Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[C:6]([C:9](O)=O)=[CH:5][NH:4][C:3]1=[O:12].[ClH:13]>>[CH3:1][N:2]1[C:7](=[O:8])[C:6]([CH2:9][Cl:13])=[CH:5][NH:4][C:3]1=[O:12]
Reactant: Cn1c(=O)[nH]cc(C(=O)O)c1=O
Reactant: Cl
Product: Cn1c(=O)[nH]cc(CCl)c1=O
Yield: 52 %

Procedure:
3-methyluracil-5-carboxylic acid was treated with HCl and CH2 using standard chloromethylation conditions to give 3-methyl-5-chloromethyl uracil in 52% yield (following standard work-up and recrystallization from ethyl acetate). NMR (DMSO-6): chemical shifts, peak integrations & D2O exchange experiments diagnostic for structure.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH2:5][NH:6][CH2:7][C:8]1[S:12][C:11](B(O)O)=[CH:10][CH:9]=1.Br[C:17]1[CH:18]=[C:19]2[C:23](=[C:24]([C:26]([NH2:28])=[O:27])[CH:25]=1)[NH:22][CH:21]=[C:20]2[CH:29]1[CH2:34][CH2:33][N:32]([S:35]([CH2:38][CH3:39])(=[O:37])=[O:36])[CH2:31][CH2:30]1.C([O-])([O-])=O.[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:38]([S:35]([N:32]1[CH2:31][CH2:30][CH:29]([C:20]2[C:19]3[C:23](=[C:24]([C:26]([NH2:28])=[O:27])[CH:25]=[C:17]([C:11]4[S:12][C:8]([CH2:7][NH:6][CH2:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:9][CH:10]=4)[CH:18]=3)[NH:22][CH:21]=2)[CH2:34][CH2:33]1)(=[O:37])=[O:36])[CH3:39]
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(Br)cc23)CC1
Reactant: COCCCNCc1ccc(B(O)O)s1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4ccc(CNCCCOC)s4)cc23)CC1
Yield: 9 %

Procedure:
Following the general procedure of 5-(5-{[(2-ethylbutyl)amino]methyl}-2-thienyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide, (5-formyl-2-thienyl)boronic acid (50 mg, 0.32 mmol), [3-(methyloxy)propyl]amine (29 mg, 0.32 mmol), and NaCNBH3 (40 mg, 0.64 mmol) were reacted to give 30 mg of crude [5-({[3-(methyloxy)propyl]amino}methyl)-2-thienyl]boronic acid. The crude [5-({[3-(methyloxy)propyl]amino}methyl)-2-thienyl]boronic acid was then reacted with 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (65 mg, 0.157 mmol), K2CO3 (130 mg, 0.942 mmol), and tetrakis(triphenylphosphine)palladium(0) (9 mg, 0.0079 mmol). The crude product was purified once on an Agilent MDAP using the procedure shown in preparation of 5-(5-{[(2-ethylbutyl)amino]methyl}-2-thienyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide to give 7.6 mg of the title compound (9%).
Reaction SMILES: [C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][N:11]=2)[CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=1)([CH3:3])=[CH2:2]>C(O)C.[Pd]>[CH:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][N:11]=2)[CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=1)([CH3:3])[CH3:2]
Reactant: C=C(C)c1cc(C(=O)OC)cc(-c2ccc(C)cn2)n1
Agent: [Pd]
Solvent: CCO
Product: COC(=O)c1cc(-c2ccc(C)cn2)nc(C(C)C)c1
Reaction time: 0.58 h

Procedure:
To a solution of methyl 6-isopropenyl-5′-methyl-2,2′-bipyridine-4-carboxylate (0.25 g, 0.93 mmol) in ethanol (9.3 mL) was palladium (10% on carbon; 49.6 mg, 0.047 mmol). The mixture was purged with hydrogen (3×) and stirred under hydrogen (1 atm). After 35 min, the mixture was filtered with Celite and the filtrate was concentrated. MS 271.2 (M+1).
Reaction SMILES: CS(O)(=O)=O.[NH2:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[N:12]([CH:18]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]1=[O:25])[CH2:11]2.[C:26]([C:30]1[CH:38]=[CH:37][C:33]([C:34](Cl)=[O:35])=[CH:32][CH:31]=1)([CH3:29])([CH3:28])[CH3:27].Cl>C(#N)C>[C:26]([C:30]1[CH:31]=[CH:32][C:33]([C:34]([NH:6][CH2:7][C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[C:13](=[O:17])[N:12]([CH:18]2[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]2=[O:25])[CH2:11]3)=[O:35])=[CH:37][CH:38]=1)([CH3:29])([CH3:27])[CH3:28]
Reactant: CC(C)(C)c1ccc(C(=O)Cl)cc1
Reactant: NCc1ccc2c(c1)CN(C1CCC(=O)NC1=O)C2=O
Agent: CS(=O)(=O)O
Agent: Cl
Solvent: CC#N
Product: CC(C)(C)c1ccc(C(=O)NCc2ccc3c(c2)CN(C2CCC(=O)NC2=O)C3=O)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 89 %

Procedure:
To a stirred mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methanesulfonate (0.50 g, 1.4 mmol) and 4-tert-butylbenzoyl chloride (0.28 g, 1.4 mmol) in acetonitrile (30 mL) at 0° C. was added TEA (0.28 g, 2.8 mmol) dropwise over 10 min. The mixture was stirred at ambient temperature for 2 h and then 10% aqueous HCl solution (30 mL) was added. The solid precipitate was filtered, washed with water (30 mL) and dried in vacuo providing 4-tert-butyl-N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-benzamide as a white solid (0.54 g, 92% yield); mp 238-240° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 ml/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 4.89 (99.23%); 1H NMR (DMSO-d6) δ 1.30 (s, 9H, t-butyl), 1.91-2.08 (m, 1H, CHH), 2.27-2.45 (m, 1H, CHH), 2.54-2.67 (m, 1H, CHH), 2.81-3.01 (m, 1H, CHH), 4.30 (d, 1H, CHH), 4.44 (d, 1H, CHH), 4.59 (d, J=5.5 Hz, 2H, CH2 and CHH), 5.10 (dd, 1H, CH), 7.40-7.58 (m, 4H, Ar), 7.69 (d, 1H, Ar), 7.85 (d, J=8.1 Hz, 2H, Ar), 9.08 (t, 1H, NH), 10.99 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.49, 30.92, 31.20, 34.59, 42.63, 47.12, 51.56, 121.95, 122.91, 125.08, 125.35, 126.97, 127.11, 129.17, 130.32, 131.38, 142.36, 144.10, 154.11, 166.12, 167.93, 170.98, 172.85; LCMS: MH=434; Anal. Calcd for C25H27N3O4+3.0H2O: C, 68.41; H, 6.34; N, 9.57. Found: C, 68.54; H, 6.47; N, 9.18.
Reaction SMILES: [OH:1][C:2]1[C:7]2[S:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:6]=2[S:5](=[O:16])(=[O:15])[N:4]([CH3:17])[C:3]=1[C:18](OC)=[O:19].[CH2:22]([C:25]1[S:29][C:28]([NH2:30])=[N:27][CH:26]=1)[CH2:23][CH3:24]>>[OH:1][C:2]1[C:7]2[S:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:6]=2[S:5](=[O:16])(=[O:15])[N:4]([CH3:17])[C:3]=1[C:18]([NH:30][C:28]1[S:29][C:25]([CH2:22][CH2:23][CH3:24])=[CH:26][N:27]=1)=[O:19]
Reactant: COC(=O)C1=C(O)c2sc3ccccc3c2S(=O)(=O)N1C
Reactant: CCCc1cnc(N)s1
Product: CCCc1cnc(NC(=O)C2=C(O)c3sc4ccccc4c3S(=O)(=O)N2C)s1
Yield: 37 %

Procedure:
Prepared analogous to Example 1 from methyl 4-hydroxy-2-methyl-2H-[1] benzothieno [2,3-e]-1,2-thiazine-3-carboxylate-1,1-dioxide and 5-propyl-2-thiazolamine with a yield of 37% of theory.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[I:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1.O>CN(C)C=O>[I:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:25][CH:24]=1
Reactant: COc1cc2ncnc(Cl)c2cc1OC
Reactant: Oc1ccc(I)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc2ncnc(Oc3ccc(I)cc3)c2cc1OC
Temperature: 25 °C
Yield: 83.3 %

Procedure:
A solution of 4-chloro-6,7-dimethoxyquinazoline (224 mg, 1.00 mmol), potassium carbonate (152 mg, 1.10 mmol) and 4-iodophenol (244 mg, 1.10 mmol) in dimethylformamide (4 ml) was heated at 110° C. for 2 hours before the reaction was allowed to cool to ambient temperature. The reaction was poured into water and the solid which had precipitated was collected by suction filtration and washed with a mixture of diethyl ether (10 ml), ethyl acetate (10 ml) and isohexane (10 ml). Drying of this material yielded, yielded 4-(4-iodophenoxy)-6,7-dimethoxyquinazoline (340 mg, 83% yield) as a white solid:
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1([OH:8])[CH2:7][CH2:6][CH2:5]1.[Cl:9][C:10]1[N:11]=[C:12](Cl)[C:13]2[C:18]([I:19])=[CH:17][N:16]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:14]=2[N:15]=1>C1COCC1>[Cl:9][C:10]1[N:11]=[C:12]([O:8][C:4]2([CH3:3])[CH2:7][CH2:6][CH2:5]2)[C:13]2[C:18]([I:19])=[CH:17][N:16]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:14]=2[N:15]=1
Reactant: CC1(O)CCC1
Reactant: C[Si](C)(C)CCOCn1cc(I)c2c(Cl)nc(Cl)nc21
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC1(Oc2nc(Cl)nc3c2c(I)cn3COCC[Si](C)(C)C)CCC1
Temperature: 60 °C
Yield: 77 %

Procedure:
To a suspension of sodium hydride (60% in mineral oil, 2.0 equiv) in dry THF (0.45 M) under a nitrogen atmosphere was added a solution of 1-methylcyclobutanol (1.2 equiv) in dry THF (0.27 M) at 0° C. The reaction mixture was stirred at 30° C. for 30 min before a solution of 2,4-dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv) in dry THF (0.23 M) was added and the resulting reaction mixture was heated at 60° C. for 2 h. After the reaction was completed, the reaction mixture was quenched with saturated aqueous ammonium chloride solution. The organic solvent was removed under vacuum and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated under reduced pressure. The product was purified by silica gel chromatography (2% ethyl acetate in petroleum ether) to afford the title compound (77% yield) as a yellow oil. MS (ESI) m/z 494.2 [M+H]+.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[Cl:28][C:29]1[CH:37]=[C:36]2[C:32]([C:33]([C:43]([OH:45])=O)=[CH:34][N:35]2[CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])=[CH:31][CH:30]=1.[NH2:46][C:47]1[S:48][CH:49]=[CH:50][N:51]=1>C(Cl)Cl>[S:48]1[CH:49]=[CH:50][N:51]=[C:47]1[NH:46][C:43]([C:33]1[C:32]2[C:36](=[CH:37][C:29]([Cl:28])=[CH:30][CH:31]=2)[N:35]([CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[CH:34]=1)=[O:45]
Reactant: Nc1nccs1
Reactant: CCCCCn1cc(C(=O)O)c2ccc(Cl)cc21
Agent: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCCCCn1cc(C(=O)Nc2nccs2)c2ccc(Cl)cc21
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 25.7 %

Procedure:
A solution of triphenylphosphine (355 mg, 1.35 mmol) in methylene chloride (3 mL) cooled to 0° C. was treated with N-bromosuccinimide (240 mg, 1.35 mmol). The reaction was stirred at 0° C. for 15 min. At this time, the reaction was treated with 6-chloro-1-pentyl-1H-indole-3-carboxylic acid (300 mg, 1.13 mmol). The reaction was stirred at 0° C. for 10 min and then was allowed to warm to 25° C. where it was stirred for 1 h. The reaction was then treated with 2-aminothiazole (283 mg, 2.83 mmol) and stirred at 25° C. for 3 d. At this time, the reaction was partitioned between water (50 mL) and ethyl acetate (50 mL). This mixture was treated with a 10% aqueous hydrochloric acid solution (15 mL), shaken, and separated. The organic layer was washed with a saturated aqueous sodium bicarbonate solution (1×30 mL), water (1×30 mL), and a saturated aqueous sodium chloride solution (1×30 mL). The organic layer was then dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 2/1 hexanes/ethyl acetate) afforded 6-chloro-1-pentyl-1H-indole-3-carboxylic acid thiazol-2-ylamide (101 mg, 25%) as a pink solid: mp 139-141° C.; EI-HRMS m/e calcd for C17H18ClN3OS (M+) 347.0859, found 347.0859.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:18]=[CH:17][C:16]([C@@H:19]([OH:22])[CH2:20][Br:21])=[CH:15][C:10]=1[C:11]([O:13][CH3:14])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CN=C1.[Si:28](Cl)([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29]>CN(C1C=CN=CC=1)C.CN(C)C=O>[CH3:14][O:13][C:11](=[O:12])[C:10]1[CH:15]=[C:16]([C@@H:19]([O:22][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[CH2:20][Br:21])[CH:17]=[CH:18][C:9]=1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1cc([C@@H](O)CBr)ccc1OCc1ccccc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: CN(C)c1ccncc1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: COC(=O)c1cc([C@H](CBr)O[Si](C)(C)C(C)(C)C)ccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 97.3 %

Procedure:
A solution of methyl 2-(benzyloxy)-5-[(1R)-2-bromo-1-hydroxyethyl]benzoate (71.0 g, 195 mmol), imidazole (18.5 g, 272 mmol), tert-butyldimethylsilyl chloride (32.2 g, 214 mmol) and 4-(N,N-dimethylamino)pyridine (440 mg, 3.60 mmol) in N,N-dimethylformamide (270 ml) was left to stir at room temperature under a nitrogen atmosphere for a period of 24 hours. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (500 ml) and water (500 ml). The organic phase was separated and washed with 2N aqueous hydrochloric acid (2×500 ml), saturated aqueous sodium bicarbonate (2×500 ml), brine (500 ml), dried (magnesium sulfate) and the solvent removed in vacuo to give the title compound as a colourless oil (91.0 g).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH:13]2[CH:11]([O:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[Cl-].[NH4+].[N-:19]=[N+:20]=[N-:21].[Na+]>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH:13]([OH:12])[CH:11]([N:19]=[N+:20]=[N-:21])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(C)OC(=O)N1CCC2OC2CC1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCC(O)C(N=[N+]=[N-])CC1
Temperature: 75 °C

Procedure:
According to scheme 10, to a stirred solution of 2,3,6,7-tetrahydro-azepine-1-carboxylic acid tert-butyl ester (XXX) in dichloromethane was added at −60° C. m-chloroperbenzoic acid (MCPBA). The mixture was allowed to slowly warm to room temperature overnight and 8-oxa-4-aza-bicyclo[5.1.0]octane-4-carboxylic acid tert-butyl ester (XXXI) was obtained. To a solution of 8-oxa-4-aza-bicyclo[5.1.0]octane-4-carboxylic acid tert-butyl ester in ethanol was added water, ammonium chloride and sodium azide. The mixture was stirred at 75° C. over night, to give 4-azido-5-hydroxy-azepane-1-carboxylic acid tert-butyl ester (XXXII). 4-Azido-5-hydroxy-azepane-1-carboxylic acid tert-butyl ester in methanol was hydrogenated in the presence of palladium on charcoal (10%) to yield 4-amino-5-hydroxy-azepane-1-carboxylic acid tert-butyl ester (XXXIII). 4-Methoxy-7-morpholin-4-yl-benzothiazole-2-carboxylic acid and 1,1′-carbonyl-diimidazole in dimethylformamide are stirred at room temperature for about 16 hours. 4-Amino-5-hydroxy-azepane-1-carboxylic acid tert-butyl ester was added and stirring was continued for 16 hours at room temperature. It was obtained 4-hydroxy-5-[(4-methoxy-7-morpholin-4-yl-benzothiazole-2-carbonyl)-amino]-azepane-1-carboxylic acid tert-butyl ester (XXXIV). To a solution of 4-hydroxy-5-[(4-methoxy-7-morpholin-4-yl-benzothiazole-2-carbonyl)-amino]-azepane-1-carboxylic acid tert-butyl ester in dimethylsulfoxide was added triethylamine, dichloromethane and a solution of sulfur trioxide pyridine complex in dimethylsulfoxide. The mixture was stirred for 18 hours at room temperature. After purification 4-[(4-methoxy-7-morpholin-4-yl-benzothiazole-2-carbonyl)-amino]-5-oxo-azepane-1-carboxylic acid tert-butyl ester (VIII) was obtained.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]2[O:8][CH2:9][O:10][C:3]=12.C([Li])CCC.C[O:17][B:18](OC)[O:19]C>C1COCC1>[F:1][C:2]1([B:18]([OH:19])[OH:17])[CH:7]=[CH:6][CH:5]=[C:4]2[O:8][CH2:9][O:10][CH:3]12
Reactant: COB(OC)OC
Reactant: Fc1cccc2c1OCO2
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OB(O)C1(F)C=CC=C2OCOC21
Temperature: -65 °C
Yield: 21.3 %

Procedure:
1-Fluoro-2,3-methylenedioxybenzene (5.0 g, 35.7 mmol) was dissolved in THF (70 mL) and the solution was cooled to −65° C. in a dry ice acetone bath. n-Butyl lithium (2.5 g, 15.7 mL, 39.3 mmol) was added to the solution via syringe with stirring. The reaction was allowed to warm to −35° C. over 1 hour, then cooled to −65° C. and treated with trimethylborate (4.1 g, 39.3 mmol) via syringe. The reaction was allowed to warm slowly to room temperature, quenched with 1N HCl (50 mL), stirred for 15 minutes, and then extracted with ether. The organic phase was then extracted with 1N sodium hydroxide and this aqueous extract was then acidified with 1N hydrochloric acid. The acidic aqueous solution was then extracted with two portions of ether and these combined ether extracts were dried and concentrated to an oily solid that was triturated with methylene chloride. The resulting solid was collected by filtration, washed with methylene chloride, and dried to give 1-fluoro-2,3-methylenedioxyphenylboronic acid (1.4 g, 7.6 mmol) as a tan solid: 1H NMR (DMSO-d6): δ 8.05 (br s, 2H), 7.08 (dd, 1H, J=7.8, 5.1 Hz), 6.76 (d, 1H, J=7.8 Hz), 6.08 (s, 2H).
Reaction SMILES: [C:1]([C:3]1[CH:22]=[CH:21][C:6]([CH2:7][N:8]([CH3:20])[CH:9]([CH:17]([CH3:19])[CH3:18])[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[C:5]([F:23])[CH:4]=1)#[N:2].[NH2:24][OH:25]>C(O)C.O>[NH2:2][C:1](=[N:24][OH:25])[C:3]1[CH:22]=[CH:21][C:6]([CH2:7][N:8]([CH3:20])[C@H:9]([C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[CH:17]([CH3:19])[CH3:18])=[C:5]([F:23])[CH:4]=1
Reactant: CC(C)C(C(=O)OC(C)(C)C)N(C)Cc1ccc(C#N)cc1F
Reactant: NO
Solvent: CCO
Solvent: O
Product: CC(C)[C@@H](C(=O)OC(C)(C)C)N(C)Cc1ccc(C(N)=NO)cc1F
Temperature: -20 °C
Reaction time: 12 h

Procedure:
To a stirred solution of tert-butyl 2-[(4-cyano-2-fluorobenzyl)(methyl)amino]-3-methylbutanoate (3.4 g, 0.011 mol), in ethanol (30 mL), was added 50% aqueous. hydroxylamine (1.4 mL, 0.021 mol). The mixture was stirred at −20° C., for 12 h. The reaction mixture was diluted with water and extracted in dichloromethane (100 mL), dried over Na2SO4 and concentrated under reduce pressure. The solid was recrystallised with ethyl acetate (5 mL), filtered and dried under vacuum, affording the title compound as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 9.73 (s, 1H), 7.49 (m, 1H), 7.38 (m, 2H), 5.85 (s, 2H), 3.71 (d, J=14.2 Hz, 1H), 3.57 (d, J=14.2 Hz, 1H), 2.66 (d, J=10.7 Hz, 1H), 2.18 (s, 3H), 1.99-1.93 (m, 1H), 1.45 (s, 9H), 0.91-0.81 (m, 6H). LC/MS (Method B) 354.3 (M+H)+. HPLC (Method A) Rt: 2.66 min (Purity 98.6%).
Reaction SMILES: [CH2:1]([N:3]([CH2:6][CH2:7][CH2:8][CH:9]([NH2:11])[CH3:10])[CH2:4][CH3:5])[CH3:2].Cl.[N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([C:23](Cl)=[O:24])=[CH:15][CH:14]=1>O>[CH3:10][CH:9]([NH:11][C:23]([C:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:13]=[CH:14][CH:15]=1)=[O:24])[CH2:8][CH2:7][CH2:6][N:3]([CH2:4][CH3:5])[CH2:1][CH3:2]
Reactant: CCN(CC)CCCC(C)N
Reactant: O=C(Cl)c1ccnc2ccccc12
Agent: Cl
Solvent: O
Product: CCN(CC)CCCC(C)NC(=O)c1ccnc2ccccc12

Procedure:
2-[4'-(5"-nitrofuryl-2")-1,3-butadienyl]quinoline-4-carboxylic acid (α-methyl-δ-diethylaminobutyl)amide was prepared from 4.74 g (0.03 mol.) of diethylamino-4-aminopentane and 3.91 g (0.01 mol.) of 2-[4-(5"-nitrofuryl-2")-1,3-butadienyl]quinoline-4-carboxylic acid chloride hydrochloride in 50 ml of water. The process was conducted as described in Example 7.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[OH:10])([CH3:3])[CH3:2].[CH2:11]1[O:14][CH:12]1[CH3:13]>>[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][CH2:11][CH:12]([OH:14])[CH3:13])([CH3:3])[CH3:2]
Reactant: CC1CO1
Reactant: CC(C)c1ccccc1O
Product: CC(O)COc1ccccc1C(C)C
Yield: 100 %

Procedure:
The title compound is prepared as described in Example 33, except that 2-isopropylphenol and propylene oxide are used as starting materials to give the crude product in a yield of 100%; Rf=0.1 (toluene).
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.Cl.[F:12][C:13]([F:37])([F:36])[C:14]1[CH:15]=[C:16]([CH:29]=[C:30](C(F)(F)F)[CH:31]=1)[CH2:17][O:18][CH2:19][CH:20]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:21][NH2:22].C(N(CC)CC)C>C(Cl)Cl>[F:36][C:13]([F:37])([F:12])[C:14]1[CH:15]=[C:16]([CH:29]=[CH:30][C:31]=1[C:13]([F:37])([F:36])[F:12])[CH2:17][O:18][CH2:19][CH:20]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[CH2:21][NH:22][C:6](=[O:7])[C:5]1[CH:9]=[CH:10][C:2]([F:1])=[CH:3][CH:4]=1
Reactant: O=C(Cl)c1ccc(F)cc1
Reactant: NCC(COCc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1ccccc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(NCC(COCc1ccc(C(F)(F)F)c(C(F)(F)F)c1)c1ccccc1)c1ccc(F)cc1
Yield: 188.2 %

Procedure:
A solution of 4-fluorobenzoyl chloride (1.2 mL, 10 mmol) in CH2Cl2 (20 mL) was dropped into a solution of the compound produced in Example 17 (3.31 g, 8.0 mmol) and triethylamine (2.8 mL, 20 mmol) in CH2Cl2 (50 mL) during 30 minutes under cooling with ice. After the solvent was evaporated therefrom in vacuo, water was added to the residue and the mixture was extracted with ethyl acetate. The organic layers were combined, washed with water and a saturated saline solution and dried over anhydrous sodium sulfate. The residual oily product produced by evaporation of the solvent therefrom in vacuo was crystallized from petroleum ether to give the Compound 57 (3.76 g, 94%).
Reaction SMILES: [CH2:1]([S:17][CH2:18][CH:19]([CH2:22][O:23][CH3:24])[CH2:20][NH2:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[Cl:25][CH2:26][CH2:27][CH2:28][S:29](NCC(OC)CSCCCCCCCCCCCCCCCC)(=[O:31])=[O:30]>>[Cl:25][CH2:26][CH2:27][CH2:28][S:29]([NH:21][CH2:20][CH:19]([CH2:22][O:23][CH3:24])[CH2:18][S:17][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])(=[O:31])=[O:30]
Reactant: CCCCCCCCCCCCCCCCSCC(CNS(=O)(=O)CCCCl)OC
Reactant: CCCCCCCCCCCCCCCCSCC(CN)COC
Product: CCCCCCCCCCCCCCCCSCC(CNS(=O)(=O)CCCCl)COC

Procedure:
3-Hexadecylthio-2-methoxymethylpropylamine IVk3 is allowed to react and worked up by the same procedure as described in (4). m.p. 41.5°-43° C. The summary of the experimental and the physical data of the product are listed in Table 7.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:7]([C:8]([OH:10])=O)[C:6]([NH2:12])=[CH:5][CH:4]=1.C(O)(=O)C.[O-:17][C:18]#[N:19].[K+].[OH-].[Na+]>O>[OH:17][C:18]1[N:19]=[C:8]([OH:10])[C:7]2[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:11]=2)[N:12]=1
Reactant: COc1ccc(N)c(C(=O)O)c1
Reactant: N#C[O-]
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Product: COc1ccc2nc(O)nc(O)c2c1
Yield: 82 %

Procedure:
A mixture of 5-methoxy anthranilic acid (40 g, 0.24M), acetic acid (18.0 g, 0.3M) and 1 liter warm water (35° ) was stirred and allowed to cool. A solution of potassium cyanate (24.3 g, 0.3M) in water (100 ml) was added over 15 minutes and then stirred for a further 30 minutes. Sodium hydroxide (320 g, 8.0M) solid was added portionwise and the reaction was then heated at 90° for 30 minutes and allowed to cool overnight. The solid was filtered off and dissolved in hot water (500 ml) and then acidified with dilute sulphuric acid to precipitate the product. The solid was filtered off and washed free of acid with water and then dried at 100°/vacuum to yield the title compound (37.7 g) m.p. >290°.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[F:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH:17]=[CH:16][CH:15]=[CH:14]2)=[CH:9][CH:8]=1.[C:18](=O)([O-])[O-:19].[K+].[K+]>CN(C)C=O>[F:6][C:7]1[CH:8]=[CH:9][C:10]([N:13]2[CH:17]=[CH:16][CH:15]=[C:14]2[CH:18]=[O:19])=[CH:11][CH:12]=1
Reactant: Fc1ccc(-n2cccc2)cc1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: O=P(Cl)(Cl)Cl
Solvent: CN(C)C=O
Product: O=Cc1cccn1-c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 36.3 %

Procedure:
Phosphorus oxychloride (96.5 g) was added dropwise under ice-cooling to dimethylformamide (600 ml) containing 1-(4-fluorophenyl)pyrrole (101 g) over 1 h, and the mixture was stirred for 2 h and at room temperature for one day. The reaction mixture was added to 3 Liters of aqueous solution containing potassium carbonate (130 g) and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. Diisopropyl ether was added to the residue to allow crystallization. The crystals were recrystallized from a mixed solvent of toluene-diisopropyl ether (ratio=1:10) to give 1-(4-fluorophenyl)-2-formylpyrrole (43 g), melting point: 82–83° C.