Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: NC1C=C(C(F)(F)F)C=C(Cl)C=1OC1C=CC([N+]([O-])=O)=C(C=1)C(OC)=O.S(Cl)(Cl)=O.CS(N)(=O)=O.[CH3:36][S:37]([NH:40][C:41](=[O:63])[C:42]1[CH:47]=[C:46]([O:48][C:49]2[CH:54]=[C:53]([C:55]([F:58])([F:57])[F:56])[CH:52]=[CH:51][C:50]=2[Cl:59])[CH:45]=[CH:44][C:43]=1[N+]([O-])=O)(=[O:39])=[O:38]>N1C=CC=CC=1>[CH3:36][S:37]([NH:40][C:41](=[O:63])[C:42]1[CH:43]=[CH:44][CH:45]=[C:46]([O:48][C:49]2[CH:54]=[C:53]([C:55]([F:58])([F:57])[F:56])[CH:52]=[CH:51][C:50]=2[Cl:59])[CH:47]=1)(=[O:38])=[O:39]
Reactant: CS(=O)(=O)NC(=O)c1cc(Oc2cc(C(F)(F)F)ccc2Cl)ccc1[N+](=O)[O-]
Agent: COC(=O)c1cc(Oc2c(N)cc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Agent: CS(N)(=O)=O
Solvent: c1ccncc1
Solvent: O=S(Cl)Cl
Product: CS(=O)(=O)NC(=O)c1cccc(Oc2cc(C(F)(F)F)ccc2Cl)c1

Procedure:
The acid from (b) (0.8 g) was treated with thionyl chloride followed by methanesulphonamide and pyridine as described in paragraph (d) above for compound 32. The product was recrystallised from a mixture of ether and petroleum (b.p. 40°-60°) to give compound 31 with a melting point of 132°-133°.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([N:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:11]([CH3:20])([CH3:19])[O:10][C:9]2=[O:21])[CH:5]=[CH:4][N:3]=1.[NH2:22][NH2:23]>>[NH:22]([C:2]1[CH:7]=[C:6]([N:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:11]([CH3:20])([CH3:19])[O:10][C:9]2=[O:21])[CH:5]=[CH:4][N:3]=1)[NH2:23]
Reactant: NN
Reactant: CC1(C)OC(=O)N(c2ccnc(Cl)c2)[C@H]1c1ccccc1
Product: CC1(C)OC(=O)N(c2ccnc(NN)c2)[C@H]1c1ccccc1
Temperature: 140 °C

Procedure:
A mixture of (S)-3-(2-chloropyridin-4-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one (1.44 g, 4.76 mmol) and anhydrous hydrazine (7.46 mL, 238 mmol, commercially available from Sigma-Aldrich, Milwaukee, Wis.) was heated at 140° C. for 15 minutes. LC-MS indicated complete consumption of starting material with the desired product as the major product. After cooling to room temperature, the solution was concentrated under reduced pressure. The residue thus obtained was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 10% MeOH in DCM, to provide (S)-3-(2-hydrazinylpyridin-4-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one. m/z (ESI) 299.2 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].C(N(CC)CC)C.[Br:19][C:20]([CH3:25])([CH3:24])[C:21](Br)=[O:22]>C1(C)C=CC=CC=1>[Br:19][C:20]([CH3:25])([CH3:24])[C:21]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8])=[O:22]
Reactant: Nc1ccc(O)c(C(=O)O)c1
Reactant: CC(C)(Br)C(=O)Br
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CC(C)(Br)C(=O)Nc1ccc(O)c(C(=O)O)c1

Procedure:
To a suspension of 5-amino-2-hydroxybenzoic acid (3.0 g, 19.6 mmol) in a solution of freshly distilled triethylamine (4.1 mL, 29.4 mmol, 1.5 eq.) in 100 mL of anhydrous toluene was added dropwise 2-bromoisobutyryl bromide (6.8 mL, 53.8 mmol). Addition was performed at 0° C. under inert atmosphere. The mixture was then refluxed for 15 hours. Volatiles were removed under vacuum leaving oily crude materials. The product initiator C was extracted with ethanol concentrated and crystallized at −30° C. Yield: 30%. Analysis: 1H NMR (CDCl3, 300 MHz, 298 K): δ 9.81 (s broad, 3H, NHCO and OH), 8.24 (s, 1H, Hortho), 7.76 (d, 1J=10.5 Hz, 1H, Hmeta), 6.82 (d, 1J=9.8 Hz, 1H, Hpara), 2.10 (s, 6H, Me). 13C NMR (CDCl3, 125 MHz, 298 K): δ 170.6 (CO—N), 167.2 (CO—O), 160.0 (C(aromatic)-OH), 130.8 (C(aromatic)-NH), 124.1 (C(aromatic)-H), 122.2 (C(aromatic)-H), 118.6 (C(aromatic)-H), 114.2 (C(aromatic)-CO2H), 58.9 (C—Br), 33.6 (CH3), confirming the product to be 5-(2-bromo-2-methylpropanamido)-2-hydroxybenzoic acid initiator (initiator C).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=2)[CH:11]=[N:12]O)=[CH:5][CH:4]=1>C(O)(=O)C.[Zn]>[CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[CH:9]=[C:10]([CH2:11][NH2:12])[CH:14]=[CH:15][CH:16]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc(Oc2cccc(C=NO)c2)cc1
Agent: [Zn]
Solvent: CC(=O)O
Product: COc1ccc(Oc2cccc(CN)c2)cc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
The 3-(4-methoxyphenoxy)benzaldehyde oxime (0.11 g, 0.44 mmol) was taken up in acetic acid (5.0 mL) at rt and the Zinc dust (0.14 g, 2.2 mmol) was added. The reaction was stirred at r.t. for 18 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to give crude 1-[3-(4-methoxyphenoxy)phenyl]methanamine as a dark oil. Analytical LCMS (M+H)+: m/z=, 229.9
Reaction SMILES: [Br-].[C:2]([C:5]1[CH:30]=[CH:29][C:8]([CH2:9][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:7][C:6]=1[F:31])([OH:4])=[O:3].[CH:32]([C:34]1[N:35]=[C:36]([NH:39][C:40](=[O:42])[CH3:41])[S:37][CH:38]=1)=O.CC(C)([O-])C.[K+].O>CN(C)C=O>[C:40]([NH:39][C:36]1[S:37][CH:38]=[C:34]([CH:32]=[CH:9][C:8]2[CH:29]=[CH:30][C:5]([C:2]([OH:4])=[O:3])=[C:6]([F:31])[CH:7]=2)[N:35]=1)(=[O:42])[CH3:41]
Reactant: O=C(O)c1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1F
Reactant: CC(=O)Nc1nc(C=O)cs1
Agent: CC(C)(C)[O-]
Agent: [Br-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(=O)Nc1nc(C=Cc2ccc(C(=O)O)c(F)c2)cs1
Temperature: 25 °C
Reaction time: 3 h
Yield: 69.9 %

Procedure:
To a solution of (4-carboxy-3-fluorobenzyl)(triphenyl)phosphoniumbromide (2.037 g, 4.112 mmol) and N-(4-formyl-1,3-thiazol-2-yl)acetamide (599.5 mg, 3.523 mmol) in anhydrous N,N-dimethylformamide (15 ml) was added potassium tert-butoxide (1.180 g, 10.52 mmol), and the mixture was stirred at room temperature for 3 hr. Water (150 ml) was added to the reaction mixture, and the mixture was washed 3 times with ethyl acetate. While stirring, 1M hydrochloric acid (10.5 ml) was added to the aqueous layer. The precipitated solid was collected by filtration and washed with water. The solid was dried under reduced pressure to give 4-{2-[2-(acetylamino)-1,3-thiazol-4-yl]vinyl}-2-fluorobenzoic acid (753.9 mg, 2.461 mmol, yield 69.9%) as a yellow solid.
Reaction SMILES: [Si:1]([O:8][C@H:9]1[CH2:35][CH2:34][C@@:33]2([CH3:36])[C@@H:11]([CH2:12][CH2:13][C@@H:14]3[C@@H:32]2[C@@H:31]([OH:37])[C@@H:30]([O:38][C:39](=[O:41])[CH3:40])[C@@:29]2([CH3:42])[C@H:15]3[CH2:16][C@@H:17]3[O:22][C@@:21]4([O:28][CH2:27][C@H:25]([CH3:26])[CH2:24][CH2:23]4)[C@@H:19]([CH3:20])[C@@H:18]32)[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:43][Si:44](OS(C(F)(F)F)(=O)=O)([CH3:46])[CH3:45].N1C(C)=CC=CC=1C>C(Cl)Cl>[Si:1]([O:8][C@H:9]1[CH2:35][CH2:34][C@@:33]2([CH3:36])[C@@H:11]([CH2:12][CH2:13][C@@H:14]3[C@@H:32]2[C@@H:31]([O:37][Si:44]([CH3:46])([CH3:45])[CH3:43])[C@@H:30]([O:38][C:39](=[O:41])[CH3:40])[C@@:29]2([CH3:42])[C@H:15]3[CH2:16][C@@H:17]3[O:22][C@@:21]4([O:28][CH2:27][C@H:25]([CH3:26])[CH2:24][CH2:23]4)[C@@H:19]([CH3:20])[C@@H:18]32)[CH2:10]1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]
Reactant: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: CC(=O)O[C@@H]1[C@H](O)[C@H]2[C@@H](CC[C@H]3C[C@@H](O[Si](C)(C)C(C)(C)C)CC[C@@]32C)[C@@H]2C[C@@H]3O[C@]4(CC[C@@H](C)CO4)[C@@H](C)[C@@H]3[C@@]12C
Solvent: Cc1cccc(C)n1
Solvent: ClCCl
Product: CC(=O)O[C@@H]1[C@H](O[Si](C)(C)C)[C@H]2[C@@H](CC[C@H]3C[C@@H](O[Si](C)(C)C(C)(C)C)CC[C@@]32C)[C@@H]2C[C@@H]3O[C@]4(CC[C@@H](C)CO4)[C@@H](C)[C@@H]3[C@@]12C

Procedure:
(3β,5α,11β,12β,25R)-3-(t-butyldimethylsilyloxy)-12-acetoxyspirostan-11-ol was silylated with trimethylsilyltriflate and 2,6-lutidine in methylene chloride according to the procedure described in Tetrahedron Letters, 1981, 22, 3455.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@@H:15]3[C:19]([CH3:21])([CH3:20])[C@@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[NH:10]1.Br[CH2:24][CH2:25][C:26]([F:29])([F:28])[F:27].[I-].ClCCl>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@@H:15]3[C:19]([CH3:21])([CH3:20])[C@@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[N:10]1[CH2:24][CH2:25][C:26]([F:29])([F:28])[F:27]
Reactant: FC(F)(F)CCBr
Reactant: CC1(C)[C@@H]2CC[C@@]1(C)c1[nH]n(-c3ccc(F)cc3F)c(=O)c12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC1(C)[C@@H]2CC[C@@]1(C)c1c2c(=O)n(-c2ccc(F)cc2F)n1CCC(F)(F)F
Temperature: 100 °C
Yield: 17.4 %

Procedure:
A mixture of (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 14; 200 mg, 0.66 mmol), tetrabutylammonium iodide (190 mg, 0.51 mmol) and 3-bromo-1,1,1-trifluoropropane (Aldrich; 5.00 g, 28.25 mmol) in dimethylformamide (2 mL) was heated in a pressure tube in an oil-bath at 100° C. for 4 days. An additional portion of tetrabutylammoiun iodide (190 mg, 0.51 mmol) was added and the reaction mixture was heated at 100° C. for 3 days and then cooled to room temperature. Dichloromethane (150 mL) was added and the solution was washed with water (5×25 mL) and aqueous sodium thiosulfate (25 mL), dried (magnesium sulfate), filtered, evaporated and purified using an ISCO 40 g column, eluting with 30-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated and the residue was triturated with petroleum ether. The mixture was evaporated again and dried at 70° C. under high vacuum to give (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1-(3,3,3-trifluoro-propyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (46 mg, 17%) as a light yellow solid. ES(+)-MS (M+H) 401.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]([C:23]3[N:24]=[C:25]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[O:26][C:27]=3[CH2:28][CH3:29])=[O:22])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl>C(OCC)(=O)C>[NH:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:15]=[CH:16][C:17]([NH:20][C:21]([C:23]3[N:24]=[C:25]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)[O:26][C:27]=3[CH2:28][CH3:29])=[O:22])=[CH:18][CH:19]=2)[CH2:10][CH2:9]1
Reactant: CCc1oc(-c2ccccc2)nc1C(=O)Nc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2)cc1
Agent: Cl
Solvent: CCOC(C)=O
Product: CCc1oc(-c2ccccc2)nc1C(=O)Nc1ccc(C2CCNCC2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 59.5 %

Procedure:
To 4-{4-[(2-phenyl-5-ethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidine-1-carboxylic acid tert-butyl ester (330 mg, 0.694 mmol) was added 2N HCl in ethyl acetate (80 mL). The solution was stirred at room temperature for 1 hr. Solvents were evaporated and the residue was diluted with ethyl acetate (100 mL). The organic layer was washed with saturated sodium bicarbonate (3×) and dried over magnesium sulfate The solvent was evaporated to give 2-phenyl-5-ethyl-oxazole-4-carboxylic acid (4-piperidin-4-yl-phenyl)-amide (155 mg). LC-MS calcd for C23H25N3O2 (m/e) 375, obsd 376 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([NH:12][CH:13]([CH3:15])[CH3:14])[C:5]([C:6]([NH:8][NH2:9])=[O:7])=[CH:4][N:3]=1.CCN(CC)CC.Cl[C:24](=[O:29])[C:25]([O:27][CH3:28])=[O:26]>C(Cl)Cl>[Cl:1][C:2]1[CH:11]=[C:10]([NH:12][CH:13]([CH3:15])[CH3:14])[C:5]([C:6]([NH:8][NH:9][C:24](=[O:29])[C:25]([O:27][CH3:28])=[O:26])=[O:7])=[CH:4][N:3]=1
Reactant: COC(=O)C(=O)Cl
Reactant: CC(C)Nc1cc(Cl)ncc1C(=O)NN
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)C(=O)NNC(=O)c1cnc(Cl)cc1NC(C)C
Temperature: 0 °C
Reaction time: 6 h

Procedure:
To a stirred solution of 6-chloro-4-(isopropylamino)nicotinohydrazide (10) (200 mg, 0.35 mmol) in DCM (10 mL), Et3N (3.1 mmol, 3 equiv) was added and cooled to 0° C. Methyl 2-chloro-2-oxoacetate (0.42 mmol, 1.2 equiv) was added dropwise and stirred for 6 h at room temperature. The reaction mixture was quenched with aq. NaHCO3 solution and extracted in DCM. The organic layer was separated, dried over Na2SO4, filtered and concentrated. The crude material was purified by column chromatography through silica gel and MeOH: DCM as eluent to afford methyl 2-(2-(6-chloro-4-(isopropylamino)nicotinoyl)hydrazinyl)-2-oxoacetate.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].C([O:9][C:10](=O)[CH2:11][CH2:12][S:13][C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17](O)=[O:18])C>C1COCC1>[OH:18][CH2:17][C:16]1[CH:15]=[C:14]([S:13][CH2:12][CH2:11][CH2:10][OH:9])[CH:22]=[CH:21][CH:20]=1
Reactant: CCOC(=O)CCSc1cccc(C(=O)O)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCCCSc1cccc(CO)c1
Temperature: 25 °C

Procedure:
A solution of lithium aluminum hydride (2M in THF, 2.2 mL) was added portionwise over 5 minutes to a solution of 3-(3-ethoxy-3-oxopropylthio)benzoic acid [Aromatic Intermediate 15, step a] (1.0 g) in THF (20 mL), pre-cooled in ice-water. After ˜½ the addition the mixture formed a thick precipitate and was diluted with more THF (15 mL) to maintain stirring. The mixture was removed from the cooling bath and stirred at room temperature for 3.5 hours. The mixture was cooled back down in ice-water and treated with more lithium aluminum hydride (2M in THF, 2.2 mL). The mixture was removed from the cooling bath and stirred at room temperature overnight. The cloudy solution was cooled in ice water and then quenched by the careful addition of methanol (5 mL), added portionwise over 30 minutes. After ˜½ of the addition, the mixture was removed from the cooling bath and allowed to warm to room temperature for 45 minutes. The mixture was poured into aqueous HCl (2M) and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure to give the subtitled compound as a pale yellow oil. Yield 0.55 g.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[C:7]([CH3:14])[CH:6]=1)(=O)[CH3:2].O[CH2:16]C(CO)O.OS(O)(=O)=O>>[CH3:14][C:7]1[CH:6]=[C:5]2[C:10]([CH:16]=[CH:2][CH:1]=[N:4]2)=[CH:9][C:8]=1[N+:11]([O-:13])=[O:12]
Reactant: CC(=O)Nc1ccc([N+](=O)[O-])c(C)c1
Reactant: OCC(O)CO
Agent: O=S(=O)(O)O
Product: Cc1cc2ncccc2cc1[N+](=O)[O-]
Yield: 34.4 %

Procedure:
4-Acetamido-2-methylnitrobenzene (4.5 g; 23.2 mmol) glycerol (9 g; 100 mmol), H2SO4 conc (6.75 g) and As2O5.5H2O (3.6 g; 46.4 mmol) were heated at 130° C. for 20 h. The reaction mixture was poured on water, adjusted to pH 7-8 by adding NH3conc. and extracted with EtOAc three times. The combined organic phases were dried over Na2SO4, evaporated and purified via chromatography (SiO2; TBME/hexanes 70/30) to yield the title compound (1.5 g; 34%). The isomeric 5-methyl-6-nitroquinoline was eluted from the column after the title compound (850 mg; 19%).
Reaction SMILES: [Na][Na].[NH2:3][C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[C:7]([NH2:20])=[C:6]([S:21]([OH:24])(=[O:23])=[O:22])[C:5]=1S(O)(=O)=O.C([NH:32][C:33]1[CH:38]=[CH:37][C:36]([OH:39])=[CH:35][CH:34]=1)(=O)C.C(=O)([O-])[O-].[K+].[K+]>O.Cl.CN(C)C=O>[NH2:3][C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[C:7]([NH2:20])=[C:6]([S:21]([OH:24])(=[O:23])=[O:22])[C:5]=1[O:39][C:36]1[CH:37]=[CH:38][C:33]([NH2:32])=[CH:34][CH:35]=1
Reactant: Nc1c2c(c(N)c(S(=O)(=O)O)c1S(=O)(=O)O)C(=O)c1ccccc1C2=O
Reactant: CC(=O)Nc1ccc(O)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Nc1ccc(Oc2c(N)c3c(c(N)c2S(=O)(=O)O)C(=O)c2ccccc2C3=O)cc1
Temperature: 140 °C
Reaction time: 3 h

Procedure:
A mixture of 43 parts of disodium salt of 1,4-diaminoanthraquinone-2,3-disulfonic acid, 30 parts of p-acetylaminophenol, 11 parts of potassium carbonate and 80 parts of dimethylformamide was stirred at 140° C for 3 hours. This reaction solution was poured into 1000 parts of water. The mixture was filtered to remove insoluble components. 300 parts of sodium chloride was added to the filtrate and was filtered again. The cake was washed with 500 parts of a 20% aqueous solution of sodium chloride. The cake thus obtained was dissolved in 450 parts of water and 130 parts of hydrochloric acid was added to the solution. The solution was heated to 95° C and stirred for 10 hours. After cooling the solution was filtered to obtain 1,4-diamino-2-(4'-aminophenoxy)anthraquinone-3-sulfonic acid. 4 parts of sulfanilic acid were added to 200 parts of water and the solution was adjusted to pH 7 with soda ash. 4.1 parts of cyanuric chloride were added to the solution at 0° C, the reaction was continued for 1 hour and after the solution was neutralized, excess cyanuric chloride was removed by filtration. To the filtrate there were added 9 parts of 1,4-diamino-2-(4'-aminophenoxy) anthraquinone-3-sulfonic acid, the solution was kept at 35 - 40° C, a 10% solution of soda ash was added and the reaction was carried out for 2 hours while adjusting the pH to 5 - 7. 60 parts of sodium chloride were added to the reaction solution. The dye precipitated was filtered and dried. There was obtained 13 parts of a dye represented by the following formula: ##STR20## μ max. : 580 mμ in pure water
Reaction SMILES: [CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH:3]([C:11]([O:13]CC)=O)[NH:2]1.[N:16](CCCCCC)=[C:17]=[O:18]>>[C:11]1(=[O:13])[CH:3]2[N:2]([CH2:1][C:10]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[CH2:4]2)[C:17](=[O:18])[NH:16]1
Reactant: CCCCCCN=C=O
Reactant: CCOC(=O)C1Cc2ccccc2CN1
Product: O=C1NC(=O)N2Cc3ccccc3CC12

Procedure:
10,10a-Dihydro-5H-imidazo[1,5-b]isoquinoline-1,3-dione was prepared from ethyl 1,2,3,4-tetrahydroisoquinoline-3-carboxylate in analogy to example 23 (yield: 85%) and then 1.48 mmol were reacted as described in example 23 with isocyanatohexane. Yield: 61 mg (12%), M+H+:330.20.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([S:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[CH:5]=[CH:4][C:3]=1[CH2:19][CH2:20][CH2:21][C:22]([NH:29][C:30]([O:32][CH3:33])=[O:31])([CH3:28])[C:23](OCC)=[O:24].[BH4-].[Li+].C(O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([S:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:17])([F:18])[F:16])[CH:10]=2)[CH:5]=[CH:4][C:3]=1[CH2:19][CH2:20][CH2:21][C:22]([NH:29][C:30]([O:32][CH3:33])=[O:31])([CH3:28])[CH2:23][OH:24]
Reactant: CCOC(=O)C(C)(CCCc1ccc(Sc2cccc(C(F)(F)F)c2)cc1Cl)NC(=O)OC
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCO
Product: COC(=O)NC(C)(CO)CCCc1ccc(Sc2cccc(C(F)(F)F)c2)cc1Cl
Yield: 90.2 %

Procedure:
To a solution of the compound of Example 54 (15.6 g) in THF (249 mL) was added under ice cooling lithium borohydride (3.75 g), and then ethanol (16.6 mL) was added dropwise. The resultant solution was then stirred for 1 hour under ice cooling. To the reaction solution was added 10% aqueous citric acid, extracted with ethyl acetate, washed with water and saturated brine in that order, and then dried over anhydrous sodium sulfate. The solvent was evaporated, and the resultant residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to obtain the target product (12.9 g) as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:3]=1[C:4]([NH:6][CH:7]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH:8]1[CH2:11][N:10](C(OC(C)(C)C)=O)[CH2:9]1)=[O:5].Cl.CCN(C(C)C)C(C)C.[CH2:40]([S:43](Cl)(=[O:45])=[O:44])[CH2:41][CH3:42]>O1CCOCC1>[Cl:1][C:2]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:3]=1[C:4]([NH:6][CH:7]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH:8]1[CH2:9][N:10]([S:43]([CH2:40][CH2:41][CH3:42])(=[O:45])=[O:44])[CH2:11]1)=[O:5]
Reactant: CCCS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)N1CC(C(NC(=O)c2ccc(Cl)cc2Cl)c2ccccc2)C1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Product: CCCS(=O)(=O)N1CC(C(NC(=O)c2ccc(Cl)cc2Cl)c2ccccc2)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 56.1 %

Procedure:
To a solution of 2 (500 mg, 1.15 mmol) in 1,4-dioxane (10 mL) was added 4N HCl in dioxane (5.0 mL) and stirred at room temperature for 2 h. The reaction was concentrated under vacuum. The residue was dissolved in CH2Cl2 (10 mL) and DIPEA (300 mg, 2.30 mmol) and added 1-propanesulfonyl chloride (164 mg, 1.15 mmol). The reaction was stirred at room temperature for 20 h. The reaction was concentrated under vacuum and the residue was purified by column chromatography (silica gel) using 0 to 35% EtOAc in hexanes to afford 3a as white solid (285 mg, 56%); 1H-nmr (300 MHz, CDCl3) δ 7.69 (d, J=8.5 Hz, 1H), 7.60-7.30 (m, 10H), 7.08 (d, J=8.5 Hz, 1H), 5.68 (dd, J=9.5, 6.5 Hz, 1H), 5.29 (br s, 1H), 3.76-3.71 (m, 2H), 3.55-3.35 (m, 2H), 3.19-3.01 (m, 2H), 2.69 (br s, 1H), 1.98-1.82 (m, 2H), 1.08 (t, J=7 Hz, 9H); LC-MS (214) 98%, 3.30 min, m/z 475 (MMeOH+).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CI.[C:25](=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH3:25])[C:13]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1cc2cc(OCc3ccccc3)ccc2[nH]1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: CCOC(=O)c1cc2cc(OCc3ccccc3)ccc2n1C
Temperature: 150 °C
Reaction time: 2 h

Procedure:
To a solution of ethyl 5-(benzyloxy)-1H-indole-2-carboxylate (5.00 g, 16.93 mmol) and methyl iodide (1.14 mL, 18.28) in 17 mL dimethylformamide was added potassium carbonate (2.57 g, 18.62 mmol). The resulting suspension was stirred for 2 h at 150° C. in a sealed reaction vessel. Solids were filtered and the liquor concentrated to give crude ethyl 5-(benzyloxy)-1-methyl-1H-indole-2-carboxylate. Used without further purification or characterization.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([Sn](CCCC)(CCCC)CCCC)=[N:6][CH:7]=1.Cl[C:22]1[N:27]=[C:26]([CH3:28])[N:25]=[C:24]([N:29]2[CH2:32][CH:31]([C:33]3[N:37]([CH3:38])[C:36]4[CH:39]=[CH:40][CH:41]=[CH:42][C:35]=4[N:34]=3)[CH2:30]2)[CH:23]=1>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.CN(C=O)C>[CH3:38][N:37]1[C:36]2[CH:39]=[CH:40][CH:41]=[CH:42][C:35]=2[N:34]=[C:33]1[CH:31]1[CH2:32][N:29]([C:24]2[CH:23]=[C:22]([C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=3)[N:27]=[C:26]([CH3:28])[N:25]=2)[CH2:30]1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(C)cn1
Reactant: Cc1nc(Cl)cc(N2CC(c3nc4ccccc4n3C)C2)n1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: Cc1ccc(-c2cc(N3CC(c4nc5ccccc5n4C)C3)nc(C)n2)nc1
Temperature: 110 °C

Procedure:
To a microwave vial was added 5-methyl-2-(tributylstannyl)pyridine (97 mg, 2.6 mmol), Intermediate 3 (40 mg, 0.13 mmol), tetrakis(triphenylphosphine)palladium(0) (15 mg, 0.013 mmol), and DMF (1 mL). The vial was sealed and heated in a heating block at 110° C. for 16 h. The reaction was cooled to room temperature, passed through a syringe filter, and purified by reverse-phase chromatography (5-55% acetonitrile/water/0.1% TFA). The product fractions were poured into aqueous NaHCO3 and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated to give Example 94 as a white solid. 1H NMR: (400 MHz, CDCl3) δ 8.50 (s, 1H), 8.28 (d, J=8.0 Hz, 1H), 7.75 (d, J=7.3 Hz, 1H), 7.61 (d, J=8.0 Hz, 1H), 7.29 (m, 3H), 7.15 (s, 1H), 4.66 (m, 4H), 4.29 (m, 1H), 3.74 (s, 3H), 2.60 (s, 3H), 2.40 (s, 3H) ppm. MS: m/z=371.5 (M+H).
Reaction SMILES: C(OC([N:6]1[CH2:11][CH2:10][CH:9]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[CH:18][CH:19]=3)[NH:14][CH:13]=2)[CH2:8][CH2:7]1)=O)C.Br[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1>>[NH:6]1[CH2:7][CH2:8][CH:9]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[CH:18][CH:19]=3)[N:14]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[CH:13]=2)[CH2:10][CH2:11]1
Reactant: CCOC(=O)N1CCC(c2c[nH]c3ncccc23)CC1
Reactant: BrCc1ccccn1
Product: c1ccc(Cn2cc(C3CCNCC3)c3cccnc32)nc1

Procedure:
This compound was prepared following the procedure described in example 24, parts C and D, starting with 0.2 g (0.66 mmol) of 4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-piperidine-1-carboxylic acid ethyl ester and 0.149 g (0.86 mmol) of 2-bromomethylpyridine. After standard work-up, 0.21 g (72% of yield) of the expected product were isolated.