Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([N:3]([CH2:15][CH3:16])[C:4](=[O:14])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:6]=1[CH3:13])C.[Li]CCCC.[C:22]([C:26]1[CH:33]=[CH:32]C(C#N)=[CH:28][CH:27]=1)([CH3:25])([CH3:24])[CH3:23]>C1COCC1>[C:22]([C:26]1[CH:33]=[CH:32][C:16]([C:15]2[NH:3][C:4](=[O:14])[C:5]3[C:6]([CH:13]=2)=[CH:7][C:8]([O:11][CH3:12])=[CH:9][CH:10]=3)=[CH:28][CH:27]=1)([CH3:25])([CH3:24])[CH3:23]
Reactant: CC(C)(C)c1ccc(C#N)cc1
Reactant: CCN(CC)C(=O)c1ccc(OC)cc1C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COc1ccc2c(=O)[nH]c(-c3ccc(C(C)(C)C)cc3)cc2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 51.8 %

Procedure:
To a stirred solution of N,N-diethyl-4-methoxy-2-methylbenzamide (1 g, 4.52 mmol) in THF (10 ml) was added n-BuLi (2.82 ml, 4.52 mmol, in hexane) at −78° C. and stirred for 1 h. Then to this 4-(tert-butyl)benzonitrile (0.72 g, 4.52 mmol) was added at same temperature and allowed to warm to room temperature and continued the stirring for another 1 h at room temperature. The reaction mixture was quenched with saturated NH4Cl solution and extracted with EtOac (2*100 ml). The organic phase was washed with brine, dried on Na2SO4, and evaporated under reduced pressure to get crude compound. The crude compound was purified by silica gel chromatography (20% ethyl acetate in pet ether) to get desired compound (0.72 g, 46.7%) as a solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.26(s, 1H), 8.11-8.09 (d, J=8 Hz, 1H), 7.73-7.71 (d, J=8 Hz, 2H), 7.52-7.50 (d, J=8 Hz, 2H), 7.06 (s, 1H), 7.05-7.03 (d, J=8 Hz, 1H), 6.82 (s, 1H), 3.89 (s, 3H), 1.32 (s, 9H); MS: MS m/z 308.2 (M++1).
Reaction SMILES: [N+](C1C=CC(COC([NH:12][C@H:13]2[CH2:17][CH2:16][N:15]([C:18]([C@@H:20]3[CH2:24][C@H:23]([S:25][C:26]4[C@H:27]([CH3:50])[C@@H:28]5[C@@H:45]([C@H:46]([OH:48])[CH3:47])[C:44](=[O:49])[N:29]5[C:30]=4[C:31]([O:33]CC4C=CC([N+]([O-])=O)=CC=4)=[O:32])[CH2:22][N:21]3C(OCC3C=CC([N+]([O-])=O)=CC=3)=O)=[O:19])[CH2:14]2)=O)=CC=1)([O-])=O.[ClH:66]>O1CCCC1.O>[ClH:66].[NH2:12][C@H:13]1[CH2:17][CH2:16][N:15]([C:18]([C@@H:20]2[CH2:24][C@H:23]([S:25][C:26]3[C@H:27]([CH3:50])[C@@H:28]4[C@@H:45]([C@H:46]([OH:48])[CH3:47])[C:44](=[O:49])[N:29]4[C:30]=3[C:31]([OH:33])=[O:32])[CH2:22][NH:21]2)=[O:19])[CH2:14]1
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](C(=O)N4CC[C@H](NC(=O)OCc5ccc([N+](=O)[O-])cc5)C4)N(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)[C@H](C)[C@H]12
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(S[C@@H]3CN[C@H](C(=O)N4CC[C@H](N)C4)C3)[C@H](C)[C@H]12

Procedure:
1.0 g of 4-nitrobenzyl (1R, 5S, 6S)-2-{(2S, 4S)-2-[(3S)-3-(4-nitrobenzyloxycarbonyl)aminopyrrolidin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio}-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate [prepared as described in step (a) above] were dissolved in 30 ml of a 2:1 by volume mixture of tetrahydrofuran and water, after which 1.0 ml of 1N aqueous hydrochloric acid was added, and the mixture was hydrogenated by bubbling hydrogen through it at room temperature for 2hours in the presence of 1.5 g of 10% w/w palladium-on-charcoal. The catalyst was filtered off, and the filtrate was washed with diethyl ether. The washed aqueous solution was concentrated by evaporation under reduced pressure, and the residue was purified by reverse phase column chromatography through 19 ml of Cosmo Sil 75C18 -PREP (a trade mark for a product of Nacalai Tesque), using water as the eluent. Those fractions containing the title compound were combined, concentrated by evaporation under reduced pressure and lyophilized to give 169 mg of the title compound as a powder.
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]=[N:8][N:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=2)[N:10]=1)=[O:5])C.O.[Li+].[OH-]>C1COCC1>[Cl:17][C:13]1[CH:12]=[C:11]([N:9]2[N:8]=[N:7][C:6]([C:4]([OH:5])=[O:3])=[N:10]2)[CH:16]=[CH:15][CH:14]=1
Reactant: CCOC(=O)c1nnn(-c2cccc(Cl)c2)n1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1nnn(-c2cccc(Cl)c2)n1

Procedure:
7.00 g (27.7 mmol) 2-(3-chloro-phenyl)-2H-tetrazole-5-carboxylic acid ethyl ester was dissolved in 50 mL THF and 50 mL water and treated with 2.33 g (55.4 mmol) LiOH at RT for 14 h. The reaction mixture was concentrated and acidified with 1 M aqueous hydrochlorid acid. The precipitate was filtered off, washed with water and dried.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].CC1C=CC(S(O[CH:21]2[CH2:24][O:23][CH2:22]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.O.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:21]2[CH2:24][O:23][CH2:22]2)=[CH:4][C:3]=1[F:9]
Reactant: Cc1ccc(S(=O)(=O)OC2COC2)cc1
Reactant: Oc1ccc(Br)c(F)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CS(C)=O
Product: Fc1cc(OC2COC2)ccc1Br
Temperature: 60 °C

Procedure:
4-bromo-3-fluorophenol (1.185 g, 6.20 mmol), oxetan-3-yl 4-methyl-benzenesulfonate (1.77 g, 7.75 mmol) and cesium carbonate (5.05 g, 15.51 mmol) were dissolved in DMSO (7.75 mL) and heated to 60° C. overnight. The reaction mixture was diluted with water and EtOAc. The aqueous phase was extracted with EtOAc (×2) and the combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by column chromatography on a Biotage™ 50 g column by eluting with 2% to 50% EtOAc:Hexane to give the desired product. 1H NMR δ (ppm) 7.39 (t, 1H), 6.50 (d, 1H), 6.40 (d, 1H), 5.17-5.12 (m, 1H), 4.97 (t, 2H), 4.73 (t, 2H).
Reaction SMILES: [Cl:1][C:2]1[C:7]2[C:8](I)=[CH:9][N:10]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:6]=2[CH:5]=[CH:4][N:3]=1.[Cu][C:21]#[N:22].C1(C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C(=CC=CC=2)C=CC=1P(C1C=CC=CC=1)C1C=CC=CC=1>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]>[Cl:1][C:2]1[C:7]2[C:8]([C:21]#[N:22])=[CH:9][N:10]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:6]=2[CH:5]=[CH:4][N:3]=1
Reactant: C[Si](C)(C)CCOCn1cc(I)c2c(Cl)nccc21
Reactant: N#C[Cu]
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: C1COCCO1
Product: C[Si](C)(C)CCOCn1cc(C#N)c2c(Cl)nccc21
Temperature: 110 °C
Reaction time: 18 h

Procedure:
To a mixture of C7 (1.2 g, 2.9 mmol) and copper(I) cyanide (540 mg, 6.0 mmol) in 1,4-dioxane (40 mL) were added tris(dibenzylideneacetone)dipalladium(0) (275 mg, 0.300 mmol) and 1,1′-binaphthalene-2,2′-diylbis(diphenylphosphane) (BINAP, 540 mg, 0.87 mmol). After the reaction mixture had been stirred at 110° C. for 18 hours, it was filtered and concentrated under reduced pressure. Purification via silica gel chromatography (Gradient: 5% to 20% ethyl acetate in petroleum ether) afforded the product as a yellow solid. Yield: 380 mg, 1.2 mmol, 41%. 1H NMR (400 MHz, CDCl3) δ 8.27 (d, J=5.8 Hz, 1H), 7.80 (s, 1H), 7.43 (d, J=5.8 Hz, 1H), 5.52 (s, 2H), 3.47-3.54 (m, 2H), 0.88-0.95 (m, 2H), −0.02 (s, 9H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([C:12]2[S:16][C:15]3[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:14]=3[C:13]=2[CH3:22])(=[O:11])=[O:10])=[C:4]([CH2:23][S:24][CH3:25])[CH:3]=1.[N:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1>COCCOC.C(O)C.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:25][S:24][CH2:23][C:4]1[CH:3]=[C:2]([C:29]2[CH:30]=[CH:31][N:26]=[CH:27][CH:28]=2)[CH:7]=[CH:6][C:5]=1[NH:8][S:9]([C:12]1[S:16][C:15]2[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:14]=2[C:13]=1[CH3:22])(=[O:11])=[O:10]
Reactant: CSCc1cc(Br)ccc1NS(=O)(=O)c1sc2ccc(F)cc2c1C
Reactant: OB(O)c1ccncc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: CCO
Product: CSCc1cc(-c2ccncc2)ccc1NS(=O)(=O)c1sc2ccc(F)cc2c1C
Yield: 66.8 %

Procedure:
This compound was prepared in analogy to Example 2 starting from 5-fluoro-3-methyl-benzo[b]thiophene-2-sulfonic acid(4-bromo-2-methylsulfanylmethyl-phenyl)-amide (0.23 g) and 4-pyridineboronic acid (0.092 g) in 1,2-dimethoxyethane (10 ml), ethanol (2 ml) and 2 M aqueous sodium carbonate solution (2 ml) with tetrakis(triphenylphosphine)palladium (0.058 g) to obtain the title compound (0.153 g) as a brownish foam (0.153 g). MS (ISN): 457.2 (M−H)−
Reaction SMILES: [C:1]([O:5][C:6](=[O:9])[CH2:7][NH2:8])([CH3:4])([CH3:3])[CH3:2].[CH2:10]([CH:12]([CH2:15][CH3:16])[CH:13]=O)[CH3:11]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:9])[CH2:7]/[N:8]=[CH:13]/[CH:12]([CH2:15][CH3:16])[CH2:10][CH3:11])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCC(C=O)CC
Reactant: CC(C)(C)OC(=O)CN
Solvent: ClCCl
Product: CCC(/C=N/CC(=O)OC(C)(C)C)CC
Yield: 93.8 %

Procedure:
In a manner similar to the method described in Example 1a, glycine tert-butyl ester (0.65 g, 5 mmol) was reacted with 2-ethylbutyraldehyde (Aldrich) (0.55 g, 5 mmol) in CH2Cl2 at room temperature for 18 h to give [2-ethyl-but-(E)-ylideneamino]-acetic acid tert-butyl ester as a colorless oil (1 g, 94%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([N+:12]([O-:14])=[O:13])=[C:6]([NH:8]C(=O)C)[CH:7]=1.ClC1C=CC([N+]([O-])=O)=C(C=1)N.[CH3:26][O:27][C:28]([C:30]1(OC)[CH2:34][CH2:33][CH:32](OC)O1)=[O:29]>CC(O)=O>[CH3:26][O:27][C:28]([C:30]1[N:1]([C:2]2[CH:3]=[CH:4][C:5]([N+:12]([O-:14])=[O:13])=[C:6]([NH2:8])[CH:7]=2)[CH:32]=[CH:33][CH:34]=1)=[O:29]
Reactant: COC(=O)C1(OC)CCC(OC)O1
Reactant: CC(=O)Nc1cc(N)ccc1[N+](=O)[O-]
Agent: Nc1cc(Cl)ccc1[N+](=O)[O-]
Solvent: CC(=O)O
Product: COC(=O)c1cccn1-c1ccc([N+](=O)[O-])c(N)c1

Procedure:
The title compound was prepared from N-(5-amino-2-nitro-phenyl)-acetamide [prepared from commercially available 5-chloro-2-nitroaniline as described in Example F6] and 2,5-dimethoxy-tetrahydro-furan-2-carboxylic acid methyl ester [CAS-no. 39658-49-6] in HOAc at 60° C. for 2 h according to the general procedure F. Obtained as a light yellow solid (757 mg). Deacetylation of this material was perfomed by stirring with 10 eq. NaOMe-sol. in MeOH at 23° C. for 1 h. Obtained as a yellow solid (594 mg).
Reaction SMILES: [CH2:1]([O:4][CH:5]([C:10]1[N:14]([CH3:15])[N:13]=[CH:12][C:11]=1[N+:16]([O-:18])=[O:17])[CH2:6][CH2:7][CH:8]=[CH2:9])C=C.CN1C(C2CCCC=C[O:26]2)=C([N+]([O-])=O)C=N1.C1C=C(Cl)C=C(C(OO)=O)C=1>C(Cl)Cl.Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1>[CH:8]12[O:26][CH:7]1[CH2:6][CH:5]([C:10]1[N:14]([CH3:15])[N:13]=[CH:12][C:11]=1[N+:16]([O-:18])=[O:17])[O:4][CH2:1][CH2:9]2
Reactant: C=CCCC(OCC=C)c1c([N+](=O)[O-])cnn1C
Reactant: Cn1ncc([N+](=O)[O-])c1C1CCCC=CO1
Agent: Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)(=Cc2ccccc2)[P](C2CCCCC2)(C2CCCCC2)C2CCCCC2)c(C)c1
Agent: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: Cn1ncc([N+](=O)[O-])c1C1CC2OC2CCO1
Temperature: 40 °C
Reaction time: 4 h

Procedure:
5-(1-Allyloxypent-4-enyl)-1-methyl-4-nitro-pyrazole (7.08 g, 28.2 mmol) was dissolved in DCM (910 mL) and the mixture degassed for 30 min before Grubbs 2nd generation catalyst (1.19 g, 1.41 mmol) was added. The reaction mixture was heated at 40° C. for 18 hr and concentrated under reduced pressure. Purification via silica gel column chromatography (0-10% EtOAc/isohexane) followed by reverse-phase preparative HPLC gave a mixture of isomers of 1-methyl-4-nitro-5-(tetrahydrooxepin-2-yl)pyrazole (66/34) as a clear oil (2.3 g). To a solution of this oil (2.3 g, 10.31 mmol) in DCM (50 mL) was added m-CPBA (70-75%, 3.56 g, 14.40 mmol) and the reaction mixture was stirred at room temperature for 4 hr. The reaction mixture was diluted with DCM (50 mL) and the organic layer was washed with saturated aqueous NaHCO3 (2×50 mL), water (50 mL) and brine (50 mL), dried over MgSO4, and concentrated under reduced pressure. Purification via silica gel column chromatography (0-30% EtOAc/isohexane) gave 5-(4,8-dioxabicyclo[5.1.0]octan-5-yl)-1-methyl-4-nitro-pyrazole as a colourless solid (1.0 g, 14% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 5.51-5.44 (m, 1H), 4.02 (s, 3H), 3.93 (dt, J=12.7, 3.4 Hz, 1H), 3.62-3.53 (m, 1H), 3.35-3.27 (m, 2H), 2.58-2.51 (m, 1H), 2.41-2.25 (m, 3H).
Reaction SMILES: [OH:1][CH:2]1[C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH:5]([NH:11][C:12]([NH2:14])=[O:13])[CH2:4][CH2:3]1.[C:15](Cl)(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O>N1C=CC=CC=1>[C:15]([O:1][CH:2]1[C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH:5]([NH:11][C:12]([NH2:14])=[O:13])[CH2:4][CH2:3]1)(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: NC(=O)NC1CCC(O)c2sccc21
Reactant: O=C(Cl)c1ccccc1
Solvent: c1ccncc1
Solvent: O
Product: NC(=O)NC1CCC(OC(=O)c2ccccc2)c2sccc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
In 5 ml of pyridine, 0.53 g of 4,5,6,7-tetrahydro-7-hydroxybenzo[b]thien-4-ylurea is stirred and 0.39 g of benzoyl chloride added under a nitrogen atmosphere. The mixture is stirred at room temperature and after 1 hr, an additional 0.2 g of benzoyl chloride is added. After another 0.75 hr, the mixture is poured into H2O and the white precipitate is collected. The solid is washed with H2O, dried, dissolved in acetone-hexane and filtered to remove an insoluble material. The filtrate is evaporated to dryness and the acetone-hexane treatments are repeated twice to remove additional side product. The solid from the filtrate is recrystallized from ethyl acetate to give a solid with m.p. 199° C-205° C.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[C:5]([O:12][C:13]2[N:18]=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([O:21][CH3:22])[N:14]=2)=[CH:4][CH:3]=1.Cl.[N:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30](Cl)=[O:31].C(=O)([O-])[O-].[K+].[K+].CCC(C)=O>O>[N:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]([NH:1][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[C:5]([O:12][C:13]2[N:18]=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([O:21][CH3:22])[N:14]=2)=[CH:4][CH:3]=1)=[O:31]
Reactant: O=C(Cl)c1ccccn1
Reactant: COC(=O)c1nc(N)ccc1Oc1nc(OC)cc(OC)n1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Solvent: O
Product: COC(=O)c1nc(NC(=O)c2ccccn2)ccc1Oc1nc(OC)cc(OC)n1
Yield: 40.7 %

Procedure:
2.0 g (6.5 mmol) of methyl 6-amino-3-[(4,6-dimethoxypyrimidin-2-yl)oxy]picolinate, 1.2 g (6.5 mmol) of picolinoyl chloride hydrochloride and 2.0 g (14.8 mmol) of potassium carbonate were added to 30 ml of MEK, and the mixture was refluxed for 6 hours under stirring. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with water and dried. The solvent was distilled off to obtain crude crystals. The crude crystals were washed with diisopropyl ether-ethyl acetate to obtain the desired product as colorless needle-like crystals.
Reaction SMILES: [CH3:1][N:2]1[C:6](B2OC(C)(C)C(C)(C)O2)=[CH:5][CH:4]=[N:3]1.Br[CH:17]=[CH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+].C(O)C>C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C)C=O>[CH3:1][N:2]1[C:6]([CH:17]=[CH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:5][CH:4]=[N:3]1
Reactant: Cn1nccc1B1OC(C)(C)C(C)(C)O1
Reactant: BrC=Cc1ccccc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cn1nccc1C=Cc1ccccc1
Temperature: 75 °C
Reaction time: 6 h
Yield: 74.5 %

Procedure:
Under a nitrogen atmosphere, a mixture of 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.50 g), β-bromostyrene (1.45 g), bis(triphenylphosphine)palladium(II) dichloride (506 mg), potassium carbonate (1.30 g), ethanol (3.8 mL) and dimethylformamide (7.5 mL) was stirred at 75° C. for 6 hours. Thereafter, 13-bromostyrene (1.45 g) was further added to the reaction solution, and the obtained solution was then stirred at 75° C. for 4 hours. Subsequently, the reaction solution was diluted with ethyl acetate, and was then washed with water. The organic layer was dried over anhydrous magnesium sulfate, and was then concentrated under a reduced pressure. The residue was purified by column chromatography (silica gel 60N, hexane:ethyl acetate=4:1 to 3:1), so as to obtain the title compound (990 mg) in the form of a light yellow solid.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][O:11][Si](C(C)(C)C)(C)C)[N:5]=1)(=[O:3])[CH3:2].[SiH3]O[SiH3].O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][OH:11])[N:5]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)c1cccc(CO[Si](C)(C)C(C)(C)C)n1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Agent: [SiH3]O[SiH3]
Solvent: C1CCOC1
Solvent: O
Product: CC(=O)c1cccc(CO)n1
Reaction time: 0.67 h
Yield: 99.2 %

Procedure:
To a THF (10 mL) solution of the silyl ether 2-Acetyl-6-(((tert-butyldimethylsilyl)oxy)methyl)pyridine (0.8 g, 3.0 mmol) was added tetrabutylammonium fluoride hydrate (870 mg, 3.3 mmol) at room temperature, and the mixture was stirred for 40 min. It was extracted with EtOAc (150 mL) and washed with water (6 mL×3) and brine (6 mL). The extract was dried over MgSO4 and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluted with hexane/EtOAc 4:1 to give the title compound (450 mg, 99%) as an oil. 1H NMR (CDCl3) δ 8.00 (d, 1H, J=7.2 Hz, H-3), 7.88 (m, 1H, H-4), 7.49 (d, 1H, J=7.7 Hz, H-5), 4.88 (d, 2H, J=5.0 Hz, CH2), 3.84 (d, 1H, J=3.2 Hz, OH), 2.78 (s, 3H, CH3); 13C NMR (CDCl3) δ 200.0 (CO), 159.1 (C-6), 152.7 (C-2), 138.0 (C-4), 124.4 (C-5), 120.8 (C-3), 64.3 (CH2), 26.3 (CH3).
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:19][CH2:20][CH2:21][CH2:22][C:23]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)OCCO1.CO.Cl.C([BH3-])#N.[Na+]>C(Cl)Cl.C(OCC)C>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:14])([F:15])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[N:19]1[CH2:20][CH2:21][CH2:22][CH:23]1[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1
Reactant: O=C(N1CCc2ccc(Cl)c(NCCCC3(c4ccccc4)OCCO3)c2CC1)C(F)(F)F
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CCOCC
Solvent: ClCCl
Product: O=C(N1CCc2ccc(Cl)c(N3CCCC3c3ccccc3)c2CC1)C(F)(F)F
Temperature: 25 °C
Reaction time: 16 h
Yield: 70.6 %

Procedure:
Dissolve 7-chloro-3-(2,2,2-trifluoroacetyl)-6-[3-(2-phenyl-[1,3]dioxolan-2-yl)-propylamino]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (2.78 g, 5.76 mmol) in DCM (25 mL) and add methanol (1 mL) and 2 N HCl in diethyl ether (25 mL) and stir at RT for 16 h. Concentrate and dissolve the residue in acetic acid (30 mL) and add sodium cyanoborohydride (1.81 g, 28.78 mmol). Stir the reaction at RT for 1 h then concentrate. Dissolve the residue in EtOAc (500 mL) and extract with saturated sodium bicarbonate solution (500 mL). Extract the aqueous layer with EtOAc (100 mL) and combine the organic fractions, dry (sodium sulfate), concentrate and purify (silica gel chromatography, eluting with 10:90 EtOAc:hexanes) to give the title compound as a foam (1.72 g, 71%).
Reaction SMILES: [O-][N+:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=2)[CH:3]=1.C(OC(=O)C)(=[O:20])C>>[O:20]=[C:3]1[C:4]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=2)=[CH:5][CH:6]=[CH:7][NH:2]1
Reactant: COC(=O)c1ccc(-c2ccc[n+]([O-])c2)cc1
Reactant: CC(=O)OC(C)=O
Product: COC(=O)c1ccc(-c2ccc[nH]c2=O)cc1
Temperature: 130 °C
Reaction time: 24 h

Procedure:
Acetic anhydride (20 mL) was added to methyl 4-(1-oxidopyridin-3-yl)benzoate (704 mg), followed by stirring at 130° C. for 24 hours. The reaction mixture was concentrated under reduced pressure, followed by two times azeotropy with toluene. The resulting residue was purified by NH-silica gel column chromatography (methanol/chloroform=0% to 10%) to obtain methyl 4-(2-oxo-1,2-dihydropyridin-3-yl)benzoate (651 mg) as a pale brown solid.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[CH:3]1.[Li]CCCC.CCCCCC.Cl[Si](CC)(CC)CC.CON(C)[C:29](=[O:36])[C:30]1[CH:35]=[CH:34][CH:33]=[N:32][CH:31]=1>C1COCC1>[CH3:1][N:2]1[C:6]([C:29]([C:30]2[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=2)=[O:36])=[CH:5][N:4]=[CH:3]1
Reactant: CON(C)C(=O)c1cccnc1
Reactant: Cn1ccnc1
Agent: CC[Si](Cl)(CC)CC
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: Cn1cncc1C(=O)c1cccnc1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
To a heat-gun dried flask containing 1-methyl-1H-imidazole (1.55 mL, 19.5 mmol) and THF (20 mL) at −78° C. was added 1.6 M n-BuLi in hexane (12.8 mL, 20.5 mmol). After stirring at −78° C. for 30 min, chlorotriethylsilane (3.3 mL, 19.7 mmol) in neat was introduced slowly. The mixture was stirred at −78° C. for 30 min. 1.6 M n-BuLi in hexane (12.8 mL, 20.5 mmol) was added, and the mixture was stirred for 45 min. A solution of N-methoxy-N-methylnicotinamide (2.70 g, 16.2 mmol, Intermediate 10, step a) in THF (20 mL) was added via cannula, and the mixture was stirred at −78° C. to room temperature for 2 hours. The reaction was quenched with NH4Cl (aqueous), the organic layer was separated, and the aqueous layer was extracted with CH2Cl2. The combined organic phases were dried (Na2SO4), filtered, concentrated, and purified by flash column chromatography (40 g silica gel column, 50-100% EtOAc in heptane, then 5-10% MeOH in CH2Cl2) to obtain the title compound as an off-white solid.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[O:22][C@H:21]([CH2:23][O:24][C:25](=[O:27])[CH3:26])[C@@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:6]1[O:7][C:8](=[O:10])[CH3:9])(=O)[CH3:2].C([Br:31])CO.C(OCC)(=O)C>ClCCl>[C:8]([O:7][C@@H:6]1[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@@H:21]([CH2:23][O:24][C:25](=[O:27])[CH3:26])[O:22][C@H:5]1[O:4][CH2:1][CH2:2][Br:31])(=[O:10])[CH3:9]
Reactant: CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: OCCBr
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(=O)OC[C@H]1O[C@@H](OCCBr)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O

Procedure:
A solution of 9.46 g (24.3 mmol) of penta-O-acetyl-β-D-glucopyranose and 3.04 g (24.3 mmol) of ethylene bromohydrin in 100 mL of dichloromethane was put in a 200 mL round bottom flask in an argon atmosphere. Subsequently, 10 mL of boron trifluoride diethyl ether complex was slowly added dropwise to this solution with stirring. The resulting mixture was continuously stirred with ice cooling for another one hour and then stirred at room temperature overnight while protecting it from light. After the stirring, the color of the reaction solution turned orange. An adequate amount of ethyl acetate was added to the reaction solution, and the organic phase was washed with water, a saturated aqueous sodium hydrogen carbonate and a saturated saline successively. After the organic solution was dried over anhydrous sodium sulfate, the organic phase was filtered, and the solvent was evaporated under reduced pressure to give 2-bromoethyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside in the form of an oil (yield 11.0 g; 100%)