Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]([OH:10])([C:5]#[C:6][C:7]([CH3:9])=[CH2:8])[CH:3]=[CH2:4].C(N(CC)CC)C.CN(C1C=CC=CN=1)C.[CH:27]([SiH:30]([CH:32]([CH3:34])[CH3:33])Cl)([CH3:29])[CH3:28]>>[CH3:1][C:2]([O:10][SiH:30]([CH:32]([CH3:34])[CH3:33])[CH:27]([CH3:29])[CH3:28])([C:5]#[C:6][C:7]([CH3:9])=[CH2:8])[CH:3]=[CH2:4]
Reactant: C=CC(C)(O)C#CC(=C)C
Reactant: CC(C)[SiH](Cl)C(C)C
Agent: CN(C)c1ccccn1
Solvent: CCN(CC)CC
Product: C=CC(C)(C#CC(=C)C)O[SiH](C(C)C)C(C)C

Procedure:
3,6-Dimethylhepta-1,6-dien-4-yn-3-ol (6d) (1.523 g, 11.18 mmol), triethylamine (1.2 g, 11.86 mmol), dimethylaminopyridine (0.153 g, 1.275 mmol) and diisopropylchlorosilane (1.657 g, 10.99 mmol) were used according to the general procedure. The brown, clear crude product was purified by column chromatography to produce the title compound (7d) as a clear colorless solution (2.641 g, 10.54 mmol, 96.3%): Rf 0.91 (hexanes/Et2O, 4:1); 1H NMR (300 MHz, CDCl3) δ 5.92 (dd, J=17.0, 10.2 Hz, 1H, H-2), 5.44 (d, J=17.0 Hz, 1H, H-1), 5.28 (bs, 1H, H-7), 5.22 (p, J=1.5 Hz, 1H, H-7), 5.07 (d, J=10.2 Hz, 1H, H-1), 4.36 (s, 1H, H-10), 1.89 (s, 3H, H-8), 1.56 (s, 3H, H-9), 0.95-1.14 (m, 14H, H-11, 12); 13C NMR (300 MHz, CDCl3) δ 142.6 (C-2), 126.4 (C-6), 121.6 (C-7), 112.8 (C-1), 89.9 (C-4), 86.9 (C-5), 70.5 (C-3), 31.6 (C-9), 23.3 (C-8), 17.6 (C-12), 17.55 (C-12), 17.53 (C-12), 12.7 (C-11), 12.6 (C-11); HRMS calcd for C15H26OSi (M+) 250.1753. found 250.1744.
Reaction SMILES: [CH3:1][C:2]([C:9]1[NH:10][C:11]2[C:16]([CH:17]=1)=[CH:15][C:14]([N+:18]([O-:20])=[O:19])=[CH:13][CH:12]=2)([CH3:8])[C:3]([O:5]CC)=[O:4].O[Li].O.Cl>C1COCC1.O>[CH3:8][C:2]([C:9]1[NH:10][C:11]2[C:16]([CH:17]=1)=[CH:15][C:14]([N+:18]([O-:20])=[O:19])=[CH:13][CH:12]=2)([CH3:1])[C:3]([OH:5])=[O:4]
Reactant: CCOC(=O)C(C)(C)c1cc2cc([N+](=O)[O-])ccc2[nH]1
Agent: Cl
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C(=O)O)c1cc2cc([N+](=O)[O-])ccc2[nH]1
Temperature: 50 °C
Reaction time: 3 h
Yield: 100.1 %

Procedure:
Ethyl 2-methyl-2-(5-nitro-1H-indol-2-yl)propanoate (4.60 g, 16.7 mmol) was dissolved in THF/water (2:1, 30 mL). LiOH.H2O (1.40 g, 33.3 mmol) was added and the mixture was stirred at 50° C. for 3 h. The mixture was made acidic by the careful addition of 3N HCl. The product was extracted with ethylacetate and the combined organic phases were washed with brine and dried over magnesium sulfate to give 2-methyl-2-(5-nitro-1H-indol-2-yl)propanoic acid (4.15 g, 99%).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:11]([O:12][CH3:13])=[CH:10][C:9]([C:14](=[O:20])/[CH:15]=[CH:16]/N(C)C)=[C:8]([N+:21]([O-])=O)[CH:7]=1>C(O)(=O)C.[Fe]>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:9]([C:14](=[O:20])[CH:15]=[CH:16][NH:21]2)=[CH:10][C:11]=1[O:12][CH3:13]
Reactant: COc1cc(C(=O)/C=C/N(C)C)c([N+](=O)[O-])cc1OCCCCl
Agent: [Fe]
Solvent: CC(=O)O
Product: COc1cc2c(=O)cc[nH]c2cc1OCCCCl
Temperature: 40 °C
Reaction time: 2 h
Yield: 67.1 %

Procedure:
Intermediate IV (150 g, 0.44 mol) was added to glacial acetic acid (8 v/w, 1200 mL). The mixture was warmed up to 40° C. After Intermediate IV was dissolved completely, iron powder (123.1 g, 2.20 mol) was slowly added in batch. The mixture was warmed up to 80° C. and reacted under mechanical stirring for 2 h. After completion of the reaction, the reaction solution was filtered by suction when it is still hot. The filtrate was collected. After cooling the filtrate, a great deal of solid separated out and was filtered by suction to produce a lutescens solid. The filtered cake was dissolved in glacial acetic acid. The mixture was stirred at 80° C. for about 30 min, and was filtered by suction again when it is still hot. The filtrate was collected. After cooling the filtrate, a solid separated out and was filtered by suction to produce a lutescens solid. The solids were combined, and washed with water several times until the filtrate became neutral. The filtered cake was dried to produce a pale yellow solid (79 g) in a yield of 65%.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[OH-].[Na+].[CH2:11](Br)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].O>C(O)C>[CH2:11]([O:8][C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=1)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CCCCCCCCCCBr
Reactant: Oc1ccc(Br)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CCCCCCCCCCOc1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 57.5 %

Procedure:
In 200 g of ethanol were dissolved 86.5 g (0.5 mol) of 4-bromophenol and 22 g (0.55 mol) of sodium hydroxide. To the solution at 70° C., 121.8 g (0.55 mol) of n-decyl bromide was added dropwise. The solution was allowed to ripen for 4 hours and cooled to room temperature, after which 120 g of water was added. The oily matter was separated therefrom and concentrated by a rotary evaporator, followed by vacuum distillation (boiling point 143-145° C./0.5 Torr), yielding 90 g of 4-n-decyloxyphenyl bromide.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([NH:21][S:22]([CH3:25])(=[O:24])=[O:23])[C:18]([O:26][CH:27]([CH3:29])[CH3:28])=[CH:17][C:11]=3[C:12]=2[C:13]([O:15][CH3:16])=[O:14])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:36][O:37][C:38]1[CH:45]=[CH:44][C:41]([CH2:42]Br)=[CH:40][CH:39]=1>CN(C)C=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH2:42][C:41]4[CH:44]=[CH:45][C:38]([O:37][CH3:36])=[CH:39][CH:40]=4)[S:22]([CH3:25])(=[O:23])=[O:24])[C:18]([O:26][CH:27]([CH3:29])[CH3:28])=[CH:17][C:11]=3[C:12]=2[C:13]([O:15][CH3:16])=[O:14])=[CH:4][CH:3]=1
Reactant: COc1ccc(CBr)cc1
Reactant: COC(=O)c1c(-c2ccc(F)cc2)oc2cc(NS(C)(=O)=O)c(OC(C)C)cc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(Cc3ccc(OC)cc3)S(C)(=O)=O)c(OC(C)C)cc12
Temperature: 70 °C

Procedure:
Methyl 2-(4-fluorophenyl)-5-isopropoxy-6-(methylsulfonamido)benzofuran-3-carboxylate (0.65 g, 1.5 mmol) was dissolved in 10 mL N,N-dimethylformamide and treated sequentially with potassium carbonate (0.26 g, 1.85 mmol) and 4-methoxybenzyl bromide (0.27 mL, 1.85 mmol). The slurry was stirred and heated at 70° C. for 3 hours. The reaction mixture was concentrated in vacuo to a pasty solid. The residue was dissolved in 100 mL ethyl acetate, washed with 1 N aqueous H3PO4 and 10% aqueous sodium chloride, dried over anhydrous sodium sulfate(s), filtered and the solvent was removed in vacuo leaving a yellow oil, 0.8 g.
Reaction SMILES: [C:1](O)(=[O:3])[CH3:2].[C:5]([C:8]1[CH:21]=[CH:20][C:11]([O:12][CH2:13][CH2:14][N:15]2[CH:19]=[CH:18][N:17]=[CH:16]2)=[CH:10][CH:9]=1)(=[O:7])[NH2:6]>CN(C)C=O>[C:1]([NH:6][C:5]([C:8]1[CH:9]=[CH:10][C:11]([O:12][CH2:13][CH2:14][N:15]2[CH:19]=[CH:18][N:17]=[CH:16]2)=[CH:20][CH:21]=1)=[O:7])(=[O:3])[CH3:2]
Reactant: CC(=O)O
Reactant: NC(=O)c1ccc(OCCn2ccnc2)cc1
Solvent: CN(C)C=O
Product: CC(=O)NC(=O)c1ccc(OCCn2ccnc2)cc1
Reaction time: 0.08 h
Yield: 16.6 %

Procedure:
N,N'-Carbonyldiimidazole (4.9 g) was dissolved in dry N,N-dimethylformamide (10 ml) and acetic acid (1.8 g) was added. The solution was stirred for 5 minutes and then 1-[2-(4-carbamoylphenoxy)ethyl]imidazole (4.6 g) was added. The solution was heated under reflux for 3 hours and then evaporated. The residue was treated with aqueous sodium bicarbonate and the mixture was extracted several times with ethyl acetate. The combined ethyl acetate extracts were washed with water, dried (Na2SO4) and evaporated to give an oil which was chromatographed on silica gel. Elution with chloroform gave some impurity. Further elution with chloroform/methanol (50:1) gave a solid which was crystallised from 2-butanone to give 1-[2-(4-acetylcarbamoylphenoxy)ethyl]imidazole (0.9 g), m.p. 164°-165° C. Found: C, 61.28; H, 5.54; N, 15.51. C14H15N3O3 requires: C, 61.53; H, 5.53; N, 15.38%.
Reaction SMILES: [NH2:1][C:2](=[O:20])[CH:3]([NH:9]C(=O)OCC1C=CC=CC=1)[CH2:4][C:5]([F:8])([F:7])[F:6].[H][H]>CO.[Pd]>[NH2:9][CH:3]([CH2:4][C:5]([F:8])([F:7])[F:6])[C:2]([NH2:1])=[O:20]
Reactant: [H][H]
Reactant: NC(=O)C(CC(F)(F)F)NC(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CO
Product: NC(=O)C(N)CC(F)(F)F
Yield: 93.5 %

Procedure:
A solution of benzyl 1-amino-4,4,4-trifluoro-1-oxobutan-2-ylcarbamate (175 mg, 0.603 mmol) and Pd—C (10%, 55 mg) in MeOH (5 mL) was hydrogenated under balloon hydrogen for 2 h. The mixture was filtered through celite. The filtrate was concentrated in vacuo to give 2-amino-4,4,4-trifluorobutanamide (88 mg).
Reaction SMILES: Cl[C:2]1[N:9]=[C:8]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[NH:13][N:12]=2)[CH:7]=[C:6]([CH3:17])[C:3]=1[C:4]#[N:5].Cl.[Cl:19][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][C:29]=1[F:30])[O:23][CH2:24][CH2:25][NH2:26].C(=O)([O-])O.[Na+].CS(C)=O>O>[Cl:19][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][C:29]=1[F:30])[O:23][CH2:24][CH2:25][NH:26][C:2]1[N:9]=[C:8]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[NH:13][N:12]=2)[CH:7]=[C:6]([CH3:17])[C:3]=1[C:4]#[N:5]
Reactant: Cc1cc(Nc2cc(C)c(C#N)c(Cl)n2)n[nH]1
Reactant: NCCOc1ccc(F)c(Cl)c1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: Cc1cc(Nc2cc(C)c(C#N)c(NCCOc3ccc(F)c(Cl)c3)n2)n[nH]1
Temperature: 100 °C
Reaction time: 27 h
Yield: 5.3 %

Procedure:
Compound A (300 mg, 1.22 mmol), 2-(3-chloro-4-fluorophenoxy)ethylamine hydrochloride (824 mg) and sodium hydrogencarbonate (1.02 g) were added to DMSO (10 ml), and the mixture was stirred at 100° C. for 27 hr. After stirring, the reaction mixture was added to cold water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and concentrated, and the residue was washed by suspending in ethyl acetate to give the object compound of 2-(2-(3-chloro-4-fluorophenoxy)ethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)-4-methylnicotinonitrile (26 mg).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][C:3]([C:6]2[S:7][CH:8]=[CH:9][N:10]=2)=[CH:2]1.N1C2[C:15](=[CH:16][CH:17]=[C:18]3[C:23]=2[N:22]=[CH:21][CH:20]=[CH:19]3)[CH:14]=[CH:13][CH:12]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[Cu]I>[S:7]1[CH:8]=[CH:9][N:10]=[C:6]1[C:3]1[CH:4]=[CH:5][N:1]([C:15]2[CH:16]=[C:17]([C:18]3[CH:23]=[N:22][CH:21]=[CH:20][CH:19]=3)[CH:12]=[CH:13][CH:14]=2)[CH:2]=1
Reactant: c1csc(-c2cc[nH]c2)n1
Reactant: c1cnc2c(c1)ccc1cccnc12
Agent: [Cu]I
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: c1cncc(-c2cccc(-n3ccc(-c4nccs4)c3)c2)c1

Procedure:
A solution of 2-(1H-pyrrol-3-yl)-1,3-thiazole (0.100 g, 0.67 mmol) 3-(3-iodophenyl)pyridine (0.224 g, 0.8 mmol), copper(I) iodide (0.038 g, 0.2 mmol), 1,10-phenanthroline (0.360 g, 2 mmol), potassium phosphate (0.440 g, 2.0 mmol) in dioxane (2 mL) was heated at 220° C. for ½ hr under microwave irradiation. The reaction mixture was quenched with H2O (30 mL), then extracted with EtOAc (3×30 mL) and the combined organic extracts washed with brine. The organic phase was dried over Na2SO4 and concentrated in vacuo. The crude purified by liquid chromatography on silica gel using an ISCO single channel system (EtOAc 100%) to afford 3-{3-[3-(1,3-thiazol-2-yl)-1H-pyrrol-1-yl]phenyl}pyridine as a slightly yellow oil. The free base in anhydrous diethyl ether was treated with 1.5 equivalent HCl (1M in Ether) to give HCl salt.
Reaction SMILES: Cl[S:2]([C:5]1[CH:6]=[C:7]([CH:41]=[CH:42][CH:43]=1)[C:8]([NH:10][C:11]1[S:12][C:13]2[CH2:40][CH2:39][CH2:38][CH2:37][C:14]=2[C:15]=1[C:16]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][C:27]2[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=2)=[CH:21][CH:20]=1)=[O:17])=[O:9])(=[O:4])=[O:3].Cl.[NH2:45][CH2:46][CH2:47][CH2:48][C:49]([O:51][CH2:52][CH3:53])=[O:50].C(N(CC)CC)C>ClCCl>[CH2:52]([O:51][C:49](=[O:50])[CH2:48][CH2:47][CH2:46][NH:45][S:2]([C:5]1[CH:6]=[C:7]([CH:41]=[CH:42][CH:43]=1)[C:8]([NH:10][C:11]1[S:12][C:13]2[CH2:40][CH2:39][CH2:38][CH2:37][C:14]=2[C:15]=1[C:16]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][C:27]2[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=2)=[CH:21][CH:20]=1)=[O:17])=[O:9])(=[O:4])=[O:3])[CH3:53]
Reactant: COC(=O)c1ccc(CCc2ccc(NC(=O)c3c(NC(=O)c4cccc(S(=O)(=O)Cl)c4)sc4c3CCCC4)cc2)cc1
Reactant: CCOC(=O)CCCN
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)CCCNS(=O)(=O)c1cccc(C(=O)Nc2sc3c(c2C(=O)Nc2ccc(CCc4ccc(C(=O)OC)cc4)cc2)CCCC3)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 64.1 %

Procedure:
A mixture of 600 mg of methyl 4-[2-(4-{[(2-{[3-(chlorosulfonyl)benzoyl]amino}-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}phenyl)ethyl]benzoate, 394 mg of ethyl 4-aminobutyrate hydrochloride, 0.27 mL of triethylamine, and 6.0 mL of dichloromethane was stirred at room temperature for 2 hours. The reaction mixture was purified by silica gel column chromatography (hexane-chloroform) to obtain 442 mg of methyl 4-{2-[4-({[2-({3-[(4-ethoxy-4-oxobutyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoate as a pale yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:6])[CH:4]=[CH2:5].[NH2:7][CH2:8][CH2:9][CH:10]1[CH2:19][CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[O:11]1>CO>[O:11]1[C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:18][CH2:19][CH:10]1[CH2:9][CH2:8][NH:7][CH2:5][CH2:4][C:3]([O:2][CH3:1])=[O:6]
Reactant: C=CC(=O)OC
Reactant: NCCC1CCc2ccccc2O1
Solvent: CO
Product: COC(=O)CCNCCC1CCc2ccccc2O1
Reaction time: 16 h
Yield: 55.3 %

Procedure:
3.01 g (35 mmol) of acrylic acid methyl ester are added at 0°-5°, while stirring, to a solution of 6.2 g (35 mmol) of 2-(2-aminoethyl)chroman in 200 ml of methanol. Stirring is continued for a further 16 hours at 0°-5° and the mixture is then concentrated by evaporation in vacuo. 8.76 g (95.2%) of crude product are obtained and are chromatographed on 250 g of silica gel (0.040-0.063 mm) using ethyl acetate as the eluant. 5.10 g (55.4%) of N-[2-(chroman-2-yl)ethyl]-N-(2-methoxycarbonylethyl)-amine are thus obtained in the form of a yellow oil. The N-[2-(chroman-2-yl)ethyl]-N-(2-methoxycarbonylethyl)-amine hydrochloride produced therefrom using hydrochloric acid in diethyl ether crystallises from methanol/diethyl ether and melts at 152°-153°.
Reaction SMILES: N1C=CC=CC=1.[O:7]([Si:15]([CH3:18])([CH3:17])[CH3:16])S(C(F)(F)F)(=O)=O.[CH2:19]([C:21](O)([CH2:52][CH3:53])[C:22]#[C:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([CH2:49][CH3:50])([C:33]2[CH:38]=[CH:37][C:36]([B:39]3[O:43][C:42]([CH3:45])([CH3:44])[C:41]([CH3:47])([CH3:46])[O:40]3)=[C:35]([CH3:48])[CH:34]=2)[CH2:31][CH3:32])=[CH:26][C:25]=1[CH3:51])[CH3:20].C(=O)(O)[O-].[Na+]>ClCCl>[CH2:31]([C:30]([C:33]1[CH:38]=[CH:37][C:36]([B:39]2[O:40][C:41]([CH3:46])([CH3:47])[C:42]([CH3:45])([CH3:44])[O:43]2)=[C:35]([CH3:48])[CH:34]=1)([C:27]1[CH:28]=[CH:29][C:24]([C:23]#[C:22][C:21]([CH2:19][CH3:20])([O:7][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH2:52][CH3:53])=[C:25]([CH3:51])[CH:26]=1)[CH2:49][CH3:50])[CH3:32]
Reactant: CCC(O)(C#Cc1ccc(C(CC)(CC)c2ccc(B3OC(C)(C)C(C)(C)O3)c(C)c2)cc1C)CC
Reactant: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCC(C#Cc1ccc(C(CC)(CC)c2ccc(B3OC(C)(C)C(C)(C)O3)c(C)c2)cc1C)(CC)O[Si](C)(C)C
Reaction time: 1 h
Yield: 78.7 %

Procedure:
Pyridine (0.116 mL, 1.432 mmol) and trimethylsilyl triflate (0.129 mL, 0.716 mmol) were added to a solution of 3-ethyl-1-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-1-pentyn-3-ol (Example 125-(2); 175 mg, 0.358 mmol) in dichloromethane (5 mL) at 0° C., and the mixture was stirred for one hour. The reaction mixture was then poured into a saturated aqueous sodium bicarbonate solution, followed by extraction with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=100:0 to 70:30) to give the target compound as a colorless oil (158 mg, 79%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([O:11][Si:12]([CH2:17][CH3:18])([CH2:15][CH3:16])[CH2:13][CH3:14])[CH2:9]I)=[CH:4][C:3]=1[NH:19][S:20]([CH3:23])(=[O:22])=[O:21].[CH2:24]([NH:31][CH2:32][CH2:33][OH:34])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C1(C)C=CC=CC=1>CCOCC>[CH2:24]([N:31]([CH2:32][CH2:33][OH:34])[CH2:9][C@@H:8]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])[CH:4]=1)[O:11][Si:12]([CH2:17][CH3:18])([CH2:15][CH3:16])[CH2:13][CH3:14])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: OCCNCc1ccccc1
Reactant: CC[Si](CC)(CC)O[C@@H](CI)c1ccc(Cl)c(NS(C)(=O)=O)c1
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: CC[Si](CC)(CC)O[C@@H](CN(CCO)Cc1ccccc1)c1ccc(Cl)c(NS(C)(=O)=O)c1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
(R)—N-(2-Chloro-5-(2-iodo-1-(triethylsilyloxy)ethyl)phenyl)methanesulfonamide (3 g) and 2-(benzylamino)ethanol (6 mL; Tokyo Chemical Industry, Co., Ltd.) were admixed with each other and stirred overnight at 100° C. The reaction solution was cooled to room temperature, added with toluene and Et2O, and then washed with water three times. The organic layer was dried over magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (“COLUMN-B”; n-hexane:ethyl acetate=84:16→64:36) to obtain the title compound (2.1894 g).
Reaction SMILES: [C:1]([O:9][C@H:10]1[C@@H:15]([O:16][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@H:14]2[CH2:25][C@@H:11]1[C:12](=[O:33])[N:13]2[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>CO>[C:1]([O:9][C@@H:10]1[C@@H:11]([CH2:12][OH:33])[CH2:25][C@@H:14]([NH:13][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@@H:15]1[O:16][C:17](=[O:24])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1C(=O)[C@H]2C[C@@H]1[C@H](OC(=O)c1ccccc1)[C@@H]2OC(=O)c1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(C)(C)OC(=O)N[C@@H]1C[C@H](CO)[C@@H](OC(=O)c2ccccc2)[C@H]1OC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 71.3 %

Procedure:
To a solution of tert-butyl (1R,4S,5R,6S)-5,6-bis(benzoyloxy)-3-oxo-2-azabicyclo[2.2.1]heptane-2-carboxylate (2.09 g, 4.62 mmol) in MeOH (60.0 mL) was added sodium borohydride (700. mg, 18.5 mmol) at 0° C. and the reaction was allowed to warm to rt. After 1.5 h, the mixture was quenched with 1.00 N HCl solution (20.0 mL), and concentrated in vacuo. The aqueous layer was extracted with DCM (3×50 mL) and the combined organic layers were washed with H2O (100. mL), dried over MgSO4 and concentrated in vacuo. The residue was purified via silica gel chromatography eluting with a gradient of 20 to 60% EtOAc in hexanes to afford the title compound (1.50 g, 80%). LC/MS: Rt=1.95 min, ES+ 456 (FA standard).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[NH:14][CH:15]([CH3:26])[CH2:16][C:17]([CH3:25])([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH3:18])=[CH:4][CH:3]=1.[CH2:27]([O:29][C:30](=[O:50])[CH2:31][C:32]1([C:35]2[CH:40]=[CH:39][C:38](B3OC(C)(C)C(C)(C)O3)=[CH:37][CH:36]=2)[CH2:34][CH2:33]1)[CH3:28]>>[CH2:27]([O:29][C:30](=[O:50])[CH2:31][C:32]1([C:35]2[CH:36]=[CH:37][C:38]([C:2]3[CH:3]=[CH:4][C:5]([C:8]4[O:12][N:11]=[C:10]([CH3:13])[C:9]=4[NH:14][CH:15]([CH3:26])[CH2:16][C:17]([CH3:25])([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH3:18])=[CH:6][CH:7]=3)=[CH:39][CH:40]=2)[CH2:33][CH2:34]1)[CH3:28]
Reactant: Cc1noc(-c2ccc(Br)cc2)c1NC(C)CC(C)(C)c1ccccc1
Reactant: CCOC(=O)CC1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Product: CCOC(=O)CC1(c2ccc(-c3ccc(-c4onc(C)c4NC(C)CC(C)(C)c4ccccc4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 1, Step 7, using [5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-(1,3-dimethyl-3-phenyl-butyl)-amine and {1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropyl}-acetic acid ethyl ester.
Reaction SMILES: [Cl:1][C:2]1[C:3](F)=[C:4]([F:26])[CH:5]=[C:6]2[C:11]=1[N:10]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([NH:19][CH3:20])[C:13]=1[F:21])[CH:9]=[C:8]([C:22]([OH:24])=[O:23])[C:7]2=[O:25].CN.[N:30]1C=CC=C[CH:31]=1>C(O)C>[Cl:1][C:2]1[C:3]([NH:30][CH3:31])=[C:4]([F:26])[CH:5]=[C:6]2[C:11]=1[N:10]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([NH:19][CH3:20])[C:13]=1[F:21])[CH:9]=[C:8]([C:22]([OH:24])=[O:23])[C:7]2=[O:25]
Reactant: CNc1c(F)ccc(-n2cc(C(=O)O)c(=O)c3cc(F)c(F)c(Cl)c32)c1F
Reactant: c1ccncc1
Agent: CN
Solvent: CCO
Product: CNc1c(F)ccc(-n2cc(C(=O)O)c(=O)c3cc(F)c(NC)c(Cl)c32)c1F
Temperature: 25 °C
Reaction time: 3 h
Yield: 156.5 %

Procedure:
8-Chloro-6,7-difluoro-1-(2,4-difluoro-3-methylaminophenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (120 mg) and a 40% aqueous solution (120 mg) of methylamine were added to pyridine (500 mg), and the mixture was stirred at room temperature for 3 hours. Ethanol (1 ml) was added to the reaction mixture, and the resultant mixture was stirred for 2 hours. Deposits were collected by filtration and washed successively with ethanol and diisopropyl ether to obtain the title compound (193 mg) as a colorless powder.
Reaction SMILES: [N:1]([CH2:4][C:5]1[C:17]([C:18]#[N:19])=[CH:16][C:8]([C:9]([O:11]C(C)(C)C)=[O:10])=[C:7]([O:20][CH2:21][CH3:22])[CH:6]=1)=[N+:2]=[N-:3]>ClCCl.FC(F)(F)C(O)=O>[N:1]([CH2:4][C:5]1[C:17]([C:18]#[N:19])=[CH:16][C:8]([C:9]([OH:11])=[O:10])=[C:7]([O:20][CH2:21][CH3:22])[CH:6]=1)=[N+:2]=[N-:3]
Reactant: CCOc1cc(CN=[N+]=[N-])c(C#N)cc1C(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCOc1cc(CN=[N+]=[N-])c(C#N)cc1C(=O)O
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
After dissolving tert-butyl 4-(azidomethyl)-5-cyano-2-ethoxybenzoate (1.923 g) in dichloromethane (12 ml), trifluoroacetic acid (3 ml) was added while cooling on ice. The mixture was stirred at room temperature for 20 minutes and concentrated. The title compound was obtained as light red crystals.
Reaction SMILES: [C:1]([CH2:5][C:6]([CH2:9][C:10]([F:13])([F:12])[F:11])(Cl)Cl)([F:4])([F:3])[F:2].Cl.[OH:15]S(O)(=O)=O>>[C:1]([CH2:5][C:6]([CH2:9][C:10]([F:13])([F:12])[F:11])=[O:15])([F:4])([F:3])[F:2]
Reactant: O=S(=O)(O)O
Reactant: FC(F)(F)CC(Cl)(Cl)CC(F)(F)F
Agent: Cl
Product: O=C(CC(F)(F)F)CC(F)(F)F
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 56 %

Procedure:
A mixture of 20 mL 100% H2SO4, 10.6 g (0.049 mol) HgO; and 12.0 g (0.048 mol) CF3CH2CCl2CH2CF3 was shaken periodically over 45 min, during which time a thick, nearly white paste resulted. An exothermic reaction also occurred after approximately 10 min and subsided after about 0.5 h. The cooled reaction mixture was added to 75 g ice and 25 mL concentrated HCl. The lower liquid phase was separated and the aqueous layer was extracted with 3×35 mL ether. The combined organic extracts (including the original organic layer) were washed with 10 mL water, dried with Na2SO4 and distilled. Five and three tenths g (56% yield) of 97% pure CF3CH2C(O)CH2CF3 were obtained (boiling point 122-123° C.). 1H NMR: 3.4 (q, J=10.2 Hz). 19F NMR: -63.0 (t, J=10.2 Hz) ppm. IR: 1746 (C=O) cmc-1. MS: 194 (3.4), 111 (100), 91 (17.5), 83 (21.8), 69 (11.9).