Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([CH:6]([C:30]1[CH:35]=[CH:34][C:33]2[O:36][CH2:37][O:38][C:32]=2[CH:31]=1)[O:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][N:15]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[N:17](C(OCC)=O)[C:16]2=[O:29])=[CH:10][CH:9]=1)([O:3]CC)=[O:2].C(O)C.[OH-].[Na+].Cl>C(Cl)Cl>[C:1]([CH:6]([C:30]1[CH:35]=[CH:34][C:33]2[O:36][CH2:37][O:38][C:32]=2[CH:31]=1)[O:7][C:8]1[CH:9]=[CH:10][C:11]([CH2:14][N:15]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[NH:17][C:16]2=[O:29])=[CH:12][CH:13]=1)([OH:3])=[O:2]
Reactant: CCOC(=O)C(Oc1ccc(Cn2c(=O)n(C(=O)OCC)c3ccccc32)cc1)c1ccc2c(c1)OCO2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: ClCCl
Product: O=C(O)C(Oc1ccc(Cn2c(=O)[nH]c3ccccc32)cc1)c1ccc2c(c1)OCO2
Temperature: 25 °C
Reaction time: 8 h
Yield: 76.5 %

Procedure:
A round bottom flask was charged with 0.025 g (0.05 mmol) of the product of step C, 0.5 mL of ethanol and the flask and its contents were placed in a sonicator bath. Methylene chloride (0.3 mL) was then added in order to completely dissolve the starting material. Next, 20 μL of a 5.0 N solution of sodium hydroxide were added and the reaction was stirred at room temperature overnight. The reaction mixture was then adjusted to pH=5 with dropwise addition of 6 N hydrochloric acid, and then concentrated in vacuo. The residue was suspended in water to dissolve inorganic salts and filtered. The flitrate was washed with methanol and dried in vacuo to afford 0.016 g (80%) of the title compound.
Reaction SMILES: [CH3:1][S:2]([C:5]1[S:9][C:8]([N:10]2[CH:15]([OH:16])[CH2:14][CH2:13][N:12]([CH2:17][CH:18]=[CH2:19])[C:11]2=[O:20])=[N:7][N:6]=1)(=[O:4])=[O:3].Cl[C:22]([O:24][CH2:25][C:26]#[CH:27])=[O:23]>N1C=CC=CC=1>[CH3:1][S:2]([C:5]1[S:9][C:8]([N:10]2[CH:15]([O:16][C:22]([O:24][CH2:25][C:26]#[CH:27])=[O:23])[CH2:14][CH2:13][N:12]([CH2:17][CH:18]=[CH2:19])[C:11]2=[O:20])=[N:7][N:6]=1)(=[O:4])=[O:3]
Reactant: C=CCN1CCC(O)N(c2nnc(S(C)(=O)=O)s2)C1=O
Reactant: C#CCOC(=O)Cl
Solvent: c1ccncc1
Product: C#CCOC(=O)OC1CCN(CC=C)C(=O)N1c1nnc(S(C)(=O)=O)s1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Tetrahydro-1-(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)-3-allyl-6-hydroxy-2(1H)-pyrimidinone (0.05 mole) dissolved in pyridine (80 ml) is charged into a glass reaction vessel equipped with a mechanical stirrer and thermometer. The solution is cooled to a temperature of about 10° C. and propargyl chloroformate (0.06 mole) dissolved in pyridine (25 ml) is slowly added with stirring over a period of about 15 minutes. After the addition is completed, the reaction mixture is warmed to room temperature and is stirred for an additional period of about 20 minutes to ensure completion of the reaction. After this time the reaction mixture is filtered. The filtrate is then combined with water (100 ml) resulting in the formation of a precipitate. This precipitate is recovered by filtration and is dissolved in ether. The ether solution is washed with dilute aqueous sodium carbonate, is dried over anhydrous magnesium sulfate and is filtered. The filtrate is then stripped of ether to yield the desired product tetrahydro-1-(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)-3-allyl-6-propargyloxycarbonyloxy-2(1H)-pyrimidinone as the residue.
Reaction SMILES: I[C:2]1[CH:3]=[CH:4][C:5]([O:13][CH3:14])=[C:6]([CH:8]2[O:12][CH2:11][CH2:10][O:9]2)[CH:7]=1.[NH:15]1[CH:19]=[CH:18][N:17]=[CH:16]1>O1CCCC1.[Cu]>[NH:15]1[CH:19]=[CH:18][N:17]=[C:16]1[C:2]1[CH:3]=[CH:4][C:5]([O:13][CH3:14])=[C:6]([CH:8]2[O:12][CH2:11][CH2:10][O:9]2)[CH:7]=1
Reactant: COc1ccc(I)cc1C1OCCO1
Reactant: c1c[nH]cn1
Agent: [Cu]
Solvent: C1CCOC1
Product: COc1ccc(-c2ncc[nH]2)cc1C1OCCO1
Temperature: 140 °C
Yield: 36.9 %

Procedure:
In a Pyrex high pressure reaction tube, a solution of the preceding dioxolane (200 mg, 0.66 mmol), 140 mg (2.06 mmol) of imidazole and 90 mg (1.4 mmol) of copper powder in 1 mL of anhydrous tetrahydrofuran (THF) was stirred until homogeneous. The solvent was then evaporated under nitrogen, and the tube was sealed and heated in an oil bath at 140° C. for 16 hours. After cooling, the residue was dissolved in 20 mL of THF, filtered through a pad of diatomaceous earth and concentrated in vacuo to an oil. Chromatography on silica gel (100% ethyl acetate (EtOAc)) gave 60 mg of 2-(5-(2-imidazolyl)-2-methoxyphenyl)-1,3-dioxolane as a yellow oil.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[C:4]1[CH:16]=[CH:15][C:14]([C:17]([O:19][CH3:20])=[O:18])=[CH:13][C:5]=1[C:6](=[O:12])[NH:7]2.[NH2:21][C:22]1[CH:27]=[CH:26][C:25]([NH:28][C:29](=[O:36])[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:24][CH:23]=1.Cl>CN1C(=O)CCC1.O>[C:29]([NH:28][C:25]1[CH:24]=[CH:23][C:22]([NH:21][C:2]2[CH:11]=[CH:10][N:9]=[C:8]3[C:3]=2[C:4]2[CH:16]=[CH:15][C:14]([C:17]([O:19][CH3:20])=[O:18])=[CH:13][C:5]=2[C:6](=[O:12])[NH:7]3)=[CH:27][CH:26]=1)(=[O:36])[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1
Reactant: Nc1ccc(NC(=O)c2ccccc2)cc1
Reactant: COC(=O)c1ccc2c(c1)c(=O)[nH]c1nccc(Cl)c12
Agent: Cl
Solvent: O
Solvent: CN1CCCC1=O
Product: COC(=O)c1ccc2c(c1)c(=O)[nH]c1nccc(Nc3ccc(NC(=O)c4ccccc4)cc3)c12
Temperature: 115 °C
Reaction time: 30 h
Yield: 86.4 %

Procedure:
266 (250 mg, 0.77 mol), N-(4-aminophenyl)benzamide (179 mg, 0.85 mmol), and HCl (19 μm, 0.77 mmol, 4.0 M in dioxane) were suspended in NMP (5 mL) and stirred for 30 h at 115° C. The reaction mixture was diluted with H2O. The resulting precipitate was filtered, washed with H2O and MeOH, and dried under vacuum to provide 267 (341 mg, 96% yield) as a white solid. LC-MS (M+H=465, obsd.=465).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([OH:14])=[O:13])[CH:6]=[CH:5]2.[CH3:15][C@@H:16]([CH2:19][CH3:20])[CH2:17]O.S(=O)(=O)(O)O.OC1C=CC(C(O)=O)=CC=1>C(Cl)(Cl)Cl.C1C=CC=CC=1>[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([O:14][CH2:15][C@@H:16]([CH3:17])[CH2:19][CH3:20])=[O:13])[CH:6]=[CH:5]2
Reactant: CC[C@H](C)CO
Reactant: O=C(O)c1ccc2cc(O)ccc2c1
Agent: O=C(O)c1ccc(O)cc1
Agent: O=S(=O)(O)O
Solvent: c1ccccc1
Solvent: ClC(Cl)Cl
Product: CC[C@H](C)COC(=O)c1ccc2cc(O)ccc2c1
Temperature: 25 °C
Yield: 93 %

Procedure:
In a flask equipped with a Dean-Stark trap 6.78 g (0.036 mole) 6-hydroxyl-2-naphthaleneformic acid, 4.76 g (0.054 mole) (S)-2-methyl-1-butanol, 0.2 ml sulfuric acid and 15 ml anhydrous benzene were charged and refluxed for about 15 hours until all the 4-hydroxybenzoic acid was dissolved. The esterification reaction mixture was cooled to room temperature, extracted with ethyl ether, and washed with 5% (w/w) sodium hydrogen carbonate aqueous solution. The ethyl ether layer was collected, concentrated, and purified with column chromatography (ethyl acetate/n-hexane) to obtained light yellow solid. Yield: 93%. The optical rotation: [α]25D =+2.97 (c=1.0 g/dl, chloroform).
Reaction SMILES: [CH3:1][C:2]1[C:3]([NH:7][CH:8]([P:17](=[O:24])([O:21]CC)[O:18]CC)[P:9](=[O:16])([O:13]CC)[O:10]CC)=[N:4][O:5][CH:6]=1>Cl>[CH3:1][C:2]1[C:3]([NH:7][CH:8]([P:17](=[O:18])([OH:24])[OH:21])[P:9](=[O:10])([OH:13])[OH:16])=[N:4][O:5][CH:6]=1
Reactant: CCOP(=O)(OCC)C(Nc1nocc1C)P(=O)(OCC)OCC
Agent: Cl
Product: Cc1conc1NC(P(=O)(O)O)P(=O)(O)O
Yield: 79.4 %

Procedure:
A solution of 3.2 g of tetraethyl [(4-methyl-3-isoxazolyl)amino]methylene-bis(phosphonate) in 32 ml of concentrated hydrochloric acid was heated under reflux for 4 hours. After the reaction mixture was concentrated, the solid obtained was washed with a mixture of methanol-acetonitrile-acetone to give 1.8 g of [(4-methyl-3-isoxazolyl)amino]methylene-bis(phosphonic acid) as a solid.
Reaction SMILES: C([NH:11][CH:12]([CH2:20][CH2:21][Br:22])[C:13]([O:15]C(C)(C)C)=[O:14])(OCC1C=CC=CC=1)=O.Br.NC1CCOC1=O.CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=O.[Cl-].[Ca+2].[Cl-]>>[BrH:22].[NH2:11][CH:12]([CH2:20][CH2:21][Br:22])[C:13]([OH:15])=[O:14]
Reactant: CC(C)(C)OC(=O)C(CCBr)NC(=O)OCc1ccccc1
Agent: Br
Agent: CC(=O)OCc1c2ccccc2c(COC(C)=O)c2ccccc12
Agent: NC1CCOC1=O
Product: NC(CCBr)C(=O)O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
This compound is prepared by a modification of the procedure used by Nollet, Huting and Pandit to prepare tertiary butyl 2-(N-carbobenzyloxy)amino-4-bromobutyrate. (Tetrahedron, 25, 5971 (1969) ##STR11## To 3.64 g (20.0 mmoles) of 2-aminobutyrolactone hydrobromide is added 182 ml of glacial acetic in a 500 ml three-necked flask equipped with a fritted glass gas bubbler, calcium chloride drying tube, and magnetic stirrer. Hydrogen bromide gas is then vigorously bubbled into the resultant suspension while stirring at ambient temperature. After three hours, all of the starting material has gone into solution and hydrogen bromide addition is discontinued. The reaction mixture is stirred at ambient temperature overnight and then is concentrated to dryness at reduced pressure yielding 5.2 g of crude 2-amino-4-bromobutyric acid hydrobromide as a white solid. This crude acid is dissolved in 25 mls absolute methanol after which hydrogen bromide gas is bubbled in for one minute. Monitoring reaction progress by NMR (BrCH2 --:CH3 --O-integration) indicates negligible reaction after stirring overnight at room temperature. After refluxing for 72 hours the reaction is judged to be complete. The reaction mixture is then concentrated to dryness at reduced pressure yielding crude methyl 2-amino-2-bromobutyrate hydrobromide as a colorless oil. To a solution of this crude ester in 25 ml water is added 3.70 g (44.0 mmoles) of sodium bicarbonate while stirring vigorously in an ice bath. Immediately, 3.8 mls (4.1 g; 24 mmoles) of benzylchloroformate is added dropwise over ca. two minutes. After ten minutes, the ice bath is removed, allowing the reaction mixture to warm to room temperature over 30 minutes. It is then poured into a separatory funnel and extracted with ether (3×25 ml), the combined portions of which are washed with saturated sodium bicarbonate (3×25 ml), dried over magnesium sulfate and concentrated, yielding 5.44 g of an oily white solid. Recrystallization from hexane-ether yields 1.96 of methyl-2-(N-carbobenzyloxy)-amino-4-bromo-butyrate (A) as white clusters having mp 87°-9°. This represents a 30% overall yield from 2-amino-butyrolactone hydrobromide. Tlc (Silica Gel F-254; CHCl3) shows one spot having Rf =0.15.
Reaction SMILES: [N+:1]([C:4]12[CH:11]3[CH:6]4[C:7]5([N+:12]([O-:14])=[O:13])[CH:10]3[CH:9]1[CH:8]5[CH:5]24)([O-:3])=[O:2].C(Cl)(=O)C([Cl:18])=O>>[Cl:18][C:8]12[CH:5]3[CH:6]4[CH:11]5[C:4]3([N+:1]([O-:3])=[O:2])[CH:9]1[CH:10]5[C:7]24[N+:12]([O-:14])=[O:13]
Reactant: O=[N+]([O-])C12C3C4C1C1C2C3C41[N+](=O)[O-]
Reactant: O=C(Cl)C(=O)Cl
Product: O=[N+]([O-])C12C3C4C1C1(Cl)C2C3C41[N+](=O)[O-]
Reaction time: 18 h

Procedure:
A mixture of 1,4-dinitrocubane, 1, (388 mg, 2.0 mmol) in oxalyl chloride (50 mL) was photolyzed under a sunlamp for 18 h at room temperature. Oxalyl chloride was removed on a rotary evaporator and the solid residue was partioned between EtOAc (40 mL) and NaOH solution (5%, 30 mL). After stirring for 3 h, the organic phase was separated, washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was chromatogrphed on silica gel using hexane/CH2Cl2 (1:1) to give 2-chloro-1,4-dinitrocubane 3, m.p. 145-147° C.; 1H NMR (CDCl3); δ 4.84 (m, 2H); 4.71 (m, 3H); and 2,5-dichloro-1,4-dinitrocubane, 4, m.p. 188-190° C.; 1H NMR (CDCl3); δ 4.90 (dd, 2H); 4.78 (dd, 2H).
Reaction SMILES: O[CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[C:9]3[N:25]([CH3:26])[CH:24]=[CH:23][C:10]3=[N:11][C:12]=2[C@@H:13]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH3:14])[CH2:3]1.[C:27]1(=[O:37])[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29](=[O:36])[NH:28]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[O:37]=[C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29](=[O:36])[N:28]1[CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[C:9]3[N:25]([CH3:26])[CH:24]=[CH:23][C:10]3=[N:11][C:12]=2[C@@H:13]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:20])([CH3:19])[CH3:21])[CH3:14])[CH2:3]1
Reactant: C[C@H](NC(=O)OC(C)(C)C)c1nc2ccn(C)c2cc1N1CCC(O)C1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: C[C@H](NC(=O)OC(C)(C)C)c1nc2ccn(C)c2cc1N1CCC(N2C(=O)c3ccccc3C2=O)C1
Temperature: 0 °C
Yield: 58.9 %

Procedure:
A mixture of tert-butyl ((1S)-1-(6-(3-hydroxypyrrolidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)carbamate (250 mg, 0.694 mmol), isoindoline-1,3-dione (153 mg, 1.04 mmol) and PPh3 (328 g, 1.25 mmol) in THF (2 mL) was stirred at 0° C. Next, diethyl azodicarboxylate (217 mg, 1.25 mmol) was added dropwise at 0° C. and the mixture was stirred at 20° C. for 16 hours. The solvent was evaporated in vacuo, and the residue was purified by preparative TLC to give the title compound as a white solid (200 mg, 42.3%). ESI-MS m/z [M+H]+ calc'd for C22H31N5O4, 490. found 490.
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].[N:7]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH:19]([CH:23]([C:44]([NH2:46])=[O:45])[C:24]2[CH:43]=[CH:42][C:27]([C:28](NNS(C3C=CC(C)=CC=3)(=O)=O)=[O:29])=[CH:26][CH:25]=2)[CH2:20][CH2:21][CH3:22])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1>C(O)CO>[N:7]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH:19]([CH:23]([C:44]([NH2:46])=[O:45])[C:24]2[CH:25]=[CH:26][C:27]([CH:28]=[O:29])=[CH:42][CH:43]=2)[CH2:20][CH2:21][CH3:22])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1
Reactant: CCCC(c1ccccc1N1CCCCC1)C(C(N)=O)c1ccc(C(=O)NNS(=O)(=O)c2ccc(C)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: OCCO
Product: CCCC(c1ccccc1N1CCCCC1)C(C(N)=O)c1ccc(C=O)cc1
Temperature: 170 °C
Reaction time: 0.02 h

Procedure:
A quantity of 6.6 gm (62 m mol) of sodium carbonate was heated together with 62 ml of ethylene glycol in a bath at 170° C., and, within one minute, 6.2 gm (11 m mol) of N1 -[4-[(1-(2-piperidino-phenyl)-1-butyl)-aminocarbonylmethyl]-benzoyl]-N2 -tosyl-hydrazine [melting point 195° C. (decomposition)] were added thereto, with rapid stirring, whereupon there was a vigorous development of gas. The mixture was then heated for a further two and one-half minutes at 170° C. and then immediately poured onto ice. It was extracted with ether, and the ether solution was dried, filtered, and concentrated by evaporation in vacuo. The evaporation residue was purified by column chromatography on silica gel [chloroform/acetone (20:1)].
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:12]([N:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)=O)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.Cl.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1>[CH3:20][N:17]1[CH2:18][CH2:19][N:14]([CH2:12][C:4]2[CH:3]=[C:2]([CH:7]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:5]=2)[NH2:1])[CH2:15][CH2:16]1
Reactant: CN1CCN(C(=O)c2cc(N)cc(C(F)(F)F)c2)CC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CN1CCN(Cc2cc(N)cc(C(F)(F)F)c2)CC1
Reaction time: 6 h
Yield: 30.7 %

Procedure:
In 50 mL of tetrahydrofuran, 6.14 g (21 mmol) of (3-amino-5-(trifluoromethyl)phenyl)-(4-methylpiperazin-1-yl)methanone was dissolved, and 65 mL of a borane tetrahydrofuran complex (a 1N tetrahydrofuran solution) was added thereto and the mixture solution was refluxed with stirring for six hours. To the reaction solution, 60 mL of concentrated hydrochloric acid was added dropwise and the mixture solution was stirred at room temperature for 12 hours. The reaction solution was neutralized with solid sodium carbonate and extracted with diethyl ether. The extract was washed with water and a saturated sodium chloride solution and concentrated under reduced pressure, and the residue was recrystallized from hexane and diethyl ether to obtain 1.76 g (30%) of a target product as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8](O)[C:9]([F:16])([F:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:5]=[CH:6][CH:7]=1.C(N(S(F)(F)[F:24])CC)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([F:24])[C:9]([F:16])([F:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:5]=[CH:6][CH:7]=1
Reactant: CCN(CC)S(F)(F)F
Reactant: CCOC(=O)C(F)(F)C(O)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCOC(=O)C(F)(F)C(F)c1cccc(Cl)c1
Reaction time: 3 h
Yield: 80.7 %

Procedure:
A solution of 25 g of ethyl 3-(3-chlorophenyl)-3-hydroxy-2,2-difluoropropionate in 140 mL CH2Cl2 was treated with a solution of 14 g of diethylaminosulfurtrifluoride in 10 mL CH2Cl2 at room temperature. After 3 hours, the mixture was poured into aqueous NaHCO3, extracted with ethyl acetate, dried (Na2SO4) and evaporated. The residue was distilled (0.1 mm Hg) to give 18.7 g of an oil which was used directly.
Reaction SMILES: O1C=[CH:4][C:3]([C:6](O)=O)=[CH:2]1.[S:9]1[CH:13]=[CH:12][C:11]([C:14]([OH:16])=[O:15])=[CH:10]1>>[C:14]([C:13]1[S:9][CH:10]=[C:11]([C:14]([O:16][C:3]([CH3:2])([CH3:4])[CH3:6])=[O:15])[CH:12]=1)(=[O:15])[CH2:11][CH3:10]
Reactant: O=C(O)c1ccsc1
Reactant: O=C(O)c1ccoc1
Product: CCC(=O)c1cc(C(=O)OC(C)(C)C)cs1

Procedure:
Instead of the starting material compound of Reference Example 104, that is, 3-furan carboxylic acid, 3-thiophencarboxylic acid was used for the similar procedure as in Reference Example 104 to obtain tert-butyl 5-propionyl-3-thiophencarboxylate.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[CH:6]=[CH:5]2.[C:13]1([CH3:35])[CH:18]=[CH:17][C:16]([N:19]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)[C:20]2[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][CH:21]=2)=[CH:15][CH:14]=1>>[C:31]1([CH3:34])[CH:32]=[CH:33][C:28]([N:19]([C:20]2[CH:21]=[CH:22][C:23]([CH3:24])=[CH:26][CH:27]=2)[C:16]2[CH:17]=[CH:18][C:13]([CH:35]=[CH:12][C:7]3[CH:6]=[CH:5][C:4]4[C:9](=[CH:10][CH:11]=[C:2]([CH3:1])[CH:3]=4)[N:8]=3)=[CH:14][CH:15]=2)=[CH:29][CH:30]=1
Reactant: Cc1ccc(N(c2ccc(C)cc2)c2ccc(C=O)cc2)cc1
Reactant: Cc1ccc2nc(C)ccc2c1
Product: Cc1ccc(N(c2ccc(C)cc2)c2ccc(C=Cc3ccc4cc(C)ccc4n3)cc2)cc1

Procedure:
By using 14 g of 6-methylquinaldine and 25 g of p-di(p-tolyl)aminobenzaldehyde and in the same manner as in Synthetic Example 1 the compound 2-[p-di(p-tolyl)aminostyryl]-6-methylquinoline was obtained. The yield was 24 g and the melting point thereof was 200°-202.5° C. This compound may also be used satisfactorily as a charge transport substance.
Reaction SMILES: [O:1]=[C:2]1[C:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:11][CH:10]=2)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]2[N:26]=[CH:27][CH:28]=[C:4]2[N:3]1[C@H:29]1[CH2:34][CH2:33][C@H:32]([O:35][CH2:36][C:37](=[O:39])[CH3:38])[CH2:31][CH2:30]1.[CH:40]1([Mg]Br)[CH2:42][CH2:41]1.C(OCC)(=O)C>O1CCCC1>[CH:40]1([C:37]([OH:39])([CH3:38])[CH2:36][O:35][C@H:32]2[CH2:31][CH2:30][C@H:29]([N:3]3[C:2](=[O:1])[C:7]([CH2:8][C:9]4[CH:14]=[CH:13][C:12]([C:15]5[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=5)=[CH:11][CH:10]=4)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]4[N:26]=[CH:27][CH:28]=[C:4]34)[CH2:34][CH2:33]2)[CH2:42][CH2:41]1
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@H](OCC(C)=O)CC2)c2ccnn12
Reactant: Br[Mg]C1CC1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@H](OCC(C)(O)C3CC3)CC2)c2ccnn12
Reaction time: 2 h

Procedure:
To a solution of 4′-({5-oxo-4-[trans-4-(2-oxopropoxy)cyclohexyl]-7-propyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (0.30 g) in tetrahydrofuran (3 mL) was added dropwise cyclopropylmagnesium bromide (0.5M tetrahydrofuran solution, 2.3 mL) at 0° C., and the mixture was stirred for 2 hr. To the reaction mixture were added ethyl acetate and then saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (0.22 g, 68%).
Reaction SMILES: [Br:1][C:2]1[C:3](F)=[C:4]2[C:10]([NH:11][C:12](=[O:18])[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[NH:20]1[CH2:25][CH2:24][CH2:23][C@@H:22]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:21]1>C(O)(CC)C>[Br:1][C:2]1[C:3]([N:20]2[CH2:25][CH2:24][CH2:23][C@@H:22]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32])[CH2:21]2)=[C:4]2[C:10]([NH:11][C:12](=[O:18])[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCCNC1
Reactant: CS(=O)(=O)CC(=O)Nc1c[nH]c2ncc(Br)c(F)c12
Solvent: CCC(C)O
Product: CC(C)(C)OC(=O)N[C@@H]1CCCN(c2c(Br)cnc3[nH]cc(NC(=O)CS(C)(=O)=O)c23)C1
Yield: 67.3 %

Procedure:
N-(5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(methylsulfonyl)acetamide (300 mg, 0.857 mmol) and (R)-tert-butyl piperidin-3-ylcarbamate (515 mg, 2.57 mmol) in s-BuOH (5 mL) were heated to 135° C. in a sealed tube for 24 hours. After cooling down, the residue was concentrated and purified by reverse phase chromatography (SP4, 25M, water/ACN 80/20→0/100, 30 CV) to yield (R)-tert-butyl 1-(5-bromo-3-(2-(methylsulfonyl)acetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (306 mg, 67.3% yield) as a solid.
Reaction SMILES: [CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.[C:57]([O:61][C:62]([N:64]1[CH2:69][CH2:68][CH:67]([NH2:70])[CH2:66][CH2:65]1)=[O:63])([CH3:60])([CH3:59])[CH3:58].[OH-].[Na+]>O.ClCCl.C(N(CC)CC)C>[C:57]([O:61][C:62]([N:64]1[CH2:69][CH2:68][CH:67]([NH:70][C:26](=[O:27])[C:25]2[CH:29]=[CH:30][C:22]([NH:21][C:19]3[N:18]=[CH:17][C:8]4[N:9]([CH3:16])[C:10](=[O:15])[C:11]([F:13])([F:14])[CH2:12][N:6]([CH:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)[C:7]=4[N:20]=3)=[C:23]([O:31][CH3:32])[CH:24]=2)[CH2:66][CH2:65]1)=[O:63])([CH3:60])([CH3:58])[CH3:59]
Reactant: COc1cc(C(=O)O)ccc1Nc1ncc2c(n1)N(C1CCCC1)CC(F)(F)C(=O)N2C
Reactant: CC(C)(C)OC(=O)N1CCC(N)CC1
Agent: CN(C)C(N(C)C)=[N+]1N=[N+]([O-])c2ncccc21
Agent: F[P-](F)(F)(F)(F)F
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: COc1cc(C(=O)NC2CCN(C(=O)OC(C)(C)C)CC2)ccc1Nc1ncc2c(n1)N(C1CCCC1)CC(F)(F)C(=O)N2C
Reaction time: 8 h
Yield: 61.3 %

Procedure:
To a mixture of 0.265 g (0.59 mmole) of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-22), 0.2256 g (0.59 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 8 mL of dichloromethane, 0.25 mL of triethylamine was added followed by 0.1181 g (0.59 mmole) of 4-amino-piperidine-1-carboxylic acid tert-butyl ester. After stirring overnight, 16 mL of dichloromethane, 14 mL of water and 0.8 mL of 1M sodium hydroxide was added. The dichloromethane layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with hexanes-ethyl acetate (gradient, 40:60-10:90) to give 0.2278 g of 4-[4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoylamino]-piperidine-1-carboxylic acid tert-butyl ester.