Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH2:6][C:7]2[N:11]([CH:12]([CH2:15][CH3:16])[CH2:13][CH3:14])[C:10]3[CH:17]=[CH:18][C:19]([C:21]([OH:23])=O)=[CH:20][C:9]=3[N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C=O)C.C(Cl)(=O)C([Cl:32])=O>ClCCl>[CH:1]1([CH2:6][C:7]2[N:11]([CH:12]([CH2:15][CH3:16])[CH2:13][CH3:14])[C:10]3[CH:17]=[CH:18][C:19]([C:21]([Cl:32])=[O:23])=[CH:20][C:9]=3[N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CCC(CC)n1c(CC2CCCC2)nc2cc(C(=O)O)ccc21
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CCC(CC)n1c(CC2CCCC2)nc2cc(C(=O)Cl)ccc21
Reaction time: 16 h
Yield: 100 %

Procedure:
To 8.00 g of 2-cyclopentylmethyl-1-(1-ethyl-propyl)-1H-benzoimidazole-5-carboxylic acid in 100 ml of dichloromethane 0.1 ml of DMF and 4 ml of oxalyl chloride were added. The reaction was stirred at it for 16 h, then concentrated and co-distilled with toluene to obtain 8.45 g (100%) of the crude product as a brown solid, which was used without further purification.
Reaction SMILES: CCN(C(C)C)C(C)C.[Br:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[CH:16][C:15]([C:21]([NH2:23])=[O:22])=[C:14]2Cl.Cl.[CH3:26][O:27][CH:28]1[CH2:31][CH:30]([NH2:32])[CH2:29]1>CC(N(C)C)=O.O>[Br:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[CH:16][C:15]([C:21]([NH2:23])=[O:22])=[C:14]2[NH:32][C@H:30]1[CH2:31][C@@H:28]([O:27][CH3:26])[CH2:29]1
Reactant: NC(=O)c1cnc2ccc(Br)cc2c1Cl
Reactant: COC1CC(N)C1
Agent: Cl
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(=O)N(C)C
Product: CO[C@H]1C[C@@H](Nc2c(C(N)=O)cnc3ccc(Br)cc23)C1
Temperature: 100 °C
Reaction time: 18 h
Yield: 68.3 %

Procedure:
DIPEA (13.76 mL, 78.80 mmol) was added to a mixture of 6-bromo-4-chloroquinoline-3-carboxamide (7.5 g, 26.27 mmol) and 3-methoxycyclobutan-1-amine hydrochloride (3.98 g, 28.89 mmol) in DMA (35 mL) and the resulting mixture stirred at 100° C. for 18 h. The reaction mixture was diluted with water (250 mL) and the precipitate was collected by filtration, washed with water (50 mL) and dried under vacuum to afford the desired material (6.28 g, 68.3%) as a tan solid, which was used without further purification. NMR Spectrum: 1H NMR (400 MHz, DMSO-d6) δ 2.45-2.55 (2H, m), 2.76-2.88 (2H, m), 3.17 (3H, s), 3.66 (1H, q), 4-4.16 (1H, m), 7.67 (1H, s), 7.80 (1H, dd), 7.93 (1H, dd), 8.15 (1H, s), 8.59 (1H, s), 8.69 (1H, s), 9.34 (1H, s). Mass Spectrum: m/z (ES+)[M+H]+=350, 352.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[CH2:10][C:11]([C:13]1[CH:20]=[C:19]([CH3:21])[C:16]([C:17]#[N:18])=[C:15]([CH3:22])[CH:14]=1)=[O:12].[H-].[Na+].[CH3:25]I>>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[CH:10]([CH3:25])[C:11]([C:13]1[CH:14]=[C:15]([CH3:22])[C:16]([C:17]#[N:18])=[C:19]([CH3:21])[CH:20]=1)=[O:12]
Reactant: COc1ccc(CC(=O)c2cc(C)c(C#N)c(C)c2)c(Cl)c1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Product: COc1ccc(C(C)C(=O)c2cc(C)c(C#N)c(C)c2)c(Cl)c1

Procedure:
In analogy to Example 1, step 2, 4-[2-(2-chloro-4-methoxy-phenyl)-acetyl]-2,6-dimethyl-benzonitrile was reacted with sodium hydride and methyl iodide to give the title compound as an orange oil. MS (m/e)=328.3 [M+H+].
Reaction SMILES: C(N(CC)CC)C.[C:8]([C:10]1[CH:18]=[CH:17][C:13]([C:14](Cl)=[O:15])=[CH:12][CH:11]=1)#[N:9].[CH3:19][C:20]1[C:21](=[O:49])[N:22]([C:37]2[CH:44]=[CH:43][C:40]([C:41]#[N:42])=[C:39]([C:45]([F:48])([F:47])[F:46])[CH:38]=2)[C:23](=[O:36])[C:24]=1[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1>O1CCCC1.C(OCC)(=O)C>[C:8]([C:10]1[CH:18]=[CH:17][C:13]([C:14]([N:33]2[CH2:34][CH2:35][N:30]([CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][C:24]3[C:23](=[O:36])[N:22]([C:37]4[CH:44]=[CH:43][C:40]([C:41]#[N:42])=[C:39]([C:45]([F:46])([F:47])[F:48])[CH:38]=4)[C:21](=[O:49])[C:20]=3[CH3:19])[CH2:31][CH2:32]2)=[O:15])=[CH:12][CH:11]=1)#[N:9]
Reactant: CC1=C(CCCCCN2CCNCC2)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C1=O
Reactant: N#Cc1ccc(C(=O)Cl)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC1=C(CCCCCN2CCN(C(=O)c3ccc(C#N)cc3)CC2)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
0.2 ml of a solution of triethylamine in tetrahydrofuran (1.5 mol/l) and 7 mg of 4-cyanobenzoyl chloride in 0.4 ml of tetrahydrofuran were added to a solution of 9 mg of 4-[2,5-dihydro-3-methyl-2,5-dioxo-4-[5-(piperazin-1-yl)-pentyl]-1H-pyrrol-1-yl]-2-(trifluoromethyl)benzonitrile in 0.4 ml of tetrahydrofuran, and the mixture was stirred for 8 hours at room temperature. For working-up, the reaction mixture was diluted with ethyl acetate and washed with semi-saturated sodium bicarbonate solution. After the organic phase was concentrated by evaporation, it was chromatographed with methanol/dichloromethane on silica gel, and 7 mg of the title compound was thus obtained as a yellowish oil.
Reaction SMILES: [CH:1]([C:4]1[N:5]=[C:6]([CH2:9][CH2:10][C:11]2[CH:37]=[CH:36][N:14]3[C:15](=[O:35])[C:16](/[CH:26]=[CH:27]/[C:28]([O:30]C(C)(C)C)=[O:29])=[C:17]([O:19][CH2:20][CH:21]4[CH2:25][CH2:24][O:23][CH2:22]4)[N:18]=[C:13]3[CH:12]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2]>C(Cl)Cl.C(O)=O>[CH:1]([C:4]1[N:5]=[C:6]([CH2:9][CH2:10][C:11]2[CH:37]=[CH:36][N:14]3[C:15](=[O:35])[C:16](/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29])=[C:17]([O:19][CH2:20][CH:21]4[CH2:25][CH2:24][O:23][CH2:22]4)[N:18]=[C:13]3[CH:12]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2]
Reactant: CC(C)c1csc(CCc2ccn3c(=O)c(/C=C/C(=O)OC(C)(C)C)c(OCC4CCOC4)nc3c2)n1
Solvent: ClCCl
Solvent: O=CO
Product: CC(C)c1csc(CCc2ccn3c(=O)c(/C=C/C(=O)O)c(OCC4CCOC4)nc3c2)n1
Yield: 156.7 %

Procedure:
The tert-butyl (E)-3-{8-[2-(4-isopropyl-1,3-thiazol-2-yl)ethyl]-4-oxo-2-(tetrahydro-3-furanylmethoxy)-4H-pyrido[1,2-a]pyrimidin-3-yl}-2-propenoate (10 mg) obtained in (A) was dissolved in methylene chloride (1 ml) and formic acid (1 ml), and then the mixture was stirred for 5 hours. After the solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography to obtain the title compound (14 mg).
Reaction SMILES: [CH3:1][S:2]([O:5][C@H:6]1[CH2:10][NH:9][C@H:8]([C:11]([N:13]2[CH2:17][CH2:16][NH:15][C:14]2=[O:18])=[O:12])[CH2:7]1)(=[O:4])=[O:3].[CH2:19](N(CC)CC)C.CI>CO.O1CCCC1>[CH3:1][S:2]([O:5][C@H:6]1[CH2:10][N:9]([CH3:19])[C@H:8]([C:11]([N:13]2[CH2:17][CH2:16][NH:15][C:14]2=[O:18])=[O:12])[CH2:7]1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)O[C@H]1CN[C@H](C(=O)N2CCNC2=O)C1
Reactant: CCN(CC)CC
Solvent: CI
Solvent: CO
Solvent: C1CCOC1
Product: CN1C[C@H](OS(C)(=O)=O)C[C@H]1C(=O)N1CCNC1=O
Temperature: 40 °C
Reaction time: 2 h

Procedure:
To a solution of (2S,4R)-4-methanesulfonyloxy-2-(2-oxoimidazolidin-1-yl)carbonylpyrrolidine (14.9 g) in a mixture of methanol (150 ml) and tetrahydrofuran (150 ml) were added triethylamine (32.5 ml) and methyl iodide (11.4 ml) and the mixture was stirred at 40° C. for 2 hours. The reaction mixture was evaporated in vacuo. The resulting residue was chromatographed on silica gel (600 g) eluting with a mixture of chloroform and methanol (9:1 V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give a residue. The residue was washed with dichloromethane (100 ml). The resulting precipitates were collected and dried in vacuo to give (2S,4R)-4-methanesulfonyloxy-1-methyl-2-(2-oxoimidazolidin-1-yl)carbonylpyrrolidine (2.30 g).
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:8][O:9][C:10]1[CH:11]=[C:12]([CH2:18][NH2:19])[N:13]=[N:14][C:15]=1[O:16][CH3:17].[N:20]#[C:21]Br>C(O)C.O>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:17][O:16][C:15]1[C:10]([O:9][CH3:8])=[CH:11][C:12]2[N:13]([C:21]([NH2:20])=[N:19][CH:18]=2)[N:14]=1
Reactant: COc1cc(CN)nnc1OC
Reactant: N#CBr
Solvent: CCO
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: COc1cc2cnc(N)n2nc1OC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
C-(5,6-Dimethoxypyridazin-3-yl)methylamine trifluoroacetic acid salt (37 mg) was initially charged in a mixture of ethanol and water (3.75/0.75 ml) while stirring at RT. Thereafter, cyanogen bromide solution (0.1 ml; 5M in ACN) was cautiously added dropwise and the mixture was stirred at RT for 3 h. Then further cyanogen bromide solution (0.1 ml) was added and the mixture was left to stand overnight. After again adding cyanogen bromide solution (0.1 ml), the mixture was stirred for 4 h, left to stand over the weekend and then heated to 40° C. for 2 h. Subsequently, the solvent was drawn off and the residue was purified by means of preparative HPLC. The product-containing fractions were combined, freed of the acetonitrile and freeze-dried. 18 mg of the desired compound were obtained.
Reaction SMILES: Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]#[N:12])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[CH2:13]([O:15][C:16](=[O:25])[CH:17]=[CH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)[CH3:14].C(OC(=O)C=C(C1C=CC=C2C=1C(C#N)=CN2)C1C=CC=CC=1)C>>[CH2:13]([O:15][C:16](=[O:25])[CH:17]=[C:18]([C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]#[N:12])=[CH:7][NH:8]2)=[CH:4][CH:3]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)[CH3:14]
Reactant: CCOC(=O)C=Cc1ccccn1
Reactant: N#Cc1c[nH]c2cc(Br)ccc12
Agent: CCOC(=O)C=C(c1ccccc1)c1cccc2[nH]cc(C#N)c12
Product: CCOC(=O)C=C(c1ccc2c(C#N)c[nH]c2c1)c1ccccn1

Procedure:
3-(3-Cyano-1H-indol-6-yl)-3-pyridin-2-yl-acrylic acid ethyl ester CLXX was prepared from 6-bromo-1H-indole-3-carbonitrile (CLI) and 3-pyridin-2-yl-acrylic acid ethyl ester using the procedure described for preparation of 3-(3-Cyano-1H-Indol-4-yl)-3-phenyl-acrylic acid ethyl ester LVIII (Example 14).
Reaction SMILES: [CH3:1][C:2]([CH3:20])([CH3:19])[C:3]#[C:4]/[CH:5]=[CH:6]/[CH2:7][N:8]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([NH2:18])[CH:13]=1)[CH2:9][CH3:10].[N:21]1([C:26]2[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=2)[C:29](O)=[O:30])[CH:25]=[CH:24][CH:23]=[CH:22]1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl.O1CCCC1>[CH3:20][C:2]([CH3:19])([CH3:1])[C:3]#[C:4]/[CH:5]=[CH:6]/[CH2:7][N:8]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([NH:18][C:29](=[O:30])[C:28]2[CH:32]=[CH:33][CH:34]=[C:26]([N:21]3[CH:25]=[CH:24][CH:23]=[CH:22]3)[CH:27]=2)[CH:13]=1)[CH2:9][CH3:10]
Reactant: CCN(C/C=C/C#CC(C)(C)C)Cc1cccc(N)c1
Reactant: O=C(O)c1cccc(-n2cccc2)c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Solvent: C1CCOC1
Product: CCN(C/C=C/C#CC(C)(C)C)Cc1cccc(NC(=O)c2cccc(-n3cccc3)c2)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 72.6 %

Procedure:
83 mg of (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-ethyl-3-aminobenzylamine and 100 mg of 3-(1-pyrrolyl)benzoic acid were dissolved in a mixture of 1 ml of methylene chloride and 2 ml of tetrahydrofuran, and 92 mg of N,N'-dicyclohexylcarbodiimide (DCC) was added. The mixture was stirred at room temperature for 3 hours. The reaction mixture was evaporated under reduced pressure, and the residue was dissolved in methylene chloride. The insoluble material was separated by filtration, and washed successively with a 5% aqueous solution of sodium hydrogen carbonate, 5% hydrochloric acid and a saturated aqueous solution of sodium chloride. It was dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography [Wakogel C-200, 20 g; eluting solvent: hexane/-ethyl acetate =10/1 → 3/1] to give 98 mg (yield 61%) of the captioned compound as a pale yellow oil.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH:14]([O:16]CCCC)=[CH2:15].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC>CC#N.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:14]([C:2]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])(=[O:16])[CH3:15]
Reactant: C=COCCCC
Reactant: COC(=O)c1cc(OC)ccc1Br
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Solvent: O
Solvent: CCN(CC)CC
Product: COC(=O)c1cc(OC)ccc1C(C)=O
Temperature: 99 °C
Reaction time: 16.5 h
Yield: 99.6 %

Procedure:
A mixture of methyl 2-bromo-5-methoxybenzoate (1) (5.0 g, 20.4 mmol), butyl vinyl ether (13.1 mL, 102.0 mmol), Ph3P (802.3 mg, 3.1 mmol), Et3N (3.7 mL, 26.5 mmol), and Pd(OAc)2 (343.0 mg, 1.5 mmol) in MeCN (40 mL) is stirred under argon at 99° C. for 16.5 h and then cooled to room temperature. The residue is diluted with H2O (50 mL), and the resultant suspension is filtered through Celite® (H2O rinse). The filtrate is concentrated to dryness at reduced pressure. To the residue is added tetrahydrofuran (125 mL) and 10% HCl (125 mL). The mixture is stirred for 2 h before the tetrahydrofuran is removed at reduced pressure. This residue is extracted with ethyl acetate (100 mL, 70 mL, and 60 mL). The extract is washed (brine) and dried. After solvent removal at reduced pressure, the residue is purified on silica gel (16.7% to 33.3% ethyl acetate/hexane) to give 4.23 g (99%) of 2 as a yellow liquid. IR 2958, 1730, 1683, 1270 cm−1; 1H NMR (CDCl3) δ 2.55 (s, 3H, CH3CO), 3.90 (s, 3H, CH3O), 3.94 (s, 3H, CO2CH3), 7.04 (dd, J=8.7, 2.7 Hz, 1H, 4-PhH), 7.17 (d, J=2.7 Hz, 1H, 6-PhH), 7.61 ppm (d, J=8.7 Hz, 1H, 3-PhH).
Reaction SMILES: [Cl:1][C:2]1[CH:23]=[CH:22][C:21]([NH:24][C:25](=[O:39])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])=[CH:20][C:3]=1[NH:4][C:5]1[CH2:9][C:8](=[O:10])[N:7]([C:11]2[C:16]([Cl:17])=[CH:15][C:14]([Cl:18])=[CH:13][C:12]=2[Cl:19])[N:6]=1.[C:40]([C:43]1[CH:44]=[C:45]([N:49]2[C:53]([SH:54])=[N:52][N:51]=[N:50]2)[CH:46]=[CH:47][CH:48]=1)([OH:42])=[O:41].O>CN(C)C=O>[Cl:1][C:2]1[CH:23]=[CH:22][C:21]([NH:24][C:25](=[O:39])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])=[CH:20][C:3]=1[NH:4][C:5]1[CH:9]([S:54][C:53]2[N:49]([C:45]3[CH:46]=[CH:47][CH:48]=[C:43]([C:40]([OH:42])=[O:41])[CH:44]=3)[N:50]=[N:51][N:52]=2)[C:8](=[O:10])[N:7]([C:11]2[C:12]([Cl:19])=[CH:13][C:14]([Cl:18])=[CH:15][C:16]=2[Cl:17])[N:6]=1
Reactant: CCCCCCCCCCCCCC(=O)Nc1ccc(Cl)c(NC2=NN(c3c(Cl)cc(Cl)cc3Cl)C(=O)C2)c1
Reactant: O=C(O)c1cccc(-n2nnnc2S)c1
Solvent: O
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCC(=O)Nc1ccc(Cl)c(NC2=NN(c3c(Cl)cc(Cl)cc3Cl)C(=O)C2Sc2nnnn2-c2cccc(C(=O)O)c2)c1
Reaction time: 0.5 h
Yield: 69 %

Procedure:
A mixture of 15.4 g of 3-(2-chloro-5-tetradecaneamidoanilino)-1-(2,4,6-trichlorophenyl)-2-pyrazolin-5-one and 5.4 g of 1-(3-carboxyphenyl)-5-mercaptotetrazole was dissolved in 100 ml of dimethylformamide (DMF), and a solution of 4.9 g of N-glucosuccinic acid imide in 20 ml of DMF was added dropwise thereto at room temperature. The resulting mixture was stirred for 30 minutes, and 500 ml of water was added thereto. The mixture was then extracted with ethyl acetate. The ethyl acetate was distilled away under reduced pressure, and the residue was precipitated from a mixed solvent of ethyl acetate and acetonitrile to obtain 14 g of 3-(2-chloro-5-tetradecaneamidoanilino)-1-(2,4,6-trichlorophenyl)-4-[1-(3-carboxyphenyl)-5-tetrazolylthio]-2-pyrazolin-5-one, m.p., 155°-165° C. Yield was 68%.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH3:10])[CH:7]=[CH:8][CH:9]=1)[CH3:2].P(Cl)(Cl)(Cl)=O.CN([CH:19]=[O:20])C.C([O-])(=O)C.[Na+]>C(OCC)(=O)C.CCCCCC>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:19]=[O:20])=[C:6]([CH3:10])[CH:5]=1)[CH3:2]
Reactant: CCOc1cccc(C)c1
Reactant: CN(C)C=O
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: O=P(Cl)(Cl)Cl
Product: CCOc1ccc(C=O)c(C)c1
Yield: 9.2 %

Procedure:
Using an analogous formylation procedure to that employed by Campaigne et al 3-ethoxytoluene (10.18 g, 75 mmol) was added dropwise to a mixture of phosphorous oxychloride (6.88 mL, 75 mmol) and DMF (21 mL, 0.272 mol) at 0° C. and the resultant mixture was heated to 80-90° C. for 4 hrs before being poured onto crushed ice. The solution was taken to pH 7 with saturated sodium acetate, extracted with dichloromethane and upon drying and solvent removal a clear colourless oil was obtained. Column chromatography (silica, ethyl acetate/hexane, 1:9, Rf 0.33) gave the title compound as a clear colourless oil (1.13 g, 20.40% based on reacted material). 1H n.m.r. [400 MHZ, CDCl3] δ 6 10.09, s, 1H, CHO; 7.73, d, J 8.6 Hz, 1H, H6; 6.81, dd, J 8.5, 1, 1H, H5, 6.72, d, J 1 Hz, 1H, H3; 4.09, q, J 7 Hz, 2H, OCH2CH3; 2.63, s, 3H, ArCH3; 1.43, t, J 6.95 Hz, 3H, CH2CH3. 13C n.m.r. [100 MHZ, CDCl3] d 190.95, CHO; 162.88, C4; 143.02, C2; 134.59, C6; 127.53, C1; 117.23, C3; 111.67, C5; 63.54, OCH2CH3; 19.70, ArCH3; 14.47, OCH2CH3. Mass spectrum (f.a.b.) calculated 164.083724, found 164.084.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]=[CH:7][C:8]([NH:10][C:11]1[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=1[C:13]([OH:15])=[O:14])=[O:9].C(N(CC)CC)C.[C:27](=[O:35])([O:32][CH2:33][CH3:34])[O:28][CH:29](Cl)[CH3:30].[I-].[Na+]>CC(C)=O>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]=[CH:7][C:8]([NH:10][C:11]1[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=1[C:13]([O:15][CH:29]([O:28][C:27]([O:32][CH2:33][CH3:34])=[O:35])[CH3:30])=[O:14])=[O:9]
Reactant: CCOC(=O)OC(C)Cl
Reactant: O=C(C=Cc1cccs1)Nc1ccccc1C(=O)O
Agent: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: CCN(CC)CC
Product: CCOC(=O)OC(C)OC(=O)c1ccccc1NC(=O)C=Cc1cccs1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 25.2 %

Procedure:
A mixture of 2-[3-(2-thienyl)acrylamido]benzoic acid (273 mg, 1 mmol) and triethylamine (0.2 ml, 1.4 mmol) in dry acetone (10 ml) was stirred at room temperature for 30 minutes. To the solution, 1-chloroethyl ethyl carbonate (214 mg, 1.4 mmol) and sodium iodide (210 mg, 1.4 mmol) were added under ice cooling, and the mixture was heated under reflux for 19 hours. The reaction mixture was filtered by suction and the solvent was removed from the filtrate. The residue was dissolved in chloroform, washed with saturated aqueous sodium hydrogen carbonate, then with saturated aqueous sodium chloride, and dried over magnesium sulfate. After removing the solvent, the residue was purified by silica gel column chromatography (developing solvent:benzene:ether=49:1). The second eluate was collected. After removing the solvent, the resulted oily product was crystallized with isopropyl ether to give the desired compound (98 mg, yield, 25%). m.p., 154°-156° C. (white crystals, recrystallized from methanol/tetrahydrofuran/water).
Reaction SMILES: [CH3:1]N(C)C=O.[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[NH:14][CH:15]=[C:16]([N+:18]([O-:20])=[O:19])[CH:17]=2)=[CH:9][CH:8]=1.[H-].[Na+].CI>C1(C)C=CC=CC=1.O>[F:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[N:14]([CH3:1])[CH:15]=[C:16]([N+:18]([O-:20])=[O:19])[CH:17]=2)=[CH:11][CH:12]=1
Reactant: CN(C)C=O
Reactant: O=[N+]([O-])c1c[nH]c(-c2ccc(F)cc2)c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Solvent: CI
Product: Cn1cc([N+](=O)[O-])cc1-c1ccc(F)cc1

Procedure:
To an N,N-dimethylformamide solution (0.50 mL) of 2-(4-fluorophenyl)-4-nitro-1H-pyrrole (10.0 mg, 0.0485 mmol) synthesized in Reference Synthesis Example 245, sodium hydride (2.50 mg, 0.0582 mmol) was added at 0° C. and the resultant mixture was stirred for 1 hour. Thereafter, methyl iodide (18.8 μL, 0.0582 mmol) was added to the reaction solution and the resultant mixture was stirred at room temperature for 7 hours and 30 minutes. After completion of the reaction, water was added to the reaction solution and extraction from the resultant mixture with toluene was performed. The organic layer was concentrated under reduced pressure to obtain the title compound as a crude product.
Reaction SMILES: C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)CCO.C(O)C=C.N.[CH2:41]([N:44](CC=C)[CH2:45][CH:46]=[CH2:47])[CH:42]=[CH2:43]>Cl[Pd]Cl.O>[CH2:41]([NH2:44])[CH:42]=[CH2:43].[CH2:41]([NH:44][CH2:45][CH:46]=[CH2:47])[CH:42]=[CH2:43]
Reactant: C=CCN(CC=C)CC=C
Agent: Cl[Pd]Cl
Agent: N
Agent: c1ccc(P(CCCCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Solvent: C=CCO
Solvent: OCCCO
Solvent: O
Product: C=CCN
Product: C=CCNCC=C
Reaction time: 2 h

Procedure:
To 1.8 mg (0.01 millimole) of PdCl2 was added 8.5 mg (0.02 millimole) of 1,4-bis(diphenylphosphino)butane, and 5.0 g of 1,3-propane-diol and 3.6 g of water were added and reaction between 8.4 g (145 millimoles) of allyl alcohol and 3.2 g (188 millimoles) of ammonia was carried out at 110° C. with stirring for 2 hours. As the products, there were obtained 0.26 g (4.6 millimoles) of monoallylamine, 0.53 g (5.4 millimoles) of diallylamine 0.63 g (4.6 millimoles) of triallylamine. The conversion based on allyl alcohol was 21.5% and the selectivity was 96.8%.
Reaction SMILES: [ClH:1].[CH3:2][CH:3]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=1)[C:4]([O:6][C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=1)=[O:5].[N:22]#[C:23][NH2:24].C(OCC)C>C(O)C>[ClH:1].[CH3:2][CH:3]([CH2:14][C:15]1[CH:16]=[CH:17][C:18]([NH:21][C:23]([NH2:24])=[NH:22])=[CH:19][CH:20]=1)[C:4]([O:6][C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=1)=[O:5]
Reactant: Cc1ccc(OC(=O)C(C)Cc2ccc(N)cc2)cc1
Reactant: N#CN
Agent: Cl
Solvent: CCOCC
Solvent: CCO
Product: Cc1ccc(OC(=O)C(C)Cc2ccc(NC(=N)N)cc2)cc1

Procedure:
In 200 ml of ethanol were dissolved 21.8 g of the p-methylphenyl α-methyl-β-(p-aminophenyl)-propionate hydrochloride obtained and 4.2 of cyanamide, and the resulting solution was subjected to reaction at 70° C. for 5 hours. After the reaction, the solvent was removed by distillation under reduced pressure, to obtain an oily product. A mixture of ethanol and diethyl ether was added thereto and the solution was cooled, upon which crystals precipitated. The crystals were collected by filtration and recrystallized from an ethanol-diethyl ether mixture, to obtain p-methylphenyl α-methyl-β-(p-guanidinophenyl)propionate hydrochloride in the form of colorless crystals. Yield: 17.4 g (70%); melting point: 146°-148° C.; IR (cm-1): 3500-2550, 1748, 1653, 1631; MS: M+ =m/e 312 (M.W. -HCl).
Reaction SMILES: Br[CH2:2][C:3]([NH:5][NH:6][C:7]([N:9]1[CH2:15][C:14]2[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=2[O:12][C:11]2[CH:20]=[CH:21][C:22]([Cl:24])=[CH:23][C:10]1=2)=[O:8])=[O:4].[CH2:25]([O:27][P:28]([O:32]CC)[O:29][CH2:30][CH3:31])[CH3:26].[Na+].[I-]>O1CCCC1.[Na+].[I-]>[CH2:25]([O:27][P:28]([CH2:2][C:3]([NH:5][NH:6][C:7]([N:9]1[CH2:15][C:14]2[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=2[O:12][C:11]2[CH:20]=[CH:21][C:22]([Cl:24])=[CH:23][C:10]1=2)=[O:8])=[O:4])([O:29][CH2:30][CH3:31])=[O:32])[CH3:26]
Reactant: CCOP(OCC)OCC
Reactant: O=C(CBr)NNC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21
Agent: [I-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOP(=O)(CC(=O)NNC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21)OCC
Yield: 83.5 %

Procedure:
To a stirring solution of 2.57 g (6.3 mmol) of 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-(bromoacetyl) hydrazide (19), prepared as described in Example 19 above, in 75 mL of tetrahydrofuran (THF) was added 1.25 g (7.5 mmol) of triethylphosphite and 0.15 g (1 mmol) of NaI. After 22 hours of refluxing, an additional 0.62 g (3.75 mmol) of triethylphosphite and 0.05 g (0.33 mmol) of NaI were added to the reaction, which was refluxed an additional 24 hours. The solvent was then removed under aspirator vacuum, and the reaction mixture was chromatographed to yield 2.46 g (83%) of 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[(diethoxyphosphinyl)acetyl]hydrazide (20), which was a beige foam.