Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:14]=[CH:13][C:5]2[N:6]=[C:7]([NH:9][CH2:10][CH2:11][F:12])[S:8][C:4]=2[CH:3]=1.[CH3:15][N:16]([C:24]1[CH:29]=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:25]=1)[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.CCOC(C)=O.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>[F:12][CH2:11][CH2:10][NH:9][C:7]1[S:8][C:4]2[CH:3]=[C:2]([C:27]3[CH:26]=[CH:25][C:24]([N:16]([CH3:15])[C:17](=[O:23])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[CH:29][CH:28]=3)[CH:14]=[CH:13][C:5]=2[N:6]=1
Reactant: FCCNc1nc2ccc(Br)cc2s1
Reactant: CN(C(=O)OC(C)(C)C)c1ccc(B2OC(C)(C)C(C)(C)O2)cc1
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: [Na+]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CN(C(=O)OC(C)(C)C)c1ccc(-c2ccc3nc(NCCF)sc3c2)cc1
Temperature: 100 °C

Procedure:
A mixture of afford 6-bromo-N-(2-fluoroethyl)benzo[d]thiazol-2-amine (55 mg, 0.2 mmol), tert-butyl methyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (66 mg, 0.2 mmol), and tetrakis(triphenylphosphine)palladium (7 mg, 0.006 mmol) in 2 mL dioxane and 0.5 mL of a 1 M Na2CO3 aqueous solution was heated at 100° C. in a microwave reactor for 10 min. After cooling to rt, it was diluted with EtOAc (30 mL) and washed with brine (30 mL), dried over MgSO4 and concentrated. The crude product was purified with silica chromatography (5% to 30% EtOAc in hexane) to afford tert-butyl 4-(2-(2-fluoroethylamino)benzo[d]thiazol-6-yl)phenyl(methyl)carbamate as a clear wax (25 mg, 31%). MS (ESI) m/z 402 (M+H+).
Reaction SMILES: [CH2:1]([Sn:5]([CH2:20][CH2:21][CH2:22][CH3:23])([CH2:16][CH2:17][CH2:18][CH3:19])[C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]([OH:15])([CH3:14])[CH3:13])[CH:7]=1)[CH2:2][CH2:3][CH3:4].[H-].[Na+].[CH3:26]I>C1COCC1.CCOC(C)=O>[CH3:26][O:15][C:12]([C:8]1[CH:7]=[C:6]([Sn:5]([CH2:16][CH2:17][CH2:18][CH3:19])([CH2:1][CH2:2][CH2:3][CH3:4])[CH2:20][CH2:21][CH2:22][CH3:23])[CH:11]=[CH:10][N:9]=1)([CH3:13])[CH3:14]
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccnc(C(C)(C)O)c1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)c1ccnc(C(C)(C)OC)c1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
A solution of 2-(4-tributylstannanyl-pyridin-2-yl)-propan-2-ol 12AO (0.12 g, 0.27 mmol) in THF (2 ml) was added in a dry NaH (0.02 g, 0.54 mmol). Reaction mixture was stirred for 20 min at r.t. It was cooled to 0° C. and CH3I (0.02 ml, 0.32 mmol) was added drop wise. After 30 mins at 0° C., reaction mixture was warmed up to r.t. It was diluted with EtOAc (15 ml) after 2 hr and washed with water (2×3 ml) and brine (5 ml). Organic extracts were dried over MgSO4, filtered and concentrated. The residue was purified on silica gel eluting with 1/4 EtOAc/Hexane to give the desired product 2-(1-methoxy-1-methyl-ethyl)-4-tributylstannanyl-pyridine 13AO (0.1 g, 88%).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]([CH3:21])([C:17]([F:20])([F:19])[F:18])[C:14](Cl)=[O:15].[NH3:22].O>CCOCC>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]([CH3:21])([C:17]([F:20])([F:19])[F:18])[C:14]([NH2:22])=[O:15]
Reactant: CC(OCc1ccc2ccccc2c1)(C(=O)Cl)C(F)(F)F
Reactant: N
Solvent: CCOCC
Solvent: O
Product: CC(OCc1ccc2ccccc2c1)(C(N)=O)C(F)(F)F

Procedure:
A solution of (±)-2-(2-naphthylmethoxy)-3,3,3-trifluoro-2-methylpropionyl chloride (1.3 g.) in ether (10 ml.) is added to a mixture of ammonia (d, 0.90; 10 ml.) and water (100 ml.). The mixture is shaken, and the ether is evaporated. The solid is filtered off and crystallised from light petroleum (b.p. 100°-120° C.) to give (±)-2-(2-naphthylmethoxy)-3,3,3-trifluoro-2-methylpropionamide (0.76 g.) m.p. 111°-112° C.
Reaction SMILES: O=[C:2]1[CH2:6][CH2:5][CH2:4][CH:3]1[C:7]([O:9][CH2:10][CH3:11])=[O:8].[CH3:12][C:13]1[N:18]=[C:17]([NH:19][NH2:20])[CH:16]=[CH:15][CH:14]=1>C(O)C>[CH2:10]([O:9][C:7]([CH:3]1[CH2:4][CH2:5][CH2:6][C:2]1=[N:20][NH:19][C:17]1[CH:16]=[CH:15][CH:14]=[C:13]([CH3:12])[N:18]=1)=[O:8])[CH3:11]
Reactant: CCOC(=O)C1CCCC1=O
Reactant: Cc1cccc(NN)n1
Solvent: CCO
Product: CCOC(=O)C1CCCC1=NNc1cccc(C)n1
Temperature: 25 °C
Yield: 72.8 %

Procedure:
A solution of ethyl 2-oxocyclopentanecarboxylate (6.34 g, 5.88 mL) and (6-methyl-pyridin-2-yl)-hydrazine (5 g) in ethanol (100 mL) was heated to 80° C. under an atmosphere of nitrogen for about 19 hours. The reaction mixture was cooled to room temperature and the solvent removed in vacuo to provide a crude material (7.72 g), which was directly taken to the next reaction.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:6][C:7]1[CH:14]=[CH:13][C:10]([CH2:11][SH:12])=[CH:9][CH:8]=1)[CH2:4][CH3:5].Cl[C:16]1[N:21]=[C:20]([S:22][CH3:23])[N:19]([CH2:24][CH3:25])[C:18](=[O:26])[C:17]=1[CH3:27].O>CN(C)P(=O)(N(C)C)N(C)C>[CH3:27][C:17]1[C:18](=[O:26])[N:19]([CH2:24][CH3:25])[C:20]([S:22][CH3:23])=[N:21][C:16]=1[S:12][CH2:11][C:10]1[CH:9]=[CH:8][C:7]([O:6][CH2:3][CH2:4][CH3:5])=[CH:14][CH:13]=1
Reactant: CCCOc1ccc(CS)cc1
Reactant: CCn1c(SC)nc(Cl)c(C)c1=O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: O
Product: CCCOc1ccc(CSc2nc(SC)n(CC)c(=O)c2C)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 52 %

Procedure:
Sodium hydride (55% in mineral oil) (0.70 g) was suspended in 20 ml of hexamethyl phosphoric triamide, and then 3.0 g of 4-propyloxybenzyl mercaptan was added thereto. The mixture was stirred for one hour at room temperature and then incorporated with 3.0 g of 6-chloro-5-methyl-2-methylthio-3-ethyl-4(3H)-pyrimidinone. After stirring at room temperature, resulting mixture was heated to 80° C. under stirring for 3 hours. The resulting solution was poured into water and then extracted with benzene. The extract was washed with an aqueous sodium hydroxide solution and then with water, dried over anhydrous sodium sulfate and freed of solvent by distillation udner reduced pressure. The oil thus obtained was purified by means of column chromatography (on silica gel, eluting with chloroform) to give 2.6 g of the intended product.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]([NH2:16])=[O:15])[CH2:10][CH2:9]1.[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][C:7]=2[N:8]2[CH2:13][CH2:12][CH:11]([C:14]([NH2:16])=[O:15])[CH2:10][CH2:9]2)=[CH:21][CH:20]=1
Reactant: NC(=O)C1CCN(c2ccncc2Br)CC1
Reactant: COc1ccc(B(O)O)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: COc1ccc(-c2cnccc2N2CCC(C(N)=O)CC2)cc1
Yield: 89 %

Procedure:
General procedure D (See Example 4) was followed using 1-(3-bromopyridin-4-yl)piperidine-4-carboxamide E36 (50 mg, 0.17 mmol), 4-methoxyphenylboronic acid (32 mg, 0.21 mmol), tetrakis (triphenylphosphine)palladium(0) (10 mg, 5 mol %), acetonitrile (1.2 mL) and 0.5 M sodium carbonate (0.49 mL, 0.25 mmol) for 50 min. The crude product was purified by flash column chromatography on silica gel (CH2Cl2, MeOH, gradient 97:3 to 95:5) to furnish the title compound as a white solid (49 mg, 89%), LC-MS (ESI) Rt 1.28 min, m/z 312 (100%, [M+H]+); m/z (ESI) C18H22N3O2 requires 312.1706 found [M+H]+ 312.1705.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])=[C:5]2[NH:17][C:18]1[CH:19]=[CH:20][C:21]([N:24]2[CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25]2)=[N:22][CH:23]=1.[Cl:37][C:38]1[CH:43]=[C:42](B2OC(C)(C)C(C)(C)O2)[CH:41]=[C:40]([F:53])[C:39]=1[OH:54]>>[Cl:37][C:38]1[CH:43]=[C:42]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][C:6]([C:12]([CH:14]2[CH2:15][CH2:16]2)=[O:13])=[C:5]3[NH:17][C:18]2[CH:23]=[N:22][C:21]([N:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)=[CH:20][CH:19]=2)[CH:41]=[C:40]([F:53])[C:39]=1[OH:54]
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(Nc3c(C(=O)C4CC4)cnc4ccc(Br)cc34)cn2)CC1
Reactant: CC1(C)OB(c2cc(F)c(O)c(Cl)c2)OC1(C)C
Product: O=C(c1cnc2ccc(-c3cc(F)c(O)c(Cl)c3)cc2c1Nc1ccc(N2CCNCC2)nc1)C1CC1
Yield: 50.2 %

Procedure:
Following general procedure F, tert-butyl 4-(5-(6-bromo-3-(cyclopropanecarbonyl)quinolin-4-ylamino)pyridin-2-yl)piperazine-1-carboxylate (8.4 g, 15 mmol) was reacted with 2-chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (5.0 g, 18 mmol) to obtain the protected intermediate which was subjected to general procedure A-2 to afford the desired product (3.9 g, 53% over 2 steps) as a yellow/orange solid: 1H NMR (300 MHz, MeOD) δ 9.26 (s, 1H), 8.07 (d, J=2.8 Hz, 1H), 7.89 (s, 2H), 7.75 (s, 1H), 7.47 (dd, J=9.0, 2.8 Hz, 1H), 7.02 (s, 1H), 6.96 (d, J=9.0 Hz, 1H), 6.84 (dd, J=12.2, 2.4 Hz, 1H), 3.72 (t, J=5.2 Hz, 5H), 3.12 (t, J=5.2 Hz, 5H), 2.92 (m, 1H), 1.22 (m, 2H), 1.12 (m, 2H); ESI MS m/z 518 [C28H25ClFN5O2+H]+; HPLC 98.7% (AUC), tR=8.67 min.
Reaction SMILES: [NH2:1][CH:2]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:3]([N:5]1[CH2:10][CH2:9][CH:8]([N:11]2[CH2:15][C:14]3=[CH:16][N:17]=[C:18]([CH3:19])[N:13]3[C:12]2=[O:20])[CH2:7][CH2:6]1)=[O:4].[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]=[C:35]=[O:36])=[CH:30][CH:29]=1>CN(C=O)C.C(OCC)(=O)C>[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([NH:34][C:35]([NH:1][CH:2]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:3]([N:5]2[CH2:10][CH2:9][CH:8]([N:11]3[CH2:15][C:14]4=[CH:16][N:17]=[C:18]([CH3:19])[N:13]4[C:12]3=[O:20])[CH2:7][CH2:6]2)=[O:4])=[O:36])=[CH:30][CH:29]=1
Reactant: Cc1ncc2n1C(=O)N(C1CCN(C(=O)C(N)c3ccccc3)CC1)C2
Reactant: O=C=Nc1ccc(Cl)cc1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1ncc2n1C(=O)N(C1CCN(C(=O)C(NC(=O)Nc3ccc(Cl)cc3)c3ccccc3)CC1)C2
Yield: 62.7 %

Procedure:
2-(1-(2-Amino-2-phenylacetyl)-4-piperidinyl)-5-methyl-1,2-dihydro-3H-imidazo[1,5-c]imidazol-3-one (0.10 g) obtained in Example 50b) was dissolved in DMF (3.0 ml), 4-chlorophenyl isocyanate (0.05 g) was added thereto, and mixed at room temperature for 1 hour. The reaction mixture was dissolved in ethyl acetate, washed with an aqueous sodium hydrogen carbonate solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified with basic silica gel column (ethyl acetate to methanol/ethyl acetate=1/10). The product was crystallized from ethyl acetate-diethyl ether to obtain the title compound as colorless powder (0.09 g, 59%).
Reaction SMILES: C(OC([NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[N:19]=[CH:20][C:21](=[O:25])[NH:22][C:23]=2[CH3:24])=[CH:14][CH:13]=1)=O)C1C=CC=CC=1.[BrH:26].C(O)C>C(O)(=O)C>[BrH:26].[NH2:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]2[N:19]=[CH:20][C:21](=[O:25])[NH:22][C:23]=2[CH3:24])=[CH:16][CH:17]=1
Reactant: Cc1[nH]c(=O)cnc1-c1ccc(NC(=O)OCc2ccccc2)cc1
Agent: Br
Solvent: CCO
Solvent: CC(=O)O
Product: Cc1[nH]c(=O)cnc1-c1ccc(N)cc1

Procedure:
5-(4-Benzyloxycarbonylaminophenyl)-6-methyl-2(1H)-pyrazinone (0.5 g) was treated with hydrogen bromide in acetic acid in a manner similar to that described in Example 20 to give the title compound as its hydrobromide salt (340 mg) which after digestion with hot ethanol had m.p. >300° C.; δ(D2O) inter alia 2.39 (3H, d, CH3), 8.03 (1H, q, pyrazinone ring 3-H); ν(KBr) 1705, 1750 cm-1.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[C:11](=[O:28])[C:10]=1I)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:30](N(CC)CC)[CH3:31].ClCCl>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[C:11](=[O:28])[C:10]=1[CH:30]=[CH2:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCC(n2ccc(OCc3ccccc3)c(I)c2=O)CC1
Reactant: CCN(CC)CC
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Solvent: ClCCl
Solvent: CCO
Product: C=Cc1c(OCc2ccccc2)ccn(C2CCN(C(=O)OC(C)(C)C)CC2)c1=O
Temperature: 25 °C

Procedure:
A mixture of tert-butyl 4-(4-(benzyloxy)-3-iodo-2-oxopyridin-1(2H)-yl)piperidine-1-carboxylate (2.4 g), potassium vinyl trifluoroborate (0.945 g), triethylamine (1.3 mL), a dichloromethane adduct of 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride (0.269 g), and ethanol (47 mL) was stirred overnight at 90 C in a nitrogen atmosphere. After cooling to room temperature, the solvent was distilled off under reduced pressure. Water and ethyl acetate were added to the obtained residue, and the organic layer was separated. The obtained organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate) to obtain the title compound (1.48 g).
Reaction SMILES: C(N(C(C)C)C(C)C)C.[NH2:10][C:11]1[C:12]2[C:17]([C:18]3[C:19]([O:27][CH3:28])=[C:20]([O:25][CH3:26])[CH:21]=[CH:22][C:23]=3[CH:24]=1)=[CH:16][C:15]([CH3:29])=[CH:14][CH:13]=2.[C:30](Cl)(=[O:32])[CH3:31]>C(Cl)Cl>[C:30]([NH:10][C:11]1[C:12]2[C:17]([C:18]3[C:19]([O:27][CH3:28])=[C:20]([O:25][CH3:26])[CH:21]=[CH:22][C:23]=3[CH:24]=1)=[CH:16][C:15]([CH3:29])=[CH:14][CH:13]=2)(=[O:32])[CH3:31]
Reactant: CC(=O)Cl
Reactant: COc1ccc2cc(N)c3ccc(C)cc3c2c1OC
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc2cc(NC(C)=O)c3ccc(C)cc3c2c1OC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
105.7 ml (0.750M) of N-ethyl-N,N-diisopropyl-amine are added to a solution of 100.2 g (0.375M) of 9-amino-3,4-dimethoxy-6-methyl-phenanthrene in 1000 ml methylene chloride. To the resulting mixture is added dropwise over 30 minutes a solution of 34.5 ml (0.450M) of acetyl chloride in 250 ml methylene chloride. During the addition, the temperature of the reaction mixture is maintained at 20° by cooling with ice. The reaction mixture is stirred for 2 hours at room temperature and extracted with methylene chloride. The organic phases are washed with ice cooled 2N hydrochloric acid, water and 2N sodium bicarbonate, dried over sodium sulfate and evaporated, to give the title compound. M.pt. 190°-192° after crystallization from acetone/ether.
Reaction SMILES: [OH-].[Na+].[CH3:3][C:4]1[C:5](=[O:24])[NH:6][C:7]2[C:12]([N:13]=1)=[CH:11][C:10]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([O:21]CC)=[O:20])=[CH:9][CH:8]=2.O.Cl>CO>[CH3:3][C:4]1[C:5](=[O:24])[NH:6][C:7]2[C:12]([N:13]=1)=[CH:11][C:10]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20])=[CH:9][CH:8]=2
Reactant: CCOC(=O)CCCCOc1ccc2[nH]c(=O)c(C)nc2c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: Cc1nc2cc(OCCCCC(=O)O)ccc2[nH]c1=O
Reaction time: 8 h
Yield: 96.6 %

Procedure:
2N-NaOH solution 29.6 ml was added to the compound 1036 (8.99 g, 29.6 mM) suspended in methanol 29.6 ml and the mixture was stirred overnight. Water 88.8 ml was added to the reaction mixture, and the mixture was adjusted to pH 2 by adding 6N-HCl. Precipitated crystals were collected by filtration, washed completely with water and dried to obtain the compound 1037.
Reaction SMILES: [OH:1][CH:2]([CH2:14][O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)/[CH:3]=[CH:4]/[CH:5]1[CH2:12][CH2:11][CH:10]2[CH:6]1[CH2:7][CH2:8][C:9]2=[O:13].[C:22]([Si:26]([CH3:29])([CH3:28])Cl)([CH3:25])([CH3:24])[CH3:23].N1C=CN=C1.O>CN(C)C=O>[Si:26]([O:1][CH:2]([CH2:14][O:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)/[CH:3]=[CH:4]/[CH:5]1[CH2:12][CH2:11][CH:10]2[CH:6]1[CH2:7][CH2:8][C:9]2=[O:13])([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:29])[CH3:28]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: O=C1CCC2C(/C=C/C(O)COc3ccccc3)CCC12
Agent: c1c[nH]cn1
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OC(/C=C/C1CCC2C(=O)CCC12)COc1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 110.9 %

Procedure:
A mixture of (E)-2-(3-hydroxy-4-phenoxybut-1-enyl)bicyclo[3,3,0]octan-6-one (49 mg), the less polar component prepared as described in Reference Example 45 and in the form of (±)-(E)-2β-(3β-hydroxy-4-phenoxybut-1-enyl)bicyclo[3,3,0]octan-6-one, tert-butyldimethylchlorosilane (31 mg), and imidazole (29 mg) in dimethylformamide (0.116 ml) was stirred at the ambient temperature for 2 hours. The mixture was then treated with water (10 ml) and extracted with diethyl ether. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate and concentrated under reduced pressure, to give (E)-2-(3-tert-butyldimethylsilyloxy-4-phenoxybut-1-enyl)bicyclo[3,3,0]octan-6-one (76 mg), in the form of (±)-(E)-2β-(3β-tert-butyldimethylsilyloxy-4-phenoxybut-1-enyl)bicyclo[3,3,0]octan-6-one.
Reaction SMILES: [C:1]([CH2:4][C@@H:5]([CH2:16][CH:17]([CH3:19])[CH3:18])[C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])([OH:3])=O.[CH:20]1([NH2:26])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.Cl>C(Cl)Cl>[CH:20]1([NH:26][C:1]([CH2:4][C@@H:5]([CH2:16][CH:17]([CH3:19])[CH3:18])[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])=[O:3])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1
Reactant: NC1CCCCC1
Reactant: CC(C)C[C@H](CC(=O)O)C(=O)OCc1ccccc1
Agent: Cl
Solvent: ClCCl
Product: CC(C)C[C@H](CC(=O)NC1CCCCC1)C(=O)OCc1ccccc1
Reaction time: 8 h
Yield: 59.5 %

Procedure:
To a solution of benzyl (2R)-2-carboxymethyl-4-methylvalerate (527 mg) and cyclohexylamine (238 mg) in methylene chloride (10 ml) was added WSCD.HCl (460 mg) at room temperature. After being stirred overnight, the mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (30 ml). The solution was washed with 5% HCl, water, saturated sodium bicarbonate and water, dried over magnesium sulfate and evaporated in vacuo. The residue was triturated with n-hexane to give benzyl (2R)-2-(cyclohexylcarbamoylmethyl)-4-methylvalerate (410 mg).
Reaction SMILES: [C:1]([O:4][CH2:5][C@H:6]([N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Cl:21])[C:14]=2[N+:18]([O-])=O)[C:9]1=[O:22])[CH3:7])(=[O:3])[CH3:2].C(O)C.[Cl-].[NH4+].O>[Fe]>[C:1]([O:4][CH2:5][C@H:6]([N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Cl:21])[C:14]=2[NH2:18])[C:9]1=[O:22])[CH3:7])(=[O:3])[CH3:2]
Reactant: CC(=O)OC[C@@H](C)n1ccc2c([N+](=O)[O-])c(Cl)ccc2c1=O
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: CC(=O)OC[C@@H](C)n1ccc2c(N)c(Cl)ccc2c1=O
Temperature: 85 °C
Reaction time: 1 h

Procedure:
A round bottom flask was charged with (R)-2-(6-chloro-5-nitro-1-oxoisoquinolin-2(1H)-yl)propyl acetate (160.0 mg, 0.0004927 mol) and ethanol (7 mL, 0.1 mol), and the reaction was heated at 85° C. Ammonium chloride (264 mg, 0.00493 mol) in water (7 mL, 0.4 mol) was added, followed by iron (110 mg, 0.0020 mol) in two portions. The reaction was stirred at that temperature for one hour. The reaction mixture was then poured onto dichloromethane (60 mL) and extracted. The extracts were washed with brine, dried, and the solvent removed under reduced pressure to afford the product as a colorless solid.
Reaction SMILES: [N+:1]([C:4]1[CH:10]=[CH:9][C:7]([NH2:8])=[CH:6][C:5]=1[C:11]([F:14])([F:13])[F:12])([O-:3])=[O:2].[C:15](Cl)(=[O:19])[CH:16]([CH3:18])[CH3:17]>N1C=CC=CC=1>[N+:1]([C:4]1[CH:10]=[CH:9][C:7]([NH:8][C:15](=[O:19])[CH:16]([CH3:18])[CH3:17])=[CH:6][C:5]=1[C:11]([F:12])([F:13])[F:14])([O-:3])=[O:2]
Reactant: CC(C)C(=O)Cl
Reactant: Nc1ccc([N+](=O)[O-])c(C(F)(F)F)c1
Solvent: c1ccncc1
Product: CC(C)C(=O)Nc1ccc([N+](=O)[O-])c(C(F)(F)F)c1
Temperature: 0 °C

Procedure:
To a stirred, cooled solution of 100 g. of 4-nitro-3-trifluoromethylaniline in 400 ml. of pyridine, slowly and in a dropwise fashion, add 54 g. of isobutyrylchloride and then heat the reaction mixture on a steam bath for 1.5 hours. Cool and pour the resulting mixture into ice-water, filter and water-wash the crude anilide, crystallize the product of this example from benzene to obtain analytically pure material, m.p. 111.5°-112.5° C.
Reaction SMILES: [NH2:1][CH2:2][C:3]([N:5]1[C@H:9]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:8][S:7][C@@H:6]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:4].[CH3:29][C:30]1[CH:31]=[C:32]([N:36]=[C:37]=[O:38])[CH:33]=[CH:34][CH:35]=1>>[CH3:29][C:30]1[CH:31]=[C:32]([NH:36][C:37](=[O:38])[NH:1][CH2:2][C:3]([N:5]2[C@H:9]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:8][S:7][C@@H:6]2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:4])[CH:33]=[CH:34][CH:35]=1
Reactant: Cc1cccc(N=C=O)c1
Reactant: CC(C)(C)OC(=O)[C@@H]1CS[C@H](c2ccccc2-c2ccccc2)N1C(=O)CN
Product: Cc1cccc(NC(=O)NCC(=O)N2[C@@H](c3ccccc3-c3ccccc3)SC[C@H]2C(=O)OC(C)(C)C)c1
Yield: 12.5 %

Procedure:
The procedure is similar to that described in Example 1A, but starting with 1.32 g of tert-butyl (2R,4R)-3-(2-aminoacetyl)-2-(2-phenylphenyl)-4-thiazolidinecarboxylate and 0.47 g of 3-methylphenyl isocyanate. The crude product is purified by chromatography on silica [eluent: methylene chloride/ethyl acetate (90:10 by volume)]. The fractions containing the expected product are pooled and concentrated to dryness under reduced pressure at 40° C. After vigorous stirring in pentane, 0.22 g of tert-butyl (2R,4R)-3-{2-[3-(3-methylphenyl)-ureido]acetyl}-2-(2-phenylphenyl)-4-thiazolidinecarboxylate is thereby obtained in the form of an amorphous product; [α]D25 =-9.8±0.9° (C %=0.49; CHCl3).
Reaction SMILES: [OH-].[K+].[C:3]1([S:9]([NH:12][C:13]2[S:14][CH:15]=[C:16]([CH2:18][C:19]([O:21]CC)=[O:20])[N:17]=2)(=[O:11])=[O:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(OC(=O)C)(=O)C>O>[C:3]1([S:9]([NH:12][C:13]2[S:14][CH:15]=[C:16]([CH2:18][C:19]([OH:21])=[O:20])[N:17]=2)(=[O:11])=[O:10])[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: CCOC(=O)Cc1csc(NS(=O)(=O)c2ccccc2)n1
Agent: [K+]
Agent: [OH-]
Solvent: CC(=O)OC(C)=O
Solvent: O
Product: O=C(O)Cc1csc(NS(=O)(=O)c2ccccc2)n1
Yield: 92.6 %

Procedure:
To an aqueous solution of potassium hydroxide (5.0 g.) in water (150 ml.) was added ethyl 2-benzenesulfonamidothiazol-4-ylacetate (9.1 g.) at 10° C. with stirring, and the mixture was stirred for 30 minutes at room temperature. The reaction mixture was adjusted to pH 4 to 4.5 with acetic anhydride, and the mixture was stirred under ice-cooling till the crystals precipitated. The crystals were collected by filtration and dried to give 2-benzenesulfonamidothiazol-4-ylacetic acid (7.7 g.), mp 94° to 96° C. (dec.).
Reaction SMILES: [CH2:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([OH:14])=[O:13])=[CH:7][CH:6]=1)[CH:2]=[CH2:3].[OH-].[Na+:16]>O.C(O)C>[CH2:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([O-:14])=[O:13])=[CH:7][CH:6]=1)[CH:2]=[CH2:3].[Na+:16]
Reactant: C=CCNc1ccc(CC(=O)O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: C=CCNc1ccc(CC(=O)[O-])cc1

Procedure:
A mixture of 3.62 g. of 4-(allylamino)phenylacetic acid and 25 ml. of ethanol water (9:1) containing 0.400 g. of sodium hydroxide is stirred for 4 hours. The mixture is filtered and the residue washed with 10 ml. of ethanol-water (9:1) and dried in vacuo for 24 hours to yield sodium 4-(allylamino)phenylacetate as a white solid.