Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([Mg]Br)[CH3:2].CON(C)[C:8](=[O:18])[CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14].C(OCC)(=O)C.[Cl-].[NH4+]>O1CCCC1>[O:18]=[C:8]([CH2:1][CH3:2])[CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:15])([CH3:14])[CH3:16]
Reactant: CON(C)C(=O)CNC(=O)OC(C)(C)C
Reactant: CC[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCC(=O)CNC(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 84 %

Procedure:
Ethyl magnesium bromide (1M solution in tetrahydrofuran, 13.7 ml, 13.7 mmol)) was added to a stirred solution of tert-butyl 2-[methoxy(methyl)amino]-2-oxoethylcarbamate (Synth. Commun. 1988, 18, 2273) (1 g, 4.58 mmol) in tetrahydrofuran (25 ml) at 0° C. then stirred at 0° C. for 15 minutes. The solution was allowed to warm to room temperature and was stirred for 45 minutes. Ethyl acetate (5 ml) was added, followed by saturated ammonium chloride solution. The aqueous phase was extracted with ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate solution and brine. The organic phase was then dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a solvent gradient of hexane:ethyl acetate (85:15 to 70:30), to afford the title compound as a colorless oil, 730 mg, 84% yield.
Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16](=[O:19])[CH2:17][Cl:18])=[S:7])=[O:4].[CH3:20][NH:21][CH3:22]>C1C=CC=CC=1>[ClH:18].[CH3:1][O:2][C:3]([NH:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16](=[O:19])[CH2:17][N:21]([CH3:22])[CH3:20])=[S:7])=[O:4]
Reactant: COC(=O)NC(=S)Nc1ccccc1NC(=O)CCl
Reactant: CNC
Solvent: c1ccccc1
Product: COC(=O)NC(=S)Nc1ccccc1NC(=O)CN(C)C
Product: Cl
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A suspension of 1-methoxycarbonyl-3-(2-chloroacetamidophenyl)thiourea (1.51 g) in benzene (50 ml) was treated with a solution of dimethylamine in benzene (15 ml., 10% w/w). The mixture was heated to reflux for 15 minutes with stirring. A further quantity of dimethylamine in benzene (5ml, 10% w/w) was added, and the mixture heated to reflux for a further 15 minutes with stirring. The mixture was allowed to stand for 1 hour, during which time it cooled to room temperature, and was then filtered. The filtrate was treated with an excess of a saturated solution of hydrogen chloride in diethyl ether. The precipitate was filtered off, treated with water (20 ml), some insoluble solid was filtered off, and the aqueous filtrate neutralised by treatment with 2N aqueous sodium hydroxide solution. The resultant solid was filtered off, dissolved in the minimum quantity of ethanol and the solution treated with diethyl ether, followed by an excess of a saturated solution of hydrogen chloride in diethyl ether. The resultant solid was filtered off and recrystallised from ethanol to give 1-methoxycarbonyl-3-(2-dimethylaminoacetamidophenyl)thiourea hydrochloride (0.25 g), m.p. 187°-188° C. (with decomposition).
Reaction SMILES: [I:1][C:2]1[C:3](=O)[NH:4][C:5](=[O:9])[NH:6][C:7]=1[CH3:8].[C:11](=[O:14])([O-])[O-].[K+].[K+].[CH3:17]I.O>CN(C=O)C.C(OCC)(=O)C>[I:1][C:2]1[C:11](=[O:14])[N:4]([CH3:3])[C:5](=[O:9])[N:6]([CH3:17])[C:7]=1[CH3:8]
Reactant: CI
Reactant: O=C([O-])[O-]
Reactant: Cc1[nH]c(=O)[nH]c(=O)c1I
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: Cc1c(I)c(=O)n(C)c(=O)n1C
Temperature: 25 °C
Reaction time: 24 h
Yield: 93.4 %

Procedure:
A mixture of 5-iodo-6-methyl uracil (22.18 mmol, 5.58 g) and powdered potassium carbonate (60 mmol, 8.29 g) in DMF (188 mL) was stirred for 24 h at room temperature and then methyl iodide (90.6 mmol, 3.33 mL) was added. The reaction mixture was stirred for another 76 h at room temperature and was poured into water (150 mL) and ethyl acetate (150 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined extracts were washed with brine solution (150 mL) and dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration of the solvent gave crude solid which was crystallized from ethanol:water (3:1, 150:50 mL) and stored in the refrigerator overnight. The solids were collected by filtration and washed with ethanol:water (3:1, 120 mL), water (30 mL), hexanes (30 ML) and dried under high vacuum to obtain 5.8 g (93% yield) of 5-iodo-1,3,6-trimethyl uracil as a white solid: mp 155-157° C. EI-HRMS m/e calcd for C7H9IN2O2 (M+) 279.9709, found 279.9709.
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH:11]1[C:20]2[CH:19]=[C:18]3[O:21][CH2:22][O:23][C:17]3=[CH:16][C:15]=2[NH:14][C:13](=O)[CH2:12]1)[CH2:2][CH3:3].C(OC1C=CC=CC=1C=CC(O)=O)CC.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=S.[CH:54]([NH:56]N)=O.C(#[N:60])C>C(O)(=O)C.C(N(CC)CC)C>[CH2:1]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH:11]1[C:20]2[C:15](=[CH:16][C:17]3[O:23][CH2:22][O:21][C:18]=3[CH:19]=2)[N:14]2[N:60]=[CH:54][N:56]=[C:13]2[CH2:12]1)[CH2:2][CH3:3]
Reactant: NNC=O
Reactant: CCCOc1ccccc1C1CC(=O)Nc2cc3c(cc21)OCO3
Reactant: CC#N
Agent: CCCOc1ccccc1C=CC(=O)O
Agent: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: CC(=O)O
Solvent: CCN(CC)CC
Product: CCCOc1ccccc1C1Cc2ncnn2-c2cc3c(cc21)OCO3
Temperature: 100 °C

Procedure:
8-(2-propoxyphenyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]quinolin-6(5H)-one (175 mg, 1.0 equiv—prepared essentially as described in Example 1 using 2-propoxycinnamic acid as the starting material) was dissolved in 0.8 mL dry acetonitrile and 0.54 mL triethylamine under an atmosphere of nitrogen. Phosphorus pentasulfide (179 mg, 1.5 equiv) was added in one portion and the reaction was heated to 100° C. for six hours. The solvent was removed in vacuo and the residue was partitioned between 20 mL DCM and 10 mL brine. The layers were separated and the organic portion was washed with two additional portions of brine, dried over sodium sulfate, and reduced in vacuo. The resultant crude orange foam was dissolved in 1.0 mL n-butanol in a vial under an atmosphere of nitrogen. Acetic acid (6 uL) and formohydrazide (31 mg, 1.0 equiv) were added and the vial was tightly capped and heated to 130° C. for 24 hours. The solvent was removed in vacuo and the residue was suspended in DCM and washed with three portions of brine. The organic layer was dried over sodium sulfate and condensed to give a crude oil that was purified by flash column chromatography (2% to 5% methanol in chloroform). Fractions containing product were pooled to give 125 mg of a brown oil that was recrystallized from chloroform/hexanes to give triazole compound IX as a yellow solid (31 mg, 17%) that was >99% pure by UPLC-MS (ELSD). 1H NMR (400 MHz, CDCl3) δ=8.54 (s, 1 H), 7.19 (dt, J=2.0, 8.2 Hz, 1 H), 6.99-6.92 (m, 1 H), 6.88 (d, J=8.2 Hz, 1 H), 6.76 (t, J=7.4 Hz, 1 H), 6.65 (dd, J=1.6, 7.8 Hz, 1 H), 6.59-6.54 (m, 1 H), 6.03-5.96 (m, 2 H), 4.67 (dd, J=6.4, 7.4 Hz, 1 H), 4.03-3.88 (m, 2 H), 3.55 (dd, J=7.4, 16.2 Hz, 1 H), 3.33 (dd, J=6.4, 16.2 Hz, 1 H), 1.78 (qd, J=7.1, 13.9 Hz, 2 H), 0.98 (t, J=7.4 Hz, 3 H). ESI-MS (M+H+) m/z=350.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O:20]([CH2:27][C:28]([OH:30])=O)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.ClC(Cl)(Cl)C#N.[NH2:37][C@@:38]([C:53]1[CH:58]=[CH:57][C:56]([O:59][CH2:60][CH2:61][CH2:62][C:63]([F:66])([F:65])[F:64])=[CH:55][CH:54]=1)([C:49]([F:52])([F:51])[F:50])[CH2:39][C:40]([C:42]1[CH:47]=[CH:46][C:45]([CH3:48])=[CH:44][CH:43]=1)=[O:41].N1C=CC=CC=1>C(Cl)Cl>[O:20]([CH2:27][C:28]([NH:37][C@:38]([C:53]1[CH:58]=[CH:57][C:56]([O:59][CH2:60][CH2:61][CH2:62][C:63]([F:64])([F:65])[F:66])=[CH:55][CH:54]=1)([CH2:39][C:40](=[O:41])[C:42]1[CH:43]=[CH:44][C:45]([CH3:48])=[CH:46][CH:47]=1)[C:49]([F:52])([F:51])[F:50])=[O:30])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: O=C(O)COc1ccccc1
Reactant: Cc1ccc(C(=O)C[C@](N)(c2ccc(OCCCC(F)(F)F)cc2)C(F)(F)F)cc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: N#CC(Cl)(Cl)Cl
Product: Cc1ccc(C(=O)C[C@](NC(=O)COc2ccccc2)(c2ccc(OCCCC(F)(F)F)cc2)C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 69 %

Procedure:
To a mixture of triphenylphosphine (138 mg, 0.318 mmol) in dry DCM (0.8 mL) was added 2-phenoxyacetic acid (26 mg, 0.173 mmol), followed by trichloroacetonitrile (30 mg, 0.208 mmol). The mixture was stirred at rt for 2.5 h. To the mixture was added a solution of Intermediate 2F, isomer 2 (30 mg, 0.069 mmol) in dry DCM (0.5 mL) followed by pyridine (17 μL, 0.208 mmol). The reaction was stirred at rt overnight. The mixture was concentrated and purified by preparative HPLC (MeOH/H2O/TFA) to yield the desired product (27 mg, 69%) as a brown oil. LCMS Anal. Calc'd for C29H27F6NO4 567.18, found [M+H] 568.3.
Reaction SMILES: [BH4-].[Na+].[CH3:3][O:4][C:5]1[C:14]([O:15][CH3:16])=[C:13]([O:17][CH3:18])[CH:12]=[C:11]2[C:6]=1[CH:7]=[CH:8][C:9]([CH:19]=[O:20])=[N:10]2.CO>C1COCC1>[OH:20][CH2:19][C:9]1[CH:8]=[CH:7][C:6]2[C:11](=[CH:12][C:13]([O:17][CH3:18])=[C:14]([O:15][CH3:16])[C:5]=2[O:4][CH3:3])[N:10]=1
Reactant: COc1cc2nc(C=O)ccc2c(OC)c1OC
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: COc1cc2nc(CO)ccc2c(OC)c1OC
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Sodium borohydride (418 mg) and 5,6,7-trimethoxyquinoline-2-carboaldehyde (2.14 g) were successively added to a mixed solvent of methanol (30 mL) and THF (30 mL) under ice cooling, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was then extracted with ethyl acetate. The resultant organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentrating the organic layer under reduced pressure, the residue was purified by column chromatography on silica gel (chloroform:methanol=30:1) to obtain the title compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:36])[N:7]([CH2:17][C:18]1[CH:35]=[CH:34][C:21]2[N:22]([CH2:32][CH3:33])[C:23](=[O:31])[C:24]([CH3:30])([CH3:29])[C:25](=[O:28])[N:26]([CH3:27])[C:20]=2[CH:19]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12](=[O:15])[NH:11][C:10]=1[CH3:16])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:39]I.O>CN(C=O)C>[C:1]([O:5][C:6](=[O:36])[N:7]([CH2:17][C:18]1[CH:35]=[CH:34][C:21]2[N:22]([CH2:32][CH3:33])[C:23](=[O:31])[C:24]([CH3:29])([CH3:30])[C:25](=[O:28])[N:26]([CH3:27])[C:20]=2[CH:19]=1)[CH2:8][C:9]1[C:10]([CH3:16])=[N:11][C:12]([O:15][CH3:39])=[CH:13][CH:14]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(CN(Cc3ccc(=O)[nH]c3C)C(=O)OC(C)(C)C)ccc21
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(CN(Cc3ccc(OC)nc3C)C(=O)OC(C)(C)C)ccc21
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-methyl-6-oxo-1,6-dihydropyridin-3-ylmethyl) carbamic acid tert-butyl ester (536 mg) was dissolved in DMF (20 ml), and was cooled to 0° C. in ice water bath. Sodium hydride (60% in oil, 56.1 mg) was added thereto at the same temperature, and the mixture was stirred at 0° C. for 0.5 hours. Methyl iodide (0.081 ml) was added thereto, and the mixture was stirred at 0° C. for 0.5 hours. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was dried with sodium sulfate, and was condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1). The purified product was condensed to dryness under reduced pressure to give the title compound (550 mg) as a yellow oil.
Reaction SMILES: [C:1]([C:3]1[CH:7]=[N:6][NH:5][C:4]=1[NH2:8])#[N:2].CN(C)[CH:11]=[CH:12][C:13]([C:15]1[CH:16]=[C:17]([N:21]([CH2:31][CH3:32])[S:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)(=[O:24])=[O:23])[CH:18]=[CH:19][CH:20]=1)=O.C(OCC)(=O)C>C(O)(=O)C>[C:1]([C:3]1[CH:7]=[N:6][N:5]2[C:13]([C:15]3[CH:16]=[C:17]([N:21]([CH2:31][CH3:32])[S:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)(=[O:24])=[O:23])[CH:18]=[CH:19][CH:20]=3)=[CH:12][CH:11]=[N:8][C:4]=12)#[N:2]
Reactant: CCN(c1cccc(C(=O)C=CN(C)C)c1)S(=O)(=O)c1ccccc1
Reactant: N#Cc1cn[nH]c1N
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CCN(c1cccc(-c2ccnc3c(C#N)cnn23)c1)S(=O)(=O)c1ccccc1
Yield: 46.7 %

Procedure:
A mixture of 0.15 g (1.38 mmol) of 4-cyano-2H-pyrazol-3-ylamine and 0.50 g (1.38 mmol) of N-[3-[3-(dimethylamino)-1-oxo-2-propenyl]phenyl]-N-ethyl-benzenesulfonamide in 10 ml of glacial acetic acid was refluxed for 8 hours and then the solvent was removed by reduced pressure distillation. To the resulting residue were added 10 ml of dichloromethane and 10 ml of saturated sodium bicarbonate solution. The two layers were separated, and the aqueous layer was washed with 10 ml of dichloromethane. The organic layers were washed with 10 ml of water and dried over magnesium sulfate. The dichloromethane layer was evaporated to dryness to yield an oil which, in the presence of ethyl acetate, gave 260 mg of N-[3-(3-cyano-pyrazolo[1,5-a]pyrimidin-7-yl)-phenyl]-N-ethyl-benzenesulfonamide as a yellow solid (yield 47%).
Reaction SMILES: [OH:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[N+:13]([O-])([OH:15])=[O:14]>C(O)(=O)C>[N+:13]([C:12]1[CH:11]=[C:5]([CH:4]=[CH:3][C:2]=1[OH:1])[C:6]([O:8][CH2:9][CH3:10])=[O:7])([O-:15])=[O:14]
Reactant: CCOC(=O)c1ccc(O)cc1
Reactant: O=[N+]([O-])O
Solvent: CC(=O)O
Product: CCOC(=O)c1ccc(O)c([N+](=O)[O-])c1
Temperature: 40 °C
Reaction time: 1 h

Procedure:
To a stirred solution of 20.0 grams (0.12 mole) of ethyl 4-hydroxybenzoate in 200 mL of acetic acid was added a solution of 7.5 mL (excess) of 70% nitric acid in 30 mL of acetic acid. After the reaction mixture stirred for about one hour, it gradually turned orange and warmed to about 40° C. The reaction mixture was stirred for an additional eighteen hours and then was poured into 800 mL of ice-water. The mixture was stirred until the ice melted, and filtered to collect a solid, which was dissolved in ethyl acetate and dried with magnesium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure, yielding 22.0 grams of ethyl 3-nitro-4-hydroxybenzoate, mp 70-71° C. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: C([O:5][C:6](=[O:29])[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH3:17])=[CH:14][CH:15]=2)[C:10]([CH:18]2[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[S:20](=[O:28])(=[O:27])[NH:19]2)=[CH:9]1)(C)(C)C.Br[CH2:31][C:32]1[S:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1>>[S:33]1[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=[C:32]1[CH2:31][N:19]1[CH:18]([C:10]2[C:11]3[C:16](=[CH:15][CH:14]=[C:13]([CH3:17])[CH:12]=3)[N:8]([CH2:7][C:6]([OH:5])=[O:29])[CH:9]=2)[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[S:20]1(=[O:27])=[O:28]
Reactant: BrCc1nc2ccccc2s1
Reactant: Cc1ccc2c(c1)c(C1NS(=O)(=O)c3ccccc31)cn2CC(=O)OC(C)(C)C
Product: Cc1ccc2c(c1)c(C1c3ccccc3S(=O)(=O)N1Cc1nc3ccccc3s1)cn2CC(=O)O

Procedure:
The title compound was prepared by the method described for example 14 using the product from example 2, step c) and 2-bromomethyl-benzothiazole. MS: ESI (negative): 502 (M−H).
Reaction SMILES: [CH:1]1[CH:10]=[C:9]([S:11]([OH:14])(=[O:13])=[O:12])[C:8]2[C:3](=[CH:4][C:5]([S:16]([OH:19])(=[O:18])=[O:17])=[CH:6][C:7]=2[NH2:15])[CH:2]=1.[OH-].[Na+:21]>O.C(O)C>[Na+:21].[Na+:21].[NH2:15][C:7]1[CH:6]=[C:5]([S:16]([O-:19])(=[O:18])=[O:17])[CH:4]=[C:3]2[C:8]=1[C:9]([S:11]([O-:14])(=[O:13])=[O:12])=[CH:10][CH:1]=[CH:2]2
Reactant: Nc1cc(S(=O)(=O)O)cc2cccc(S(=O)(=O)O)c12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Nc1cc(S(=O)(=O)[O-])cc2cccc(S(=O)(=O)[O-])c12
Yield: 87 %

Procedure:
To a solution of 25.0 g of 1-naphthylamine-3,8-disulfonic acid in 100 ml of water is added 20 ml of 5N sodium hydroxide with stirring. The mixture is warmed on a steambath and diluted with absolute ethyl alcohol to yield a crystalline precipitate. The solid is collected at room temperature and is washed with 75% aqueous ethyl alcohol, ethyl alcohol and ether. The product is dried in vacuo at 110° C. overnight to yield 22.8 g of (87%) 8-amino-1,6-naphthalenedisulfonic acid disodium salt.
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][Cl:5].[NH2:10][C:11]([NH2:13])=[S:12].CO>C(OCC)C>[ClH:5].[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][NH+:10]=[C:11]([NH2:13])[SH:12]
Reactant: Fc1ccccc1CCl
Reactant: NC(N)=S
Solvent: CO
Solvent: CCOCC
Product: Cl
Product: NC(S)=[NH+]Cc1ccccc1F
Yield: 96.8 %

Procedure:
2-Fluorobenzyl chloride (125 g, 0.86 mole, Aldrich), thiourea (66 g, 0.87 mole) and 200 mL of methanol were refluxed for 2 hours under nitrogen. The reaction was cooled and the volume was reduced to ˜40 mL. The slurry was poured into 1 liter of diethyl ether. The resulting white solid was filtered and dried under vacuum to give 184.5 g (97 %) of the title compound as a white solid.
Reaction SMILES: Cl.[NH2:2][OH:3].[Na].[C:5]([C:7]1[CH:12]=[CH:11][N:10]=[C:9]([N:13]([CH3:15])[CH3:14])[CH:8]=1)#[N:6]>CO>[CH3:14][N:13]([CH3:15])[C:9]1[CH:8]=[C:7]([C:5](=[N:2][OH:3])[NH2:6])[CH:12]=[CH:11][N:10]=1
Reactant: CN(C)c1cc(C#N)ccn1
Reactant: NO
Agent: Cl
Agent: [Na]
Solvent: CO
Product: CN(C)c1cc(C(N)=NO)ccn1
Temperature: 25 °C
Yield: 134.8 %

Procedure:
To a solution of hydroxylamine hydrochloride (0.47 g, 7.0 mmol) in methanol (10 mL) was added sodium metal (0.16 g, 7.0 mmol) portionwise. After all the sodium metal had dissolved 4-cyano-2-dimethylaminopyridine (1.0 g, 7.0 mmol) was added and the reaction was heated to reflux for 4 hours. The reaction was cooled to room temperature, filtered to remove precipitated sodium chloride and the filtrate was evaporated to dryness. The residue was dissolved in ethanol in order to crystallise the product but this was unsuccessful, so the solvent was removed in vacuo to give the title compound as a white solid (1.7 g), which was contaminated with ethanol.
Reaction SMILES: COC1C=CC(C[O:8][C:9]2[CH:10]=[CH:11][C:12]3[N:13]([CH:15]=[C:16]([NH:18][C:19]([CH:21]4[CH2:23][CH2:22]4)=[O:20])[N:17]=3)[CH:14]=2)=CC=1.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+]>FC(C1C=CC=CC=1)(F)F>[OH:8][C:9]1[CH:10]=[CH:11][C:12]2[N:13]([CH:15]=[C:16]([NH:18][C:19]([CH:21]3[CH2:22][CH2:23]3)=[O:20])[N:17]=2)[CH:14]=1
Reactant: COc1ccc(COc2ccc3nc(NC(=O)C4CC4)cn3c2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: FC(F)(F)c1ccccc1
Solvent: COc1ccccc1
Product: O=C(Nc1cn2cc(O)ccc2n1)C1CC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 87.8 %

Procedure:
To a solution of N-{6-[(4-methoxybenzyl)oxy]imidazo[1,2-a]pyridin-2-yl}cyclopropanecarboxamide (10.1 g, 29.9 mmol) and anisole (25.97 mL, 239.2 mmol) in trifluoromethylbenzene (200 mL) was added trifluoroacetic acid (40.4 mL), and the mixture was stirred at room temperature for 3 hr. Saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted 5 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure. The obtained residue was washed with ethyl acetate and collected by filtration to give the title compound (5.7 g, 88%) as a pale-brown solid.
Reaction SMILES: [Cl:1][C:2]1[C:11]([CH3:12])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.C.[CH2:14]([NH:16][C:17]([NH:19][CH2:20][CH3:21])=[S:18])[CH3:15]>CC(C)=O>[ClH:1].[CH3:12][C:11]1[C:2]([S:18][C:17](=[N:16][CH2:14][CH3:15])[NH:19][CH2:20][CH3:21])=[N:3][C:4]2[C:9]([N:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2
Reactant: Cc1nc2ccccc2nc1Cl
Reactant: CCNC(=S)NCC
Agent: C
Solvent: CC(C)=O
Product: CCN=C(NCC)Sc1nc2ccccc2nc1C
Product: Cl

Procedure:
2-Chloro-3-methylquinoxaline (15.0 g., 0.084 mole) was dissolved in 225 ml. of acetone, treated with Norit and filtered. The filtrate was added to 11.11 g. (0.084 mole) of 1,3-diethylthiourea in 175 ml. of acetone and the mixture was stirred at room temperature for 51/2 hours. The solid which separated was filtered and washed well with acetone, then with ether and dried to give 18.12 g. (69.7%) of product, m.p. 121.5°-122°.
Reaction SMILES: [C@@H:1]1([N:10]2[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]2=[O:12])[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]1[OH:3].C([Sn](=O)CCCC)CCC.C([C@@]1(O)[C@H](OCCCC)[C@@H](C(=[SnH2])O)O[C@H]1N1C=CC(=O)NC1=O)CCC.I[CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH3:63]>>[CH2:55]([O:3][C@@H:2]1[C@H:4]([OH:5])[C@@H:6]([CH2:7][OH:8])[O:9][C@H:1]1[N:10]1[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]1=[O:12])[CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH3:63]
Reactant: O=c1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)[nH]1
Reactant: CCCCCCCCCI
Agent: CCCCO[C@@H]1[C@@H](C(O)=[SnH2])O[C@@H](n2ccc(=O)[nH]c2=O)[C@@]1(O)CCCC
Agent: CCCC[Sn](=O)CCCC
Product: CCCCCCCCCO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1ccc(=O)[nH]c1=O

Procedure:
As per the procedure of Example 49, uridine (22.5 g) was treated with dibutyl tin oxide (22.5 g, 1 eq). The resulting 2',3'-O-dibutylstannyleneuridine was treated with iodononane (11 ml, 1.3 eq.) at 130°-140° C. as per Example 50 to give the 2' and 3' isomers (11.2 g) as an oil.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]=[N:11][C:12]1[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:13]=1[OH:19])([O-])=[O:2].C1C2C(=O)C3C(=CC=CC=3)C=2C=CC=1.O=C[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.N(C1C=CC=CC=1)=NC1C=CC=CC=1>O.CO>[OH:19][C:13]1[CH:14]=[CH:15][C:16]([CH3:18])=[CH:17][C:12]=1[N:11]1[N+:1]([O-:2])=[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]2=[N:10]1
Reactant: Cc1ccc(O)c(N=Nc2ccccc2[N+](=O)[O-])c1
Agent: O=C1c2ccccc2-c2ccccc21
Agent: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: c1ccc(N=Nc2ccccc2)cc1
Solvent: O
Solvent: CO
Product: Cc1ccc(O)c(-n2nc3ccccc3[n+]2[O-])c1

Procedure:
A mixture of methanol 60 ml, water 30 ml, 97% sodium hydroxide, 12.4 g and 2-nitro-2'-hydroxy-5'-methyl azobenzene 12.9 g was heated and stirred at 45°~50° C. 9-fluorenone 1.0 g and then glucose 5.5 g were added to the resultant mixture over 30 minutes while stirring. The mixture was further stirred at 75° C. (boiling point) for 7 hours. As this result, the azobenzene disappeared to produce 2-(2'-hydroxy-5'-methylphenyl)benzotriazole-N-oxide, thus the reaction of Process (b) being completed.
Reaction SMILES: C([O-])(=O)C.[Y+3:5].C([O-])(=O)C.C([O-])(=O)C.[CH2:14]([CH:16]([CH2:20][CH2:21][CH2:22][CH3:23])[C:17]([OH:19])=[O:18])[CH3:15]>>[Y:5].[CH2:14]([CH:16]([CH2:20][CH2:21][CH2:22][CH3:23])[C:17]([O-:19])=[O:18])[CH3:15].[CH2:14]([CH:16]([CH2:20][CH2:21][CH2:22][CH3:23])[C:17]([O-:19])=[O:18])[CH3:15].[CH2:14]([CH:16]([CH2:20][CH2:21][CH2:22][CH3:23])[C:17]([O-:19])=[O:18])[CH3:15].[Y+3:5]
Reactant: CCCCC(CC)C(=O)O
Agent: CC(=O)[O-]
Agent: [Y+3]
Product: CCCCC(CC)C(=O)[O-]
Product: [Y]

Procedure:
A yttrium containing solution was prepared by mixing and reacting yttrium acetate with a stoichiometric excess of 2-ethylhexanoic acid to produce yttrium tri(2-ethylhexanoate) in 2-ethylhexanoic acid. The resulting solution contained 7.01 percent by weight yttrium, based on total weight.
Reaction SMILES: CC1(C)[O:9][C:8](=[O:10])[C:5]2([CH2:7][CH2:6]2)[C:4](=[O:11])O1.[NH2:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=1>C(O)C>[C:18]([C:17]1[CH:20]=[CH:21][C:14]([N:13]2[CH2:6][CH2:7][CH:5]([C:8]([OH:9])=[O:10])[C:4]2=[O:11])=[CH:15][CH:16]=1)#[N:19]
Reactant: N#Cc1ccc(N)cc1
Reactant: CC1(C)OC(=O)C2(CC2)C(=O)O1
Solvent: CCO
Product: N#Cc1ccc(N2CCC(C(=O)O)C2=O)cc1
Yield: 35.5 %

Procedure:
A mixture of 6,6-dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione (0.500 g, 2.94 mmol) and 4-aminobenzonitrile (1.04 g, 8.82 mmol) in ethanol (3 mL) was irradiated in a microwave oven for 3 minutes at 100° C. The solution was concentrated under reduced pressure and the residue was dissolved in a solution of sodium hydroxide 6N, washed with dichloromethane, acidified with a solution of sodium hydrogen phosphate (1M) to pH=2, extracted with ethyl acetate dried and concentrated under reduced pressure to yield 0.240 g (36%) of a brown solid, which was used in the next step without further purification.