Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:3][CH:4]=[CH:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:16])[N:14]=2)[CH:11]=1)C.O.[Br:25]N1C(=O)CCC1=O>O1CCCC1>[Br:25][CH:5]([C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:16])[N:14]=2)[CH:11]=1)[CH:4]=[O:3]
Reactant: CCOC=Cc1ccc2nc(C(=O)Nc3ccccc3)cn2c1
Reactant: O=C1CCC(=O)N1Br
Solvent: O
Solvent: C1CCOC1
Product: O=CC(Br)c1ccc2nc(C(=O)Nc3ccccc3)cn2c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 168 mg of 6-(2-ethoxyvinyl)-N-phenylimidazo[1,2-a]pyridine-2-carboxamide in 5.1 mL of tetrahydrofuran are added 1.4 mL of water followed by addition, after cooling to 0° C., of a solution of 97 mg of N-bromosuccinimide in 0.7 mL of tetrahydrofuran. The reaction mixture is stirred for 3 hours at room temperature. The 6-(1-bromo-2-oxoethyl)-N-phenylimidazo[1,2-a]pyridine-2-carboxamide formed is not isolated from the reaction mixture, which is treated with 42 mg of thiourea and stirred for a further 16 hours after allowing the temperature to return to 20° C. The solid formed is filtered off by suction, washed with water and then with methanol and dried to give 51 mg of 6-(2-aminothiazol-5-yl)-N-phenylimidazo[1,2-a]pyridine-2-carboxamide in the form of a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[CH:4][C:3]=1[CH3:16].[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[C:19]=1[N:25]=[C:26]=[O:27]>C1COCC1>[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[C:19]=1[NH:25][C:26](=[O:27])[NH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][C:12]([CH3:13])([CH3:15])[CH3:14])=[O:10])=[CH:4][C:3]=1[CH3:16]
Reactant: O=C=Nc1c(Cl)cccc1Cl
Reactant: Cc1cc(CC(=O)OC(C)(C)C)ccc1N
Solvent: C1CCOC1
Product: Cc1cc(CC(=O)OC(C)(C)C)ccc1NC(=O)Nc1c(Cl)cccc1Cl
Reaction time: 3 h
Yield: 74.1 %

Procedure:
To a mixture of tert-butyl 4-amino-3-methylphenylacetate (1.88 g, 8.51 mmol), 2,6-dichlorophenyl isocyanate (1.60 g, 8.51 mmol) in THF (40 ml) was added Et3 N (0.24 ml, 1.70 mmol) at room temperature. After 3 h stirring, the reaction mixture was concentrated in vacuo. The residue was triturated by the addition of n-hexane, to give tert-butyl 4-[N′-(2,6-dichlorophenyl)ureido]-3-methylphenylacetate (2.58 g, 74%) as a colorless powder. mp 243–244° C. (dec.); 1H-NMR (CDCl3) δ 1.45 (s, 9H), 2.30 (s, 3H), 3.49 (s, 2H), 6.24 (s, 2H), 7.12–7.16 (m, 3H), 7.35 (d, J=8.3 Hz, 2H), 7.51 (d, J=7.8 Hz, 1H).
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].Br[CH2:17][CH2:18][CH2:19][CH:20]=[CH2:21].[Mg]>C1COCC1>[C:7]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:8]=[CH:9][C:4]([C:1]([OH:3])([CH2:21][CH2:20][CH2:19][CH:18]=[CH2:17])[CH3:2])=[CH:5][CH:6]=1
Reactant: C=CCCCBr
Reactant: CC(=O)c1ccc(-c2ccccc2)cc1
Agent: [Mg]
Solvent: C1CCOC1
Product: C=CCCCC(C)(O)c1ccc(-c2ccccc2)cc1

Procedure:
4-Acetylbiphenyl (2 g) was dissolved in anhydrous THF (30 ml) and reacted with a grignard prepared from 5-bromopentene and magnesium in THF (15 ml) as described in example 23 to give the title compound as a yellow powder.
Reaction SMILES: [CH2:1]([N:8]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:9][C:10]([C:12]1[CH:20]=[C:16]([C:17]([NH2:19])=[O:18])[C:15]([OH:21])=[CH:14][CH:13]=1)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].C1(C)C=CC(S(O[CH2:41][CH2:42][O:43][CH2:44][CH2:45][O:46][CH2:47][CH3:48])(=O)=O)=CC=1>CN(C)C=O>[CH2:22]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH2:9][C:10]([C:12]1[CH:13]=[CH:14][C:15]([O:21][CH2:41][CH2:42][O:43][CH2:44][CH2:45][O:46][CH2:47][CH3:48])=[C:16]([CH:20]=1)[C:17]([NH2:19])=[O:18])=[O:11])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: CCOCCOCCOS(=O)(=O)c1ccc(C)cc1
Reactant: NC(=O)c1cc(C(=O)CN(Cc2ccccc2)Cc2ccccc2)ccc1O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOCCOCCOc1ccc(C(=O)CN(Cc2ccccc2)Cc2ccccc2)cc1C(N)=O
Yield: 93.1 %

Procedure:
A solution of 5-(N,N-dibenzylglycyl)salicylamide (10 g.) in dimethylformamide (75 ml) was added dropwise to a stirred suspension of sodium hydride (0.875 g) in dimethylformamide (25 ml). 2-(2 -Ethoxyethoxy)ethyl p-toluenesulphonate (12.75 g) was then added and the solution heated at 100° for 2 hours. The solvent was evaporated to give a yellow oily solid which was partitioned between ethyl acetate and water. The ethyl acetate layer was dried (MgSO4), concentrated to 30 ml and chromatographed on alumina (60 g.). The column was eluted with ethyl acetate (100 ml portions). The first fraction was discarded and the subsequent four fractions yielded an oil (12.2 g) which crystallised from ethanol to give the ether as colourless plates (5.8 g) m.p. 91.5°-92.5°. Recrystallisation of a sample raised the m.p. to 92.5°-94°.
Reaction SMILES: O.[Br:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[OH-].[Na+].Cl.[CH2:16](O)[CH3:17]>>[Br:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:16][CH3:17]
Reactant: CCO
Reactant: CCCCCCCCCCBr
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCCCCCCCCCCBr
Temperature: 75 °C

Procedure:
The ground polymer of Example 23 (5 g) was placed in a 500 mL 3-necked round-bottomed flask and suspended in 100 mL deionized water and the suspension was stirred with a mechanical stirrer. To this swollen gel, a solution of 15 g 1-bromodecane in 100 mL ethanol was added and the reaction mixture was stirred for 10 minutes. 2 g 50% aqueous sodium hydroxide was then added and the reaction mixture was stirred at room temperature for 40 minutes followed by heating to 75° C. Subsequently, an additional 4 g 50% NaOH was added in a 1 g batch at an interval of 1.5 hr (the base addition maintained a pH between 10 to 12). The reaction mixture was allowed to stir at 75° C. for a total period of 20 hr. After cooling to 30° C., 2 mL concentrated HCl was added and the mixture was stirred for 30 minutes. The polymer was filtered off and washed with 500 mL deionized water and 500 mL methanol. The filtered polymer particles were slurried in methanol (400 mL), stirred for 40 minutes and reisolated by filtration. This process was then repeated. The polymer was suspended in 500 mL 2M NaCl solution and the suspension was stirred for 40 minutes. The polymer was filtered off and this NaCl treatment was repeated two more times. The fitered polymer cake was washed with 500 mL deionized water and suspended in 500 mL deionized water. After stirring the suspension for 30 minutes, the polymer was filtered off and resuspended in 500 mL deionized water. The resulting suspension was stirred for 30 minutes. 1 mL concentrated HCl was added to the suspension, which was then stirred for 35 minutes. The pH of the suspension was found to be 2.2. The polymer was then filtered off and dried at 60° C. in a forced air oven, yielding 13.3 g of the alkylated polymer as a pale white solid. The polymer was ground and passed through a 140 mesh sieve.
Reaction SMILES: Br[C:2]1[N:3]=[CH:4][N:5]([C:7]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=3)[CH:10]=[C:9]([CH3:21])[N:8]=2)[CH:6]=1.[NH2:22][C:23]1[CH:28]=[CH:27][C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][N:24]=1>>[Cl:20][C:15]1[CH:14]=[C:13]([C:11]2[CH:10]=[C:9]([CH3:21])[N:8]=[C:7]([N:5]3[CH:6]=[C:2]([C:26]4[CH:27]=[CH:28][C:23]([NH2:22])=[N:24][CH:25]=4)[N:3]=[CH:4]3)[N:12]=2)[CH:18]=[CH:17][C:16]=1[Cl:19]
Reactant: CC1(C)OB(c2ccc(N)nc2)OC1(C)C
Reactant: Cc1cc(-c2ccc(Cl)c(Cl)c2)nc(-n2cnc(Br)c2)n1
Product: Cc1cc(-c2ccc(Cl)c(Cl)c2)nc(-n2cnc(-c3ccc(N)nc3)c2)n1

Procedure:
The title compound was prepared from 2-(4-bromo-imidazol-1-yl)-4-(3,4-dichlorophenyl)-6-methyl-pyrimidine (example E.61) (0.16 g, 0.42 mmol) and commercially available 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.12 g, 0.54 mmol) according to the general procedure VI. Obtained as a yellow solid (0.06 g, 36%). MS (ISP) 397.1 [(M+H)+]; mp 213° C.
Reaction SMILES: [CH3:1][C:2]1[C:3]([S:16][C:17]2[S:18][C:19]([C:22]([O:24]CC)=[O:23])=[CH:20][N:21]=2)=[CH:4][C:5]2[C:6]([CH3:15])([CH3:14])[CH2:7][CH2:8][C:9]([CH3:13])([CH3:12])[C:10]=2[CH:11]=1.[Li+].[OH-].CO>C1COCC1>[CH3:1][C:2]1[C:3]([S:16][C:17]2[S:18][C:19]([C:22]([OH:24])=[O:23])=[CH:20][N:21]=2)=[CH:4][C:5]2[C:6]([CH3:15])([CH3:14])[CH2:7][CH2:8][C:9]([CH3:12])([CH3:13])[C:10]=2[CH:11]=1
Reactant: CCOC(=O)c1cnc(Sc2cc3c(cc2C)C(C)(C)CCC3(C)C)s1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: Cc1cc2c(cc1Sc1ncc(C(=O)O)s1)C(C)(C)CCC2(C)C
Temperature: 50 °C
Yield: 77.1 %

Procedure:
To a solution of 0.183 g (0.47 mmol) of ethyl 2-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthylthio)-5-thiazolecarboxylate (Compound 14) in 2.0 mL of THF was added 1.0 mL of LiOH (2.1N aqueous solution) and 1.0 mL of MeOH. The solution was heated at 50° C. for 1 h, cooled to room temperature and concentrated in vacuo. The residue was diluted with water, the aqueous layer acidified to pH=1 using 10% HCl and extracted with ether. The combined organic layers were washed with brine, dried (MgSO4), filtered, and the solvents removed in vacuo to give the title compound as a white solid (131 mg, 78%): PNMR (300 MHz, CD3OD) δ 1.28 (s, 6H), 1.32 (s, 6H), 1.73 (s, 4H), 2.40 (s, 3H), 7.42 (s, 1H), 7.63 (s, 1H), 8.12 (s, 1H).
Reaction SMILES: [CH2:1]([OH:12])[C@H:2]1[O:8][C:6](=[O:7])[C@H:5]([OH:9])[C@@H:4]([OH:10])[C@@H:3]1[OH:11].[CH3:13][NH2:14]>C(O)(C)C.CO>[CH3:13][NH:14][C:6]([C@@H:5]([C@H:4]([C@@H:3]([C@@H:2]([CH2:1][OH:12])[OH:8])[OH:11])[OH:10])[OH:9])=[O:7]
Reactant: O=C1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Reactant: CN
Solvent: CO
Solvent: CC(C)O
Product: CNC(=O)[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
A suspension of 50 g gluconolactone in 500 ml of isopropanol/methanol (4/1) was treated with 23.8 ml of a 40% N-methylamine solution for 30 minutes. The N-methylgluconamide obtained in quantitative yields, was treated at 60° C. with 69 ml acetic anhydride and 35 ml acetic acid in the presence of 1% concentrated sulphuric acid.
Reaction SMILES: [NH3:1].[C:2]([O:8][CH2:9][CH2:10][CH3:11])(=[O:7])[CH2:3][C:4]([CH3:6])=O>C(OCC)C>[NH:1]=[C:4]([CH3:6])[CH2:3][C:2]([O:8][CH2:9][CH2:10][CH3:11])=[O:7]
Reactant: N
Reactant: CCCOC(=O)CC(C)=O
Solvent: CCOCC
Product: CCCOC(=O)CC(C)=N

Procedure:
Ammonia gas was passed into a stirred solution of n-propyl acetoacetate (prepared by the method of Fisher, J.A.C.S., 1934, 56, 1766; 72 g.) in diethyl ether (100 ml.) at ambient temperature for 20 hours. The solution was then dried over sodium sulphate, filtered and distilled under reduced pressure to give n-propyl 3-iminobutyrate (18.2 g.), b.p. 114°-118° C./20 mm Hg.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.N(C(C)(C)C#N)=NC(C)(C)C#N.C(Cl)(Cl)(Cl)[Cl:25]>>[Cl:25][CH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: Cc1ccc2ccccc2n1
Reactant: ClC(Cl)(Cl)Cl
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Product: ClCc1ccc2ccccc2n1

Procedure:
2-Methylquinoline (5.0 g) was dissolved in carbon tetrachloride (25 mL), imide N-bromosuccinate (6.2 g) and 2,2′-azobisisobutyronitrile (AIBN) (57 mg) were added thereto, and the mixture was refluxed for 4 hr. After ice-cooling, the reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=5:1) to give the title compound (3.7 g) as a pale-yellow solid.
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:38][CH2:39][CH3:40])[C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH:20]([C:21]3[CH:26]=[CH:25][C:24]([C:27](=[O:31])[N:28]([CH3:30])[CH3:29])=[CH:23][CH:22]=3)[C:19](=O)[C:18]3[C:17]([C:33]([O:35]CC)=O)=[CH:16][CH:15]=[CH:14][C:13]=3[NH:12]2)=[CH:7][CH:6]=1)[CH3:2].O.[NH2:42][NH2:43]>CO>[CH2:1]([O:3][CH:4]([O:38][CH2:39][CH3:40])[C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[NH:12][C:13]3[C:18]4[C:19](=[N:42][NH:43][C:33](=[O:35])[C:17]=4[CH:16]=[CH:15][CH:14]=3)[CH:20]2[C:21]2[CH:26]=[CH:25][C:24]([C:27]([N:28]([CH3:30])[CH3:29])=[O:31])=[CH:23][CH:22]=2)=[CH:7][CH:6]=1)[CH3:2]
Reactant: NN
Reactant: CCOC(=O)c1cccc2c1C(=O)C(c1ccc(C(=O)N(C)C)cc1)C(c1ccc(C(OCC)OCC)cc1)N2
Solvent: O
Solvent: CO
Product: CCOC(OCC)c1ccc(C2Nc3cccc4c(=O)[nH]nc(c34)C2c2ccc(C(=O)N(C)C)cc2)cc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 76 %

Procedure:
Ethyl 2-(4-(diethoxymethyl)phenyl)-3-(4-(dimethylcarbamoyl)phenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (250 mg, 0.46 mmol) and hydrazine monohydrate (85%, 5 mL) were added in MeOH (15 mL) and the mixture was stirred room temperature for 5 h. The resulting mixture was concentrated under reduced pressure to a volume of 15 mL and then filtered; the filtrate was evaporated to give the title compound as a white solid (180 mg, yield 76%). LC-MS (ESI) m/z: 513(M+1)+.
Reaction SMILES: [OH:1][CH:2]([C:7]1[N:12]([CH3:13])[C:11](=[O:14])[C:10]2[NH:15][CH:16]=[CH:17][C:9]=2[C:8]=1[C:18]1[C:19]([CH3:28])=[C:20]2[C:25](=[CH:26][CH:27]=1)[O:24][CH2:23][CH2:22][CH2:21]2)[C:3]([O:5][CH3:6])=[O:4].C(O[C:33]([CH3:36])([CH3:35])[CH3:34])(=O)C.Cl(O)(=O)(=O)=O>CO.C(Cl)Cl>[C:33]([O:1][CH:2]([C:7]1[N:12]([CH3:13])[C:11](=[O:14])[C:10]2[NH:15][CH:16]=[CH:17][C:9]=2[C:8]=1[C:18]1[C:19]([CH3:28])=[C:20]2[C:25](=[CH:26][CH:27]=1)[O:24][CH2:23][CH2:22][CH2:21]2)[C:3]([O:5][CH3:6])=[O:4])([CH3:36])([CH3:35])[CH3:34]
Reactant: COC(=O)C(O)c1c(-c2ccc3c(c2C)CCCO3)c2cc[nH]c2c(=O)n1C
Reactant: CC(=O)OC(C)(C)C
Agent: [O-][Cl+3]([O-])([O-])O
Solvent: ClCCl
Solvent: CO
Product: COC(=O)C(OC(C)(C)C)c1c(-c2ccc3c(c2C)CCCO3)c2cc[nH]c2c(=O)n1C
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 46.1 %

Procedure:
An ice cold solution of methyl 2-hydroxy-2-(6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (425 mg, 1.111 mmol) in tert-butyl acetate (15.000 mL, 111 mmol) was treated with perchloric acid (0.191 mL, 2.223 mmol), and stirred for 5 min. The reaction was then kept in the refrigerator without stirring overnight. The reaction was quenched with sat. NaHCO3 at 0° C., extracted with EtOAc 2×, washed with Brine, dried with Na2SO4, filtered, and concentrated. Purification with column chromatography (0-100% EtOAc/Hexane, then 0-20% MeOH/DCM) gave methyl 2-(tert-butoxy)-2-(6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (224.7 mg, 0.512 mmol, 46.1% yield) as off white solid. NMR showed 2:1 diastereomer. 1H NMR (400 MHz, CHLOROFORM-d) ppm 9.93 (br. s., 1H), 7.19-7.12 (m, 1.4H), 6.99 (d, J=8.4 Hz, 0.6H), 6.77-6.68 (m, 1H), 5.91-5.77 (m, 1H), 5.36-5.10 (m, 1H), 4.27-4.16 (m, 2H), 3.81-3.74 (m, 3H), 3.74-3.62 (m, 3H), 2.77-2.60 (m, 2H), 2.17-2.06 (m, 2H), 1.95-1.88 (m, 3H), 1.16-1.07 (m, 6H), 1.00-0.94 (m, 3H); LCMS (m/z) ES+=439 (M+1).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[CH2:6][CH2:5]2.[C:12]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:17]=[CH:16][C:15]([C:18](Cl)=[O:19])=[CH:14][CH:13]=1.C(N(CC)CC)C>C1COCC1>[O:11]=[C:7]1[C:8]2[C:4](=[CH:3][C:2]([NH:1][C:18]([C:15]3[CH:16]=[CH:17][C:12]([C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)=[CH:13][CH:14]=3)=[O:19])=[CH:10][CH:9]=2)[CH2:5][CH2:6]1
Reactant: Nc1ccc2c(c1)CCC2=O
Reactant: O=C(Cl)c1ccc(-c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(Nc1ccc2c(c1)CCC2=O)c1ccc(-c2ccccc2)cc1
Yield: 60 %

Procedure:
5-amino-indan-1-one (73 mg, 0.50 mmol) in THF (6 mL) with 4-biphenylcarbonyl chloride (140 mg, 0.65 mmol) in presence of triethylamine (90 μL, 0.65 mmol) according to method A gave biphenyl-4-carboxylic acid (1-oxo-indan-5-yl)-amide (100 mg, 0.30 mmol, 60% yield) as a brown powder after purification by washing the crude product with ethyl acetate.
Reaction SMILES: O=P(Cl)(Cl)[Cl:3].[C:6]([C:8]1[C:9]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=2)=[N:10][C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:12][C:13]=1O)#[N:7].CN(C)C1C=CC=CC=1>O1CCOCC1>[Cl:3][C:13]1[N:12]=[C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:10]=[C:9]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=2)[C:8]=1[C:6]#[N:7]
Reactant: O=P(Cl)(Cl)Cl
Reactant: N#Cc1c(O)nc(-c2ccccc2)nc1-c1cccc([N+](=O)[O-])c1
Solvent: CN(C)c1ccccc1
Solvent: C1COCCO1
Product: N#Cc1c(Cl)nc(-c2ccccc2)nc1-c1cccc([N+](=O)[O-])c1
Reaction time: 3 h

Procedure:
POCl3 (50 ml) was added to a stirred solution of 5-cyano-4-(3-nitrophenyl)-2-phenyl-6-hydroxy-pyrimidine (example 31(a), 15.0 g) and dimethylaniline (0.5 ml) in dry 1,4-dioxane p.a. (200 ml). After 3 h at 90° C., the warm mixture was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in 1,4-dioxane and ice water was added. The resulting precipitate was filtered off and washed with water. Residual water was removed by coevaporation with 1,4-dioxane.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[Cl:9])[NH2:5].[C:10]([O:15][CH3:16])(=[O:14])[C:11]([CH3:13])=O>>[CH3:16][O:15][C:10](=[O:14])[C@H:11]([CH3:13])[NH:5][C:4]1[CH:6]=[CH:7][C:8]([Cl:9])=[C:2]([Cl:1])[CH:3]=1
Reactant: Nc1ccc(Cl)c(Cl)c1
Reactant: COC(=O)C(C)=O
Product: COC(=O)[C@H](C)Nc1ccc(Cl)c(Cl)c1

Procedure:
Following General Procedure A above and using 3,4-dichloroaniline (Aldrich) and methyl pyruvate (Aldrich), the title compound was prepared as an oil. The reaction was monitored by tlc on silica gel (Rf=0.55 in 25% EtOAc/hexanes) and purification was by flash chromatography (silica gel using 25% EtOAc/hexanes as the eluant).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1.[CH3:11][C:12]([C:14]1[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([O:24][CH3:25])[CH:15]=1)=[O:13].[OH-].[Na+].Cl>CO>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6](/[CH:7]=[CH:11]/[C:12]([C:14]2[CH:15]=[C:16]([O:24][CH3:25])[C:17]([O:22][CH3:23])=[C:18]([O:20][CH3:21])[CH:19]=2)=[O:13])=[CH:5][CH:4]=1
Reactant: COc1cc(C(C)=O)cc(OC)c1OC
Reactant: COc1ccc(C=O)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: COc1ccc(/C=C/C(=O)c2cc(OC)c(OC)c(OC)c2)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 50.9 %

Procedure:
To a stirred solution of 4-methoxybenzaldehyde (1.0 g, 7.3 mmol) and 3,4,5-trimethoxyacetophenone (1.54 g, 7.3 mmol) in methanol (30 ml) was added a 50% w/v solution of aqueous NaOH (1 ml). The mixture was stirred for 24 h at room temperature, acidified with 2N HCl and extracted with ethyl acetate (3×30 ml). The combined organic phase was dried over anhydrous MgSO4, filtered, and the solvent evaporated in vacuo. The product was purified by column chromatography followed by recrystallisation from methanol to afford the title compound as a pale yellow solid 1.22 g (51%). 1H NMR (CDCl3) δ 7.8 (1H, d), 7.6 (2H, m), 7.4 (1H, d), 7.3 (2H, d), 7.0 (2H, d), 3.9 (9H, s), 3.8 (3H s). Mass Spectrum (FAB) m/e 329 (M+1).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([N:14]1[CH:18]([C:19](OCC)=[O:20])[CH2:17][CH2:16][CH:15]1[C:24](OCC)=[O:25])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.O>O1CCCC1>[CH2:7]([N:14]1[CH:18]([CH2:19][OH:20])[CH2:17][CH2:16][CH:15]1[CH2:24][OH:25])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: CCOC(=O)C1CCC(C(=O)OCC)N1Cc1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: OCC1CCC(CO)N1Cc1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 96.6 %

Procedure:
To a suspension of lithium aluminum hydride (10.25 g) in tetrahydrofuran (550 ml) was added dropwise a solution of 1-benzyl-2,5-bis(ethoxycarbonyl)pyrrolidine (55 g) in tetrahydrofuran (100 ml). The reaction mixture was stirred for 30 minutes at 0° C., allowed to warm to room temperature and then stirred at the same temperature for 1 hour. And then water was added carefully until excess lithium aluminum hydride was decomposed. After the precipitate was filtered off, the filtrate was evaporated under reduced pressure to give crude 1-benzyl-2,5-bis(hydroxymethyl)pyrrolidine (38.52 g).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:16][C:17]1[CH:18]=[C:19]([CH:26]=[O:27])[C:20]([OH:25])=[C:21]([CH:23]=[O:24])[CH:22]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH3:16][C:17]1[CH:18]=[C:19]([CH:26]=[O:27])[C:20]([O:25][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[C:21]([CH:23]=[O:24])[CH:22]=1
Reactant: Cc1cc(C=O)c(O)c(C=O)c1
Reactant: BrCCCCCCCCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1cc(C=O)c(OCCCCCCCCc2ccccc2)c(C=O)c1
Temperature: 80 °C

Procedure:
8-Phenyloctyl bromide (2.69 g, 10 mmol) was added to a stirred mixture of 5-methyl-2-hydroxy-1,3-benzenedicarboxaldehyde (1.64 g, 10 mmol) and anhydrous potassium carbonate (1.38 g, 10 mmol) in dry dimethylformamide (20 ml) at room temperature under nitrogen. The suspension was heated to 80° C. for 3 hours then allowed to cool. Water (40 ml) was added and the mixture extracted with diethyl ether (2×40 ml). The extracts were dried, filtered and evaporated to a yellow solid. Recrystallisation from methanol (25 ml) gave the title product as pale yellow crystals, m.p. 59° C.
Reaction SMILES: [CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][CH:9]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])[CH2:8][C@H:7]1[CH2:19][OH:20])=[O:5])[CH3:2].[Cl:21][C:22]1[CH:27]=[CH:26][C:25](O)=[CH:24][CH:23]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(N=NC(OC(C)(C)C)=O)=O)(C)(C)C>ClCCl.O1CCCC1>[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][CH:9]([O:11][Si:12]([C:15]([CH3:16])([CH3:18])[CH3:17])([CH3:13])[CH3:14])[CH2:8][C@H:7]1[CH2:19][O:20][C:25]1[CH:26]=[CH:27][C:22]([Cl:21])=[CH:23][CH:24]=1)=[O:5])[CH3:2]
Reactant: Oc1ccc(Cl)cc1
Reactant: CCOC(=O)[C@@H]1CC(O[Si](C)(C)C(C)(C)C)C[C@H]1CO
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: ClCCl
Product: CCOC(=O)[C@@H]1CC(O[Si](C)(C)C(C)(C)C)C[C@H]1COc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 60 h
Yield: 89.1 %

Procedure:
To a cold (ice bath) mixture of (1R,2R)-4-(tert-Butyl-dimethyl-silanyloxy)-2-hydroxymethyl-cyclopentanecarboxylic acid ethyl ester (epimeric mixture, 250 mg), 4-chlorophenol (136 mg) and triphenylphoshine (256 mg) in dichloromethane (4 mL) and tetrahydrofuran (1.5 mL) was slowly added a solution of di-tert-butyl-azodicarboxylate (225 mg) in tetrahydrofuran (2.5 mL). The reaction mixture was stirred at room temperature for 2.5 days then concentrated in vacuo and the residue was purified by flash chromatography on silica gel with a gradient of cyclohexane/ethylacetate (1:0 to 9:1 v/v) as eluant to afford the title compound (0.304 g, 89%) as light yellow oil. MS (EI): 413.2 (M+H)+.