Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11](=O)[CH2:12][CH2:13][C:14](=O)[CH3:15])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:15][C:14]1[N:18]([C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=2)[C:11]([C:8]2[CH:9]=[CH:10][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:6][CH:7]=2)=[CH:12][CH:13]=1
Reactant: Cc1ccc(N)cc1
Reactant: CC(=O)CCC(=O)c1ccc(S(C)(=O)=O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: Cc1ccc(-n2c(C)ccc2-c2ccc(S(C)(=O)=O)cc2)cc1
Yield: 90.8 %

Procedure:
A mixture of 1-(4-methylsulfonylphenyl)-1,4-pentanedione (Example 1, Step 2) (335 mg, 1.32 mmol), p-toluidine (156 mg, 1.45 mmol) and p-toluenesulfonic acid (25 mg) in toluene (100 ml) was heated to reflux for 20 hours. The reaction mixture was cooled, filtered and concentrated. The crude solid (560 mg) was purified by chromatography (silica gel, hexane/ethyl acetate, 7/3) to give 2-methyl-1-(4-methylphenyl)-5-[4-(methylsulfonyl)phenyl]-1H-pyrrole (390 mg, 91%) as a white solid: mp (DSC) 144° C. Anal Calc'd. for C19H19NSO2 : C, 70.13; H, 5.88; N, 4.30; S, 9.85. Found: C, 69.99; H, 6.23; N, 4.18; S, 9.74.
Reaction SMILES: [CH3:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[OH:11].Br[CH:13]([CH2:19][CH3:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[CH3:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[O:11][CH:13]([CH2:19][CH3:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15]
Reactant: Cc1c(O)cccc1[N+](=O)[O-]
Reactant: CCOC(=O)C(Br)CC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)C(CC)Oc1cccc([N+](=O)[O-])c1C
Temperature: 25 °C
Reaction time: 18 h
Yield: 93.5 %

Procedure:
A mixture of 5.0 g (32 mmole) of 2-methyl-3-nitrophenol, 4.8 ml (ca. 32 mmole) of ethyl 2-bromobutanoate, and 4.5 g (32 mmole) of potassium carbonate in 50 ml of dimethylformamide was stirred for 18 hours at room temperature. The mixture was then poured over ice, diluted with water, and extracted twice with diethyl ether. The combined organic extract was washed with water, dried over magnesium sulfate, filtered, and concentrated in vacuo to give 8.0 g of the title compound as an analytically pure solid. Structure assignment was supported by nmr and infrared spectra and by elemental analysis.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([O:26][CH3:27])=[CH:5][C:6]2[N:12]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:11](=[O:20])[N:10]([CH2:21][CH2:22][CH2:23]Cl)[CH2:9][CH2:8][C:7]=2[CH:25]=1.[NH2:28][C:29]1[C:34]([Cl:35])=[CH:33][C:32]([NH:36][CH2:37][CH2:38][NH2:39])=[CH:31][C:30]=1[Cl:40]>>[CH3:1][O:2][C:3]1[C:4]([O:26][CH3:27])=[CH:5][C:6]2[N:12]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:11](=[O:20])[N:10]([CH2:21][CH2:22][CH2:23][NH:39][CH2:38][CH2:37][NH:36][C:32]3[CH:31]=[C:30]([Cl:40])[C:29]([NH2:28])=[C:34]([Cl:35])[CH:33]=3)[CH2:9][CH2:8][C:7]=2[CH:25]=1
Reactant: NCCNc1cc(Cl)c(N)c(Cl)c1
Reactant: COc1cc2c(cc1OC)N(Cc1ccccc1)C(=O)N(CCCCl)CC2
Product: COc1cc2c(cc1OC)N(Cc1ccccc1)C(=O)N(CCCNCCNc1cc(Cl)c(N)c(Cl)c1)CC2

Procedure:
The title compound is prepared from 3-(7,8-dimethoxy-1-benzyl-1,3,4,5-tetrahydro-2H-1,3-benzdiazepin-2-on-3-yl)-1-chloropropane and 2-(4-amino-3,5-dichloro-phenylamino)-ethylamine analogously to Example 6.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@H:12]([CH:13]=[O:14])[CH2:11][O:10][C:9]1([CH3:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:17][C:18]([Si](C)(C)C)([F:20])[F:19].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:15][C:9]1([CH3:16])[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C@H:12]([CH:13]([OH:14])[C:18]([F:20])([F:19])[F:17])[CH2:11][O:10]1
Reactant: C[Si](C)(C)C(F)(F)F
Reactant: CC(C)(C)OC(=O)N1[C@H](C=O)COC1(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1[C@H](C(O)C(F)(F)F)COC1(C)C
Temperature: 25 °C
Reaction time: 60 h
Yield: 92.7 %

Procedure:
To a mixture of (S)-4-formyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (1.0 g, 4.36 mmol), (trifluoromethyl)trimethylsilane (2.0 M solution in THF, 2.6 mL, 5.20 mmol) in THF (10 mL) was added tetrabutylammonium fluoride (1.0 M solution in THF, 0.1 mL, 0.10 mmol) at 0° C. After addition, the mixture was stirred at room temperature for 60 h. Then, tetrabutylammonium fluoride (1.0 M solution in THF, 9 mL, 9.0 mmol) was added and the mixture stirred for another 6 h and subsequently quenched by adding saturated aq. NaHCO3 solution, extracted with EtOAc. The extracts were washed with saturated aq. NaHCO3 solution, water, brine and dried over Na2SO4. Concentration and purification gave (S)-tert-butyl 2,2-dimethyl-4-(2,2,2-trifluoro-1-hydroxyethyl)oxazolidine-3-carboxylate (1.21 g, 92%), which showed a complicated NMR spectrum because of the different comformers.
Reaction SMILES: [NH2:1][C:2]1[C:7]([Br:8])=[CH:6][N:5]=[C:4]([CH2:9][S:10][C:11]2[NH:15][C:14]3[CH:16]=[CH:17][C:18]([O:20][CH3:21])=[CH:19][C:13]=3[N:12]=2)[CH:3]=1.ClC1C=CC=C(C(OO)=[O:30])C=1>ClCCl>[NH2:1][C:2]1[C:7]([Br:8])=[CH:6][N:5]=[C:4]([CH2:9][S:10]([C:11]2[NH:15][C:14]3[CH:16]=[CH:17][C:18]([O:20][CH3:21])=[CH:19][C:13]=3[N:12]=2)=[O:30])[CH:3]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COc1ccc2[nH]c(SCc3cc(N)c(Br)cn3)nc2c1
Solvent: ClCCl
Product: COc1ccc2[nH]c(S(=O)Cc3cc(N)c(Br)cn3)nc2c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2 -(4 -amino-5 -bromo-2 -pyridylmethylthio)-5 -methoxy-(1H)-benzimidazole (0.58 g, 0.0016 M) was dissolved in dichloromethane (160 ml) and cooled to -40°. m-Chloroperbenzoic acid (0.33 g, 0.0019 M) in dichloromethane (10 ml) was added dropwise over 20 mins, keeping the temperature at 30 ° to -40°. The solution was stirred at -30 ° for 1 hour and then stored at -20 ° overnight, or until reaction was complete. Ammonia was then bubbled through the solution at 50, the mixture allowed to warm up to room temperature, and then filtered. The filtrate and washings were washed with 10 % Na2CO3 (10 ml) an dried. Back extraction of the aqueous layers with dichloromethane (3×100 ml) gave further organic layers which were dried and combined with layers obtained from the first extraction. Evaporation of the combined organic layers gave a brown solid. Purification, by heating in presence of decolouring charcoal in ethyl acetate/methanol, followed by recrystallisation from methanol gave 2 -(4 -amino-5 -bromo-2 -pyridylmethylsulphinyl)-5 -methoxy-(1H)-benzimidazole, 0.21 g, m.p. 130°-132°.
Reaction SMILES: OO.[CH3:3]C(C1C=CC(OC(C)C(O)=O)=CC=1)=C.[OH:18][C:19]1[CH:30]=[CH:29][C:22]([O:23][CH:24]([CH3:28])[C:25]([OH:27])=[O:26])=[CH:21][CH:20]=1>CO>[OH:18][C:19]1[CH:20]=[CH:21][C:22]([O:23][CH:24]([CH3:28])[C:25]([O:27][CH3:3])=[O:26])=[CH:29][CH:30]=1
Reactant: CC(Oc1ccc(O)cc1)C(=O)O
Reactant: C=C(C)c1ccc(OC(C)C(=O)O)cc1
Agent: OO
Solvent: CO
Product: COC(=O)C(C)Oc1ccc(O)cc1
Reaction time: 1.5 h

Procedure:
Hydrogen peroxide (67% H2O2, 0.60 equivalents) was added to a mixture of 0.005 equivalents of Dowex® MSC-1 sulfonic acid resin in the proton form, 0.050 equivalents 2-(4-(1-methylethenyl)phenoxy)propanoic acid (prepared by base hydrolysis of methyl 2-(4-(1-methylethenyl)phenoxy)propanoate), and 11 ml methanol at room temperature. The mixture was refluxed about 10 hours. (The oxidation was complete after about 1.5 hour, but about 10 hours were required for the simultaneous esterification.) Workup gave 8.3 g of methyl 2-(4-hydroxyphenoxy)propanoate containing a small amount of 2-(4-hydroxyphenoxy)propanoic acid.
Reaction SMILES: P(=O)(O)(O)O.[CH:6]1[C:11](Cl)=[CH:10][C:9]2[C:13]([C:15]3[C:20]([NH:21][C:8]=2[CH:7]=1)=[CH:19][C:18]1[C:22]([C:24]2[CH:30]=[C:29](Cl)[CH:28]=[CH:27][C:25]=2[NH:26][C:17]=1[CH:16]=3)=[O:23])=[O:14]>O>[CH:29]1[CH:30]=[C:24]2[C:22]([C:18]3[C:17]([NH:26][C:25]2=[CH:27][CH:28]=1)=[CH:16][C:15]1[C:13]([C:9]2[C:8]([NH:21][C:20]=1[CH:19]=3)=[CH:7][CH:6]=[CH:11][CH:10]=2)=[O:14])=[O:23]
Reactant: O=c1c2cc(Cl)ccc2[nH]c2cc3c(=O)c4cc(Cl)ccc4[nH]c3cc12
Agent: O=P(O)(O)O
Solvent: O
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12

Procedure:
was cyclized in phosphoric acid to form 2,9-dichloroquinacridone. The phosphoric acid containing the thus-formed 2,9-dichloroquinacridone was dispersed in water, and the 2,9-dichloroquinacridone (crude C.I. Pigment Red 202) was then sufficiently washed, dried and pulverized to obtain Quinacridone pigment composition (2-5).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][C:13]=1[O:22][CH3:23].CN1CCOCC1.[C:31](Cl)(=[O:37])[CH2:32][CH2:33][CH2:34][CH2:35][CH3:36].Cl>ClCCl>[C:31]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][C:13]=1[O:22][CH3:23])(=[O:37])[CH2:32][CH2:33][CH2:34][CH2:35][CH3:36]
Reactant: COC(=O)c1ccc(Cc2c[nH]c3ccc(N)cc23)c(OC)c1
Reactant: CCCCCC(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: CCCCCC(=O)Nc1ccc2[nH]cc(Cc3ccc(C(=O)OC)cc3OC)c2c1
Reaction time: 2 h
Yield: 91.2 %

Procedure:
A stirred solution of methyl 4-(5-aminoindol-3-ylmethyl)-3-methoxybenzoate (A) (0.2 g.) in dichloromethane (5 ml.) under an atmosphere of nitrogen, was treated with N-methylmorpholine (0.25 g.), followed by hexanoyl chloride (0.103 g.). After being stirred for 2 hours, the mixture was poured into 1M hydrochloric acid (20 ml.). This mixture was extracted with ethyl acetate (2×20 ml.). The combined organic extracts were dried (MgSO4) and evaporated. The yellow oil obtained was purified by flash chromatography on silica gel (75 ml.), eluting with 6:4 v/v ethyl acetate:hexane, to give the title compound (0.24 g., 92%) as a colorless oil; NMR: 0.83(t,3H, CH2.CH3), 1.36(m,4H, CH2.CH2.CH3), 1.57(quintet,2H, CH2.CH2.CON), 2.24(t, 2H, CH2.CON), 3.80(s,3H, COOCH3), 3.90(s,3H, OCH3), 3.99(s,2H, CH 2.Ar), 7.1(m, 2H), 7.21(m,2H), 7.44(m,2H), 7.69(s,1H,H -indole), 9.59(s,1H, CONH), 10.77(s,1H, H1 -indole)
Reaction SMILES: [C:1]1([CH3:10])[CH:6]=[CH:5][C:4]([C:7](=[O:9])[CH3:8])=[CH:3][CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:21][C:22]([S@@:25](/[N:27]=[C:28](\[C:33]1[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][C:45]([F:48])([F:47])[F:46])=[CH:35][CH:34]=1)/[C:29]([F:32])([F:31])[F:30])=[O:26])([CH3:24])[CH3:23]>C1COCC1>[CH3:24][C:22]([S@@:25]([NH:27][C@:28]([C:33]1[CH:34]=[CH:35][C:36]([O:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][C:45]([F:48])([F:46])[F:47])=[CH:37][CH:38]=1)([CH2:8][C:7](=[O:9])[C:4]1[CH:5]=[CH:6][C:1]([CH3:10])=[CH:2][CH:3]=1)[C:29]([F:30])([F:32])[F:31])=[O:26])([CH3:21])[CH3:23]
Reactant: CC(C)(C)[S@](=O)/N=C(\c1ccc(OCCCCCC(F)(F)F)cc1)C(F)(F)F
Reactant: CC(=O)c1ccc(C)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: Cc1ccc(C(=O)C[C@](N[S@@](=O)C(C)(C)C)(c2ccc(OCCCCCC(F)(F)F)cc2)C(F)(F)F)cc1
Temperature: -78 °C
Reaction time: 0.33 h
Yield: 59.3 %

Procedure:
To a solution of 1-(p-tolyl)ethanone (609 mg, 4.31 mmol) in THF (10 mL) was cooled to −78° C. and to this solution was added lithium bis(trimethylsilyl)amide (4.31 mL, 4.31 mmol). The resulting mixture was stirred at −78° C. for 20 min and then Intermediate 8C (620 mg, 1.437 mmol) in THF (3 mL) was added dropwise. The resulting mixture was stirred at −78° C. for 1.5 h and then at 0° C. for 1.5 h. The reaction was quenched with NH4Cl and concentrated. The crude product was purified by silica gel chromatography (80 g silica gel, eluted with EtOAc in hexanes) to afford Intermediate 8D (482 mg, 59%) as the slower eluting diastereomer on silica gel column. LCMS Anal. Calc'd for C27H33F6NO3S 565.21, found [M+H] 566.0.
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH3:7])=[C:5]([C:8]([NH:10][C:11]2[CH:33]=[CH:32][C:14]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:23](=O)[O:24]C4C=CC=CC=4)[CH:17]=3)=[C:13]([F:34])[CH:12]=2)=[O:9])[C:4](=[O:35])[N:3]1[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[CH3:42][NH:43][CH2:44][CH3:45]>CN1C(=O)CCC1>[CH2:44]([N:43]([CH3:42])[C:23](=[O:24])[NH:22][C:18]1[CH:17]=[C:16]([O:15][C:14]2[CH:32]=[CH:33][C:11]([NH:10][C:8]([C:5]3[C:4](=[O:35])[N:3]([C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=4)[N:2]([CH3:1])[C:6]=3[CH3:7])=[O:9])=[CH:12][C:13]=2[F:34])[CH:21]=[CH:20][N:19]=1)[CH3:45]
Reactant: CCNC
Reactant: Cc1c(C(=O)Nc2ccc(Oc3ccnc(NC(=O)Oc4ccccc4)c3)c(F)c2)c(=O)n(-c2ccccc2)n1C
Solvent: CN1CCCC1=O
Product: CCN(C)C(=O)Nc1cc(Oc2ccc(NC(=O)c3c(C)n(C)n(-c4ccccc4)c3=O)cc2F)ccn1
Temperature: 40 °C
Yield: 58.9 %

Procedure:
A mixture of phenyl (4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-2-fluorophenoxy)pyridin-2-yl)carbamate (100 mg, 0.18 mmol), NMP (5 mL) and N-methylethanamine (12 mg, 0.2 mmol) was heated at 40° C. for 2 hours. The solvent was evaporated under reduced pressure at 40° C., and then diluted with water (10 mL). The precipitate was collected by filtration, and then purified by a silica gel column chromatography (DCM/MeOH (v/v)=60/1) to give the title compound as a white solid (55 mg, 62%).
Reaction SMILES: [C:1]([OH:4])(=[O:3])[CH3:2].[O:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:12]=2[S:20]([NH:23][C:24]2[CH:29]=[C:28]([O:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])[C:27]([C:47]([CH3:54])([CH3:53])[CH2:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[CH:26][C:25]=2O)(=[O:22])=[O:21])[CH2:7][CH2:6]1.C(OC(=O)C)(=O)C.C([O-])(=O)C.[Na+]>O>[C:1]([O:4][C:25]1[CH:26]=[C:27]([C:47]([CH3:54])([CH3:53])[CH2:48][C:49]([CH3:52])([CH3:50])[CH3:51])[C:28]([O:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])=[CH:29][C:24]=1[NH:23][S:20]([C:12]1[CH:13]=[C:14]([N+:17]([O-:19])=[O:18])[CH:15]=[CH:16][C:11]=1[N:8]1[CH2:7][CH2:6][O:5][CH2:10][CH2:9]1)(=[O:21])=[O:22])(=[O:3])[CH3:2]
Reactant: CC(=O)O
Reactant: CCCCCCCCCCCCCCCCOc1cc(NS(=O)(=O)c2cc([N+](=O)[O-])ccc2N2CCOCC2)c(O)cc1C(C)(C)CC(C)(C)C
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Solvent: O
Product: CCCCCCCCCCCCCCCCOc1cc(NS(=O)(=O)c2cc([N+](=O)[O-])ccc2N2CCOCC2)c(OC(C)=O)cc1C(C)(C)CC(C)(C)C
Temperature: 80 °C
Reaction time: 2 h

Procedure:
A solution of acetic acid (70 ml) containing 21 g (0.0287 mol) of the compound obtained in Step (c) above, 15 ml of acetic anhydride and 9.8 g of sodium acetate was stirred at 80° C. for 2 hours. After cooling, the reaction mixture was added to 500 ml of water and the precipitate was extracted with ethyl acetate. The ethyl acetate was concentrated and to the residue was added 100 ml of methanol and the crystals thus-precipitated were collected by filtration. Yield: 20.6 g (93%).
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([S:8](=[O:16])(=[O:15])[NH:9][C:10]2[CH:14]=[CH:13][O:12][N:11]=2)=[CH:4][C:3]=1/[CH:17]=[CH:18]/[C:19]([O:21]CC)=O.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:74][O:75][C:76]1[CH:82]=[CH:81][CH:80]=[CH:79][C:77]=1[NH2:78]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[O:12]1[CH:13]=[CH:14][C:10]([NH:9][S:8]([C:5]2[CH:4]=[C:3]3[C:2](=[CH:7][CH:6]=2)[N:78]([C:77]2[CH:79]=[CH:80][CH:81]=[CH:82][C:76]=2[O:75][CH3:74])[C:19](=[O:21])[CH:18]=[CH:17]3)(=[O:15])=[O:16])=[N:11]1
Reactant: CCOC(=O)/C=C/c1cc(S(=O)(=O)Nc2ccon2)ccc1I
Reactant: COc1ccccc1N
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: COc1ccccc1-n1c(=O)ccc2cc(S(=O)(=O)Nc3ccon3)ccc21
Temperature: 80 °C
Reaction time: 4 h
Yield: 64.6 %

Procedure:
(E)-Ethyl 3-(2-iodo-5-(N-(isoxazol-3-yl)sulfamoyl)phenyl)acrylate (0.043 g, 0.096 mmol), xantphos (8.33 mg, 0.014 mmol), Pd2(dba)3 (4.39 mg, 4.80 μmol), and freshly ground potassium phosphate (0.061 g, 0.288 mmol) were added to a 1 dram vial and purged with N2. 1,4-dioxane (0.5 ml) and 2-methoxyaniline (0.022 ml, 0.192 mmol) were added and the mixture was evacuated and backfilled with N2 twice and then stirred at 80° C. for 4 hr. The reaction was then cooled to rt and diluted with 1.5 mL MeOH then heated to 80° C. overnight. The reaction was concentrated to remove MeOH, then diluted with EtOAc and 1N HCl. The aqueous layer was extracted twice with EtOAc, the combined organics were washed with brine, dried over Na2SO4, and concentrated. MPLC purification (12 g Snap, 40% [3:1 EtOAc:EtOH]:heptanes) provided N-(isoxazol-3-yl)-1-(2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (24.8 mg, 0.062 mmol, 65.1% yield) as a light yellow solid. m/z (ESI) 396.0 (M−H)−.
Reaction SMILES: [OH:1][C:2]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)([C:6]1[N:7]=[CH:8][N:9]([C:11]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:10]=1)[CH:3]([CH3:5])[CH3:4].Br[C:40]1[CH:41]=[C:42]([CH:49]=[CH:50][CH:51]=1)[C:43]([NH:45][CH:46]([CH3:48])[CH3:47])=[O:44]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:1][C:2]([C:30]1[CH:35]=[CH:34][C:33]([C:50]2[CH:51]=[CH:40][CH:41]=[C:42]([C:43]([NH:45][CH:46]([CH3:48])[CH3:47])=[O:44])[CH:49]=2)=[CH:32][CH:31]=1)([C:6]1[N:7]=[CH:8][N:9]([C:11]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:10]=1)[CH:3]([CH3:5])[CH3:4]
Reactant: CC(C)C(O)(c1ccc(B(O)O)cc1)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Reactant: CC(C)NC(=O)c1cccc(Br)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: CC(C)NC(=O)c1cccc(-c2ccc(C(O)(c3cn(C(c4ccccc4)(c4ccccc4)c4ccccc4)cn3)C(C)C)cc2)c1
Yield: 44.8 %

Procedure:
By the reaction in the same manner as in Example 33-(ii) using 4-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]phenylboronic acid (3.40 g), 3-bromo-N-isopropylbenzamide (1.70 g) and tetrakis(triphenylphosphine)palladium(0) (0.220 g), the title compound (1.88 g) was obtained as a colorless amorphous powder.
Reaction SMILES: [F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[C:5]([NH:13][C:14](SC)=[C:15]([S:18]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)(=[O:20])=[O:19])[C:16]#[N:17])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:32][C@H:33]([NH2:37])[CH:34]([CH3:36])[CH3:35]>>[F:31][C:2]([F:30])([F:1])[C:3]1[CH:4]=[C:5]([NH:13][C:14]([NH:37][C@@H:33]([CH3:32])[CH:34]([CH3:36])[CH3:35])=[C:15]([S:18]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)(=[O:19])=[O:20])[C:16]#[N:17])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
Reactant: CC(C)[C@H](C)N
Reactant: CSC(Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1)=C(C#N)S(=O)(=O)c1ccc(Cl)cc1
Product: CC(C)[C@H](C)NC(Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1)=C(C#N)S(=O)(=O)c1ccc(Cl)cc1
Yield: 18 %

Procedure:
3-(3,5-Bis(trifluoromethyl)phenylamino)-2-(4-chloro-phenylsulfonyl)-3-methylsulfanyl-2-propenenitrile (0.200 g, 0.4 mmol) was stirred in (S)-1,2-dimethylpropylamine (0.2 ml) at 80° C. in a sealed flask for 20 h. Work up as described in Example 1, 2) gave 40 mg (18%) of the title compound as white crystals. 1H NMR (300 MHz, CDCl3): d=0.85 (dd, 6H), 1.05 (d, 3H), 1.7 (m,1H) 3.10 (m, 1H), 7.43 (s, 2H), 7.48 (d, 2H), 7.70 (s, 1H), 7.80 (d, 2H).
Reaction SMILES: [CH3:1][S:2]([NH:5][C:6]1[CH:21]=[CH:20][C:9]2[NH:10][C:11]([CH2:16][C:17]([OH:19])=O)=[N:12][S:13](=[O:15])(=[O:14])[C:8]=2[CH:7]=1)(=[O:4])=[O:3].[CH2:22]([O:24][C:25]([CH:27]1[CH2:31][CH2:30][CH2:29][CH:28]1[NH:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=1)=[O:26])[CH3:23].Cl.CN(C)CCCN=C=NCC.CN1CCOCC1.Cl>CN(C)C=O>[CH2:22]([O:24][C:25]([CH:27]1[CH2:31][CH2:30][CH2:29][CH:28]1[N:32]([CH2:33][C:34]1[CH:35]=[CH:36][C:37]([Cl:40])=[CH:38][CH:39]=1)[C:17](=[O:19])[CH2:16][C:11]1[NH:10][C:9]2[CH:20]=[CH:21][C:6]([NH:5][S:2]([CH3:1])(=[O:3])=[O:4])=[CH:7][C:8]=2[S:13](=[O:14])(=[O:15])[N:12]=1)=[O:26])[CH3:23]
Reactant: CCOC(=O)C1CCCC1NCc1ccc(Cl)cc1
Reactant: CS(=O)(=O)Nc1ccc2c(c1)S(=O)(=O)N=C(CC(=O)O)N2
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: CCOC(=O)C1CCCC1N(Cc1ccc(Cl)cc1)C(=O)CC1=NS(=O)(=O)c2cc(NS(C)(=O)=O)ccc2N1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
(7-Methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1j, 0.1665 g, 0.5 mmol) was dissolved in anhydrous N,N-dimethylformamide (3 mL). 2-(4-Chloro-benzylamino)-cyclopentanecarboxylic acid ethyl ester (0.1406 g, 0.5 mmol) was added followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.1003 g, 0.525 mmol). Then N-methylmorpholine (115 μL, 1.05 mmol) was added. The mixture was stirred at 25° C. for 5 h. The solution was poured into 1.0 M aqueous hydrochloric acid solution (100 mL). The aqueous layer was extracted with ethyl acetate (2×100 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo to afford the crude product, 2-{(4-chloro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclopentanecarboxylic acid ethyl ester, as a yellow oil. LC-MS (ESI) calcd for C25H29ClN4O7S2 596.12, found 597.2 [M+H+].
Reaction SMILES: [CH3:1][CH:2]([NH:4][C:5]([CH:7]1[CH:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[O:8]1)=[O:6])[CH3:3].[Cl:16][C:17]1[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=1.[H-].[Na+].C1OCCOCCOCCOCCOCCOC1>C(#N)C>[OH:8][CH:7]([CH:9]([O:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([Cl:16])[CH:18]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:5]([NH:4][CH:2]([CH3:1])[CH3:3])=[O:6]
Reactant: Oc1cccc(Cl)c1
Reactant: CC(C)NC(=O)C1OC1c1ccccc1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: CC#N
Product: CC(C)NC(=O)C(O)C(Oc1cccc(Cl)c1)c1ccccc1

Procedure:
This compound was prepared from N-(1-methylethyl)-3-phenyl-2-oxiranecarboxamide (6.16 g.) m-chlorophenol (3.9 g.), sodium hydride (50% oil dispersion, 1.5 g.), 18-crown-6 (0.9 g.), and acetonitrile (250 ml.) as described in Example 12. The product which was purified by recrystallization from ether melted at 151°-153°, and weighed 1.4 g.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[C:9](Br)[CH:10]=1)=[O:4].[Cl:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][C:20]=1[CH3:28].C([O-])([O-])=O.[Na+].[Na+].C(OCC)(=O)C.CCCCCCC>CS(C)=O.O>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C:9]2[C:8]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[N:7][CH:6]=[C:5]([CH:10]=2)[C:3]([O:2][CH3:1])=[O:4])=[CH:21][C:20]=1[CH3:28]
Reactant: COC(=O)c1cnc(OCC(F)(F)F)c(Br)c1
Reactant: Cc1cc(B(O)O)ccc1Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Solvent: CCCCCCC
Product: COC(=O)c1cnc(OCC(F)(F)F)c(-c2ccc(Cl)c(C)c2)c1
Temperature: 80 °C
Reaction time: 2.5 h
Yield: 106.4 %

Procedure:
5-Bromo-6-(2,2,2-trifluoroethoxy)-3-pyridinecarboxylic acid methyl ester (CAN 1211589-51-3; 4.0 g; 12.7 mmol) and 4-chloro-3-methylphenylboronic acid (CAN 161950-10-3; 3.26 g, 19.1 mmol) were combined in DMSO (100 mL) to give a white suspension. To this suspension was added, Na2CO3 (4.05 g, 38.2 mmol) in water (10 mL) and 1,1′-bis(diphenylphosphino)-ferrocene-palladium(II)dichloride dichloromethane complex (1.04 g, 1.27 mmol). The reaction mixture was heated to 80° C. and stirred for 2.5 h, cooled and poured into 200 mL ethyl acetate:heptane (1:1) and extracted with H2O (3×100 mL) and brine (1×150 ml). The aqueous layer was extracted with EtOAc:Heptane (1:1) (1×200 mL). The organic layers were combined, dried with Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 70 g, 0% to 100% ethyl acetate in heptane) to yield 4.86 g (90%) of the title compound as light red solid; MS (EI): 360.1 (M+H)+.