Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:3](=[O:21])[N:4]([CH2:14][C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[C:5](=[O:13])[C:6]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:22][O:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][CH:25]=1>CN(C=O)C>[CH3:22][O:23][C:24]1[CH:30]=[CH:29][C:27]([NH:28][C:2]2[C:3](=[O:21])[N:4]([CH2:14][C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)[C:5](=[O:13])[C:6]=2[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[CH:26][CH:25]=1
Reactant: COc1ccc(N)cc1
Reactant: O=C1C(Cl)=C(c2ccccc2)C(=O)N1Cc1cccnc1
Solvent: CN(C)C=O
Product: COc1ccc(NC2=C(c3ccccc3)C(=O)N(Cc3cccnc3)C2=O)cc1
Temperature: 150 °C
Yield: 40 %

Procedure:
To a solution of 3-chloro-4-phenyl-1-(pyridin-3-ylmethyl)-1H-pyrrole-2,5-dione (0.50 mmol, 149 mg) in DMF (1 mL) was added 4-methoxyaniline (1.10 mmol, 135 mg) The mixture was heated in a microwave reactor at 150° C. for five min. After cooling, the reaction mixture was purified by HPLC (95% 0.1M ammonium acetate buffer: 5% CH3CN→100% CH3CN) to give 77 mg (40%) of the title compound. 1H NMR (400 MHz, CDCl3) δ 8.71 (d, J=1.8 Hz, 1H), 8.54 (dd, J1=4.7 Hz, J2=1.6 Hz, 1H), 7.80-7.75 (m, 1H), 7.35 (bs, 1H), 7.26 (dd, J1=7.8 Hz, J2=4.7 Hz, 1H), 7.15-7.05 (m, 3H), 6.98-6.94 (m, 2H), 6.62-6.50 (m, 4H), 4.78 (s, 2H), 3.68 (s, 3H).
Reaction SMILES: [CH:1]1([CH:6]([OH:9])[CH:7]=[CH2:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.[F:10][C:11]1[CH:16]=[C:15](Br)[CH:14]=[CH:13][C:12]=1[CH:18]([F:20])[F:19].C([O-])(O)=O.[Na+].O>CN1C(=O)CCC1>[CH:1]1([C:6](=[O:9])[CH2:7][CH2:8][C:15]2[CH:14]=[CH:13][C:12]([CH:18]([F:20])[F:19])=[C:11]([F:10])[CH:16]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Fc1cc(Br)ccc1C(F)F
Reactant: C=CC(O)C1CCCC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN1CCCC1=O
Solvent: O
Product: O=C(CCc1ccc(C(F)F)c(F)c1)C1CCCC1
Temperature: 140 °C
Yield: 33.4 %

Procedure:
A mixture of 1-cyclopentyl-2-propen-1-ol (34 g, 0.266 mol), 2-fluoro-4-bromo-difluoromethyl benzene, (40 g, 0.177 mol, 1.5 equiv), and NaHCO3 (17.8 g, 0.212 mol, 1.2 equiv) in anhydrous NMP (200 mL) was heated to 140° C. for 1 h, resulting in complete conversion by TLC. The reaction mixture was poured into water and extracted with CH2Cl2. The organic layer was separated, washed with brine and dried over anhydrous Na2SO4. After the removal of the solvent, the residue was purified by column chromatography using hexanes/ethyl acetate, and the product-containing fractions combined and concentrated. The residue was fractionally distilled through a Vigreux column to give 16 g (33%) of the desired product (bp 100° C./0.2 Torr).
Reaction SMILES: [CH:1]([C@@H:4]1[CH2:9][CH2:8][C@@H:7]([CH3:10])[CH2:6][C@H:5]1[O:11][C:12]([C@@H:14]1[CH2:27][C:26]2[CH:25]=[C:24]3[C:19]([O:20][C@@H:21]([C:30]4[CH:35]=[CH:34][C:33]([O:36][CH2:37][C:38]5[CH:43]=[CH:42][C:41]([Cl:44])=[C:40]([Cl:45])[CH:39]=5)=[CH:32][CH:31]=4)[C:22](=[O:29])[N:23]3[CH3:28])=[CH:18][C:17]=2[CH2:16][NH:15]1)=[O:13])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].Br[CH:52]([C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)[CH2:53][CH3:54].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[CH:1]([C@@H:4]1[CH2:9][CH2:8][C@@H:7]([CH3:10])[CH2:6][C@H:5]1[O:11][C:12]([C@@H:14]1[CH2:27][C:26]2[CH:25]=[C:24]3[C:19]([O:20][C@@H:21]([C:30]4[CH:31]=[CH:32][C:33]([O:36][CH2:37][C:38]5[CH:43]=[CH:42][C:41]([Cl:44])=[C:40]([Cl:45])[CH:39]=5)=[CH:34][CH:35]=4)[C:22](=[O:29])[N:23]3[CH3:28])=[CH:18][C:17]=2[CH2:16][N:15]1[C@H:52]([C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)[CH2:53][CH3:54])=[O:13])([CH3:2])[CH3:3]
Reactant: CCC(Br)c1ccccc1
Reactant: CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)[C@@H]1Cc2cc3c(cc2CN1)O[C@@H](c1ccc(OCc2ccc(Cl)c(Cl)c2)cc1)C(=O)N3C
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC[C@@H](c1ccccc1)N1Cc2cc3c(cc2C[C@H]1C(=O)O[C@@H]1C[C@H](C)CC[C@H]1C(C)C)N(C)C(=O)[C@H](c1ccc(OCc2ccc(Cl)c(Cl)c2)cc1)O3
Temperature: 50 °C
Reaction time: 48 h

Procedure:
(3S,7S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-1-methyl-2-oxo-2,3,5,6,7,8-hexahydro-1H-4-oxa-1,6-diaza-anthracene-7-carboxylic acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester (3.5 g, 5.37 mmol) was dissolved in 10 mL DMF and sodium bicarbonate (21.5 mmol) and (1-Bromo-propyl)-benzene (10.7 mmol) added. The mixture was stirred at 50° C. for 20 h and room temperature for 48 hours. The mixture was poured onto diethyl ether and 10% sodium carbonate. The aqueous layer was extracted with ether and organic layers combined. The organic layer was dried over sodium sulfate and concentrated. The residue was purified over silica (EtOAc-hexanes-DCM-TEA, 0.5/5/4.5/0.02) to provide (3S,7S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-1-methyl-2-oxo-6-((S)-1-phenyl-propyl)-2,3,5,6,7,8-hexahydro-1H-4-oxa-1,6-diaza-anthracene-7-carboxylic acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester (803 mg, 1H NMR (400 MHz, d6 acetone): 7.7 (d, 1H), 7.6 (d, 1H), 7.46 (d, 1H), 7.33 (m, 7H), 6.98 (m, 2H), 6.87 (s, 1H), 6.77 (s, 1H), 5.65 (s, 1H), 5.13 (s, 2H), 4.55 (m, 1H), 4.20 (s, 2H), 3.9 (m, 1H), 3.55 (m, 1H), 3.38 (s, 3H), 2.95 (m, 2H), 1.6 (m, 6H), 1.15 (m, 1H), 0.95 (m, 1H) 0.9 (m, 2H), 0.8 (m, 4H), 0.7 (d, 3H), 0.65 (m, 6H).
Reaction SMILES: S1C2C=CC=CC=2N=C1NN=CC1OC([N+]([O-])=O)=CC=1.[N+:21]([C:24]1[S:28][C:27]([CH:29]=O)=[CH:26][CH:25]=1)([O-:23])=[O:22].[NH:31]([C:33]1[S:34][C:35]2[CH:41]=[C:40]([O:42][C:43]([F:46])([F:45])[F:44])[CH:39]=[CH:38][C:36]=2[N:37]=1)[NH2:32]>>[F:46][C:43]([F:44])([F:45])[O:42][C:40]1[CH:39]=[CH:38][C:36]2[N:37]=[C:33]([NH:31][N:32]=[CH:29][C:27]3[S:28][C:24]([N+:21]([O-:23])=[O:22])=[CH:25][CH:26]=3)[S:34][C:35]=2[CH:41]=1
Reactant: NNc1nc2ccc(OC(F)(F)F)cc2s1
Reactant: O=Cc1ccc([N+](=O)[O-])s1
Agent: O=[N+]([O-])c1ccc(C=NNc2nc3ccccc3s2)o1
Product: O=[N+]([O-])c1ccc(C=NNc2nc3ccc(OC(F)(F)F)cc3s2)s1

Procedure:
The compound 3j was prepared according procedure described for 3a by employing 5-nitrothiophen aldehyde (157 mg, 1 mmol) and 2-hydrazino-6-trifluoromethoxy-benzothiazole (249 mg, 1 mmol) at 70° C. for 2 h (yield 219 mg, 75%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH:8]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:7][CH2:6]2.[I:18]I>C(O)C.C(OCC)(=O)C.S([O-])([O-])(=O)=O.[Ag+2]>[I:18][C:11]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][CH:8]2[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:4][C:3]=1[O:2][CH3:1]
Reactant: II
Reactant: CCOC(=O)CC1CCc2cc(OC)ccc21
Agent: [Ag+2]
Agent: O=S(=O)([O-])[O-]
Solvent: CCOC(C)=O
Solvent: CCO
Product: CCOC(=O)CC1CCc2cc(OC)c(I)cc21
Temperature: 25 °C

Procedure:
Ethyl (5-methoxy-2,3-dihydro-1H-inden-1-yl)acetate (472 mg, 2.015 mmol) was dissolved in ethanol (20 mL). Iodine (511 mg, 2.015 mmol) and silver sulfate (628 mg, 2.015 mmol) were added and the reaction was stirred vigorously at room temperature, protected from light, for 1 hour. The reaction was diluted with ethyl acetate (75 mL) and filtered to remove solids. The filtrate was washed with sodium bisulfite (2×50 mL), water (70 mL), and brine (70 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 0 to 50% ethyl acetate/hexanes. Further purification by SFC on a chiral AD column with 15% IPA/heptanes removed a minor regioisomer and separated the two enantiomers of ethyl (6-iodo-5-methoxy-2,3-dihydro-1H-inden-1-yl)acetate. 1H NMR (CDCl3, 500 MHz) δ 7.55 (s, 1H), 6.72 (s, 1H), 4.17 (m, 2H), 3.85 (s, 3H), 3.53 (m, 1H), 2.95-2.65 (m, 3H), 2.60-2.42 (m, 2H), 1.78 (m, 1H), 1.28 (t, J=7.1 Hz, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]([CH3:13])[CH:10]=[CH:9][C:4]=1[C:5]([O:7][CH3:8])=[O:6].[I:14]Cl>CO>[I:14][C:10]1[C:11]([CH3:13])=[CH:12][C:3]([O:2][CH3:1])=[C:4]([CH:9]=1)[C:5]([O:7][CH3:8])=[O:6]
Reactant: ClI
Reactant: COC(=O)c1ccc(C)cc1OC
Solvent: CO
Product: COC(=O)c1cc(I)c(C)cc1OC
Temperature: 50 °C

Procedure:
Methyl 2-methoxy-4-methylbenzoate (1.5 g, 8.32 mmol, 1 eq) was dissolved in methanol. To this solution was added dropwise iodine monochloride (6.75 g, 41.6 mmol, 5 eq) in methanol at room temperature. The reaction mixture was heated at 50° C. for 15 h. Finally, methanol was concentrated, diluted with water and extracted with ethyl acetate. The organic layer was washed with 0.1 N HCl (50 ml), water (100 ml) and brine solution (100 ml). The product was purified by column chromatography using 60-120 silica gel and using 5% ethyl acetate/hexane as eluent. Yield: 1.7 g (80%). 1HNMR (400 MHz, CDCl3): δ 2.44 (s, 3H), 3.86 (s, 3H), 3.88 (s, 3H), 6.86 (s, 1H), 8.20 (s, 1H). LCMS: (ES+) m/z=307.0 (M+H).
Reaction SMILES: C[Si]([C:5]#[C:6][C:7]1[C:15]2[C:11](=[N:12][S:13][N:14]=2)[C:10]([C:16]#[C:17][Si](C)(C)C)=[CH:9][CH:8]=1)(C)C.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>CO>[C:16]([C:10]1[C:11]2[C:15](=[N:14][S:13][N:12]=2)[C:7]([C:6]#[CH:5])=[CH:8][CH:9]=1)#[CH:17]
Reactant: C[Si](C)(C)C#Cc1ccc(C#C[Si](C)(C)C)c2nsnc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CO
Product: C#Cc1ccc(C#C)c2nsnc12
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
4,7-Bis(trimethylsilylethynyl)benzo[c][1,2,5]thiadiazole (0.126 g, 3.83×10−4 mol), K2CO3 (0.214 g, 1.55×10−3 mol), CH2Cl2 (5.0 ml) and MeOH (5.0 ml) were added to a 100-ml round-bottom flask. The reaction mixture was stirred at room temperature for 2.5 h under Ar. The reaction mixture was fdtered and the solvent was evaporated. The residue was chromatographed on short silica gel column with CH2Cl2 as the eluent. Yield=0.0663 g (94% based on 0.126 g of 4,7-bis(trimethylsilylethynyl)benzo[c][1,2,5]thiadiazole). 1H NMR (300 MHz, CDCl3): δ 7.78 (s, 2H, Ph-H), 3.70 (s, 2H, ethynyl-H). CI MS m/z: 184.010 (M+) (calcd 184.010).
Reaction SMILES: [CH2:1]([NH:3]Cl)[CH3:2].N1C=CC=CC=1.[CH3:11][C@@H:12]1[C@:17]([CH2:19][C:20]2[C:26](=[O:27])[CH:25]=[CH:24][C:22](=[O:23])[CH:21]=2)([CH3:18])[C@@H:16]2[CH2:28][CH2:29][CH:30]=[C:31]([CH3:32])[C@@:15]2([CH3:33])[CH2:14][CH2:13]1>C(O)C>[CH3:2][CH2:1][NH:3][C:24]1[C:22](=[O:23])[CH:21]=[C:20]([CH2:19][C@@:17]2([CH3:18])[C@@H:16]3[CH2:28][CH2:29][CH:30]=[C:31]([CH3:32])[C@@:15]3([CH3:33])[CH2:14][CH2:13][C@@H:12]2[CH3:11])[C:26](=[O:27])[CH:25]=1
Reactant: CC1=CCC[C@H]2[C@](C)(CC3=CC(=O)C=CC3=O)[C@@H](C)CC[C@]12C
Reactant: CCNCl
Solvent: CCO
Solvent: c1ccncc1
Product: CCNC1=CC(=O)C(C[C@]2(C)[C@@H](C)CC[C@]3(C)C(C)=CCC[C@@H]23)=CC1=O

Procedure:
Add 2.5 g of ethylamino hydrochloride and 5 ml of pyridine to a solution of 500 mg avarone in 1000 ml of 50% ethanol, and distill off the ethanol under water-jet vacuum after 20 hours. Extract the aqueous residue with dichloromethane and chromatograph the reduced dichloromethane extract using a silica gel column and dichloromethane as extraction agent. In the course of this process 3'-ethylamino and 4'-ethylamino avarone is obtained.
Reaction SMILES: C(O[C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH:6]([CH3:14])[N:5]=1)C.[NH2:15][NH2:16]>>[NH:15]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH:6]([CH3:14])[N:5]=1)[NH2:16]
Reactant: NN
Reactant: CCOC1=NC(C)Cc2ccccc21
Product: CC1Cc2ccccc2C(NN)=N1

Procedure:
The reaction between 1-ethoxy-3-methyl-3,4-dihydroisoquinoline and hydrazine, which produced 1-hydrazino-3-methyl-3,4-dihydroisoquinoline, also produced a dimer, recrystallization of which from methanol-ethanol afforded 1,1'-azinobis(3-methyl-1,2,3,4-tetrahydroisoquinoline) (II: Y=CH3, Y' =Z=Z' =H) (2.2 g., m.p. 168°-171° C.).
Reaction SMILES: C(OC(NCC1(O)CCNC1)=O)(C)(C)C.Cl[CH2:17][CH2:18][C:19]1[C:27]2[C:22](=[CH:23][CH:24]=[C:25]([N:28]3[CH:32]=[N:31][N:30]=[CH:29]3)[CH:26]=2)[NH:21][CH:20]=1.[CH2:33]([NH:40][CH2:41][C:42]1([OH:65])[CH2:47][CH2:46][N:45]([CH2:48]CCC2C3C(=CC=C(N4C=NN=C4)C=3)NC=2)CC1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.N1C2C(=CC=CC=2)C=C1>O.CS(C)=O>[CH2:33]([NH:40][CH2:41][C:42]1([OH:65])[CH2:47][CH2:46][N:45]([CH2:17][CH2:18][C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([N:28]4[CH:32]=[N:31][N:30]=[CH:29]4)[CH:26]=3)[NH:21][CH:20]=2)[CH2:48]1)[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1
Reactant: OC1(CNCc2ccccc2)CCN(CCCc2c[nH]c3ccc(-n4cnnc4)cc23)CC1
Reactant: ClCCc1c[nH]c2ccc(-n3cnnc3)cc12
Agent: CC(C)(C)OC(=O)NCC1(O)CCNC1
Agent: c1ccc2[nH]ccc2c1
Solvent: CS(C)=O
Solvent: O
Product: OC1(CNCc2ccccc2)CCN(CCc2c[nH]c3ccc(-n4cnnc4)cc23)C1

Procedure:
The title compound was prepared from 3-(t-butyloxycarbonylamino) methyl-3-hydroxypyrrolidine and 1-chloro-2-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]ethane (prepared from 2-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]ethanol), followed by deprotection and functionalisation as described for 4-(benzylamino)methyl-4-hydroxy-1-(3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propyl)piperidine. mp>56° C. MS, ES+, m/z=417 for (M+H)+ ; δ (360 MHz, D6 -DMSO) 1.60-1.68 (1H, m, CH), 1.80-1.88 (1H, m, CH), 2.40-2.76 (8H, m, 4×CH2N), 2.84 (2H, t, J=7 Hz, CH2 -indole), 3.72 (2H, s, NHCH2Ar), 4.56 (1H, s, OH), 7.17-7.36 (7H, m, Ar--H), 7.47 (1H, d, J=8 Hz, Ar--H), 7.78 (1H, d, J=2 Hz, Ar--H), 9.01 (2H, s, triazole-H), 11.07 (1H, s, indole-NH). (Found: C, 67.40; H, 6.68; N, 19.54. C24H28N6O.0.5 H2O requires C, 67.74; H, 6.87; N, 19.75%).
Reaction SMILES: [S:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=[C:2]1[O:10][C:11]1[CH:22]=[CH:21][C:14]2[C:15]([CH2:18][CH2:19][OH:20])=[CH:16][O:17][C:13]=2[CH:12]=1.CCN(C(C)C)C(C)C.[O:32](S(C)(=O)=O)[S:33]([CH3:36])(=O)=[O:34]>C(Cl)Cl.CN(C)C1C=CN=CC=1>[S:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=[C:2]1[O:10][C:11]1[CH:22]=[CH:21][C:14]2[C:15]([CH2:18][CH2:19][O:20][S:33]([CH3:36])(=[O:34])=[O:32])=[CH:16][O:17][C:13]=2[CH:12]=1
Reactant: OCCc1coc2cc(Oc3nc4ncccc4s3)ccc12
Reactant: CS(=O)(=O)OS(C)(=O)=O
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CS(=O)(=O)OCCc1coc2cc(Oc3nc4ncccc4s3)ccc12
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 102.5 %

Procedure:
To a solution of 2-[6-(thiazolo[4,5-b]pyridin-2-yloxy)-benzofuran-3-yl]-ethanol (0.4 g, 1.3 mmol) in DCM (13 mL) was added 4-dimethylaminopyridine (16 mg, 0.13 mmol), DIEA (0.27 mL, 1.5 mmol) and Ms2O (0.27 g, 1.5 mmol) and the resulting solution was stirred (rt, 15 min). The reaction mixture was diluted with DCM (40 mL). The organic layer was washed with saturated NH4Cl (2×50 mL), brine (2×50 mL), dried, filtered and concentrated in vacuo to provide the title compound as a clear oil (0.52 g, 100%). MS (ESI): mass calcd. for C17H14N2O5S2, 390.4; m/z found, 391.1 [M+H]+.
Reaction SMILES: CC(O)=O.[NH2:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[C:11]([CH3:16])[C:10]([C:17]([O:19][CH3:20])=[O:18])=[C:9]2[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[CH2:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:29][C:28]1=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[CH2:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:29][CH:28]1[NH:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[C:11]([CH3:16])[C:10]([C:17]([O:19][CH3:20])=[O:18])=[C:9]2[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: O=C1Cc2ccccc2C1
Reactant: COC(=O)c1c(C)nc2ccc(N)cc2c1-c1ccccc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCCl
Product: COC(=O)c1c(C)nc2ccc(NC3Cc4ccccc4C3)cc2c1-c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 72.5 %

Procedure:
A method of Abdel-Magid et al (J. Org. Chem., 61, 3849, 1996) was used: Glacial AcOH (0.2 ml) was added to a solution of the product of Step 2 (0.91 g, 3.31 mmol), 1H-inden-2(3H)-one (0.41 g, 3.31 mmol) and NaBH(OAc)3 (1.05 g, 4.9 mmol) in anhydrous 1,2-dichloroethane (12.5 ml). The resulting mixture was stirred overnight at room temperature under N2 than quenched by addition of 1N NaOH aq (1 ml). This was diluted to 60 ml with Et2O and washed with N2. The organic phase was dried over anhydrous MgSO4, filtered and filtrate evaporated to dryness under reduced pressure. The residue was purified by flash column chromatography (SiO2, CH2Cl2) to give pure product as a yellow solid (0.98 g, 72%). 1H NMR (300 MHz, CDCl3) δ 7.84 (d, J=9.0 Hz, 1H), 7.34-7.49(m, 5H), 7.15-7.18(m, 4H), 7.07(dd, J=1.7, 9.0 Hz, 1H), 6.49(d, J=1.7 Hz, 1H), 4.11-4.18(m, 2H), 3.55(s, 3H), 3.2(dd, J=6.2, 16 Hz, 2H), 2.8(dd, J=6.2, 16 Hz, 2H), 2.68(s, 3H).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:11]=[C:12]([S:14]([F:19])([F:18])([F:17])([F:16])[F:15])[CH:13]=1)[C:7]([O:9][CH3:10])=[O:8])([O-])=O.CC(O)=O.[H][H]>CO.[Pd]>[NH2:1][C:4]1[CH:5]=[C:6]([CH:11]=[C:12]([S:14]([F:19])([F:15])([F:16])([F:17])[F:18])[CH:13]=1)[C:7]([O:9][CH3:10])=[O:8]
Reactant: COC(=O)c1cc([N+](=O)[O-])cc(S(F)(F)(F)(F)F)c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CO
Product: COC(=O)c1cc(N)cc(S(F)(F)(F)(F)F)c1
Yield: 92.3 %

Procedure:
3.0 g of methyl 3-nitro-5-pentafluorosulfanylbenzoate were dissolved in 50 ml of MeOH and 5 ml of HOAc and 200 mg of Pd/C (10%) were added. The mixture was hydrogenated under a standard pressure of hydrogen atmosphere for 20 h, then hydrogenation was effected under 6 bar of hydrogen for a further 2 days. The catalyst was filtered off and the solvent removed under reduced pressure to obtain 2.5 g of an amorphous solid.
Reaction SMILES: [Si:1]([O:8][C@H:9]([C:46]1[CH:51]=[CH:50][C:49]([F:52])=[CH:48][CH:47]=1)[CH2:10][CH2:11][C@@H:12]1[C@@H:15]([C:16]2[CH:21]=[CH:20][C:19](B3OC(C)(C)C(C)(C)O3)=[CH:18][C:17]=2[O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[N:14]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:13]1=[O:45])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:53]([O:56][C@@H:57]1[C@@H:62]([O:63][C:64](=[O:66])[CH3:65])[C@H:61]([O:67][C:68](=[O:70])[CH3:69])[C@@H:60]([CH2:71][O:72][C:73](=[O:75])[CH3:74])[O:59][C@H:58]1[C:76]1[CH:81]=[CH:80][CH:79]=[C:78](Br)[CH:77]=1)(=[O:55])[CH3:54].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(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>[C:53]([O:56][C@@H:57]1[C@@H:62]([O:63][C:64](=[O:66])[CH3:65])[C@H:61]([O:67][C:68](=[O:70])[CH3:69])[C@@H:60]([CH2:71][O:72][C:73](=[O:75])[CH3:74])[O:59][C@H:58]1[C:76]1[CH:77]=[C:78]([C:19]2[CH:20]=[CH:21][C:16]([C@@H:15]3[C@@H:12]([CH2:11][CH2:10][C@H:9]([O:8][Si:1]([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2])[C:46]4[CH:51]=[CH:50][C:49]([F:52])=[CH:48][CH:47]=4)[C:13](=[O:45])[N:14]3[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[C:17]([O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:33])[CH3:34])[CH:18]=2)[CH:79]=[CH:80][CH:81]=1)(=[O:55])[CH3:54]
Reactant: CC(=O)OC[C@H]1O[C@@H](c2cccc(Br)c2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: CC1(C)OB(c2ccc([C@@H]3[C@@H](CC[C@H](O[Si](C)(C)C(C)(C)C)c4ccc(F)cc4)C(=O)N3c3ccccc3)c(O[Si](C)(C)C(C)(C)C)c2)OC1(C)C
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: [K+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: CC(=O)OC[C@H]1O[C@@H](c2cccc(-c3ccc([C@@H]4[C@@H](CC[C@H](O[Si](C)(C)C(C)(C)C)c5ccc(F)cc5)C(=O)N4c4ccccc4)c(O[Si](C)(C)C(C)(C)C)c3)c2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 25 °C
Yield: 27 %

Procedure:
The resulting brown oil which is (3R,4S)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-4-[2-{[tert-butyl(dimethyl)silyl]oxy}-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-phenylazetidin-2-one was dissolved with (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-(3-bromophenyl)-D-glucitol in 4.0 mL of toluene and 0.5 mL of ethanol. 0.150 mL of 4 N potassium carbonate was added followed by 7 mg of tetrakis(triphenylphosphine)palladium(0). The entire reaction was degassed three times with argon then heated to reflux for 1.5 h. After this time the reaction was cooled to room temperature and diluted with 25 mL of water and extracted with 1:1 hexane-ethyl acetate (3×75 mL). The organic layers were combine, dried over sodium sulfate, filtered, concentrated and purified by column chromatography (12 g silica gel, 5% to 95% ethyl acetate-hexane) to afford 41.6 mg (27%) of (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-(3′-{[tert butyl(dimethyl)silyl]oxy}-4′-{(2S,3R)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-4-oxo-1-phenylazetidin-2-yl}biphenyl-3-yl)-D-glucitol as a clear oil.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([NH:11][C:12](=[O:22])[O:13][C@H:14]3[CH:19]4[CH2:20][CH2:21][N:16]([CH2:17][CH2:18]4)[CH2:15]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[F:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1B(O)O>CC([O-])=O.CC([O-])=O.[Pd+2]>[N:16]12[CH2:21][CH2:20][CH:19]([CH2:18][CH2:17]1)[C@H:14]([O:13][C:12](=[O:22])[NH:11][C:8]1([C:5]3[CH:6]=[CH:7][C:2]([C:27]4[CH:26]=[CH:25][C:24]([F:23])=[CH:29][C:28]=4[F:30])=[CH:3][CH:4]=3)[CH2:10][CH2:9]1)[CH2:15]2
Reactant: OB(O)c1ccc(F)cc1F
Reactant: O=C(NC1(c2ccc(Br)cc2)CC1)O[C@@H]1CN2CCC1CC2
Agent: [Pd+2]
Agent: CC(=O)[O-]
Product: O=C(NC1(c2ccc(-c3ccc(F)cc3F)cc2)CC1)O[C@@H]1CN2CCC1CC2
Yield: 22.8 %

Procedure:
Using general procedure E, (S)-quinuclidin-3-yl 1-(4-bromophenyl)cyclopropylcarbamate (0.446 g, 1.22 mmol), 2,4-difluorophenyl boronic acid (0.386 g, 2.44 mmol) and Pd(OAc)2 (0.015 g, 0.067 mmol) gave the title compound as a tan solid (0.111 g, 23%). 1H NMR (CDCl3) δ 7.43 (dd, J=8.4, 1.6 Hz, 2H), 7.40-7.33 (m, 1H), 7.31 (d, J=7.7 Hz, 2H), 6.99-6.81 (m, 2H), 5.54 (d, J=48.0 Hz, 1H), 4.82-4.65 (m, 1H), 3.30-3.07 (m, 1H), 2.98-2.44 (m, 5H), 1.97 (d, J=32.7 Hz, 1H), 1.83 (d, J=10.3 Hz, 1H), 1.64 (s, 1H), 1.52 (s, 1H), 1.39 (s, 1H), 1.31 (d, J=6.8 Hz, 4H) ppm. 13C NMR major rotomer (CDCl3) δ 162.2 (dd, J=12.8, 249.1 Hz), 159.8 (dd, J=11.8, 251.0 Hz), 156.9, 156.0, 142.6, 133.1, 131.3 (m), 128.9, 125.6, 124.9, 111.5 (dd, J=3.9, 21.2 Hz) 104.4 (dd, J=25.2, 29.4 Hz), 72.1, 71.6, 55.7, 47.4, 46.5, 35.7, 35.3, 25.5, 24.6, 24.4, 19.5, 18.1 ppm. Purity: LCMS>99.3% (214 nm & 254 nm); retention time 0.90 min; (M+1) 399.0
Reaction SMILES: [C:1]1([C:7]#[C:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][O:15]C2CCCCO2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1.COCCOCCOC>[C:1]1(/[CH:7]=[CH:8]/[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][OH:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C(#Cc1ccccc1)CCCCCCOC1CCCCO1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: COCCOCCOC
Product: OCCCCCC/C=C/c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 87.6 %

Procedure:
To 150 ml of a mixture of tetrahydrofuran-diglyme (2:15) were added 12 g of 1-phenyl-8-(2-tetrahydropyranyloxy)-1-octyne and 3.35 g of lithium aluminum hydride. The mixture was heated and tetrahydrofuran was distilled off until the inner temperature became 120° C. After heating under reflux at the same temperature for 1 hour, the mixture was ice-cooled. Ice was added to the mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% hydrochloric acid, water, sodium hydrogen carbonate solution, saline water in the order mentioned, dried, and then the solvent was distilled off. The residue was dissolved in 250 ml of methanol and 1.1 g of p-toluenesulfonic acid was added thereto. The mixture was stirred at room temperature for 1 hour and 2 ml of triethylamine was added to the mixture. Methanol was distilled off and the residue was purified by silica gel column chromatorgraphy (solvent: hexane-ethyl acetate=3:1) to give 7.5 g of (E)-8-phenyl-7-octen- 1-ol as an oily substance.