Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=O.C([CH2:14][C:15]([OH:17])=[O:16])#N.C(O)(=O)C.C([O-])(=O)C.[NH4+]>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH2:10][C:9]2[C:4]([C:3]=1[CH2:14][C:15]([OH:17])=[O:16])=[CH:5][CH:6]=[CH:7][CH:8]=2
Reactant: N#CCC(=O)O
Reactant: CC1Cc2ccccc2C1=O
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Product: CC1=C(CC(=O)O)c2ccccc2C1
Reaction time: 21 h

Procedure:
2-Methylindanone (0.112 mole), cyanacetic acid (10.5 g., 0.123 mole), acetic acid (6.6 g.), and ammonium acetate (1.7 g.) in dry toluene (15.5 ml.) was refluxed with stirring for 21 hrs., as the liberated water was collected in a Dean Stark trap. The toluene was concentrated and the residue dissolved in 60 ml. of hot ethanol and 14 ml. of 2.2 N aqueous potassium hydroxide solution. 22 g. Of 85% KOH in 150 ml. of water was added and the mixture refluxed for 13 hr. under N2. The ethanol was removed under vacuum, 500 ml. water added, the aqueous solution washed well with ether and then boiled with charcoal. The aqueous filtrate was acidified to pH 2 with 50% hydrochloric acid, cooled and the precipitate of 2-methylinden-3-acetic acid was collected.
Reaction SMILES: [Si]([O:8][CH2:9][CH2:10][C:11]1([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=2)[O:16][CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12]1)(C(C)(C)C)(C)C.B1(Br)OC2C(=CC=CC=2)O1.O.[OH-].[Na+]>C(Cl)Cl>[Cl:31][C:26]1[CH:25]=[C:24]([C:11]2([CH2:10][CH2:9][OH:8])[O:16][CH2:15][CH2:14][NH:13][CH2:12]2)[CH:29]=[CH:28][C:27]=1[Cl:30]
Reactant: CC(C)(C)OC(=O)N1CCOC(CCO[Si](C)(C)C(C)(C)C)(c2ccc(Cl)c(Cl)c2)C1
Agent: BrB1Oc2ccccc2O1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: OCCC1(c2ccc(Cl)c(Cl)c2)CNCCO1
Temperature: 25 °C
Reaction time: 2 h
Yield: 100.2 %

Procedure:
7.80 g (15.9 mmole) of 2-[4-t-butoxycarbonyl-2-(3,4-dichlorophenyl)-morpholin-2-yl]ethanol t-butyldimethylsilyl ether [prepared as described in step (c) above] were dissolved in 150 ml of methylene chloride and 7.05 g (35.5 mmole) of B-bromocatecholborane were added. The mixture was then stirred under a stream of nitrogen at room temperature for 2 hours. At the end of this time, 150 ml of water were added to the reaction mixture, and the mixture was then stirred for a further 2 hours. The reaction mixture was made basic by adding a 1 N aqueous solution of sodium hydroxide. It was then extracted with methylene chloride and the extract was washed with a saturated aqueous solution of sodium chloride. The organic extract was then dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting residue was purified by silica gel column chromatography, using a gradient elution method, with mixtures of methylene chloride and methanol ranging from 19:1 to 17:3 by volume as the eluent, to obtain 4.40 g of the title compound.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=1)[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=1)=[O:12].[Cl:28][C:29]1[CH:34]=[C:33](F)[C:32]([F:36])=[CH:31][C:30]=1[S:37]([CH3:40])(=[O:39])=[O:38].O>CN1C(=O)CCC1>[Cl:28][C:29]1[C:30]([S:37]([CH3:40])(=[O:39])=[O:38])=[CH:31][C:32]([F:36])=[C:33]([CH:34]=1)[O:7][C:8]1[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=1)[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=1)=[O:12]
Reactant: C[C@@H](CO)Oc1cc(O)cc(C(=O)Nc2ccn(C)n2)c1
Reactant: CS(=O)(=O)c1cc(F)c(F)cc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN1CCCC1=O
Product: C[C@@H](CO)Oc1cc(Oc2cc(Cl)c(S(C)(=O)=O)cc2F)cc(C(=O)Nc2ccn(C)n2)c1
Temperature: 115 °C
Yield: 49.5 %

Procedure:
Potassium carbonate (1.00 g) was added to a solution of 3-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (1.41 g) and 1-chloro-4,5-difluoro-2-(methylsulfonyl)benzene (0.79 g) in NMP (20 mL). The mixture was heated to 115° C. for 3.5 hours and left to cool before being poured into water (300 mL) and extracted with ethyl acetate (2×150 mL). The combined organics were washed with water, brine and dried (MgSO4) before evaporation in vacuo. Chromatography on silica, eluting with 0 to 10% methanol in ethyl acetate, afforded the desired compound (0.86 g)
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[S:16](=[O:25])(=[O:24])[CH2:15][CH2:14]2)[CH:3]=1.[F:26][C@@H:27]1[CH2:31][NH:30][CH2:29][C@H:28]1[NH:32]C(=O)OC(C)(C)C>>[O:24]=[S:16]1(=[O:25])[C:17]2[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=2[CH2:19][N:13]([C:4]2[CH:3]=[C:2]([N:30]3[CH2:31][C@@H:27]([F:26])[C@H:28]([NH2:32])[CH2:29]3)[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=3)[N:5]=2)[CH2:14][CH2:15]1
Reactant: Cc1ccc2nc(N3CCS(=O)(=O)c4ccccc4C3)cc(Cl)c2c1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CNC[C@H]1F
Product: Cc1ccc2nc(N3CCS(=O)(=O)c4ccccc4C3)cc(N3C[C@@H](N)[C@H](F)C3)c2c1

Procedure:
The title compound was prepared in analogy to Example 78-1 in Scheme 7 by using 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide and tert-butyl (trans-4-fluoropyrrolidin-3-yl)carbamate. MS obsd. (ESI+) [(M+H)+] 441, 1H NMR (400 MHz, CD3OD) δ ppm 7.98 (dd, J=7.71, 1.89 Hz, 1 H), 7.91-7.75 (m, 2 H), 7.62 (t, J=7.45 Hz, 1 H), 7.52 (d, J=8.59 Hz, 1 H), 7.45 (td, J=7.58, 3.28 Hz, 1 H), 7.32 (d, J=8.59 Hz, 1 H), 6.19 (s, 1 H), 5.18 (brs, 2 H), 5.06 (m, 1 H), 4.53 (brs, 2 H), 4.17 (m, 1 H), 4.03 (dd, J=9.98, 5.43 Hz, 1 H), 3.81-3.54 (m, 4 H), 3.45-3.35 (m, 1 H), 2.42 (s, 3 H).
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1.CS(O)(=O)=O.[CH3:18][OH:19]>>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:19][CH3:18])=[CH:7][NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1
Reactant: O=c1[nH]ccc2ccc(F)cc12
Reactant: CO
Agent: CS(=O)(=O)O
Product: COc1c[nH]c(=O)c2cc(F)ccc12
Yield: 84 %

Procedure:
To a solution of 7-fluoroisoquinolin-1(2H)-one (11 g, 67.4 mmol) in methanol was added iodozobenzenediacetate (21.7 g, 67.4 mmol) followed by methane sulphonic acid (7.78 g, 81 mmol) at room temperature. The reaction mass was heated at reflux for 3 h. The solvent was evaporated and the residue was diluted with cold water. The precipitated solid was filtered and washed with water to get crude compound (11 g, 84%) as light red color solid. 1H NMR (400 MHz, CD3OD): δ ppm 8.06-8.04 (m, 1H), 7.96-7.93 (m, 1H), 7.62-7.54 (m, 2H), 6.74 (s, 1H), 3.89 (s, 3H); MS: MS m/z 194.1 (M++1).
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[CH2:5][CH:4]([C:6]([C:8]2[CH:18]=[CH:17][C:11]([C:12]([O:14]CC)=[O:13])=[CH:10][CH:9]=2)=[O:7])[CH2:3]1.O1CCCC1.[OH-].[Na+]>CO>[CH3:1][C:2]1([CH3:19])[CH2:3][CH:4]([C:6]([C:8]2[CH:9]=[CH:10][C:11]([C:12]([OH:14])=[O:13])=[CH:17][CH:18]=2)=[O:7])[CH2:5]1
Reactant: CCOC(=O)c1ccc(C(=O)C2CC(C)(C)C2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CC1(C)CC(C(=O)c2ccc(C(=O)O)cc2)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 77.1 %

Procedure:
To a flask containing ethyl 4-(3,3-dimethylcyclobutanecarbonyl)benzoate (3.00 g, 12.0 mmol) was added anhydrous tetrahydrofuran (28.8 mL), methanol (28.8 mL), and 1 N sodium hydroxide (28.8 mL, 28.8 mmol). After 1 h, the reaction was concentrated to a white solid. The solid was the redissolved in 700 mL of water. With vigorous stirring, 1 N HCl (29.0 mL) was added dropwise and the suspension was stirred for 30 min. at room temperature. The solid was then collected with a Buchner funnel and the solid was washed two times with water. The solid was then azeotrophed with toluene to give 4-(3,3-dimethylcyclobutanecarbonyl)benzoic acid (2.15 g, 92% yield) as a white solid. 1H NMR (400 MHz, CDCl3, δ): 8.21-8.15 (m, 2H), 8.01-7.94 (m, 2H), 3.91 (quin, J=8.9 Hz, 1H), 2.28-2.17 (m, 2H), 2.15-2.04 (m, 2H), 1.28 (s, 3H), 1.09 (s, 3H). MS (M−1): 231.4.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[CH:11]=[C:10]([C:24]([F:27])([F:26])[F:25])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:28][C:29]1[CH:34]=[CH:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][N:30]=1>>[F:25][C:24]([F:27])([F:26])[C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2]([C:32]3[CH:33]=[CH:34][C:29]([NH2:28])=[N:30][CH:31]=3)[CH:7]=[CH:6][CH:5]=2)[CH:13]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[CH:11]=1
Reactant: FC(F)(F)c1ccc(-c2cc(-c3cccc(Br)c3)nc(C(F)(F)F)c2)cc1
Reactant: CC1(C)OB(c2ccc(N)nc2)OC1(C)C
Product: Nc1ccc(-c2cccc(-c3cc(-c4ccc(C(F)(F)F)cc4)cc(C(F)(F)F)n3)c2)cn1

Procedure:
The title compound was prepared from 2-(3-bromo-phenyl)-6-trifluoromethyl-4-(4-trifluoromethyl-phenyl)-pyridine (example E.81) (0.20 g, 0.45 mmol) and commercially available 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.109 g, 0.49 mmol) according to the general procedure VI. Obtained as a white solid (0.110 g, 53%). MS (ISP) 460.2 [(M+H)+]; mp 166° C.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][C:12]1[CH:25]=[CH:24][C:15]([CH2:16][N:17]2[CH2:22][CH2:21][CH:20]([OH:23])[CH2:19][CH2:18]2)=[CH:14][CH:13]=1.C(N(CC)CC)C.[Cl-].[NH4+]>C(Cl)Cl>[CH3:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:16][N:17]2[CH2:18][CH2:19][C:20](=[O:23])[CH2:21][CH2:22]2)=[CH:24][CH:25]=1
Reactant: Cc1ccc(CN2CCC(O)CC2)cc1
Agent: O=C(Cl)C(=O)Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: ClCCl
Product: Cc1ccc(CN2CCC(=O)CC2)cc1
Reaction time: 0.08 h
Yield: 80.8 %

Procedure:
To 2.8 mL (32 mmol) of oxalyl chloride in 75 mL of CH2Cl2 at −78° C. was added 4.6 mL (64 mmol) of DMSO. To this mixture was added 5.3 g (26 mmol) of 1-(4-methylbenzyl)-4-piperidinol 123 in 10 mL of CH2Cl2, and the mixture was stirred 5 min in the cold. The mixture was quenched with 18 mL (129 mmol) of triethylamine and allowed to come to room temperature, and saturated aqueous ammonium chloride was added. The organic phase was washed with water and brine, dried, and evaporated to give 4.27 g (81%) of 1-(4-methylbenzyl)-4-piperidinone (124), which was used as is without further purification. GC/MS showed 100% purity with a molecular ion of 203.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]([CH3:27])([CH3:26])[CH2:10][C:11]([NH:13][C@H:14]1[C:20](=[O:21])[NH:19][C:18]2[CH:22]=[CH:23][CH:24]=[CH:25][C:17]=2[S:16][CH2:15]1)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].I([O-])(=O)(=O)=[O:29].[Na+]>CO.O>[C:1]([O:5][C:6]([NH:8][C:9]([CH3:27])([CH3:26])[CH2:10][C:11]([NH:13][C@H:14]1[C:20](=[O:21])[NH:19][C:18]2[CH:22]=[CH:23][CH:24]=[CH:25][C:17]=2[S:16](=[O:29])[CH2:15]1)=[O:12])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: CC(C)(CC(=O)N[C@@H]1CSc2ccccc2NC1=O)NC(=O)OC(C)(C)C
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CC(C)(CC(=O)N[C@@H]1CS(=O)c2ccccc2NC1=O)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A solution of 179 mg (0.46 mmol) of 3-t-butoxycarbonylamino-3-methyl-N-[3,4-dihydro-4-oxo-1,5-benzothiazepin-3(S)-yl]-butanamide (Example 46, Step A) in 4.5 mL of methanol/water (5:1) was treated with 102 mg (0.48 mmol, 1.05 eq) of sodium periodate and stirred at room temperature for 48 hours. The reaction mixture was filtered and the filtrate concentrated under vacuum. The residue was redissolved in chloroform, dried over potassium carbonate, filtered and concentrated under vacuum. Purification by flash chromatography on silica, eluting with ethyl acetate, afforded 47 mg (0.12 mmol, 25%) of the less polar, minor diastereomer A in addition to 105 mg (0.26 mmol, 56%) of the more polar, major diastereomer B.
Reaction SMILES: [H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][CH2:11][C:12]1([CH3:18])[CH2:16][O:15][C:14](=[O:17])[NH:13]1.[CH2:19](Br)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].O>CN(C)C=O.O1CCCC1>[CH2:19]([O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][CH2:11][C:12]1([CH3:18])[CH2:16][O:15][C:14](=[O:17])[NH:13]1)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]
Reactant: CCCCCCCBr
Reactant: CC1(CCc2ccccc2O)COC(=O)N1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCCOc1ccccc1CCC1(C)COC(=O)N1
Temperature: 25 °C
Reaction time: 2 h
Yield: 83.1 %

Procedure:
To a suspension of sodium hydride (90 mg) in dimethylformamide (1 ml), under ice-cooling, a solution of 4-(2-(2-hydroxyphenyl)ethyl)-4-methyl-2-oxazolidinone (0.50 g) in dimethylformamide (2 ml) was added and the mixture was stirred at room temperature for 2 hours. To the solution, a solution of heptyl bromide (0.47 g) in tetrahydrofuran (2 ml) was added and the mixture was stirred at the same temperature for 5.5 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated brine and dried over magnesium sulfate. The solvent was distilled away under reduced pressure and the residue was subjected to silica gel chromatography (eluent; hexane ethyl acetate=1:1) to give the subject compound (0.60 g).
Reaction SMILES: Br[CH2:2][C:3](=O)[CH2:4][CH2:5][C:6]#[C:7][Si:8]([CH3:11])([CH3:10])[CH3:9].C(=O)([O-])[O-].[K+].[K+].[F:19][C:20]1[CH:21]=[CH:22][C:23]([NH2:26])=[N:24][CH:25]=1>CCO>[F:19][C:20]1[CH:21]=[CH:22][C:23]2[N:24]([CH:2]=[C:3]([CH2:4][CH2:5][C:6]#[C:7][Si:8]([CH3:11])([CH3:10])[CH3:9])[N:26]=2)[CH:25]=1
Reactant: C[Si](C)(C)C#CCCC(=O)CBr
Reactant: Nc1ccc(F)cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: C[Si](C)(C)C#CCCc1cn2cc(F)ccc2n1
Temperature: 80 °C
Yield: 30.4 %

Procedure:
To a stirred solution of 1-bromo-6-(trimethylsilyl)hex-5-yn-2-one (2.50 g, 10.11 mmol) in EtOH (8 mL) was added potassium carbonate (350 mg, 2.53 mmol) and 5-fluoropyridin-2-amine (567 mg, 5.06 mmol). The mixture was heated at 80° C. overnight. The mixture was concentrated, the residue was dissolved in EtOAc, and the organic layer was washed with brine, dried over MgSO4 filtered and concentrated under reduced pressure. The crude residue was purified over silicagel chromatography (prepacked 70 g silicagel column, from DCM/MeOH: 100/0 to 96/4 as eluent) to afford 400 mg of 6-fluoro-2-(4-(trimethylsilyl)but-3-ynyl)-imidazo[1,2-a]pyridine (Yield: 30%) as an orange-brown solid.
Reaction SMILES: [CH2:1](P(=O)(OCC)OCC)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH:18]([C:20]1[CH:25]=[CH:24][C:23]([N:26]([C:34]2[C:47]3[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=3)[C:41]([C:48]3[C:49]4[C:54]([C:55]([N:62]([C:71]5[CH:76]=[CH:75][CH:74]=[CH:73][C:72]=5[CH3:77])[C:63]5[CH:68]=[CH:67][C:66]([CH:69]=O)=[CH:65][CH:64]=5)=[C:56]5[C:61]=3[CH:60]=[CH:59][CH:58]=[CH:57]5)=[CH:53][CH:52]=[CH:51][CH:50]=4)=[C:40]3[C:35]=2[CH:36]=[CH:37][CH:38]=[CH:39]3)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])=[CH:22][CH:21]=1)=O>CS(C)=O>[CH:18]([C:20]1[CH:25]=[CH:24][C:23]([N:26]([C:34]2[C:47]3[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=3)[C:41]([C:48]3[C:49]4[C:54]([C:55]([N:62]([C:71]5[CH:76]=[CH:75][CH:74]=[CH:73][C:72]=5[CH3:77])[C:63]5[CH:68]=[CH:67][C:66]([CH:69]=[CH:1][C:2]6[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=6)=[CH:65][CH:64]=5)=[C:56]5[C:61]=3[CH:60]=[CH:59][CH:58]=[CH:57]5)=[CH:53][CH:52]=[CH:51][CH:50]=4)=[C:40]3[C:35]=2[CH:36]=[CH:37][CH:38]=[CH:39]3)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])=[CH:22][CH:21]=1)=[CH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOP(=O)(Cc1ccccc1)OCC
Reactant: Cc1ccccc1N(c1ccc(C=O)cc1)c1c2ccccc2c(-c2c3ccccc3c(N(c3ccc(C=O)cc3)c3ccccc3C)c3ccccc23)c2ccccc12
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: Cc1ccccc1N(c1ccc(C=Cc2ccccc2)cc1)c1c2ccccc2c(-c2c3ccccc3c(N(c3ccc(C=Cc4ccccc4)cc3)c3ccccc3C)c3ccccc23)c2ccccc12
Temperature: 50 °C
Reaction time: 3 h
Yield: 70.9 %

Procedure:
10,10′-Bis(p-tolylphenylamino)-9,9′-bianthryl(19 g; yield 54%) was prepared as described in Preparation Example 3, except that 20 g of diphenylamine was replaced with 22 g of p-tolylphenylamine. Then, 7 g of 10,10′-bis(p-tolylphenylamino)-9,9′-bianthryl was dissolved in 50 mL of toluene, to which 3.7 g of phosphorus oxychloride was then added, and the mixture was stirred at room temperature. To the mixture was added dropwise 2.7 g of N-methylformanilide, and the mixture was stirred at 50° C. for 5 hours. After completion of the reaction, the mixture was slowly poured into 100 mL of cold water. The mixture was transferred into a separatory funnel and the toluene layer was washed several times until pH of the washing become neutral. The organic layer was dried over magnesium sulfate and evaporated to give 4.5 g (yield 60%) of 10,10′-bis(N-p-formylphenyl-N-tolylamino)-9,9′-bianthryl. To 50 mL of dimethylsulfoxide were added 2.9 g of diethyl benzylphosphonate and 0.6 g of sodium hydride. To the stirred mixture was added dropwise 4.5 g of 10,10′-bis(N-p-formylphenyl-N-tolylamino)-9,9′-bianthryl in 50 mL of dimethylsulfoxide, and the reaction mixture was stirred at 50° C. for 3 hours. After completion of the reaction, the solution was poured into 50 mL of ice-water. The mixture was neutralized with an acid and extracted with ethyl acetate. After evaporating the solvent under a reduced pressure, the residue was purified by column chromatography on silica gel eluting with chloroform, and the product was recrystallized from ethanol to give 3.8 g (yield 70%) of 10,10′-bis(N-p-styrylphenyl-N-tolylamino)-9,9′-bianthryl.
Reaction SMILES: BrCCO[Si](C(C)(C)C)(C)C.Cl[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:16][CH:15]=1.[CH3:28][C:29]1[CH:33]=[C:32]([N:34]2[CH2:38][CH2:37][NH:36][C:35]2=[O:39])[S:31][C:30]=1[C:40]([O:42][CH2:43][CH3:44])=[O:41]>>[C:23]([O:22][C:21]([NH:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][N:36]2[CH2:37][CH2:38][N:34]([C:32]3[S:31][C:30]([C:40]([O:42][CH2:43][CH3:44])=[O:41])=[C:29]([CH3:28])[CH:33]=3)[C:35]2=[O:39])=[CH:15][CH:16]=1)=[O:27])([CH3:26])([CH3:25])[CH3:24]
Reactant: CC(C)(C)OC(=O)Nc1ccc(CCl)cc1
Reactant: CCOC(=O)c1sc(N2CCNC2=O)cc1C
Agent: CC(C)(C)[Si](C)(C)OCCBr
Product: CCOC(=O)c1sc(N2CCN(Cc3ccc(NC(=O)OC(C)(C)C)cc3)C2=O)cc1C
Yield: 80 %

Procedure:
Following the procedure as described in Example 50, making variations as required to replace (2-bromoethoxy)(tert-butyl)dimethylsilane with tert-butyl 4-(chloromethyl)phenylcarbamate to react with ethyl 3-methyl-5-(2-oxoimidazolidin-1-yl)thiophene-2-carboxylate, the title compound was obtained as an off-white solid in 80% yield: 1H NMR (300 MHz, CDCl3) δ 7.34 (d, J=8.2 Hz, 2H), 7.22 (d, J=8.2 Hz, 2H), 6.49 (br s, 1H), 6.14 (s, 1H), 4.41 (s, 2H), 4.27 (q, J=7.1 Hz, 2H), 3.81-3.73 (m, 2H), 3.45-3.37 (m, 2H), 2.49 (s, 3H), 1.51 (s, 9H), 1.34 (t, J=7.1 Hz, 3H); MS (ES+) m/z 482.5 (M+23).
Reaction SMILES: [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:12](OCC)(OCC)([O:14][CH2:15][CH3:16])[CH3:13]>>[C:1]([C:2](=[C:12]([O:14][CH2:15][CH3:16])[CH3:13])[C:3]([O:5][CH2:6][CH3:7])=[O:4])([O:9][CH2:10][CH3:11])=[O:8]
Reactant: CCOC(=O)CC(=O)OCC
Reactant: CCOC(C)(OCC)OCC
Product: CCOC(=O)C(C(=O)OCC)=C(C)OCC
Temperature: 159 °C
Yield: 73 %

Procedure:
160 g (1 mol) of diethyl malonate, 649 g (4 mol) of triethyl orthoacetate and 0.5 g of catalyst from Example 1 were heated to 130° C. in a glass apparatus having a distillation column. The metering-in of 102 g of acetic anhydride over the course of 7 h was then begun. The bottom temperature was increased to 159° C. with the distillation of low-boiling components at a head temperature of 72° to 73° C. After the end of the reaction, the residual low-boiling components were distilled off under a low vacuum and the excess triethyl orthoacetate was removed at 15 mbar. The desired product was then distilled over at 0.3 mbar and a head temperature of 100° to 102° C. Ethyl 2-carboethoxy-3-ethoxy-2-butenoate was obtained in a yield of 73% of the theoretical yield.
Reaction SMILES: [C:1]([N:5]1[C:9](=[O:10])[CH:8]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][C@H:18]([NH:22][S:23]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=3)(=[O:25])=[O:24])[C:19]([NH2:21])=O)=[CH:13][CH:12]=2)[S:6]1(=[O:37])=[O:36])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(Cl)(Cl)C(Cl)=O>C(Cl)Cl.C(OCC)(=O)C>[C:1]([N:5]1[C:9](=[O:10])[CH:8]=[C:7]([C:11]2[CH:12]=[CH:13][C:14]([CH2:17][CH:18]([NH:22][S:23]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:33])[F:34])[CH:27]=3)(=[O:25])=[O:24])[C:19]#[N:21])=[CH:15][CH:16]=2)[S:6]1(=[O:36])=[O:37])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)N1C(=O)C=C(c2ccc(C[C@H](NS(=O)(=O)c3cccc(C(F)(F)F)c3)C(N)=O)cc2)S1(=O)=O
Agent: O=C(Cl)C(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CC(C)(C)N1C(=O)C=C(c2ccc(CC(C#N)NS(=O)(=O)c3cccc(C(F)(F)F)c3)cc2)S1(=O)=O
Temperature: 0 °C
Reaction time: 2 h
Yield: 44.2 %

Procedure:
A solution of 1.37-B of Step 2 (367 mg, 0.66 mmol) in methylene chloride (7.6 mL) was treated with triethylamine (274 μL, 2.0 mmol) followed by trichloroacetyl chloride (117 μL, 1.1 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 2 h, diluted with ethyl acetate (25 mL), washed with water (2×20 mL) and brine (20 mL), dried with sodium sulfate, filtered, and concentrated to a crude residue which was purified by flash column chromatography to yield the desired product (158 mg, 45%). LCMS found for C23H26F3N4O5S2 (M+NH4)+: m/z=559.
Reaction SMILES: C(O)C.[N+:4]([C:7]1[CH:15]=[CH:14][C:10]2[N:11]=[CH:12][NH:13][C:9]=2[CH:8]=1)([O-])=O.[CH2:16]([O:18][C:19](=[O:29])[CH2:20][C:21](=O)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH3:17].S([O-])([O-])(=O)=O.[Ca+2]>O.CC(O)=O>[N:11]1[C:10]2[CH:14]=[CH:15][C:7]([NH:4][C:24]3[CH:23]=[C:22]([CH:27]=[CH:26][CH:25]=3)[CH:21]=[CH:20][C:19]([O:18][CH2:16][CH3:17])=[O:29])=[CH:8][C:9]=2[NH:13][CH:12]=1
Reactant: CCOC(=O)CC(=O)c1ccccc1
Reactant: O=[N+]([O-])c1ccc2nc[nH]c2c1
Agent: O=S(=O)([O-])[O-]
Agent: [Ca+2]
Solvent: O
Solvent: CC(=O)O
Solvent: CCO
Product: CCOC(=O)C=Cc1cccc(Nc2ccc3nc[nH]c3c2)c1

Procedure:
A solution of 900 ml. of ethanol and 82 g. (0.5 mole) of 5-nitrobenzimidazole with 4 g. of 5% PdC, 50% H2O catalyst is reduced on the Parr Apparatus. A pressure drop of 104 psi. is observed (calcd. 100). After the reduction stopped, the bottle is removed from the apparatus, and the catalyst filtered. Then 96 g. (0.5 mole) of ethylbenzoylacetate, 20 g. of anhydrous calcium sulfate and 0.5 ml. of HOAc are added to the filtrate. The solution is refluxed for 2 hours and filtered. The filtrate is concentrated to a dark sticky resin. Crystallization is induced by scratching. The product after cooling is filtered, washed with ethanol and air-dried. The product weighs 55 g. m.p. 188°-190° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[C:6]([OH:11])[CH:5]=1.I[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])=[C:6]([O:11][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9])[CH:5]=1
Reactant: CCCCCCCI
Reactant: COC(=O)c1ccc(O)c(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: CCCCCCCOc1ccc(C(=O)OC)cc1OCCCCCCC
Yield: 198.2 %

Procedure:
A mixture of 25 g of product from Example 102, 72.3 g of 1-iodoheptane, 61.65 g of potassium carbonate and 500 ml of 2-butanone is heated at reflux temperature for 44 hours. The cooled reaction mixture is filtered and concentrated in vacuo. The oily residue is purified by chromatography (silica gel: 10% ethyl acetate/hexane) to give 53.7 g of the desired product.