H), 7.1 (m, 4H), 4.2 (d, 2H), 3.5 (m, 6H), 3.3 (m, 2H).