Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([C:14](O)=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[C:19]([F:25])[CH:18]=2)[N:3]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[F:40][C:41]1[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=1>CN(C=O)C.CCOC(C)=O.O>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([NH:45][C:44]3[CH:46]=[CH:47][C:41]([F:40])=[CH:42][CH:43]=3)=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[C:19]([F:25])[CH:18]=2)[N:3]=1
Reactant: N#Cc1ccc(-c2cc(N3CCC[C@H](C(=O)O)C3)nc(N)n2)cc1F
Reactant: Nc1ccc(F)cc1
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: ClCCCl
Solvent: O
Product: N#Cc1ccc(-c2cc(N3CCC[C@H](C(=O)Nc4ccc(F)cc4)C3)nc(N)n2)cc1F
Temperature: 25 °C
Reaction time: 4 h
Yield: 47.2 %

Procedure:
To a solution of (3S)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-3-piperidinecarboxylic acid (150 mg, 0.439 mmol), EDC (118 mg, 0.615 mmol), and HOBT (83 mg, 0.615 mmol) in DMF (8 mL) was added 4-fluoroaniline (68.4 mg, 0.615 mmol), and the reaction mixture was stirred at room temperature for 4 hours. LCMS showed reaction was completed. The reaction was poured into water, and EtOAc was added to extract the product. The product stayed in the EtOAc layer. The organic solution was concentrated to dryness to give the title compound (90 mg) as a yellow solid. LC-MS (ES) m/z=435 [M+H]+.
Reaction SMILES: [CH2:1]([C:8]1[C:13](=[O:14])[N:12]2[CH:15]=[CH:16][CH:17]=[CH:18][C:11]2=[N:10][C:9]=1[CH:19]=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:21]([Mg]Br)([CH3:23])=[CH2:22]>C1COCC1>[CH2:1]([C:8]1[C:13](=[O:14])[N:12]2[CH:15]=[CH:16][CH:17]=[CH:18][C:11]2=[N:10][C:9]=1[CH:19]([OH:20])[C:21]([CH3:23])=[CH2:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=Cc1nc2ccccn2c(=O)c1Cc1ccccc1
Reactant: C=C(C)[Mg]Br
Solvent: C1CCOC1
Product: C=C(C)C(O)c1nc2ccccn2c(=O)c1Cc1ccccc1
Temperature: -78 °C
Reaction time: 2 h
Yield: 105.3 %

Procedure:
A mixture of 500 mg (1.9 mmol) of the product from Step 6 (16) in 15 ml THF was cooled to −78° C. To the resulting solution was added dropwise 7.6 ml (3.8 mmol) of isopropenylmagnesium bromide and stirred at −78° C. for 2 hours. The reaction was quenched with saturated NH4Cl and extracted with ethyl acetate (2×). The combined organic layers were dried over MgSO4 and the solvent was removed in vacuo yielding 613 mg (2.0 mmol, 106%) of 3-benzyl-2-(1-hydroxy-2-methylprop-2-enyl)-4H-pyrido [1,2-a]pyrimidin-4-one (17) as a pale yellow solid. This was purified by flash chromatography.
Reaction SMILES: COC(=O)C1C=CC=C(C2C=NC(N)=C(C3SC4C=CC=CC=4N=3)C=2)C=1.C[O:28][C:29](=[O:52])[C:30]1[CH:35]=[CH:34][C:33]([C:36]2[CH:37]=[N:38][C:39]([NH2:51])=[C:40]([C:42]3[S:43][C:44]4[CH:50]=[CH:49][CH:48]=[CH:47][C:45]=4[N:46]=3)[CH:41]=2)=[CH:32][CH:31]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O>[NH2:51][C:39]1[N:38]=[CH:37][C:36]([C:33]2[CH:32]=[CH:31][C:30]([C:29]([OH:52])=[O:28])=[CH:35][CH:34]=2)=[CH:41][C:40]=1[C:42]1[S:43][C:44]2[CH:50]=[CH:49][CH:48]=[CH:47][C:45]=2[N:46]=1
Reactant: COC(=O)c1ccc(-c2cnc(N)c(-c3nc4ccccc4s3)c2)cc1
Agent: COC(=O)c1cccc(-c2cnc(N)c(-c3nc4ccccc4s3)c2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: Nc1ncc(-c2ccc(C(=O)O)cc2)cc1-c1nc2ccccc2s1

Procedure:
Following the procedure for 3-(6-amino-5-benzothiazol-2-ylpyridin-3-yl)-benzoic acid methyl ester, the title compound was prepared from 4-(6-amino-5-benzothiazol-2-ylpyridin-3-yl)-benzoic acid methyl ester (1.2 g, 3.3 mmol) and K2CO3 (1.5 g, 11 mmol) in dioxane/H2O (5:1, 30 mL). 1H NMR (400 MHz, DMSO-d6): δ=13.0 (very brs, 1H), 8.62 (d, J=2.2 Hz, 1H), 8.29 (d, J=2.2 Hz, 1H), 8.19-8.13 (m, 3H), 8.12 (d, J=7.8 Hz, 1H), 8.04-8.00 & 7.88-7.84 (AA′BB′, 4H), 7.57 (ddd, J=1.0, 7.0, 8.0 Hz, 1H), 7.49 (ddd, J=1.0, 7.4, 8.0 Hz, 1H). MS(ES+): m/z=348.08 (100) [MH+]. HPLC: tR=3.29 min (polar—5 min, ZQ2).
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([OH:10])(=[O:9])=[O:8])=[CH:3][CH:2]=1.[CH2:12]([O:20][C:21](=[O:30])[CH2:22][CH2:23][CH:24]([NH2:29])[C:25](C)=[C:26]=[CH2:27])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].[K+].[Br-]>>[C:1]1([CH3:11])[CH:2]=[CH:3][C:4]([S:7]([OH:10])(=[O:8])=[O:9])=[CH:5][CH:6]=1.[NH2:29][CH:24]([CH:25]=[C:26]=[CH2:27])[CH2:23][CH2:22][C:21]([O:20][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[O:30]
Reactant: C=C=C(C)C(N)CCC(=O)OCCCCCCCC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Br-]
Agent: [K+]
Product: C=C=CC(N)CCC(=O)OCCCCCCCC

Procedure:
In the same manner, octyl-4-amino-5-methyl-5,6-heptadienoate para-toluene-sulfonic acid salt was made. mp. 62° C., IR (KBr): 1760, 1725 cm-1 ; 'H NMR (δCDCl3): 0.8-2.5 (m, 21H), 2.37 (s, 3H, CH3Ph), 3.7 (m, 1H, CHN), 4.0 (t, 2H, J=6.7 Hz, OCH2), 4.9 (m, 2H, H2C=C), 7.15, 7.77 (d, 4H, Ph), 7.25 (broad s, 3H, NH, OH).
Reaction SMILES: [C:1]1([C:7]2([CH3:14])[CH2:11][O:10][C:9]([CH3:13])([CH3:12])[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N.[Li].[Cl-].[NH4+]>C(O)C>[C:1]1([C:7]2([CH3:14])[CH2:11][O:10][C:9]([CH3:13])([CH3:12])[CH2:8]2)[CH2:2][CH:3]=[CH:4][CH2:5][CH:6]=1
Reactant: CC1(C)CC(C)(c2ccccc2)CO1
Agent: N
Agent: [Cl-]
Agent: [Li]
Solvent: CCO
Product: CC1(C)CC(C)(C2=CCC=CC2)CO1
Temperature: -33 °C
Reaction time: 2 h
Yield: 84 %

Procedure:
A 150 g sample of 4-phenyl-2,2,4-trimethyltetrahydrofuran was added to 1000 ml of anhydrous ammonia, followed by 109 g of anhydrous ethanol. To this mixture was added portionwise over 1 hr 18.7 g of lithium wire. The mixture was allowed to stir at -33° C. for an additional 2 hrs., then sufficient ammonium chloride was added to discharge any residual blue color. The ammonia was allowed to evaporate and the residue was treated with 500 ml of hexane and 500 ml of water. The organic layer was separated and washed with 10% sulfuric acid solution until slightly acidic. The organic layer was washed with 10% soda ash solution and the solvent was removed on a rotary evaporator. Distillation afforded 128 g (84% yield) of the desired 4-(1,4-cyclohexadienyl)-2,2,4-trimethyltetrahydrofuran (bp 83°-84°/0.6 mm Hg) with a purity of 95%. Spectral data were in full agreement with the assigned structure. This material possesses a citrus, grapefruit, floral odor.
Reaction SMILES: [N:1]1([CH:7]2[CH2:12][CH2:11][N:10]([C:13]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[NH:20][C:19]([C:24]([N:26]3[CH2:31][CH2:30][C:29]([F:33])([F:32])[CH2:28][CH2:27]3)=[O:25])=[CH:18]4)=[O:14])[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[CH:37]([CH3:39])[CH3:38]>CN(C)C=O>[N:1]1([CH:7]2[CH2:12][CH2:11][N:10]([C:13]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[N:20]([CH:37]([CH3:39])[CH3:38])[C:19]([C:24]([N:26]3[CH2:31][CH2:30][C:29]([F:33])([F:32])[CH2:28][CH2:27]3)=[O:25])=[CH:18]4)=[O:14])[CH2:9][CH2:8]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CC(C)Br
Reactant: O=C(c1ccc2[nH]c(C(=O)N3CCC(F)(F)CC3)cc2c1)N1CCC(N2CCCCC2)CC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)n1c(C(=O)N2CCC(F)(F)CC2)cc2cc(C(=O)N3CCC(N4CCCCC4)CC3)ccc21
Yield: 62 %

Procedure:
The title compound was synthesized in analogy to example 51, from [5-([1,4′]bipiperidinyl-1′-carbonyl)-1H-indol-2-yl]-(4,4-difluoro-piperidin-1-yl)-methanone (example 168), sodium hydride and 2-bromopropane in N,N-dimethylformamide, to give the desired product as a brown oil (62%).
Reaction SMILES: C[O:2][C:3](=[O:18])[C:4]1[C:9]([NH:10][CH:11]([CH2:14][CH3:15])[CH2:12][CH3:13])=[CH:8][C:7]([CH3:16])=[N:6][C:5]=1[Cl:17].O[Li].O>O.O1CCOCC1>[Cl:17][C:5]1[N:6]=[C:7]([CH3:16])[CH:8]=[C:9]([NH:10][CH:11]([CH2:14][CH3:15])[CH2:12][CH3:13])[C:4]=1[C:3]([OH:18])=[O:2]
Reactant: CCC(CC)Nc1cc(C)nc(Cl)c1C(=O)OC
Agent: [Li]O
Solvent: O
Solvent: C1COCCO1
Product: CCC(CC)Nc1cc(C)nc(Cl)c1C(=O)O

Procedure:
The title compound was prepared by reaction of 2-chloro-4-(1-ethyl-propylamino)-6-methyl-nicotinic acid methyl ester with LiOH.H2O in a mixture of water and dioxane at room temperature. The desired product was acidified to pH 3 and extracted with ethyl acetate. The organic layer was dried and concentrated to dryness. The title compound was obtained as white crystals after titration with ethyl acetate. mp. 164–165° C.; anal. For C12H17Cl2O2 cacl. C, 56.14; H, 6.67; N, 10.91; found: C, 56.40; H, 6.53; H, 10.93.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[N:6][C:5]([NH:8][NH2:9])=[CH:4][N:3]=1.[CH:10](=O)[CH:11]([CH3:13])[CH3:12].C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1>C(Cl)Cl>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:6]([C:10]([CH:11]([CH3:13])[CH3:12])=[N:9][N:8]=2)[CH:7]=1
Reactant: NNc1cnc(Cl)cn1
Reactant: CC(C)C=O
Solvent: ClCCl
Solvent: CC(=O)O
Solvent: Ic1ccccc1
Product: CC(C)c1nnc2cnc(Cl)cn12
Reaction time: 0.5 h
Yield: 62.9 %

Procedure:
The 2-chloro-5-hydrazinylpyrazine (0.325 g, 2.248 mmol) was suspended in DCM (4 mL) then the isobutyraldehyde (0.195 g, 2.70 mmol) was added. The mixture was stirred for about 30 min, the solvent was concentrated under reduced pressure and the solid was dissolved in DCM (4 mL). Iodobenzene diacetate (0.724 g, 2.24 mmol) was added and the solution was stirred at ambient temperature for about 2 h. The mixture was diluted with DCM (20 mL), extracted with saturated aqueous NaHCO3, dried over MgSO4, filtered and concentrated under reduced pressure. The material was purified by flash chromatography on silica gel using DCM/EtOAc (1:1) as an eluent to give the title compound (0.278 g, 63%): LC/MS (Table 1, Method g) Rt=1.74 min; MS m/z: 197.1 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8](F)[C:7]([F:11])=[CH:6][C:3]=1[CH:4]=[O:5].[CH3:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][OH:19].C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O>[Cl:1][C:2]1[CH:9]=[C:8]([O:19][CH2:18][CH2:17][O:16][CH2:15][CH2:14][O:13][CH3:12])[C:7]([F:11])=[CH:6][C:3]=1[CH:4]=[O:5]
Reactant: O=Cc1cc(F)c(F)cc1Cl
Reactant: COCCOCCO
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: COCCOCCOc1cc(Cl)c(C=O)cc1F
Temperature: 90 °C
Reaction time: 8 h

Procedure:
To 2-chloro-4,5-difluoro-benzaldehyde (110, 0.40 g, 0.0023 mol) in N,N-dimethylformamide (10.0 mL), 2-(2-methoxyethoxy)-ethanol (0.327 g, 2.72 mmol) and cesium carbonate (0.886 g, 2.72 mmol) were added. The reaction was stirred at 90° C. overnight. The reaction was poured into water, acidified to pH around 5, and extracted with ethyl acetate. The organic layer was dried over an hydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 30% ethyl acetate in hexane to give a white solid (121, 0.15 g, 24.0%).
Reaction SMILES: [CH3:1][C:2]([C:10]1[CH:11]=[C:12]([OH:27])[C:13]2[C:18]3=[CH:19][C:20](=[O:23])[CH2:21][CH2:22][CH:17]3[C:16]([CH3:25])([CH3:24])[O:15][C:14]=2[CH:26]=1)([CH3:9])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[Li].N.[Cl-].[NH4+]>O1CCCC1>[CH3:9][C:2]([C:10]1[CH:11]=[C:12]([OH:27])[C:13]2[C@@H:18]3[CH2:19][C:20](=[O:23])[CH2:21][CH2:22][C@H:17]3[C:16]([CH3:25])([CH3:24])[O:15][C:14]=2[CH:26]=1)([CH3:1])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCC(C)(C)c1cc(O)c2c(c1)OC(C)(C)C1CCC(=O)C=C21
Agent: N
Agent: [Cl-]
Agent: [Li]
Solvent: C1CCOC1
Product: CCCCCCC(C)(C)c1cc(O)c2c(c1)OC(C)(C)[C@@H]1CCC(=O)C[C@@H]21

Procedure:
A solution of 1.5 g. of dl-3-(1',1'-dimethylheptyl)-6,6a,7,8-tetrahydro-1-hydroxy-6,6-dimethyl-9H-dibenzo[b,d]pyran-9-one in 50 ml. of anhydrous tetrahydrofuran (THF) was added dropwise to a solution of lithium metal in liquid ammonia at -80°C. Excess lithium metal was added in chunks to the solution as the blue color, indicating free dissolved lithium, disappeared. After the addition was complete, ammonium chloride was added to react with any excess lithium metal still present. The mixture was then allowed to warm to room temperature in a nitrogen atmosphere during which process the ammonia evaporated. The reaction mixture was then acidified in 1N aqueous hydrochloric acid, and the organic constituents extracted with ethyl acetate. The ethyl acetate extracts were combined, washed with water and dried. Evaporation of the ethyl acetate under reduced pressure yielded 1.4 g of crude dl-trans-3-(1',1'-dimethylheptyl)-6,6a,7,8,10,10a-hexahydro-1-hydroxy-6,6-dimethyl-9H-dibenzo[b,d]pyran-9-one. The crude product was chromatographed over 50 g. of silica gel from benzene solution and the desired product was eluted in 20 ml. fractions with a benzene eluant containing 2 percent ethyl acetate. Fractions 200-240 contained 808 mg. of a white crystalline solid comprising purified dl-trans-3-(1',1'-dimethylheptyl)-6,6a,7,8,10,10a-hexahydro-1-hydroxy-6,6-dimethyl-9H-dibenzo[b,d]pyran-9-one. The purified compound melted at 159°-160°C. after recrystallization from an ethyl acetate-hexane solvent mixture. Rf = 0.45 (silica gel, 20% ethyl acetate:benzene). UV(ethanol) λmax 207/280mμ (ε=47,000/250); IR(CHCl3) 5.85 μ(C=O); NMR (CDCl3) δ7.75(s/1H/exchanges with D2O), δ6.36/6.34 (2d/J= 2 cps/2H/H2 and H4), δ4.15(d broad/J=14,3 cps/1H/H10α), δ3.08-0.7 (multiplet/32H), especially δ1.47/1.13 (2s/each 3H/6α and 6β CH3), δ1.21 (s/6H/gem-dimethyl at C-1') and δ0.83 ppm (t/3H/ω-methyl); molecular ion, m/e 372.
Reaction SMILES: [C:1]([C:3](=[CH:9][NH:10][C:11]1[CH:12]=[CH:13][C:14]2[S:18](=[O:20])(=[O:19])[CH2:17][CH2:16][C:15]=2[CH:21]=1)[C:4]([O:6]CC)=O)#[N:2].CCCCCC>C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1>[O:6]=[C:4]1[C:21]2[C:11](=[CH:12][CH:13]=[C:14]3[S:18](=[O:19])(=[O:20])[CH2:17][CH2:16][C:15]3=2)[NH:10][CH:9]=[C:3]1[C:1]#[N:2]
Reactant: CCOC(=O)C(C#N)=CNc1ccc2c(c1)CCS2(=O)=O
Solvent: c1ccc(Oc2ccccc2)cc1
Solvent: c1ccc(-c2ccccc2)cc1
Solvent: CCCCCC
Product: N#Cc1c[nH]c2ccc3c(c2c1=O)CCS3(=O)=O
Temperature: 290 °C
Reaction time: 0.5 h
Yield: 377.9 %

Procedure:
1.5 g (0.85 mmol) of ethyl 2-cyano-3-[(1,1-dioxido-2,3-dihydro-1-benzothien-5-yl)amino]acrylate were suspended in 15 ml of Dowtherm A and heated in a metal bath at 290° C. for about 1 h. The reaction mixture was then cooled to RT. The mixture was subsequently mixed with hexane and stirred at RT for 30 min; the precipitate produced thereby was filtered off with suction and washed with hexane. 836 mg (65%) of the desired product were obtained in the form of brownish crystals.
Reaction SMILES: [CH3:1][N:2]([CH3:19])[S:3]([N:6]1[C:10]2[CH:11]=[C:12]([O:17][CH3:18])[C:13]([O:15][CH3:16])=[CH:14][C:9]=2[N:8]=[CH:7]1)(=[O:5])=[O:4].C([Li])CCC.Cl[C:26]([O:28][CH2:29][CH3:30])=[O:27]>C1COCC1.CCCCCC>[CH3:19][N:2]([CH3:1])[S:3]([N:6]1[C:10]2[CH:11]=[C:12]([O:17][CH3:18])[C:13]([O:15][CH3:16])=[CH:14][C:9]=2[N:8]=[C:7]1[C:26]([O:28][CH2:29][CH3:30])=[O:27])(=[O:4])=[O:5]
Reactant: CCOC(=O)Cl
Reactant: COc1cc2ncn(S(=O)(=O)N(C)C)c2cc1OC
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCOC(=O)c1nc2cc(OC)c(OC)cc2n1S(=O)(=O)N(C)C
Temperature: -60 °C
Reaction time: 0.5 h
Yield: 71.9 %

Procedure:
1-(N,N-dimethylsulfamoyl)-5,6-dimethoxybenzimidazole (5.70 g) was dissolved in dry THF (170 ml) in a dry argon atmosphere, cooled to -60° C. and a solution of n-butyl lithium (1.58M) in hexane (15.2 ml) was added dropwise and stirred for 30 minutes. After ethyl chloroformate (2.60 g) was added dropwise, the mixture was slowly returned to room temperature and allowed to react overnight. THF was distilled off, the residue was dissolved in ethyl acetate, washed with water and dried over anhydrous Na2SO4, and the solvent was distilled off. Purification of the residue by column chromatography on silica gel gave the title compound (5.13 g) as an oily product.
Reaction SMILES: C[O:2][C:3](=[O:26])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH:10][C:11](=[O:25])[CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:15][CH:14]=2)[CH:5]=1.Cl>C1COCC1.O>[C:16]1([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:17]=[CH:18][C:13]([CH2:12][C:11]([NH:10][C:6]2[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=2)[C:3]([OH:26])=[O:2])=[O:25])=[CH:14][CH:15]=1
Reactant: COC(=O)c1cccc(NC(=O)Cc2ccc(-c3ccccc3)cc2)c1
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: O=C(Cc1ccc(-c2ccccc2)cc1)Nc1cccc(C(=O)O)c1
Yield: 57.6 %

Procedure:
3-(2-biphenyl-4-yl-acetylamino)-benzoic acid methyl ester (133.6 mg, 0.39 mmol) in THF/H2O (1:1, 4 mL) was treated with LiOHH2O (32.7 mg, 0.78 mmol) at room temperature. The reaction mixture was then acidified with 10% HCl to PH 2. Resulting mixture was collected by filtration, and recrystallized with mixture of CH2Cl2 and MeOH to give 3-(2-biphenyl-4-yl-acetylamino)-benzoic acid as a white solid (74.4 mg, 58.1% yield).
Reaction SMILES: C([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([NH:15][C:16]([C:18]1[O:22][C:21]([C:23]([NH:25][C:26]3[CH:27]=[C:28]4[C:32](=[CH:33][CH:34]=3)[NH:31][C:30]([C:35]([O:37]CC)=[O:36])=[CH:29]4)=[O:24])=[CH:20][CH:19]=1)=[O:17])=[CH:10][CH:9]=2)=[O:5])C.[OH-].[Na+]>CO>[O:22]1[C:21]([C:23]([NH:25][C:26]2[CH:27]=[C:28]3[C:32](=[CH:33][CH:34]=2)[NH:31][C:30]([C:35]([OH:37])=[O:36])=[CH:29]3)=[O:24])=[CH:20][CH:19]=[C:18]1[C:16]([NH:15][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:4]([OH:5])=[O:3])=[CH:14]2)=[O:17]
Reactant: CCOC(=O)c1cc2cc(NC(=O)c3ccc(C(=O)Nc4ccc5[nH]c(C(=O)OCC)cc5c4)o3)ccc2[nH]1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1cc2cc(NC(=O)c3ccc(C(=O)Nc4ccc5[nH]c(C(=O)O)cc5c4)o3)ccc2[nH]1
Yield: 41 %

Procedure:
5,5'-[2,5-furandiylbis(carbonylimino)]bis-1H-indole-2-carboxylic acid diethyl ester (60 mg, 0.11 mM) is suspended in methanol (0.4 mL) and treated with N NaOH (0.25 mL). After 5 days the reaction is evaporated in vacuo and the residue dissovlved in water and the solution acidified to pH 2 with N HCl. This solution is freeze dried leaving 5,5'-[2,5-furandiylbis(carbonylimino)]bis-1H-indole-2-carboxylic acid (22 mg).
Reaction SMILES: C[O:2][C:3](=O)[C@@H:4]1[O:6][C@H:5]1[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1.[NH3:16]>CN(C)C=O>[CH3:14][O:13][C:10]1[CH:11]=[CH:12][C:7]([C@@H:5]2[O:6][C@H:4]2[C:3]([NH2:16])=[O:2])=[CH:8][CH:9]=1
Reactant: COC(=O)[C@@H]1O[C@H]1c1ccc(OC)cc1
Reactant: N
Solvent: CN(C)C=O
Product: COc1ccc([C@@H]2O[C@H]2C(N)=O)cc1
Yield: 85 %

Procedure:
To a mixture of (2R,3S)-3-(4-methoxyphenyl)-2,3-epoxypropionic acid methyl ester (2.08 g) and N,N-dimethylformamide (3 ml) is added 28% aqueous ammonia (6.1 g) under ice-cooling. The mixture is reacted at room temperature for two hours, and the precipitated crystals are collected by filtration, washed with water, and dried at 50° C. to give (2R,3S)-3-(4-methoxyphenyl)-2,3-epoxypropionamide (1.64 g).
Reaction SMILES: [CH3:1][C:2]1[C:14]2[C:13](=[O:15])[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([N+:16]([O-])=O)[CH:11]=3)[NH:6][C:5]=2[N:4]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)[N:3]=1>CN(C)C=O.[C].[Pd]>[NH2:16][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[NH:6][C:5]1[N:4]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)[N:3]=[C:2]([CH3:1])[C:14]=1[C:13]2=[O:15]
Reactant: Cc1nn(-c2ccccn2)c2[nH]c3ccc([N+](=O)[O-])cc3c(=O)c12
Agent: [Pd]
Solvent: CN(C)C=O
Product: Cc1nn(-c2ccccn2)c2[nH]c3ccc(N)cc3c(=O)c12
Yield: 68.2 %

Procedure:
A solution of 3-methyl-6-nitro-1-(2-pyridinyl)-1,9-dihydro-4H-pyrazolo[3,4-b]quinolin-4-one (4.64 g, 14.4 mmol) and 5% palladium-carbon (4.64 g, 50% hydrate) in N,N-dimethylformamide (400 mL) was stirred at room temperature under hydrogen atmosphere for 4 hours. The reaction solution was filtered to remove the catalyst, and the filtrate was evaporated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (chloroform:methanol=99:1 to chloroform:methanol=95:5) to give the title compound (2.86 g, 69% yield).
Reaction SMILES: [OH:1][CH2:2][C:3]([CH2:16][OH:17])([CH2:6][O:7][CH2:8][C:9]([CH2:14][OH:15])([CH2:12][OH:13])[CH2:10][OH:11])[CH2:4][OH:5].[C:18]([OH:26])(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.O[CH:28]([CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])[C:29]([OH:31])=[O:30]>[Sn](Cl)(Cl)(Cl)Cl.O>[OH:11][CH2:10][C:9]([CH2:14][OH:15])([CH2:8][O:7][CH2:6][C:3]([CH2:16][OH:17])([CH2:4][OH:5])[CH2:2][OH:1])[CH2:12][OH:13].[C:18]([OH:26])(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[OH:1][CH:41]([CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:28][C:29]([OH:31])=[O:30]
Reactant: CCCCCCCCCCCCCCCCC(O)C(=O)O
Agent: Cl[Sn](Cl)(Cl)Cl
Agent: O=C(O)c1ccccc1
Agent: OCC(CO)(CO)COCC(CO)(CO)CO
Solvent: O
Product: CCCCCCC(O)CCCCCCCCCCC(=O)O

Procedure:
A four-neck flask equipped with a stirrer, a temperature gauge, a nitrogen gas blowing tube and a water separator was charged with 89.8 g (1.0 mol) of dipentaerythritol (trade name: DiPentarit, manufactured by Koei Kagaku Co., Ltd), 86.2 g (2.0 mol) of benzoic acid (trade name: PuroxB, manufactured by DSM Company) and 424.0 g (4.0 mol) of hydroxystearic acid (trade name: Hydroxystearic acid, manufactured by Kawaken Fine Chemicals Co., Ltd) and the mixture was reacted using 0.6 g of tin chloride as a catalyst at 180° C. to 200° C. under a nitrogen stream for about 15 hours. After the reaction was finished, the reaction mixture was purified by a usual method, to obtain 391.6 g of the target ester compound of dipentaerythritol, and benzoic acid and 12-hydroxystearic acid, the ester compound having a saponification value of 211.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([NH:13][C:14](=[O:26])[C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:17][CH:16]=2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-])=O)([O-])=O.[C:27]1([NH:33][C:34]([C:36]2[CH:43]=[CH:42][C:39]([CH:40]=O)=[CH:38][CH:37]=2)=[O:35])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>>[C:27]1([NH:33][C:34](=[O:35])[C:36]2[CH:37]=[CH:38][C:39]([C:40]3[NH:10][C:9]4[CH:8]=[CH:7][C:6]([NH:13][C:14](=[O:26])[C:15]5[CH:20]=[CH:19][C:18]([N:21]6[CH2:25][CH2:24][CH2:23][CH2:22]6)=[CH:17][CH:16]=5)=[CH:5][C:4]=4[N:1]=3)=[CH:42][CH:43]=2)[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: O=Cc1ccc(C(=O)Nc2ccccc2)cc1
Reactant: O=C(Nc1ccc([N+](=O)[O-])c([N+](=O)[O-])c1)c1ccc(N2CCCC2)cc1
Product: O=C(Nc1ccccc1)c1ccc(-c2nc3cc(NC(=O)c4ccc(N5CCCC5)cc4)ccc3[nH]2)cc1

Procedure:
Compound 213 was prepared according to the procedure similar to that described in Scheme III from N-(3,4-dinitrophenyl)-4-pyrrolidinylbenzamide and 4-phenylaminocarbonylbenzaldehyde. [M+H]+ calcd for C31H27N5O2: 502.23; found: 502.03.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH2:19][CH2:20][CH3:21])[CH:16]=3)[CH:11]([C:22]3[CH:27]=[CH:26][C:25]4[O:28][CH2:29][O:30][C:24]=4[CH:23]=3)[CH:10]2[C:31]([OH:33])=[O:32])=[C:5]([O:34][CH2:35][O:36][CH3:37])[CH:4]=1.[CH2:38]1CCN2C(=NCCC2)CC1.IC>C(#N)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH2:19][CH2:20][CH3:21])[CH:16]=3)[CH:11]([C:22]3[CH:27]=[CH:26][C:25]4[O:28][CH2:29][O:30][C:24]=4[CH:23]=3)[CH:10]2[C:31]([O:33][CH3:38])=[O:32])=[C:5]([O:34][CH2:35][O:36][CH3:37])[CH:4]=1
Reactant: C1CCC2=NCCCN2CC1
Reactant: CCCOc1ccc2c(c1)C(c1ccc(OC)cc1OCOC)C(C(=O)O)C2c1ccc2c(c1)OCO2
Solvent: CI
Solvent: CC#N
Product: CCCOc1ccc2c(c1)C(c1ccc(OC)cc1OCOC)C(C(=O)OC)C2c1ccc2c(c1)OCO2
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 87.9 %

Procedure:
To a solution of (1RS,2SR,3RS)-3-(4-methoxy-2-methoxymethoxyphenyl)-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indane-2-carboxylic acid (1.98 g, 3.91 mmol) in acetonitrile (15 ml) was added DBU (0.655 g, 4.3 mmol) followed by iodomethane (2.77 g, 19.5 mmol). The reaction mixture was stirred at room temperature 3.5 h then partitioned between EtOAc and 3N HCl. The organic extract was washed with H2O, saturated NaHCO3 solution, H2O, then brine, dried (Na2SO4) and solvent removed in vacuo to provide the title compound (1.79 g, 88%) as an oil.