Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:12]2([C:35]([F:38])([F:37])[F:36])[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([N:25]4[CH2:29][C:28](=[O:30])[NH:27][CH2:26]4)=[O:24])=[C:19]([C:31]([F:34])([F:33])[F:32])[CH:18]=3)[CH2:13]2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.CN(C)C=O.[H-].[Na+].FC(F)(F)S(O[CH2:52][C:53]([F:56])([F:55])[F:54])(=O)=O>CC#N>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2([C:35]([F:36])([F:37])[F:38])[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([N:25]4[CH2:29][C:28](=[O:30])[N:27]([CH2:52][C:53]([F:56])([F:55])[F:54])[CH2:26]4)=[O:24])=[C:19]([C:31]([F:33])([F:34])[F:32])[CH:18]=3)[CH2:13]2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1
Reactant: O=C1CN(C(=O)c2ccc(C3=NOC(c4cc(Cl)cc(C(F)(F)F)c4)(C(F)(F)F)C3)cc2C(F)(F)F)CN1
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CC#N
Product: O=C1CN(C(=O)c2ccc(C3=NOC(c4cc(Cl)cc(C(F)(F)F)c4)(C(F)(F)F)C3)cc2C(F)(F)F)CN1CC(F)(F)F
Reaction time: 1 h

Procedure:
Into a 50-mL round bottom flask, was placed 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl)carbonyl]imidazolidin-4-one (50 mg, 0.09 mmol, 1.00 equiv), N,N-dimethylformamide (1 mL), sodium hydride (7 mg, 0.17 mmol, 2.00 equiv, 60%), The resulting solution was stirred for 20 min at 25° C. Added 2,2,2-trifluoroethyl trifluoromethanesulfonate (40 mg, 0.17 mmol, 1.98 equiv). The resulting solution was allowed to react, with stirring, for an additional 1 h at r t. The reaction was then quenched by the addition of 10 ml of water. The resulting solution was extracted with 2×10 ml of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×10 mL of brine. The resulting mixture was concentrated under vacuum. The residue was applied onto a TLC plate with PE/EA (2/1). This resulted in 23.7 mg (37%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl)carbonyl]-3-(2,2,2-trifluoroethyl)imidazolidin-4-one as yellow oil. ES, m/z): [M+CH3CN]+697.0; 1H NMR (300 MHz, CDCl3): δ8.12-8.22 (m, 2H), 7.98 (s, 1H), 7.86 (d, J=7.8 Hz, 2H), 7.73 (d, J=7.8 Hz, 1H), 5.17 (s, 1H), 4.79 (s, 1H), 4.44 (d, J=18.0 Hz, 1H), 4.01-4.31 (m, 4H), 3.93 (s, 1H).
Reaction SMILES: C(N(CC)CC)C.C(O)=O.[F:11][C:12]([F:29])([F:28])[C:13]([NH:15][C@H:16]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([F:26])[CH:24]=2)[C:19](=[O:27])[CH2:18][CH2:17]1)=[O:14]>CN(C=O)C>[F:29][C:12]([F:11])([F:28])[C:13]([NH:15][C@H:16]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([F:26])[CH:24]=2)[C@H:19]([OH:27])[CH2:18][CH2:17]1)=[O:14]
Reactant: O=C1CC[C@@H](NC(=O)C(F)(F)F)c2cc(F)ccc21
Solvent: O=CO
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: O=C(N[C@@H]1CC[C@@H](O)c2ccc(F)cc21)C(F)(F)F
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 16.2 %

Procedure:
To ice bath-cooled triethylamine (13.3 mL, 95.2 mmol, 7.4 equiv.) was added dropwise formic acid (3.65 mL, 95.2 mmol, 7.4 equiv.). The reaction solution was stirred at RT for 20 min. A solution of (R)-2,2,2-trifluoro-N-(7-fluoro-4-oxo-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide (3.54 g, 12.9 mmol, 1 equiv) in DMF (10 ml) and Noyori catalyst (R,R form) (204.3 mg, 2.5 mol %) were added and stirred at RT overnight. TLC was checked and found only small amount of product formed. The reaction solution was stirred at 40° C. for 16 h. TLC showed reaction completed. The solvents were evaporated off The residue was treated with CH2Cl2 to result a white solid precipitate, which was collected on funnel and washed with small amount of CH2Cl2 (2.15 g). The filtrate gave additional 0.58 g of product after chromatography (ISCO, 30-40% EtOAc-hexane). Total: 2.73 g (77%). 1H NMR (400 MHz, DMSO-d6) δ 9.83 (s, 1H), 7.52 (q, 1H), 7.13 (m, 1H), 6.85 (dd, 1H), 5.36 (d, 1H), 5.05 (m, 1H), 4.55-4.62 (m, 1H), 2.06-2.14 (m, 2H), 1.64-1.80 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[C:4]1[C:9]([CH3:10])=[CH:8][C:7]([F:11])=[CH:6][C:5]=1I.[CH3:14][N:15](C=O)C>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Zn].[C-]#N.[Zn+2].[C-]#N>[CH3:1][O:2][C:3](=[O:13])[C:4]1[C:9]([CH3:10])=[CH:8][C:7]([F:11])=[CH:6][C:5]=1[C:14]#[N:15]
Reactant: CN(C)C=O
Reactant: COC(=O)c1c(C)cc(F)cc1I
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: [C-]#N
Solvent: CCOC(C)=O
Product: COC(=O)c1c(C)cc(F)cc1C#N
Temperature: 150 °C
Reaction time: 1 h
Yield: 91 %

Procedure:
A mixture of 2-iodo-4-fluoro-6-methyl-benzoic acid methyl ester (0.294 g, 1.0 mmol), PdCl2(dppf)2 (0.018 g, 0.025 mmol), zinc (0.002 g, 0.03 mmol), Zinc cyanide (0.234 g, 2 mmol) and DMF (3 mL) was stirred at 150° C. for 1 h. The reaction mixture was cooled to room temperature, dissolved in ethyl acetate (50 mL) and washed with water. Combined organic layer was dried (MgSO4), filtered and concentrated. Silica gel column chromatography using 10:1 hexane-ethyl acetate afforded 2-cyano-4-fluoro-6-methyl-benzoic acid methyl ester (0.175 g, 91%).
Reaction SMILES: O1CCOCC1.[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:15]=[C:16]([CH:26]3[CH2:31][CH2:30][CH:29]([CH2:32][C:33]#[N:34])[CH2:28][CH2:27]3)[NH:17][C:18]=2[C:19]2[C:20](F)=[N:21][CH:22]=[CH:23][CH:24]=2)=[C:10]([N+:35]([O-])=O)[CH:9]=1.S(S([O-])=O)([O-])=O.[Na+].[Na+].[OH-].[NH4+]>O>[F:7][C:8]1[CH:13]=[CH:12][C:11]2[C:14]3[N:15]=[C:16]([CH:26]4[CH2:31][CH2:30][CH:29]([CH2:32][C:33]#[N:34])[CH2:28][CH2:27]4)[NH:17][C:18]=3[C:19]3[CH:24]=[CH:23][CH:22]=[N:21][C:20]=3[NH:35][C:10]=2[CH:9]=1
Reactant: N#CCC1CCC(c2nc(-c3ccc(F)cc3[N+](=O)[O-])c(-c3cccnc3F)[nH]2)CC1
Agent: O=S([O-])S(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: N#CCC1CCC(c2nc3c([nH]2)-c2cccnc2Nc2cc(F)ccc2-3)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 58.9 %

Procedure:
To a mixture of 1,4-dioxane (1 mL) with 4-[4-(4-fluoro-2-nitrophenyl)-5-(2-fluoropyridin-3-yl)-1H-imidazol-2-yl]cyclohexylacetonitrile (0.17 g, 0.40 mmol) was added a solution of sodium dithionite (0.2 g, 0.001 mol) and ammonium hydroxide (0.4 mL, 0.003 mol) in water (1 mL), The reaction was stirred at 25° C. for 1 hour, concentrated, and was then extracted with isopropanol (3×1 mL each). The combined extracts were heated in a microwave reactor at 160° C. for 15 minutes, concentrated, and purified via column chromatography on silica gel (50% ethyl acetate 50% hexanes) to give 0.088 g of the desired product. 1H NMR (400 MHz, DMSO-d6): δ 8.42 (br s, 1H), 7.07 (m, 1H), 7.66 (m, 1H), 6.99 (m, 1H), 6.80-6.91 (m, 2H), 3.09 (m, 1H), 1.10-2.05 (m, 11H); MS [M+H]=374.0.
Reaction SMILES: CC(C)([O-])C.[K+].[F:7][C:8]([F:12])([F:11])[CH2:9][OH:10].[Br:13][C:14]1[CH:19]=[C:18](F)[CH:17]=[C:16]([F:21])[CH:15]=1.O>CS(C)=O>[Br:13][C:14]1[CH:19]=[C:18]([O:10][CH2:9][C:8]([F:12])([F:11])[F:7])[CH:17]=[C:16]([F:21])[CH:15]=1
Reactant: Fc1cc(F)cc(Br)c1
Reactant: OCC(F)(F)F
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: Fc1cc(Br)cc(OCC(F)(F)F)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 27 %

Procedure:
To a 50 mL flask flushed with nitrogen, equipped with a stir bar and cooled in a water bath was added potassium tertbutoxide (1.2 g, 11 mmol, 95%). DMSO was added (4 mL) followed by addition of a solution of 2,2,2-trifluoroethanol (1.1 g, 11 mmol) in DMSO (1 mL). The water bath was removed and 1-bromo-3,5-difluorobenzene (1.1 mL, 9.5 mmol) was added and the reaction mixture stirred at room temperature for 1 h. An additional portion of 2,2,2-trifluoroethanol was added (1.1 g, 11 mmol) and the reaction mixture stirred for 14 h. Additional potassium tertbutoxide (0.24 g, 2.2 mmol, 95%) was added followed by addition of a further aliquot of 2,2,2-trifluoroethanol (0.44 g, 4.4 mmol) and the resulting turbid solution stirred for 2 h. Water was added (200 mL), and the aqueous phase extracted with ether (1×200 mL). The organic portion was then washed successively with water (2×200 mL) and saturated NaCl solution (2×200 mL), dried over Na2SO4, decanted and concentrated under reduced pressure yielding a crude yellow liquid (2.1 g). A portion of the crude product (1.3 g) was purified by distillation under reduced pressure at 80° C. yielding 1-bromo-3-fluoro-5-(2,2,2-trifluoroethoxy)benzene as a colorless oil (0.70 g, 35% yield). 1H NMR (CDCl3, 400 MHz): 7.05 ppm (d, 1H), 6.90 ppm (s, 1H), 6.55 ppm (d, 1H), 4.32 ppm (q, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8](Cl)=[O:9])[CH:3]=1.C(N(CC)CC)C.[CH2:18]([O:20][C:21](=[O:31])[CH2:22][NH:23][C:24]1[C:29]([NH2:30])=[CH:28][CH:27]=[CH:26][N:25]=1)[CH3:19]>>[CH2:18]([O:20][C:21](=[O:31])[CH2:22][NH:23][C:24]1[C:29]([NH:30][C:8]([C:4]2[CH:3]=[C:2]([Cl:1])[CH:7]=[CH:6][N:5]=2)=[O:9])=[CH:28][CH:27]=[CH:26][N:25]=1)[CH3:19]
Reactant: CCOC(=O)CNc1ncccc1N
Reactant: O=C(Cl)c1cc(Cl)ccn1
Solvent: CCN(CC)CC
Product: CCOC(=O)CNc1ncccc1NC(=O)c1cc(Cl)ccn1
Reaction time: 8 h

Procedure:
The crude 4-chloro picolinoyl chloride and triethylamine (5.55 g, 0.055 mole) were added dropwise simultaneously to the above stirred filtrate of N-(3-amino-2-pyridinyl)glycine ethyl ester at room temperature and allowed to stir overnight.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:21])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([NH:16][CH2:17][CH:18]3[CH2:20][CH2:19]3)=[O:15])=[CH:10][CH:9]=2)[CH:7]=1.[S:22]1[CH:26]=[C:25]([C:27](O)=[O:28])[N:24]=[CH:23]1>>[CH:18]1([CH2:17][NH:16][C:14]([C:11]2[CH:12]=[CH:13][C:8]([C:6]3[C:5]([CH3:21])=[CH:4][CH:3]=[C:2]([NH:1][C:27]([C:25]4[N:24]=[CH:23][S:22][CH:26]=4)=[O:28])[CH:7]=3)=[CH:9][CH:10]=2)=[O:15])[CH2:20][CH2:19]1
Reactant: Cc1ccc(N)cc1-c1ccc(C(=O)NCC2CC2)cc1
Reactant: O=C(O)c1cscn1
Product: Cc1ccc(NC(=O)c2cscn2)cc1-c1ccc(C(=O)NCC2CC2)cc1

Procedure:
N-(4′-{[(Cyclopropylmethyl)amino]carbonyl}-6-methyl-1,1′-biphenyl-3-yl)thiazole-4-carboxamide was prepared from 5′-amino-N-(cyclopropylmethyl)-2′-methyl-1,1′-biphenyl-4- carboxamide and thiazole-4-carboxylic acid using method D. NMR; δH [2H6]—DMSO 10.35, (1H, s), 9.26,(1H, d), 8.62,(1H, t), 8.47,(1H, d), 7.92,(2H, d), 7.78-7.76,(2H, m), 7.44,(2H, d), 7.28,(1H, d), 3.16,(2H, t), 2.20,(3H, s), 1.04,(1H, m), 0.44,(2H, m), 0.24,(2H, m). LCMS: retention time 3.25 min, MH+392.
Reaction SMILES: [S-2:1].[Na+].[Na+].[S].Cl[C:6]1[CH:15]=[CH:14][C:9]([C:10]([O:12][CH3:13])=[O:11])=[CH:8][C:7]=1[N+:16]([O-:18])=[O:17]>CO.O.CO>[N+:16]([C:7]1[CH:8]=[C:9]([CH:14]=[CH:15][C:6]=1[S:1][S:1][C:6]1[CH:15]=[CH:14][C:9]([C:10]([O:12][CH3:13])=[O:11])=[CH:8][C:7]=1[N+:16]([O-:18])=[O:17])[C:10]([O:12][CH3:13])=[O:11])([O-:18])=[O:17]
Reactant: COC(=O)c1ccc(Cl)c([N+](=O)[O-])c1
Reactant: [S-2]
Agent: [Na+]
Agent: [S]
Solvent: CO
Solvent: O
Product: COC(=O)c1ccc(SSc2ccc(C(=O)OC)cc2[N+](=O)[O-])c([N+](=O)[O-])c1
Reaction time: 0.25 h
Yield: 65 %

Procedure:
A solution of sodium sulfide.nanohydrate (1.15 g, 4.9 mmol) in methanol-water (ca. 10 mL, 1:1) is warmed on a hot plate. To this solution is added elemental sulfur (150 mg, 4.6 mmol). Heating is continued for 15 min before the solution is poured into a separate solution of 1.0 g (4.6 mmol) of methyl 4-chloro-3-nitrobenzoate (see: Kuene, J. Am. Chem. Soc. 1962, 48, 837.) in MeOH (5.0 mL). The mixture is stirred for 30 min, followed by cooling in a refrigerator overnight. The solid precipitate is filtered, washed with water and methanol, and dried in vacuo at 50° C. to afford 650 mg (65%) of dimethyl 4,4′-dithio-bis-(3-nitrobenzoate) as a yellow solid: 1H NMR (400 MHz, CDCl3) δ 9.0, 8.2, 7.9, 4.0.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][C@H:11]([CH2:13][CH3:14])[CH3:12])[CH:5]=[O:6].O.S(=O)(=O)(O)[OH:17]>CC(C)=O.[O-2].[Cr+6].[O-2].[O-2]>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][C@H:11]([CH2:13][CH3:14])[CH3:12])[C:5]([OH:17])=[O:6]
Reactant: CC[C@H](C)Oc1ccc(C=O)cc1F
Reactant: O=S(=O)(O)O
Agent: [Cr+6]
Agent: [O-2]
Solvent: O
Solvent: CC(C)=O
Product: CC[C@H](C)Oc1ccc(C(=O)O)cc1F
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 130 mg (0.66 mmol) of 3-fluoro-4-(2-(S)-butoxy)benzaldehyde in 1 mL of acetone was treated with a 73 mg (0.73 mmol) of chromium (VI) oxide in a 3:1 v/v mixture of water/sulfuric acid at 0° C. The reaction was allowed to warm to rt and was stirred for 2 hr then extracted with 10 mL of EtOAc, washed with brine, dried over MgSO4 and concentrated to afford 130 mg of the title compound: 1H NMR (500 Mhz) δ 1.00 (t, J=7.6, 3H), 1.36 (d, J=6.2, 3H), 1.70 (m, 1H), 1.82 (m, 1H), 4.44 (m, 1H), 6.99 (t, J=8.2, 1H), 7.79 (d, J=8.2, 1H), 7.85 (s, 1H).
Reaction SMILES: [OH:1][N:2]=[C:3]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]([C:14](=[O:24])[C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)[CH2:6][CH2:5][CH2:4]1.[H-].[Na+].Br[CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30]>CN(C)C=O>[CH2:32]([O:31][C:29]([CH2:28][O:1][N:2]=[C:3]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]([C:14](=[O:24])[C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)[CH2:6][CH2:5][CH2:4]1)=[O:30])[CH3:33]
Reactant: O=C(c1ccc([N+](=O)[O-])cc1)N1CCCC(=NO)c2ccccc21
Reactant: CCOC(=O)CBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)CON=C1CCCN(C(=O)c2ccc([N+](=O)[O-])cc2)c2ccccc21
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
A solution of 5-hydroxyimino-1-(4-nitrobenzoyl) -2,3,4,5-tetrahydro-1H-1-benzazepine (500 mg) in N,N-dimethylformamide (10 ml) was treated with sodium hydride (72 mg, 60% w/w in mineral oil) at 0° C. The reaction mixture was stirred at 0° C. for 5 minutes and then at ambient temperature for 30 minutes. Ethyl bromoacetate (301 mg) was added, and the reaction mixture was stirred for 2 hours. The reaction was quenched with aqueous hydrochloric acid and the mixture was diluted with ethyl acetate. The organic phase was washed with 0.5N hydrochloric acid, water, saturated aqueous sodium hydrogen carbonate, and brine. The organic solution was dried over magnesium sulfate and concentrated to give crude 5-ethoxycarbonylmethoxyimino-1-(4-nitrobenzoyl) -2,3,4,5-tetrahydro-1H-1-benzazepine. This product was taken on without further purification (700 mg).
Reaction SMILES: CCO.Cl[C:5]1[O:9][C:8]([C:10]2[C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:13]([CH3:21])[O:12][N:11]=2)=[CH:7][CH:6]=1.[K+].[Br-]>O=[Pt]=O.CCCCCC>[O:9]1[CH:5]=[CH:6][CH:7]=[C:8]1[C:10]1[C:14]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[C:13]([CH3:21])[O:12][N:11]=1
Reactant: Cc1onc(-c2ccc(Cl)o2)c1-c1ccccc1
Agent: O=[Pt]=O
Agent: [Br-]
Agent: [K+]
Solvent: CCO
Solvent: CCCCCC
Product: Cc1onc(-c2ccco2)c1-c1ccccc1
Reaction time: 7 h
Yield: 89 %

Procedure:
A solution of EtOH (2 ml) containing 3-(5-chlorofuran-2-yl)-4-phenyl-5-methylisoxazole (97 mg, 0.374 mmoles), PtO2 (5 mg) is kept in an atmosphere of H2 (1 atm) at ambient temperature, stirring for 7 h. The catalyst is then filtered on celite and the solvent is evaporated at reduced pressure. The residue is crystallised from hexane. A white powder is obtained with 89% yield and a m.p. 93-96° C. (hexane). FT-IR (KBr): 3149, 3122, 3059, 2962, 2925, 2853, 1633, 1605, 1511, 1496, 1448, 1438, 1417, 1239, 1225, 1176, 1070, 1020, 976, 923, 891, 782, 714, 700 cm−1. 1H NMR (400 MHz, CDCl3, δ): 7.47-7.41 (m, 4H, aromatic protons); 7.31-7.28 (m, 2H, aromatic protons); 6.37-6.35 (dd, 1H, J=3.3 Hz, J=1.8 Hz, furyl proton); 6.34-6.33 (d, 1H, J=3.3 Hz, furyl proton); 2.39 (s, 3H). 13C NMR (100 MHz, CDCl3, δ): 166.6, 153.1, 144.0, 143.6, 130.0, 129.8, 128.7, 128.1, 114.9, 111.5, 111.1, 11.2. GC-MS (70 eV) m/z (rel.int.): 225 (M+, 40), 184 (14), 183 (100), 154 (17), 127 (13), 102 (12), 43 (11). Anal. Calc. for C14H11NO2: C, 74.65; H, 4.92; N, 6.22; O, 14.21. Found: C, 74.48; H, 4.94; N, 6.19.
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[OH:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]1[N:17]([CH2:44][CH2:45][CH3:46])[N:18]=[C:19]2[C:28]=1[C:27]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[N:21]=[C:20]2[N:29]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31].C(N(CC)CC)C>ClCCl>[O:11]=[CH:12][CH2:13][CH2:14][CH2:15][C:16]1[N:17]([CH2:44][CH2:45][CH3:46])[N:18]=[C:19]2[C:28]=1[C:27]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[N:21]=[C:20]2[N:29]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31]
Reactant: CCCn1nc2c(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)nc3ccccc3c2c1CCCCO
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CS(C)=O
Product: CCCn1nc2c(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)nc3ccccc3c2c1CCCC=O
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 107.7 %

Procedure:
To dichloromethane (5 mL) at −78° C. was added dimethylsulfoxide (0.12 mL, 1.6 mmol) and oxalyl chloride (0.11 mL, 1.2 mmol). After several minutes, a solution di(tert-butyl) 1-(4-hydroxybutyl)-2-propyl-2H-pyrazolo[3,4-c]quinolin-4-ylimidodicarbonate (0.5449 g, 1.093 mmol) and triethylamine (0.46 mL, 3.3 mmol) in dichloromethane (5 mL) was added dropwise to the −78° C. solution. After 15 minutes, the cooling bath was removed and the solution was allowed to warm to ambient temperature, during which time more dichloromethane (20 mL) was added. The solution was transferred to a separatory funnel and washed with aqueous potassium carbonate, water, and brine. The solution was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting oil was dried under vacuum to yield 0.5845 g of di(tert-butyl) 1-(4-oxobutyl)-2-propyl-2H-pyrazolo[3,4-c]quinolin-4-ylimidodicarbonate that contained a small amount of dimethylsulfoxide, but was used without further purification.
Reaction SMILES: [CH3:1][N:2]([CH3:25])[CH2:3][CH2:4][CH:5]=[C:6]1[C:12]2[CH:13]=[C:14]([S:17]([CH3:20])(=[O:19])=[O:18])[CH:15]=[CH:16][C:11]=2[CH:10]=[CH:9][C:8]2[CH:21]=[CH:22][CH:23]=[CH:24][C:7]1=2>[Ni].C(O)C>[CH3:25][N:2]([CH3:1])[CH2:3][CH2:4][CH:5]=[C:6]1[C:12]2[CH:13]=[C:14]([S:17]([CH3:20])(=[O:18])=[O:19])[CH:15]=[CH:16][C:11]=2[CH2:10][CH2:9][C:8]2[CH:21]=[CH:22][CH:23]=[CH:24][C:7]1=2
Reactant: CN(C)CCC=C1c2ccccc2C=Cc2ccc(S(C)(=O)=O)cc21
Agent: [Ni]
Solvent: CCO
Product: CN(C)CCC=C1c2ccccc2CCc2ccc(S(C)(=O)=O)cc21

Procedure:
5-(3-Dimethylaminopropylidene)-3-methylsulfonyl-5H-dibenzo[a,d]cycloheptene (α-isomer), (1.39 g., 0.0039 mole), dissolved in 20 ml. of ethanol, is hydrogenated over Raney nickel at 65° C. under an initial hydrogen pressure of 440 p.s.i. The catalyst is separated and the solvent evaporated under reduced pressure. Recrystallization from cyclohexane gives 10,11-dihydro-5-(3-dimethylaminopropylidene)-3-methylsulfonyl-5H-dibenzo[a,d]cycloheptene (α-isomer), m.p. 121°-121.5° C. (sintered, 120° C.; cleared, 122.5° C.).
Reaction SMILES: C(B(CC)[C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)C.[CH3:12][O:13][C:14](=[O:22])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17](I)[CH:16]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.[Pd]>[CH3:12][O:13][C:14](=[O:22])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:4]2[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=2)[CH:16]=1
Reactant: CCB(CC)c1cccnc1
Reactant: COC(=O)c1cccc(I)c1
Agent: [Pd]
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1cccc(-c2cccnc2)c1
Reaction time: 10 h
Yield: 68.1 %

Procedure:
A mixture of diethyl(3-pyridyl)borane (176.4 g, 1.2 mole), methyl-3-iodobenzoate (262 g, 1 mole), potassium phosphate (318.4 g, 1.5 mole) and tetrakistriphenlyphosphine palladium (0) (57.8 g, 0.05 mole) in DMF (1000 ml) was heated at 80 degrees under argon. After 10 h, the mixture was diluted with water and extracted with ethyl acetate. The organic layer was filtered and washed with water. To the organic fraction was added concentrated HCL (65 ml). The organic layer was separated and extracted with aqueous HCl. The combined acid extractions were treated with ethyl acetate, followed by 50% aqueous sodium hydroxide (55 ml). The organic layer was separated, washed with water and saturated sodium bicarbonate solution, then dried over sodium sulfate. The solution was filtered and concentrated to give methyl-3-(pyridin-3-yl)benzoate (145.3 g).
Reaction SMILES: [I-].C[S+](C)C.[Li][CH2:7]CCC.[CH2:11]([C@H:19]1[CH2:21][O:20]1)[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.O>C1COCC1>[C:13]1([CH2:12][CH2:11][C@H:19]([OH:20])[CH:21]=[CH2:7])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: c1ccc(CC[C@H]2CO2)cc1
Reactant: [Li]CCCC
Agent: C[S+](C)C
Agent: [I-]
Solvent: C1CCOC1
Solvent: O
Product: C=C[C@@H](O)CCc1ccccc1
Temperature: -20 °C
Yield: 66.2 %

Procedure:
A modified procedure of Falck was used (Alcaraz, L. et al., Tetrahedron Letters 1994, 35, 5449). A suspension of trimethylsulfonium iodide (18.2 g, 89.1 mmol) in anhydrous THF (220 ml) was stirred and cooled to −20° C. 1.6 M n-BuLi (55.7 ml, 89.1 mmol) was added slowly and the reaction stirred at −20° C. for 1 h. A solution of epoxide 63 (4.40 g, 29.7 mmol) in anhydrous THF (50.0 ml) was added slowly. The reaction was stirred at −20° C. for 1 h and then allowed to warm to r.t. slowly. The reaction mixture was poured into water (200 ml) and extracted with Et2O (1×200 ml, 1×100 ml). The combined organic phases were washed with saturated NaCl solution (100 ml) before being dried (MgSO4), filtered, and concentrated to give the crude material. This was purified by column chromatography (130 g silica), eluting with petrol/EtOAc (9:1), to give partially purified material. This was re-purified by column chromatography (50 g silica), eluting with petrol/EtOAc (9:1), to give allylic alcohol 66 (3.19 g, 66%) as a pale yellow liquid. The analytical data matched that described for the racemic material above.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[C:21](Br)[C:15]=3[O:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH3:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[C:25]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>CC1C=CC=CC=1[P](C1C=CC=CC=1C)([Pd](Cl)(Cl)[P](C1=C(C)C=CC=C1)(C1C=CC=CC=1C)C1C=CC=CC=1C)C1C=CC=CC=1C>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[C:21]([C:25]4[C:26]([CH3:30])=[CH:27][CH:28]=[CH:29][C:24]=4[CH3:23])[C:15]=3[O:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: Cc1cccc(C)c1B(O)O
Reactant: Cc1ccc(S(=O)(=O)OCC2Cc3cccc(Br)c3O2)cc1
Agent: Cc1ccccc1[P](c1ccccc1C)(c1ccccc1C)[Pd](Cl)(Cl)[P](c1ccccc1C)(c1ccccc1C)c1ccccc1C
Agent: O=C([O-])[O-]
Agent: [K+]
Product: Cc1ccc(S(=O)(=O)OCC2Cc3cccc(-c4c(C)cccc4C)c3O2)cc1
Yield: 18 %

Procedure:
Treatment of (±)-(7-bromo-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (1.00 g, 2.61 mmol) with 2,6-dimethylphenylboronic acid (0.783 g, 5.22 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.103 g, 0.135 mmol), and potassium carbonate (0.90 g, 6.52 mmol) generally according to the procedure described for Intermediate 37 provided 0.192 g (18%) of (±)-[7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a yellow oil. Anal. calcd. for C24H24O4S: C, 70.56; H, 5.92. Found: C, 68.01; H, 5.6.
Reaction SMILES: [N+:1]([CH:4]([CH3:6])[CH3:5])([O-:3])=O.[CH:7]1[CH:15]=[CH:14][C:13]2[C:9](=[N:10][O:11][N+]=2[O-])[CH:8]=1.C(NCC)C>O1CCCC1>[CH3:5][C:4]1([CH3:6])[N+:1]([O-:3])=[C:13]2[CH:14]=[CH:15][CH:7]=[CH:8][C:9]2=[N+:10]1[O-:11]
Reactant: [O-][n+]1onc2ccccc21
Reactant: CC(C)[N+](=O)[O-]
Solvent: C1CCOC1
Solvent: CCNCC
Product: CC1(C)[N+]([O-])=c2ccccc2=[N+]1[O-]
Reaction time: 8 h

Procedure:
To a mixture containing 2-nitropropane (10.7 g., 0.12 moles), benzofuroxan (13.6 g., 0.10 moles) and tetrahydrofuran (50 ml.) is added dropwise diethylamine (8.7 g., 0.12 mole). The reaction temperature rises during addition. Upon completion of addition, the reaction mixture is allowed to sit overnight at room temperature.