Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]([CH2:14][CH3:15])[CH2:10][C:11]([OH:13])=[O:12].[CH3:16]O.S(=O)(=O)(O)O>CCOCC>[F:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]([CH2:14][CH3:15])[CH2:10][C:11]([O:13][CH3:16])=[O:12]
Reactant: CO
Reactant: CCC(CC(=O)O)c1cccc(O)c1F
Agent: O=S(=O)(O)O
Solvent: CCOCC
Product: CCC(CC(=O)OC)c1cccc(O)c1F
Temperature: 80 °C
Reaction time: 1 h
Yield: 90 %

Procedure:
A 500 mL round bottom flask was charged with 77.E (21.5 g, 101 mmol), MeOH (300 mL), and sulfuric acid (1.08 mL, 20.3 mmol). The solution was stirred for 1 hour at 80° C., cooled to room temperature, and diluted with ether. The organic layers were washed with saturated aqueous NaHCO3, water, and brine, dried (MgSO4), and concentrated. The crude product was purified by silica gel flash chromatography (0-30% EtOAc/hexane) to afford 77.F (20.6 g, 90% yield) as a yellow oil.
Reaction SMILES: CI.[CH3:3][C:4]1([CH3:11])[NH:9][CH2:8][CH2:7][NH:6][C:5]1=[O:10].[C:12](=O)([O-])[O-].[K+].[K+]>COCCOC>[CH3:3][C:4]1([CH3:11])[N:9]([CH3:12])[CH2:8][CH2:7][NH:6][C:5]1=[O:10]
Reactant: CC1(C)NCCNC1=O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: COCCOC
Product: CN1CCNC(=O)C1(C)C
Temperature: 45 °C
Reaction time: 3 h

Procedure:
A mixture of ethyl-2-bromoisobutyrate (14.6 g, 74.9 mmol), ethylene diamine (33 mL, 487 mmol, 6.5 equiv) and potassium carbonate (11.4 g, 82.4 mmol, 1.1 equiv) in toluene (150 mL) was stirred for 22 h at reflux, cooled and filtered. The filtrate was concentrated and the residue triturated in Et2O to afford 6.3 g of 3,3-dimethyl-piperazin-2-one as a white solid. Methyl iodide (4 mL, 64.0 mmol, 1.3 equiv) was added dropwise to a suspension of 3,3-dimethyl-piperazin-2-one (6.3 g, 49.2 mmol) and potassium carbonate (8.8 g, 64.0 mmol, 1.3 equiv) in DME (20 mL). The reaction mixture was heated to 45° C., stirred for 3 h, cooled and filtered, washing the filter cake with DME. The filtrate was concentrated and the residue triturated in DME to afford 2.8 g (batch 1) of the title compound as a white solid. The filtrate from the trituration was concentrated and the residue purified by silica gel column chromatography (DCM/MeOH, 9:1) to afford 1.75 g (batch 2) of the title compound as a white solid. Title compound: ESI-MS: 143.1 [M+H]+; TLC: Rf=0.25 (DCM/MeOH, 9:1).
Reaction SMILES: C(OC([NH:11][CH2:12][CH:13]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14]1)=O)C1C=CC=CC=1>CO.[C].[Pd]>[NH2:11][CH2:12][CH:13]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14]1
Reactant: O=C(NCC1Cc2ccccc2C1)OCc1ccccc1
Agent: [Pd]
Solvent: CO
Product: NCC1Cc2ccccc2C1
Reaction time: 4 h
Yield: 90.8 %

Procedure:
Dissolved in 100 ml of methanol were 10.6 g (37.7 mmol) of 2-(benzyloxycarbonylaminomethyl)indane, and 1.3 g of 10% palladium-carbon were added to the solution. The mixture was stirred for 4 hours under a hydrogen atmosphere. After separating the catalyst by filtration, the solvent was distilled off to obtain 5.04 g of 2-(aminomethyl)indane. This compound was immediately dissolved in 150 ml of methylene chloride, and 100 ml of water and 6.2 g of potassium carbonate were added to the solution, followed by vigorous stirring of the resultant mixture. While chilling with ice water, 8.02 g (38.0 mmol) of 4-chlorobenzenesulfonyl chloride were added in small portions. Thereafter, the mixture was stirred for 30 minutes. After an organic layer separated was taken out and dried, the solvent was distilled out of the organic layer. The resultant crystalline residue was recrystallized from a mixed solvent of ethyl acetate and hexane to obtain 9.82 g of 2-[(4-chlorophenyl)sulfonylaminomethyl]indane as a colorless needle crystal. Yield: 76%.
Reaction SMILES: [CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[C:16]3[CH2:21][NH:20][CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)=[O:5])[CH3:2].Cl[C:29]([O:31][CH3:32])=[O:30]>>[CH2:1]([NH:3][C:4](=[O:5])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)[C:16]3[CH2:21][N:20]([C:29]([O:31][CH3:32])=[O:30])[CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)[CH3:2]
Reactant: COC(=O)Cl
Reactant: CCNC(=O)Nc1ccc(-c2nc3c(c(N4CCOCC4)n2)CNC3)cc1
Product: CCNC(=O)Nc1ccc(-c2nc3c(c(N4CCOCC4)n2)CN(C(=O)OC)C3)cc1

Procedure:
Compound ee was prepared according to the procedure described in Example 5 by reacting 1-ethyl-3-(4-(4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea with methyl chloroformate. LC-MS: m/z=+427 (M+H)+.
Reaction SMILES: [CH:1]1([CH:7]2[C:12]3[N:13]=[CH:14][NH:15][C:11]=3[CH2:10][CH2:9][NH:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:16][N:17]=[C:18]=[S:19]>C(#N)C>[CH:1]1([CH:7]2[C:12]3[N:13]=[CH:14][NH:15][C:11]=3[CH2:10][CH2:9][N:8]2[C:18](=[S:19])[NH:17][CH3:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: c1nc2c([nH]1)CCNC2C1CCCCC1
Reactant: CN=C=S
Solvent: CC#N
Product: CNC(=S)N1CCc2[nH]cnc2C1C1CCCCC1

Procedure:
Operating as in Example 14, 15.5 g of 4-cyclohexyl-4,5,6,7-tetrahydro-imidazo-[4,5-c]-pyridine, m.p. 150°, are obtained from 18.4 g of histamine dihydrochloride and 24.4 ml of hexahydrobenzaldehyde. A solution of 2.05 g of 4-cyclohexyl-4,5,6,7-tetrahydro-imidazo-[4,5-c]-pyridine and 1.1 g of methyl isothiocyanate in 30 ml of acetonitrile is refluxed for 5 h. The solution is cooled and filtered, and 2.50 g of the title compound, m.p. 232°, are collected.
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[C:4]([NH:6][C:7]([O:9]C1C=CC([N+]([O-])=O)=CC=1)=O)=[O:5].[Cl:24][C:25]1[CH:26]=[CH:27][C:28]([NH2:31])=[N:29][CH:30]=1>>[Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[C:4]([NH:6][C:7]([NH:31][C:28]1[CH:27]=[CH:26][C:25]([Cl:24])=[CH:30][N:29]=1)=[O:9])=[O:5]
Reactant: Nc1ccc(Cl)cn1
Reactant: O=C(NC(=O)c1c(F)cccc1Cl)Oc1ccc([N+](=O)[O-])cc1
Product: O=C(NC(=O)c1c(F)cccc1Cl)Nc1ccc(Cl)cn1

Procedure:
A portion of 2-chloro-6-fluorobenzamidocarboxylic acid, 4-nitrophenyl ester, is combined with a portion of 5-chloro-2-aminopyridine in an inert organic solvent. The reaction mixture is stirred at elevated temperature for a period of time, and is then evaporated under vacuum. The product named in the heading above, identical to the product of Example 3, is isolated by recrystallization.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14]O)=[CH:10][CH:9]=2)=[N:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:35]N1C(=O)CCC1=O>C(Cl)Cl>[Br:35][CH2:14][C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=2)=[CH:9][CH:10]=1
Reactant: OCc1ccc(-c2ccc(F)cn2)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: Fc1ccc(-c2ccc(CBr)cc2)nc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 87.2 %

Procedure:
A solution of alcohol 111 (305 mg, 1.50 mmol) and triphenylphosphine (474 mg, 1.81 mmol) in anhydrous CH2Cl2 (12 mL) was carefully treated with recrystallized N-bromosuccinimide (322 mg, 1.81 mmol) (water bath cooling), and the mixture was stirred at room temperature for 3 h. The resulting solution was concentrated, and then added to excess pentane at the top of a silica gel column (20 g in pentane), rinsing on with minimal extra CH2Cl2. Elution with pentane firstly gave foreruns, and then further elution with 20-50% Et2O/pentane gave 2-[4-(bromomethyl)phenyl]-5-fluoropyridine (112) (348 mg, 87%) as a white solid that was used directly in the next step; 1H NMR (CDCl3) δ 8.54 (d, J=2.9 Hz, 1H), 7.92 (dt, J=8.4, 1.9 Hz, 2H), 7.72 (ddd, J=8.7, 4.3, 0.4 Hz, 1H), 7.52-7.43 (m, 3H), 4.54 (s, 2H); HRESIMS calcd for C12H10BrFN m/z [M+H]+ 267.9955, 265.9975, found 267.9959, 265.9979.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH2:11][CH2:12][CH2:13][CH:14]2[C:19](O)=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:22]([C:25]1[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=1)([CH3:24])[CH3:23]>>[CH2:1]([O:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH2:11][CH2:12][CH2:13][CH:14]2[C:19]([NH:29][C:28]1[CH:30]=[CH:31][C:25]([CH:22]([CH3:24])[CH3:23])=[CH:26][CH:27]=1)=[O:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)c1ccc(N)cc1
Reactant: O=C(O)C1CCCc2c(OCc3ccccc3)cccc21
Product: CC(C)c1ccc(NC(=O)C2CCCc3c(OCc4ccccc4)cccc32)cc1

Procedure:
By the reaction and treatment in the same manner as in Preparation Example 11 using 5-benzyloxy-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid (5.48 g) and 4-isopropylaniline (3.90 mL) as starting materials, 5-benzyloxy-N-(4-isopropylphenyl)-1,2,3,4-tetrahydronaphthalene-1-carboxamide (5.94 g) was obtained. melting point: 170.4° C.
Reaction SMILES: [N+:1]([C:4]1[C:5](=[O:21])[NH:6][C:7]([CH2:12][O:13]CC2C=CC=CC=2)=[C:8]([CH2:10][CH3:11])[CH:9]=1)([O-])=O>O1CCCC1.CO.[Pd]>[NH2:1][C:4]1[C:5](=[O:21])[NH:6][C:7]([CH2:12][OH:13])=[C:8]([CH2:10][CH3:11])[CH:9]=1
Reactant: CCc1cc([N+](=O)[O-])c(=O)[nH]c1COCc1ccccc1
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: CCc1cc(N)c(=O)[nH]c1CO
Reaction time: 84 h
Yield: 90 %

Procedure:
A solution of 3-nitro-5-ethyl-6-benzyloxymethyl-2(1H)-pyridinone (576 mg, 2.0 mmol) in tetrahydrofuran (15 mL) and methanol (15 mL) containing 10% palladium/charcoal (130 mg) was hydrogenated at atomspheric pressure, monitoring the progress by thin layer chromatography (tlc). Additional catalyst was added in 100 mg portions after day 2 and day 3. After 3-4 days, the catalyst was filtered and the solvents evaporated. The catalyst was vigorously washed with methanol/chloroform and combined solvents evaporated. The residue was triturated with methylene chloride and productcollected by filtration to give 136 mg of 90% pure product. This material was used without further purfification.
Reaction SMILES: COC[O:4][C:5]1[CH:6]=[CH:7][C:8]([O:16][CH2:17][CH:18]2[CH2:20][O:19]2)=[C:9]([CH:15]=1)[C:10]([O:12][CH2:13][CH3:14])=[O:11].[C:21]1([C:27]2[C:35]3[C:34]([N:36]4[CH2:41][CH2:40][CH:39]([NH2:42])[CH2:38][CH2:37]4)=[N:33][CH:32]=[N:31][C:30]=3[S:29][CH:28]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[OH:4][C:5]1[CH:6]=[CH:7][C:8]([O:16][CH2:17][CH:18]([OH:19])[CH2:20][NH:42][CH:39]2[CH2:40][CH2:41][N:36]([C:34]3[C:35]4[C:27]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)=[CH:28][S:29][C:30]=4[N:31]=[CH:32][N:33]=3)[CH2:37][CH2:38]2)=[C:9]([CH:15]=1)[C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: CCOC(=O)c1cc(OCOC)ccc1OCC1CO1
Reactant: NC1CCN(c2ncnc3scc(-c4ccccc4)c23)CC1
Product: CCOC(=O)c1cc(O)ccc1OCC(O)CNC1CCN(c2ncnc3scc(-c4ccccc4)c23)CC1
Yield: 48 %

Procedure:
Synthesis followed SP6 (6 h), using 250 μmol ethyl 5-(methoxymethoxy)-2-(oxiran-2-ylmethoxy)benzoate and 1-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-4-amine to give MOM intermediate upon purification by prep. TLC (2 mm silica gel, PE/CH2Cl2/MeOH 4:6:1) with 48% yield. Product was obtained by MOM-removal according to SP8 with 32% yield upon purification by prep. TLC (1 mm silica gel, PE/CH2Cl2/MeOH 2:5:1).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][C:12]2[C:13]([F:18])=[N:14][CH:15]=[CH:16][CH:17]=2)=[C:6]([CH:10]=1)[C:7]([OH:9])=O.[CH2:19]([NH:21][CH2:22][CH3:23])[CH3:20].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][C:12]2[C:13]([F:18])=[N:14][CH:15]=[CH:16][CH:17]=2)=[C:6]([CH:10]=1)[C:7]([N:21]([CH2:22][CH3:23])[CH2:19][CH3:20])=[O:9]
Reactant: O=C(O)c1cc(Br)ccc1Oc1cccnc1F
Reactant: CCNCC
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Product: CCN(CC)C(=O)c1cc(Br)ccc1Oc1cccnc1F
Reaction time: 8 h

Procedure:
A mixture of crude 5-bromo-2-(2-fluoropyridin-3-yloxy)benzoic acid (8.00 g, 25.6 mmol), diethylamine (6.63 mL, 64.1 mmol) and TBTU (8.23 g, 25.6 mmol) in 8 mL of DMF was stirred overnight. The reaction was quenched with Sat. NaHCO3, extracted with EA/H=2:1, washed with brine, dried over Na2SO4, filtered and evaporated to dryness. CC (DCM to DCM/EA 100:5 to 100:10 to 100:20 to 3:1) gave 5-bromo-N,N-diethyl-2-(2-fluoropyridin-3-yloxy)benzamide as a yellow solid.
Reaction SMILES: [C:1]1([N:7]2[C:15]3[C:10](=[CH:11][C:12]([O:20][CH3:21])=[C:13]([O:18][CH3:19])[C:14]=3OC)[CH:9]=[C:8]2[C:22]([O:24]C)=[O:23])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[K+].[CH2:28]([OH:30])C>>[C:1]1([N:7]2[C:15]3[C:10](=[C:11]([O:30][CH3:28])[C:12]([O:20][CH3:21])=[C:13]([O:18][CH3:19])[CH:14]=3)[CH:9]=[C:8]2[C:22]([OH:24])=[O:23])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)c1cc2cc(OC)c(OC)c(OC)c2n1-c1ccccc1
Reactant: CCO
Agent: [K+]
Agent: [OH-]
Product: COc1cc2c(cc(C(=O)O)n2-c2ccccc2)c(OC)c1OC
Reaction time: 0.5 h

Procedure:
Methyl 1-phenyl-5,6,7-trimethoxyindole-2-carboxylate (280 mg) was dissolved in ethanol (5 mL), a 10% aqueous solution (2 mL) of potassium hydroxide was added to the solution, and the mixture was stirred for 30 minutes under reflux. After cooling, the reaction mixture was concentrated under reduced pressure, and the residue was dissolved in water and washed with ether. The water layer was then neutralized with hydrochloric acid and extracted with ethyl acetate. The resultant organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to obtain the title compound.
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@H:8]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[O:7][C@@H:6]1[N:19]1[CH:23]=[N:22][C:21]([C:24]([O:26]C)=O)=[N:20]1)(=[O:3])[CH3:2].[NH3:28]>CO>[C:1]([O:4][C@H:5]1[C@@H:14]([O:15][C:16](=[O:18])[CH3:17])[C@H:8]([CH2:9][O:10][C:11](=[O:13])[CH3:12])[O:7][C@@H:6]1[N:19]1[CH:23]=[N:22][C:21]([C:24]([NH2:28])=[O:26])=[N:20]1)(=[O:3])[CH3:2]
Reactant: COC(=O)c1ncn([C@H]2O[C@@H](COC(C)=O)[C@H](OC(C)=O)[C@@H]2OC(C)=O)n1
Reactant: N
Solvent: CO
Product: CC(=O)OC[C@@H]1O[C@H](n2cnc(C(N)=O)n2)[C@@H](OC(C)=O)[C@H]1OC(C)=O

Procedure:
Methyl 1,2,4-triazole-3-carboxylate and 1,2,3,5-tetra-O-acetyl-β-L-ribofuranose are heated under reduced pressure in the presence of trifluoromethanesulfonic acid or bis(p-nitrophenyl)-phosphate. The residue is recrystallized from ethanol or methanol to obtain methyl 1-(2,3,5-tri-O-acetyl-β-L-ribofuranosyl)-1,2,4-triazole-3-carboxylate. Subsequently, the obtained methyl 1-(2,3,5-tri-O-acetyl-β-L-ribofuranosyl)-1,2,4-triazole-3-carboxylate is treated with ammonia in a methanol solvent, and the resultant mixture is then recrystallized from ethanol to obtain a crude product of 1-(2,3,5-tri-O-acetyl-β-L-ribofuranosyl)-1,2,4-triazole-3-carboxamide. The obtained compound is further recrystallized from an ethanol aqueous solution, so as to obtain high-purity 1-(2,3,5-tri-O-acetyl-β-L-ribofuranosyl)-1,2,4-triazole-3-carboxamide.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]([C:6]1[CH:20]=[CH:19][C:9]2[N:10]=[C:11]([NH:13][C:14]([NH:16][CH2:17][CH3:18])=[O:15])[S:12][C:8]=2[CH:7]=1)=[O:5].C(N(CC)CC)C.[C:28](Cl)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CN(C=O)C>[CH2:17]([NH:16][C:14]([NH:13][C:11]1[S:12][C:8]2[CH:7]=[C:6]([C:4](=[O:5])[CH2:3][CH2:2][NH:1][C:28](=[O:35])[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:20]=[CH:19][C:9]=2[N:10]=1)=[O:15])[CH3:18]
Reactant: CCNC(=O)Nc1nc2ccc(C(=O)CCN)cc2s1
Reactant: O=C(Cl)c1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCNC(=O)Nc1nc2ccc(C(=O)CCNC(=O)c3ccccc3)cc2s1
Reaction time: 0.08 h
Yield: 27.7 %

Procedure:
A solution of 1-(6-(3-aminopropanoyl)-2-benzothiazolyl)-3-ethylurea (0.033 g, 0.10 mmol) in 1 mL anhydrous DMF was treated with triethylamine (0.028 mL, 0.20 mmol, 2.0 eq) at room temperature. It was stirred for about 5 min, followed by the addition of benzoyl chloride (0.014 mL, 0.12 mmol, 1.2 eq). It was stirred for about 2.5 hours, quenched with MeOH, filtered, concentrated, and purified by HPLC to give the desired compound 0.011 g (28%). LC/MS 396.7 (M+1); LC retention time 2.74 min.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[N:10]2[CH:11]=[C:12]([C:15]3[C:16]([C:39]4[S:43][C:42]([C:44]#[N:45])=[CH:41][CH:40]=4)=[N:17][N:18]([C:20]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH:19]=3)[CH:13]=[CH:14][C:9]2=[N:8][CH:7]=1.[N-:46]=[N+:47]=[N-:48].[Na+].[Cl-].[NH4+].O>CN(C)C=O>[NH:46]1[C:44]([C:42]2[S:43][C:39]([C:16]3[C:15]([C:12]4[CH:13]=[CH:14][C:9]5[N:10]([C:6]([C:2]6[S:1][CH:5]=[CH:4][N:3]=6)=[CH:7][N:8]=5)[CH:11]=4)=[CH:19][N:18]([C:20]([C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:17]=3)=[CH:40][CH:41]=2)=[N:45][N:48]=[N:47]1
Reactant: N#Cc1ccc(-c2nn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cc2-c2ccc3ncc(-c4nccs4)n3c2)s1
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: c1ccc(C(c2ccccc2)(c2ccccc2)n2cc(-c3ccc4ncc(-c5nccs5)n4c3)c(-c3ccc(-c4nnn[nH]4)s3)n2)cc1
Temperature: 100 °C
Reaction time: 18 h
Yield: 56.1 %

Procedure:
100 mg 5-[4-(3-thiazol-2-yl-imidazo[1,2-a]pyridin-6-yl)-1-trityl-1H-pyrazol-3-yl]-thiophen-2-carbonitrile (compound in Example 440) was dissolved in 3 mL N,N-dimethylformamide, and 12 mg sodium azide and 9.5 mg ammonium chloride were added thereto and stirred at 100° C. for 18 hours in a stream of nitrogen. 24 mg sodium azide and 19 mg ammonium chloride were further added thereto and stirred for additional 24 hours. Water was added to the reaction solution which was then extracted with ethyl acetate and purified by silica gel column chromatography (ethyl acetate/hexane), to give 60 mg of the title compound (pale pink solid).
Reaction SMILES: Br[C:2]1[C:3]2[O:23][CH:22]=[CH:21][C:4]=2[C:5](=[O:20])[N:6]([CH2:8][CH2:9][C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)[CH:7]=1.[N:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1>>[N:24]1[CH:29]=[CH:28][C:27]([C:2]2[C:3]3[O:23][CH:22]=[CH:21][C:4]=3[C:5](=[O:20])[N:6]([CH2:8][CH2:9][C:10]3[CH:19]=[CH:18][C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[N:11]=3)[CH:7]=2)=[CH:26][CH:25]=1
Reactant: OB(O)c1ccncc1
Reactant: O=c1c2ccoc2c(Br)cn1CCc1ccc2ccccc2n1
Product: O=c1c2ccoc2c(-c2ccncc2)cn1CCc1ccc2ccccc2n1

Procedure:
165.2 but using 7-bromo-5-(2-(quinolin-2-yl)ethyl)furo[3,2-c]pyridin-4(5H)-one (61.7 mg, 0.167 mmol) and pyridin-4-ylboronic acid (22.82 mg, 0.167 mmol mmol). The title compound was obtained as yellowish solid (yield: 22 mg, 35.8.9%).
Reaction SMILES: [C:1]([O:5][C:6](=[O:21])[NH:7][C:8]1[CH:13]=[C:12]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[CH:11]=[CH:10][C:9]=1[NH2:20])([CH3:4])([CH3:3])[CH3:2].C([O:26][C:27](=O)[CH2:28][C:29](=[O:42])[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([C:36]2[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=2)[CH:31]=1)(C)(C)C>>[C:1]([O:5][C:6](=[O:21])[NH:7][C:8]1[CH:13]=[C:12]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[CH:11]=[CH:10][C:9]=1[NH:20][C:27](=[O:26])[CH2:28][C:29](=[O:42])[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([C:36]2[CH:37]=[CH:38][N:39]=[CH:40][CH:41]=2)[CH:31]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)CC(=O)c1cccc(-c2ccncc2)c1
Reactant: CC(C)(C)OC(=O)Nc1cc(OCC(F)(F)F)ccc1N
Product: CC(C)(C)OC(=O)Nc1cc(OCC(F)(F)F)ccc1NC(=O)CC(=O)c1cccc(-c2ccncc2)c1

Procedure:
The title compound was prepared from [2-amino-5-(2,2,2-trifluoro-ethoxy)-phenyl]-carbamic acid tert-butyl ester (Example J13) (230 mg, 0.75 mmol) and 3-oxo-3-(3-pyridin-4-yl-phenyl)-propionic acid tert-butyl ester (Example K2) (223 mg, 0.75 mmol) according to the general procedure M. Obtained as a light brown solid (258 mg).
Reaction SMILES: [CH3:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(N(C(C)C)CC)(C)C.[C:20]12([CH2:30][NH2:31])[CH2:29][CH:24]3[CH2:25][CH:26]([CH2:28][CH:22]([CH2:23]3)[CH2:21]1)[CH2:27]2.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[C:20]12([CH2:30][NH:31][C:4](=[O:6])[C:3]3[CH:7]=[CH:8][CH:9]=[N:10][C:2]=3[CH3:1])[CH2:27][CH:26]3[CH2:25][CH:24]([CH2:23][CH:22]([CH2:28]3)[CH2:21]1)[CH2:29]2
Reactant: Cc1ncccc1C(=O)O
Reactant: NCC12CC3CC(CC(C3)C1)C2
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ncccc1C(=O)NCC12CC3CC(CC(C3)C1)C2
Temperature: 25 °C
Reaction time: 17 h

Procedure:
To a mixture of 2-methylnicotinic acid (2.06 g, 15 mmol) in 40 mL of DMF is added sequentially diisopropylethylamine (5.2 mL, 30 mmol), 1-adamantan-1-ylmethanamine (2.5 g, 15 mmol), and benzotriazol-1-yloxytris-(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent, 8 g, 18 mmol). The resulting mixture is stirred at rt for 17 h. The mixture is then poured into ice water (150 mL), and the precipitated solid is collected by vacuum filtration and dried in vacuo to afford the title compound as an off-white solid. Mass spec. (285.19, M+H).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([F:37])=[C:21]([NH:25][S:26]([C:29]3[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=3[F:36])(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[CH:5]=[CH:4][N:3]=1.[NH3:38].CO>>[NH2:38][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([F:37])=[C:21]([NH:25][S:26]([C:29]3[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=3[F:36])(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[CH:5]=[CH:4][N:3]=1
Reactant: N
Reactant: O=S(=O)(Nc1cccc(-c2nc(C3CCOCC3)sc2-c2ccnc(Cl)n2)c1F)c1cc(F)ccc1F
Solvent: CO
Product: Nc1nccc(-c2sc(C3CCOCC3)nc2-c2cccc(NS(=O)(=O)c3cc(F)ccc3F)c2F)n1

Procedure:
Following a procedure analogous to the procedure described in Example 52, Step B using N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide (0.150 g, 0.265 mmol) and 7N ammonia in methanol (5.67 mL, 39.7 mmol), the title compound was obtained as a white solid (93 mg, 64% yield). MS (ESI): 548 [M+H]+.
Reaction SMILES: N[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5](SC2C(C)=C(S(O)(=O)=O)C(C)=C(N)C=2C)=[CH:4][C:3]=1S(O)(=O)=O>N1C=CC=CC=1>[CH:9]1[C:8]2[C:7](=[O:17])[C:6]3[C:15](=[CH:2][CH:3]=[CH:4][CH:5]=3)[C:14](=[O:16])[C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: Cc1c(N)c(C)c(S(=O)(=O)O)c(C)c1Sc1cc(S(=O)(=O)O)c(N)c2c1C(=O)c1ccccc1C2=O
Solvent: c1ccncc1
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
Example 27 was repeated, except that the compounds shown in 1st, 2nd and 3rd columns of the following table were used in place of the 1-amino-4-(3'-amino-2',4',6'-trimethyl-5'-sulfophenylthio)anthraquinone-2-sulfonic acid, 1-aminobenzene-3-β-sulfatoethylsulfone and pyridine, respectively, thereby obtaining a corresponding anthraquinone compound. The color shade on cotton of the compound is as shown in a 4th column of the table.
Reaction SMILES: COC1C=CC(C[N:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][O:23][CH3:24])[CH2:9]2)=CC=1.ClC(OC(Cl)C)=O.CO>ClCCCl>[CH3:24][O:23][CH2:22][CH2:21][O:20][CH2:19][CH2:18][O:17][C:14]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:15]=1[CH2:16][NH:8][CH2:9]2
Reactant: COCCOCCOc1cccc2c1CN(Cc1ccc(OC)cc1)C2
Agent: CC(Cl)OC(=O)Cl
Solvent: ClCCCl
Solvent: CO
Product: COCCOCCOc1cccc2c1CNC2
Reaction time: 17 h

Procedure:
A solution of 2-(4-methoxy-benzyl)-4-[2-(2-methoxy-ethoxy)-ethoxy]-2,3-dihydro-1H-isoindole (45 mg, 0.13 mmol) in 1,2-dichloroethane (2 mL) was treated with α-chloroethyl chloroformate (0.1 mL, 0.93 mmol). After 17 hours, methanol (5 mL) was added and the mixture stirred for 3 hours. The solvents were removed in vacuo to afford the title compound as a greenish-black solid, which was used without further purification. 1H NMR (methanol-d4) 7.36 (1H, t), 6.98 (2H, d), 4.60 (2H, s), 4.57 (2H, s), 4.23-4.21 (2H, m), 3.85-3.83 (2H, m), 3.69-3.67 (2H, m), 3.57-3.54 (2H, m), 3.36 (3H, s). MS: [M+H]+ 238.