Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].[F:9][C:10]([F:22])([F:21])[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([OH:20])=[O:19])=[CH:13][CH:12]=1.I[CH2:24][CH:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1>O1CCCC1.CN(C)P(N(C)C)(N(C)C)=O.CN(C)P(N(C)C)(N(C)C)=O>[CH:25]1([CH2:24][CH:17]([C:14]2[CH:13]=[CH:12][C:11]([C:10]([F:21])([F:22])[F:9])=[CH:16][CH:15]=2)[C:18]([OH:20])=[O:19])[CH2:29][CH2:28][CH2:27][CH2:26]1
Reactant: O=C(O)Cc1ccc(C(F)(F)F)cc1
Reactant: ICC1CCCC1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: C1CCOC1
Product: O=C(O)C(CC1CCCC1)c1ccc(C(F)(F)F)cc1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 65.2 %

Procedure:
A solution of freshly prepared lithium diisopropylamide (23 mL of a 0.31M stock solution, 7.13 mmol) cooled to −78° C. was treated with (4-trifluoromethyl-phenyl)-acetic acid (693 mg, 3.4 mmol) in tetrahydrofuran/hexamethylphosphoramide (8.5 mL, 3:1). The resulting solution was stirred at −78° C. for 30 min. Iodomethylcyclopentane (784 mg, 3.7 mmol) was then added in hexamethylphosphoramide (1 mL). The mixture was stirred at −78° C. for 4 h. The reaction was then warmed to 25° C. and was stirred at 25° C. for 16 h. The reaction mixture was then quenched by the dropwise addition of a saturated aqueous ammonium chloride solution (10 mL). The excess solvent was removed in vacuo. The residue was acidified to pH=1 with a 1N aqueous hydrochloric acid solution. The mixture was then poured into water (150 mL) and extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 75/25 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-trifluoromethyl-phenyl)-propionic acid (634.9 mg, 65%) as a white solid: mp 94–95° C.; EI-HRMS m/e calcd for C15H17F3O2 (M+) 309.1079, found 309.1072.
Reaction SMILES: BrC1C=CC2C3C(=CC(Br)=CC=3)[C:5]([CH2:24][CH2:25][CH2:26][CH2:27]CCCC)([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])C=2C=1.[CH2:32]([Li])[CH2:33][CH2:34][CH3:35].CO[Si:39](OC)([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>CCCCCC.C1(C)C=CC=CC=1.C(OCC)C>[C:35]1([Si:39]([C:20]2[C:19]3[CH2:18][C:17]4[C:26](=[CH:25][CH:24]=[CH:5][CH:16]=4)[C:27]=3[CH:23]=[CH:22][CH:21]=2)([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:34]2[CH2:35][C:25]3[C:32](=[CH:17][CH:16]=[CH:5][CH:24]=3)[C:33]=2[CH:32]=[CH:33][CH:34]=1
Reactant: [Li]CCCC
Reactant: CCCCCCCCC1(CCCCCCCC)c2cc(Br)ccc2-c2ccc(Br)cc21
Reactant: CO[Si](OC)(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Solvent: CCCCCC
Solvent: CCOCC
Product: c1ccc([Si](c2ccccc2)(c2cccc3c2Cc2ccccc2-3)c2cccc3c2Cc2ccccc2-3)cc1

Procedure:
Under a nitrogen gas atmosphere, 4.90 g (8.94 mmol) of 2,7-dibromo-9,9-dioctylfluorene, 20 ml of diethyl ether and 10 ml of toluene were added to a 100 ml three-necked flask equipped with a reflux condenser and a dropping funnel. Under cooling by an ice bath, 6.1 ml (9.76 mmol) of a hexane solution of n-butyllithium (1.6 M) was added dropwise. As the hexane solution of butyllithium was added dropwise, the solution turned red. The solution was agitated “as is” for approximately 1 hour; then, 1.03 g (4.21 mmol) of dimethoxydiphenylsilane was added, and this mixture was reacted under agitation all night.
Reaction SMILES: [NH2:1][C:2]1[N:25]=[C:5]2[NH:6][C:7]([CH3:24])=[C:8]([C:22]#[N:23])[CH:9]([C:10]3[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][C:11]=3[S:18]([CH3:21])(=[O:20])=[O:19])[N:4]2[N:3]=1.[C:26]1(=O)[O:31][C:29](=[O:30])[C:28]2=[CH:32][CH:33]=[CH:34][CH:35]=[C:27]12.C(N(CC)CC)C>C1(C)C=CC=CC=1.N1C=CC=CC=1>[C:16]([C:13]1[CH:14]=[CH:15][C:10]([CH:9]2[N:4]3[N:3]=[C:2]([N:1]4[C:29](=[O:30])[C:28]5[C:27](=[CH:35][CH:34]=[CH:33][CH:32]=5)[C:26]4=[O:31])[N:25]=[C:5]3[NH:6][C:7]([CH3:24])=[C:8]2[C:22]#[N:23])=[C:11]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:12]=1)#[N:17]
Reactant: O=C1OC(=O)c2ccccc21
Reactant: CC1=C(C#N)C(c2ccc(C#N)cc2S(C)(=O)=O)n2nc(N)nc2N1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CC1=C(C#N)C(c2ccc(C#N)cc2S(C)(=O)=O)n2nc(N3C(=O)c4ccccc4C3=O)nc2N1

Procedure:
Under argon, (rac)-2-amino-7-[4-cyano-2-(methylsulfonyl)phenyl]-5-methyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile (60 mg, 0.17 mmol) together with phthalic anhydride (50.02 mg, 0.34 mmol, 2.0 eq.) was suspended in a mixture of toluene (4 ml) and pyridine (2 ml), triethylamine (4.7 μl, 0.034 mmol, 0.2 eq.) was added and the mixture was heated under reflux for 2 h. The reaction mixture was then concentrated under reduced pressure. From the residue, the product was precipitated by addition of ethanol (2 ml) in an ultrasonic bath. The precipitate was filtered off and dried under high vacuum. This gave 67 mg (75.6% of theory) of the title compound.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][CH:3]([OH:6])[CH2:2]1.C(N(CC)CC)C.[S:14](Cl)([CH3:17])(=[O:16])=[O:15].O>C(Cl)Cl>[O:1]1[CH2:5][CH2:4][CH:3]([O:6][S:14]([CH3:17])(=[O:16])=[O:15])[CH2:2]1
Reactant: CS(=O)(=O)Cl
Reactant: OC1CCOC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: CS(=O)(=O)OC1CCOC1
Reaction time: 1 h
Yield: 0.1 %

Procedure:
A solution of tetrahydrofuran-3-ol (4.6 g, 52.2 moles) in methylene chloride (70 ml) at 0° C. was added with triethylamine (8.36 ml, 60 moles) and mesyl chloride (4.44 ml, 57.4 moles) in methylene chloride (85 ml). The temperature was left to rise to room value and after 1 hour the mixture was poured into water and in methylene chloride. The organic phases were anhydrified and dried to give 8.12 g of the title product (yield: 93%).
Reaction SMILES: [Cl:1][C:2]([F:14])([F:13])[C:3]1[NH:8][C:7](=[O:9])[C:6]([C:10]([OH:12])=O)=[CH:5][CH:4]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:27][O:28][CH2:29][CH2:30][NH2:31]>O1CCCC1>[Cl:1][C:2]([F:14])([F:13])[C:3]1[NH:8][C:7](=[O:9])[C:6]([C:10]([NH:31][CH2:30][CH2:29][O:28][CH3:27])=[O:12])=[CH:5][CH:4]=1
Reactant: O=C(O)c1ccc(C(F)(F)Cl)[nH]c1=O
Reactant: COCCN
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: COCCNC(=O)c1ccc(C(F)(F)Cl)[nH]c1=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
500 mg (2.2 mmol) of 6-[chloro(difluoro)methyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid were dissolved in 10 ml of tetrahydrofuran, 508 mg (3.1 mmol) of N,N-carbonyldiimidazole were added and the mixture was then stirred initially at room temperature for 30 min and then under reflux for min. A solution of 202 mg (2.7 mmol) of 2-methoxyethylamine in 2 ml of tetrahydrofuran was then added dropwise, and the mixture was heated under reflux for a further 2 h. The solution was evaporated to dryness, the residue was taken up in ethyl acetate and the solution was washed with 1N hydrochloric acid and water, dried and concentrated. This gave 360 mg (54% of theory) of a light-brown powder.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:10][CH:11]1[C:19]2[C:14](=[CH:15][C:16]([N+:20]([O-])=O)=[CH:17][CH:18]=2)[C:13](=[O:23])[CH2:12]1.C(N(CC)CC)C.C(OCC)(=O)C>ClCCl>[CH3:10][CH:11]1[C:19]2[C:14](=[CH:15][C:16]([NH:20][C:1](=[O:8])[C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:17][CH:18]=2)[C:13](=[O:23])[CH2:12]1
Reactant: O=C(Cl)c1ccccc1
Reactant: CC1CC(=O)c2cc([N+](=O)[O-])ccc21
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CC1CC(=O)c2cc(NC(=O)c3ccccc3)ccc21
Reaction time: 2 h
Yield: 87.7 %

Procedure:
As presented in the following reaction formula, a solution of benzoyl chloride (PhCOCl; 6.7 g, 0.043 mol) in dichloromethane (DCM; 20 mL) was added at 0° C. to a mixture of 3-methyl-6-nitro-2,3-dihydro-1-H-inden-1-one (7 g, 0.043 mol) and triethylamine (9.6 g, 0.095 mol) in dichloromethane (DCM; 100 mL), and the reaction mixture was stirred for 2 hours. After the completion of reaction, the mixture was washed with water (50 mL), saturated sodium hydrogen carbonate (50 mL) and saturated brine (50 mL) and then concentrated to give a crude product. The crude product was purified by silica gel (50 g) column chromatography (product of Merck Co., Ltd.) using an eluent of pentane (PE):ethyl acetate (10:1 (by volume)) to give the desired product N-(1-methyl-3-oxo-indan-5-yl)benzamide (10 g, yield: 87%) as a yellow solid.
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:6]=[C:7]([C:9]([F:13])=[CH:10][C:11]=1[Cl:12])[NH2:8])[CH:2]=[CH2:3].[CH2:14]1[CH:19]2[C:20]([O:22][C:23](=O)[CH:18]2[CH2:17][CH:16]=[CH:15]1)=[O:21].C(O)(=O)C>O>[CH2:1]([O:4][C:5]1[CH:6]=[C:7]([N:8]2[C:20](=[O:21])[C:19]3[CH2:14][CH2:15][CH2:16][CH2:17][C:18]=3[C:23]2=[O:22])[C:9]([F:13])=[CH:10][C:11]=1[Cl:12])[CH:2]=[CH2:3]
Reactant: C=CCOc1cc(N)c(F)cc1Cl
Reactant: O=C1OC(=O)C2CC=CCC12
Solvent: O
Solvent: CC(=O)O
Product: C=CCOc1cc(N2C(=O)C3=C(CCCC3)C2=O)c(F)cc1Cl
Temperature: 25 °C

Procedure:
A mixture of 9.0 g of 19A, 6.8 g of THPA and 100 mL of glacial acetic acid was heated at reflux temperature for 4 hours. The resulting mixture was cooled to room temperature, poured into 450 mL of water and extracted with ether. The extract phase was washed with water, dried (Na2SO4), and filtered, and the solvent was evaporated from the filtrate. The residue was flash-chromatographed on silica gel, with a 15:85 v:v mixture of ethyl acetate and hexane as eluent, to give N-(3-(allyloxy)-4-chloro-6-fluorophenyl)-3,4,5,6-tetrahydrophthalimide (19B), as an orange oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C:13](Cl)=[O:14])=[CH:10][C:9]=2[C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)=[CH:4][CH:3]=1.[BH4-].[Na+]>O1CCOCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:12][C:11]([CH2:13][OH:14])=[CH:10][C:9]=2[C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)=[CH:6][CH:7]=1
Reactant: CS(=O)(=O)c1ccc(-c2cc(C(=O)Cl)sc2-c2ccc(F)cc2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: CS(=O)(=O)c1ccc(-c2cc(CO)sc2-c2ccc(F)cc2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 49.9 %

Procedure:
A mixture of 5-(4-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]thiophene-2-carbonyl chloride (1.2 g) and sodium borohydride (0.21 g) in dioxane (15 ml) was stirred at ambient temperature for 2 hours. The mixture was diluted with ethyl acetate, washed with water, dilute hydrochloric acid, an aqueous solution of sodium bicarbonate, successively, dried and concentrated. The residue (1.2 g) was recrystallized from ethanol to give pale brown crystals of 5-(4-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]thiophene-2-methanol (0.55 g).
Reaction SMILES: C1(N=C=NC2CCCCC2)CCCCC1.[C:16]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][C:35]([C:37]2[CH:45]=[CH:44][C:43]([C:46]([O:48][C:49]3[CH:54]=[CH:53][C:52]([O:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][O:62][C:63](=[O:66])[CH:64]=[CH2:65])=[CH:51][CH:50]=3)=[O:47])=[CH:42][C:38]=2[C:39]([OH:41])=[O:40])=[O:36])=[CH:30][CH:29]=1)(=[O:19])[CH:17]=[CH2:18].[N+:67]([C:70]1[CH:75]=[CH:74][C:73]([N:76]=[N:77][C:78]2[CH:94]=[CH:93][C:81]([C:82]([O:84][C:85]3[CH:90]=[CH:89][C:88]([CH2:91]O)=[CH:87][CH:86]=3)=[O:83])=[CH:80][CH:79]=2)=[CH:72][CH:71]=1)([O-:69])=[O:68].O>CN(C)C1C=CN=CC=1.ClCCl>[C:16]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:29]=[CH:30][C:31]([O:34][C:35]([C:37]2[CH:45]=[CH:44][C:43]([C:46]([O:48][C:49]3[CH:50]=[CH:51][C:52]([O:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][O:62][C:63](=[O:66])[CH:64]=[CH2:65])=[CH:53][CH:54]=3)=[O:47])=[CH:42][C:38]=2[C:39]([O:41][CH2:91][C:88]2[CH:89]=[CH:90][C:85]([O:84][C:82](=[O:83])[C:81]3[CH:80]=[CH:79][C:78]([N:77]=[N:76][C:73]4[CH:74]=[CH:75][C:70]([N+:67]([O-:69])=[O:68])=[CH:71][CH:72]=4)=[CH:94][CH:93]=3)=[CH:86][CH:87]=2)=[O:40])=[O:36])=[CH:32][CH:33]=1)(=[O:19])[CH:17]=[CH2:18]
Reactant: C=CC(=O)OCCCCCCOc1ccc(OC(=O)c2ccc(C(=O)Oc3ccc(OCCCCCCOC(=O)C=C)cc3)c(C(=O)O)c2)cc1
Reactant: O=C(Oc1ccc(CO)cc1)c1ccc(N=Nc2ccc([N+](=O)[O-])cc2)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: O
Product: C=CC(=O)OCCCCCCOc1ccc(OC(=O)c2ccc(C(=O)Oc3ccc(OCCCCCCOC(=O)C=C)cc3)c(C(=O)OCc3ccc(OC(=O)c4ccc(N=Nc5ccc([N+](=O)[O-])cc5)cc4)cc3)c2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 44.1 %

Procedure:
0.2 g of N,N'-dicyclohexylcarbodiimide is added at room temperature while stirring to a solution of 0.6 g of 2,5-bis[4-(6-acryloyloxyhexyloxy)phenylcarboxy]benzoic acid, 0.4 g of (4-[4-(4-nitrophenylazo)benzoyloxy]phenyl)methanol and 0.04 g of 4-dimethylaminopyridine in 20 ml of dichloromethane. The reaction as mixture is stirred at room temperature overnight, poured into 100 ml of water and then extracted three times with 50 ml of dichloromethane each time. The organic phases are combined, washed twice with 100 ml of water each time, dried over magnesium sulphate, filtered and the filtrate is concentrated. Chromatographic purification of the residue on silica gel with hexane/ethyl acetate (vol. 1:1) and two-fold recrystallization from acetone of the fractions which are pure according to thin-layer chromatography gives 0.4 g of (4-[4-(4-nitrophenylazo)benzoyloxy]phenyl)methyl 2,5-bis[4-(6-acryloyloxyhexyloxy)phenylcarboxy]benzoate.
Reaction SMILES: [F:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:19]=[C:18](O)[CH:17]=[C:16]([CH3:21])[N:15]=2)=[N:6]1.C(=O)([O-])[O-].[Na+].[Na+].P(Cl)(Cl)([Cl:34])=O>>[Cl:34][C:18]1[CH:17]=[C:16]([CH3:21])[N:15]=[C:14]([C:7]2[C:8]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[N:5]([CH2:4][C:3]3[CH:22]=[CH:23][CH:24]=[CH:25][C:2]=3[F:1])[N:6]=2)[N:19]=1
Reactant: Cc1cc(O)nc(-c2nn(Cc3ccccc3F)c3ncccc23)n1
Reactant: O=P(Cl)(Cl)Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: Cc1cc(Cl)nc(-c2nn(Cc3ccccc3F)c3ncccc23)n1
Temperature: 100 °C

Procedure:
300 mg (0.90 mmol) of 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-methyl-4-pyrimidinol (example I, step 6) are suspended in 2 ml of phosphoryl chloride and stirred at 100° C. After the reaction is complete, a concentrated aqueous sodium carbonate solution is added, and the mixture is extracted with diethyl ether. The organic phase is dried over magnesium sulfate and filtered, and the solvent is removed in vacuo. 256 mg (77% of theory) of the product are obtained.
Reaction SMILES: C1(=O)[N:5]([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:17]=[C:18]([C:24]#[N:25])[C:19](=[O:23])[NH:20][C:21]=3[CH3:22])=[CH:12][CH:11]=2)C(=O)C2=CC=CC=C12.O.NN>C(O)C>[NH2:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH:17]=[C:18]([C:24]#[N:25])[C:19](=[O:23])[NH:20][C:21]=2[CH3:22])=[CH:14][CH:15]=1
Reactant: Cc1[nH]c(=O)c(C#N)cc1-c1ccc(OCCCN2C(=O)c3ccccc3C2=O)cc1
Agent: NN
Solvent: O
Solvent: CCO
Product: Cc1[nH]c(=O)c(C#N)cc1-c1ccc(OCCCN)cc1
Yield: 67.7 %

Procedure:
A solution of 1.885 g (4.70 mmol) of 5-(4-phthalimidopropyloxyphenyl)-6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile and 251 μl (5.17 mmol) of hydrazine monohydrate in 50 ml of ethanol is heated 16 hr at reflux. The volatiles are removed under vacuum and the residue is taken up in 15 ml of 1:1 CHCl3 :CH3 and flashchromatographed through a 6 inch length column of silica gel (90:10:2 CHCl3 :CH3OH:NH4OH). The solid obtained form the chromatography is recrystallized from CHCl3 :CH3OH to give 901 mg of 5-(4-aminopropyloxyphenyl)-6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile as a yellow powder. 1H-NMR (d6 -DMSO): δ 1.80 (t,2H); 2.73 (t,2H); 3.70 (s broad, 2H); 4.03 (t,2H); 6.92 (d,2H); 7.20 (d,2H); 7.85 (s, 1H).
Reaction SMILES: ClC1C=CC(C(F)(F)F)=CC=1OC1C=C(C=CC=1)C(O)=O.S(Cl)(Cl)=O.CS(N)(=O)=O.[CH3:31][S:32]([NH:35][C:36](=[O:58])[C:37]1[CH:42]=[C:41]([O:43][C:44]2[CH:49]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:47]=[CH:46][C:45]=2[Cl:54])[CH:40]=[CH:39][C:38]=1[N+]([O-])=O)(=[O:34])=[O:33]>C(OCCCC)(=O)C.N1C=CC=CC=1>[CH3:31][S:32]([NH:35][C:36](=[O:58])[C:37]1[CH:38]=[CH:39][CH:40]=[C:41]([O:43][C:44]2[CH:49]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:47]=[CH:46][C:45]=2[Cl:54])[CH:42]=1)(=[O:33])=[O:34]
Reactant: CS(=O)(=O)NC(=O)c1cc(Oc2cc(C(F)(F)F)ccc2Cl)ccc1[N+](=O)[O-]
Agent: CS(N)(=O)=O
Agent: O=C(O)c1cccc(Oc2cc(C(F)(F)F)ccc2Cl)c1
Solvent: c1ccncc1
Solvent: O=S(Cl)Cl
Solvent: CCCCOC(C)=O
Product: CS(=O)(=O)NC(=O)c1cccc(Oc2cc(C(F)(F)F)ccc2Cl)c1

Procedure:
The acid from (b) (0.8 g) was treated with thionyl chloride followed by methanesulphonamide and pyridine as described in paragraph (d) above for compound 32. The product was recrystallised from a mixture of ether and petroleum (b.p. 40°-60°) to give compound 31 with a melting point of 132°-133°.
Reaction SMILES: [F:1][CH:2]1[CH2:4][CH:3]1[N:5]1[C:14]2[C:9](=[CH:10][C:11]([F:17])=[C:12](F)[C:13]=2[F:15])[C:8](=[O:18])[C:7]([C:19]([OH:21])=[O:20])=[CH:6]1.[CH3:22][N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>CS(C)=O>[F:1][CH:2]1[CH2:4][CH:3]1[N:5]1[C:14]2[C:9](=[CH:10][C:11]([F:17])=[C:12]([N:26]3[CH2:27][CH2:28][N:23]([CH3:22])[CH2:24][CH2:25]3)[C:13]=2[F:15])[C:8](=[O:18])[C:7]([C:19]([OH:21])=[O:20])=[CH:6]1
Reactant: CN1CCNCC1
Reactant: O=C(O)c1cn(C2CC2F)c2c(F)c(F)c(F)cc2c1=O
Solvent: CS(C)=O
Product: CN1CCN(c2c(F)cc3c(=O)c(C(=O)O)cn(C4CC4F)c3c2F)CC1
Temperature: 110 °C
Reaction time: 1 h
Yield: 32.9 %

Procedure:
In 3 ml of dimethyl sulfoxide was dissolved 60 mg of 1-(2-fluorocyclopropyl)-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid. After addition of 100 mg of N-methylpiperazine, the mixture was stirred at 110° C. for 1 hour. The solvent was removed, and the residue was distributed between chloroform and water. The chloroform layer was dried, and the solvent was removed by distillation. The residue was crystallized from chloroform-ethanol to yield 25 mg of the product. m.p. 251°-253° C. (dec.)
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([N:10]2[C@@:14]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)([CH3:15])[C@@:13]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)([CH3:23])[N:12]=[C:11]2[C:31]2[CH:32]=[N:33][C:34]([C:40]([CH3:43])([CH3:42])[CH3:41])=[CH:35][C:36]=2[O:37][CH2:38][CH3:39])=[O:9])[CH2:4][CH2:3]1.[CH:44]1[CH:49]=[N:48][CH:47]=[C:46]([N:50]=[C:51]=[O:52])[CH:45]=1>>[C:40]([C:34]1[N:33]=[CH:32][C:31]([C:11]2[N:10]([C:8]([N:5]3[CH2:4][CH2:3][CH:2]([NH:1][C:51]([NH:50][C:46]4[CH:47]=[N:48][CH:49]=[CH:44][CH:45]=4)=[O:52])[CH2:7][CH2:6]3)=[O:9])[C@@:14]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)([CH3:15])[C@@:13]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)([CH3:23])[N:12]=2)=[C:36]([O:37][CH2:38][CH3:39])[CH:35]=1)([CH3:42])([CH3:41])[CH3:43]
Reactant: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCC(N)CC1
Reactant: O=C=Nc1cccnc1
Product: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCC(NC(=O)Nc2cccnc2)CC1

Procedure:
In a manner similar to the method described in example 160, (4-Amino-piperidin-1-yl)-[(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-methanone (example 204) was reacted with pyridine-3-isocyanate (Oakwood Products) to give the title compound. HR-MS (ES, m/z) calculated for C40H46Cl2N7O3 [(M+H)+] 742.3034, observed 742.3029.
Reaction SMILES: O.Cl.[Cl:3][C:4]1[CH:12]=[C:11]2[C:7]([C:8]([S:13]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[C:18]([N+:23]([O-])=O)[CH:17]=3)(=[O:15])=[O:14])=[CH:9][NH:10]2)=[CH:6][CH:5]=1.C(OC(=O)C)C>C(O)C.[Fe]>[Cl:3][C:4]1[CH:12]=[C:11]2[C:7]([C:8]([S:13]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[C:18]([NH2:23])[CH:17]=3)(=[O:15])=[O:14])=[CH:9][NH:10]2)=[CH:6][CH:5]=1
Reactant: Cc1ccc(S(=O)(=O)c2c[nH]c3cc(Cl)ccc23)cc1[N+](=O)[O-]
Agent: [Fe]
Agent: Cl
Solvent: O
Solvent: CCO
Solvent: CCOC(C)=O
Product: Cc1ccc(S(=O)(=O)c2c[nH]c3cc(Cl)ccc23)cc1N
Temperature: 92.5 °C
Reaction time: 0.08 h

Procedure:
To a 250 mL round bottomed flask, added Iron powder (1.56 grams, 27.9 mmol), 10 mL demineralized water and heated to 90-95° C. At this temperature, 4 mL of concentrated hydrochloric acid was added drop wise. The mass was further heated at 90-95° C. for 1 hour. Then cooled the mass to 60° C. and added absolute ethanol (25 mL). A solution of 6-chloro-3-(4-methyl-3-nitro benzenesulfonyl)-1H-indole (obtained from above step) (2.8 grams, 7.9 mmol) in 10 mL absolute ethanol was added lot wise over a period of 15 minutes. Then the mass was refluxed for 3 hours at 80° C. The mass was cooled to 25° C., added ethylacetate (200 mL) and stirred for 5 minutes. The reaction mass was then filtered through buckner funnel, washed with ethylacetate (3×50 mL). Aqueous layer separated from the filtrate and the organic layer was washed with brine solution (1×50 mL), dried over anhydrous sodium sulfate and solvent was concentrated to obtain oily mass. The technical product was further purified by column chromatography to obtain the title product, the eluent being 70% ethylacetate and 30% n-hexane. Yield: 1.47 grams
Reaction SMILES: [CH:1]1([N:6]2[C:11]3[N:12]=[C:13]([S:16][CH3:17])[N:14]=[CH:15][C:10]=3[CH:9]=[C:8]([CH2:18][O:19][C:20](=[O:22])[CH3:21])[C:7]2=[O:23])[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(S(N2C(C3C=CC=CC=3)O2)(=O)=[O:31])C=CC=CC=1.C(OCC)C>ClCCl>[CH:1]1([N:6]2[C:11]3[N:12]=[C:13]([S:16]([CH3:17])=[O:31])[N:14]=[CH:15][C:10]=3[CH:9]=[C:8]([CH2:18][O:19][C:20](=[O:22])[CH3:21])[C:7]2=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=S(=O)(c1ccccc1)N1OC1c1ccccc1
Reactant: CSc1ncc2cc(COC(C)=O)c(=O)n(C3CCCC3)c2n1
Solvent: CCOCC
Solvent: ClCCl
Product: CC(=O)OCc1cc2cnc(S(C)=O)nc2n(C2CCCC2)c1=O
Temperature: 25 °C
Reaction time: 5 h

Procedure:
Acetic acid 8-cyclopentyl-2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-ylmethyl ester (0.85 g, 2.55 mmol), prepared as in Example 26, and 2-benzenesulfonyl-3-phenyl-oxaziridine (0.8 g, 3.06 mmol) were mixed in dichloromethane (20 ml) and stirred at room temperature for 5 hours. To this mixture was added diethyl ether giving a solid precipitate which was filtered and dried in vacuo to provide acetic acid 8-cyclopentyl-2-methanesulfinyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-ylmethyl ester as a solid (0.81 g,(91%). MS (APCI) M++1; Calc'd 350.41, Found 350.2.
Reaction SMILES: Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@@H:11]1[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@H:12]1[OH:13].[Cl:20][C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[CH2:23][NH2:24].CN(C)C=O.C(O)(C)C>C(N(CC)CC)C>[Cl:20][C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[CH2:23][NH:24][C:2]1[C:3]2[N:4]=[CH:5][N:6]([C:7]=2[N:8]=[CH:9][N:10]=1)[C@@H:11]1[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@H:12]1[OH:13]
Reactant: NCc1ccccc1Cl
Reactant: OC[C@H]1O[C@@H](n2cnc3c(Cl)ncnc32)[C@H](O)[C@@H]1O
Solvent: CCN(CC)CC
Solvent: CC(C)O
Solvent: CN(C)C=O
Product: OC[C@H]1O[C@@H](n2cnc3c(NCc4ccccc4Cl)ncnc32)[C@H](O)[C@@H]1O
Reaction time: 96 h

Procedure:
A mixture of 28.6 g of 6-chloro-9(β-D-ribofuranosyl)-purine, 14.2 g of o-chlorobenzyl amine, 400 ml of dimethylformamide, 400 ml of isopropanol and 50 ml of triethylamine is left to stand at 20° for 4 days. The mixture is evaporated, the residue is dissolved in chloroform, the chloroform solution is washed with 1% aqueous acetic acid and evaporated again and the residue is triturated with ether to give N6 -o-chlorobenzyl-adenosine (Ia). M.p.: 182°-183°.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([N:8]=[C:9]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=3)[N:10]=2)[CH:7]=1.[S:20]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21]1>>[S:20]1[CH:24]=[CH:23][C:22]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([N:8]=[C:9]([NH:11][C:12](=[O:19])[C:13]4[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=4)[N:10]=3)[CH:7]=2)=[CH:21]1
Reactant: O=C(Nc1nc2ccc(Br)cn2n1)c1cccnc1
Reactant: OB(O)c1ccsc1
Product: O=C(Nc1nc2ccc(-c3ccsc3)cn2n1)c1cccnc1
Yield: 23.5 %

Procedure:
The title compound was prepared following procedure described for intermediate A1 step a), but starting from N-(6-bromo[1,2,4]triazolo[1,5-a]pyridin-2-yl)nicotinamide ((B6), 75 mg; 0.24 mmol; 1.0 eq.) and 3-thienylboronic acid (60 mg; 0.47 mmol; 2.0 eq.). Purification by flash chromatography on silica (MeOH/EtOAc, 5:95) gave the title compound as a beige powder (18.1 mg, 23%). HPLC, Rt: 2.13 min. (purity 94.3%). LC/MS, M+(ESI): 322.3, M−(ESI): 320.2.