Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2](C(OC(C)(C)C)=O)[CH:3]([CH2:5]/[CH:6]=[CH:7]/[C:8]1[CH:9]=[N:10][CH:11]=[C:12]([O:14][CH2:15][CH3:16])[CH:13]=1)[CH3:4].FC(F)(F)C(O)=O>C1(OC)C=CC=CC=1>[CH3:1][NH:2][CH:3]([CH2:5]/[CH:6]=[CH:7]/[C:8]1[CH:9]=[N:10][CH:11]=[C:12]([O:14][CH2:15][CH3:16])[CH:13]=1)[CH3:4]
Reactant: CCOc1cncc(/C=C/CC(C)N(C)C(=O)OC(C)(C)C)c1
Solvent: COc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: CCOc1cncc(/C=C/CC(C)NC)c1
Reaction time: 0.75 h
Yield: 99.9 %

Procedure:
Under a nitrogen atmosphere, a cold (0–5° C.), stirring solution of (4E)-N-methyl-N-(tert-butoxycarbonyl)-5-(5-ethoxy-3-pyridyl)-4-penten-2-amine (0.67 g, 2.09 mmol) in anisole (10 mL) was treated dropwise over 30 min with trifluoroacetic acid (10.40 g, 91.17 mmol). The resulting solution was stirred for 45 min at 0–5° C. and was then concentrated by rotary evaporation. The light-yellow oil was further dried under high vacuum at 0.5 mm Hg. The resulting oil was cooled (0–5° C.), basified with 10% NaOH solution (10 mL), treated with saturated NaCl solution (7.5 mL), and extracted with CHCl3 (4×10 mL). The combined light-yellow CHCl3 extracts were washed with saturated NaCl solution (20 mL), dried (Na2SO4), filtered, concentrated by rotary evaporation, followed by further drying at 0.5 mm Hg producing a brown oil (0.46 g). The crude product was purified by column chromatography on silica gel (56 g), eluting with CH3OH-Et3N (98:2, v/v). Selected fractions containing the product (Rf 0.35) were combined and concentrated on a rotary evaporator. The residue was dissolved in CHCl3, and the CHCl3 solution was dried (Na2SO4), filtered, concentrated by rotary evaporation, and vacuum dried to give 327.5 mg (71.0%) of a light-yellow oil.
Reaction SMILES: [NH2:1][C:2]1[N:3]=[CH:4][N:5]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:13][CH:12]=2)[C:6]=1[C:7]([NH2:9])=[O:8].[C:21]([O:25][C:26]([N:28]([C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=1)[C:33](O)=[O:34])[CH3:29])=[O:27])([CH3:24])([CH3:23])[CH3:22]>>[C:17]([C:14]1[CH:15]=[CH:16][C:11]([CH2:10][N:5]2[C:6]([C:7]([NH2:9])=[O:8])=[C:2]([NH:1][C:33](=[O:34])[C:32]3[CH:36]=[CH:37][CH:38]=[C:30]([N:28]([C:26]([O:25][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:27])[CH3:29])[CH:31]=3)[N:3]=[CH:4]2)=[CH:12][CH:13]=1)([CH3:20])([CH3:19])[CH3:18]
Reactant: CN(C(=O)OC(C)(C)C)c1cccc(C(=O)O)c1
Reactant: CC(C)(C)c1ccc(Cn2cnc(N)c2C(N)=O)cc1
Product: CN(C(=O)OC(C)(C)C)c1cccc(C(=O)Nc2ncn(Cc3ccc(C(C)(C)C)cc3)c2C(N)=O)c1
Yield: 65 %

Procedure:
An amidation reaction and post-treatment were carried out under the same conditions as in Example 17, using 4.31 g (14.0 mmol) of 4-amino-1-(4-t-butylbenzyl)-5-imidazolecarboxamide which was prepared in the same manner as in Example 57 and 3-(N-t-butyloxycarbonyl-N-methylamino)benzoic acid instead of 3-pyridylacetic acid hydrochloride to obtain 4.59 g of 1-(4-t-butylbenzyl)-4-(3-(N-t-butyloxycarbonyl-N-methylamino)benzoylamino)-5-imidazolecarboxamide (yield 65%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][OH:8])=[CH:5][CH:4]=1.C(N(CC)CC)C.[Br:18][CH2:19][CH2:20][CH2:21][C:22](Cl)=[O:23]>ClCCl>[Br:18][CH2:19][CH2:20][CH2:21][C:22]([O:8][CH2:7][C:6]1[CH:9]=[CH:10][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)=[O:23]
Reactant: O=C(Cl)CCCBr
Reactant: COc1ccc(CO)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(COC(=O)CCCBr)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of 4-methoxybenzyl alcohol and triethylamine in dichloromethane was added 4-bromobutyryl chloride at 0° C. The mixture was stirred at 0° C. for 30 minutes, and the solvent was evaporated. The residue was diluted with ethyl acetate, and the organic solution was washed with water and brine, dried over magnesium sulfate and concentrated. The concentrate was chromatographed on a silica gel column to give the object compound.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[O:11])=[CH:2]1.[Cl:12][C:13]1[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:14]=1[S:20](Cl)(=[O:22])=[O:21].C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>C(Cl)Cl>[Cl:12][C:13]1[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:14]=1[S:20]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[O:11])=[CH:2]1)(=[O:22])=[O:21]
Reactant: O=S(=O)(Cl)c1cccc(Cl)c1Cl
Reactant: O=Cc1c[nH]c2ccccc12
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=Cc1cn(S(=O)(=O)c2cccc(Cl)c2Cl)c2ccccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 80.2 %

Procedure:
A solution of 1H-indole-3-carboxaldehyde (0.290 g, 2.00 mmol) in methylene chloride (4 mL) was added with 2,3-dichlorophenylsulfonyl chloride (0.589 g, 2.40 mmol) and diisopropylethylamine (0.310 g, 2.40 mmol), and the mixture was stirred overnight at room temperature. The reaction mixture was added with saturated aqueous sodium hydrogencarbonate to terminate the reaction, and then extracted three times with methylene chloride. The organic layer was dried over anhydrous magnesium sulfate, then the solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain 1-(2,3-dichlorophenylsulfonyl)-1H-indole-3-carboxaldehyde (0.568 g, 80%).
Reaction SMILES: C[C@@:2]12[C@@H:18]([OH:19])[C@H:17](O)[CH2:16][C@H:15]1[C@H]1[C@@H](C3C=CC(O)=CC=3CC1)CC2>N1C=CC=CC=1>[CH2:2]1[CH2:18][CH2:17][CH:16]([O:19][CH:18]2[CH2:2][CH2:15][CH2:16][CH2:17]2)[CH2:15]1
Reactant: C[C@]12CC[C@@H]3c4ccc(O)cc4CC[C@H]3[C@@H]1C[C@@H](O)[C@@H]2O
Solvent: c1ccncc1
Product: C1CCC(OC2CCCC2)C1

Procedure:
In a vial, protected against the light, is dissolved: 2.5g of 3-cyclopentyl ether of estriol obtained in (a) above, in 25 cc of anhydrous pyridine.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:14]=[C:13]([OH:15])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Br:16])[CH:11]=2)[CH:6]=1)=[O:4].C(=O)([O-])[O-].[K+].[K+].C(S([C:28]1[CH:33]=[CH:32][C:31]([S:34]([CH2:37][CH3:38])(=[O:36])=[O:35])=[CH:30][N:29]=1)(=O)=O)C.CN(C)C=O>C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:14]=[C:13]([O:15][C:28]2[CH:33]=[CH:32][C:31]([S:34]([CH2:37][CH3:38])(=[O:35])=[O:36])=[CH:30][N:29]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Br:16])[CH:11]=2)[CH:6]=1)=[O:4]
Reactant: CCS(=O)(=O)c1ccc(S(=O)(=O)CC)nc1
Reactant: COC(=O)c1cc(O)c2cc(Br)ccc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCS(=O)(=O)c1ccc(Oc2cc(C(=O)OC)cc3ccc(Br)cc23)nc1
Temperature: 100 °C
Yield: 41.5 %

Procedure:
A mixture of 6-bromo-4-hydroxy-naphthalene-2-carboxylic acid methyl ester (423 mg, 1.5 mmol), potassium carbonate (414 mg, 3 mmol), 2,5-bis-ethanesulfonyl-pyridine (420 mg, 1.6 mmol) and N,N-dimethylformamide (4 mL) was vigorously stirred and heated at 100° C. overnight under an argon atmosphere, then cooled to room temperature, and diluted with ethyl acetate (10 mL). The resulting mixture was washed with water (10 mL×3). The combined aqueous layers were extracted with ethyl acetate (10 mL). The organic layers were combined, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography (silica gel, 100-200 mesh, 30% ethyl acetate in petroleum ether) to give 6-bromo-4-(5-ethanesulfonyl-pyridin-2-yloxy)-naphthalene-2-carboxylic acid methyl ester (280 mg, 41%, crude yield) as a yellow solid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18](=[O:28])[CH:19]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=3)[OH:20])=[CH:14][CH:15]=2)[CH:10]=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.[CH3:35][S:36](Cl)(=[O:38])=[O:37]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18](=[O:28])[CH:19]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=3)[O:20][S:36]([CH3:35])(=[O:38])=[O:37])=[CH:14][CH:15]=2)[CH:10]=[N:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)n1ncc2cc(NC(=O)C(O)c3cccc(Cl)c3)ccc21
Reactant: CS(=O)(=O)Cl
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)n1ncc2cc(NC(=O)C(OS(C)(=O)=O)c3cccc(Cl)c3)ccc21
Yield: 99.9 %

Procedure:
5-Amino-indazole-1-carboxylic acid tert-butyl ester was prepared following the procedure outlined by S. J. Brickner, WO9002744. 5-Amino-indazole-1-carboxylic acid tert-butyl ester was then coupled with 2-(3-chlorophenyl)-2-hydroxyacetic acid following the procedure as described in Example 1 to afford 5-[2-(3-chloro-phenyl)-2-hydroxy-acetylamino]-indazole-1-carboxylic acid tert-butyl ester. To a solution of 5-[2-(3-chloro-phenyl)-2-hydroxy-acetylamino]-indazole-1-carboxylic acid tert-butyl ester (7.47 mmol) in dry THF (20 mL) at 0° C. was added pyridine (37.33 mmol, 5 equivalents) followed by methanesulfonyl chloride (22.40 mmol, 3 equivalents) added in a dropwise fashion. The resultant solution was stirred at ambient temperature overnight. The reaction mixture was then concentrated in vacuo and the resulting oil was partitioned between EtOAc and brine. The organic layer was washed with brine (thrice), dried over sodium sulphate, filtered and concentrated in vacuo to afford the title compound (3.58 g, qunatitative yield), which was used without further purification.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH2:13][CH3:14])[C:9]=2[NH:15][C:16]2[O:17][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N:19][N:20]=2)=[CH:4][CH:3]=1.[CH2:27]([O:29][C:30]([C:32]1([C:35]2[CH:40]=[CH:39][C:38](B3OC(C)(C)C(C)(C)O3)=[CH:37][CH:36]=2)[CH2:34][CH2:33]1)=[O:31])[CH3:28]>Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH2:27]([O:29][C:30]([C:32]1([C:35]2[CH:40]=[CH:39][C:38]([C:2]3[CH:7]=[CH:6][C:5]([C:8]4[O:12][N:11]=[C:10]([CH2:13][CH3:14])[C:9]=4[NH:15][C:16]4[O:17][C:18]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)=[N:19][N:20]=4)=[CH:4][CH:3]=3)=[CH:37][CH:36]=2)[CH2:33][CH2:34]1)=[O:31])[CH3:28]
Reactant: CCc1noc(-c2ccc(Br)cc2)c1Nc1nnc(-c2ccccc2)o1
Reactant: CCOC(=O)C1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(CC)c4Nc4nnc(-c5ccccc5)o4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 1, Step 10, using [5-(4-bromo-phenyl)-3-ethyl-isoxazol-4-yl]-(5-phenyl-[1,3,4]oxadiazol-2-yl)-amine and 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarboxylic acid ethyl ester. (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) was used in place of tetrakis(triphenylphosphine)palladium(0).
Reaction SMILES: C([Li])CCC.CC1(C)CCCC(C)(C)N1.[I:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1.C([O:27][B:28](OC(C)C)[O:29]C(C)C)(C)C.Cl>O1CCCC1>[F:23][C:20]1[CH:21]=[CH:22][C:17]([I:16])=[CH:18][C:19]=1[B:28]([OH:29])[OH:27]
Reactant: Fc1ccc(I)cc1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: CC1(C)CCCC(C)(C)N1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OB(O)c1cc(I)ccc1F
Temperature: -78 °C
Reaction time: 3 h

Procedure:
Add a 2 M solution of n-butyllithium in hexanes (63 mL, 157.5 mmol) to a −20° C. solution of 2,2,6,6-tetramethylpiperidine (28 mL, 165 mmol) in tetrahydrofuran (400 μL). Cool to −78° C. and add 1-iodo-4-fluorobenzene (17.3 mL, 150 mmol) dropwise over 10 min. Stir the reaction mixture at −78° C. for 3 h and add triisopropylborate (40 mL, 172.5 mmol) dropwise over 20 min. Stir for another 30 min and warm the reaction to 40° C. and add of 5 N hydrochloric acid (75 mL). Partition the reaction mixture between diethyl ether (500 mL) and add 1 N hydrochloric acid (500 mL). Separate the organic layer and extract with 2 N sodium hydroxide (400 mL). Make the aqueous layer slightly acidic (pH ˜5-6) by dropwise addition of 5 N hydrochloric acid and collect the resulting white precipitate by filtration. Dry the precipitate overnight under vacuum to provide 2-fluoro-5-iodophenylboronic acid as a white solid, which is used directly without further purification (39g, 98%).
Reaction SMILES: [O:1]([CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:13]=[C:14]([C:21]([OH:23])=[O:22])[C:15](=[CH:19][CH:20]=1)[C:16]([OH:18])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC(=O)C)(=O)C>>[O:1]([CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:13]=[C:14]2[C:21](=[O:22])[O:23][C:16](=[O:18])[C:15]2=[CH:19][CH:20]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1ccc(OCCCOc2ccccc2)cc1C(=O)O
Solvent: CC(=O)OC(C)=O
Product: O=C1OC(=O)c2cc(OCCCOc3ccccc3)ccc21

Procedure:
4-(3-phenoxypropoxy)phthalic acid (41 g; 0.134 mole) was refluxed for 30 minutes with excess acetic anhydride and the product evaporated to dryness in vacuo. Recrysta lisation of the resulting white solid from ethyl acetate afforded material of m.p. 96°-98°. (Found; C, 68.48; H, 4.75; C17H14O5 requires; C, 68.45; H, 4.73%).
Reaction SMILES: [C:1]([O:9][CH:10]([CH3:14])[C:11]([NH2:13])=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:24])=CC=1>COCCOC.C(OCC)(=O)C>[C:1]([O:9][CH:10]([CH3:14])[C:11]([NH2:13])=[S:24])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(OC(=O)c1ccccc1)C(N)=O
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: COCCOC
Solvent: CCOC(C)=O
Product: CC(OC(=O)c1ccccc1)C(N)=S
Temperature: 25 °C
Reaction time: 24 h
Yield: 148.4 %

Procedure:
To a solution of 2-amino-1-methyl-2-oxoethyl benzoate (10.0 g, 52.0 mmol) in 1,2-dimethoxyethane (90 mL) was added Lawesson's reagent (11.2 g, 27.7 mmol) at 0° C. and the reaction mixture was allowed to warm up to room temperature. The resulting mixture was stirred at room temperature for 24 hours and the precipitate was removed by filtration. The resulting solution was concentrated under reduced pressure to give a residue. The residue was dissolved in ethyl acetate and the solution was washed with brine. The organic solution was dried, and concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography (hexane-ethyl acetate=2:1) to obtain a crude crystal. The crude crystal was recrystallized from ethyl acetate-hexane to give a title compound (8.60 g, yield 79%).
Reaction SMILES: [F:1][C:2]([F:6])([F:5])[CH2:3][OH:4].C(N(CC)CC)C.[CH3:14][S:15](Cl)(=[O:17])=[O:16]>C(OCC)(=O)C>[CH3:14][S:15]([O:4][CH2:3][C:2]([F:6])([F:5])[F:1])(=[O:17])=[O:16]
Reactant: CS(=O)(=O)Cl
Reactant: OCC(F)(F)F
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CS(=O)(=O)OCC(F)(F)F
Reaction time: 1 h

Procedure:
To a mixture of 2,2,2-trifluoroethanol (5 g), triethylamine (14 ml) and ethyl acetate (120 ml) was added dropwise methanesulfonyl chloride (5.8 ml) with cooling it on ice, and stirred at this temperature for 1 hour. The reaction solution was filtered through a small amount of silica gel, followed by NH silica gel, which in turn was washed with ethyl acetate. The filtrate was concentrated under reduced pressure to yield the title compound (9.5 g).
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[O:25]=[C:26]1[C:38]2[C:37]3[C:36]([C:39]([O:41][CH3:42])=[O:40])=[CH:35][CH:34]=[CH:33][C:32]=3[NH:31][C:30]=2[CH2:29][NH:28][CH2:27]1.[CH2:43]([O:50][C:51]([NH:53][C:54]([CH3:59])([CH3:58])[C:55](O)=[O:56])=[O:52])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH2:43]([O:50][C:51]([NH:53][C:54]([CH3:59])([CH3:58])[C:55]([N:28]1[CH2:27][C:26](=[O:25])[C:38]2[C:37]3[C:36]([C:39]([O:41][CH3:42])=[O:40])=[CH:35][CH:34]=[CH:33][C:32]=3[NH:31][C:30]=2[CH2:29]1)=[O:56])=[O:52])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1
Reactant: COC(=O)c1cccc2[nH]c3c(c12)C(=O)CNC3
Reactant: CC(C)(NC(=O)OCc1ccccc1)C(=O)O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COC(=O)c1cccc2[nH]c3c(c12)C(=O)CN(C(=O)C(C)(C)NC(=O)OCc1ccccc1)C3

Procedure:
A solution of HATU (86 mg) in DMF (2 ml) was added to a mixture of methyl 4-oxo-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-5-carboxylate (36 mg), 2-(((benzyloxy)carbonyl)amino)-2-methylpropanoic acid (21 mg), diisopropylethylamine (58) and DMF (8 ml) and the resultant mixture was stirred at ambient temperature for 16 hours. The DMF was evaporated to give methyl 2-(2-(((benzyloxy)carbonyl)amino)-2-methylpropanoyl)-4-oxo-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-5-carboxylate which was used in the next step without further purification.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[S:10][CH2:9][CH2:8][C:6]=2[N:7]=1.C(N(C(C)C)CC)(C)C.[NH2:21][CH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1>O1CCOCC1>[Cl:1][C:2]1[N:3]=[C:4]([NH:21][CH:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[S:10][CH2:9][CH2:8][C:6]=2[N:7]=1
Reactant: Clc1nc(Cl)c2c(n1)CCS2
Reactant: NC1CCOCC1
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: Clc1nc2c(c(NC3CCOCC3)n1)SCC2
Temperature: 130 °C

Procedure:
0.68 g (II) are placed in 6 ml dioxane, then 1.72 ml diisopropylethylamine followed by 0.6 g 4-aminotetrahydropyran are added. The reaction mixture is heated to 130° C. until there is no further reaction and after cooling evaporated down. The product is treated with water in the ultrasound bath and the solid is suction filtered and dried. 0.66 g (III-3) are obtained. Analytical HPLC-MS (method A): RT=1.08 min.
Reaction SMILES: [CH2:1]1[CH2:6]CC(N=C=NC2CCCCC2)C[CH2:2]1.[C:16]([O:20][C:21]([NH:23][CH2:24][C:25]([C:27]1[CH:37]=[CH:36][C:30]([O:31][CH2:32][C:33]([OH:35])=[O:34])=[CH:29][CH:28]=1)=[O:26])=[O:22])([CH3:19])([CH3:18])[CH3:17].CC(O)C>CCOC(C)=O.CN(C1C=CN=CC=1)C>[CH:1]([O:34][C:33](=[O:35])[CH2:32][O:31][C:30]1[CH:29]=[CH:28][C:27]([C:25](=[O:26])[CH2:24][NH:23][C:21]([O:20][C:16]([CH3:19])([CH3:17])[CH3:18])=[O:22])=[CH:37][CH:36]=1)([CH3:6])[CH3:2]
Reactant: CC(C)(C)OC(=O)NCC(=O)c1ccc(OCC(=O)O)cc1
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: CC(C)O
Solvent: CCOC(C)=O
Product: CC(C)OC(=O)COc1ccc(C(=O)CNC(=O)OC(C)(C)C)cc1
Reaction time: 2 h

Procedure:
A solution of DCC (2.06 g; 10 mmol) in EtOAc (10 ml) was added with stirring, at 0° C. to a mixture of the compound of example 1f (2.78 g; 9 mmol) and propane-2-ol (2 ml) in EtOAc (20 ml). DMAP (1.1 g; 9 mmol) was added after 10 min and stirring continued for 2 h at 0° C. The reaction mixture was stored in a freezer overnight. The precipitated DCU was filtered and the filtrate was washed with brine, dried (Na2SO4), concentrated and purified using flash chromatography (silica gel, 5% CH3CN in CHCl3) to obtain the title compound. Yield, 3.0 g (94.9%); mp, 62-64° C. (EtOAc-PE 60-80° C.); analysis: C18H25NO6 requires C, 61.53; H, 7.17; N, 3.99. found: C, 61.94; H, 7.19; N, 3.95%.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH2:6][C:7]1[C:8](=[O:13])[CH2:9][CH:10]([OH:12])[CH:11]=1)=[O:5])[CH3:2].[O:14]1[CH:19]=[CH:18][CH2:17][CH2:16][CH2:15]1>ClCCl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:1]([O:3][C:4]([CH2:6][C:7]1[C:8](=[O:13])[CH2:9][CH:10]([O:12][CH:15]2[CH2:16][CH2:17][CH2:18][CH2:19][O:14]2)[CH:11]=1)=[O:5])[CH3:2]
Reactant: C1=COCCC1
Reactant: CCOC(=O)CC1=CC(O)CC1=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: O
Product: CCOC(=O)CC1=CC(OC2CCCCO2)CC1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 95.1 %

Procedure:
100 g of 2-ethoxycarbonylmethyl-4-hydroxy-2-cyclopenten-1-one was dissolved in 1000 ml dichloromethane, and added with 55 g of 3,4-dihydro-2H-pyran and 2 g of p-toluenesulfonic acid monohydrate, and then stirred at room temperature for about 3 hours. Upon completion of the reaction, the reaction mixture was washed with 400 ml of a saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and concentrated to obtain 2-ethoxycarbonylmethyl-4-tetrahydropyranyloxy-2-cyclopenten-1-one (138.5 g). 1H-NMR (CDCl3/TMS): δ 7.40-7.68 (m, 1H), 4.70˜5.02 (m, 2H), 4.15 (q, 2H), 3.88 (m, 1H), 3.54 (m,1H), 3.23 (q, 2H), 2.79 (m,1H), 2.37 (m, 1H), 1.77 (m, 2H), 1.55 (m, 4H), 1.25 (t, 3H).
Reaction SMILES: [N:1]1([CH2:6][C:7]([OH:9])=[O:8])[CH:5]=[N:4][N:3]=[N:2]1.Cl.O1CCOC[CH2:12]1>CO>[N:1]1([CH2:6][C:7]([O:9][CH3:12])=[O:8])[CH:5]=[N:4][N:3]=[N:2]1
Reactant: C1COCCO1
Reactant: O=C(O)Cn1cnnn1
Agent: Cl
Solvent: CO
Product: COC(=O)Cn1cnnn1

Procedure:
A mixture of tetrazol-1-yl acetic acid (5 g, 39 mmol) and 4M hydrochloric acid in dioxan (100 μL) in methanol (50 mL) was heated under reflux for 18 hours. The cooled mixture was evaporated under reduced pressure to provide the title compound.
Reaction SMILES: [OH:1][N:2]=[C:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:4]#[N:5].[CH3:12][O:13][C:14]1[C:15]2[C:20]([C:21]([O:32][CH3:33])=[C:22]3[C:27]=1[CH:26]=[C:25]([S:28](Cl)(=[O:30])=[O:29])[CH:24]=[CH:23]3)=[CH:19][CH:18]=[CH:17][CH:16]=2.ClCCl>C(N(CC)CC)C>[CH3:12][O:13][C:14]1[C:15]2[C:20]([C:21]([O:32][CH3:33])=[C:22]3[C:27]=1[CH:26]=[C:25]([S:28]([O:1][N:2]=[C:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:4]#[N:5])(=[O:30])=[O:29])[CH:24]=[CH:23]3)=[CH:19][CH:18]=[CH:17][CH:16]=2
Reactant: COc1c2ccccc2c(OC)c2cc(S(=O)(=O)Cl)ccc12
Reactant: N#CC(=NO)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1c2ccccc2c(OC)c2cc(S(=O)(=O)ON=C(C#N)c3ccccc3)ccc12
Yield: 93.8 %

Procedure:
From a mixture of 1.26 g of 2-hydroxyimino-2-phenylacetonitrile, 2.91 g of 9,10-dimethoxyanthracene-2-sulfonyl chloride, 50 ml of dichloromethane, and 0.87 g of triethylamine was obtained 3.61 g of a yellow solid product by the same procedures as in Example 1. The light irradiation was carried out on this compound in the same way as in Example 1, and the leuco dye of the above formula (VI) was added. The compound became a brilliant blue color, and the generation of an acid was observed.
Reaction SMILES: [C:1]1([NH:7][C:8](=S)[NH:9][NH2:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.Cl[CH2:14][C:15]([CH2:17][C:18](=O)[CH3:19])=[O:16]>O1CCCC1>[NH:7]([C:8]1[C:17]([C:15](=[O:16])[CH3:14])=[C:18]([CH3:19])[NH:10][N:9]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(=O)CC(=O)CCl
Reactant: NNC(=S)Nc1ccccc1
Agent: Cl
Solvent: C1CCOC1
Product: CC(=O)c1c(Nc2ccccc2)n[nH]c1C
Reaction time: 12 h

Procedure:
50 g of 4-phenylthiosemicarbazide is suspended in 300 ml of tetrahydrofuran and 0.5 ml of concentrated HCl is added. Then 40.4 g of 3-chloroacetyl acetone is allowed to run in all at once and the whole is cooled with an ice-bath. After 12 hours' stirring, the precipitate formed is suction filtered, washed with acetone and then boiled in a water/acetone mixture (1:1). This hot solution is filtered off from the sulfur and neutralized with aqueous ammonia solution. The product is then suction filtered and recrystallized from acetone; m.p. 246°-247° C.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][N:8]=2)[CH:3]=[CH:2]1.C1C=C(Cl)C=C(C(OO)=[O:18])C=1>C1COCC1>[NH:1]1[C:9]2=[N+:8]([O-:18])[CH:7]=[CH:6][CH:5]=[C:4]2[CH:3]=[CH:2]1
Reactant: c1cnc2[nH]ccc2c1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: C1CCOC1
Product: [O-][n+]1cccc2cc[nH]c21
Yield: 34 %

Procedure:
7-Azaindole (commercially available from Aldrich) (Intermediate C1) (31 mmol) in THF (70 mL) was reacted with MCPBA: 3-chloroperoxybenzoic acid (˜35 mmol) at rt for 18 h. The solvent was removed under reduced pressure and partitioned between 2N NaOH and ethyl acetate. The product was extracted multiple times with ethyl acetate and the layers were combined, dried over Na2SO4, filtered, and reduced under vacuum. The residue was purified by column chromatography on SiO2 6% NH3-MeOH in CH2Cl2 to yield 1H-pyrrolo[2,3-b]pyridine 7-oxide (Intermediate C2) (34%) (see: Minakata, S. et. aL Synthesis 1992, 661. ). 1H-pyrrolo[2,3-b]pyridine 7-oxide (Intermediate C2) (8.95 mmol) in THF (60 mL) was treated with hexamethyldisilazane (HMDS): (90 mmol) and a dropwise addition of benzoylchloride (22.5 mmol). The mixture was allowed to stir at rt for 1 h. The mixture was diluted with sat. NaHCO3 and the aqueous layer extracted with ethyl acetate. The organic layers were combined, dried over MgSO4, filtered and freed of solvent. The residue was purified by column chromatography (10% EtOAc:hexane) to give the product 6-chloro-pyrrolo[2,3-b]pyridin-1-yl-phenyl-methanone (Intermediate C3) as a solid.