Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CO[C:3](=[O:15])[NH:4][S:5]([C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1)(=[O:7])=[O:6].N1C=CC=CC=1.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:33]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:32][NH:31][N:30]=2)=[CH:25][CH:24]=1>O1CCOCC1>[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([C:29]2[CH:33]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH2:32][N:31]([C:3]([NH:4][S:5]([C:8]3[CH:9]=[CH:10][C:11]([Cl:14])=[CH:12][CH:13]=3)(=[O:6])=[O:7])=[O:15])[N:30]=2)=[CH:27][CH:28]=1
Reactant: Clc1ccc(C2=NNCC2c2ccccc2)cc1
Reactant: COC(=O)NS(=O)(=O)c1ccc(Cl)cc1
Solvent: C1COCCO1
Solvent: c1ccncc1
Product: O=C(NS(=O)(=O)c1ccc(Cl)cc1)N1CC(c2ccccc2)C(c2ccc(Cl)cc2)=N1
Temperature: 100 °C
Reaction time: 4 h
Yield: 83.4 %

Procedure:
Part A: To a solution of N-((4-chlorophenyl)sulfonyl)carbamic acid methyl ester (CAS: 34543-04-9) (2.99 gram, 12.0 mmol) and pyridine (4 ml) in 1,4-dioxane (20 ml) was added 3-(4-chlorophenyl)-4,5-dihydro-4-phenyl-1H-pyrazole (3.39 gram, 13.2 mmol) and the resulting mixture was stirred for 4 hours at 100° C. After concentration in vacuo the residue was dissolved in dichloromethane, successively washed with water, 1 N HCl and water, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to a volume of 20 ml. Methyl-tert-butyl ether (60 ml) was added and the resulting solution was concentrated to a volume of 20 ml. The formed crystals were collected by filtration and recrystallised from methyl-tert-butyl ether to give 3-(4-chlorophenyl)-N-((4-chlorophenyl)sulfonyl)-4,5-dihydro-4-phenyl-1H-pyrazole-1-carboxamide (4.75 gram, 76% yield). Melting point: 211-214° C.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([CH:15]=[C:16]([N+:18]([O-:20])=[O:19])[CH:17]=1)[C:8]([NH:10][CH2:11][C:12]([OH:14])=O)=[O:9])=[O:4].C(Cl)(=O)O.[CH3:25][NH2:26]>O1CCCC1.C(N(CC)CC)C>[CH3:25][NH:26][C:12](=[O:14])[CH2:11][NH:10][C:8](=[O:9])[C:7]1[CH:15]=[C:16]([N+:18]([O-:20])=[O:19])[CH:17]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:6]=1
Reactant: COC(=O)c1cc(C(=O)NCC(=O)O)cc([N+](=O)[O-])c1
Reactant: CN
Agent: O=C(O)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CNC(=O)CNC(=O)c1cc(C(=O)OC)cc([N+](=O)[O-])c1
Reaction time: 0.17 h

Procedure:
Process 2: 8.5 g. (0.03 mole) of N-(3-metoxycarbonyl-5-nitrobenzoyl-glycine (VIa) dissolved in 130 ml. of absolute tetrahydrofuran, is cooled to -15° C., after the addition of 4.2 ml. of triethylamine, and mixed under agitation with 3 ml. of the ethyl ester of chlorocarbonic acid. The reaction mixture is agitated for about 10 minutes at -10° to -5° C., and a solution of 2.8 ml. of methylamine in 20 ml. of absolute tetrahydrofuran, cooled to -15° C., is gradually added thereto dropwise under agitation. Then, the mixture is stirred for another 30 minutes at -15° C. and subsequently overnight at room temperature; the triethylamine hydrochloride is filtered off, the filtrate concentrated under vacuum, and the residue recrystallized from acetonitrile; yield 4.6 g. m.p. 173°-174° C.
Reaction SMILES: [NH2:1][C:2]1[C:3]([S:9][C:10]([CH3:19])([CH3:18])[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.O=[C:21]1[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]1.FC(F)(F)C(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl>[C:14]([O:13][C:11](=[O:12])[C:10]([S:9][C:3]1[C:2]([NH:1][CH:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)=[CH:7][C:6]([Cl:8])=[CH:5][N:4]=1)([CH3:19])[CH3:18])([CH3:17])([CH3:16])[CH3:15]
Reactant: CC(C)(C)OC(=O)C(C)(C)Sc1ncc(Cl)cc1N
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCCl
Product: CC(C)(C)OC(=O)N1CCC(Nc2cc(Cl)cnc2SC(C)(C)C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 89.2 %

Procedure:
To a 1,2-dichloroethane solution (2 ml) of tert-butyl 2-[(3-amino-5-chloropyridin-2-yl)thio]-2-methylpropanoate (334 mg) and tert-butyl 4-oxopiperidine-1-carboxylate (272 mg) was added at room temperature trifluoroacetic acid (0.084 ml), followed by stirring for 15 minutes. Sodium triacetoxyborohydride (356 mg) was added to the reaction solution, and stirred at 45° C. overnight. Cooling to room temperature, tert-butyl 4-oxopiperidine-1-carboxylate (264 mg) and trifluoroacetic acid (0.084 ml) were added. After the reaction solution was stirred for 10 minutes, sodium triacetoxyborohydride (345 mg) was added, and further stirred at 45° C. overnight. After the reaction solution was cooled to room temperature, 1 N aqueous sodium hydroxide solution was added, and extracted with dichloromethane. The collected organic layer was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford tert-butyl 4-({2-[(2-tert-butoxy-1,1-dimethyl-2-oxoethyl)thio]-5-chloropyridin-3-yl}amino)piperidine-1-carboxylate (478 mg).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4](F)[C:3]=1[N+:10]([O-:12])=[O:11].[NH3:13]>O1CCCC1.CO>[F:1][C:2]1[C:3]([N+:10]([O-:12])=[O:11])=[C:4]([CH:5]=[C:6]([F:8])[CH:7]=1)[NH2:13]
Reactant: N
Reactant: O=[N+]([O-])c1c(F)cc(F)cc1F
Solvent: C1CCOC1
Solvent: CO
Product: Nc1cc(F)cc(F)c1[N+](=O)[O-]
Reaction time: 8 h

Procedure:
A solution of the 1,3,5-trifluoro-2-nitrobenzene (7.08 g, 39.98 mmol) in tetrahydrofuran (50 mL) was stirred at 0 degrees Centigrade while a solution of 7N ammonia in methanol (23 mL) was added. The reaction turned deep red and was stirred overnight in a sealed tube. The mixture was filtered to remove NH4F and the solvent removed to give a red-orange solid which was purified by silica gel chromatography using 2:1 hexanes/ethyl acetate to give 6.27 g of 3,5-difluoro-2-nitroaniline.
Reaction SMILES: [BH4-].[Na+].[O:3]=[C:4]([C:30]1[CH:35]=[CH:34][C:33]([O:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:32][N:31]=1)[CH:5]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([O:23][C:24]([F:29])([F:28])[CH:25]([F:27])[F:26])[CH:18]=1)[C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7].Cl.C(=O)([O-])O.[Na+]>C(OCC)C.[Cl-].[Zn+2].[Cl-].O>[OH:3][CH:4]([C:30]1[CH:35]=[CH:34][C:33]([O:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:32][N:31]=1)[CH:5]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([O:23][C:24]([F:29])([F:28])[CH:25]([F:27])[F:26])[CH:18]=1)[C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7]
Reactant: O=C(OCc1ccccc1)C(Cc1cccc(OC(F)(F)C(F)F)c1)C(=O)c1ccc(Oc2ccccc2)cn1
Agent: Cl
Agent: O=C([O-])O
Agent: [BH4-]
Solvent: CCOCC
Solvent: O
Product: O=C(OCc1ccccc1)C(Cc1cccc(OC(F)(F)C(F)F)c1)C(O)c1ccc(Oc2ccccc2)cn1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of zinc chloride (4.57 g, 33.6 mmol) in diethyl ether (100 ml) was added sodium borohydride (2.54 g, 67.1 mmol), and the mixture was stirred at room temperature for 30 min. Insoluble material was filtered off, and to the filtrate was added a solution of benzyl 3-oxo-3-(5-phenoxypyridin-2-yl)-2-[3-(1,1,2,2-tetrafluoroethoxy)-benzyl]propanoate (9.32 g, 16.8 mmol, crude) in diethyl ether (100 ml) at 0° C. The mixture was stirred for 30 min. and 1N hydrochloric acid was added to stop the reaction. After neutralization with saturated aqueous sodium hydrogen carbonate, water (200 ml) was further added and the mixture was extracted with ethyl acetate (500 ml×2). The extract was washed with water and saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1-1:1) to give the objective substance (5.07 g, 54%, crude). The present compound was used for the next reaction as a crude compound.
Reaction SMILES: [CH3:1][C@H:2]([CH2:6][CH2:7][CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:3][CH:4]=O.[CH3:12][C:13]([CH3:15])=[O:14].[OH-].[K+]>[Cl-].[Na+].O>[CH3:1][C@H:2]([CH2:6][CH2:7][CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:3]/[CH:4]=[CH:12]/[C:13](=[O:14])[CH3:15]
Reactant: CC(C)=O
Reactant: CC(C)CCC[C@@H](C)CC=O
Agent: [Cl-]
Agent: [K+]
Agent: [Na+]
Solvent: O
Product: CC(=O)/C=C/C[C@H](C)CCCC(C)C
Reaction time: 48 h

Procedure:
A 3L 3-necked flask fitted with a reflux condenser, a mechanical stirrer and an argon inlet tube was charged with 161.5 g (1.033 mol) of (R)-3,7-dimethyloctanal (fractions 1-5 from Example 3, GC purity 97.3%), 413 mL of acetone and 1.24 L of 1% aq. KOH. The reaction mixture was stirred vigorously and refluxed for 48 hours. The course of the reaction was monitored by GC. The amount of starting material present was 5% after 25 hours and 3.6% after 48 hours. After cooling in an ice bath, the reaction mixture was poured into a separatory funnel containing 200 mL of brine and extracted with 3×800 mL of hexane/ether 1:1 (parts by volume). The combined organic fractions were washed with 300 mL of brine, dried over MgSO4, filtered and evaporated. Vacuum distillation of the residue through a 30 cm Vigreus column afforded (3E,6R)-6,10-dimethyl-3-undecen-2-one in the following fractions:
Reaction SMILES: Br.Cl[CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([CH3:16])[S:14][CH:15]=2)=[CH:7][CH:6]=1.[C:17]1([N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][CH:18]=1.C(N(C(C)C)CC)(C)C.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+]>CC(CC(C)C)=O>[C:17]1([N:27]2[CH2:32][CH2:31][N:30]([CH2:3][CH2:4][C:5]3[CH:10]=[CH:9][C:8]([C:11]4[N:12]=[C:13]([CH3:16])[S:14][CH:15]=4)=[CH:7][CH:6]=3)[CH2:29][CH2:28]2)[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][CH:18]=1
Reactant: c1ccc2c(N3CCNCC3)cccc2c1
Reactant: Cc1nc(-c2ccc(CCCl)cc2)cs1
Agent: Br
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(=O)CC(C)C
Product: Cc1nc(-c2ccc(CCN3CCN(c4cccc5ccccc45)CC3)cc2)cs1

Procedure:
To a 125 ml round-bottomed flask equipped with condenser and N2 inlet were added 2.39 g (7.5 mmol) of 4-(4-(2-chloroethyl)phenyl)-2-methylthiazole hydrobromide, 1.59 g (7.5 mmol) of N-(1-naphthyl)piperazine, 1.31 ml (7.5 mmol) of diisopropylethylamine, 1.59 g (15 mmol) of sodium carbonate, 5 mg of sodium iodide, and 50 ml of methylisobutylketone. The reaction was heated at reflux for 5 days, cooled, and the precipitate filtered. The solid was taken up in methylene chloride, washed with sodium bicarbonate, dried over sodium sulfate, treated with methylene chloride saturated with hydrochloride, evaporated, and the residue triturated with ether to afford a white solid, m.p. 305°-307° C., 1.76 g (48%).
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([N:19]3[C@@H:24]([CH3:25])[CH2:23][O:22][CH2:21][C@@H:20]3[CH3:26])=[O:18])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[C:27]([O:30][CH2:31][C:32]1[C:33]([N:47]2[CH2:58][CH2:57][N:56]3[C:49](=[CH:50][C:51]4[CH2:52][C:53]([CH3:60])([CH3:59])[CH2:54][C:55]=43)[C:48]2=[O:61])=[N:34][CH:35]=[CH:36][C:37]=1B1OC(C)(C)C(C)(C)O1)(=[O:29])[CH3:28].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>O.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].C(#N)C>[C:27]([O:30][CH2:31][C:32]1[C:33]([N:47]2[CH2:58][CH2:57][N:56]3[C:49](=[CH:50][C:51]4[CH2:52][C:53]([CH3:60])([CH3:59])[CH2:54][C:55]=43)[C:48]2=[O:61])=[N:34][CH:35]=[CH:36][C:37]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([N:19]3[C@@H:24]([CH3:25])[CH2:23][O:22][CH2:21][C@@H:20]3[CH3:26])=[O:18])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1)(=[O:29])[CH3:28]
Reactant: CC(=O)OCc1c(B2OC(C)(C)C(C)(C)O2)ccnc1N1CCn2c(cc3c2CC(C)(C)C3)C1=O
Reactant: C[C@H]1COC[C@H](C)N1C(=O)c1ccc(Nc2cc(Cl)nn(C)c2=O)nc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: CC(=O)[O-]
Solvent: O
Solvent: CC#N
Product: CC(=O)OCc1c(-c2cc(Nc3ccc(C(=O)N4[C@@H](C)COC[C@@H]4C)cn3)c(=O)n(C)n2)ccnc1N1CCn2c(cc3c2CC(C)(C)C3)C1=O
Temperature: 100 °C
Yield: 52.3 %

Procedure:
A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 324b (40 mg, 0.11 mmol), (2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate 199e (105 mg, 0.22 mmol), K3PO4 (47 mg, 0.22 mmol), sodium acetate (18 mg, 0.22 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (20 mg, 0.022 mmol), acetonitrile (10 mL), and water (6 drops). The system was subjected to three cycles of vacuum/nitrogen flush and heated at 100° C. under N2 protection for 1.5 h. LCMS analysis showed complete conversion to the desired product. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was diluted with dichloromethane (50 mL) and water (50 mL). The aqueous layer was separated and extracted with dichloromethane (3×20 mL). The combined extract was dried over Na2SO4, filtered, and concentrated under reduced pressure. The dark residue was purified by silica-gel column chromatography eluting with 60:1 dichloromethane/methanol to afford 324c (40 mg, 52%) as a black solid. MS-ESI: [M+H]+ 695.3
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:31]([F:34])([F:33])[F:32])=[C:6]([CH:30]=1)[CH2:7][N:8]1[CH2:13][CH2:12][NH:11][C:10]2[N:14]=[CH:15][C:16]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([N:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]4)[CH:19]=3)=[CH:17][C:9]1=2.[C:35](Cl)(=[O:37])[CH3:36].C(N(CC)CC)C>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:31]([F:32])([F:34])[F:33])=[C:6]([CH:30]=1)[CH2:7][N:8]1[CH2:13][CH2:12][NH:11][C:10]2[N:14]=[CH:15][C:16]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([N:24]4[CH2:25][CH2:26][N:27]([C:35](=[O:37])[CH3:36])[CH2:28][CH2:29]4)[CH:19]=3)=[CH:17][C:9]1=2
Reactant: CC(=O)Cl
Reactant: FC(F)(F)c1ccc(Cl)cc1CN1CCNc2ncc(-c3ccnc(N4CCNCC4)c3)cc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(=O)N1CCN(c2cc(-c3cnc4c(c3)N(Cc3cc(Cl)ccc3C(F)(F)F)CCN4)ccn2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 56 %

Procedure:
To a solution of 1-[5-chloro-2-(trifluoromethyl)benzyl]-7-(2-piperazin-1-yl-pyridin-4-yl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine (63 mg, 0.000129 mol) in anhydrous DMF (1 mL) was added acetyl chloride (0.012 mL) and triethylamine (0.020 mL). The mixture was stirred at room temperature under nitrogen overnight and then concentrated. The residue was purified on normal phase silica gel chromatography to give the title compound as a yellow solid (56% yield). m.p.=241° C., LCMS: m/z=531.31 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 2.15 (3H, s), 3.47 (2H, m), 3.52 (2H, m), 3.57 (2H, m), 3.62 (2H, m), 3.73 (4H, m), 4.61 (2H, s), 5.25 (1H, bs), 6.55 (2H, m), 6.69 (1H, d, J=5.3 Hz), 7.37 (1H, d, J=8.3 Hz), 7.52 (1H, s), 7.65 (1H, d, J=8.3 Hz), 7.78 (1H, bs), 8.12 (1H, d, J=5.3 Hz).
Reaction SMILES: O=[C:2]([CH:4]=[C:5]([CH3:7])[CH3:6])[CH3:3].[P:8]([OH:11])([OH:10])[OH:9].C(OC(=O)C)(=O)C>C(O)(=O)C>[CH3:6][C:5](=[CH2:7])[CH:4]=[C:2]([P:8]([OH:11])(=[O:9])[OH:10])[CH3:3]
Reactant: CC(=O)C=C(C)C
Reactant: OP(O)O
Solvent: CC(=O)O
Solvent: CC(=O)OC(C)=O
Product: C=C(C)C=C(C)P(=O)(O)O

Procedure:
For example, mesityl oxide was reacted with phosphorous acid in the presence of acetic anhydride and acetic acid under mild conditions to yield 4-methylpenta-2,4-diene-2-phosphonic acid in more than 90% purity.
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][CH2:27][C@@H:28]1[O:32][N:31]=[C:30]([C:33]2[CH:38]=[CH:37][C:36]([C:39]3[CH:44]=[CH:43][C:42]([N:45]4[CH2:49][C@H:48]([CH2:50][NH:51][C:52](=[O:54])[CH3:53])[O:47][C:46]4=[O:55])=[CH:41][CH:40]=3)=[CH:35][CH:34]=2)[CH2:29]1)(C(C)(C)C)(C)C.C(OCC)(=O)C>C1COCC1>[OH:26][CH2:27][C@@H:28]1[O:32][N:31]=[C:30]([C:33]2[CH:34]=[CH:35][C:36]([C:39]3[CH:40]=[CH:41][C:42]([N:45]4[CH2:49][C@H:48]([CH2:50][NH:51][C:52](=[O:54])[CH3:53])[O:47][C:46]4=[O:55])=[CH:43][CH:44]=3)=[CH:37][CH:38]=2)[CH2:29]1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(-c3ccc(C4=NO[C@@H](CO[Si](C)(C)C(C)(C)C)C4)cc3)cc2)C(=O)O1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(=O)NC[C@H]1CN(c2ccc(-c3ccc(C4=NO[C@@H](CO)C4)cc3)cc2)C(=O)O1
Reaction time: 2 h
Yield: 59.7 %

Procedure:
A solution of tetrabutylammonium fluoride in THF (1M, 0.69 ml, 0.69 mM) was added to a solution of N-[((5S)-3-{4′-[(5R)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4,5-dihydroisoxazol-3-yl]-1,1′-biphenyl-4-yl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide (300 mg, 0.57 mM) in THF (5 ml). After approximately 2 hours, ethyl acetate was added and the resulting suspension was filtered. The filter cake was washed with water and ethyl acetate to give 140 mg of the title product.
Reaction SMILES: [C:1]1([C:7]2[S:11][C:10]([CH:12]=O)=[N:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][N:16]1[CH2:21][CH2:22][CH2:23][NH2:24].CO.[BH4-].[Na+]>ClCCl>[CH3:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][N:16]1[CH2:21][CH2:22][CH2:23][NH:24][CH2:12][C:10]1[S:11][C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:8][N:9]=1
Reactant: CC1CCCCN1CCCN
Reactant: O=Cc1ncc(-c2ccccc2)s1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: CC1CCCCN1CCCNCc1ncc(-c2ccccc2)s1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Experimental condition analogous to Example 18, from 5-phenyl-thiazole-2-carbaldehyde 0.16 g (1.05 mmol), 3-(2-methyl-piperidin-1-yl)-propylamine 0.2 g (1.05 mmol), in 5 mL of dry dichloromethane was added 2 g of molecular sieve. The reaction was stirred overnight at room temperature. The molecular sieve was filtered and dichloromethane was concentrated under vaccum. To the mixture was added 15 mL of dry methanol and sodium borohydride 0.04 g (1.155 mmol) was added at 0° C. after 30 minutes reaction goes to completion. The reaction was quenched with 2 mL acetone, methanol was concentrated under vacuum, and was diluted with chloroform, organic layer was washed with 2 times 20 mL water, followed with brine. The organic layer was dried over magnesium sulfate and concentrated under vaccum. Yield 0.3 g of compound.
Reaction SMILES: C[Si](C)(C1C=CC=CC=1)[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[CH:9]1[CH2:13][CH2:12][CH2:11][N:10]1[CH3:14].F.[K].OO.O.C([O-])([O-])=[O:28].[K+].[K+]>CO>[CH3:14][N:10]1[CH2:11][CH2:12][CH2:13][CH:9]1[C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:3]=1[OH:28]
Reactant: CN1CCCC1c1cnccc1[Si](C)(C)c1ccccc1
Reactant: O=C([O-])[O-]
Agent: F
Agent: OO
Agent: [K+]
Solvent: O
Solvent: CO
Product: CN1CCCC1c1cnccc1O
Temperature: 55 °C
Yield: 82 %

Procedure:
To a solution of II (0.9 g, 3.2 mmol) in 10 mL of methanol was added potassium hydrogen fluoride (0.25 g, 3.2 mmol). A solution of 30% hydrogen peroxide in water (0.88 mL, 7.7 mmol) was slowly added, and the reaction mixture was stirred and heated at 55° C. for 8 h. To the crude mixture was added K2CO3 until the pH of the solution became slightly basic (pH 8–9). After filtration of the solid and evaporation of the solvent, the crude product was purified by radial PLC (EtOAc) to yield 82% of III as a white solid. IR (neat) 2598, 23448, 1643 cm−1; 1H NMR (300 MHz, CDCl3) δ 8.68 (s, 1H), 8.58–8.56 (m, 1H), 8.12 (dd, 1H, J=1.5 and 8 Hz), 7.47 (dd, 1H, J=5.1 ans 8 Hz), 4.61 (dd, 1H, J=7.2 and 12 Hz), 3.79–3.59 (m, 2H), 2.94 (s, 3H), 2.72–2.1 (m, 4H); 13C NMR (75 MHz, CD3OD) δ 170.5, 152.8, 151.4, 141.3, 124.9, 78.3, 71.4, 54.1, 29.5, 21.1. HRMS Calcd for C10H14N2O: 179.1184. Found: 179.1190 [M+H]+. [α]D25: +23.8 (c=0.8, MeOH). IR (neat) 2598, 23448, 1643 cm−1, 1H NMR (300 MHz,) δ 8.68 (s, 1H), 8.58–8.56 (m, 1H), 8.12 (dd, 1H, J=1.5 and 8 Hz), 7.47 (dd, 1H, J=5.1 ans 8 Hz), 4.61 (dd, 1H, J=7.2 and 12 Hz), 3.79–3.59 (m, 2H), 2.94 (s, 3H), 2.72–2.1 (m, 4H); 13C NMR (75 MHz, CD3OD) δ 170.5, 152.8, 151.4, 141.3, 124.9, 78.3, 71.4, 54.1, 29.5, 21.1. HRMS Calcd for C10H14N2O: 179.1184. Found: 179.1190 [M+H]+. [α]D25+23.8 (c 8, MeOH).
Reaction SMILES: [OH:1][CH:2]([CH2:15][OH:16])[CH2:3][NH:4][C:5](=[O:14])[O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH3:17][C:18]([Si:21](Cl)([CH3:23])[CH3:22])([CH3:20])[CH3:19].N1C=CN=C1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C=O)C.CO.CCOC(C)=O>[Si:21]([O:1][CH:2]([CH2:15][OH:16])[CH2:3][NH:4][C:5](=[O:14])[O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([C:18]([CH3:20])([CH3:19])[CH3:17])([CH3:23])[CH3:22]
Reactant: O=C(NCC(O)CO)OCc1ccccc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CO
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)OC(CO)CNC(=O)OCc1ccccc1
Reaction time: 20 h

Procedure:
To a solution of benzyl 2,3-dihydroxypropylcarbamate in DMF (0.1 M) was added TBDMSCl (2.2 eq.) and imidazole (2.5 eq.) at room temperature. After stirred for 20 h, the reaction mixture was worked up with EtOAc, which was washed with water and brine. The organic layer was separated, dried and concentrated to give the crude bis-silylated product, which was dissolved in methanol (0.16 M) followed by addition of p-toluenesulfonic acid (0.1 equiv.) at 0° C. The reaction mixture was stirred for 1.5 h at the same temperature. After quenched with saturated NaHCO3 aqueous solution, the reaction mixture was extracted with EtOAc, which was washed with water and brine. The organic layer was separated, dried, concentrated, and purified on silica gel with 0-100% EtOAc/Hexanes gradient elution to provide the pure benzyl 2-(tert-butyldimethylsilyloxy)-3-hydroxypropylcarbamate.
Reaction SMILES: [C:1]([O:4][C:5]1[CH:6]=[C:7](/[CH:13]=[CH:14]/[C:15]([OH:17])=O)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12])(=[O:3])[CH3:2].S(Cl)(Cl)=O.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([NH2:29])=[CH:25][C:24]=1[O:30][CH2:31][C:32]1[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=1.C(N(C(C)C)CC)(C)C>C1COCC1.C(Cl)Cl>[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:15](=[O:17])/[CH:14]=[CH:13]/[C:7]2[CH:8]=[CH:9][C:10]([O:11][CH3:12])=[C:5]([O:4][C:1](=[O:3])[CH3:2])[CH:6]=2)=[CH:25][C:24]=1[O:30][CH2:31][C:32]1[CH:33]=[CH:34][N:35]=[CH:36][CH:37]=1
Reactant: Nc1ccc(Cl)c(OCc2ccncc2)c1
Reactant: COc1ccc(/C=C/C(=O)O)cc1OC(C)=O
Solvent: C1CCOC1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(/C=C/C(=O)Nc2ccc(Cl)c(OCc3ccncc3)c2)cc1OC(C)=O
Temperature: 35 °C
Yield: 72.6 %

Procedure:
A solution (E)-3-(3-acetoxy-4-methoxy-phenyl)-acrylic acid (0.20 g, 0.76 mmol) and thionyl chloride (0.069 mL, 0.95 mmol) in dry THF (4 mL) was stirred at reflux temperature for 2.5 hrs. Then a further aliquot of thionyl chloride (0.008 mL, 0.11 mmol) was added and the mixture was stirred at reflux temperature for additional 5 hrs. After cooling to about 35° C., a solution of 4-chloro-3-(pyridin-4-ylmethoxy)-phenylamine (0.232 mg, 0.99 mmol) and diisopropylethylamine (0.54 mL, 3.04 mmol) in dry THF (0.5 mL) was added dropwise. After stirring at reflux temperature for 2 hrs, the reaction mixture was diluted with DCM and washed with water, aqueous sodium hydrogencarbonate, and brine. The organic layer was then dried over sodium sulphate and evaporated. The resulting raw material was purified by column chromatography over silica gel (eluant DCM/MeOH 98/2) to give 250 mg of the title (E)-N-[4-chloro-3-(pyridin-4-ylmethoxy)-phenyl]-3-(3-acetoxy-4-methoxy-phenyl)-acrylamide as a light brown solid.
Reaction SMILES: [CH3:1][C:2](O)([C:4]#[CH:5])[CH3:3].C[O:8][C:9]([CH3:11])=[CH2:10].CC([O-])=O.[Na+]>C1(C=CC(O)=CC=1)O.CS(O)(=O)=O.CCCCCCC>[CH3:1][C:2]([CH3:3])=[C:4]=[CH:5][CH2:8][C:9](=[O:10])[CH3:11]
Reactant: C=C(C)OC
Reactant: C#CC(C)(C)O
Agent: CC(=O)[O-]
Agent: CS(=O)(=O)O
Agent: Oc1ccc(O)cc1
Solvent: CCCCCCC
Product: CC(=O)CC=C=C(C)C
Yield: 88.3 %

Procedure:
21.1 g 2-methyl-3-butin-2-ol, 54.1 g isopropenyl methyl ether, 0.05 g hydroquinone and 100 mL n-heptane were initially introduced into a 500 ml flask. 20.7 mg methanesulfonic acid were added, while stirring. The reaction mixture was stirred under reflux for 6.5 hours. After cooling, it was neutralized with 2 ml methanolic NaOAc solution (10 g/1) and evaporated. After distillation in vacuo, 27.5 g 6-methyl-4,5-heptadien-2-one were obtained, corresponding to a yield of 89%.