Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[C:5]([Cl:17])=[CH:4][N:3]=1.[F:18][C:19]1[C:25]([N+:26]([O-:28])=[O:27])=[CH:24][C:22]([NH2:23])=[C:21]([O:29][CH3:30])[CH:20]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(O)CCC>[Cl:17][C:5]1[C:6]([C:8]2[CH:9]=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)=[N:7][C:2]([NH:23][C:22]2[CH:24]=[C:25]([N+:26]([O-:28])=[O:27])[C:19]([F:18])=[CH:20][C:21]=2[O:29][CH3:30])=[N:3][CH:4]=1
Reactant: COc1cc(F)c([N+](=O)[O-])cc1N
Reactant: Clc1ncc(Cl)c(-c2cnn3ccccc23)n1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCCC(C)O
Solvent: O
Product: COc1cc(F)c([N+](=O)[O-])cc1Nc1ncc(Cl)c(-c2cnn3ccccc23)n1
Yield: 79 %

Procedure:
A mixture of 3-(2,5-dichloropyrimidin-4-yl)pyrazolo[1,5-a]pyridine (Intermediate 21, 1.4 g, 5.28 mmol), 4-fluoro-2-methoxy-5-nitroaniline (Intermediate 23, 1.032 g, 5.55 mmol) and p-toluenesulfonic acid monohydrate (1.105 g, 5.81 mmol) was heated at 125° C. in 2-pentanol (40 mL) for 18 h. The mixture was then cooled and a solid was collected by filtration. The solid was washed with CH3OH and diethyl ether, and was then dried on the filter to give the title compound (1.73 g, 79%) as a yellow powder; 1H NMR: 3.98 (3H, s), 7.16 (1H, td), 7.33-7.48 (2H, m), 8.49 (1H, d), 8.53 (1H, d), 8.66 (1H, d), 8.86 (1H, d), 8.90 (1H, s), 8.96 (1H, s).
Reaction SMILES: [NH:1]([C:8]1[N:13]=[C:12]([C:14]2[N:22]3[C:17]([CH2:18][O:19][CH2:20][CH2:21]3)=[N:16][CH:15]=2)[CH:11]=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:23]([Li])CCC.IC>CCCCCC>[NH:1]([C:8]1[N:13]=[C:12]([C:14]2[N:22]3[C:17]([CH:18]([CH3:23])[O:19][CH2:20][CH2:21]3)=[N:16][CH:15]=2)[CH:11]=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [Li]CCCC
Reactant: c1ccc(Nc2nccc(-c3cnc4n3CCOC4)n2)cc1
Solvent: CI
Solvent: CCCCCC
Product: CC1OCCn2c(-c3ccnc(Nc4ccccc4)n3)cnc21
Yield: 39 %

Procedure:
By an analogous process to Example 10, 2-Anilino-4-(5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazin-3-yl)pyrimidine (Example 5; 163 mg, 0.556 mmol) was treated with n-butyllithium (0.73 ml of a 1.6M solution in hexane, 1.168 mmol) and iodomethane (36 μl, 0.583 mmol) to give the title compound (67 mg, 39%) as a pale yellow solid. NMR: 1.5 (d, 3H), 3.9 (m, 1H), 4.18 (m, 1H), 4.32 (m, 1H), 4.63 (m, 1H), 4.87 (q, 1H), 6.95 (t, 1H), 7.13 (d, 1H), 7.3 (t, 2H), 7.67 (d, 2H), 7.75 (s, 1H), 8.37 (d, 1H), 9.4 (s, 1H); m/z 308.
Reaction SMILES: NC(N)=O.[NH2:5][C:6]1[C:7]([OH:21])=[C:8]([S:13]([NH:16][CH2:17][CH:18]2[CH2:20][CH2:19]2)(=[O:15])=[O:14])[C:9]([Cl:12])=[CH:10][CH:11]=1.[Cl:22][C:23]1[C:28]([Cl:29])=[CH:27][CH:26]=[CH:25][C:24]=1[N:30]=[C:31]=[O:32]>>[Cl:12][C:9]1[CH:10]=[CH:11][C:6]([NH:5][C:31]([NH:30][C:24]2[CH:25]=[CH:26][CH:27]=[C:28]([Cl:29])[C:23]=2[Cl:22])=[O:32])=[C:7]([OH:21])[C:8]=1[S:13]([NH:16][CH2:17][CH:18]1[CH2:20][CH2:19]1)(=[O:14])=[O:15]
Reactant: O=C=Nc1cccc(Cl)c1Cl
Reactant: Nc1ccc(Cl)c(S(=O)(=O)NCC2CC2)c1O
Agent: NC(N)=O
Product: O=C(Nc1ccc(Cl)c(S(=O)(=O)NCC2CC2)c1O)Nc1cccc(Cl)c1Cl
Yield: 53.8 %

Procedure:
Following the general procedure for urea formation outlined in example 15, 3-amino-6-chloro-N-cyclopropylmethyl-2-hydroxybenzenesulfonamide (0.23 g, 0.77mmol) and 2,3-dichlorophenylisocyanate (100 μL, 0.76 mmol) were coupled to form the desired urea (0.19 g, 53%). LC-MS m/z 464 (M+).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](Cl)=[C:8]([C:11]([NH2:13])=[O:12])[CH:7]=[N:6][N:5]2[CH:14]=1.[NH2:15][CH:16]1[CH2:20][N:19]([C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])[CH2:18][C:17]1([CH3:32])[CH3:31].O>CN(C)C=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH:15][CH:16]3[CH2:20][N:19]([C:21]([O:23][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[O:22])[CH2:18][C:17]3([CH3:32])[CH3:31])=[C:8]([C:11](=[O:12])[NH2:13])[CH:7]=[N:6][N:5]2[CH:14]=1
Reactant: NC(=O)c1cnn2cc(Br)cc2c1Cl
Reactant: CC1(C)CN(C(=O)OCc2ccccc2)CC1N
Solvent: CN(C)C=O
Solvent: O
Product: CC1(C)CN(C(=O)OCc2ccccc2)CC1Nc1c(C(N)=O)cnn2cc(Br)cc12
Temperature: 90 °C
Reaction time: 3 h
Yield: 64.4 %

Procedure:
A solution of 6-bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (Intermediate 2, 63.0 mg, 0.230 mmol) in N,N-dimethylformamide (0.5 mL), was added benzyl 4-amino-3,3-dimethylpyrrolidine-1-carboxylate (Intermediate 11, 57 mg, 0.230 mmol) and N,N-diiospropylethylamine (0.121 mL), and heated at 90° C. for 16 h. The reaction was added water, stirred at rt for a 3 hours and filtered. The solid was rinsed with water and dried under vacuum to give benzyl 4-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-3,3-dimethylpyrrolidine-1-carboxylate (72 mg, 64.5% yield) as a yellow solid. 1H NMR (400 MHz, METHANOL-d4) δ 10.83-10.77 (m, 1H), 8.16 (s, 1H), 7.67 (s, 1H), 7.41-7.27 (m, 7H), 7.09-7.04 (m, 1H), 5.18-5.08 (m, 2H), 4.56-4.45 (m, 1H), 4.16-3.95 (m, 1H), 3.42 (d, J=2.2 Hz, 3H), 1.20 (d, J=13.9 Hz, 6H); MS (ES+) m/z: 486.4, 487.9 (M+H); LC retention time: 4.02 min (analytical HPLC Method I).
Reaction SMILES: N1C=CC=CC=1.P(Cl)(Cl)(Cl)(Cl)Cl.C1(CC([NH:22][CH:23]2[C:54](=[O:55])[N:25]3[C:26]([C:38]([O:40][CH:41]([C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)[C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)=[O:39])=[C:27]([CH:30]=[CH:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=4)[CH2:28][S:29][C@H:24]23)=O)C=CC=CC=1.CO>C(Cl)Cl>[NH2:22][CH:23]1[C:54](=[O:55])[N:25]2[C:26]([C:38]([O:40][CH:41]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)=[O:39])=[C:27]([CH:30]=[CH:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=3)[CH2:28][S:29][C@H:24]12
Reactant: O=C(Cc1ccccc1)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(C=Cc3ccccn3)CS[C@H]12
Agent: ClP(Cl)(Cl)(Cl)Cl
Solvent: CO
Solvent: c1ccncc1
Solvent: ClCCl
Product: NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(C=Cc3ccccn3)CS[C@H]12
Yield: 68.8 %

Procedure:
To a suspension of pyridine-phosphorus pentachloride complex prepared from pyridine (48 g) and phosphorus pentachloride (12.7 g) in methylene chloride (120 ml) was added benzhydryl 7-phenylacetamido-3-[2-(2-pyridyl)vinyl]-3-cephem-4-carboxylate (trans isomer) (12 g) under ice-cooling with stirring. The mixture was stirred at the same temperature for 30 minutes and poured into methanol (90 ml) at -25° C. The mixed solution was further stirred at -5° to -15° C. for 10 minutes and then was evaporated under reduced pressure. To the residue was added a mixture of tetrahydrofuran (200 ml), ethyl acetate (200 ml) and water (200 ml) and the mixture was adjusted to pH 6.5 with a saturated aqueous solution of sodium bicarbonate. The separated organic layer was washed with brine, dried over magnesium sulfate and evaporated to give benzhydryl 7-amino-3-[2-(2-pyridyl)vinyl]-3-cephem-4-carboxylate (trans isomer) (6.6 g).
Reaction SMILES: CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:34][C:35]([CH3:40])([CH3:39])[C:36](O)=[O:37].[NH2:41][C@H:42]1[C:50]2[C:45](=[CH:46][CH:47]=[C:48]([C:51]([O:53][CH3:54])=[O:52])[CH:49]=2)[CH2:44][CH2:43]1>C1COCC1>[F:34][C:35]([CH3:40])([CH3:39])[C:36]([NH:41][C@H:42]1[C:50]2[C:45](=[CH:46][CH:47]=[C:48]([C:51]([O:53][CH3:54])=[O:52])[CH:49]=2)[CH2:44][CH2:43]1)=[O:37]
Reactant: CC(C)(F)C(=O)O
Reactant: COC(=O)c1ccc2c(c1)[C@H](N)CC2
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: COC(=O)c1ccc2c(c1)[C@H](NC(=O)C(C)(C)F)CC2
Reaction time: 0.25 h
Yield: 52 %

Procedure:
DIPEA (1.68 ml, 10.2 mmol, 3 eq) and HATU (1.29 g, 3.4 mmol, 1 eq) were added to a solution, cooled to 0° C., of 2-fluoro-2-methylpropanoic acid (360 mg, 3.4 mmol, 1 eq) in THF (15 ml). The reaction mixture was stirred for 15 min, then a solution of (R)-methyl 3-amino-2,3-dihydro-1H-indene-5-carboxylate (A-07) (650 mg, 3.4 mmol, 1 eq) in THF (5 ml) was added and stirring was carried out for 16 h at room temperature. The reaction mixture was concentrated under reduced pressure, taken up in dichloromethane (50 ml) and washed with saturated sodium hydrogen carbonate solution (20 ml), saturated ammonium chloride solution (20 ml), water (20 ml) and saturated sodium chloride solution (20 ml). It was then dried over sodium sulfate and concentrated under reduced pressure, and the crude product was purified by column chromatography (silica gel, 2% methanol/dichloromethane). Yield: 52% (500 mg, 1.79 mmol)
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]([Cl:6])=[O:5].[Cl-].[C:8]([O:11][CH:12]([CH2:30][O:31][C:32](=[O:34])[CH3:33])[CH2:13][NH:14][C:15](=[O:29])[C:16]1[C:24]([I:25])=[C:23]([NH2:26])[C:22]([I:27])=[C:18]([C:19]([OH:21])=[O:20])[C:17]=1[I:28])(=[O:10])[CH3:9]>O1CCOCC1>[Cl-:6].[C:8]([O:11][CH:12]([CH2:30][O:31][C:32](=[O:34])[CH3:33])[CH2:13][NH:14][C:15](=[O:29])[C:16]1[C:24]([I:25])=[C:23]([NH:26][C:4](=[O:5])[CH2:3][O:2][CH3:1])[C:22]([I:27])=[C:18]([C:19]([OH:21])=[O:20])[C:17]=1[I:28])(=[O:10])[CH3:9]
Reactant: COCC(=O)Cl
Reactant: CC(=O)OCC(CNC(=O)c1c(I)c(N)c(I)c(C(=O)O)c1I)OC(C)=O
Agent: [Cl-]
Solvent: C1COCCO1
Product: COCC(=O)Nc1c(I)c(C(=O)O)c(I)c(C(=O)NCC(COC(C)=O)OC(C)=O)c1I

Procedure:
24.7 g (150 mmol) of methoxyacetyl chloride is added at room temperature to a suspension of 73.4 g (100 mmol) of 5-amino-2,4,6-triiodisophthalic acid-N-(2,3-diacetoxypropyl)-amide-chloride (EP 0308364) in 500 ml of anhydrous dioxane, stirred with exclusion of moisture. The batch is refluxed for several hours, until no more feedstock can be detected according to thin-layer chromatography, then it is concentrated by evaporation, the residue is taken up in dichloromethane and shaken out with saturated aqueous sodium bicarbonate solution. After drying on anhydrous magnesium sulfate, the organic phase is concentrated by evaporation and the residue is recrystallized from ethyl acetate/tert-butyl methyl ether.
Reaction SMILES: [Cl:1][C:2]1[C:7]2[N:8]([CH3:12])[C:9](=[O:11])[S:10][C:6]=2[CH:5]=[C:4]([Cl:13])[C:3]=1[CH3:14].[Br:15]N1C(=O)CCC1=O>N(C(C)(CC(C)(OC)C)C#N)=NC(C)(CC(OC)(C)C)C#N.ClCCl>[Br:15][CH2:14][C:3]1[C:4]([Cl:13])=[CH:5][C:6]2[S:10][C:9](=[O:11])[N:8]([CH3:12])[C:7]=2[C:2]=1[Cl:1]
Reactant: Cc1c(Cl)cc2sc(=O)n(C)c2c1Cl
Reactant: O=C1CCC(=O)N1Br
Agent: COC(C)(C)CC(C)(C#N)N=NC(C)(C#N)CC(C)(C)OC
Solvent: ClCCl
Product: Cn1c(=O)sc2cc(Cl)c(CBr)c(Cl)c21
Yield: 70 %

Procedure:
A mixture of 4,6-dichloro-3,5-dimethyl-2-benzothiazolinone (1.30 g), N-bromosuccinimide (1.03 g), 2,2'-azobis-(2,4-dimethyl-4-methoxyvaleronitrile) (65 mg) and dichloromethane (26 ml) was heated under reflux for 2 hours. N-Bromosuccinimide (500 mg) was added therein and the mixture was heated under reflux for additional 4 hours. The reaction mixture was washed with water twice and brine, dried over magnesium sulfate and evaporated in vacuo. The residue was crystallized from diethyl ether to give 5-bromomethyl-4,6-dichloro-3-methyl-2-benzothiazolinone (1.20 g) as crystals.
Reaction SMILES: C(OC[C:6]1[CH2:13][S:12][C@H:11]2[N:8]([C:9](=[O:18])[C@H:10]2[NH:14][C:15]([NH2:17])=[S:16])[C:7]=1[C:19]([O:21][CH:22]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20])(=O)C.Br[CH2:36][C:37](=O)[C:38]([O:40][CH2:41][CH3:42])=[O:39].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:41]([O:40][C:38]([C:37]1[N:17]=[C:15]([NH:14][CH:10]2[C:9](=[O:18])[N:8]3[CH:11]2[S:12][CH2:13][CH:6]=[C:7]3[C:19]([O:21][CH:22]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[O:20])[S:16][CH:36]=1)=[O:39])[CH3:42]
Reactant: CCOC(=O)C(=O)CBr
Reactant: CC(=O)OCC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)[C@@H](NC(N)=S)[C@H]2SC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)c1csc(NC2C(=O)N3C(C(=O)OC(c4ccccc4)c4ccccc4)=CCSC23)n1
Reaction time: 8 h

Procedure:
A mixture of 450 mg of (6R-trans)-3-[(acetyloxy)methyl]-7-[(aminothioxomethyl)amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, diphenylmethyl ester, 195 mg of 3-bromo-2-oxopropanoic acid, ethyl ester, 70 mg of potassium carbonate and 7 ml of acetonitrile was stirred overnight and then filtered through hydrous magnesium silicate. The filtrate was evaporated, giving 510 mg of (6R-trans)-3-[acetyloxy)methyl]-7-[[4-(ethoxycarbonyl)-2-thiazolyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, diphenylmethyl ester.
Reaction SMILES: [CH3:1][C:2]1([CH3:33])[CH2:11][CH:10]=[C:9]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][CH3:19])=[CH:14][CH:13]=2)[C:8]2[CH:7]=[C:6]([C:20]#[C:21][C:22]3[CH:32]=[CH:31][C:25]([C:26]([O:28]CC)=[O:27])=[CH:24][CH:23]=3)[CH:5]=[CH:4][C:3]1=2.[OH-].[Na+].Cl>CCO.C1COCC1>[CH3:33][C:2]1([CH3:1])[CH2:11][CH:10]=[C:9]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][CH3:19])=[CH:14][CH:13]=2)[C:8]2[CH:7]=[C:6]([C:20]#[C:21][C:22]3[CH:23]=[CH:24][C:25]([C:26]([OH:28])=[O:27])=[CH:31][CH:32]=3)[CH:5]=[CH:4][C:3]1=2
Reactant: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2ccc(CC)cc2)=CCC3(C)C)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: CCc1ccc(C2=CCC(C)(C)c3ccc(C#Cc4ccc(C(=O)O)cc4)cc32)cc1
Temperature: 50 °C

Procedure:
To a solution of ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(4-ethylphenyl)-2-naphthalenyl)ethynyl]benzoate (Compound 5) 47.0 mg (0.108 mmol) in 3 ml of EtOH and 2 ml of THF was added 28.0 mg (0.70 mmol, 0.7 ml) of NaOH (1.0 M aqueous solution). The solution was heated to 50° C. for 2 hours, cooled to room temperature, and acidified with 10% HCl. Extraction with EtOAc, followed by drying over Na2SO4, and removal of the solvents under reduced pressure afforded the title compound as a colorless solid. 1H NMR (DMSO): δ 7.90 (2H, d, J=8.3 Hz), 7.59 (2H, d, J=8.3 Hz), 7.46 (2H, s), 7.29-7.21 (4H, m), 7.02 (1H, s), 6.01 (1H, t, J=4.5 Hz), 2.64 (2H, q, J=7.5 Hz), 2.33 (2H, d, J=4.5 Hz), 1.29 (6H, s), 1.22 (3H, t, J=7.5 Hz).
Reaction SMILES: Br[C:2]1[CH:15]=[CH:14][C:13]2[C:4](=[C:5]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:6]3[C:11]([C:12]=2[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH:3]=1.C([Li])CCC.C[O:34][B:35](OC)[O:36]C.Cl>C1COCC1>[C:16]1([C:12]2[C:11]3[C:6]([C:5]([C:4]4[CH:13]=[CH:14][CH:15]=[CH:2][CH:3]=4)=[C:22]4[C:23]=2[CH:24]=[C:25]([B:35]([OH:36])[OH:34])[CH:26]=[CH:27]4)=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Brc1ccc2c(-c3ccccc3)c3ccccc3c(-c3ccccc3)c2c1
Reactant: COB(OC)OC
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OB(O)c1ccc2c(-c3ccccc3)c3ccccc3c(-c3ccccc3)c2c1
Temperature: -78 °C
Reaction time: 1 h
Yield: 80.8 %

Procedure:
Dehydrated THF 50 mL was added to 3.5 g (8.6 mmol) of 2-bromo-9,10-diphenylanthracene under argon atmosphere and cooled down to −78° C., and 6.0 mL of n-butyllithium (in 1.6M hexane) was dropwise added thereto. After stirring at −78° C. for one hour, the temperature was elevated up to 0° C. The solution was cooled down again to −78° C., and 2.9 mL (26 mmol) of trimethoxyborane was dropwise added thereto. The solution was stirred at −78° C. for one hour and then stirred at room temperature for 2 hours. 10% HCl 50 mL was added thereto, and the solution was stirred for one hour and then filtered. The solid matter thus obtained was washed with toluene to obtain 2.6 g (yield: 80%) of 9,10-diphenylanthracene-2-boronic acid.
Reaction SMILES: O=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+].C(#N)C.[C:31]([C:34]1([CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][C:58]([NH2:60])=[O:59])[CH2:42][C:41]2[C:36](=[C:37]([O:49]C)[C:38]([O:47][CH3:48])=[C:39]([O:45][CH3:46])[C:40]=2[O:43]C)[CH2:35]1)(=[O:33])[NH2:32]>O>[C:31]([C:34]1([CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][C:58]([NH2:60])=[O:59])[CH2:42][C:41]2[C:40](=[O:43])[C:39]([O:45][CH3:46])=[C:38]([O:47][CH3:48])[C:37](=[O:49])[C:36]=2[CH2:35]1)(=[O:33])[NH2:32]
Reactant: COc1c2c(c(OC)c(OC)c1OC)CC(CCCCCCCC(N)=O)(C(N)=O)C2
Agent: O=[N+]([O-])[O-]
Agent: [Ce+4]
Agent: [NH4+]
Solvent: CC#N
Solvent: O
Product: COC1=C(OC)C(=O)C2=C(CC(CCCCCCCC(N)=O)(C(N)=O)C2)C1=O
Reaction time: 0.25 h
Yield: 36.6 %

Procedure:
A water (1.0 ml) solution of CAN (334 mg, 0.610 mmols) was dropwise added to an acetonitrile (2.0 ml) solution of 8-(2-carbamoyl-4,5,6,7-tetramethoxyindan-2-yl)octanamide (103 mg, 0.244 mmols) with cooling with ice and stirring was continued for 15 minutes. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and then dried. The solvent was evaporated out in vacuo and the resulting crude product was purified by silica gel column chromatography (ethyl acetate) followed by recrystallization from ethyl acetate to obtain the entitled compound (35 mg) as crystals.
Reaction SMILES: [F:1][C:2]1[C:7]([CH3:8])=[C:6]([F:9])[C:5]([F:10])=[C:4](F)[C:3]=1[F:12].[CH2:13]([OH:16])[CH2:14][CH3:15].[OH-].[Na+].[Br:19]N1C(=O)CCC1=O>O>[CH2:13]([O:16][C:4]1[C:5]([F:10])=[C:6]([F:9])[C:7]([CH2:8][Br:19])=[C:2]([F:1])[C:3]=1[F:12])[CH2:14][CH3:15]
Reactant: Cc1c(F)c(F)c(F)c(F)c1F
Reactant: CCCO
Reactant: O=C1CCC(=O)N1Br
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCOc1c(F)c(F)c(CBr)c(F)c1F

Procedure:
This compound can be prepared by reacting pentafluorotoluene with propanol and sodium hydroxide in water, as described for the preparation of compound 37, followed by bromination with N-bromosuccinimide.
Reaction SMILES: [NH2:1][CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]#[N:13])[CH:10]=2)[O:5][C:4]([CH3:15])([CH3:14])[CH:3]1[OH:16].[F:17][C:18]([F:30])([F:29])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[S:25](Cl)(=[O:27])=[O:26]>N1C=CC=CC=1>[C:12]([C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[O:5][C:4]([CH3:14])([CH3:15])[C@@H:3]([OH:16])[C@@H:2]2[NH:1][S:25]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[C:18]([F:17])([F:29])[F:30])(=[O:27])=[O:26])#[N:13]
Reactant: O=S(=O)(Cl)c1ccccc1C(F)(F)F
Reactant: CC1(C)Oc2ccc(C#N)cc2C(N)C1O
Solvent: c1ccncc1
Product: CC1(C)Oc2ccc(C#N)cc2[C@@H](NS(=O)(=O)c2ccccc2C(F)(F)F)[C@@H]1O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of 1 g of 4-amino-6-cyano-2,2-dimethyl-3-hydroxychroman and 1 g of 2-trifluoromethylbenzenesulfonyl chloride in 25 ml of pyridine is stirred at room temperature for 18 hours.
Reaction SMILES: [H-].[Na+].FC(F)CO.C([NH:12][S:13]([C:16]1[C:21]([I:22])=[CH:20][CH:19]=[CH:18][C:17]=1[F:23])(=[O:15])=[O:14])(C)(C)C.FC(F)(F)C(O)=O>O1CCCC1>[F:23][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]([I:22])[C:16]=1[S:13]([NH2:12])(=[O:14])=[O:15]
Reactant: CC(C)(C)NS(=O)(=O)c1c(F)cccc1I
Agent: OCC(F)F
Agent: [H-]
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: C1CCOC1
Product: NS(=O)(=O)c1c(F)cccc1I
Temperature: 25 °C

Procedure:
0.64 g (26.57 mmol) of sodium hydride is introduced in 10 ml of dry tetrahydrofuran and this initial charge is slowly admixed at room temperature with 2.18 g (26.57 mmol) of 2,2-difluoroethanol. The reaction mixture is stirred at room temperature until the evolution of gas ceases. Thereafter 4.00 g (13.29 mmol) of 2-fluoro-6-iodo-benzenesulfonamide, obtained from the reaction of N-(tert-butyl)-2-fluoro-6-iodobenzenesulfonamide with trifluoroacetic acid in analogy to example A3, in solution in 20 ml of dry tetrahydrofuran, are added dropwise. This reaction mixture is exposed to a microwave energy of 100 watts at 150° C. for 30 min. Thereafter the pH is adjusted to 4-5 using 2 N hydrochloric acid and the mixture is partitioned in water/ethyl acetate, the organic phase being dried and evaporated. This gives 3.00 g (62% of theory) of 2-(2,2-difluoroethoxy)-6-iodobenzenesulfonamide.
Reaction SMILES: [Cl:1][C:2]1[C:16]([Cl:17])=[CH:15][C:5]2[NH:6][C:7]([C:9](=[O:14])[C:10]([F:13])([F:12])[F:11])=[N:8][C:4]=2[CH:3]=1.[C:18]1([Mg]Br)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C1COCC1.C(Cl)Cl>[Cl:17][C:16]1[C:2]([Cl:1])=[CH:3][C:4]2[NH:8][C:7]([C:9]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)([OH:14])[C:10]([F:13])([F:11])[F:12])=[N:6][C:5]=2[CH:15]=1
Reactant: O=C(c1nc2cc(Cl)c(Cl)cc2[nH]1)C(F)(F)F
Reactant: Br[Mg]c1ccccc1
Solvent: ClCCl
Solvent: C1CCOC1
Product: OC(c1ccccc1)(c1nc2cc(Cl)c(Cl)cc2[nH]1)C(F)(F)F
Temperature: 0 °C
Reaction time: 4 h

Procedure:
To 1-(5,6-dichloro-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanone (595 mg) in THF (5 mL) at −78° C. was added phenyl magnesium bromide (4.6 mL of 1 M in THF) dropwise. The resulting mixture was stirred at 0° C. for 4 hr. The reaction was quenched with H2O and 1 N HCl, extracted with EtOAc, dried over Na2SO4, filtered, and concentrated to a residue. The residue was purified by flash chromatography with Biotage 40s+ column and elution with 10%-40% EtOAc/hexanes to yield a yellow solid. The yellow solid was dissolved in a minimal amount of CH2Cl2 and triturated with hexanes to yield the title compound as a tan solid.
Reaction SMILES: [CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[O:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1.[CH2:19]([Li])[CH2:20][CH2:21][CH3:22].[O-][Si]([O-])=O.[Mg+2]>[Cu](Cl)Cl.O.CCCCCC>[C:1]1([C:19]2[C:16]3[C:17]4[CH:9]=[CH:1][CH:2]=[CH:3][C:18]=4[O:14][C:15]=3[CH:22]=[CH:21][CH:20]=2)[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: [Li]CCCC
Reactant: C1CCOC1
Reactant: c1ccc2c(c1)oc1ccccc12
Agent: Cl[Cu]Cl
Agent: O=[Si]([O-])[O-]
Agent: [Mg+2]
Solvent: O
Solvent: CCCCCC
Product: c1ccc2c(c1)oc1cccc(-c3cccc4oc5ccccc5c34)c12
Temperature: -80 °C
Reaction time: 2 h
Yield: 60 %

Procedure:
Into a 500-mL three-neck flask was put 6.0 g (35 mmol) of dibenzofuran, and the air in the flask was replaced with nitrogen. To this flask was added 100 mL of tetrahydrofuran (abbreviation: THF), and this solution was cooled down to −80° C. Then, 22 mL (35 mmol) of n-butyllithium (a 1.6 mol/L hexane solution) was dripped into this solution with a syringe. After that, this mixture solution was stirred for 2 hours while its temperature was increased to room temperature. After the stirring, the solution was cooled down to −80° C., 4.8 g (36 mmol) of copper(II) chloride was added thereto, and the mixture was stirred for 15 hours while its temperature was returned to room temperature. After the stirring, approximately 500 mL of water was added to this solution, followed by stirring for 1 hour to precipitate a solid. The precipitated solid was collected by suction filtration. The collected solid was dissolved in approximately 200 mL of hot toluene, this mixture was stirred and suction-filtered through Celite (Catalog No. 531-16855, produced by Wako Pure Chemical Industries, Ltd.), alumina, and Florisil (Catalog No. 540-00135, produced by Wako Pure Chemical Industries, Ltd.). The obtained filtrate was recrystallized from toluene/hexane to give 3.5 g of white powder, which was an objective substance, in 60% yield. Synthesis Scheme (c-1) of Step 1 is shown below.
Reaction SMILES: [SiH:1]([Cl:4])([CH3:3])[CH3:2].[SiH:5]([Cl:8])([Cl:7])[Cl:6].[CH2:9]([Cl:12])[CH:10]=[CH2:11]>>[Si:5]([CH2:11][CH2:10][CH2:9][Cl:12])([Cl:8])([Cl:7])[Cl:6].[Si:1]([CH2:11][CH2:10][CH2:9][Cl:12])([CH3:3])([CH3:2])[Cl:4]
Reactant: C=CCCl
Reactant: C[SiH](C)Cl
Reactant: Cl[SiH](Cl)Cl
Product: C[Si](C)(Cl)CCCCl
Product: ClCCC[Si](Cl)(Cl)Cl
Yield: 8.6 %
Yield: 60.4 %

Procedure:
In a 100 ml apparatus, there were combined 7.1 g (0.075 mol) of Me2SiHCl, 10.2 g (0.075 mol) of Cl3SiH, and 5.7 g (0.075 mol) of allyl chloride. Pt catalyst solution (0.01 ml) was added at 33° C., causing an exothermic reaction to 47° C. in 7 min. VPC analysis 14 min. later showed a complete reaction. Vacuum distillation yielded 60.4% Cl3SiCH2CH2CH2Cl and 8.6% Me2SiClCH2CH2CH2Cl. This example shows that Me2SiHCl is an effective promoter for the reaction of Cl3SiH with allyl chloride at the equimolar level.