Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[N:2]1.Cl[CH:7]([C:9]1[CH:21]=[CH:20][C:19]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12][C:11]=2[CH:10]=1)[CH3:8]>O>[CH:10]1[C:11]2[CH2:12][C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:19]=2[CH:20]=[CH:21][C:9]=1[CH:7]([N:1]1[CH:5]=[CH:4][N:3]=[N:2]1)[CH3:8]
Reactant: c1c[nH]nn1
Reactant: CC(Cl)c1ccc2c(c1)Cc1ccccc1-2
Solvent: O
Product: CC(c1ccc2c(c1)Cc1ccccc1-2)n1ccnn1
Temperature: 120 °C
Yield: 49.3 %

Procedure:
1H-1,2,3-Triazole (1.64 g) was added to 2-(1-chloroethyl)-9H-fluorene (1.1 g), followed by heating at 120° C. for 30 minutes. After cooling, water was added and the mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate, the solvent was evaporated and then the thus obtained residue was subjected to silica gel column chromatography. Crude crystals obtained from the chloroform eluent were recrystallized from ethyl acetate to obtain 0.62 g of 1-[1-(9H-fluoren-2-yl)ethyl]-1H-1,2,3-triazole.
Reaction SMILES: [Br-].[K+].[OH:3][CH2:4][C@H:5]1[O:10][C:9]([CH3:12])([CH3:11])[O:8][C@@H:7]([CH2:13][C:14]([N:16]([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:19])[CH3:18])=[O:15])[CH2:6]1.Cl[O-].[Na+]>C(Cl)Cl>[CH:4]([C@H:5]1[O:10][C:9]([CH3:11])([CH3:12])[O:8][C@@H:7]([CH2:13][C:14]([N:16]([CH:17]([CH3:19])[CH3:18])[CH:20]([CH3:21])[CH3:22])=[O:15])[CH2:6]1)=[O:3]
Reactant: CC(C)N(C(=O)C[C@H]1C[C@@H](CO)OC(C)(C)O1)C(C)C
Agent: [Br-]
Agent: [K+]
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)N(C(=O)C[C@H]1C[C@@H](C=O)OC(C)(C)O1)C(C)C

Procedure:
1 gram of potassium bromide and 0.1 gram of 2,2,6,6-tetramethyl-1-piperidinyloxy free radical is added to the a solution of 25 grams of 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl)-N,N-diisopropylacetamide in methylene chloride at 0-5° C. Added sodium hypochlorite to the above reaction mixture at 0-5° C. in 1 hour. Stirred the reaction for 30 minutes at 0-5° C. Quenched the reaction mixture with 10% sodium thio sulphate solution. Separated the organic and inorganic phases. Washed the organic layer with water. Dried the organic layer over sodium sulfate. Distilled the solvent completely under reduced pressure to get the title compound.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][N:8]=[C:9]([F:12])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:13]#[N:14].[NH2:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[C:19]#[N:20]>>[C:19]([C:18]1[CH:17]=[C:16]([NH:15][C:2]2[C:11]3[C:6](=[CH:7][N:8]=[C:9]([F:12])[CH:10]=3)[N:5]=[CH:4][C:3]=2[C:13]#[N:14])[CH:23]=[CH:22][CH:21]=1)#[N:20]
Reactant: N#Cc1cnc2cnc(F)cc2c1Cl
Reactant: N#Cc1cccc(N)c1
Product: N#Cc1cccc(Nc2c(C#N)cnc3cnc(F)cc23)c1
Yield: 29.1 %

Procedure:
Following the procedure described above in Example 13, 4-chloro-6-fluoro-1,7-naphthyridine-3-carbonitrile (0.300 g, 1.45 mmol) was reacted with 3-aminobenzonitrile (0.188 g, 1.59 mmol). The crude product was purified by flash chromatography over silica gel (15-30% EtOAc in CH2Cl2) to give pure 4-(3-cyanophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile (0.122 g, 29% yield): 1H NMR (400 MHz, DMSO-D6) δ 7.57-7.80 (m, 3 H) 7.88 (s, 1 H) 8.16 (s, 1 H) 8.75 (s, 1 H) 9.11 (s, 1 H) 10.23 (s, 1 H).
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[CH2:11]([CH:13]1[O:15][CH2:14]1)Cl>>[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH:13]2[CH2:14][O:15]2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2]
Reactant: ClCC1CO1
Reactant: CC(C)c1ccc(O)cc1
Product: CC(C)c1ccc(OCC2CO2)cc1

Procedure:
The title compound was prepared from 4-isopropyl-phenol and epichlorohydrin employing the procedures as set forth in Step 1 of Example 2.
Reaction SMILES: [O:1]=[S:2](=[O:24])([CH2:7][C:8]#[C:9][CH2:10][C:11]#[C:12][CH2:13][C:14]#[C:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH2:3][C:4]([OH:6])=[O:5].[CH3:25]O>S(=O)(=O)(O)O>[O:1]=[S:2](=[O:24])([CH2:7][C:8]#[C:9][CH2:10][C:11]#[C:12][CH2:13][C:14]#[C:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH2:3][C:4]([O:6][CH3:25])=[O:5]
Reactant: CO
Reactant: CCCCCCCCC#CCC#CCC#CCS(=O)(=O)CC(=O)O
Agent: O=S(=O)(O)O
Product: CCCCCCCCC#CCC#CCC#CCS(=O)(=O)CC(=O)OC

Procedure:
A solution of 1 g of 3,3-dioxo-3-thia-5,8,11-eicosatriynoic acid in 50 cm3 of methanol is heated under reflux in the presence of a sulfuric acid catalyst for 48 hours. The mixture is then filtered at ambient temperature. The methanol is evaporated off under reduced pressure.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[C:7]([CH2:11][OH:12])[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O>C(Cl)Cl>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([CH:8]=[CH:9][CH:10]=1)[CH:11]=[O:12])(=[O:3])=[O:4]
Reactant: CS(=O)(=O)c1cccc(CO)c1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CS(=O)(=O)c1cccc(C=O)c1
Yield: 74.2 %

Procedure:
A solution of [3-(methylsulfonyl)phenyl]methanol (680 mg, 3.66 mmol) in anhydrous CH2Cl2 (20 mL) was treated with PCC (1.03 g, 4.75 mmol) at room temperature for 2 hours. The solvent was removed and the residue was purified by flash column chromatography (20-60% EtOAc in hexanes) to give the product (500 mg, 74% yield). 1H NMR (300 MHz, CDCl3) δ: 3.13 (s, 3H), 7.77-7.82 (m, 1H), 8.18-8.24 (m, 2H), 8.46-8.48 (m, 1H), 10.12 (s, 1H).
Reaction SMILES: C(OC([NH:11][CH2:12][C:13]1[CH:14]=[C:15]([NH:24][C:25](=[O:66])[CH2:26][O:27][C:28]2[C:33]([CH3:34])=[CH:32][C:31]([CH:35]([NH:39][C:40]3[CH:41]=[C:42]4[C:47](=[CH:48][CH:49]=3)[C:46]([N:50]([C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])=[N:45][CH:44]=[CH:43]4)[C:36]([OH:38])=[O:37])=[CH:30][C:29]=2[CH3:65])[CH:16]=[CH:17][C:18]=1[S:19]([CH2:22][CH3:23])(=[O:21])=[O:20])=O)C1C=CC=CC=1>CO.[Pd]>[NH2:11][CH2:12][C:13]1[CH:14]=[C:15]([NH:24][C:25](=[O:66])[CH2:26][O:27][C:28]2[C:29]([CH3:65])=[CH:30][C:31]([CH:35]([NH:39][C:40]3[CH:41]=[C:42]4[C:47](=[CH:48][CH:49]=3)[C:46]([N:50]([C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[C:51]([O:53][C:54]([CH3:55])([CH3:57])[CH3:56])=[O:52])=[N:45][CH:44]=[CH:43]4)[C:36]([OH:38])=[O:37])=[CH:32][C:33]=2[CH3:34])[CH:16]=[CH:17][C:18]=1[S:19]([CH2:22][CH3:23])(=[O:21])=[O:20]
Reactant: CCS(=O)(=O)c1ccc(NC(=O)COc2c(C)cc(C(Nc3ccc4c(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)nccc4c3)C(=O)O)cc2C)cc1CNC(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CO
Product: CCS(=O)(=O)c1ccc(NC(=O)COc2c(C)cc(C(Nc3ccc4c(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)nccc4c3)C(=O)O)cc2C)cc1CN
Reaction time: 1 h
Yield: 93 %

Procedure:
To a solution of 79D (190 mg, 0.205 mmol) in 5 mL methanol, was added 10% Pd—C (30 mg). The reaction was evacuated and flushed with H2 (3×), then stirred under an atmosphere of H2 for 1 h. The reaction was filtered and concentrated to afford 151 mg (93%) of 79E as an orange solid. MS (ESI) m/z 926.5 (M+H)+.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([CH2:22][C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)=[CH:18][N:17]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.[O:29]1C2C=CC(C3(C(NC4C=CC(Br)=CN=4)=O)CC3)=CC=2O[CH2:30]1.[Cl-].COC1C=CC(C[Zn+])=CC=1>>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([CH2:22][C:23]5[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=5)=[CH:18][N:17]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: O=C(Nc1ccc(Br)cn1)C1(c2ccc3c(c2)OCO3)CC1
Reactant: O=C(Nc1ccc(Cc2ccccc2)cn1)C1(c2ccc3c(c2)OCO3)CC1
Agent: COc1ccc(C[Zn+])cc1
Agent: [Cl-]
Product: COc1ccc(Cc2ccc(NC(=O)C3(c4ccc5c(c4)OCO5)CC3)nc2)cc1

Procedure:
1-(Benzo[d][1,3]dioxol-5-yl)-N-(5-(4-methoxybenzyl)pyridin-2-yl)cyclopropanecarboxamide was synthesized using the procedure of 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-benzylpyridin-2-yl)cyclopropanecarboxamide by reacting 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-bromopyridin-2-yl)cyclopropanecarboxamide with (4-methoxybenzyl)zinc(II) chloride.
Reaction SMILES: [C:1]([Si:5]([CH3:8])([CH3:7])Cl)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[S:16]1[CH:20]=[CH:19][C:18]([CH2:21][OH:22])=[CH:17]1>CN(C=O)C>[C:1]([Si:5]([CH3:8])([CH3:7])[O:22][CH2:21][C:18]1[CH:19]=[CH:20][S:16][CH:17]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OCc1ccsc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCc1ccsc1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
A mixture of tert-butyldimethylchlorosilane (1.58 g), triethylamine (2.44 ml), 3-thiophenemethanol (0.822 ml) and DMF (20 ml) was stirred at 60° C. for 1 h. Additional DMF (20 ml) was added to the reaction mixture, and the mixture was stirred at 60° C. for 2 h. The mixture was quenched with saturated NaHCO3 solution, and extracted with EtOAc. The organic layer was separated, washed with water and brine successively, dried over MgSO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane) to give the title compound (1.6 g) as a colorless oil.
Reaction SMILES: [NH2:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:17])=[CH:6][C:5]([Cl:18])=[CH:4][N:3]=1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]=[C:27]=[S:28])=[CH:22][CH:21]=1.C1(C)C=CC=CC=1>CCOCC>[Cl:17][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([F:16])[C:10]=1[CH2:9][O:8][C:7]1[C:2]([NH:1][C:27]([NH:26][C:23]2[CH:24]=[CH:25][C:20]([Cl:19])=[CH:21][CH:22]=2)=[S:28])=[N:3][CH:4]=[C:5]([Cl:18])[CH:6]=1
Reactant: S=C=Nc1ccc(Cl)cc1
Reactant: Nc1ncc(Cl)cc1OCc1c(F)cccc1Cl
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: Fc1cccc(Cl)c1COc1cc(Cl)cnc1NC(=S)Nc1ccc(Cl)cc1

Procedure:
A mixture of 2-amino-3-(2-chloro-6-fluorobenzyloxy)-5-chloropyridine (0.82 g, 0.0028 mol), 4-chlorophenyl isothiocyanate (0.56 g, 0.0033 mol) and toluene (10 ml) was heated under reflux for 16 hours, then cooled and diluted with ether to induce crystallisation of the product, which was triturated with ethanol. Yield 0.68 g (54%), m.p. 158°-160 ° C.
Reaction SMILES: [CH:1]([NH:4][C:5]1[C:6]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([C:19]3[CH:27]=[CH:26][C:22]([C:23]([OH:25])=O)=[CH:21][N:20]=3)=[O:18])[CH2:13][CH2:12]2)=[N:7][CH:8]=[CH:9][CH:10]=1)([CH3:3])[CH3:2].C1(N=C=NC2CCCCC2)CCCCC1.ON1C2C=CC=CC=2N=N1.[NH2:53][CH2:54][C:55]1[CH:56]=[N:57][CH:58]=[CH:59][CH:60]=1>C(Cl)Cl.O1CCCC1>[CH:1]([NH:4][C:5]1[C:6]([N:11]2[CH2:12][CH2:13][N:14]([C:17]([C:19]3[CH:27]=[CH:26][C:22]([C:23]([NH:53][CH2:54][C:55]4[CH:56]=[N:57][CH:58]=[CH:59][CH:60]=4)=[O:25])=[CH:21][N:20]=3)=[O:18])[CH2:15][CH2:16]2)=[N:7][CH:8]=[CH:9][CH:10]=1)([CH3:2])[CH3:3]
Reactant: NCc1cccnc1
Reactant: CC(C)Nc1cccnc1N1CCN(C(=O)c2ccc(C(=O)O)cn2)CC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: C1CCOC1
Product: CC(C)Nc1cccnc1N1CCN(C(=O)c2ccc(C(=O)NCc3cccnc3)cn2)CC1
Reaction time: 2 h
Yield: 75 %

Procedure:
6-[1-[3-(isopropylamino)-2-pyridyl]piperazin-4-yl-carbonyl]nicotinic acid (2 g) was added to a co-solvent of tetrahydrofuran (30 ml) and methylene chloride (30 ml) and with the successive addition of 1,3-dicyclohexylcarbodimide (2.4 g) and 1-hydroxybenzotriazole (0.85 g) at 15° C.˜20° C., the mixture was reacted at the same temperature for 2 hours. With the addition of 3-(aminomethyl)pyridine (0.65 g) at 20° C., the reaction mixture was stirred at 20° C.˜25° C. for 2 hours. With the addition of methylene chloride (60 ml). The mixture was washed with water 3 times, dried over magnesium sulfate and concentrated under reduced pressure. The concentrated residue was chromatographed on column (hexane/chloroform/ethanol=5/2/1, v/v/v). The purified solution was concentrated under reduced pressure, and then, the residue was treated with ether for crystallization to give a desired compound of 1.87 g (yield: 75%).
Reaction SMILES: C([O:8][C:9]([CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH2:24][C:25]1[CH:26]=[CH:27][C:28]3[O:32][C:31]([C:33]4[S:34][CH:35]=[C:36]([C:38]([CH3:41])([CH3:40])[CH3:39])[N:37]=4)=[CH:30][C:29]=3[CH:42]=1)[CH:19]=[C:18]2[CH2:43][C:44]([O:46][CH3:47])=[O:45])=[O:10])C1C=CC=CC=1.O1CCCC1>CO>[C:38]([C:36]1[N:37]=[C:33]([C:31]2[O:32][C:28]3[CH:27]=[CH:26][C:25]([CH2:24][N:20]4[C:21]5[C:17](=[CH:16][C:15]([O:14][CH2:13][CH2:12][CH2:11][C:9]([OH:10])=[O:8])=[CH:23][CH:22]=5)[C:18]([CH2:43][C:44]([O:46][CH3:47])=[O:45])=[CH:19]4)=[CH:42][C:29]=3[CH:30]=2)[S:34][CH:35]=1)([CH3:41])([CH3:39])[CH3:40]
Reactant: COC(=O)Cc1cn(Cc2ccc3oc(-c4nc(C(C)(C)C)cs4)cc3c2)c2ccc(OCCCC(=O)OCc3ccccc3)cc12
Solvent: CO
Solvent: C1CCOC1
Product: COC(=O)Cc1cn(Cc2ccc3oc(-c4nc(C(C)(C)C)cs4)cc3c2)c2ccc(OCCCC(=O)O)cc12

Procedure:
A solution of methyl 5-[3-(benzyloxycarbonyl)propoxy]-1-{[2-(4-tert-butylthiazol-2-yl)benzofuran-5-yl]methyl}indole-3-acetate in a mixed solvent of tetrahydrofuran (2 ml) and methanol (2 ml) was hydrogenated over 10% Pd--C (60 mg) at room temperature under atmosphere pressure. After removal of the catalyst by filtration, the filtrate was concentrated under reduced pressure to give methyl 1-{[2-(4-tert-butylthiazol-2-yl)benzofuran-5-yl]methyl}-5-(3-carboxypropoxy)indole-3-acetate (0.16 g).
Reaction SMILES: [Br:1][C:2]1[C:10]2[S:9][C:8]([NH:11]C(=O)C)=[N:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.BrC1C=CC2N=C(NC(=O)C)SC=2C=1.[OH-].[Na+].Cl>CO.O>[Br:1][C:2]1[C:10]2[S:9][C:8]([NH2:11])=[N:7][C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: CC(=O)Nc1nc2cccc(Br)c2s1
Agent: CC(=O)Nc1nc2ccc(Br)cc2s1
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CO
Product: Nc1nc2cccc(Br)c2s1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 116 %

Procedure:
The mixture (562 mg, 2.07 mmol) of N-(7-bromobenzo[d]thiazol-2-yl)acetamide and N-(6-bromobenzo[d]thiazol-2-yl)acetamide were suspended in MeOH (10 mL) and water (2 mL), sodium hydroxide (468.1 mg, 11.70 mmol) were added. The flask was fit with a reflux condenser and placed in a preheated oil bath (78° C.-80° C.) and stirred under nitrogen for 90 minutes. The reaction was cooled to RT and treated with 5N HCl to lower the pH to about 2. The suspension was filtered, and the solid was washed with water. The filtrate was treated with saturated sodium bicarbonate to adjust pH to about 7, and it was filtered again. The solid was collected and purified on an HPLC (10-95% MeCN/water with 0.1% TFA over 40 minutes) to provide 7-bromobenzo[d]thiazol-2-amine (550.3 mg).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:5]([O:21][CH3:22])=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH:30]2[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]2)=[CH:26][CH:25]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:22][O:21][C:5]1[C:6]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][C:17]([O:19][CH3:20])=[O:18])=[N:7][C:2]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([CH:30]3[CH2:31][CH2:32][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:34][CH2:35]3)=[CH:26][CH:25]=2)=[N:3][CH:4]=1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(N)cc2)CC1
Reactant: COC(=O)Cc1ccccc1C#Cc1nc(Cl)ncc1OC
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: COC(=O)Cc1ccccc1C#Cc1nc(Nc2ccc(C3CCN(C(=O)OC(C)(C)C)CC3)cc2)ncc1OC
Temperature: 120 °C
Reaction time: 1 h

Procedure:
To a solution of methyl 2-(2-((2-chloro-5-methoxypyrimidin-4-yl)ethynyl)phenyl)acetate (A98) (0.10 g, 0.32 mmol) in 1,4-dioxane (6 mL) was added tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate (0.087 g, 0.32 mmol), Cs2CO3 (0.41 g, 1.3 mmol), Pd2(dba)3 (0.030 g, 0.032 mmol) and Xantphos (0.055 g, 0.095 mmol). The resulting mixture was degassed with nitrogen for 5 minutes, before heating under microwave irradiation for 30 minutes at 120° C., then for 60 minutes at 120° C. EtOAc (100 mL) was added and the mixture was washed with water (2×25 mL), brine (25 mL), dried (MgSO4) and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-25% EtOAc in petroleum benzine 40-60° C.) to give the title compound A99 as a yellow oil (0.11 g, 64%); 1H NMR (400 MHz, CDCl3) δ 8.18 (s, 1H), 7.66 (d, J=7.6 Hz, 1H), 7.52 (d, J=8.5 Hz, 2H), 7.43-7.29 (m, 3H), 7.16 (d, J=8.5 Hz, 2H), 6.98 (s, 1H), 4.38-4.17 (m, 2H), 4.02 (s, 2H), 3.94 (s, 3H), 3.70 (s, 3H), 2.80 (t, J=11.9 Hz, 2H), 2.62 (tt, J=12.0, 3.3 Hz, 1H), 1.82 (d, J=13.0 Hz, 2H), 1.68-1.51 (m, peak obscured), 1.49 (s, 9H). LCMS-A: rt 6.69 min; m/z 557.3 [M+H]+.
Reaction SMILES: [C:1]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][C:4]([CH:7]=O)=[CH:3][CH:2]=1.[C:15]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)(=[O:17])[CH3:16]>>[C:1]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][C:4]([CH:7]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:17])=[CH:3][CH:2]=1
Reactant: O=Cc1ccc(-c2ccccc2)cc1
Reactant: CC(=O)c1ccccc1
Product: O=C(C=Cc1ccc(-c2ccccc2)cc1)c1ccccc1

Procedure:
By a procedure similar to that of example 1.59.1, starting from 4-biphenylcarboxaldehyde and acetophenone, 3-(biphenyl-4-yl)-1-phenylprop-2-en-1-one was obtained as yellowish solid.
Reaction SMILES: [CH2:1]([N:8]1[C:12]2([CH2:17][O:16][P:15](OC3C=CC=CC=3)[O:14][CH2:13]2)[CH2:11][O:10][P:9]1[O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:32]([C:36]1[CH:41]=[C:40]([C:42]([CH3:45])([CH3:44])[CH3:43])[CH:39]=[CH:38][C:37]=1[OH:46])([CH3:35])([CH3:34])[CH3:33].C[O-].[Na+]>>[CH2:1]([N:8]1[C:12]2([CH2:17][O:16][P:15]([O:46][C:37]3[CH:38]=[CH:39][C:40]([C:42]([CH3:45])([CH3:44])[CH3:43])=[CH:41][C:36]=3[C:32]([CH3:35])([CH3:34])[CH3:33])[O:14][CH2:13]2)[CH2:11][O:10][P:9]1[O:25][C:26]1[CH:27]=[CH:28][C:29]([C:2]([CH3:7])([CH3:3])[CH3:1])=[CH:30][C:31]=1[C:12]([CH3:17])([CH3:13])[CH3:11])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)c1ccc(O)c(C(C)(C)C)c1
Reactant: c1ccc(CN2P(Oc3ccccc3)OCC23COP(Oc2ccccc2)OC3)cc1
Agent: C[O-]
Agent: [Na+]
Product: CC(C)(C)c1ccc(OP2OCC3(CO2)COP(Oc2ccc(C(C)(C)C)cc2C(C)(C)C)N3Cc2ccccc2)c(C(C)(C)C)c1

Procedure:
The product of Example 18 is reacted with two equivalents of 2,4-di-tert-butylphenol and sodium methoxide at reduced pressure and at an elevated temperature to afford the title compound.
Reaction SMILES: [OH:1][CH:2]([CH2:13][N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:3][N:4]([CH3:12])[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].[N+:23]([C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28](F)[CH:27]=1)([O-:25])=[O:24].[H-].[Na+].O>CN(C=O)C.CCOC(C)=O.[NH4+].[Cl-]>[F:32][C:30]1[CH:29]=[C:28]([CH:27]=[C:26]([N+:23]([O-:25])=[O:24])[CH:31]=1)[O:1][CH:2]([CH2:13][N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:3][N:4]([CH3:12])[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8]
Reactant: O=[N+]([O-])c1cc(F)cc(F)c1
Reactant: CN(CC(O)CN(C)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: O
Product: CN(CC(CN(C)C(=O)OC(C)(C)C)Oc1cc(F)cc([N+](=O)[O-])c1)C(=O)OC(C)(C)C
Yield: 47.8 %

Procedure:
To 15.0 g (47.1 mmol) of di-tert-butyl 2-hydroxypropane-1,3-diylbis(methylcarbamate) and 11.9 g (75 mmol) of 1-nitro-3,5-difluorobenzene in 100 ml DMF under N2 at 0° C. was added 2.4 g (60 mmol) of NaH in portions. The resultant mixture was stirred at 0° C. for 30 min after which approximately 1 mL of H2O was added slowly. The reaction mixture was diluted with 200 mL EtOAc and 200 mL saturated NH4Cl. The layers were separated and the organic layer was washed with 200 mL of saturated NH4Cl. The organic layer was dried and concentrated. Then the residue was purified by column chromatography over silica gel (EtOAc:Hex=1:6) to give 10.3 g (45%) of di-tert-butyl 2-(3-fluoro-5-nitrophenoxy)propane-1,3-diylbis(methylcarbamate).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([F:9])[CH:8]=1)[NH2:5].[N-:10]([C:13]#[N:14])[C:11]#[N:12].[Na+]>>[C:11]([N:10]=[C:13]([NH2:14])[NH:5][C:4]1[CH:3]=[C:2]([F:1])[CH:8]=[C:7]([F:9])[CH:6]=1)#[N:12]
Reactant: N#C[N-]C#N
Reactant: Nc1cc(F)cc(F)c1
Agent: [Na+]
Product: N#CN=C(N)Nc1cc(F)cc(F)c1

Procedure:
3,5-Difluoroaniline and sodium dicyanamide were procesed as described in Example 71A to provide the desired compound.
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[CH:10]=[C:9]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16](N)=[CH:15][CH:14]=2)[CH:8]=[CH:7][N:6]=1)=[O:4].[N+:20](C1C=CC(O)=CC=1)([O-])=O>>[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[C:9]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([NH2:20])[CH:14]=2)[CH:8]=[CH:7][N:6]=1)=[O:4]
Reactant: O=[N+]([O-])c1ccc(O)cc1
Reactant: CNC(=O)c1cc(COc2ccc(N)cc2)ccn1
Product: CNC(=O)c1cc(COc2cccc(N)c2)ccn1

Procedure:
The title compound was prepared in the same manner described for 4-(4-aminophenoxymethyl)pyridine-2-carboxylic acid methylamide, substituting 3-nitrophenol for 4-nitrophenol. 1H-NMR (CD3OD) δ 8.40 (d, J=4.5 Hz, 1H), 7.54 (d, J=2.1 Hz, 1H), 7.13 (t, J=6.3 Hz, 1H), 7.00 (dd, J=4.2, 1.8 Hz, 1H), 6.62 to 6.59 (m, 1H), 6.43 (t, J=1.8 Hz, 1H), 6.37 to 6.34 (m, 1H), 4.89 (s, 2H), 2.93 (s, 3H).
Reaction SMILES: [N+:1]([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[CH:7]=[CH:6][CH:5]=1)([O-])=O.S([O-])([O-])(=O)=O.[Na+].[Na+].[N+]([O-])([O-])=O.[Na+].[SH-].[Na+]>O>[NH2:1][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[CH:7]=[CH:6][CH:5]=1
Reactant: O=C1c2ccccc2C(=O)c2c1cccc2[N+](=O)[O-]
Agent: O=S(=O)([O-])[O-]
Agent: O=[N+]([O-])[O-]
Agent: [Na+]
Solvent: O
Product: Nc1cccc2c1C(=O)c1ccccc1C2=O

Procedure:
A slurried mixture of a nitroanthraquinone and water having dissolved therein sodium sulfate and sodium nitrate (nitroanthraquinone concentration: 5.28%, sodium sulfate and sodium nitrate concentration: 4%, the remainder being water) and a 30.9% sodium hydrosulfide aqueous solution were supplied into a 1,500-volume-part stainless steel vessel under agitation at the rates of 383.3 part/hr, and 41.7 part/hr, respectively, and three hours after start of supply, withdrawal of the reaction mixture was started at a constant rate of 425 part/hr. The reaction temperature was maintained at 97°-98° C. during this operation. The effluent was cooled to 70°-80° C., filtered, washed and dried to obtain an aminoanthraquinone (dry cake). The aminoanthraquinone efflux rate from the 6th hour and afterward after start of withdrawal was 16.8 part/hr.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][CH2:15][OH:16])[O:8][C:7]([CH3:18])([CH3:17])[CH:6]=[C:5]2[C:19]([F:22])([F:21])[F:20].O[C:24]1[CH:38]=[CH:37][C:27]([O:28][C@@:29]([CH3:36])([CH2:34][CH3:35])[C:30]([O:32][CH3:33])=[O:31])=[CH:26][CH:25]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][CH2:15][O:16][C:24]1[CH:38]=[CH:37][C:27]([O:28][C@@:29]([CH3:36])([CH2:34][CH3:35])[C:30]([O:32][CH3:33])=[O:31])=[CH:26][CH:25]=1)[O:8][C:7]([CH3:18])([CH3:17])[CH:6]=[C:5]2[C:19]([F:20])([F:22])[F:21]
Reactant: CC1(C)C=C(C(F)(F)F)c2cc(Cl)c(OCCCO)cc2O1
Reactant: CC[C@](C)(Oc1ccc(O)cc1)C(=O)OC
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC[C@](C)(Oc1ccc(OCCCOc2cc3c(cc2Cl)C(C(F)(F)F)=CC(C)(C)O3)cc1)C(=O)OC
Temperature: 25 °C
Reaction time: 16 h
Yield: 61 %

Procedure:
To a solution of 3-((6-chloro-2,2-dimethyl-4-(trifluoromethyl)-2H-chromen-7-yl)oxy)propan-1-ol (0.5 g, 1.48 mmol), (2S)-Methyl 2-(4-hydroxyphenoxy)-2-methylbutanoate (0.35 g, 1.56 mmol), and triphenylphosphine (0.42 g, 1.6 mmol) in THF (20 mL) was added diethyl azodicarboxylate (0.28 g, 1.6 mmol) and the solution stirred at ambient temperature for 16 h. After concentrating under reduced pressure, the residue thus obtained was chromatographed over silica gel using AcOEt/hexanes to furnish the desired compound (0.49 g).