Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]([C:8]1[O:9][CH2:10][C:11](=O)[C:12]=1[C:13]([OH:15])=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.[Cl:32][C:33]1[CH:39]=[CH:38][C:36]([NH2:37])=[CH:35][CH:34]=1.Cl>C(Cl)Cl.O.C(N(CC)CC)C>[C:2]1([NH:1][C:8]([C:12]2[C:13](=[O:15])[O:14][CH2:10][C:11]=2[NH:37][C:36]2[CH:38]=[CH:39][C:33]([Cl:32])=[CH:34][CH:35]=2)=[O:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)C1=C(Nc2ccccc2)OCC1=O
Reactant: Nc1ccc(Cl)cc1
Agent: Cl
Agent: O=C1OCCN1P(=O)(Cl)N1CCOC1=O
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(Nc1ccccc1)C1=C(Nc2ccc(Cl)cc2)COC1=O
Reaction time: 0.75 h

Procedure:
Under nitrogen atmosphere, 8.5 ml of triethylamine was added dropwise over a period of 40 min to a solution of 2-anilino-4-oxo-3-furoic acid (13.37 grams, 0.061 mol) in 110 ml methylene chloride at 0° C. Then BOP-Cl was added in one portion and the mixture was stirred at 0°-5° C. for 45 min. A solution of p-chloroaniline (7.8 grams, 61 mmol) in 50 ml methylene chloride was added rapidly over 10 min followed by the dropwise addition (1.5 hours) of a solution of triethylamine (8.5 ml) in 10 ml methylene chloride. The reaction mixture was stirred at 0°-5° C. for 30 min and at room temperature for 20 hours. After cooling, 150 ml of water were added and the reaction mixture was acidified with 4N hydrochloric acid (pH 1), and then extracted with methylene chloride. The organic extract was washed sequentially with water, 5% aqueous solution of sodium bicarbonate, and water. The washed extract was dried over sodium sulfate and the solvent evaporated under reduced pressure. The crude product was recrystallized from toluene. Yield: 9.2 gram, mp 209°-210° C. (R=C6H4Cl--p).
Reaction SMILES: [N:1]1([C:7]2[S:8]C=C(CO)[N:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.CO>C(Cl)(Cl)Cl>[NH2:11][C:7]([N:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1)=[S:8]
Reactant: OCc1csc(N2CCOCC2)n1
Solvent: ClC(Cl)Cl
Solvent: CO
Product: NC(=S)N1CCOCC1
Yield: 65 %

Procedure:
Using the procedure of Example 9C but replacing 2-(N,N-dimethylamino)-4-(hydroxymethyl)thiazole with 2-(4-morpholinyl)-4-(hydroxymethyl)thiazole provided, after silica gel chromatography using 1% methanol in chloroform, the desired compound, Rf 0.54 (4% methanol in chloroform), in 65% yield. 1H NMR (CDCl3) δ0.97 (d, J=7 Hz, 3H), 1.00 (d, J=7 Hz, 3H), 2.25 (m, 1H), 3.50 (dd, J=5, 4 Hz, 2H), 3.76 (s, 3H), 3.84 (dd, J=5, 4 Hz, 2H), 4.67 (dd, J=9, 5 Hz, 1H), 7.63 (br d, 1H), 8.02 (s, 1H).
Reaction SMILES: C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO.O[C:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[NH:25][N:24]=1.C[CH2:33][O:34]C(/N=N/C(OCC)=O)=O.N#N>C1COCC1>[CH3:33][O:34][C:29]1[CH:30]=[C:31]2[C:26](=[CH:27][CH:28]=1)[NH:25][N:24]=[CH:23]2
Reactant: CCOC(=O)/N=N/C(=O)OCC
Reactant: Oc1n[nH]c2ccccc12
Agent: N#N
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CO
Solvent: C1CCOC1
Product: COc1ccc2[nH]ncc2c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred mixture of PPh3 (1.67 g, 6.4 mmol), MeOH (204 mg, 6.4 mmol) and the hydroxyindazole prepared above (2.0 g, 5.3 mmol) in THF (20 mL) was added DEAD (1.11 g, 6.4 mmol) dropwise under N2. The resulting mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue was purified with flash chromatography on silica gel (gradient elution with 50:1 to 5:1 petroleum ether:EtOAc) to afford the desired 5-methoxyindazole as a yellow oil. MS (ESI) m/z=391.1 [M+1]+.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][C:16]3[C:25]4[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=4)[N:19]=[CH:18][CH:17]=3)[CH:13]=2)[N:8]([C:27]2[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=2)[C:7]=1[CH2:38][C:39]([O:41]CC)=[O:40])=[O:5])C.[OH-].[Na+].O>CCO>[C:39]([CH2:38][C:7]1[N:8]([C:27]2[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:35])[F:36])=[CH:29][CH:28]=2)[C:9]2[C:14]([C:6]=1[C:4]([OH:5])=[O:3])=[CH:13][C:12]([O:15][C:16]1[C:25]3[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=3)[N:19]=[CH:18][CH:17]=1)=[CH:11][CH:10]=2)([OH:41])=[O:40]
Reactant: CCOC(=O)Cc1c(C(=O)OCC)c2cc(Oc3ccnc4cc(Cl)ccc34)ccc2n1-c1ccc(OC(F)(F)F)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)Cc1c(C(=O)O)c2cc(Oc3ccnc4cc(Cl)ccc34)ccc2n1-c1ccc(OC(F)(F)F)cc1

Procedure:
A mixture of 5-(7-chloroquinolin-4-yloxy)-2-ethoxycarbonylmethyl-1-(4-trifluoromethoxyphenyl)indole-3-carboxylic acid ethyl ester (40 mg, 0.065 mmol, see step (a) above), NaOH (50 mg), water (1 mL) and EtOH (1 mL) was heated at reflux for 1 h. The EtOH was removed in vacuo and the mixture was acidified with HCl (aq, 1 M) to pH 4. The solid was filtered off to give the title compound. Yield 33 mg (91%).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][NH2:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:18]1(=[O:24])[O:23][C:21](=[O:22])[CH2:20][CH2:19]1>>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][NH:17][C:18](=[O:24])[CH2:19][CH2:20][C:21]([OH:23])=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)NCCOCCOCCN
Reactant: O=C1CCC(=O)O1
Product: CC(C)(C)OC(=O)NCCOCCOCCNC(=O)CCC(=O)O
Yield: 98 %

Procedure:
Preparation from 1-(t-butyloxycarbonylamino)-3,6-dioxa-8-octanamine) (5 g, 20.16 mmol) and succinic anhydride (2.218 g, 22.18 mmol) gave a thick yellow oil which crystallised on standing (6.5 g, yield 98%). LCMS (Method 6): Rt 2.99 min; m/z (M+1) 349; Calcd.: 349.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[C@@H:12]3[CH2:15][C@@H:16]([OH:18])[CH2:17][N:11]3[C:10]2=[O:19])[CH:5]=[C:6]([Cl:8])[CH:7]=1.CN(C1C=CC=CN=1)C.[C:29](O)(=[O:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl>[C:29]([O:18][C@H:16]1[CH2:17][N:11]2[C:10](=[O:19])[N:9]([C:4]3[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=3)[C:13](=[O:14])[C@@H:12]2[CH2:15]1)(=[O:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: O=C(O)c1ccccc1
Reactant: O=C1[C@@H]2C[C@@H](O)CN2C(=O)N1c1cc(Cl)cc(Cl)c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Product: O=C(O[C@@H]1C[C@H]2C(=O)N(c3cc(Cl)cc(Cl)c3)C(=O)N2C1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 95 %

Procedure:
To a solution of (6R,7aS)-2-(3,5-dichlorophenyl)-6-hydroxytetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione (1.2 g) (4 mmol) (Preparation 6), dimethylaminopyridine (50 mg) (0.1 eq.) and benzoic acid (0.49 g) (1 eq.) in 10 mL of dry DCM at 0° C. was added DCC (0.9 g) (1 eq.) in a minimal volume of DCM. The reaction mixture was stirred to RT overnight. After filtering off the insoluble material, the reaction mixture is washed with a dilute NaHCO3 aqueous solution, with dilute HCl solution, with water, dried over MgSO4, and evaporated under reduced pressure to afford to afford the titled compound as a viscous oil (1.54 g). 1H NMR (CDCl3): 8.05 (2H,d), 7.65 (1H,m), 7.5 (1H,d), 7.43 (2H,d), 7.38 (1H,m), 5.81 (1H,t), 4.62 (1H,dd), 4.23 (1H,dd), 3.56 (1H,d), 2.68 (1H,dd), 2.05–2.20 (1H,m).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]([C:14]2[O:15][C:16](Br)=[CH:17][CH:18]=2)=[O:13])[CH:6]=1.[Cl:21][C:22]1[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O>>[CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]([C:14]2[O:15][C:16]([C:26]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:21])[C:27]=3[Cl:28])=[CH:17][CH:18]=2)=[O:13])[CH:6]=1
Reactant: OB(O)c1cccc(Cl)c1Cl
Reactant: COC(=O)Cc1cccc(NC(=O)c2ccc(Br)o2)c1
Product: COC(=O)Cc1cccc(NC(=O)c2ccc(-c3cccc(Cl)c3Cl)o2)c1

Procedure:
Methyl ester (16) (100 mg, 0.30 mmol) was coupled to 2,3-dichloro-phenylboronic acid (62 mg, 0.33 mmol) using Method E. The crude compound was purified by column chromatography, eluting in 17% EtOAc in heptane to give the title compound.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH2:7][CH2:6][C:5]2=[O:12].Cl[CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=1.[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CCOC(C)=O.C(Cl)Cl.CC(C)=O>[N:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:23]=[CH:24][C:15]=1[CH2:14][O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH2:7][CH2:6][C:5]2=[O:12]
Reactant: O=C1CCOc2ccc(O)cc21
Reactant: ClCc1ccc2ccccc2n1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: CC(C)=O
Product: O=C1CCOc2ccc(OCc3ccc4ccccc4n3)cc21
Reaction time: 17 h

Procedure:
A mixture of 6-hydroxy-4-chromanone (10.0 g, 0.0609 mol), 2-chloromethylquinoline (11.9 g, 0.0670 mol), sodium iodide (10.0 g, 0.0670 mol), potassium carbonate (25.3 g, 0.183 mol), and acetone (200 ml) was refluxed overnight under N2 atmosphere. After 17 hours the reaction appeared lighter and tlc analysis (10% EtOAc/CH2Cl2) indicated complete conversion of starting material to a slightly less polar products The mixture was cooled, filtered, and the filtrate concentrated in vacuo. The residue was taken up in ethyl acetate (400 ml), washed with H2O and brine, dried over MgSO4, and concentrated in vacuo to a dark brown oil. Purification on a silica gel column eluted with 10% ethyl acetate/CH2Cl2 gave title product as an off-white solid, 15.3 g (82%), m.p. 112-114° C.; tlc (1:9 ethyl acetate:CH2Cl2) Rf 0.30.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:7].[N+:15]([O-])([OH:17])=[O:16].O>C(O)(=O)C>[N+:15]([CH:2]([CH2:3][CH2:4][CH2:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:7])[CH3:1])([O-:17])=[O:16]
Reactant: O=[N+]([O-])O
Reactant: CCCCCC(=O)Nc1ccccc1
Solvent: CC(=O)O
Solvent: O
Product: CC(CCCC(=O)Nc1ccccc1)[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 4 h

Procedure:
2-nitro-4-n-butylaniline intermediate compound 150 g of a 4-n-butyl-aniline were treated with 300 ml of acetic anhydride at 70° C. for 1 hour and then cooled to 10° C. After filtering the solid product on a Buchner funnel and drying at 60° C. under vacuum, 183 g of 4-n-butyl-acetanilide were obtained. 183 g of 4-n-butylacetanilide were dissolved in 300 ml of acetic acid and this solution, cooled at 5°-10° C., was added to a wellstirred mixture obtained by mixing 123 ml of nitric acid at a density of 1.4 and 325 ml of nitric acid at a density of 1.52. The temperature was kept below 5° C. during the whole addition and at the end the stirring was continued for 4 hours. The reaction mixture was then poured into 4 liters of ice and water under stirring, thus obtaining a yellow solid product that was filtered on a Buchner funnel and purified by recrystallization from ethanol. 217.4 g of 2-nitro-4-n-butyl-acetanilide were obtained and treated with 1,500 ml of toluolated ethanol and 600 ml of concentrated hydrochloric acid. The solution obtained was heated to reflux for two hours and the solvents removed under vacuum using a rotary evaporator. The oil residue, the analysis of which is reported hereinbelow, was used for the preparation of compound 1 without further purification.
Reaction SMILES: [F:1][C:2]1([F:31])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3[C:19]4[C:14](=[N:15][CH:16]=[C:17]([C:20]5[CH:21]=[N:22][N:23]([CH:25]6[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]6)[CH:24]=5)[CH:18]=4)[NH:13][CH:12]=3)=[CH:10][C:4]=2[O:3]1.[CH2:32](N(CC)CC)C.CI>C(Cl)Cl>[F:31][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3[C:19]4[C:14](=[N:15][CH:16]=[C:17]([C:20]5[CH:21]=[N:22][N:23]([CH:25]6[CH2:26][CH2:27][N:28]([CH3:32])[CH2:29][CH2:30]6)[CH:24]=5)[CH:18]=4)[NH:13][CH:12]=3)=[CH:10][C:4]=2[O:3]1
Reactant: CCN(CC)CC
Reactant: FC1(F)Oc2ccc(-c3c[nH]c4ncc(-c5cnn(C6CCNCC6)c5)cc34)cc2O1
Solvent: CI
Solvent: ClCCl
Product: CN1CCC(n2cc(-c3cnc4[nH]cc(-c5ccc6c(c5)OC(F)(F)O6)c4c3)cn2)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 324 (50 mg, 0.1182 mmol) in DCM was added triethylamine (17.9 mg, 0.236 mmol). Methyl iodide (18.3 mg, 0.130 mmol) was added to the reaction and stirred for 2 h at rt. The reaction mixture was diluted with dichloromethane and washed with water twice. The organic layer was dried over sodium sulphate and concentrated to get the crude, which was purified by flash column using 100-200 mesh silica gel. The compound was eluted at 2% methanol in chloroform as off white coloured solid 3-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-5-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine 341.
Reaction SMILES: [CH:1]([C:4]1[CH2:5][C:6]2[C:11]([CH:12]=1)=[C:10]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH:9]=[CH:8][CH:7]=2)([CH3:3])[CH3:2].C([Li])CCC.[CH3:24][Si:25](Cl)([CH3:36])[CH:26]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[C:27]1[CH3:35].[Cl-].[NH4+]>[Cu](C#N)C#N.CCCCCC.C(OCC)C>[CH3:24][Si:25]([CH3:36])([CH:5]1[C:6]2[C:11](=[C:10]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:9]=[CH:8][CH:7]=2)[CH:12]=[C:4]1[CH:1]([CH3:3])[CH3:2])[CH:26]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[C:27]1[CH3:35]
Reactant: CC1=Cc2ccccc2C1[Si](C)(C)Cl
Reactant: CC(C)C1=Cc2c(cccc2-c2ccccc2)C1
Agent: N#C[Cu]C#N
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CCOCC
Product: CC1=Cc2ccccc2C1[Si](C)(C)C1C(C(C)C)=Cc2c(-c3ccccc3)cccc21
Temperature: 25 °C
Reaction time: 12 h
Yield: 98.2 %

Procedure:
In a 200-ml two-necked flask were charged 4.0 g (17.1 mmol) of 2-i-propyl-4-phenylindene, 42.3 mg (0.445 mmol) of copper cyanide, and 40 ml of diethyl ether. To the mixture was added at -78° C. 11.8 ml of 1.62 M hexane solution of n-butyllithium and the mixture was stirred at room temperature for 2 hours. Subsequently, 4.2 g (18.8 mmol) of dimethyl(2-methylindenyl)silyl chloride was added at -78° C. and the mixture was stirred at room temperature for 12 hours. After addition of aqueous ammonium chloride solution to the reaction mixture, the organic layer was washed with saturated saline and dried over sodium sulfate. The sodium sulfate was removed by filtration and the organic solvent was distilled off under reduced pressure. The residue was purified by column chromatography (silica gel, development solvent: hexane methylene chloride=9:1) to obtain 7.22 g (16.8 mmol, yield: 95%) of a pale yellow oil. The product was confirmed to be a mixture of two isomers by 1H-NMR.
Reaction SMILES: [CH3:1][N:2]([CH3:26])[C:3]([NH:5][C:6]1[S:7][C:8](=[CH:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20]3)=[CH:15][CH:14]=2)[C:9](=[O:11])[N:10]=1)=[NH:4].[NH2:27][CH2:28][C@H:29]([OH:39])[CH2:30][O:31][C:32]1[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][CH:33]=1>>[OH:39][C@H:29]([CH2:30][O:31][C:32]1[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][CH:33]=1)[CH2:28][NH:27][CH:22]1[CH2:23][CH2:24][N:19]([C:16]2[CH:17]=[CH:18][C:13]([CH:12]=[C:8]3[S:7][C:6]([NH:5][C:3](=[NH:4])[N:2]([CH3:1])[CH3:26])=[N:10][C:9]3=[O:11])=[CH:14][CH:15]=2)[CH2:20][CH2:21]1
Reactant: CN(C)C(=N)NC1=NC(=O)C(=Cc2ccc(N3CCC(=O)CC3)cc2)S1
Reactant: NC[C@H](O)COc1ccc(O)cc1
Product: CN(C)C(=N)NC1=NC(=O)C(=Cc2ccc(N3CCC(NC[C@H](O)COc4ccc(O)cc4)CC3)cc2)S1

Procedure:
The title compound was prepared from N,N-dimethyl-N′-{4-oxo-5-[4-(4-oxo-piperidin-1-yl)-benzylidene]-4,5-dihydro-thiazol-2-yl}-guanidine (which was obtained in Intermediate 23) and 4-((2S)-3-amino-2-hydroxy-propoxy)-phenol (which was obtained in Intermediate 5) according to the procedure of Example 1 as a yellowish solid; 1 H NMR (300 MHz, DMSO-d6) δ1.20-1.40 (m, 2 H), 1.75-1.95 (m, 2 H), 2.50-3.30 (m, 9 H), 3.70-3.90 (m, 7 H), 4.90 (brs, 1 H), 6.66 (d, J=6.8 Hz, 1 H), 6.74 (d, J=6.8 Hz, 1 H), 7.01 (d, J=8.8 Hz, 2 H), 7.41 (d, J=8.8 Hz, 2 H), 7.47 (s, 1 H); MS (ES) m/z: 270.0 ((M+2H)2+, 100%); 539.1 (MH+, 10%); HRMS Calcd. for C27H35N6O4S (MH+): 539.2441. Found: 539.2422.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7](=[O:12])[NH:8][NH:9][C:10]=1[CH3:11])=[O:5])[CH3:2].C([O-])([O-])=O.[K+].[K+].Br[CH:20]([CH3:31])[C:21]([C:23]1[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][C:24]=1[CH3:30])=[O:22].O>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:7]([O:12][CH:20]([CH3:31])[C:21]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][C:24]=2[CH3:30])=[O:22])=[N:8][NH:9][C:10]=1[CH3:11])=[O:5])[CH3:2]
Reactant: Cc1ccc(C(=O)C(C)Br)c(C)c1
Reactant: CCOC(=O)c1c(C)[nH][nH]c1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1c(OC(C)C(=O)c2ccc(C)cc2C)n[nH]c1C

Procedure:
To a well stirred mixture of 5-methyl-3-oxo-2,3-dihydro-1H-pyrazole4-carboxylic acid ethyl ester (200 mg, 1.18 mmol, 1 eq.) and K2CO3 (179 mg, 1.29 mmol, 1.1 eq.) in DMF (5 ml) is added dropwise a solution of 2-bromo-1-(2,4-dimethyl-phenyl)-propan-1-one (Intermediate BA) (298 mg, 1.23 mmol, 1.05 eq.) in DMF (2.5 ml) at 50° C. After the addition, the reaction mixture is further stirred at 50° C. for 1 h then poured into water (50 ml) and extracted with EtOAc (2×25 ml). The combined organic fractions are dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. The resulting crude residue is purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, [iso-hexane/DCM 1:1]/TBME 95:5→7:3) to yield the title compound as a white solid. TLC: RF=0.74 (iso-hexane/DCM/TBME 1:1:2); HPLC: AtRet=2.30; MS: m/z 331.3 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 1.24 (t, J 7.1, 3H), 1.43 (d, J 6.8, 3H), 2.31 (s, 6H), 2.33 (s, 3H), 4.15 (m, 2H), 5.75 (q, J 6.8, 1H), 7.13 (m, 2H), 7.83 (m, 1H), 12.24 (br. s., 1H).
Reaction SMILES: S(=O)(=O)(O)[OH:2].[CH3:6]/[C:7](=[CH:11]\[CH2:12][CH2:13][CH:14]([CH3:16])[CH3:15])/[CH2:8][CH2:9][OH:10]>O.CC(C)=O.O.O.O.[Cr]>[CH3:6][C:7](=[CH:11][CH2:12][CH2:13][CH:14]([CH3:16])[CH3:15])[CH2:8][C:9]([OH:2])=[O:10]
Reactant: O=S(=O)(O)O
Reactant: C/C(=C\CCC(C)C)CCO
Agent: [Cr]
Solvent: CC(C)=O
Solvent: O
Product: CC(=CCCC(C)C)CC(=O)O
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
A solution of 8.84 g (88.4 mmol, 3 eq) of chromium VI oxide in 25 mL of water in the presence of 8.2 mL of 95% sulphuric acid is added to a solution of 4.6 g (29.5 mmol, 1 eq) of (E)-3,7-dimethyloct-3-enol in 250 mL of acetone, at 0° C., while maintaining the temperature at 0° C. After addition, the reaction mixture is stirred for 15 minutes at 0° C. and the reaction is then quenched by adding 250 mL of water. The reaction medium is extracted with 2×250 mL of diethyl ether. The organic phases are combined, washed with saturated sodium chloride solution and dried over anhydrous sodium sulphate, and the residue is then filtered through silica gel: eluent (95/5→75/25 Cy/EtOAc).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[C:13]([CH2:15][C:16]([O:18][CH3:19])=[O:17])#[N:14].CO>N1CCCCC1.C(Cl)Cl>[C:13]([C:15](=[CH:9][C:8]1[CH:11]=[CH:12][C:5]([NH:4][C:1](=[O:3])[CH3:2])=[CH:6][CH:7]=1)[C:16]([O:18][CH3:19])=[O:17])#[N:14]
Reactant: COC(=O)CC#N
Reactant: CC(=O)Nc1ccc(C=O)cc1
Solvent: ClCCl
Solvent: CO
Solvent: C1CCNCC1
Product: COC(=O)C(C#N)=Cc1ccc(NC(C)=O)cc1

Procedure:
A mixture of p-acetamidobenzaldehyde (4.08 g, 0.025 m), methyl cyanoacetate (2.50 g, 0.026 m), methanol (75 ml) and piperidine (10 drops) is heated and stirred at reflux for 0.5 hour. The reaction mixture is cooled and the pale yellow solid collected by filtration and dried in air. Recrystallization of the product from 50/50 isopropanol/toluene (by volume) gives 4.5 g of pure UV absorber product by mass spectrum analysis which has an absorption maximum at 346 nm in methylene chloride.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:10]2[O:11][C:12]3[CH:22]=[C:21]4[C:16]([CH:17]=[CH:18][CH:19]=[CH:20]4)=[CH:15][C:13]=3[N:14]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[CH:23]1[C:28]([C:29]([OH:31])=[O:30])=[CH:27][C:26]2[C:32]([O:34][C:35](=O)[C:25]=2[CH:24]=1)=[O:33]>>[CH3:9][O:8][C:7]1[CH:6]=[CH:5][C:4]([C:10]2[O:11][C:12]3[CH:22]=[C:21]4[C:16]([CH:17]=[CH:18][CH:19]=[CH:20]4)=[CH:15][C:13]=3[N:14]=2)=[CH:3][C:2]=1[N:1]1[C:32](=[O:33])[C:26]2[C:25](=[CH:24][CH:23]=[C:28]([C:29]([OH:31])=[O:30])[CH:27]=2)[C:35]1=[O:34]
Reactant: O=C(O)c1ccc2c(c1)C(=O)OC2=O
Reactant: COc1ccc(-c2nc3cc4ccccc4cc3o2)cc1N
Product: COc1ccc(-c2nc3cc4ccccc4cc3o2)cc1N1C(=O)c2ccc(C(=O)O)cc2C1=O

Procedure:
Prepared by the method of Example 1b), from 2-(3-amino-4-methoxyphenyl)naphth[2,3-d]oxazole (67 mg, 0.23 mmol) and 1,2,4-benzenetricarboxylic anhydride (50 mg, 0.26 mmol) the title compound was obtained, 40 mg (37%). 1H NMR (DMSO) δ 8.34(m, 4H), 8.24(d, 1H), 8.15(s, 1H), 8.01(m, 3H), 8.43(m, 3H), 3.81(s, 3H). MS 463 m/z (M−H)−.
Reaction SMILES: C([Li])CCC.Br[C:7]1[C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[S:10][CH:11]=1.[C:16]1([CH2:22][CH2:23][N:24]2[CH2:29][CH2:28][CH:27]([CH:30]=[O:31])[CH2:26][CH2:25]2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CCCCCC.C(OCC)C>[C:16]1([CH2:22][CH2:23][N:24]2[CH2:29][CH2:28][CH:27]([CH:30]([C:7]3[C:8]4[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=4[S:10][CH:11]=3)[OH:31])[CH2:26][CH2:25]2)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: Brc1csc2ccccc12
Reactant: O=CC1CCN(CCc2ccccc2)CC1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CCOCC
Product: OC(c1csc2ccccc12)C1CCN(CCc2ccccc2)CC1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
Dissolve n-butyllithium (9.4 mL of a 2.5M solution in hexane, 23.46 mmol) in anhydrous ethyl ether (100 mL), place under an argon atmosphere and cool to -78° C. Add, by dropwise addition, a solution of 3-bromobenzo[b]thiophene (5.0 g, 23.46 mmol) in anhydrous ethyl ether (50 mL). Stir at -78° C. for 30 minutes then add, by dropwise addition, a solution of 1-(2-phenylethyl)-4-piperidinecarboxaldehyde (5.10 g, 23.46 mmol) in anhydrous ethyl ether (50 mL). Stir for 5 hours at -78° C., remove the ice bath and stir for an additional 1 hour. Quench with saturated ammonium chloride (150 mL) and stir overnight. Separate the organic phase and extract the aqueous phase with ethyl ether and methylene chloride. Combine the organic phases, dry (MgSO4) and evaporate the solvent in vacuo. Purify by recrystallization (isopropanol) to give the title compound as an off-white solid.
Reaction SMILES: [C@H:1]12[CH2:8][O:7][C:6](=[O:9])[C@H:5]1[CH2:4][CH2:3][CH2:2]2.[NH3:10].ClCCl.CO>C(O)C>[OH:7][CH2:8][C@@H:1]1[CH2:2][CH2:3][CH2:4][C@@H:5]1[C:6]([NH2:10])=[O:9]
Reactant: O=C1OC[C@@H]2CCC[C@H]12
Reactant: N
Solvent: CCO
Solvent: CO
Solvent: ClCCl
Product: NC(=O)[C@H]1CCC[C@H]1CO
Yield: 61.7 %

Procedure:
(1R,5S)-(+)-7-oxabicyclo[3.3.0]octan-6-one (1 gram) was dissolved in 5 ml of absolute ethanol, followed by the addition of 0.5 gram of gaseous ammonia. The solution was kept in a stoppered flask, and the progress of the reaction was followed by thin layer chromatography (eluent dichloromethane/methanol 20:1). After the reaction was judged complete, the ethanol was evaporated and the resulting residue redissolved in ethyl acetate. Ammonia was removed by extraction with 1% HCl, and the ethyl acetate solution was dried over MgSO4, filtered, and rotary evaporated to leave 0.7 grams of (1S,2R)-2-hydroxymethyl-1-cydopentanecarboxamide.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-])=O)[CH:10]=1)(=[O:8])=[O:7])=[O:4]>[Pd].O.C(O)C>[F:19][C:2]([F:1])([F:18])[C:3]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([NH2:15])[CH:10]=1)(=[O:7])=[O:8])=[O:4]
Reactant: O=C(NS(=O)(=O)c1cccc([N+](=O)[O-])c1)C(F)(F)F
Agent: [Pd]
Solvent: O
Solvent: CCO
Product: Nc1cccc(S(=O)(=O)NC(=O)C(F)(F)F)c1
Yield: 69.7 %

Procedure:
In the same way as that described in Example 11, Step 2, using 1-(trifluoromethylcarbonylaminosulphonyl)-3-nitrobenzene (2.7 g, 9.1 mmol), 10% palladium on carbon (0.25 g, 9% (w/w)) in water (3 ml) and ethanol (70 ml), the title compound (1.7 g, 70%) was afforded as a colourless solid. mp 106°-108° C. 1H NMR (360 MHz, D6 -DMSO) δ 6.59 (1H, m), 6.88 (1H, m), 7.02 (2H, m).