Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [BH4-].[Na+].[C:3]1([CH:9]([O:16][C:17]([C:19]2[N:24]3[C:25](=[O:38])[C@@H:26]([NH:27][C:28](=[O:37])[CH2:29][O:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C@H:23]3[S:22][CH2:21][C:20]=2[OH:39])=[O:18])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl>CN(C)C=O.C(O)=O>[C:3]1([CH:9]([O:16][C:17]([C@@H:19]2[N:24]3[C:25](=[O:38])[C@@H:26]([NH:27][C:28](=[O:37])[CH2:29][O:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C@H:23]3[S:22][CH2:21][CH:20]2[OH:39])=[O:18])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: O=C(COc1ccccc1)N[C@@H]1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(O)CS[C@H]12
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O=CO
Product: O=C(COc1ccccc1)N[C@@H]1C(=O)N2[C@@H]1SCC(O)[C@@H]2C(=O)OC(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 77.8 %

Procedure:
28.4 mg of sodium borohydride are added to a solution of 516 mg of 3-hydroxy-7β-phenoxyacetylamino-3-cephem-4-carboxylic acid diphenylmethyl ester in 4 ml of dimethylformamide and 1 ml of formic acid at room temperature. After stirring the reaction mixture for one hour at room temperature, it is poured onto a mixture of ice and 2 N hydrochloric acid and extracted with ethyl acetate. The combined organic phases are washed successively with water, three times with saturated sodium bicarbonate solution and saturated, aqueous sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. The residue is substantially freed from dimethylformamide under a high vacuum. The resulting white foam (580 mg) is subjected to chromatography on preparative silica gel thick-layer plates with toluene/ethyl acetate 1:1 and yields 403 mg of the title compound.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:22])=[C:11]([CH2:13][C:14]([N:16]3[CH2:20][CH2:19][CH2:18][C@H:17]3[CH3:21])=O)[N:12]=2)=[CH:4][CH:3]=1.Cl.Cl[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([CH3:32])[N:27]=1>>[CH3:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([CH2:32][O:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]3[O:9][C:10]([CH3:22])=[C:11]([CH2:13][CH2:14][N:16]4[CH2:20][CH2:19][CH2:18][C@H:17]4[CH3:21])[N:12]=3)=[CH:4][CH:3]=2)[N:27]=1
Reactant: Cc1oc(-c2ccc(O)cc2)nc1CC(=O)N1CCC[C@H]1C
Reactant: Cc1cccc(CCl)n1
Agent: Cl
Product: Cc1cccc(COc2ccc(-c3nc(CCN4CCC[C@H]4C)c(C)o3)cc2)n1

Procedure:
The title compound is prepared in a manner substantially similar to Example 58 from 2-[2-(4-Hydroxy-phenyl)-5-methyl-oxazol-4-yl]-1-(2-(R)-methyl-pyrrolidin-1-yl)-ethanone (See Example 56) and 2-chloromethyl-6-methyl-pyridine hydrochloride [CAS 3099-30-7]. MS (m/e): 392.3 (M+1)
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][CH:8]([CH3:11])[NH:7][CH:6]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:4].[CH2:18]([O:25][C:26](Cl)=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C([O-])(O)=O.[Na+]>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:10][CH2:9][C@@H:8]([CH3:11])[N:7]([C:26]([O:25][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:27])[C@H:6]1[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:4]
Reactant: COC(=O)C1CCC(C)NC1c1ccccc1
Reactant: O=C(Cl)OCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Product: COC(=O)[C@@H]1CC[C@@H](C)N(C(=O)OCc2ccccc2)[C@H]1c1ccccc1
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 63 %

Procedure:
(A mixture of two diastereomers and their enantiomers.) To 6-Methyl-2-phenyl-piperidine-3-carboxylic acid methyl ester (1.63 g, 7.0 mmol) in 20 mL of 10% aqueous NaHCO3 at 0° C. was added benzylchloroformate (1.25 g, 7.35 mmol). The mixture was stirred for 45 minutes at 0° C., and was then warmed to room temperature and stirred for an additional 30 minutes. The mixture was partitioned with ether, and the organic phase was dried over MgSO4 and concentrated. Silica gel chromatography (9:1 hexanes/EtOAc) gave 1.62 g (63%) of the title compound as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.1–7.4 (comp, 20H, both diastereomers), 6.1 (br, 1H, minor diastereomer), 5.74 (d, J=3.6, 1H, major diastereomer), 5.05–5.26 (comp, 8H, both diastereomers), 4.67 (d, J=6.0 Hz, 1H, major diastereomer), 4.57 (m, 1H, minor diastereomer), 4.10–4.20 (m, 2H, major diastereomer), 3.70 (s, 3H, major diastereomer), 3.59 (s, 3H, major diastereomer), 3.29 (app dt, J=4.5, 9.4 Hz, 1H, major diastereomer), 2.85 (m, 1H, minor diastereomer), 2.27 (app dq, J=4.1, 13.7 Hz, minor diastereomer), 1.85–2.15 (comp, 4H, both diastereomers), 1.55–1.80 (comp, 3H, both diastereomers), 1.34 (d, J=6.8 Hz, 3H, major diastereomer), 0.37 (d, J=7.1 Hz, 3H, minor diastereomer); 13C NMR (100 MHz) δ 172.8, 140.0, 136.7, 128.5, 128.4, 128.2, 128.0, 127.8, 127.7, 127.6, 127.2, 127.1, 127.0, 126.9, 126.4, 67.5, 66.9, 65.3, 56.4, 52.0, 47.5, 46.6, 44.3, 42.6, 30.2, 25.6, 22.1, 19.8, 17.2, 16.0; mass spectrum m/e calcd. for M+H=368.2. Found 368.2, 324.2 (base).
Reaction SMILES: [C:1]([CH2:3][CH2:4][N:5]1[C:13]2[C:14]3[N:15]([CH3:29])[C:16]4[C:21]([C:22]=3[C:23]3[CH2:27][NH:26][C:25](=[O:28])[C:24]=3[C:12]=2[C:11]2[CH:10]=[C:9]([O:30]C)[CH2:8][C:7](=O)[C:6]1=2)=[CH:20][CH:19]=[CH:18][CH:17]=4)#[N:2].B(Br)(Br)Br.O.C([O:41]C(C)C)(C)C.CC(C)=O>ClCCl.O1CCCC1>[C:1]([CH2:3][CH2:4][N:5]1[C:13]2[C:14]3[N:15]([CH3:29])[C:16]4[C:21]([C:22]=3[C:23]3[C:27](=[O:41])[NH:26][C:25](=[O:28])[C:24]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:30])[CH:8]=[CH:7][C:6]1=2)=[CH:20][CH:19]=[CH:18][CH:17]=4)#[N:2]
Reactant: COC1=Cc2c(n(CCC#N)c3c2c2c(c4c5ccccc5n(C)c43)CNC2=O)C(=O)C1
Reactant: CC(C)OC(C)C
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: O
Solvent: CC(C)=O
Product: Cn1c2ccccc2c2c3c(c4c5cc(O)ccc5n(CCC#N)c4c21)C(=O)NC3=O
Temperature: 20 °C
Reaction time: 3 h

Procedure:
200 mg (0.45 mmol) 13-(2-cyanoethyl)-6,7,12,13-tetrahydro-3-methoxy-12-methyl-5,1-dioxo-5H-indolo-[2,3-a]pyrrolo[3,4-c]carbazole (Example 1) in 15 ml dichloromethane are cooled to -10° C. and 0.1 ml (0.7 mmol) of a 1M solution of boron tribromide in dichloromethane added dropwise thereto. Since, after 3 hours at -10° C., no reaction is shown (TLC), 1.4 ml of the 1M solution of boron tribromide are again added thereto, followed by stirring for 16 hours at 20° C. 100 ml of water and 100 ml tetrahydrofuran are added thereto and the organic phase is separated off, washed with 100 ml of water and dried over anhydrous sodium sulphate. After filtration and evaporation, the residue is first chromatographed with dichloromethane/methanol (95:5 v/v) and then again with toluene/tetrahydrofuran (4:1 v/v). The fraction with the Rf 0.3 in toluene/tetrahydrofuran (2:1 v/v) is isolated, stirred with diisopropyl ether/acetone and the crystals formed are filtered off. 13-(2-Cyanoethyl)-6,7,12,13-tetrahydro-3-hydroxy-12-methyl-5,7-dioxo-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole is obtained in the form of yellow crystals which decompose from about 315° C.
Reaction SMILES: [CH2:1]([O:5][C:6]1[C:7]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)=[N:8][NH:9][CH:10]=1)[CH2:2][CH:3]=[CH2:4].[CH3:17]SC1C(C2C=NC=CC=2)=NNC=1>>[CH2:1]([O:5][C:6]1[C:7]([C:11]2[CH2:12][N:13]([CH3:17])[CH2:14][CH2:15][CH:16]=2)=[N:8][NH:9][CH:10]=1)[CH2:2][CH:3]=[CH2:4]
Reactant: CSc1c[nH]nc1-c1cccnc1
Reactant: C=CCCOc1c[nH]nc1-c1cccnc1
Product: C=CCCOc1c[nH]nc1C1=CCCN(C)C1

Procedure:
Compound 32D was converted to the title compound (33D), using the methodology described for the conversion of 21A to 22A (see Scheme 3).
Reaction SMILES: [ClH:1].[N:2]1([C:9]2[CH:10]=[C:11]([NH:17][S:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][CH:28]([F:30])[F:29])(=[O:20])=[O:19])[CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH2:8][CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[CH2:31]=O>[BH4-].[Na+].C(#N)C>[ClH:1].[F:29][CH:28]([F:30])[O:27][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[S:18]([NH:17][C:11]1[CH:12]=[CH:13][C:14]([O:15][CH3:16])=[C:9]([N:2]2[CH2:8][CH2:7][CH2:6][N:5]([CH3:31])[CH2:4][CH2:3]2)[CH:10]=1)(=[O:20])=[O:19]
Reactant: C=O
Reactant: COc1ccc(NS(=O)(=O)c2ccccc2OC(F)F)cc1N1CCCNCC1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CC#N
Product: COc1ccc(NS(=O)(=O)c2ccccc2OC(F)F)cc1N1CCCN(C)CC1

Procedure:
The title compound was prepared from the title compound of Example 3 under reductive amination conditions employing an aqueous solution of formaldehyde and sodium borohydride in acetonitrile as solvent.
Reaction SMILES: [BH4-].[Na+].[O:3]=[C:4]([C:25]1[CH:30]=[CH:29][C:28]([O:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:27][CH:26]=1)[CH:5]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]([F:24])([F:23])[CH:20]([F:22])[F:21])[CH:13]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7].Cl.O>C(OCC)C.[Cl-].[Zn+2].[Cl-]>[OH:3][CH:4]([C:25]1[CH:26]=[CH:27][C:28]([O:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:29][CH:30]=1)[CH:5]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]([F:24])([F:23])[CH:20]([F:22])[F:21])[CH:13]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7]
Reactant: CCOC(=O)C(Cc1cccc(OC(F)(F)C(F)F)c1)C(=O)c1ccc(Oc2ccccc2)cc1
Agent: Cl
Agent: [BH4-]
Agent: [Cl-]
Solvent: O
Solvent: CCOCC
Product: CCOC(=O)C(Cc1cccc(OC(F)(F)C(F)F)c1)C(O)c1ccc(Oc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 67.3 %

Procedure:
To a solution of zinc chloride (5.34 g, 39.2 mmol) in diethyl ether (120 ml) was added sodium borohydride (2.97 g, 78.4 mmol), and the mixture was stirred at room temperature for 30 min. Insoluble material was filtered off, and a solution of ethyl 3-oxo-3-(4-phenyloxyphenyl)-2-((3-((1,1,2,2-tetrafluoroethyl)oxy)phenyl)methyl)propionate (9.61 g, 19.6 mmol) in diethyl ether (60 ml) was added to the filtrate. The mixture was stirred at room temperature for 30 min. 1N Hydrochloric acid was added to the reaction solution under ice-cooling to quench the reaction. Then, water (150 ml) was added and the mixture was extracted with ethyl acetate (200 ml×2). The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to give ethyl (2RS,3RS)-3-hydroxy-3-(4-(phenyloxy)phenyl)-2-((3-((1,1,2,2-tetrafluoroethyl)oxy)phenyl)methyl)propionate (6.50 g, 67%) as a colorless oil.
Reaction SMILES: [Cl-].[CH3:2][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C([Li])CCC.[CH3:27][O:28][C:29]1[CH:38]=[C:37]2[C:32]([C:33]([C:39]([C:41]3[CH:46]=[CH:45][C:44]([N+:47]([O-:49])=[O:48])=[CH:43][CH:42]=3)=O)=[CH:34][CH:35]=[N:36]2)=[CH:31][CH:30]=1>C1COCC1>[CH3:27][O:28][C:29]1[CH:38]=[C:37]2[C:32]([C:33]([C:39]([C:41]3[CH:46]=[CH:45][C:44]([N+:47]([O-:49])=[O:48])=[CH:43][CH:42]=3)=[CH2:2])=[CH:34][CH:35]=[N:36]2)=[CH:31][CH:30]=1
Reactant: COc1ccc2c(C(=O)c3ccc([N+](=O)[O-])cc3)ccnc2c1
Reactant: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C=C(c1ccc([N+](=O)[O-])cc1)c1ccnc2cc(OC)ccc12
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
To a mixture of methyltriphenylphosphonium chloride (0.54 g, 1.7 mmol) in THF (10 mL) at −78° C. was added n-butyllithium, 2.5 M in hexanes (0.80 ml, 2.0 mmol). After 20 min, a mixture of (7-methoxyquinolin-4-yl)(4-nitrophenyl)methanone (0.177 g, 0.57 mmol) in THF (5 mL) was slowly added. After 10 min, the mixture was allowed to warm to RT. The reaction was quenched with saturated aqueous NH4Cl. The mixture was diluted with EtOAc and washed with water and brine. After drying the organic fraction with Na2SO4, the solvent was removed in vacuo and the residue purified by silica gel chromatography using 40-100% hexanes:EtOAc to afford 7-methoxy-4-(1-(4-nitrophenyl)vinyl)quinoline as a yellow foam. MS: M+H+=307.1.
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]([C:9]1[CH:14]=[CH:13][C:12]([CH2:15]O)=[C:11]([CH2:17][CH2:18][CH3:19])[CH:10]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].C(N(CC)CC)C.CS(Cl)(=O)=O.[CH:34]1([CH2:37][NH:38][C:39]([NH:41][C:42]2[CH:47]=[CH:46][C:45]([C:48]([N:50]3[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]3)=[O:49])=[CH:44][CH:43]=2)=[O:40])[CH2:36][CH2:35]1.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[CH:34]1([CH2:37][NH:38][C:39]([NH:41][C:42]2[CH:43]=[CH:44][C:45]([C:48]([N:50]3[CH2:55][CH2:54][N:53]([CH2:15][C:12]4[CH:13]=[CH:14][C:9]([C:3]([OH:8])([C:4]([F:5])([F:6])[F:7])[C:2]([F:21])([F:20])[F:1])=[CH:10][C:11]=4[CH2:17][CH2:18][CH3:19])[CH2:52][CH2:51]3)=[O:49])=[CH:46][CH:47]=2)=[O:40])[CH2:35][CH2:36]1
Reactant: CCCc1cc(C(O)(C(F)(F)F)C(F)(F)F)ccc1CO
Reactant: O=C(NCC1CC1)Nc1ccc(C(=O)N2CCNCC2)cc1
Agent: CS(=O)(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCc1cc(C(O)(C(F)(F)F)C(F)(F)F)ccc1CN1CCN(C(=O)c2ccc(NC(=O)NCC3CC3)cc2)CC1
Temperature: 0 °C
Reaction time: 1 h
Yield: 20.6 %

Procedure:
1,1,1,3,3,3-Hexafluoro-2-(4-(hydroxymethyl)-3-propylphenyl)propan-2-ol (0.509 mmol, 161 mg) was dissolved in dichloromethane (4 mL) and triethylamine (1.527 mmol, 155 mg) was added. The mixture was cooled to 0° C. before the addition of methanesulfonyl chloride (0.611 mmol, 70.0 mg). The mixture was stirred at 0° C. for 1 hour before warming to room temperature and stirring for 1 hour. The reaction mixture was diluted with dichloromethane (50 mL) and washed with water (2×10 mL). The organic phase was dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile (4 mL) and 1-(cyclopropylmethyl)-3-(4-(piperazine-1-carbonyl)phenyl)urea (0.510 mmol, 154 mg) was added followed by potassium carbonate (1.529 mmol, 211 mg). The mixture was heated to reflux for 16 hours. The mixture was cooled, diluted with dichloromethane (50 mL) and washed with water (2×20 mL). The organic phase was dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by HPLC and treated with strong cation exchange column chromatography to afford the title compound (63 mg). MS (ESI) m/z 601.3 [M+H]+
Reaction SMILES: CO.[C:3]([C:5]1[C:10]([F:11])=[C:9]([F:12])[C:8]([OH:13])=[C:7]([F:14])[C:6]=1[F:15])#[N:4].[C:16](Cl)(=[O:20])[C:17]([CH3:19])=[CH2:18].O>[Na]>[C:16]([O:13][C:8]1[C:7]([F:14])=[C:6]([F:15])[C:5]([C:3]#[N:4])=[C:10]([F:11])[C:9]=1[F:12])(=[O:20])[C:17]([CH3:19])=[CH2:18]
Reactant: N#Cc1c(F)c(F)c(O)c(F)c1F
Reactant: C=C(C)C(=O)Cl
Agent: [Na]
Solvent: CO
Solvent: O
Product: C=C(C)C(=O)Oc1c(F)c(F)c(C#N)c(F)c1F
Yield: 33.2 %

Procedure:
In 50 ml of methanol having 0.94 g (0.0236 mol) of sodium hydroide dissolved therein, 3.0 g (0.0157 mol) of 4-cyano-2,3,5,6-tetrafluorophenol was dissolved. The resultant solution was kept with ice at 0° C. To the cooled solution, 1.80 g (0.0173 mol) of methacrylic acid chloride as slowly added dropwise. After completion of this dropwise addition, the resultant mixture was stirred at the same temperature for two hours. It was then mixed with 50 ml of pure water and adjusted to pH 10 by addition of an aqueous 20% sodium hydroide solution. As the result, white crystals occurred. The white crystals were filtered, washed with cold water, and then dried to obtain 1.35 g of 4-cyano-2,3,5,6-tetrafluorophenyl methacrylate (purity 98% and yield 32 mol % based on 4-cyano-2,3,5,6-tetrafluorophenol). The analyses obtained of this novel substance for the determination of its chemical structure were the same as those of Example 2.
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([CH:14]=O)[CH:12]=2)[N:7]=[CH:6][N:5]=1)[CH3:2].[F:16][C:17]1[CH:18]=[C:19]([CH2:23][CH2:24][NH:25][C:26]2[S:27][CH2:28][C:29](=[O:31])[N:30]=2)[CH:20]=[CH:21][CH:22]=1.N1CCCCC1>C(O)C>[CH2:1]([O:3][C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11](/[CH:14]=[C:28]3/[C:29](=[O:31])[N:30]=[C:26]([NH:25][CH2:24][CH2:23][C:19]4[CH:20]=[CH:21][CH:22]=[C:17]([F:16])[CH:18]=4)[S:27]/3)[CH:12]=2)[N:7]=[CH:6][N:5]=1)[CH3:2]
Reactant: CCOc1ncnc2ccc(C=O)cc12
Reactant: O=C1CSC(NCCc2cccc(F)c2)=N1
Solvent: CCO
Solvent: C1CCNCC1
Product: CCOc1ncnc2ccc(/C=C3\SC(NCCc4cccc(F)c4)=NC3=O)cc12
Yield: 28.4 %

Procedure:
The mixture of 4-ethoxy-quinazoline-6-carbaldehyde (example 10b, 20 mg, 0.1 mmol,), 2-[2-(3-Fluoro-phenyl)-ethylamino]-thiazol-4-one (example 10c, 24 mg, 0.1 mmol) and piperidine (10 ul, 0.1 mmol) in anhydrous ethyl alcohol (1 ml) was microwaved at 160° C. for 25 min. After cooling the reaction to room temperature, the solid was collected by filtration, then washed with MeOH and dried to afford 5-[1-(4-ethoxy-quinazolin-6-yl)-meth-(Z)-ylidene]-2-[2-(3-fluoro-phenyl)-ethylamino]-thiazol-4-one (12 mg, 30%) as light yellow solid. LC-MS m/e 423 (MH+).
Reaction SMILES: [OH-].[K+].C1OCCOCCOCCOCCOCCOC1.C([O:23][C:24]([C:26]1([CH2:56][O:57][CH3:58])[CH2:31][CH2:30][N:29]([CH2:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[N:43]=[C:42]([C:44]4[CH:49]=[CH:48][C:47]([CH:50]5[CH2:54][CH2:53][CH2:52][CH2:51]5)=[C:46]([Cl:55])[CH:45]=4)[O:41][N:40]=3)=[CH:35][CH:34]=2)[CH2:28][CH2:27]1)=[O:25])C>C1(C)C=CC=CC=1>[Cl:55][C:46]1[CH:45]=[C:44]([C:42]2[O:41][N:40]=[C:39]([C:36]3[CH:37]=[CH:38][C:33]([CH2:32][N:29]4[CH2:30][CH2:31][C:26]([CH2:56][O:57][CH3:58])([C:24]([OH:25])=[O:23])[CH2:27][CH2:28]4)=[CH:34][CH:35]=3)[N:43]=2)[CH:49]=[CH:48][C:47]=1[CH:50]1[CH2:51][CH2:52][CH2:53][CH2:54]1
Reactant: CCOC(=O)C1(COC)CCN(Cc2ccc(-c3noc(-c4ccc(C5CCCC5)c(Cl)c4)n3)cc2)CC1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [K+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: COCC1(C(=O)O)CCN(Cc2ccc(-c3noc(-c4ccc(C5CCCC5)c(Cl)c4)n3)cc2)CC1

Procedure:
Potassium hydroxide powder (85% assay, 0.32 g, 0.0049 mol) and 18-crown-6-ether (0.01 g) are added to a solution of 1-{4-[5-(3-chloro-4-cyclopentylphenyl)-[1,2,4]-oxadiazol-3-yl]benzyl}-4-methoxymethylpiperidine-4-carboxylic acid ethyl ester (0.3 g, 0.00056 mol) in dry toluene (15 mL). The reaction mixture is refluxed for 3 hrs. It is then concentrated under reduced pressure and the residue is acidified to pH˜4-5 with 20% aqueous solution of acetic acid (10 mL). The precipitated solid is filtered, dried and washed with demineralised water (2×10 mL) and acetone (2×5 mL). Solid mass is dissolved in a solution of methanol:dichlromethane:t-butylamine (1:8.9:0.1; 5 mL) and concentrated under reduced pressure to get crude residue which is purified by column chromatography (silica gel 230-400 mesh, methanol:dichloromethane:t-butylamine, 1:8.9:0.1) to give 1-{4-[5-(3-chloro-4-cyclopentylphenyl)-[1,2,4]-oxadiazol-3-yl]benzyl}-4-methoxymethylpiperidine-4-carboxylic acid.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:26])[C:8]([CH2:24][CH3:25])=[C:9]([C:22]#[N:23])[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([C:17]2[NH:21][N:20]=[N:19][N:18]=2)=[CH:13][CH:12]=1)=[O:5])[CH3:2].[H-].[Na+].[CH2:29](I)[CH2:30][CH2:31][CH3:32]>CN(C=O)C.[Cl-].[Na+].O>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:26])[C:8]([CH2:24][CH3:25])=[C:9]([C:22]#[N:23])[C:10]=1[C:11]1[CH:12]=[CH:13][C:14]([C:17]2[N:18]([CH2:29][CH2:30][CH2:31][CH3:32])[N:19]=[N:20][N:21]=2)=[CH:15][CH:16]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1c(-c2ccc(-c3nnn[nH]3)cc2)c(C#N)c(CC)n1C
Reactant: CCCCI
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCCn1nnnc1-c1ccc(-c2c(C#N)c(CC)n(C)c2C(=O)OCC)cc1
Temperature: 0 °C
Yield: 33.9 %

Procedure:
Into a round bottom flask containing a solution of 4-cyano-5-ethyl-1-methyl-3-[4-(1H-tetrazol-5-yl)-phenyl]-1H-pyrrole-2-carboxylic acid ethyl ester (0.150 g, 0.428 mmol, prepared in example E-242) in DMF (2 mL) cooled to 0° C. while stirring add NaH (0.019 g, 0.479 mmol, 60% in mineral oil). Let stir for 1 h, then add butyl iodide (0.054 mL, 0.479 mmol) and let stir for 2.5 h. Dilute the mixture with brine (20 mL) and extract the mixture with EtOAc (3×15 mL). Combine the organic layers and wash with brine (2×20 mL), aqueous NH4Cl (1×20 mL), aqueous NaHCO3 (1×20 mL) and water (1×20 mL). Dry the organic layer over anhydrous Na2 SO4, filter, and concentrate under reduced pressure. Purify the residue via silica gel chromatography (eluent: 20 to 98% EtOAc in hexanes). Concentrate under reduced pressure the purified fractions and place under vacuum to provide the title compound as a colorless oil (0.059 g); mass spectrum (m/e): 407.4 (M+H)
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([CH3:12])([CH3:11])[N:10]=2)=[CH:4][CH:3]=1.[CH:13]([C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)=[CH2:14].C1C(O)=CC=C(O)C=1>C1C=CC=CC=1>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH2:14][CH:13]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)[C:9]([CH3:11])([CH3:12])[N:10]=2)=[CH:6][CH:7]=1
Reactant: C=Cc1ccncc1
Reactant: Cc1ccc(C2=NC2(C)C)cc1
Agent: Oc1ccc(O)cc1
Solvent: c1ccccc1
Product: Cc1ccc(C2=NC(C)(C)C(c3ccncc3)C2)cc1

Procedure:
16 G. of 3-(p-methylphenyl)-2,2-dimethyl-2H-azirine and 26 g. of freshly distilled 4-vinylpyridine are irradiated in 2 l. of absolute benzene for 6 hours under the conditions given in Example 11 with the addition of 0.05 g. of p-hydroquinone. After evaporation of the solution under reduced pressure there remains a brown oil from which the excess 4-vinylpyridine is distilled off at 41°-42° C. and 0.01 Torr. The residue is taken up in a small amount of acetone. The crude crystallizate obtained from the acetone solution is chromatographed withe benzene/acetone (95:5) on silica gel. The combined fractions are evaporated to dryness under reduced pressure. Then, the residue is recrystallized twice with n-hexane, the solution which results is then decolorized with active carbon to yield 4-[2-(p-methylphenyl)-5,5-dimethyl-1-pyrrolin-4-yl]-pyridine with a melting point of 102° C.
Reaction SMILES: [C:1]([O:20][CH2:21][CH3:22])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C(O)(=O)CCCCCCCCCCCCCCC>>[C:1]([O:20][CH2:21][CH3:22])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)OCC
Agent: CCCCCCCCCCCCCCCC(=O)O
Product: CCCCCCCCCCCCCCCCCC(=O)OCC
Yield: 50 %

Procedure:
Using the procedure described in Example 1 and substituting therein 20 g. of ethyl oleate for the palmitic acid and employing 5 g. of catalyst and adjusting the deuterium flow rate to 150 ml./minute, there is obtained after 17 days of exchange a 50% yield of ethyl stearate of 99 atom % D.
Reaction SMILES: OC1C=C2C(CCC2=O)=CC=1OC.[N:14]1C=CC=CC=1.[N+:20]([C:23]1[CH:45]=[CH:44][C:26]([CH2:27][O:28]/[N:29]=[C:30]2\[CH2:31]C[CH2:33][C:34]3[C:39]\2=[CH:38][C:37]([O:40]C)=[C:36]([O:42][CH3:43])[CH:35]=3)=[CH:25][CH:24]=1)([O-:22])=O.C(OCC)(=O)C.CCCCCC>C(O)C>[N:20]1[O:22][N:14]=[C:24]2[CH:25]=[C:26]([CH2:27][O:28]/[N:29]=[C:30]3\[CH2:31][CH2:33][C:34]4[C:39]\3=[CH:38][C:37]([OH:40])=[C:36]([O:42][CH3:43])[CH:35]=4)[CH:44]=[CH:45][C:23]=12
Reactant: c1ccncc1
Reactant: COc1cc2c(cc1OC)/C(=N/OCc1ccc([N+](=O)[O-])cc1)CCC2
Agent: COc1cc2c(cc1O)C(=O)CC2
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: CCCCCC
Product: COc1cc2c(cc1O)/C(=N/OCc1ccc3nonc3c1)CC2
Yield: 9 %

Procedure:
6-Hydroxy-5-methoxy-1-indanone (76 mg, 0.43 mmol) was subjected to reaction with 0-(benzo[c][1,2,5]oxadiazol-5-ylmethyl)hydroxylamine hydrochloride (97 mg, 0.48 mmol) in ethanol (2 mL) and pyridine (0.2 mL, 2.58 mmol) under the same conditions as described for (E)-6,7-dimethoxy-3,4-dihydronaphthalen-1(2H)-one O-4-nitrobenzyl oxime. Subjection of the material obtained on work up to flash chromatography (3:7 v/v ethyl acetate/hexane elution) afforded the title compound as off-white crystals (13 mg, 9%), m.p. 145° C. (with decomposition), Rf 0.3.