Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:15]=[CH:14][CH:13]=[CH:12][C:6]=1[O:7][CH2:8][CH:9]1[O:11][CH2:10]1)[CH:2]=[CH2:3].[NH2:16][CH2:17][CH2:18][O:19][C:20]1[CH:21]=[C:22]([C:26]2[CH:27]([CH3:33])[CH2:28][C:29](=[O:32])[NH:30][N:31]=2)[CH:23]=[CH:24][CH:25]=1>>[CH2:1]([O:4][C:5]1[CH:15]=[CH:14][CH:13]=[CH:12][C:6]=1[O:7][CH2:8][CH:9]([OH:11])[CH2:10][NH:16][CH2:17][CH2:18][O:19][C:20]1[CH:21]=[C:22]([C:26]2[CH:27]([CH3:33])[CH2:28][C:29](=[O:32])[NH:30][N:31]=2)[CH:23]=[CH:24][CH:25]=1)[CH:2]=[CH2:3]
Reactant: C=CCOc1ccccc1OCC1CO1
Reactant: CC1CC(=O)NN=C1c1cccc(OCCN)c1
Product: C=CCOc1ccccc1OCC(O)CNCCOc1cccc(C2=NNC(=O)CC2C)c1

Procedure:
Prepared analogously to Example 1 from 1-(2-allyloxy-phenoxy)-2,3-epoxypropane and 6-[3-(2-aminoethoxy)phenyl]-4,5-dihydro-5-methyl-3(2H)-pyridazinone.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([N+:20]([O-:22])=[O:21])=[C:13]([CH:15]([OH:19])[C:16]([CH3:18])=[CH2:17])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>ClCCl.[O-2].[O-2].[Mn+4]>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([N+:20]([O-:22])=[O:21])=[C:13]([C:15](=[O:19])[C:16]([CH3:18])=[CH2:17])[CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C=C(C)C(O)c1cc(OCc2ccccc2)ccc1[N+](=O)[O-]
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Product: C=C(C)C(=O)c1cc(OCc2ccccc2)ccc1[N+](=O)[O-]
Temperature: 25 °C
Yield: 85.4 %

Procedure:
3.67 g (42.23 mmol) of manganese dioxide are suspended in a solution of 1.58 g (5.28 mmol) of 1-[5-(benzyloxy)-2-nitrophenyl]-2-methyl-2-propen-1-ol in 30 ml of dichloromethane. The suspension is heated under reflux overnight, and after cooling to room temperature the mixture is filtered through kieselguhr, the residue is washed with dichloromethane and the filtrate is concentrated in vacuo and dried. 1.34 g (85%) of 1-[5-(benzyloxy)-2-nitrophenyl]-2-methyl-2-propen-1-one are obtained.
Reaction SMILES: Br[C:2]1[C:10]2[N:9]3[CH2:11][CH2:12][CH2:13][NH:14][C:15](=[O:16])[C:8]3=[CH:7][C:6]=2[CH:5]=[C:4]([C:17]#[N:18])[CH:3]=1.[C:19]1(B(O)O)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[O:16]=[C:15]1[C:8]2=[CH:7][C:6]3[CH:5]=[C:4]([C:17]#[N:18])[CH:3]=[C:2]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[C:10]=3[N:9]2[CH2:11][CH2:12][CH2:13][NH:14]1
Reactant: N#Cc1cc(Br)c2c(c1)cc1n2CCCNC1=O
Reactant: OB(O)c1ccccc1
Product: N#Cc1cc(-c2ccccc2)c2c(c1)cc1n2CCCNC1=O

Procedure:
The title compound, light grey solid (66 mg, 88%), MS (ISP) m/z=302.5 [(M+H)+], mp 237.5° C., was prepared in accordance with the general method of example 1 from 7-bromo-1-oxo-2,3,4,5-tetrahydro-[1,4]diazepino[1,2-a]indole-9-carbonitrile (intermediate 20) (76.0 mg, 0.25 mmol) and commercially available phenylboronic acid (39.6 mg, 0.325 mmol).
Reaction SMILES: [CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]3[N:36](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:35]=[N:34][N:33]=3)=[CH:22][CH:21]=2)[C:7]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:8]([C:10]([OH:13])([CH3:12])[CH3:11])[N:9]=1)[CH3:2].C(O)(=O)C.C(O)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>O>[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]3[NH:36][N:35]=[N:34][N:33]=3)=[CH:22][CH:21]=2)[C:7]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:8]([C:10]([OH:13])([CH3:11])[CH3:12])[N:9]=1)[CH3:2]
Reactant: CCOCc1nc(C(C)(C)O)c(C(=O)OCC)n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: OC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: O
Solvent: CC(=O)O
Product: CCOCc1nc(C(C)(C)O)c(C(=O)OCC)n1Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1
Yield: 99.6 %

Procedure:
A solution of 600 mg of ethyl 2-ethoxymethyl -4-(1-hydroxy-1-methylethyl)-1-{4-[2-(trityltetrazol-5-yl)phenyl]phenyl}methylimidazole-5-carboxylate [prepared as described in step (a) above] in 10 ml of a 25% v/v aqueous solution of acetic acid was stirred at 60° C. for 2 hours. 10 ml of water were then added, and the mixture was then cooled with ice. The trityl alcohol which appeared as crystals was filtered off. The filtrate was concentrated by distillation under reduced pressure, and then acetic acid and water were distilled off as azeotropic mixtures with toluene, to give 400 mg of the title compound in an amorphous powder.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([CH3:16])[N:11]=2)=[CH:5][C:4]([C:17]2[C:22]([CH:23]=[O:24])=[C:21]([N:25]3[CH2:36][CH2:35][N:34]4[C:27](=[CH:28][C:29]5[CH2:30][C:31]([CH3:38])([CH3:37])[CH2:32][C:33]=54)[C:26]3=[O:39])[N:20]=[CH:19][CH:18]=2)=[CH:3]1.[BH4-].[Na+]>CO.ClCCl>[OH:24][CH2:23][C:22]1[C:21]([N:25]2[CH2:36][CH2:35][N:34]3[C:33]4[CH2:32][C:31]([CH3:37])([CH3:38])[CH2:30][C:29]=4[CH:28]=[C:27]3[C:26]2=[O:39])=[N:20][CH:19]=[CH:18][C:17]=1[C:4]1[CH:5]=[C:6]([NH:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([CH3:16])[N:11]=2)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1
Reactant: Cc1nccc(Nc2cc(-c3ccnc(N4CCn5c(cc6c5CC(C)(C)C6)C4=O)c3C=O)cn(C)c2=O)n1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: Cc1nccc(Nc2cc(-c3ccnc(N4CCn5c(cc6c5CC(C)(C)C6)C4=O)c3CO)cn(C)c2=O)n1
Reaction time: 1 h
Yield: 68.5 %

Procedure:
To a solution of 179a (262 mg, 0.50 mmol) in methanol/dichloromethane (10/10 mL) was added NaBH4 (57 mg, 1.5 mmol) at room temperature. After the reaction was stirred for 1 h, LCMS indicated the reaction was complete. Then the mixture was concentrated under reduced pressure. The residue was diluted with water (5 mL) and dichloromethane (20 mL. The water phase was separated and extracted with dichloromethane (3×10 mL). The combined organic layer was washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue solid was purified by reverse-phase prep-HPLC to afford 179 (180 mg, 69%) as white solid. MS-ESI: [M+H]+ 526. 1H NMR (500 MHz, CDCl3) δ 8.93 (d, J=2.0 Hz, 1H), 8.53 (d, J=5.5 Hz, 1H), 8.28 (d, J=5.5 Hz, 1H), 8.07 (s, 1H), 8.03 (d, J=2.0 Hz, 1H), 7.36 (s, 1H), 6.86 (s, 1H), 6.60 (d, J=6.0 Hz, 1H), 5.18-5.16 (m, 1H), 4.70-4.67 (m, 1H), 4.55-4.53 (m, 1H), 4.33-4.31 (m, 1H), 4.18-4.16 (m, 2H), 3.91-3.90 (m, 1H), 3.74 (s, 3H), 2.60 (s, 3H), 2.58 (d, J=5.5 Hz, 2H), 2.52 (s, 2H), 1.28 (s, 6H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:19])=[C:6]([C:8]2[NH:17][C:16](=O)[C:15]3[C:10](=[N:11][CH:12]=[CH:13][N:14]=3)[N:9]=2)[CH:7]=1.[OH:20][CH2:21][CH2:22][NH2:23].C(N(C1C=CN=CC=1)C1C2C(=NC=CN=2)N=C(C2C=C(Br)C=CC=2F)N=1)CCC>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:19])=[C:6]([C:8]2[N:17]=[C:16]([NH:23][CH2:22][CH2:21][OH:20])[C:15]3[C:10](=[N:11][CH:12]=[CH:13][N:14]=3)[N:9]=2)[CH:7]=1
Reactant: NCCO
Reactant: O=c1[nH]c(-c2cc(Br)ccc2F)nc2nccnc12
Agent: CCCCN(c1ccncc1)c1nc(-c2cc(Br)ccc2F)nc2nccnc12
Product: OCCNc1nc(-c2cc(Br)ccc2F)nc2nccnc12

Procedure:
The title product was synthesized by reaction of the 2-(5-bromo-2-fluorophenyl)-pteridin-4-one 104 with 2-hydroxyethylamine following the procedure described for 4-[(butyl)(4-pyridyl)amino]-2-(5-bromo-2-fluorophenyl)pteridine 3.
Reaction SMILES: B#B.[CH2:3]([N:6]([CH2:20][CH2:21][CH3:22])[C:7](=O)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([O:17][CH3:18])[CH:10]=1)[CH2:4][CH3:5].CO>O1CCCC1>[CH2:20]([N:6]([CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([O:17][CH3:18])[CH:10]=1)[CH2:3][CH2:4][CH3:5])[CH2:21][CH3:22]
Reactant: CCCN(CCC)C(=O)Cc1ccc(OC)c(OC)c1
Agent: B#B
Solvent: C1CCOC1
Solvent: CO
Product: CCCN(CCC)CCc1ccc(OC)c(OC)c1

Procedure:
To 200 ml. (0.20 mole) of a 1M solution of diborane in tetrahydrofuran cooled in an ice bath was added dropwise a solution of 27.8 g. (0.10 mole) of N,N-di-(n-propyl)-3,4-dimethoxyphenylacetamide in about 200 ml. of anhydrous tetrahydrofuran, under argon. The mixture was refluxed for one and one-quarter hours, cooled and methanol added carefully. When the bubbling subsided the reaction mixture was evaporated in vacuo. The residue was dissolved in methanol, ethereal hydrogen chloride was added and the mixture evaporated in vacuo slowly. This residue was dissolved in water, washed with ether, basified and extracted with ether. The dried solution was evaporated to yield N,N-di-(n-propyl)-3,4-dimethoxyphenethylamine.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:25])[CH:5]([C:20]([CH:22]1[CH2:24][CH2:23]1)=O)[C:6](=O)[CH2:7][N:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:18])[CH3:2].Cl.[NH2:27][NH2:28]>>[CH2:1]([O:3][C:4]([C:5]1[C:6]([CH2:7][N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:18])=[N:27][NH:28][C:20]=1[CH:22]1[CH2:24][CH2:23]1)=[O:25])[CH3:2]
Reactant: CCOC(=O)C(C(=O)CN1C(=O)c2ccccc2C1=O)C(=O)C1CC1
Reactant: NN
Agent: Cl
Product: CCOC(=O)c1c(CN2C(=O)c3ccccc3C2=O)n[nH]c1C1CC1
Yield: 36 %

Procedure:
In analogy to the procedure described in Example 160B]), 2-cyclopropanecarbonyl-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-oxo-butyric acid ethyl ester and hydrazine.hydrochloride gave the title compound as a light yellow solid (36%). MS: 338.5 (M−H−).
Reaction SMILES: [CH3:1][N:2]1[CH2:6][CH2:5][CH:4]([N:7]2[CH:11]=[C:10]([N+:12]([O-])=O)[CH:9]=[N:8]2)[CH2:3]1>CO.[Ni]>[CH3:1][N:2]1[CH2:6][CH2:5][CH:4]([N:7]2[CH:11]=[C:10]([NH2:12])[CH:9]=[N:8]2)[CH2:3]1
Reactant: CN1CCC(n2cc([N+](=O)[O-])cn2)C1
Agent: [Ni]
Solvent: CO
Product: CN1CCC(n2cc(N)cn2)C1
Reaction time: 3 h

Procedure:
A solution of 1-(1-Methylpyrrolidin-3-yl)-4-nitro-1H-pyrazole (3.0 g, 18 mmol, 1 eq.) in methanol (40 mL) was hydrogenated (3 bars) in presence of Ra—Ni (1 g) at RT. After 3 h, the catalyst was filtered off and the filtrate was concentrated under reduced pressure to give the title compound as brown liquid. 1H NMR (400 MHz, DMSO-d6) δ 7.06 (s, 1H), 6.85 (m, 1H), 4.67 (m, 1H), 3.82 (brs, 2H) 2.63-2.74 (m, 2H), 2.58-2.61 (m, 1H), 2.38-2.44 (m, 1H), 2.21-2.28 (m, 1H), 2.27 (s, 3H), 1.89-1.97 (m, 1H).
Reaction SMILES: [I-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Li+].[CH3:23][CH2:24][CH2:25][CH2-:26].[C:27]1([N:33]2CCC(=O)[CH2:35][CH2:34]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C1COCC1>[CH2:23]=[C:24]1[CH2:35][CH2:34][N:33]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:26][CH2:25]1
Reactant: [CH2-]CCC
Reactant: O=C1CCN(c2ccccc2)CC1
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [I-]
Agent: [Li+]
Solvent: C1CCOC1
Product: C=C1CCN(c2ccccc2)CC1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
In a 50 mL round bottom flask, methyltriphenylphosphonium iodide (1.384 g, 3.42 mmol) was suspended in THF (10.0 mL) and cooled to 0° C. N-Butyllithium (1.370 mL, 3.42 mmol) was added drop-wise and the resulting yellow suspension was stirred at 0° C. for 30 min. A solution of 1-phenylpiperidin-4-one (0.500 g, 2.85 mmol) in THF (5.0 mL) was added drop-wise and the orange, yellow suspension was then allowed to slowly warm to 23° C. over 2 hr. The reaction mixture was quenched with sat. NH4Cl (30 mL), the aq. layer was extracted with EtOAc (2×50 mL) and the combined organic extracts were washed with brine (30 mL), dried over MgSO4, filtered, and concentrated in vacuo. The crude yellow oil was purified by flash chromatography (EtOAc:Hex, 1:9 isocratic) affording the title compound as a clear, light yellow oil (0.0906 g, 18.33% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.14-2.39 (m, 4H) 3.12-3.29 (m, 4 H) 4.74 (s, 2H) 6.64-6.85 (m, 1H) 6.87-7.07 (m, 2H) 7.08-7.29 (m, 2H). ESI-MS: m/z 174.1 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:8][CH:9]=[N:10][N:11]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].O1CCCC1.[Cl:33][C:34]1[C:35]([F:45])=[CH:36][C:37]([F:44])=[C:38]([S:40](Cl)(=[O:42])=[O:41])[CH:39]=1.[Cl-].[NH4+]>CC1CCCO1.O>[Cl:33][C:34]1[C:35]([F:45])=[CH:36][C:37]([F:44])=[C:38]([S:40]([N:6]([CH2:5][C:4]2[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:3]=2[O:2][CH3:1])[C:7]2[S:8][CH:9]=[N:10][N:11]=2)(=[O:42])=[O:41])[CH:39]=1
Reactant: O=S(=O)(Cl)c1cc(Cl)c(F)cc1F
Reactant: COc1ccc(CNc2nncs2)c(OC)c1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Agent: [Li+]
Solvent: O
Solvent: CC1CCCO1
Solvent: C1CCOC1
Product: COc1ccc(CN(c2nncs2)S(=O)(=O)c2cc(Cl)c(F)cc2F)c(OC)c1
Temperature: 15 °C
Reaction time: 0.75 h
Yield: 58.5 %

Procedure:
N-(2,4-Dimethoxybenzyl)-1,3,4-thiadiazol-2-amine (Preparation 14, 203.4 g, 0.809 mol) was dissolved in 2-methyltetrahydrofuran (1.63 L) and the yellow suspension cooled to between −38° C. and −45° C. A 1M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (890 mL, 0.890 mol) was added slowly over 15 minutes keeping the temperature between −38° C. and −45° C. to give an orange suspension. This orange suspension was stirred at −38° C. to −45° C. for 45 minutes and then a solution of 5-chloro-2,4-difluorobenzenesulfonyl chloride, (200 g, 0.809 mol) in 2-methyltetrahydrofuran (407 mL) added slowly over 20 minutes keeping the temperature between −38° C. and −45° C. The mixture was warmed to 15° C. over 1 hour. The reaction was quenched with a solution of ammonium chloride (203.4 g, 3.80 mol) in water (1.02 L) and stirred vigorously for 5 minutes. The layers were separated and the organic layer washed with water (813.6 mL) and concentrated in vacuo to give an orange solid which was triturated with isopropyl acetate (1.22 L) to afford the title compound as a yellow-orange solid (218.6 g).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].[Cl:10][C:11]1[CH:12]=[C:13]([OH:17])[CH:14]=[CH:15][CH:16]=1.[H-].[Na+].Cl>N1C=CC=CC=1.O>[Cl:10][C:11]1[CH:12]=[C:13]([CH:14]=[CH:15][CH:16]=1)[O:17][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6]
Reactant: Oc1cccc(Cl)c1
Reactant: O=Cc1cccc(Br)c1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: c1ccncc1
Solvent: O
Product: O=Cc1cccc(Oc2cccc(Cl)c2)c1

Procedure:
A mixture of 3-bromobenzaldehyde (6.0g), 3-Chlorophenol (4.8g), sodium hydride (1.3 g of an 80% suspension in oil) and cuprous cloride (1 g) was heated under reflux in pyridine (125 ml) under an atmosphere of nitrogen gas for 16 hours. The mixture was cooled, diluted with water, acidified with hydrochloric acid and extracted with diethyl ether. The etheral extracts were dried (Na2SO4), concentrated and purified by chromatography on silica gel eluting with ethyl acetate-petroleum ether (1:9) to give the title compound as a colourless oil.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[CH3:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:13][NH:14][CH:15]=O)=[N:11][CH:12]=1>C1(C)C=CC=CC=1>[CH3:6][C:7]1[CH:8]=[CH:9][C:10]2[N:11]([CH:15]=[N:14][CH:13]=2)[CH:12]=1
Reactant: Cc1ccc(CNC=O)nc1
Solvent: Cc1ccccc1
Solvent: O=P(Cl)(Cl)Cl
Product: Cc1ccc2cncn2c1
Temperature: 100 °C
Reaction time: 8 h
Yield: 41 %

Procedure:
In a round-bottomed flask, N-(5-methyl-pyridin-2-ylmethyl)-formamide (crude from step 2) was dissolved in toluene (30 ml) and phosphorus oxychloride (1.2 ml, 12.9 mmol) was added. The reaction mixture was stirred at 100° C. in an oil bath overnight then cooled to 0° C. and carefully quenched with ice. Aqueous 25% ammonium hydroxide was added until pH=˜9. The mixture was diluted with water and extracted with dichloromethane (2×). The organic layers were combined, dried over sodium sulfate, filtered and concentrated. The residue was absorbed on silica gel and chromatographed with EtOAc/hexanes (gradient 0-80% EtOAc) to give 386 mg (41%, 3 steps) of 6-methyl-imidazo[1,5-a]pyridine as a light brown solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.09 (s, 1H), 7.74 (s, 1H), 7.32-7.43 (m, 2H), 6.60 (dd, J=9.4, 1.1 Hz, 1H), 2.25 (d, J=1.1 Hz, 3H).
Reaction SMILES: C(O[N:4]=[C:5]([C:7]1[N:8]=[CH:9][N:10]([C@@H:13]2[O:19][C@H:18]([CH2:20][OH:21])[C@@H:16]([OH:17])[C@H:14]2[OH:15])[C:11]=1[NH2:12])[NH2:6])C.[C:22](=S)=[S:23]>N1C=CC=CC=1.CO>[CH:9]1[N:10]([C@@H:13]2[O:19][C@H:18]([CH2:20][OH:21])[C@@H:16]([OH:17])[C@H:14]2[OH:15])[C:11]2[C:7](=[C:5]([NH2:6])[NH:4][C:22]([N:12]=2)=[S:23])[N:8]=1
Reactant: S=C=S
Reactant: CCON=C(N)c1ncn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c1N
Solvent: c1ccncc1
Solvent: CO
Product: Nc1[nH]c(=S)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Yield: 65 %

Procedure:
0.45 g of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide O-ethyl-oxime was dissolved in a mixture of 0.3 ml of pyridine, 5 ml of methanol and 0.5 ml of carbon disulfide. The resulting mixture was allowed to react in an autoclave at 120° C for 6 hours under autogenous pressure (about 10 Kg/cm2). The reaction mixture was concentrated to dryness, and the residue was dissolved in water. The aqueous solution was adjusted to a pH of 2 with hydrochloric acid to precipitate the crude product, which was then recovered by filtration. The filter cake was dissolved in aqueous ammonia, the solution was filtered, and the filtrate was adjusted to a pH of 2 with hydrochloric acid to obtain 0.31 g of pure 2-thioadenosine as crystals having a melting point of 199° C (with decomposition) in a 65% yield.
Reaction SMILES: [C:1]([N:11]1[CH2:14][C:13]([CH3:30])([C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:25][C@@H:24]([CH2:26][NH2:27])[O:23][C:22]3=[O:28])=[CH:17][C:16]=2[F:29])[CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].N1C=CC=CC=1.[C:37](OC(=O)C)(=[O:39])[CH3:38]>ClCCl>[F:29][C:16]1[CH:17]=[C:18]([N:21]2[CH2:25][C@H:24]([CH2:26][NH:27][C:37](=[O:39])[CH3:38])[O:23][C:22]2=[O:28])[CH:19]=[CH:20][C:15]=1[C:13]1([CH3:30])[CH2:14][N:11]([C:1]([O:3][CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)=[O:2])[CH2:12]1
Reactant: CC1(c2ccc(N3C[C@@H](CN)OC3=O)cc2F)CN(C(=O)OCc2ccccc2)C1
Reactant: CC(=O)OC(C)=O
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(=O)NC[C@H]1CN(c2ccc(C3(C)CN(C(=O)OCc4ccccc4)C3)c(F)c2)C(=O)O1
Temperature: 0 °C
Yield: 84 %

Procedure:
The title compound was prepared as follows: (R)-(-)-N-carbobenzyloxy-3-methyl-3-[2-fluoro-4-[5-aminomethyl-2-oxo-3-oxazolidinyl]phenyl]azetidine was diluted with 220 mL dichloromethane, cooled to 0° C., and successively treated with 3.7 mL pyridine (46 mmol) and 1.8 mL acetic anhydride (19 mmol) with no observable change. The cooling bath was removed and the reaction mixture was warmed to room temperature for 16 hours. The visually unchanged solution was concentrated to a yellow foam, rediluted with 50 mL dichloromethane, and filtered to remove the remaining insoluble precipitate. The filtrate was purified by LC on 340 g (230-400) silica gel eluting with 2.5% methanol/ethyl acetate to afford 5.85 g (84%) of (S)-N-[[3-[3-fluoro-4-[1-(carbobenzyloxy)-(3-methyl)-3-azetidinyl]-phenyl]-2-oxo-5-oxazolidinyl]methyl]-acetamide as a colorless glass. Rf 0.24 (2.5% methanol/ethyl acetate); [α]D - 19°(c 0.9971, methanol); IR (mull) 1754, 1706, 1676, 1516, 1430, 1415, 1357, 1227, 1194, 1075 cm-1 ; 1H NMR (300 MHz, CDCl3) δ7.42 (dd, 1H, J=2.1 Hz, J=12.9 Hz, aromatic), 7.33 (m, 5H, aromatic), 7.13 (dd, 1H, J=2.2 Hz, J=8.5 Hz, aromatic), 7.04 (t, 1H, J=8.5 Hz, aromatic), 6.56 (bt, 1H, J=6.2 Hz, NH), 5.10 (s, 2H, Ph-CH2), 4.79 (m, 1H, methine), 4.30 (d, 2H, J=8.2 Hz, Ph-C--CH2 as), 4.01 (m, 3H, Ph-C--CH2b s, Ph-N--CH2a), 3.78 (dd, 1H, J=6.7 Hz, J=9.1 Hz, Ph-N--CH2b), 3.64 (m, 2H, NH--CH2 s), 2.02 (s, 3H, O=C--CH3), 1.60, (s, 3H, Ph-C--CH3); 13C NMR (75 MHz, CDCl3) 171.2, 160.3 (d, JCF =246 Hz), 156.6, 154.2, 137.9 (d, JCF =11 Hz), 136.5, 128.9 (d, JCF =14 Hz), 128.4, 127.9, 127.2 (d, JCF =7 Hz), 113.2 (d, JCF =2 Hz), 106.4 (d, JCF =28 Hz), 72.0, 66.6, 60.7, 60.3, 47.3, 41.7, 36.1, 28.1, 22.9; Anal. Calcd for C24H26N3O5F1 : C, 63.29; H, 5.75; N, 9.23. Found: C, 62.98; H, 5.96; N, 8.98.
Reaction SMILES: [C:1]([O:5][C:6](=[O:23])[CH2:7][C@H:8]([CH2:12][C@H:13]([CH3:22])[CH2:14][CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)C(O)=O)(C)(C)C.C([N:26](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>C1(C)C=CC=CC=1>[CH3:1][O:5][C:6](=[O:23])[CH2:7][C@@H:8]([NH2:26])[CH2:12][C@H:13]([CH3:22])[CH2:14][CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1
Reactant: CCN(CC)CC
Reactant: C[C@H](CCC1CCCCC1)C[C@@H](CC(=O)OC(C)(C)C)C(=O)O
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Product: COC(=O)C[C@@H](N)C[C@H](C)CCC1CCCCC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A flask was charged with 2.19 g (6.71 mmol) of (S)-2-((R)-4-cyclohexyl-2-methyl-butyl)-succinic acid 4-tert-butyl ester, 40 mL of toluene, 0.935 mL (6.71 mmol) of triethylamine, and 1.45 mL (6.71 mmol) of diphenylphosphorylazide. The mixture was stirred for 15 minutes at room temperature and then heated to 110° C. and stirred for 6 hours. The toluene was removed under reduced pressure, and the residue was taken up in diethyl ether. The ether layer was washed with 3M HCl aq., water, and brine. The ether was removed under reduced pressure, and the crude isocyanate was taken up in 3 M HCl aq. and heated at reflux for 8 hours. The water was removed under reduced pressure, and the residue was triturated with ether. This provided 1.45 g of an impure white solid. A portion of the white solid was dissolved in methanol, and HCl gas was bubbled through for 15 minutes. The acidic solution was stirred 2 hours. The methanol was removed under reduced pressure, and the crude ester was purified by column chromatography (4:1 dichloromethane: methanol). This gave 0.356 g of the pure ester: 1H NMR (400 MHz, CDCl3) δ ppm 0.85 (m, 2 H) 0.88 (d, J=8.00 Hz, 3 H) 1.15 (m, 6 H) 1.26 (m, 1 H) 1.36 (ddd, J=13.73, 9.21, 4.64 Hz, 1 H) 1.51 (m, 1 H) 1.65 (m, 7 H) 2.28 (dd, J=15.86, 8.78 Hz, 1 H) 2.43 (dd, J=16.0, 4.00 Hz, 1 H) 3.28 (m, J=8.97, 8.97, 4.39, 4.27 Hz, 1 H) 3.69 (s, 3H). MS (APCl) m+1/z=256.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][CH3:22])[CH:16]=2)=[CH:11][CH:10]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:23]([CH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][C:32]1=O)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1(OC)C=CC=CC=1.[Pd]>[C:23]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[NH:1][C@@H:2]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][CH3:22])[CH:16]=2)=[CH:11][CH:10]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4])(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: O=C1CCCCC1C(=O)c1ccccc1
Reactant: CCOC(=O)[C@@H](N)Cc1ccc(-c2cccc(NC)c2)cc1
Agent: [Pd]
Solvent: COc1ccccc1
Product: CCOC(=O)[C@H](Cc1ccc(-c2cccc(NC)c2)cc1)Nc1ccccc1C(=O)c1ccccc1
Yield: 55.8 %

Procedure:
5.7 g (22.1 mmol) of ethyl (S)-2-amino-3-(3′-methylaminobiphenyl-4-yl)propionate and 5.8 g (28.7 mmol) of 2-benzoylcyclohexanone are dissolved in 10 ml of anisole. 0.6 g of 10% palladium-on-charcoal are added and the reaction medium is then refluxed using a Dean-Stark apparatus for 16 h. The cooled reaction medium is filtered through celite, rinsed with ethyl acetate and concentrated. The residue obtained is purified by chromatography on a column of silica and eluted with a 7/3 heptane/ethyl acetate mixture. 5.9 g of desired product are isolated with a 49% yield.
Reaction SMILES: [C:1]([C:6](=[CH:12][NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]([O:22][CH3:23])=[O:21])[C:7]([O:9]CC)=O)(=[O:5])[CH2:2][CH2:3][CH3:4]>C1(OC2C=CC=CC=2)C=CC=CC=1>[C:1]([C:6]1[C:7](=[O:9])[C:19]2[C:14](=[C:15]([C:20]([O:22][CH3:23])=[O:21])[CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)(=[O:5])[CH2:2][CH2:3][CH3:4]
Reactant: CCCC(=O)C(=CNc1ccccc1C(=O)OC)C(=O)OCC
Solvent: c1ccc(Oc2ccccc2)cc1
Product: CCCC(=O)c1c[nH]c2c(C(=O)OC)cccc2c1=O

Procedure:
Ethyl 2-butyryl-3-(2-carbomethoxyphenylamino)acrylate (8.63 g, 27.0 mmol) was added to boiling diphenyl ether (40 ml), and heated at reflux for 1 hour. On cooling, methyl 3-butyryl-4(1H)-quinolone-8-carboxylate (4.06 g, 55%) crystallised and was filtered off and washed with ether, m.p. 151-153°.