Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.Br[C:12]1[CH:13]=[CH:14][C:15]([F:21])=[C:16]([N+:18]([O-:20])=[O:19])[CH:17]=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:21][C:15]1[CH:14]=[CH:13][C:12]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([NH2:1])[CH:3]=2)=[CH:17][C:16]=1[N+:18]([O-:20])=[O:19]
Reactant: Nc1cccc(B(O)O)c1
Reactant: O=[N+]([O-])c1cc(Br)ccc1F
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: [Na+]
Solvent: Cc1ccccc1
Product: Nc1cccc(-c2ccc(F)c([N+](=O)[O-])c2)c1
Temperature: 0 °C
Yield: 183.8 %

Procedure:
3-Aminophenylboronic acid (3.9 g), 5 g 5-bromo-2-fluoronitrobenzene, 0.8 g tetrakis(triphenylphosphine)palladium and 23 mL of 2 M sodium bicarbonate solution in 50 mL of toluene were refluxed under nitrogen for 2.5 hours. The reaction mixture was poured into 200 mL of ice water and the mixture extracted three times with 50 mL of ethyl acetate. The combined organic layers were washed with 50 mL of water and 20 mL of brine, dried over anhydrous sodium sulfate and concentrated to give 9.7 g (92% yield) of 2-fluoro-5-(3-aminophenyl)nitrobenzene as a dark brown oil.
Reaction SMILES: B(O[O-])=O.[Na+].[I-:6].[K+].S(=O)(=O)(O)O.[C:13]([C:15]1[CH:20]=[CH:19][C:18]([NH:21]C(=O)C)=[C:17]([F:25])[CH:16]=1)#[N:14].S([O-])([O-])(=O)=S.[Na+].[Na+].S(=O)(O)[O-].[Na+]>C(O)(=O)C.C(OC(=O)C)(=O)C.O.[O-][W]([O-])(=O)=O.[Na+].[Na+]>[NH2:21][C:18]1[C:19]([I:6])=[CH:20][C:15]([C:13]#[N:14])=[CH:16][C:17]=1[F:25]
Reactant: [I-]
Reactant: CC(=O)Nc1ccc(C#N)cc1F
Agent: O=[W](=O)([O-])[O-]
Agent: O=BO[O-]
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(=O)O
Solvent: CC(=O)OC(C)=O
Product: N#Cc1cc(F)c(N)c(I)c1
Temperature: 50 °C
Reaction time: 1 h
Yield: 15.3 %

Procedure:
A solution of sodium perborate (4.2 g, 27.3 mmols) and sodium tungstate (450 mg, 1.4 mmol) in a mixture of 20 mL of glacial acetic acid and 15 mL of acetic anhydride was treated with a solution of potassium iodide (2.3 g, 13.9 mmols) in 15 mL of water. The mixture was treated with 7.5 mL of concentrated sulfuric acid over 15 minutes. A suspension of N-(4-cyano-2-fluorophenyl)acetamide (1.79 g, 10 mmols) in 15 mL of glacial acetic acid was added to and the resulting mixture was heated at 50° C. After 1 hour, the mixture was poured into 300 mL of crushed ice and treated with 100 mL of a saturated solution of sodium thiosulfate followed by 100 mL of a sodium bisulfite solution. The mixture was extracted with three 100 mL portions of dichloromethane and the combined organic layers were washed with three 50 mL portions of sodium bicarbonate solution, three 50 mL portions of water, dried over sodium sulfate, and concentrated in vacuo to give a light brownish solid. Chromatography on SiO2 (50% ethyl acetate in hexanes) afforded 400 mg of the title product as a light brownish solid (15% yield).
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[OH-].[K+].[CH3:12][N:13]1[CH2:18][CH2:17][CH2:16][CH2:15][C:14]1=O.P(=O)(O)(O)O>COCCOC.CCOCC>[CH:1]1([C:16]2([CH:1]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[CH:3]=[CH:2]3)[CH2:17][CH2:18][N:13]([CH3:12])[CH2:14][CH2:15]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: CN1CCCCC1=O
Reactant: C1=Cc2ccccc2C1
Agent: O=P(O)(O)O
Agent: [K+]
Agent: [OH-]
Solvent: CCOCC
Solvent: COCCOC
Product: CN1CCC(C2C=Cc3ccccc32)(C2C=Cc3ccccc32)CC1

Procedure:
0.25 mole of indene was added within 0.5 hours under vigorous stirring to the suspension of 15 g of KOH powder in 150 ml of DME. The mixture was heated to reflux. Then 0.1 mole of 1-methylpiperidone dissolved in 10 ml of DME was added dropwise within 0.5 hours and the mixture was stirred under reflux for additional 2 hours. The resulting mixture was cooled, treated by 200 ml of diluted phosphoric acid till the neutralization and by 100 ml of Et2O. The organic layer was separated and treated by 20% excess of diluted acetic acid. The aqueous layer was separated, washed twice with Et2O and neutralissed with a diluted alkali solution. The 4,4-bis-indenyl-1-methyl-piperidine was extracted with CH2Cl2, the organic layer was separated, the solvent was removed and the residue was recrystallized from hexane. The yield of the 4,4-bis-indenyl-1-1methyl-piperidine was 67%. 1H NMR (C6D6, 30° C.) δ: 7.57(d,2H); 7.20(d,2H); 7.04(t,2H); 6.97(t,2H); 6.28(s,2H); 3.08(s,4H); 2.58(m,4H); 2.44(m,4H); 2.17(s,3H).
Reaction SMILES: [CH3:1][Si](C=[N+]=[N-])(C)C.[C:8](/[CH:11]=[CH:12]/[C:13]1[N:14]([C:18]2[CH:19]=[C:20]([CH:27]=[CH:28][CH:29]=2)[C:21]([N:23]=[C:24]([NH2:26])[NH2:25])=[O:22])[CH:15]=[CH:16][CH:17]=1)([OH:10])=[O:9].C(O)(=O)C.C(=O)([O-])[O-].[K+].[K+]>CCCCCC.O1CCCC1.CO.O.C(OCC)(=O)C>[CH3:1][O:9][C:8](/[CH:11]=[CH:12]/[C:13]1[N:14]([C:18]2[CH:19]=[C:20]([CH:27]=[CH:28][CH:29]=2)[C:21]([N:23]=[C:24]([NH2:26])[NH2:25])=[O:22])[CH:15]=[CH:16][CH:17]=1)=[O:10]
Reactant: NC(N)=NC(=O)c1cccc(-n2cccc2/C=C/C(=O)O)c1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: C1CCOC1
Solvent: CCCCCC
Product: COC(=O)/C=C/c1cccn1-c1cccc(C(=O)N=C(N)N)c1
Temperature: 25 °C
Reaction time: 0.42 h

Procedure:
2M (Trimethylsilyl)diazomethane in hexane solution (0.84 ml) was added to a mixture of 2-[3-[2-((E)-2-carboxyethenyl)pyrrol-1-yl]benzoyl]guanidine (0.25 g) in tetrahydrofuran (5 ml) and methanol (5 ml) and the mixture was stirred for 25 minutes at the ambient temperature. To the reaction mixture was added acetic acid (2 ml) and stirred for 5 minutes. The mixture of ethyl acetate and water was added to the above mixture and adjusted to pH 8 with 20% aqueous potassium carbonate solution. The separated organic layer was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was recrystallized from a mixture of ethanol and diisopropyl ether to give 2-[3-[2-((E)-2-methoxycarbonylethenyl)pyrrol-1-yl]benzoyl]guanidine (0.15 g).
Reaction SMILES: [C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[CH:39][C:38]2=[N:42][C:35]3=[CH:36][N:37]2[C:12]=1[N:13]1[CH2:48][CH2:47][C:16]([CH3:49])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:46])[O:23][C:24]2[CH:25]=[C:26]([CH3:45])[C:27]([CH3:44])=[CH:28][C:29]=2[C:30]2[CH:43]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:15][CH2:14]1)[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].C(O[C@@H](C1C(C)=CC2=NC3=CN2C=1N1CCC(C)(OCC=CC[C@H](C)OC2C=C(F)C=CC=2C2C=C3C=CC=2)CC1)C(O)=O)(C)(C)C>>[C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[CH:39][C:38]2=[N:42][C:35]3=[CH:36][N:37]2[C:12]=1[N:13]1[CH2:14][CH2:15][C:16]([CH3:49])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:46])[O:23][C:24]2[CH:25]=[C:26]([CH3:45])[C:27]([CH3:44])=[CH:28][C:29]=2[C:30]2[CH:43]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:47][CH2:48]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc3cn2c1N1CCC(C)(CC1)OCCCC[C@H](C)Oc1cc(C)c(C)cc1-c1cccc-3c1
Agent: Cc1cc2nc3cn2c(c1[C@H](OC(C)(C)C)C(=O)O)N1CCC(C)(CC1)OCC=CC[C@H](C)Oc1cc(F)ccc1-c1cccc-3c1
Product: Cc1cc2c(cc1C)-c1cccc(c1)-c1cn3c(c([C@H](OC(C)(C)C)C(=O)O)c(C)cc3n1)N1CCC(C)(CC1)OCCCC[C@H](C)O2
Yield: 37 %

Procedure:
Prepared in 37% yield from methyl(2S)-2-(tert-butoxy)-2-[(22S)-4,17,18,22,28-pentamethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate following the procedure for (2S)-2-(tert-butoxy)-2-[(22S)-18-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18,24-undecaen-3-yl]acetic acid. 1H NMR (400 MHz, CD3OD) δ 8.12 (s, 1H), 8.05 (s, 1H), 7.96 (d, J=8.1 Hz, 1H), 7.52 (t, J=7.8 Hz, 1H), 7.35 (d, J=7.6 Hz, 1H), 7.30 (s, 1H), 7.11 (s, 1H), 6.92 (s, 1H), 6.04 (s, 1H), 4.57 (dt, J=6.2, 3.2 Hz, 1H), 3.98 (t, J=11.1 Hz, 1H), 3.80-3.74 (m, 1H), 3.58-3.50 (m, 2H), 3.31-3.28 (m, 1H), 2.78 (d, J=8.3 Hz, 1H), 2.55 (s, 3H), 2.32 (s, 3H), 2.26 (s, 3H), 2.00-1.65 (m, 10H), 1.28 (s, 3H), 1.26 (s, 9H), 1.09 (d, J=6.1 Hz, 3H); LCMS (ESI, M): 653.4.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][CH2:7][CH2:6][CH:5]([NH:12]C(=O)C)[C:4]=2[N:3]=1.[OH-].[Na+]>Cl>[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][CH2:7][CH2:6][CH:5]([NH2:12])[C:4]=2[N:3]=1
Reactant: CC(=O)NC1CCCc2ccc(C)nc21
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: Cc1ccc2c(n1)C(N)CCC2
Temperature: 25 °C
Yield: 90.6 %

Procedure:
N-(2-Methyl-5,6,7,8-tetrahydroquinolin-8-yl)acetamide (4.51 g, 22.1 mmol) was dissolved in 6 N HCl (40 mL). The mixture was heated at reflux for 17 h. The reaction mixture was cooled to room temperature, basified with saturated NaOH (pH>14) and extracted with chloroform (5×100 mL). The organic extracts were dried (MgSO4) and concentrated. The crude material was purified by distillation (bp 102-104° C. at 0.20 mm Hg) to yield the product as a clear liquid (3.25 g, 99%). 1H NMR (CDCl3, 300 MHz) δ 1.62-1.82 (m, 2H), 1.84-2.00 (m, 3H), 2.11-2.20 (m, 1H), 2.49 (s, 3H), 2.61-2.82 (m, 2H), 3.93-4.00 (m, 1H), 6.91 (d, 1H), J=7.8 Hz), 7.25 (d, 1H, J=7.8 Hz); 13C NMR (CDCl3) δ 20.4, 24.6, 29.1, 32.6, 51.8, 121.7, 128.6, 137.6, 155.9, 159.0; ES-MS m/z: 163 (M+H+), 146 (M-NH2).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:27]=[CH:26][C:11]([CH2:12][O:13][C:14]([C:22]([F:25])([F:24])[F:23])([C:18]([F:21])([F:20])[F:19])[C:15]([OH:17])=[O:16])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[OH-:28].[Na+:29]>O>[OH2:13].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([CH2:12][O:13][C:14]([C:18]([F:19])([F:20])[F:21])([C:22]([F:23])([F:24])[F:25])[C:15]([O-:17])=[O:16])=[CH:26][CH:27]=2)=[CH:4][CH:3]=1.[Na+:29].[OH2:28].[OH2:13].[Na+:29].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([CH2:12][O:13][C:14]([C:18]([F:19])([F:20])[F:21])([C:22]([F:23])([F:24])[F:25])[C:15]([O-:17])=[O:16])=[CH:26][CH:27]=2)=[CH:4][CH:3]=1
Reactant: [OH-]
Reactant: O=C(O)C(OCc1ccc(-c2ccc(Cl)cc2)cc1)(C(F)(F)F)C(F)(F)F
Agent: [Na+]
Solvent: O
Product: O=C([O-])C(OCc1ccc(-c2ccc(Cl)cc2)cc1)(C(F)(F)F)C(F)(F)F

Procedure:
A stirred suspension of 2-[4-(4-chlorophenyl)benzyloxy]-3,3,3-trifluoro-2-trifluoromethylpropionic acid (750 mg.) in water (10 ml.) is treated dropwise at room temperature with 0.4 N-aqueous sodium hydroxide solution (4.50 ml.). The resultant mixture is warmed briefly to 35° C., cooled, and filtered. The filtrate is washed with ether, refiltered, then evaporated in vacuo. The solid residue is dried in vacuo at 100° C. for 12 hours giving sodium 2-[4-(4-chlorophenyl)-benzyloxy]-3,3,3-trifluoro-2-trifluoromethylpropionate sesquihydrate (0.74 g.) as a solid, which does not melt below 300° C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[N:11]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:10]1[CH:9]=[C:8]3[C:21]([CH3:29])([CH3:28])[C:22]4[C:27]([C:7]3=[CH:6][C:5]2=1)=[CH:26][CH:25]=[CH:24][CH:23]=4.[NH2:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:33][CH:32]=1.N#N.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[Fe+2].CC([O-])=O.CC([O-])=O.[Pd+2].O>[C:34]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:33]=[CH:32][C:31]([NH:30][C:2]2[CH:3]=[C:4]3[C:12](=[CH:13][CH:14]=2)[N:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:10]2[CH:9]=[C:8]4[C:21]([CH3:29])([CH3:28])[C:22]5[C:27]([C:7]4=[CH:6][C:5]3=2)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[CH:36][CH:35]=1
Reactant: Nc1ccc(-c2ccccc2)cc1
Reactant: CC1(C)c2ccccc2-c2cc3c4cc(Br)ccc4n(-c4ccccc4)c3cc21
Agent: [Fe+2]
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: Cc1ccccc1
Solvent: O
Product: CC1(C)c2ccccc2-c2cc3c4cc(Nc5ccc(-c6ccccc6)cc5)ccc4n(-c4ccccc4)c3cc21
Temperature: 25 °C

Procedure:
A degassed solution of 175 g (400 mmol) of 7-bromo-12,12-dimethyl-10-phenyl-10,12-dihydro-10-azaindeno[2,1-b]fluorene and 67.7 g (401.8 mmol) of p-aminobiphenyl in 1000 ml of toluene is saturated with N2 for 1 h. 2.47 g (4.45 mmol) of 1,1-bis(diphenylphosphino)ferrocene and 1 g (4.45 mmol) of Pd(OAc)2 are then added to the solution, and 50.01 g (521.25 mmol) of NaOtBu in the solid state are subsequently added. The reaction mixture is heated under reflux for 5 h. After cooling to room temperature, 1000 ml of water are added. The organic phase is washed with 4×250 ml of H2O, then dried using MgSO4, and the solvent is removed under reduced pressure. The pure product is obtained by recrystallisation from dioxane as a colourless solid in a yield of 182 g (347 mmol), 87%.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:24]3[CH2:29][CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)[C:3]=12.[ClH:37]>O1CCOCC1.C(OCC)C>[ClH:37].[O:17]([C:14]1[CH:13]=[CH:12][C:11]([C:10]2[C:3]3[C:4](=[N:5][CH:6]=[N:7][C:2]=3[NH2:1])[N:8]([C@@H:24]3[CH2:29][CH2:28][CH2:27][NH:26][CH2:25]3)[N:9]=2)=[CH:16][CH:15]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
Agent: Cl
Solvent: CCOCC
Solvent: C1COCCO1
Product: Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)nn2[C@@H]1CCCNC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 88 %

Procedure:
Compound 35 (700 mg, 1.48 mmol, 1 equiv) was dissolved in dioxane (8 mL). A solution of hydrogen chloride in dioxane (4 mL of a 4 N solution in dioxane, 16 mmol, 10.7 equiv) was added and the reaction was stirred at room temperature overnight. The reaction was diluted with diethyl ether (20 mL) and the resulting solids were collected by filtration under a stream of nitrogen. The product was further dried in a vacuum oven to yield 36 (550 mg, 88% yield) as an off-white solid.
Reaction SMILES: [CH3:1][C:2]1[C:6]2[C:7]([CH3:11])=[N:8][CH2:9][CH2:10][C:5]=2[S:4][CH:3]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH3:1][C:2]1[C:6]2[CH:7]([CH3:11])[NH:8][CH2:9][CH2:10][C:5]=2[S:4][CH:3]=1
Reactant: CC1=NCCc2scc(C)c21
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: Cc1csc2c1C(C)NCC2
Yield: 8 %

Procedure:
In close analogy to the procedure described above, 3,4-Dimethyl-6,7-dihydro-thieno[3,2-c]pyridine is reacted with sodium triacetoxyborohydride to provide the title compound.
Reaction SMILES: [NH3:1].Cl.CO[N:5]=[CH:6][C:7]1[CH:16]=[C:11]([C:12]([O:14][CH3:15])=[O:13])[C:10]([OH:17])=[CH:9][CH:8]=1>CO>[C:6]([C:7]1[CH:16]=[C:11]([C:12]([O:14][CH3:15])=[O:13])[C:10]([OH:17])=[CH:9][CH:8]=1)(=[NH:5])[NH2:1]
Reactant: N
Reactant: CON=Cc1ccc(O)c(C(=O)OC)c1
Agent: Cl
Solvent: CO
Product: COC(=O)c1cc(C(=N)N)ccc1O
Yield: 53.1 %

Procedure:
To a solution prepared by introducing 6.0 g of dried gaseous ammonia into 200 ml of anhydrous methanol, was added with stirring at room temperature 40.0 g of methyl 5-methoxyiminomethylsalicylate hydrochloride. The crystals dissolved, yielding a clear yellow solution and after 5 to 10 minutes there occurred precipitation of colorless crystals. The crystals were collected by filtration and washed with methanol to obtain 16.8 g of methyl 5-amidinosalicylate.
Reaction SMILES: BrP(Br)(C1C=CC=CC=1)(C1C=CC=CC=1)[C:3]1[CH:8]=CC=C[CH:4]=1.C[Si](C)(C)C#CC(O)=O.[NH2:31][C:32]1[C:33]([C:50]([NH:52][NH2:53])=[O:51])=[N:34][C:35]([C:38]2[CH:43]=[CH:42][C:41]([S:44]([CH:47]([CH3:49])[CH3:48])(=[O:46])=[O:45])=[CH:40][CH:39]=2)=[CH:36][N:37]=1.CCN(C(C)C)C(C)C.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.C(OCC)(=O)C.O>[C:3]([C:8]1[O:51][C:50]([C:33]2[C:32]([NH2:31])=[N:37][CH:36]=[C:35]([C:38]3[CH:39]=[CH:40][C:41]([S:44]([CH:47]([CH3:49])[CH3:48])(=[O:45])=[O:46])=[CH:42][CH:43]=3)[N:34]=2)=[N:52][N:53]=1)#[CH:4]
Reactant: BrP(Br)(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(C)S(=O)(=O)c1ccc(-c2cnc(N)c(C(=O)NN)n2)cc1
Agent: C[Si](C)(C)C#CC(=O)O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: CC#N
Product: C#Cc1nnc(-c2nc(-c3ccc(S(=O)(=O)C(C)C)cc3)cnc2N)o1
Reaction time: 0.5 h
Yield: 25.3 %

Procedure:
Dibromo(triphenyl)phosphorane (1.208 g, 2.862 mmol) was added to a suspension of 3-trimethylsilylprop-2-ynoic acid (84.8 mg, 0.60 mmol) and 3-amino-6-(4-(isopropylsulfonyl)phenyl)pyrazine-2-carbohydrazide (200 mg, 0.60 mmol) in acetonitrile (3.000 mL) at room temperature and the resulting solution stirred for 30 min. DIPEA (385.4 mg, 519.4 μL, 2.982 mmol) was then added and a precipitate quickly formed. The resulting mixture was stirred at room temperature for 1 h and was then filtered. The reaction mixture was concentrated in vacuo and the residue taken up in methanol (5 mL) and potassium carbonate (131.9 mg, 0.9541 mmol) added and the resulting solution stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (5 mL) and water (5 mL) and the layers separated. The aqueous layer was extracted further with ethyl acetate (2×5 mL), dried over MgSO4 and concentrated in vacuo. The material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. Product fractions were freeze dried to leave the product as a yellow solid (56.1 mg, 27% yield); 1H NMR (400 MHz, DMSO) d 1.18 (m, 6H), 3.44 (m, 1H), 5.48 (s, 1H), 7.96 (m, 2H), 8.32 (m, 2H) and 9.08 (s, 1H) ppm; MS (ES+) 370.14
Reaction SMILES: CS(O[CH2:6][CH2:7][CH:8]([C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][CH3:11])(=O)=O.[F:16][C:17]([F:29])([F:28])[CH2:18][CH2:19][S:20]([CH2:23][C:24]([O:26][CH3:27])=[O:25])(=[O:22])=[O:21].C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O>[F:13][C:12]([F:15])([F:14])[CH:8]([CH2:9][CH2:10][CH3:11])[CH2:7][CH2:6][CH:23]([S:20]([CH2:19][CH2:18][C:17]([F:16])([F:28])[F:29])(=[O:21])=[O:22])[C:24]([O:26][CH3:27])=[O:25]
Reactant: CCCC(CCOS(C)(=O)=O)C(F)(F)F
Reactant: COC(=O)CS(=O)(=O)CCC(F)(F)F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CCCC(CCC(C(=O)OC)S(=O)(=O)CCC(F)(F)F)C(F)(F)F
Temperature: 60 °C
Reaction time: 48 h
Yield: 41.1 %

Procedure:
To a solution of 3.0 g of 3-(trifluoromethyl)-hexyl methanesulfonate and 2.8 g of methyl (3,3,3-trifluoropropylsulfonyl)acetate in 50 ml of dimethyl sulfoxide was added 1.7 g of potassium carbonate at room temperature. The reaction mixture was heated to 60° C., stirred at the same temperature for 2 days, and then allowed to stand to cool to nearly room temperature. To the reaction mixture was added 10% hydrochloric acid, and then extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography to obtain 1.90 g of methyl 5-(trifluoromethyl)-2-(3,3,3-trifluoropropylsulfonyl)octanoate (hereinafter referred to as the present compound (21)).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([C:22](OCC)=[O:23])[N:12]([CH3:21])[C:13]=1[C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1.[CH:27]1([NH2:33])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[CH:27]1([NH:33][C:22]([C:11]2[N:12]([CH3:21])[C:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)=[C:9]([C:3]3[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=3[Cl:1])[N:10]=2)=[O:23])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1
Reactant: NC1CCCCC1
Reactant: CCOC(=O)c1nc(-c2ccc(Cl)cc2Cl)c(-c2ccc(Cl)cc2)n1C
Product: Cn1c(C(=O)NC2CCCCC2)nc(-c2ccc(Cl)cc2Cl)c1-c1ccc(Cl)cc1
Temperature: 90 °C

Procedure:
A mixture of ethyl 4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-1-methylimidazole-2-carboxylate (20 mg, 0.05 mmol) from Step A in neat cyclohexylamine (2 mL) was heated at 90° C. for 72 hr. Most of the amine was evaporated under a stream of nitrogen and the residue was purified by Prep TLC (1 mm, silica) (25% ethyl acetate in hexanes to afford the title compound. HPLC/MS: 462 (M+1), 464 (M+3); Rt=4.80 min.
Reaction SMILES: [C:1]1([Si:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:8][CH2:9][O:10]C(=O)C)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[K+].[K+]>CO>[C:14]1([Si:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:8][CH2:9][OH:10])[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CC(=O)OCC[Si](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: OCC[Si](c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 28 %

Procedure:
The crude (3) was dissolved in 100 mL MeOH, and 10.0 g of K2CO3 was added all at once. The reaction was complete after 1 h of stirring at room temperature. The solids were filtered off, and the filtrate was concentrated. The concentrated residue was partitioned between 100/100 mL H2O/EtOAc. After solvent removal from the organic layer, the residue was vacuum dried. Flash chromatography (18% EtOAc in cyclohexane, Rf =0.32) using a 41 mm I.D.×150 mm long silica gel column afforded 3.42 g (28%) of (4). Recrystallization from cyclohexane gave the analytical sample as a snow-white solid, mp 96°-97° C.
Reaction SMILES: [Si]([O:8][C@H:9]1[CH2:13][N:12]([S:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[C@H:11]([CH:27]2[CH2:29][CH2:28]2)[CH2:10]1)(C(C)(C)C)(C)C.C([C@H]1N(S(C2C=CC(C(F)(F)F)=CC=2)(=O)=O)CC(=O)C1)C>>[CH:27]1([C@H:11]2[N:12]([S:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:25])([F:24])[F:26])=[CH:19][CH:18]=3)(=[O:16])=[O:15])[CH2:13][C:9](=[O:8])[CH2:10]2)[CH2:28][CH2:29]1
Reactant: CC(C)(C)[Si](C)(C)O[C@@H]1C[C@@H](C2CC2)N(S(=O)(=O)c2ccc(C(F)(F)F)cc2)C1
Agent: CC[C@@H]1CC(=O)CN1S(=O)(=O)c1ccc(C(F)(F)F)cc1
Product: O=C1C[C@@H](C2CC2)N(S(=O)(=O)c2ccc(C(F)(F)F)cc2)C1

Procedure:
Compound (11) was prepared from compound (10) in an identical manner to that used for the preparation of compound (8). MS m/z 334.1 (M+H)+; retention time=7.216 min.; method [7].
Reaction SMILES: [CH2:1]1[O:5][CH:4]([CH:6]([OH:9])[CH2:7][OH:8])[C@@H:3]([OH:10])[CH:2]1[OH:11].[C:12](O)(=[O:30])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]/[CH:20]=[CH:21]\[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>P([O-])([O-])([O-])=O>[CH3:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]/[CH:21]=[CH:20]\[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][C:12]([O:8][CH2:7][CH:6]([OH:9])[C@H:4]1[O:5][CH2:1][C@H:2]([OH:11])[C@H:3]1[OH:10])=[O:30]
Reactant: OCC(O)C1OCC(O)[C@@H]1O
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: O=P([O-])([O-])[O-]
Product: CCCCCCCC/C=C\CCCCCCCC(=O)OCC(O)[C@H]1OC[C@H](O)[C@H]1O
Yield: 142.5 %

Procedure:
To 1000 ml of a phosphate buffer having a pH of 7.3 were added 4.93 g of sorbitan, 22.60 g of oleic acid and 4.0 g of LIPASE MY. The mixture was incubated and processed as in Example 1 to give 18.34 g of sorbitan oleate.