Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH2:7][S:8]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]2/[C:17](=[N:19]/[OH:20])/[NH2:18])(=[O:10])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[O:21]=[C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24](=[O:31])[N:23]1[CH2:32][C:33]1[O:37][C:36]([C:38](O)=[O:39])=[CH:35][CH:34]=1>>[CH:1]1([CH2:7][S:8]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]2/[C:17](=[N:19]/[O:20][C:38]([C:36]2[O:37][C:33]([CH2:32][N:23]3[C:24](=[O:31])[C:25]4[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=4)[C:22]3=[O:21])=[CH:34][CH:35]=2)=[O:39])/[NH2:18])(=[O:9])=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: O=C(O)c1ccc(CN2C(=O)c3ccccc3C2=O)o1
Reactant: N/C(=N\O)[C@@H]1CCCCN1S(=O)(=O)CC1CCCCC1
Product: N/C(=N\OC(=O)c1ccc(CN2C(=O)c3ccccc3C2=O)o1)[C@@H]1CCCCN1S(=O)(=O)CC1CCCCC1

Procedure:
The title compound was prepared by a similar method to Preparation 5 from (Z)-(2S)-1-[(cyclohexylmethyl)sulfonyl]-N′2-hydroxy-2-piperidinecarboximidamide [see Preparation 28] and 5-[(1,3-dioxo-2,3-dihydro-1H-2-isoindolyl)methyl]-2-furoic acid (see Preparation 98], to afford (Z)-(2S)-1-[(cyclohexylmethyl)sulfonyl]-N′2-[(5-[(1,3-dioxo-2,3-dihydro-1H-2-isoindolyl)methyl]-2-furylcarbonyl)oxy]-2-piperidinecarboximidamide as a yellow oil.
Reaction SMILES: [CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13]([SH:16])=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18].C(=O)([O-])[O-].[K+].[K+].Cl[C:26]1[S:27][C:28]2[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][C:29]=2[N:30]=1.CN(C)C=O>C(OCC)(=O)C>[CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13]([S:16][C:26]4[S:27][C:28]5[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][C:29]=5[N:30]=4)=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18]
Reactant: O=[N+]([O-])c1ccc2sc(Cl)nc2c1
Reactant: CN1C(=O)CC[C@]2(C)c3ccc(S)cc3CC[C@@H]12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CN1C(=O)CC[C@]2(C)c3ccc(Sc4nc5cc([N+](=O)[O-])ccc5s4)cc3CC[C@@H]12
Yield: 58.1 %

Procedure:
A 15 mL round bottom flask was charged with (+)-(4aR)-(10bR)-4-methyl-8-mercapto-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobezo[f]quinolin-3-one (100 mg, 0.38 mmol), potassium carbonate (158 mg, 1.14 mmol), 2-chloro-5-nitrobenzothiazole (99 mg, 0.46 mmol) and 1 mL of anhydrous dimethylformamide, fitted with a reflux condenser, and the stirred mixture was heated at 60°, under nitrogen, for 18 h. The mixture was cooled, diluted with ethyl acetate (75 mL) and washed with brine (2×25 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (ethyl acetate eluent) to give 97 mg (58%) of the title compound as an amorphous solid. mp 96°-100°. FDMS: m/e=439. α[D]589 =+61.35 (c=0.64, chloroform).
Reaction SMILES: [F:1][C@H:2]1[CH2:19][C@@:17]2([CH3:18])[C@@H:13]([CH2:14][CH2:15][C:16]2=[O:20])[C@H:12]2[C@H:3]1[C:4]1[CH:5]=[CH:6][C:7]([OH:37])=[CH:8][C:9]=1[CH2:10][C@H:11]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][N:26]([CH3:36])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35].[BH4-].[Na+].[Cl-].[Na+]>CO>[F:1][C@H:2]1[CH2:19][C@@:17]2([CH3:18])[C@@H:13]([CH2:14][CH2:15][C@@H:16]2[OH:20])[C@H:12]2[C@H:3]1[C:4]1[CH:5]=[CH:6][C:7]([OH:37])=[CH:8][C:9]=1[CH2:10][C@H:11]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][N:26]([CH3:36])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35]
Reactant: CCCCCCCCCN(C)CCCCC[C@@H]1Cc2cc(O)ccc2[C@@H]2[C@@H]1[C@@H]1CCC(=O)[C@@]1(C)C[C@@H]2F
Agent: [BH4-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Product: CCCCCCCCCN(C)CCCCC[C@@H]1Cc2cc(O)ccc2[C@@H]2[C@@H]1[C@@H]1CC[C@H](O)[C@@]1(C)C[C@@H]2F
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
85 mg of 11β-fluoro-3-hydroxy-7α-{5-[methyl-nonyl-amino]pentyl}oestra-1,3,5(10)-trien-17-one are dissolved in 3 ml of methanol and treated with 25 mg of sodium borohydride. After stirring at room temperature for 30 minutes, the solvent is for the most part stripped off in vacuo, the residue is treated with sodium chloride solution, and the mixture is extracted 3 times with methylene chloride, dried over magnesium sulphate and concentrated in vacuo. Preparative thin-layer chromatography using methylene chloride/methanol=9/1+0.5% triethylamine as a mobile phase leads to 33 mg of 11β-fluoro-7α-{5-[methyl-nonyl-amino]pentyl}-oestra-1,3,5(10)-triene-3,17β-diol as a foam.
Reaction SMILES: [CH2:1]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]=[CH:10][C:9]=1[N+:18]([O-])=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]>C1(C)C=CC=CC=1.[Pt]>[NH2:18][C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:8]=1[NH:7][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])=[CH:16][CH:15]=[CH:14][CH:13]=2
Reactant: CCCCCCNc1c([N+](=O)[O-])cnc2ccccc12
Agent: [Pt]
Solvent: Cc1ccccc1
Product: CCCCCCNc1c(N)cnc2ccccc12
Reaction time: 1.5 h

Procedure:
To a solution of 22.5 g (0.0823 mole) of 4-(n-hexyl)amino-3-nitroquinoline in 300 ml of toluene was added about 1.0 g of 5% platinum on charcoal and the mixture was hydrogenated on a Paar apparatus for 1.5 hours. Filtration followed by evaporation in vacuo provided a residue of 3-amino-4-(n-hexyl)aminoquinoline as an orange solid. Thin layer chromatographic analysis of the product on silica gel, eluting with methanol, showed one spot at Rf =0.73 and a trace at Rf=0.35.
Reaction SMILES: [CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:25]([OH:27])=[O:26])[CH2:20][CH2:21][CH2:22][CH2:23][NH2:24])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:28]1([CH2:34][S:35](Cl)(=[O:37])=[O:36])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>>[C:28]1([CH2:34][S:35]([NH:24][CH2:23][CH2:22][CH2:21][CH2:20][C@@H:19]([C:25]([OH:27])=[O:26])[NH:18][C:16]([O:15][CH2:14][CH:12]2[C:11]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[C:5]3[C:13]2=[CH:1][CH:2]=[CH:3][CH:4]=3)=[O:17])(=[O:37])=[O:36])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: O=S(=O)(Cl)Cc1ccccc1
Reactant: NCCCC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Product: O=C(N[C@@H](CCCCNS(=O)(=O)Cc1ccccc1)C(=O)O)OCC1c2ccccc2-c2ccccc21
Yield: 15 %

Procedure:
Nα-(9-fluorenylmethoxycarbonyl)-L-lysine was reacted with phenylmethylsulfonyl chloride under the conditions used in example 2 giving 15% of the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[C:12]([O:16][CH3:17])[C:13]=1[O:14][CH3:15])[CH:6]=[CH:7][C:8](Cl)=[O:9].[CH2:18]([NH:23][C:24]([CH:26]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)[CH3:27])=[O:25])[CH2:19][CH2:20][CH2:21][CH3:22]>C(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[C:12]([O:16][CH3:17])[C:13]=1[O:14][CH3:15])[CH:6]=[CH:7][C:8]([N:31]1[CH2:30][CH2:29][N:28]([CH:26]([C:24]([NH:23][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[O:25])[CH3:27])[CH2:33][CH2:32]1)=[O:9]
Reactant: CCCCCNC(=O)C(C)N1CCNCC1
Reactant: COc1cc(C=CC(=O)Cl)cc(OC)c1OC
Solvent: ClC(Cl)Cl
Product: CCCCCNC(=O)C(C)N1CCN(C(=O)C=Cc2cc(OC)c(OC)c(OC)c2)CC1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
5.62 g of 3,4,5-trimethoxycinnamoyl chloride is added with stirring at room temperature to a solution of 4.15 g of 1-[1-(pentylaminocarbonyl)ethyl]piperazine in 60 ml of chloroform, and the resulting solution is stirred at room temperature for 20 minutes.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH2:9][CH2:8][CH:7]([N:15]([CH3:17])[CH3:16])[CH2:6][C:5]2=1.[F:18][C:19]1[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=1)[C:22](Cl)=[O:23]>>[F:18][C:19]1[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=1)[C:22]([NH:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH2:9][CH2:8][CH:7]([N:15]([CH3:17])[CH3:16])[CH2:6][C:5]2=1)=[O:23]
Reactant: O=C(Cl)c1cccc(F)c1
Reactant: CN(C)C1CCc2[nH]c3ccc(N)cc3c2C1
Product: CN(C)C1CCc2[nH]c3ccc(NC(=O)c4cccc(F)c4)cc3c2C1
Yield: 66.8 %

Procedure:
Beginning with 10.4 mg (0.046 mMol) 6-amino-3-(dimethyl)amino-1,2,3,4-tetrahydro-9H-carbazole and 8.1 μL (0.051 mMol) 3-fluorobenzoyl chloride, 10.8 mg (69%) of the title compound were recovered as a beige solid.
Reaction SMILES: [C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[C:39]([CH:42]([CH3:44])[CH3:43])[C:38]2=[N:45][C:35]3=[CH:36][N:37]2[C:12]=1[N:13]1[CH2:50][CH2:49][C:16]([CH3:51])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:48])[O:23][C:24]2[CH:25]=[CH:26][C:27]([F:47])=[CH:28][C:29]=2[C:30]2[CH:46]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:15][CH2:14]1)[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].C(O[C@@H](C1C(C)=CC2=NC3=C(Cl)N2C=1N1CCC(C)(OCCCC[C@H](C)OC2C=CC(C)=CC=2C2C=C3C=CC=2)CC1)C(O)=O)(C)(C)C>>[C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[C:39]([CH:42]([CH3:43])[CH3:44])[C:38]2=[N:45][C:35]3=[CH:36][N:37]2[C:12]=1[N:13]1[CH2:14][CH2:15][C:16]([CH3:51])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:48])[O:23][C:24]2[CH:25]=[CH:26][C:27]([F:47])=[CH:28][C:29]=2[C:30]2[CH:46]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:49][CH2:50]1)[C:7]([OH:9])=[O:8])([CH3:2])([CH3:3])[CH3:4]
Reactant: COC(=O)[C@@H](OC(C)(C)C)c1c(C)c(C(C)C)c2nc3cn2c1N1CCC(C)(CC1)OCCCC[C@H](C)Oc1ccc(F)cc1-c1cccc-3c1
Agent: Cc1ccc2c(c1)-c1cccc(c1)-c1nc3cc(C)c([C@H](OC(C)(C)C)C(=O)O)c(n3c1Cl)N1CCC(C)(CC1)OCCCC[C@H](C)O2
Product: Cc1c([C@H](OC(C)(C)C)C(=O)O)c2n3cc(nc3c1C(C)C)-c1cccc(c1)-c1cc(F)ccc1O[C@@H](C)CCCCOC1(C)CCN2CC1
Yield: 98 %

Procedure:
Prepared in 98% yield from methyl(2S)-2-(tert-butoxy)-2-[(22S)-17-fluoro-4,22,28-trimethyl-5-(propan-2-yl)-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate following the procedure for (2S)-2-(tert-butoxy)-2-[(22S)-8-chloro-4,17,22,28-tetramethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetic acid. 1H NMR (500 MHz, METHANOL-d4) δ 8.15-8.10 (m, 2H), 8.00 (s, 1H), 7.51 (t, J=7.6 Hz, 1H), 7.28 (d, J=7.7 Hz, 1H), 7.13-7.07 (m, 2H), 7.06-7.00 (m, 1H), 6.01 (s, 1H), 4.55 (td, J=6.1, 3.6 Hz, 1H), 4.02 (t, J=11.2 Hz, 1H), 3.89-3.78 (m, 1H), 3.76-3.68 (m, 1H), 3.61-3.52 (m, 3H), 2.76 (d, J=10.2 Hz, 1H), 2.49 (s, 3H), 2.01-1.87 (m, 6H), 1.86-1.72 (m, 5H), 1.64 (d, J=5.2 Hz, 1H), 1.55 (dd, J=7.1, 0.9 Hz, 6H), 1.26 (s, 3H), 1.21 (s, 9H), 1.09 (d, J=6.0 Hz, 3H); LCMS (ESI, M+1): 686.4.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]1[C:8]2[CH:9]=[C:10]([O:13][CH3:14])[CH:11]=[CH:12][C:7]=2[N:6]=[CH:5]1.[F:15][C:16]([F:21])([F:20])[C:17](N)=[O:18]>>[CH3:14][O:13][C:10]1[CH:11]=[CH:12][C:7]2[N:6]=[CH:5][N:4]([CH2:3][CH2:2][NH:1][C:17](=[O:18])[C:16]([F:21])([F:20])[F:15])[C:8]=2[CH:9]=1
Reactant: NC(=O)C(F)(F)F
Reactant: COc1ccc2ncn(CCN)c2c1
Product: COc1ccc2ncn(CCNC(=O)C(F)(F)F)c2c1

Procedure:
Following the procedure of Example 13 but replacing 5-methoxytryptamine with 1-β-aminoethyl-6-methoxybenzimidazole, N-[2-(6-methoxybenzimidazol-1-yl))ethyl]-trifluoroacetamide is obtained.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:18]=[C:11]3[CH:12]=[CH:13][C:14]([C:16]#[N:17])=[CH:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1.[OH-].[Na+].[C:21](OC(=O)C)(=[O:23])[CH3:22]>S(=O)(=O)(O)O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:18]([C:21](=[O:23])[CH3:22])=[C:11]3[CH:12]=[CH:13][C:14]([C:16]#[N:17])=[CH:15][N:10]3[N:9]=2)=[CH:6][CH:7]=1
Reactant: CC(=O)OC(C)=O
Reactant: N#Cc1ccc2cc(-c3ccc(F)cc3)nn2c1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: CC(=O)c1c(-c2ccc(F)cc2)nn2cc(C#N)ccc12
Temperature: 120 °C
Reaction time: 5 h

Procedure:
A solution of 2-(4-fluorophenyl)-6-cyanopyrazolo[1,5-a]pyridine (6.7 g, 11 mmol) and concentrated sulfuric acid (2 drops) in acetic anhydride (25 mL) was heated, and stirred, at 120° C. under N2 for 5 h. The solution was cooled to room temperature, diluted with ice water and basified to pH 11 using 2 N aqueous sodium hydroxide. The solution was extracted with chloroform (3×), and the combined organic extracts were dried and the solvent was evaporated in vacuo. Trituration with methanol afforded a light brown solid which was collected and dried to give the title compound, 1.6 g (84%). 1H NMR (d6-DMSO) δ 2.19 (s, 3H), 7.35 (t, 2H, J=8.0 Hz), 7.69 (dd, 2H, J=4.0, 8.0 Hz), 7.86 (dd, 1H, J=4.0, 16 Hz), 8.30 (d, 1H, J=12 Hz), 9.75 (s, 1H). MS (ES+) m/z 280 (M++H).
Reaction SMILES: [CH2:1]([N:5]1[C:9](=[O:10])[C:8]2=[CH:11][C:12]([N+:15]([O-])=O)=[CH:13][CH:14]=[C:7]2[C:6]1=[O:18])[CH2:2][CH2:3][CH3:4].S(S([O-])=O)([O-])=O.[Na+].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>CO.O>[CH2:1]([N:5]1[C:9](=[O:10])[C:8]2=[CH:11][C:12]([NH2:15])=[CH:13][CH:14]=[C:7]2[C:6]1=[O:18])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCN1C(=O)c2ccc([N+](=O)[O-])cc2C1=O
Agent: O=C([O-])[O-]
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CCCCN1C(=O)c2ccc(N)cc2C1=O
Temperature: 70 °C
Reaction time: 0.5 h
Yield: 59.2 %

Procedure:
A solution of N-butyl-4-nitrophthalimide (1.45 g, 5.8 mmol) in methanol (30 mL) was added drop wise to a well stirred solution of sodium dithionite (6.50 g, 37.1 mmol) and sodium carbonate (3.22 g, 30.5 mmol) in water (40 mL), while the temperature was maintained at 70° C. After addition, heating at 70° C. was continued for a further 30 minutes, then the reaction mixture was allowed to cool to room temperature. The reaction volume was reduced to one third by rotary evaporation, and the residual water solution was extracted with diethyl ether (2×50 mL). The combined organic phases were dried with anhydrous Na2SO4, and then taken to dryness. The residual oil was recrystallised from ethanol/water to give 750 mg (59%) of N-butyl-4-aminophthalimide.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][NH:5][CH2:6][C:7]([F:10])([F:9])[F:8].ClCCl.Cl[C:15]([O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:16]>N1C=CC=CC=1>[Cl:1][CH2:2][CH2:3][CH2:4][N:5]([CH2:6][C:7]([F:10])([F:9])[F:8])[C:15](=[O:16])[O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: FC(F)(F)CNCCCCl
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(Oc1ccccc1)N(CCCCl)CC(F)(F)F
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Into a 500-mL round-bottom flask, was placed (3-chloropropyl)(2,2,2-trifluoroethyl)amine (5 g, 28.48 mmol, 1.00 equiv), dichloromethane (300 mL), TEA (5.8 g, 57.32 mmol, 2.00 equiv), pyridine (0.5 mL). To this was added dropwise phenyl chloroformate (4.4 g, 28.10 mmol, 1.00 equiv) at 0° C. The resulting solution was stirred for 3 h at room temperature. The resulting mixture was washed with 2×100 mL of H2O. The resulting mixture was washed with 2×100 mL of brine. The mixture was dried over sodium sulfate. The resulting mixture was concentrated under vacuum. This resulted in 1.4 g (crude) of phenyl N-(3-chloropropyl)-N-(2,2,2-trifluoroethyl)carbamate as a colorless liquide.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:4]=1[CH2:5][N:6]([C:19]1[S:23][N:22]=[CH:21][N:20]=1)[S:7]([C:10]1[CH:15]=[C:14]([F:16])[C:13](F)=[CH:12][C:11]=1[F:18])(=[O:9])=[O:8].C(=O)([O-])[O-].[K+].[K+].[Cl:36][C:37]1[CH:42]=[CH:41][C:40]([OH:43])=[C:39]([C:44]2[N:49]3[CH:50]=[CH:51][N:52]=[C:48]3[N:47]=[CH:46][CH:45]=2)[CH:38]=1>CS(C)=O.C(OCC)(=O)C.O>[Cl:36][C:37]1[CH:42]=[CH:41][C:40]([O:43][C:13]2[C:14]([F:16])=[CH:15][C:10]([S:7]([N:6]([CH2:5][C:4]3[CH:24]=[CH:25][C:26]([O:28][CH3:29])=[CH:27][C:3]=3[O:2][CH3:1])[C:19]3[S:23][N:22]=[CH:21][N:20]=3)(=[O:8])=[O:9])=[C:11]([F:18])[CH:12]=2)=[C:39]([C:44]2[N:49]3[CH:50]=[CH:51][N:52]=[C:48]3[N:47]=[CH:46][CH:45]=2)[CH:38]=1
Reactant: Oc1ccc(Cl)cc1-c1ccnc2nccn12
Reactant: COc1ccc(CN(c2ncns2)S(=O)(=O)c2cc(F)c(F)cc2F)c(OC)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CS(C)=O
Product: COc1ccc(CN(c2ncns2)S(=O)(=O)c2cc(F)c(Oc3ccc(Cl)cc3-c3ccnc4nccn34)cc2F)c(OC)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 35 %

Procedure:
To a stirred mixture of N-(2,4-dimethoxybenzyl)-2,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (0.89 g, 2.0 mmol) and potassium carbonate (0.83 g, 6.0 mmol) in dimethylsulfoxide (15 mL) at ambient temperature was added 4-chloro-2-(imidazo[1,2-a]pyrimidin-5-yl)phenol (0.45 g, 2.0 mmol). The mixture was stirred at ambient temperature for 16 h and diluted with ethyl acetate (50 mL) and water (20 mL). The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography, eluting with a 80-100% gradient of ethyl acetate in hexanes to afford 4-(4-chloro-2-(imidazo[1,2-a]pyrimidin-5-yl)phenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (0.47 g). This solid was dissolved in dichloromethane (15 mL) and trifluoroacetic acid (2 mL) was added. The mixture was stirred for 2 h at ambient temperature and concentrated in vacuo. The residue was triturated in a mixture of ethyl ether and ethyl acetate to afford 4-(4-chloro-2-(imidazo[1,2-a]pyrimidin-5-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as a colorless solid in 53% yield (0.55 g): 1H NMR (300 MHz, DMSO-d6) δ8.94 (d, J=4.2 Hz, 1H), 8.52 (s, 1H), 8.18 (d, J=1.5 Hz, 1H), 8.07 (d, J=1.2 Hz, 1H), 7.91-7.69 (m, 3H), 7.61 (d, J=4.2 Hz, 1H), 7.56-7.47 (m, 1H), 7.43 (d, J=8.7 Hz, 1H); MS (ES+) m/z 520.7 (M+1), 522.7 (M+1).
Reaction SMILES: [OH:1][C:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[S:5](=[O:13])(=[O:12])[NH:4][C:3]=1[C:14]([O:16][CH2:17][CH2:18][O:19][CH3:20])=[O:15].[CH3:21]I.[OH-].[Na+]>CC(C)=O>[OH:1][C:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[S:5](=[O:12])(=[O:13])[N:4]([CH3:21])[C:3]=1[C:14]([O:16][CH2:17][CH2:18][O:19][CH3:20])=[O:15]
Reactant: CI
Reactant: COCCOC(=O)C1=C(O)c2ccccc2S(=O)(=O)N1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Product: COCCOC(=O)C1=C(O)c2ccccc2S(=O)(=O)N1C
Temperature: 25 °C
Yield: 90.2 %

Procedure:
2-Methoxyethyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (31.0 g., 0.1035 mole) was combined with 230 ml. of acetone and cooled to 10° C. Methyl iodide (21.9 g., 0.155 mole) was added, followed by the dropwise addition, over 10 minutes, of sodium hydroxide (103.5 ml. of 1 N). The cooling bath was removed and the reaction mixture allowed to slowly warm to room temperature (about 45 minutes), then heated at 35° C. for 2 hours and finally at 39°-40° C. for 16 hours. The reaction mixture was cooled to room temperature, diluted with 200 ml. of acetone, treated with activated carbon, filtered and concentrated in vacuo at 0°-5° C. to about 50 ml. The resulting slurry was filtered, and solids washed with ice-water and then dried in vacuo to yield 2-methoxyethyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide [29.26 g., 90%; m.p. 106°-107.5° C.; m/e 313; ir(KBr) 3345, 2941, 1684, 1351, 1053 cm-1 ].
Reaction SMILES: [CH2:1]([N:3]([CH2:15][CH2:16][CH2:17][S:18][CH2:19][CH2:20][CH3:21])[CH2:4][CH:5]([C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=1)[OH:6])[CH3:2].ClC1C=CC=C(C(OO)=[O:30])C=1>>[CH2:1]([N:3]([CH2:15][CH2:16][CH2:17][S:18]([CH2:19][CH2:20][CH3:21])=[O:30])[CH2:4][CH:5]([C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=1)[OH:6])[CH3:2]
Reactant: CCCSCCCN(CC)CC(O)c1ccc(C#N)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Product: CCCS(=O)CCCN(CC)CC(O)c1ccc(C#N)cc1
Yield: 73.9 %

Procedure:
0.9 g of 4-[2-[ethyl[3-(propylthio)propyl]amino]-1-hydroxyethyl]-benzonitrile was oxidized with 0.7 g of m-chloroperbenzoic acid in analogy with example 2. Yield: 0.7 g of the title compound.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[CH2:10][CH2:11][CH2:12][CH:13]([NH:17][C:18](=[O:20])[CH3:19])[C:14]=2[C:15]=1[OH:16])=[O:5])C>[OH-].[Na+]>[C:18]([NH:17][CH:13]1[CH2:12][CH2:11][CH2:10][C:9]2[N:8]=[CH:7][C:6]([C:4]([OH:5])=[O:3])=[C:15]([OH:16])[C:14]1=2)(=[O:20])[CH3:19]
Reactant: CCOC(=O)c1cnc2c(c1O)C(NC(C)=O)CCC2
Agent: [Na+]
Agent: [OH-]
Product: CC(=O)NC1CCCc2ncc(C(=O)O)c(O)c21
Temperature: 110 °C
Yield: 55.6 %

Procedure:
5-Acetamido-4-hydroxy-5,6,7,8-tetrahydroquinoline-3-carboxylic acid ethyl ester (0.8 g) was suspended in 20 ml of 1 N sodium hydroxide. The resulting reaction mixture was heated on an oil bath at 110° C. for 2 hours. After being cooled, the reaction mixture was filtered to remove the insoluble matter, and the filtrate was adjusted to pH 2.5 with dilute hydrochloric acid. The precipitate so formed was separated by filtration to obtain a yield of 0.4 g of the desired compound. This compound melted (and decomposed) at 285°-287° C. (uncorrected values). Its infrared absorption spectrum (KBr tablet) had absorption peaks at 3420, 3340, 3260, 3080, 2940, 1710, 1650, 1635, 1290, and 810 cm-1. and its n.m.r. spectrum (CF3COOH, 60Mc, TMS) had signals at δ values of 1.8-2.6 (4H, m), 2.43 (3H, s), 2.9-3.5 (2H, m), 5.72 (1H, d, J=8.3 Hz), 8.47 (1H, d, J=8.3 Hz), and 9.0-9.3 (1H, m).
Reaction SMILES: [N:1]1([CH:6]2[CH2:20][CH:9]3[CH2:10][N:11](C(OC(C)(C)C)=O)[CH2:12][CH:8]3[CH2:7]2)[CH:5]=[N:4][N:3]=[N:2]1>Cl.O1CCOCC1>[N:1]1([CH:6]2[CH2:20][CH:9]3[CH2:10][NH:11][CH2:12][CH:8]3[CH2:7]2)[CH:5]=[N:4][N:3]=[N:2]1
Reactant: CC(C)(C)OC(=O)N1CC2CC(n3cnnn3)CC2C1
Agent: Cl
Solvent: C1COCCO1
Product: c1nnnn1C1CC2CNCC2C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 92 %

Procedure:
The title compound from Step A above (670 mg, 2.4 mmol) was dissolved in 4 M HCl in dioxane (5 mL) and stirred at RT overnight. The product was concentrated under reduced pressure and dried under high vacuum to afford the title compound (i-38) (395 mg, 92%). EST-MS calculated for C8H13N5: Exact Mass: 179.09. Found 180.05.
Reaction SMILES: C[O:2][C:3](=[O:44])[C@@H:4]([NH:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[C:36](=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13]/[CH:14]=[CH:15]/[C:16]2[CH:28]=[CH:27][C:26]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH2:19][C:18]=3[CH:17]=2)=[CH:8][CH:7]=1.[OH-].[Na+]>C(O)C.C1COCC1>[C:36]([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=1[NH:29][C@@H:4]([CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13]/[CH:14]=[CH:15]/[C:16]2[CH:28]=[CH:27][C:26]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH2:19][C:18]=3[CH:17]=2)=[CH:8][CH:7]=1)[C:3]([OH:44])=[O:2])(=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: COC(=O)[C@H](Cc1ccc(OC/C=C/c2ccc3c(c2)Cc2ccccc2-3)cc1)Nc1ccccc1C(=O)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: O=C(c1ccccc1)c1ccccc1N[C@@H](Cc1ccc(OC/C=C/c2ccc3c(c2)Cc2ccccc2-3)cc1)C(=O)O
Temperature: 25 °C
Reaction time: 16 h
Yield: 88.4 %

Procedure:
(E)-(S)-2-(2-Benzoyl-phenylamino)-3-{4-[3-(9H-fluoren-2-yl)-allyloxy]-phenyl}-propionic acid methyl ester (example 3) (600 mg, 1.0 mmol) was dissolved in a mixture of ethanol (20 ml) and THF (10 ml). 1N NaOH (5 ml) was added and the mixture was stirred for 16 h at room temperature. The mixture was concentrated in vacuo. Water (5 ml) and ethyl acetate (10 ml) was added. The mixture was neutralised with 1N HCl. The aqueous phase was isolated and extracted with ethyl acetate (×2) The organic layers were combined, washed with water, dried (MgSO4) and evaporated to give 500 mg of the title compound.
Reaction SMILES: C1(C)C=CC(S([Cl:10])(=O)=O)=CC=1.[CH2:12]([N:14]1[C:18](=[O:19])[C:17](=[C:20](O)[CH:21]=[C:22]2[N:26]([CH2:27][CH3:28])[C:25]3[CH:29]=[CH:30][CH:31]=[CH:32][C:24]=3[S:23]2)[S:16][C:15]1=[S:34])[CH3:13]>N1C=CC=CC=1.C(#N)C>[CH2:12]([N:14]1[C:18](=[O:19])[C:17](=[C:20]([Cl:10])[CH:21]=[C:22]2[N:26]([CH2:27][CH3:28])[C:25]3[CH:29]=[CH:30][CH:31]=[CH:32][C:24]=3[S:23]2)[S:16][C:15]1=[S:34])[CH3:13]
Reactant: CCN1C(=O)C(=C(O)C=C2Sc3ccccc3N2CC)SC1=S
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CC#N
Solvent: c1ccncc1
Product: CCN1C(=O)C(=C(Cl)C=C2Sc3ccccc3N2CC)SC1=S
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
p-Toluenesulfonyl chloride (1.15 g, 0.006 mol) is added to 3-ethyl-5[(3-ethyl-2-benzothiazolinylidene)-1-hydroxyethylidene]rhodanine (1.82 g, 0.005 mol) in dry pyridine (15 ml). After stirring for 30 min. at room temperature, the solution is diluted with acetonitrile (25 ml), chilled and the dye collected, washed with acetonitrile, then ether. The yield is 0.74 g (39%)