Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]([CH2:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH:12]([NH:14][C:15]2[N:20]=[C:19]([N:21]3[CH2:26][CH2:25][C:24](=[O:27])[N:23]4[CH2:28][CH:29]=[C:30]([C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)[N:31]=[C:22]34)[CH:18]=[CH:17][N:16]=2)[CH3:13])=[CH:7][CH:6]=1)=[N+]=[N-].C1CC=CCC=1>[Pd].C(OC(=O)C)C>[NH2:1][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH:12]([NH:14][C:15]2[N:20]=[C:19]([N:21]3[CH2:26][CH2:25][C:24](=[O:27])[N:23]4[CH2:28][CH:29]=[C:30]([C:32]5[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=5)[N:31]=[C:22]34)[CH:18]=[CH:17][N:16]=2)[CH3:13])=[CH:7][CH:6]=1
Reactant: CC(Cc1ccc(CN=[N+]=[N-])cc1)Nc1nccc(N2CCC(=O)N3CC=C(c4ccccc4)N=C32)n1
Agent: [Pd]
Solvent: C1=CCC=CC1
Solvent: CCOC(C)=O
Product: CC(Cc1ccc(CN)cc1)Nc1nccc(N2CCC(=O)N3CC=C(c4ccccc4)N=C32)n1

Procedure:
The mixture of 1-{2-[2-(4-azidomethyl-phenyl)-1-methyl-ethylamino]-pyrimidin-4-yl}-8-phenyl-1,2,3,6-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one, 1,4-cyclohexadiene (80 μL, 0.80 mmol) and palladium on carbon (100 mg) in ethylacetate (10 mL) was heated to reflux for 3 h and brought to room temperature. The mixture was filtered through celite and concentrated to afford a white solid. M+1=468. 1NMR (CDCl3) d (3H, 1.22 ppm), m (2H, 2.23 ppm), m (1H, 2.76 ppm), m (1H, 2.98 ppm), s (2H, 3.84 ppm), m (4H, 4.11 ppm), m (1H, 4.31 ppm), d (1H, 4.95 ppm), s (1H, 6.60 ppm), d (2H, 7.21 ppm), d (3H, 7.23 ppm), m (3H, 7.44 ppm), dd (2H, 7.91 ppm), d (1H, 8.18 ppm).
Reaction SMILES: [Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([CH:9]2[CH2:14][CH:13]([C:15]([O:17]C)=[O:16])[CH2:12][CH2:11][N:10]2[C:19]([O:21][CH3:22])=[O:20])=[CH:4][C:3]=1[F:23].[Br-].[Li+].C(N(CC)CC)C.CC(OC)(C)C>C(#N)C.O>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([CH:9]2[CH2:14][CH:13]([C:15]([OH:17])=[O:16])[CH2:12][CH2:11][N:10]2[C:19]([O:21][CH3:22])=[O:20])=[CH:4][C:3]=1[F:23]
Reactant: COC(=O)C1CCN(C(=O)OC)C(c2cc(F)c(Cl)c(F)c2)C1
Agent: [Br-]
Agent: [Li+]
Solvent: CCN(CC)CC
Solvent: CC#N
Solvent: O
Product: COC(=O)N1CCC(C(=O)O)CC1c1cc(F)c(Cl)c(F)c1
Yield: 91.2 %

Procedure:
Dimethyl 2-(4-chloro-3,5-difluorophenyl)piperidine-1,4-dicarboxylate (1.83 g, 5.26 mmol) was dissolved in acetonitrile (30 mL) and water (0.600 mL), then lithium bromide (3.66 g, 42.10 mmol) was added. Triethylamine (2.92 mL, 21.05 mmol) was added and the resulting suspension was heated under reflux for 4 h. MTBE (100 mL) and water (50 mL) were added, the phases separated and the organic layer was extracted with water. The combined aqueous layers were acidified to pH 1 with 3.8 M HCl and extracted with MTBE. The combined organic layers were dried over Na2SO4 and evaporated to yield 2-(4-chloro-3,5-difluoro-phenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (1.600 g, 91%) as a light yellow solid. MS m/z 332 (M−H)−
Reaction SMILES: [OH:1]O.[F:3][C:4]([F:37])([F:36])[C:5]1[CH:27]=[C:26]([S:28][C:29]2[CH:34]=[CH:33][C:32]([Br:35])=[CH:31][CH:30]=2)[CH:25]=[CH:24][C:6]=1[NH:7][C:8](=[O:23])[C:9]1[C:10](=[C:12]([C:19]([CH3:22])([CH3:21])[CH3:20])[CH:13]=[C:14]([C:17]#[N:18])[C:15]=1[CH3:16])[OH:11].O>C(O)(=O)C>[F:37][C:4]([F:36])([F:3])[C:5]1[CH:27]=[C:26]([S:28]([C:29]2[CH:30]=[CH:31][C:32]([Br:35])=[CH:33][CH:34]=2)=[O:1])[CH:25]=[CH:24][C:6]=1[NH:7][C:8](=[O:23])[C:9]1[C:10](=[C:12]([C:19]([CH3:21])([CH3:22])[CH3:20])[CH:13]=[C:14]([C:17]#[N:18])[C:15]=1[CH3:16])[OH:11]
Reactant: Cc1c(C#N)cc(C(C)(C)C)c(O)c1C(=O)Nc1ccc(Sc2ccc(Br)cc2)cc1C(F)(F)F
Reactant: OO
Solvent: CC(=O)O
Solvent: O
Product: Cc1c(C#N)cc(C(C)(C)C)c(O)c1C(=O)Nc1ccc(S(=O)c2ccc(Br)cc2)cc1C(F)(F)F
Temperature: 25 °C

Procedure:
30% w/v Aqueous hydrogen peroxide solution (70 μl.) is added to a suspension of 2'-trifluoromethyl-4'-(4-bromophenylthio)-5-cyano-3-t-butyl-6-methylsalicylanilide (0.25 g.) in acetic acid (4 ml.), and the mixture heated at 70°-80° C. for 1 hour. Water (2 ml.) is then added and the solution is cooled slowly to room temperature. The crystalline solid which is thus obtained is separated by filtration and dried to give 2'-trifluoromethyl-4'-(4-bromophenylsulphinyl)-5-cyano-3-t-butyl-6-methylsalicylanilide, m.p. 178°-180° C.
Reaction SMILES: [NH2:1][C:2]1[C:7](=[O:8])[NH:6][C:5]2[N:9]=[CH:10][CH:11]=[C:12]([O:13][C:14]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]([NH2:24])=[CH:16][CH:15]=3)[C:4]=2[N:3]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][C:27]=1[N:36]=[C:37]=[O:38]>>[NH2:1][C:2]1[C:7](=[O:8])[NH:6][C:5]2[N:9]=[CH:10][CH:11]=[C:12]([O:13][C:14]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]([NH:24][C:37]([NH:36][C:27]4[CH:28]=[C:29]([C:32]([F:33])([F:35])[F:34])[CH:30]=[CH:31][C:26]=4[F:25])=[O:38])=[CH:16][CH:15]=3)[C:4]=2[N:3]=1
Reactant: Nc1nc2c(Oc3ccc(N)c4ccccc34)ccnc2[nH]c1=O
Reactant: O=C=Nc1cc(C(F)(F)F)ccc1F
Product: Nc1nc2c(Oc3ccc(NC(=O)Nc4cc(C(F)(F)F)ccc4F)c4ccccc34)ccnc2[nH]c1=O

Procedure:
Method F2 was used with 2-amino-8-(4-aminonaphthalen-1-yloxy)pyrido[2,3-b]pyrazin-3(4H)-one and 1-fluoro-2-isocyanato-4-(trifluoromethyl)benzene to afford the title compound as a slightly pink solid (73 mg, 89%).
Reaction SMILES: [CH3:1][C:2]([O:5][C:6]([NH:8][CH2:9][C:10]1([OH:24])[CH2:13][N:12]([C:14]([O:16]CC2C=CC=CC=2)=O)[CH2:11]1)=[O:7])([CH3:4])[CH3:3].CCN(C(C)C)C(C)C.[F:34][C:35]1[C:36]([NH:45][C:46]2[CH:51]=[CH:50][C:49]([I:52])=[CH:48][C:47]=2[F:53])=[C:37]([CH:41]=[CH:42][C:43]=1[F:44])C(F)=O>[Pd].CO>[F:34][C:35]1[C:36]([NH:45][C:46]2[CH:51]=[CH:50][C:49]([I:52])=[CH:48][C:47]=2[F:53])=[C:37]([C:14]([N:12]2[CH2:11][C:10]([CH2:9][NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])([OH:24])[CH2:13]2)=[O:16])[CH:41]=[CH:42][C:43]=1[F:44]
Reactant: O=C(F)c1ccc(F)c(F)c1Nc1ccc(I)cc1F
Reactant: CC(C)(C)OC(=O)NCC1(O)CN(C(=O)OCc2ccccc2)C1
Agent: [Pd]
Solvent: CO
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)NCC1(O)CN(C(=O)c2ccc(F)c(F)c2Nc2ccc(I)cc2F)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 65.8 %

Procedure:
Phenylmethyl 3-[({[(1,1-dimethylethyl)oxy]carbonyl}amino)methyl]-3-hydroxyazetidine-1-carboxylate (16.5 mg, 0.05 mmol) and 10% Pd/C (8 mg) were taken into methanol (2 mL) and hydrogenated at ambient pressure over 12 hours. The catalyst was removed by filtration and the filtrate concentrated and dried in vacuo. The residue was taken into THF (1 mL) followed by addition of DIPEA (10 μL, 0.06 mmol) and 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoyl fluoride (19.8 mg, 0.05 mmol), prepared using procedures similar to those described in Reference 1, and the solution was stirred at room temperature for 30 minutes. Concentration and purification of the residue by silica gel flash chromatography using hexanes:ethyl acetate (1:1.5) afforded 1,1-dimethylethyl {[1-({3,4-difluoro-2 [(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidine-3-yl]methyl}carbamate (19 mg, 66% yield).
Reaction SMILES: CC(C)([O-])C.[Na+].Cl[C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[C:10]([F:15])[CH:9]=1.C(=[NH:29])(C1C=CC=CC=1)C1C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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]>[F:15][C:10]1[CH:9]=[C:8]([CH:13]=[C:12]([F:14])[CH:11]=1)[NH2:29]
Reactant: N=C(c1ccccc1)c1ccccc1
Reactant: Fc1cc(F)cc(Cl)c1
Agent: [Fe+2]
Agent: [Pd]
Agent: CC(C)(C)[O-]
Product: Nc1cc(F)cc(F)c1
Yield: 89 %

Procedure:
A 4-neck, 500 mL flask was equipped with a mechanical stirrer, a glass stopper, a rubber septum and a condenser with an inert gas inlet. To this flask was added, in order, tris(dibenzylideneacetone)dipalladium (0) (Pd2(dba)3) (25 mg, 0.01 mol %), 1,1′-bis(diphenylphosphino)ferrocene (dppf) (46 mg, 0.03 mol %), sodium tert-butoxide (37 g, 1.4 eq, xylenes (90 mL), 1-chloro-3,5-difluorobenzene (49.2 g, 0.33 mol) and benzophenone imine (50 g, 0.28 mol). The mixture was refluxed for 8 hours until GC analysis confirmed that the benzophenone imine had been consumed. The reaction mixture was cooled slightly, and 150 mL of 2M HCl was added slowly to the reaction mixture with some gas evolution and the mixture was refluxed with sufficient agitation for 45 minutes. While still warm, the reaction mixture was put in a separatory funnel and the aqueous layer was collected. An additional 90 mL of xylenes was added to the separatory funnel and the organic layer was washed with 4×100 mL 1M HCl. The acidic fractions were combined and made alkaline with aqueous conc ammonium hydroxide. The free amine was extracted with 250 mL methyl tert-butyl ether. The organic layer was dried over magnesium sulfate and concentrated in vacuo to yield the expected product in 89% yield.
Reaction SMILES: [O:1]=[C:2]1[O:6][CH2:5][C@H:4]([NH:7][C:8](=[O:17])[O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:3]1.[CH3:18][NH:19][CH3:20]>C1COCC1>[CH3:18][N:19]([CH3:20])[C:2](=[O:1])[CH2:3][C@@H:4]([NH:7][C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:5][OH:6]
Reactant: O=C1C[C@@H](NC(=O)OCc2ccccc2)CO1
Reactant: CNC
Solvent: C1CCOC1
Product: CN(C)C(=O)C[C@H](CO)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 14 h
Yield: 91.5 %

Procedure:
A solution of (R)-benzyl-5-oxotetrahydrofuran-3-ylcarbamate (INTERMEDIATE 3, 18.4 g, 7.8 mmol) in THF (100 ml) was purged, at room temperature, with gaseous dimethylamine for 5 minutes. After stirring at room temp for 14 hours, the reaction mixture was concentrated to dryness, and purified by column chromatography (silica gel, eluting first with 50% ethyl acetate/hexanes followed by 100% acetone) to give the title product (20 g, yield: 91.5%).
Reaction SMILES: [CH3:1][C:2]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:7][CH2:6][C:5](=[O:8])[CH:4]=[CH:3]1.C(O[CH2:20][N:21]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:22][Si](C)(C)C)CCC.C(=O)([O-])[O-].[K+].[K+]>ClCCl.FC(F)(F)C(O)=O>[CH2:27]([N:21]1[CH2:22][CH:6]2[CH:7]([C:2]([CH3:1])([C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:3][CH2:4][C:5]2=[O:8])[CH2:20]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: CCCCOCN(Cc1ccccc1)C[Si](C)(C)C
Reactant: CC1(c2ccccc2)C=CC(=O)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC1(c2ccccc2)CCC(=O)C2CN(Cc3ccccc3)CC21
Reaction time: 0.5 h

Procedure:
To a solution of 14.5 g of 4-methyl-4-phenylcyclohex-2-enone and 24.45 cm3 of N-butoxymethyl-N-trimethylsilylmethylbenzylamine in 65 cm3 of dichloromethane are added, at a temperature of 25° C., 3 drops of trifluoroacetic acid. The reaction mixture is stirred at this temperature for 30 minutes and then heated to reflux for 2 hours. After cooling, 10 g of potassium carbonate are added, the mixture is stirred for 15 minutes and the solution is then filtered through a sinter funnel and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (particle size 0.04-0.06 mm, diameter 5 cm, height 39 cm), eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (80/20 by volume) and collecting 100 cm3 fractions. Fractions 8 to 30 are combined and concentrated to dryness under reduced pressure (2.7 kPa). 9 g of (3aRS,7SR,7aRS)-2-benzyl-7-methyl-7-phenyl-4-perhydroisoindolone are obtained in the form of a yellow oil.
Reaction SMILES: [CH2:1]([S:3]([N:6]1[CH2:11][CH2:10][CH:9]([C:12]2[C:20]3[C:15](=[C:16]([C:29]([NH2:31])=[O:30])[CH:17]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([CH:27]=O)=[CH:23][CH:22]=4)[CH:19]=3)[NH:14][CH:13]=2)[CH2:8][CH2:7]1)(=[O:5])=[O:4])[CH3:2].[CH3:32][CH:33]([NH2:35])[CH3:34].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CS(C)=O.C(O)(=O)C>[CH2:1]([S:3]([N:6]1[CH2:11][CH2:10][CH:9]([C:12]2[C:20]3[C:15](=[C:16]([C:29]([NH2:31])=[O:30])[CH:17]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([CH2:27][NH:35][CH:33]([CH3:34])[CH3:32])=[CH:23][CH:22]=4)[CH:19]=3)[NH:14][CH:13]=2)[CH2:8][CH2:7]1)(=[O:4])=[O:5])[CH3:2]
Reactant: CC(C)N
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4ccc(C=O)cc4)cc23)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CC(=O)O
Product: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4ccc(CNC(C)C)cc4)cc23)CC1
Reaction time: 2 h
Yield: 69.1 %

Procedure:
To a solution of 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(4-formylphenyl)-1H-indole-7-carboxamide (40 mg, 0.09 mmol) in DMSO (900 μL) and acetic acid (2 drops) was added 2-propanamine (93 μL, 1.08 mmol). After 2 h, sodium triacetoxyborohydride (172 mg, 0.81 mmol) was added. Reaction mixture was stirred overnight. Compound was purified by Gilson Preparatory HPLC to afford 30 mg of the title compound (69%).
Reaction SMILES: [NH2:1][CH:2]([C:10]1[C:15]([O:16][CH3:17])=[CH:14][N:13]=[CH:12][C:11]=1[O:18][CH3:19])[CH2:3][CH2:4][CH2:5][C:6]([O:8]C)=O.[CH:20]1[C:28]2[C:27]3[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=3[O:25][C:24]=2[CH:23]=[CH:22][C:21]=1[CH:33]=O>>[CH:20]1[C:28]2[C:27]3[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=3[O:25][C:24]=2[CH:23]=[CH:22][C:21]=1[CH2:33][N:1]1[CH:2]([C:10]2[C:15]([O:16][CH3:17])=[CH:14][N:13]=[CH:12][C:11]=2[O:18][CH3:19])[CH2:3][CH2:4][CH2:5][C:6]1=[O:8]
Reactant: O=Cc1ccc2oc3ccccc3c2c1
Reactant: COC(=O)CCCC(N)c1c(OC)cncc1OC
Product: COc1cncc(OC)c1C1CCCC(=O)N1Cc1ccc2oc3ccccc3c2c1

Procedure:
Prepared according to the described general procedure 1 (GP1) by reaction of methyl 5-amino-5-(3,5-dimethoxypyridin-4-yl)pentanoate with commercially available dibenzo[b,d]furan-2-carbaldehyde. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.64 min.; [M+H]+: 416.86 g/mol.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10](Cl)(=[O:12])=[O:11])([O-:3])=[O:2].[NH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1.CCN(CC)CC>C(Cl)Cl>[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([N:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:16]1[CH2:15][NH2:14])(=[O:12])=[O:11])([O-:3])=[O:2]
Reactant: NCc1ccccn1
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: NCC1C=CC=CN1S(=O)(=O)c1ccccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 3 h
Yield: 77 %

Procedure:
A solution of 2-nitrobenzenesulfonylchloride (16.62 g, 0.075 mol) in dry CH2Cl2 (120 mL) was added dropwise via cannula to a stirred solution of 2-(aminomethyl)pyridine (5.41 g, 0.05 mol) and Et3N (13.9 mL, 0.10 mol) in dry CH2Cl2 (150 mL) under nitrogen. The reaction mixture was stirred for three hours at room temperature, and then quenched with water (20 mL). The aqueous layer was separated and extracted with EtOAc (5×80 mL). The combined organic extracts were dried (MgSO4) and evaporated to small volume to give a white precipitate which was collected by filtration and washed with cold CH2Cl2 to give the desired product (11.37 g, 78%) as a white solid: 1H NMR (Acetone-d6) δ 4.46 (s, 2H), 7.19 (dd, 1H, J=7.4, 4.5 Hz), 7.25-7.35 (br s, 1H), 7.39 (d, 1H, J=7.7 Hz), 7.68 (ddd, 1H, J=7.7, 7.5, 1.8 Hz), 7.76-7.88 (m, 2H), 7.94 (dd, 1H, J=7.7, 1.5 Hz), 8.04 (dd, 1H, J=7.5, 1.8 Hz), 8.38 (d, 1H, J=4.5 Hz).
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]([C:24]3[S:25][C:26]([Br:29])=[CH:27][CH:28]=3)=[O:23])=[CH:17][C:16]=2[NH:30][C:31]2[C:32]3[CH:40]=[CH:39][C:38]([CH:41]([CH3:43])[CH3:42])=[N:37][C:33]=3[N:34]=[CH:35][N:36]=2)=[CH:10][CH:9]=1)(C)(C)C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]([C:24]3[S:25][C:26]([Br:29])=[CH:27][CH:28]=3)=[O:23])=[CH:17][C:16]=2[NH:30][C:31]2[C:32]3[CH:40]=[CH:39][C:38]([CH:41]([CH3:42])[CH3:43])=[N:37][C:33]=3[N:34]=[CH:35][N:36]=2)=[CH:10][CH:9]=1
Reactant: CC(C)c1ccc2c(Nc3cc(NC(=O)c4ccc(Br)s4)ccc3Oc3ccc(NC(=O)OC(C)(C)C)cc3)ncnc2n1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)c1ccc2c(Nc3cc(NC(=O)c4ccc(Br)s4)ccc3Oc3ccc(N)cc3)ncnc2n1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
The product from Example 257c (mg, 0.462 mmol) was dissolved in a 1:1 mixture of TFA in CH2Cl2 and stirred at room temperature for 2 hrs. The solvent was removed under vacuum and the crude oil was purified by HPLC with TFA providing the product as a trifluoroacetic acid salt (16 mg, 6%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 1.32 (t, J=6.99 Hz, 6 H), 3.18-3.33 (m, 1 H), 6.82-6.91 (m, 4 H), 6.99 (d, J=9.19 Hz, 1 H), 7.39 (d, J=4.04 Hz, 1 H), 7.61 (dd, J=8.82, 2.57 Hz, 1 H), 7.81 (d, J=8.46 Hz, 1 H), 7.86 (d, J=4.04 Hz, 1 H), 7.99 (d, J=2.57 Hz, 1 H), 8.81 (s, 1 H), 8.91 (d, J=8.09 Hz, 1 H), 10.45 (s, 1 H); MS (ESI+) m/z 575 (M+TFA+H)+; (ESI−) m/z 573 (M+TFA−H)−.
Reaction SMILES: [CH3:1][C:2]([CH3:14])([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH2:3][N:4]=[N+]=[N-].CO.[H][H]>[Pd].O1CCCC1>[C:8]1([CH2:7][C:2]([CH3:14])([CH3:1])[CH2:3][NH2:4])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: [H][H]
Reactant: CC(C)(CN=[N+]=[N-])Cc1ccccc1
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(CN)Cc1ccccc1

Procedure:
A mixture of 2,2-dimethyl-3-phenyl-1-azidopropane (3 gm), 10% Pd-C, methanol (60 mL) and tetrahydrofuran (15 mL) was stirred under 1 atmosphere of hydrogen at rt for 18 h. The mixture was filtered and concentrated to give the title compound as an oil, MS (m/z): 164.1 (M+H)+; C11H17N requir. 163.1.
Reaction SMILES: [H-].[Na+].[CH3:3][C:4](=[O:9])[C:5]([CH3:8])([CH3:7])[CH3:6].[C:10](=O)([O:13]C)[O:11][CH3:12]>CN(C)P(=O)(N(C)C)N(C)C>[CH3:12][O:11][C:10](=[O:13])[CH2:3][C:4](=[O:9])[C:5]([CH3:8])([CH3:7])[CH3:6]
Reactant: COC(=O)OC
Reactant: CC(=O)C(C)(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: COC(=O)CC(=O)C(C)(C)C
Yield: 83.5 %

Procedure:
60 g of sodium hydride were suspended in 450 cc of dimethyl carbonate and 100 cc of hexamethyl phosphoric acid triamide. 100 g of pinacolone (92%) were added slowly at 45° C and on completion of the addition, the reaction mixture was processed as described in 3 above. The yield was 83.5% of pivaloyl acetic acid methyl ester.
Reaction SMILES: [Na].[Br:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:13]=[N:12][C:11]([OH:14])=[N:10]2)=[CH:5][CH:4]=1.Br[CH:16]([CH3:22])[C:17]([O:19][CH2:20][CH3:21])=[O:18]>C(O)C.CS(C)=O>[Br:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH:13]=[N:12][C:11]([O:14][CH:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH3:22])=[N:10]2)=[CH:7][CH:8]=1
Reactant: CCOC(=O)C(C)Br
Reactant: Oc1ncn(-c2ccc(Br)cc2)n1
Agent: [Na]
Solvent: CS(C)=O
Solvent: CCO
Product: CCOC(=O)C(C)Oc1ncn(-c2ccc(Br)cc2)n1
Temperature: 0 °C
Yield: 48 %

Procedure:
A 3.9 g portion of sodium was dissolved in 50 ml of ethanol and was added to a solution of 41 g of 1-(4-bromophenyl)-3-hydroxy-1,2,4-1H-triazole in 150 ml of dimethylsulfoxide. The mixture was heated at 60° for 45 minutes, and then 30.9 g of ethyl 2-bromopropionate was added. The mixture was heated for 2 hours more, and was then cooled and poured over ice-water. The solid was collected and dried, and was recrystallized from toluene. The mother liquor was concentrated under vacuum, and the residue was recrystallized from ethanol. That product was combined with the first portion of product and recrystallized from ethanol to obtain 27.9 g of the desired product, m.p. 64°-66°.
Reaction SMILES: [C:1]1([N:7]2[C:11]([C:12]3[C:17](=[O:18])[CH:16]=[CH:15][N:14]([CH:19]4[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[N:13]=3)=[CH:10][CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.I[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.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.CC(C)([O-])C.[Na+]>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].O>[C:26]1([N:22]2[CH2:23][CH2:24][CH:19]([N:14]3[CH:15]=[CH:16][C:17](=[O:18])[C:12]([C:11]4[N:7]([C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[N:8]=[CH:9][CH:10]=4)=[N:13]3)[CH2:20][CH2:21]2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: Ic1ccccc1
Reactant: O=c1ccn(C2CCNCC2)nc1-c1ccnn1-c1ccccc1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Solvent: C1COCCO1
Solvent: O
Product: O=c1ccn(C2CCN(c3ccccc3)CC2)nc1-c1ccnn1-c1ccccc1
Temperature: 100 °C
Reaction time: 3 h
Yield: 19.1 %

Procedure:
A suspension of 3-(1-phenyl-1H-pyrazol-5-yl)-1-piperidin-4-ylpyridazin-4(1H)-one (0.14 g), iodobenzene (0.13 g), Pd2(dba)3 (10 mg), Xantphos (25 mg) and sodium tert-butoxide (63 mg) in 1,4-dioxane (5 mL) was stirred at 100° C. for 3 hr under an argon atmosphere. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) and recrystallized from ethyl acetate/hexane to give the title compound (33 mg).
Reaction SMILES: CC(C(N=NC1C=CC(Cl)=CC=1[N+]([O-])=O)C(N[C:8]1[CH:13]=[CH:12][C:11]2[NH:14][C:15]([NH:17][C:10]=2[CH:9]=1)=[O:16])=O)=O.N(CCO)(CCO)CCO>O>[N:14]1[C:15](=[O:16])[N:17]=[C:10]2[CH:9]=[CH:8][CH:13]=[CH:12][C:11]=12
Reactant: CC(=O)C(N=Nc1ccc(Cl)cc1[N+](=O)[O-])C(=O)Nc1ccc2[nH]c(=O)[nH]c2c1
Solvent: OCCN(CCO)CCO
Solvent: O
Product: O=C1N=c2ccccc2=N1
Reaction time: 5 h

Procedure:
20 g of C.I. pigment orange 60 having an average primary particle diameter of 85 nm (in which the content as metal ions having a valence of at least 2 was 320 ppm), 1.6 g of the pigment derivative (a′) and 110 g of deionized water were mixed, triethanolamine was added so as to adjust pH of a mixture liquid to 9.0, and the mixture liquid was dispersed with a paint shaker in the presence of zirconia beads as media for approximately 5 hours, to obtain a pigment dispersion. The obtained water-based pigment dispersion was diluted so as to have a concentration of 3% by weight, and the diluted water-based pigment dispersion was dropped to NO.2 filter paper, to show no bleedings of the pigment derivative.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])[CH:5]=[CH:4][C:3]=1[C:16](=[O:21])[C:17](=[CH2:20])[CH2:18][CH3:19].C(=O)CCC>>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][N:11]2[CH2:12][CH2:13][CH2:15][CH2:14]2)[CH:5]=[CH:4][C:3]=1[C:16](=[O:21])[C:17](=[CH2:20])[CH2:18][CH3:19]
Reactant: C=C(CC)C(=O)c1ccc(OCCN(CC)CC)cc1Cl
Solvent: CCCC=O
Product: C=C(CC)C(=O)c1ccc(OCCN2CCCC2)cc1Cl

Procedure:
This compound is prepared by essentially the same procedure as described in Example 1 Step B except that the 1-{2-chloro-4-(2-diethylaminoethoxy)phenyl}-1-butanone of Example 1 Step B is replaced by an equimolecular quantity of 1-{2-chloro-4-[2-N-pyrrolidinyl)ethoxy]phenyl}-1-butanone. The product is obtained as a yellow oil upon distillation in vacuo (0.3 mm.).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH2:12].[N+:13]([C:16]1[CH:24]=[CH:23][C:19]([C:20](O)=O)=[CH:18][CH:17]=1)([O-:15])=[O:14]>O=P(Cl)(Cl)Cl>[N+:13]([C:16]1[CH:24]=[CH:23][C:19]([C:20]2[NH:12][C:3]3[CH:4]=[C:5]([C:8]([F:9])([F:10])[F:11])[CH:6]=[CH:7][C:2]=3[N:1]=2)=[CH:18][CH:17]=1)([O-:15])=[O:14]
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Reactant: Nc1ccc(C(F)(F)F)cc1N
Solvent: O=P(Cl)(Cl)Cl
Product: O=[N+]([O-])c1ccc(-c2nc3ccc(C(F)(F)F)cc3[nH]2)cc1

Procedure:
2-(4-Nitrophenyl)-5-trifluoromethyl benzimidazole was synthesized as follows: 1,2-diamino-4-trifluoromethylbenzene (1.76 g, 10.0 mmole) was mixed with 4-nitrobenzoic acid (1.67 g, 9.8 mmole), dissolved in POCl3 (12 ml), and heated to reflux for 2.5 hours. The reaction mixture was cooled and cautiously poured onto ice. The resulting solid was filtered, washed with NaHCO3 and used without further purification.