Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [BH4-].[Na+].[F:3][C:4]1[CH:5]=[N:6][CH:7]=[C:8]([C:12]2[CH:13]=[CH:14][C:15]3[O:19][C:18](=[O:20])[N:17]([CH3:21])[C:16]=3[CH:22]=2)[C:9]=1[CH:10]=[O:11]>C1COCC1.O.[Cl-].[Na+].O.C(Cl)Cl>[F:3][C:4]1[C:9]([CH2:10][OH:11])=[C:8]([C:12]2[CH:13]=[CH:14][C:15]3[O:19][C:18](=[O:20])[N:17]([CH3:21])[C:16]=3[CH:22]=2)[CH:7]=[N:6][CH:5]=1
Reactant: Cn1c(=O)oc2ccc(-c3cncc(F)c3C=O)cc21
Agent: [BH4-]
Agent: [Cl-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Solvent: C1CCOC1
Product: Cn1c(=O)oc2ccc(-c3cncc(F)c3CO)cc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 15 %

Procedure:
Sodium borohydride (6.3 mg, 0.17 mmol) was added to a solution of 3-Fluoro-5-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-pyridine-4-carbaldehyde (47 mg, 0.17 mmol) in THF (0.5 mL) and water (0.1 mL) at 0° C. The resulting mixture was stirred at room temperature for 2 h. Brine was added to the reaction mixture. The resulting mixture was diluted with DCM and water. The organic layer was separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by flash column (MeOH—CH2Cl2, v/v, 0-3%) and afforded the title compound (7 mg, 16%); ESI-MS m/z: 275 [M+1]+, Retention time 0.92 min; 1HNMR (MeOD, 400.3 MHz) δ 3.44 (s, 3H), 4.59 (s, 2H), 7.32 (dd, J=8.0, 1.2 Hz, 1H), 7.35 (d, J=1.2 Hz, 1H), 7.38 (d, J=80 Hz, 1H), 8.39 (s, 1H), 8.48 (d, J=1.2 Hz, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[CH3:13])[NH:9][CH:8]=[C:7](C(O)=O)[C:6]2=[O:17].CCCCCC>C1(OC2C=CC=CC=2)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[CH3:13])[NH:9][CH:8]=[CH:7][C:6]2=[O:17]
Reactant: COc1cc2c(=O)c(C(=O)O)c[nH]c2cc1C
Solvent: CCCCCC
Solvent: c1ccc(Oc2ccccc2)cc1
Product: COc1cc2c(=O)cc[nH]c2cc1C
Temperature: 25 °C
Yield: 93 %

Procedure:
6-Methoxy-7-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (22 g) was suspended in diphenyl ether (200 ml), and the suspension was heated under reflux overnight. The reaction solution was cooled to room temperature, hexane was then added to the reaction solution, and the precipitated crystal was collected by filtration to give 6-methoxy-7-methyl-1H-quinolin-4-one (16.6 g, yield 93%).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[S:18][C:17]([C:19]3[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=3)=[N:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[F:29][C:30]([F:35])([F:34])[C:31]([OH:33])=[O:32]>ClCCl>[F:29][C:30]([F:35])([F:34])[C:31]([O-:33])=[O:32].[CH3:26][O:25][C:23]([C:22]1[CH:27]=[CH:28][C:19]([C:17]2[S:18][C:14]([CH:11]3[CH2:12][CH2:13][NH2+:8][CH2:9][CH2:10]3)=[N:15][N:16]=2)=[CH:20][CH:21]=1)=[O:24]
Reactant: COC(=O)c1ccc(-c2nnc(C3CCN(C(=O)OC(C)(C)C)CC3)s2)cc1
Reactant: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC(=O)c1ccc(-c2nnc(C3CC[NH2+]CC3)s2)cc1
Product: O=C([O-])C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of methyl 4-[5-[N-(tert-butoxycarbonyl)-piperidin-4-yl]-1,3,4-thiadiazol-2-yl]benzoate (1.28 g) in dichloromethane (12 ml) was added trifluoroacetic acid (25 ml) at 0° C. and the reaction mixture was stirred for 1 hour at room temperature. The solvents were removed under reduced pressure. The precipitate was triturated with diisopropyl ether, collected by filtration, washed with diisopropyl ether and dried under reduced pressure to give 4-[5-(4-methoxycarbonylphenyl)-1,3,4-thiadiazol-2-yl]piperidinium trifluoroacetate (1.31 g).
Reaction SMILES: [CH2:1]1[CH2:5][C:4]2([CH:10]3[CH2:11][N:12]([CH2:14][CH:15]4[CH2:17][CH2:16]4)[CH2:13][CH:6]2[CH2:7][N:8]([CH2:18][CH:19]2[CH2:21][CH2:20]2)[CH2:9]3)[CH2:3][CH2:2]1.[C:22]([OH:31])(=[O:30])[C:23]1[C:24](=[CH:26][CH:27]=[CH:28][CH:29]=1)[OH:25]>C(OCC)C>[CH2:1]1[CH2:5][C:4]2([CH:10]3[CH2:11][N:12]([CH2:14][CH:15]4[CH2:17][CH2:16]4)[CH2:13][CH:6]2[CH2:7][N:8]([CH2:18][CH:19]2[CH2:21][CH2:20]2)[CH2:9]3)[CH2:3][CH2:2]1.[C:22]([O-:31])(=[O:30])[C:23]1[C:24](=[CH:26][CH:27]=[CH:28][CH:29]=1)[OH:25]
Reactant: O=C(O)c1ccccc1O
Agent: C1CCC2(C1)C1CN(CC3CC3)CC2CN(CC2CC2)C1
Solvent: CCOCC
Product: O=C([O-])c1ccccc1O
Reaction time: 0.5 h

Procedure:
10.7 g (=0.037 mole) of tedisamil were dissolved in 50 ml of diethyl ether. A solution of 5.12 g (=0.037 mole) of salicylic acid in 50 ml of diethyl ether was added to the solution. The reaction mixture was stirred for 30 minutes. The resulting precipitate was separated from the mother liquor by suction filtration, and dried in a vacuum drying oven at 60° C. 14.5 g of tedisamil salicylate were obtained. DSC gave a melting range of 140.9 to 142.2° C. The base:acid ratio determined by titration was 1:1.0. Thermogravimetric analysis showed a 0.1% weight loss on drying.
Reaction SMILES: F[C:2](F)(F)[C:3]1[C:4](=[O:10])NC(=O)N[CH:8]=1.N1[CH:18]=[CH:17][C:16](=O)NC1=O.C[Si](C)(C)CCO[CH2:26][Cl:27]>>[CH2:4]([O:10][CH2:26][Cl:27])[C:3]1[CH:2]=[CH:18][CH:17]=[CH:16][CH:8]=1
Reactant: C[Si](C)(C)CCOCCl
Reactant: O=c1[nH]cc(C(F)(F)F)c(=O)[nH]1
Reactant: O=c1cc[nH]c(=O)[nH]1
Product: ClCOCc1ccccc1

Procedure:
In a similar manner to the procedures described in Reference Example 3, reactions were carried out using 5-trifluoromethylpyrimidine-2,4-dione, instead of pyrimidine-2,4-dione, and using 2-(trimethylsilyl)ethoxymethyl chloride, instead of benzyloxymethyl chloride, to give the title compound (yield 76%) as a white powder.
Reaction SMILES: [F:1][C:2]([F:16])([F:15])[C:3]1[N:7]2[CH2:8][CH2:9][CH:10]([C:12](O)=[O:13])[CH2:11][C:6]2=[N:5][N:4]=1.C(Cl)(C(Cl)=O)=O.Cl.ClC1C(CN)=[N:27]C=CN=1.CCN(C(C)C)C(C)C>C1COCC1.CN(C=O)C>[F:1][C:2]([F:16])([F:15])[C:3]1[N:7]2[CH2:8][CH2:9][CH:10]([C:12]([NH2:27])=[O:13])[CH2:11][C:6]2=[N:5][N:4]=1
Reactant: NCc1nccnc1Cl
Reactant: O=C(O)C1CCn2c(nnc2C(F)(F)F)C1
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: NC(=O)C1CCn2c(nnc2C(F)(F)F)C1
Reaction time: 1 h
Yield: 49.3 %

Procedure:
To a solution of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid (1.63 g, 6.93 mmol) in THF (35 mL) was added dropwise (COCl)2 (4.4 g, 34.66 mmol) and 0.1 mL of DMF at 0° C., the mixture was stirred at this temperature for 1 hours and then the solvent was removed. The resulting residue was dissolved in THF (35 mL), (3-chloropyrazin-2-yl)methanamine hydrochloride (1.37 g, 7.63 mmol) and DIEA (2.68 g, 20.79 mmol) was added, the mixture was stirred at 60° C. for 1 h. Remove the solvent in vacuo and the residue was extracted with DCM and the combined organic layer was washed with water, brine and dried over anhydrous Na2SO4. The organic layer was concentrated in vacuo and the residue was purified by silica gel column chromatography (DCM/THF=100/20) to afford N4(3-chloropyrazin-2-yl)methyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxamide (0.8 g, yield 32%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[F:10])[CH:5]=[O:6].C([Sn]([C:24]1[O:25][CH:26]=[CH:27][CH:28]=1)(CCCC)CCCC)CCC.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>CN(C=O)C.C(OCC)(=O)C.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>[F:10][C:9]1[CH:8]=[CH:7][C:4]([CH:5]=[O:6])=[CH:3][C:2]=1[C:24]1[O:25][CH:26]=[CH:27][CH:28]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccco1
Reactant: O=Cc1ccc(F)c(Br)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=Cc1ccc(F)c(-c2ccco2)c1
Temperature: 110 °C
Yield: 480.8 %

Procedure:
3-Bromo-4fluorobenzaldehyde (1 g, 4.93 mmol) in DMF (25 ml) was treated with 2 (tributylstannyl)furan (2.4 ml, 1.05 mmol), di-tert-butyl dicarbonate (1.75 g, 4.94 mmol), and tetrakis(triphenylphosphine)palladium (0) (570 mg, 0.4 mmol). The mixture was heated at 110° C. in a sealed high pressure tube over night, allowed to cool to ambient temperature, diluted with ethyl acetate, and washed with brine. The organic layer was further washed with 1N HCl, saturated NaHCO3, brine, dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by flash chromatography using hexanes:diethyl ether (20:1) as eluent to provide the title compound as a pale yellow oil (0.96 g, 98%).
Reaction SMILES: CO[CH:3](OC)[CH2:4][CH:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=O.[C:17]([NH:20][CH2:21][CH2:22][NH2:23])(=[O:19])[CH3:18].FC(F)(F)C(O)=O.[OH-].[Na+]>C(O)C.O>[N:23]1([CH2:22][CH2:21][NH:20][C:17](=[O:19])[CH3:18])[CH:3]=[CH:4][C:5]2[CH2:13][C:12]3[C:7]([C:6]1=2)=[CH:8][CH:9]=[CH:10][CH:11]=3
Reactant: CC(=O)NCCN
Reactant: COC(CC1Cc2ccccc2C1=O)OC
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: CC(=O)NCCn1ccc2c1-c1ccccc1C2
Yield: 21.6 %

Procedure:
A solution of 1.7 g of (RS)-2-(2,2-dimethoxyethyl)-1-indanone, 25 g of N-acetylethylenediamine and 30 ml of trifluoroacetic acid in 500 ml of ethanol was boiled under reflux for 96 hours. After cooling and adding 21.5 g of sodium hydroxide in 100 ml of water, the mixture was evaporated to about 100 ml. The mixture was treated with 200 ml of ethyl acetate and washed in succession with 100 ml of saturated sodium chloride solution, 1N hydrochloric acid (4×100 ml), 2N sodium hydroxide solution (4×100 ml) and 100 ml of water. The aqueous washings were extracted with 100 ml of ethyl acetate and the organic phases were combined, dried with magnesium sulfate and evaporated in a vacuum. The residue was purified on basic aluminum oxide (III, dichloromethane) and then on silica gel (ethyl acetate). 0.4 g (22%) of N-[2-(1,4-dihydro-indeno[1,2-b]pyrrol-1-yl)-ethyl]-acetamide was obtained as a colorless solid.
Reaction SMILES: [CH:1]1([C:4]2[C:9]([CH2:10][C:11]([OH:13])=[O:12])=[CH:8][N:7]=[C:6]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[N:5]=2)[CH2:3][CH2:2]1.[CH3:24]O>>[CH3:24][O:12][C:11](=[O:13])[CH2:10][C:9]1[C:4]([CH:1]2[CH2:3][CH2:2]2)=[N:5][C:6]([C:14]2[CH:15]=[CH:16][C:17]([C:20]([F:22])([F:23])[F:21])=[CH:18][CH:19]=2)=[N:7][CH:8]=1
Reactant: O=C(O)Cc1cnc(-c2ccc(C(F)(F)F)cc2)nc1C1CC1
Reactant: CO
Product: COC(=O)Cc1cnc(-c2ccc(C(F)(F)F)cc2)nc1C1CC1

Procedure:
In analogy to the procedure described in example 8 d], [4-cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-acetic acid was esterified with methanol to give the title compound as yellow solid.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:18](=[O:19])[C:17]3[C:16]4[N:15]=[CH:14][CH:13]=[CH:12][C:11]=4[O:10][C:9]=3[C:8]([CH3:21])([CH3:20])[C:7]=2[CH:22]=1.Cl.N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>O>[OH:2][C:3]1[CH:4]=[CH:5][C:6]2[C:18](=[O:19])[C:17]3[C:16]4[N:15]=[CH:14][CH:13]=[CH:12][C:11]=4[O:10][C:9]=3[C:8]([CH3:20])([CH3:21])[C:7]=2[CH:22]=1
Reactant: COc1ccc2c(c1)C(C)(C)c1oc3cccnc3c1C2=O
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: O
Product: CC1(C)c2cc(O)ccc2C(=O)c2c1oc1cccnc21
Temperature: 178 °C
Yield: 54.6 %

Procedure:
Mixture of 8-methoxy-10,10-dimethyl-10H-11-oxa-4-aza-benzo[b]fluoren-5-one (Compound GT15-4, 25 mg) and pyridine hydrochloric acid salt (492 mg) was stirred and heated at 178° C. overnight. The reaction mixture was cooled, and added with water. The mixture was neutralized with saturated aqueous solution of sodium bicarbonate and extracted with DCM. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (DCM/MeOH) to obtain the title compound (13 mg, 54%).
Reaction SMILES: [CH3:1][N:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([C:11]([OH:13])=O)[C:5]=2[C:4]2([C:25]3[C:16](=[CH:17][C:18]4[O:23][CH2:22][CH2:21][O:20][C:19]=4[CH:24]=3)[O:15][CH2:14]2)[C:3]1=[O:26].C(N=C=NCCCN(C)C)C.C(N(CC)C(C)C)(C)C.O[C:48]1[C:56]2N=N[NH:53][C:52]=2[CH:51]=[CH:50][CH:49]=1.C1(N)CCCCC1>CN(C)C=O>[CH:52]1([NH:53][C:11]([C:6]2[C:5]3[C:4]4([C:25]5[C:16](=[CH:17][C:18]6[O:23][CH2:22][CH2:21][O:20][C:19]=6[CH:24]=5)[O:15][CH2:14]4)[C:3](=[O:26])[N:2]([CH3:1])[C:10]=3[CH:9]=[CH:8][CH:7]=2)=[O:13])[CH2:56][CH2:48][CH2:49][CH2:50][CH2:51]1
Reactant: Oc1cccc2[nH]nnc12
Reactant: CN1C(=O)C2(COc3cc4c(cc32)OCCO4)c2c(C(=O)O)cccc21
Agent: CCN=C=NCCCN(C)C
Solvent: CN(C)C=O
Solvent: NC1CCCCC1
Solvent: CCN(C(C)C)C(C)C
Product: CN1C(=O)C2(COc3cc4c(cc32)OCCO4)c2c(C(=O)NC3CCCCC3)cccc21
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 51.6 %

Procedure:
To a stirred solution of 1′-methyl-2′-oxo-1,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indole]-4′-carboxylic acid (0.200 g, 0.566 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (0.114 g, 0.736 mmol) in N,N-dimethylformamide (20 mL) was added N,N-diisoproylethylamine (0.30 mL, 1.72 mmol) and hydroxybenzotriazole (0.092 g, 0.68 mmol). The reaction mixture was stirred at ambient temperature for 10 min and cyclohexylamine (0.10 mL, 0.87 mmol) was added. The reaction mixture was stirred at ambient temperature for 40 h and concentrated in vacuo to remove most of the N,N-dimethylformamide. The mixture was diluted with ethyl acetate (150 mL), washed with water (3×150 mL) and brine (3×100 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate/hexanes (1/1) to afford N-cyclohexyl-1′-methyl-2′-oxo-1′,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indole]-4′-carboxamide (0.127 g, 51%) as a colorless solid: mp 139-140° C.; 1H NMR (300 MHz, CDCl3) δ7.42-7.36 (m, 1H), 7.24-7.20 (m, 1H), 6.98-6.94 (m, 1H), 6.51 (s, 1H), 6.17 (s, 1H), 5.30-5.27 (m, 1H), 4.95 (ABq, 2H), 4.24-4.04 (m, 4H), 3.71-3.61 (m, 1H), 3.26 (s, 3H), 1.78-1.57 (m, 5H), 1.36-1.22 (m, 2H), 1.12-0.99 (m, 1H), 0.89-0.82 (m, 2H); 13C NMR (75 MHz, CDCl3) δ177.6, 166.3, 155.9, 145.0, 144.3, 137.9. 134.7, 129.5, 127.4, 122.8, 120.4, 110.7, 109.9, 100.1. 78.0, 64.5, 64.0, 58.2, 48.7, 32.4, 32.1, 26.7, 25.5, 24.9, 24.7; MS (ES+) m/z 435.0 (M+1).
Reaction SMILES: [CH2:1]([C:5]1[N:6]([CH2:23][CH2:24][CH2:25][CH2:26][NH2:27])[C:7]2[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]=[C:9]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:8]=2[N:22]=1)[CH2:2][CH2:3][CH3:4].C(N(CC)CC)C.[CH3:35][N:36]([CH3:56])[CH2:37][CH2:38][O:39][CH:40]([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C:41]1[CH:49]=[CH:48][C:44]([C:45](Cl)=[O:46])=[CH:43][CH:42]=1>ClCCl>[CH2:1]([C:5]1[N:6]([CH2:23][CH2:24][CH2:25][CH2:26][NH:27][C:45](=[O:46])[C:44]2[CH:43]=[CH:42][C:41]([CH:40]([O:39][CH2:38][CH2:37][N:36]([CH3:35])[CH3:56])[C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)=[CH:49][CH:48]=2)[C:7]2[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]=[C:9]([O:15][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:8]=2[N:22]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc2c(Oc3ccccc3)nc(C)c(C)c2n1CCCCN
Reactant: CN(C)CCOC(c1ccccc1)c1ccc(C(=O)Cl)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCc1nc2c(Oc3ccccc3)nc(C)c(C)c2n1CCCCNC(=O)c1ccc(C(OCCN(C)C)c2ccccc2)cc1
Reaction time: 16 h
Yield: 47.2 %

Procedure:
Under a nitrogen atmosphere, 4-(2-butyl-6,7-dimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl)butan-1-amine (122 mg, 0.33 mmol) was dissolved in dichloromethane and triethylamine (0.093 mL, 0.67 mmol). The solution was cooled in an ice-water bath and 4-[[2-(dimethylamino)ethoxy](phenyl)methyl]benzoyl chloride (106 mg, 0.33 mmol) was dissolved/slurried in dichloromethane and added dropwise. The ice bath was removed and the reaction was stirred for an additional 16 hours. The reaction was quenched with 10% aqueous sodium carbonate. The phases were separated and the aqueous fraction was extracted with dichloromethane. The organic fractions were combined, washed with water followed by brine, dried (Na2SO4), decanted and evaporated to yield a yellow oil. Purification by flash column chromatography (silica gel, 92:8 dichloromethane/methanol gradient to 95:5 dichloromethane/methanol) provided 101 mg of N-[4-(2-butyl-6,7-dimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl)butyl]-4-[[2-(dimethylamino)ethoxy](phenyl)methyl]benzamide as a pale yellow solid. The product was determined to be 97+% pure by HPLC. MS(CI): 648 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2(O)[CH2:11][CH:10]([C:12]([OH:14])=[O:13])[CH2:9]2)=[CH:4][CH:3]=1.[C:16](#[N:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.O.[O-:25]S(C(F)(F)F)(=O)=O.[Bi+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O>C(OCC)C.CCCCCCC>[C:16]([NH:23][C:8]1([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH2:11][CH:10]([C:12]([OH:14])=[O:13])[CH2:9]1)(=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: N#Cc1ccccc1
Reactant: O=C(O)C1CC(O)(c2ccc(Cl)cc2)C1
Reactant: O=S(=O)([O-])C(F)(F)F
Agent: [Bi+3]
Solvent: CCCCCCC
Solvent: O
Solvent: CCOCC
Product: O=C(NC1(c2ccc(Cl)cc2)CC(C(=O)O)C1)c1ccccc1
Temperature: 100 °C
Yield: 143 %

Procedure:
A solution of 3-(4-chlorophenyl)-3-hydroxycyclobutanecarboxylic acid (4 g, 0.0176 mol) and benzonitrile (8.66 mL, 0.0847 mol) in water (4.4 mL, 0.245 mol) was treated with bismuth triflate (2.32 g, 0.0035 mol) and heated to 100° C. for 16 h. After cooling to 0° C., the reaction was quenched with 1 M HCl to pH˜, dichloromethane was added, the solution was stirred vigorously and the phases were separated. The product was leached from organic layer with 1 M NaOH. This aqueous solution was acidified with to pH-3 with 6 M HCl and extracted two times with diethyl ether. The combined organic layers were dried over MgSO4, filtered and concentrated to give a light brown residue. This crude product was dissolved in diethyl ether, and diluted with n-heptane to precipitate the product. It was filtrated, washed with n-heptane and dried at 45° C. to give the product as a white crystalline solid (1.65 g, 29%). 1H NMR (DMSO-d6, 600 MHz) δ 12.25 (bs, 1H), 9.16 (s, 1H), 7.82 (d, J=7.2 Hz, 2H), 7.50-7.53 (m, 3H), 7.43-7.45 (m, 2H), 7.38 (d, J=8.7 Hz, 2H), 2.94-3.00 (m, 1H), 2.72-2.78 (m, 4H). ESI MS found for C18H16ClNO3 m/z [352.3/354, 3 (M+Na+), 330.4/332.4 (M+1), 328.2/330.2 (M−1)].
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]1[C:8](=[O:9])/[C:7](=[CH:10]/[C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH3:19])=[CH:13][CH:12]=2)/[S:6][C:5]1=[O:20].[CH:21](=O)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O[C:46]1[CH:63]=[CH:62][C:49](/[CH:50]=C2/C(=O)N(CCNC)C(=O)S/2)=[CH:48][CH:47]=1)C>>[CH2:21]([N:1]([CH2:50][C:49]1[CH:62]=[CH:63][CH:46]=[CH:47][CH:48]=1)[CH2:2][CH2:3][N:4]1[C:8](=[O:9])/[C:7](=[CH:10]/[C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH3:19])=[CH:13][CH:12]=2)/[S:6][C:5]1=[O:20])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: O=Cc1ccccc1
Reactant: CCOc1ccc(/C=C2\SC(=O)N(CCNC)C2=O)cc1
Reactant: CCOc1ccc(/C=C2\SC(=O)N(CCN)C2=O)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: CCOc1ccc(/C=C2\SC(=O)N(CCN(Cc3ccccc3)Cc3ccccc3)C2=O)cc1

Procedure:
The title compound 24b was prepared from compound 76 (117 mg, 0.40 mmol), benzaldehyde (82 μL, 0.80 mmol) and sodium triacetoxyborohydride (254 mg, 1.20 mmol) in a manner similar to that described for 23a in 93.1% (176 mg) yield as a light-yellow solid.
Reaction SMILES: C1C=C2C=CC(O)=C(C3C4C(=CC=CC=4)C=CC=3O)C2=CC=1.[C:23]([S:27]/[C:28](/[O:31][Si](C)(C)C)=[CH:29]/[CH3:30])([CH3:26])([CH3:25])[CH3:24].[C:36]([O:40][CH3:41])(=[O:39])[CH:37]=[O:38].Cl.CO>C1(C)C=CC=CC=1>[C:23]([S:27][C:28](=[O:31])[CH:29]([CH3:30])[CH:37]([OH:38])[C:36]([O:40][CH3:41])=[O:39])([CH3:26])([CH3:25])[CH3:24]
Reactant: C/C=C(\O[Si](C)(C)C)SC(C)(C)C
Reactant: COC(=O)C=O
Agent: Cl
Agent: Oc1ccc2ccccc2c1-c1c(O)ccc2ccccc12
Solvent: Cc1ccccc1
Solvent: CO
Product: COC(=O)C(O)C(C)C(=O)SC(C)(C)C
Temperature: 0 °C
Yield: 80 %

Procedure:
An (S)-binaphthol-dichlorotitanium complex solution was prepared in the same manner as the preparation of the (R)-binaphthol-dichlorotitanium complex solution in Example 1 except that (S)-binaphthol was used in place of (R)-binaphthol. 0.5 ml (0.1 mmol) of the (S)-binaphtholdichlorotitanium complex solution were cooled to 0° C., and 218 mg (1 mmol) of (E)-1-t-butylthio-1-trimethylsilyloxy-1-propene (93% E) and subsequently 88 mg (1 mmol) of freshly distilled methyl glyoxylate and 0.5 ml of toluene were added thereto, followed by allowing the mixture to react at 0° C. for 2 hours. The resulting mixture was poured into 10% hydrochloric acid-methanol cooled at 0° C. The solution was filtered through a pad of Celite, and the filtrate was extracted three times with a 5 ml portion of diethyl ether. The combined organic layer was washed with a saturated sodium chloride aqueous solution, dried over magnesium sulfate, and evaporated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=15/1 by volume) to obtain mg of methyl 4-t-butylthio-2-hydroxy-3-methyl-4-oxobutyrate in a yield of 80% (16% syn, 84% ee; 84% anti, 93% ee).
Reaction SMILES: [C:1](O)(=O)[C:2]([OH:4])=[O:3].[Zn:7]>>[C:2]([O-:4])(=[O:3])[CH3:1].[Zn+2:7].[C:2]([O-:4])(=[O:3])[CH3:1]
Reactant: O=C(O)C(=O)O
Reactant: [Zn]
Product: CC(=O)[O-]
Product: [Zn+2]

Procedure:
Similarly, U.S. Pat. No. 2,839,390 addresses the removal of lead and zinc from their ores by chemical dissolution. Here, lead and zinc, if not already in the form of their sulfides, e.g., in galena and sphalerite, are converted to their sulfides. The sulfides are then reacted with oxalic acid converting the lead and zinc to their respective oxalates and evolving H2S gas. The product is filtered and the filter cake containing the oxalates is treated with an aqueous calcium acetate solution resulting in the formation of soluble lead and zinc acetates and insoluble calcium oxalate. The calcium oxalate precipitate is collected and reacted with sulfuric acid to regenerate oxalic acid while the solution is reacted with zinc so as to precipitate lead from the solution while forming more zinc acetate. The zinc may then be recovered by adding calcium hydroxide to the solution.
Reaction SMILES: C(OC([N:8]1[CH:16]2[CH:11]([CH2:12][N:13]([CH2:17][C:18]3[S:26][C:25]4[C:24]([N:27]5[CH2:32][CH2:31][O:30][CH2:29][CH2:28]5)=[N:23][C:22]([C:33]5[CH:41]=[C:40]([F:42])[CH:39]=[C:38]6[C:34]=5[CH:35]=[CH:36][NH:37]6)=[N:21][C:20]=4[CH:19]=3)[CH2:14][CH2:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl>>[F:42][C:40]1[CH:39]=[C:38]2[C:34]([CH:35]=[CH:36][NH:37]2)=[C:33]([C:22]2[N:23]=[C:24]([N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[C:25]3[S:26][C:18]([CH2:17][N:13]4[CH2:14][CH2:15][CH:16]5[NH:8][CH2:9][CH2:10][CH:11]5[CH2:12]4)=[CH:19][C:20]=3[N:21]=2)[CH:41]=1
Reactant: CC(C)(C)OC(=O)N1CCC2CN(Cc3cc4nc(-c5cc(F)cc6[nH]ccc56)nc(N5CCOCC5)c4s3)CCC21
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Fc1cc(-c2nc(N3CCOCC3)c3sc(CN4CCC5NCCC5C4)cc3n2)c2cc[nH]c2c1

Procedure:
Prepared by BOC-deprotection of 5-[2-(6-fluoro-1H-indol-4-yl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl]-octahydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester using TFA:DCM (1:6). The title compound was obtained as a white solid (8.3 mg, 7%).
Reaction SMILES: [C@H:1]12[CH2:8][O:7][C:6](=[O:9])[C@H:5]1[CH2:4][CH2:3][CH2:2]2.[NH3:10].ClCCl.CO>C(O)C>[OH:7][CH2:8][C@@H:1]1[CH2:2][CH2:3][CH2:4][C@@H:5]1[C:6]([NH2:10])=[O:9]
Reactant: N
Reactant: O=C1OC[C@@H]2CCC[C@H]12
Solvent: ClCCl
Solvent: CO
Solvent: CCO
Product: NC(=O)[C@H]1CCC[C@H]1CO
Yield: 61.7 %

Procedure:
(1R,5S)-(+)-7-oxabicyclo[3.3.0]octan-6-one (1 gram) was dissolved in 5 ml of absolute ethanol, followed by the addition of 0.5 gram of gaseous ammonia. The solution was kept in a stoppered flask, and the progress of the reaction was followed by thin layer chromatography (eluent dichloromethane/methanol 20:1). After the reaction was judged complete, the ethanol was evaporated and the resulting residue redissolved in ethyl acetate. Ammonia was removed by extraction with 1% HCl, and the ethyl acetate solution was dried over MgSO4, filtered, and rotary evaporated to leave 0.7 grams of (1S,2R)-2-hydroxymethyl-1-cydopentanecarboxamide.