Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1([CH2:22][O:23][CH2:24][C:25]2[CH:26]=[C:27]([C:35]3[CH:40]=[CH:39][C:38]([C:41]#[N:42])=[CH:37][CH:36]=3)[CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=2)[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]1>ClCCl.FC(F)(F)C(O)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1([CH2:22][O:23][CH2:24][C:25]2[CH:26]=[C:27]([C:35]3[CH:40]=[CH:39][C:38]([C:41]#[N:42])=[CH:37][CH:36]=3)[CH:28]=[C:29]([C:31]([F:34])([F:32])[F:33])[CH:30]=2)[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1
Reactant: CC(C)(C)OC(=O)N1CCC(COCc2cc(-c3ccc(C#N)cc3)cc(C(F)(F)F)c2)(c2ccc(F)cc2Br)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: N#Cc1ccc(-c2cc(COCC3(c4ccc(F)cc4Br)CCNCC3)cc(C(F)(F)F)c2)cc1
Yield: 68.8 %

Procedure:
A solution of tert-butyl 4-(2-bromo-4-fluorophenyl)-4-(((4′-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)piperidine-1-carboxylate (50 mg, 0.077 mmol) in dichloromethane (0.5 mL) and trifluoroacetic acid (2 mL) was stirred at ambient temperature for 3 hours. The reaction was evaporated to dryness and the resulting residue was purified by chromatography on silica with gradient of methanol/dichloromethane of 2% to 10%. The product 3′-(((4-(2-bromo-4-fluorophenyl)piperidin-4-yl)methoxy)methyl)-5′-(trifluoromethyl)biphenyl-4-carbonitrile (29 mg, 69% yield) was obtained as a clear oil. 1H-NMR (CDCl3, 400 MHz) δ 7.74 (d, J=6.8 Hz, 2H), 7.68 (s, 1H), 7.58 (d, J=6.7 Hz, 2H), 7.36 (s, 1H), 7.33 (s, 1H), 7.22-7.33 (m, 2H), 7.03 (m, 1H), 4.49 (s, 2H), 3.88 (s, 2H), 3.25 (m, 2H), 2.94 (m, 2H), 2.85 (m, 2H), 2.23 (m, 2H). Mass spec.: 547.12 (M+H), HPLC (method 5) 3.37 min.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=3)=[CH:12][C:11]([C:22](O)=[O:23])=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8].ClC1C=C(N2C(C3C=CC=C(OCCO)C=3)=CC(C([N:49]3[CH2:53][C:52](=[O:54])[NH:51][CH2:50]3)=O)=N2)C=CC=1>>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=3)=[CH:12][C:11]([C:22]([N:49]3[CH2:53][C:52](=[O:54])[NH:51][CH2:50]3)=[O:23])=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: COc1cccc(-c2cc(C(=O)O)nn2-c2ccc(F)c(Cl)c2)c1
Reactant: O=C1CN(C(=O)c2cc(-c3cccc(OCCO)c3)n(-c3cccc(Cl)c3)n2)CN1
Product: COc1cccc(-c2cc(C(=O)N3CNC(=O)C3)nn2-c2ccc(F)c(Cl)c2)c1

Procedure:
The preparation of the title compound takes place starting from the compound of Example 102A in analogy to the synthesis of the compound of Example 23. 7 mg (12% of theory) of the title compound are obtained.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:5]=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:3]=1.[C:20]1([C:26]2[C:27]3[C:32]([C:33]([C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)=[C:34]4[C:39]=2[CH:38]=[C:37](B(O)O)[CH:36]=[CH:35]4)=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:20]1([C:26]2[C:39]3[C:34]([C:33]([C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)=[C:32]4[C:27]=2[CH:28]=[C:29]([C:2]2[N:7]=[C:6]([C:8]5[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=5)[CH:5]=[C:4]([C:14]5[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=5)[N:3]=2)[CH:30]=[CH:31]4)=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: OB(O)c1ccc2c(-c3ccccc3)c3ccccc3c(-c3ccccc3)c2c1
Reactant: Brc1nc(-c2ccccc2)cc(-c2ccccc2)n1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: c1ccc(-c2cc(-c3ccccc3)nc(-c3ccc4c(-c5ccccc5)c5ccccc5c(-c5ccccc5)c4c3)n2)cc1
Yield: 85.9 %

Procedure:
2-Bromo-4,6-diphenylpyrimidine 3.4 g (11 mmol), 9,10-diphenylanthracene-2-boronic acid 4.9 g (13 mmol) and tetrakis(triphenylphosphine)palladium 0.25 g (0.22 mmol) were dissolved in 60 mL of 1,2-dimethoxyethane. A 2.0M sodium carbonate aqueous solution 30 mL was added thereto, and the solution was refluxed for 8 hours under argon atmosphere by heating. After finishing the reaction, the solution was filtered, and a solid matter obtained was washed with water, methanol and toluene to obtain 5.3 g (yield: 86%) of a greenish white solid matter. Mass spectral analysis of the above solid matter resulted in confirming that m/e was 560 versus a molecular weight of 560.23 and that it was the aimed compound 2.
Reaction SMILES: C([O:5][C:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:23]=[C:22]3[C:17]([C:18]([OH:33])=[C:19]([C:26](=[O:32])[CH2:27][CH2:28][C:29]([OH:31])=[O:30])[C:20](=[O:25])[N:21]3[CH3:24])=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)=[O:7])(C)(C)C.OC1C2C(=CC(C3C=CC(C(OC(C)(C)C)=O)=CC=3)=CC=2)N(C)C(=O)C=1C(=O)CCC=O.OOS([O-])=O.[K+].O>CN(C=O)C>[C:29]([CH2:28][CH2:27][C:26]([C:19]1[C:20](=[O:25])[N:21]([CH3:24])[C:22]2[C:17]([C:18]=1[OH:33])=[CH:16][CH:15]=[C:14]([C:11]1[CH:10]=[CH:9][C:8]([C:6]([OH:7])=[O:5])=[CH:13][CH:12]=1)[CH:23]=2)=[O:32])([OH:31])=[O:30]
Reactant: Cn1c(=O)c(C(=O)CCC(=O)O)c(O)c2ccc(-c3ccc(C(=O)OC(C)(C)C)cc3)cc21
Agent: Cn1c(=O)c(C(=O)CCC=O)c(O)c2ccc(-c3ccc(C(=O)OC(C)(C)C)cc3)cc21
Agent: O=S([O-])OO
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cn1c(=O)c(C(=O)CCC(=O)O)c(O)c2ccc(-c3ccc(C(=O)O)cc3)cc21
Reaction time: 1 h

Procedure:
4-(7-(4-(tert-Butoxycarbonyl)phenyl)-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)-4-oxobutanoic acid. tert-Butyl 4-(4-hydroxy-1-methyl-2-oxo-3-(4-oxobutanoyl)-1,2-dihydroquinolin-7-yl)benzoate (130 mg, 299 mmol) was dissolved in DMF (1493 n1). Oxone (184 mg, 299 mmol) was added to the mixture at room temperature, and the resulting mixture was stirred for 1 hour. Water was added to precipitate the product from solution. The mixture was filtered, washed with water and ether, and dried in a vacuum oven to give the title compound as an off-white solid.
Reaction SMILES: Cl[C:2]1[N:20]=[C:5]2[C:6]([NH:10][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[NH2:21][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1>>[CH3:19][O:18][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=1)[CH2:11][NH:10][C:6]1[C:5]2[N:4]([N:3]=[C:2]([NH:21][C:22]3[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=3)[N:20]=2)[CH:9]=[CH:8][CH:7]=1
Reactant: COc1cccc(CNc2cccn3nc(Cl)nc23)c1
Reactant: Nc1cccnc1
Product: COc1cccc(CNc2cccn3nc(Nc4cccnc4)nc23)c1

Procedure:
N(8)-(3-Methoxy-benzyl)-N(2)-pyridin-3-yl-[1,2,4]triazolo[1,5-a]pyridine-2,8-diamine was prepared from (2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-(3-methoxy-benzyl)-amine (99.9 mg, 0.346 mmol) and 3-aminopyridine (36.47 mg, 0.3875 mmol) in a manner analogous to Example 2d. Product isolated as an off-white foam (6.22 mg, 5%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.65 (s, 1H), 8.89 (s, 1H), 8.22 (d, J=8.6 Hz, 1H), 8.08 (m, 1H), 7.97 (d, J=6.4 Hz, 1H), 7.32-7.20 (m, 2H), 6.97 (s, 2H), 6.82-6.72 (m, 2H), 6.62 (m, 1H), 6.32 (d, J=8.1 Hz, 1H), 4.50 (d, J=6.1 Hz, 2H), 3.72 (s, 3H). MS=347 (MH)+.
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15]CC2C=CC=CC=2)=[CH:11][C:10]=1[CH:23]([CH3:33])[CH2:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)C1C=CC=CC=1.C(O)C.Cl.[H][H]>C(OCC)(=O)C.[Pd]>[OH:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH:23]([CH3:33])[CH2:24][CH2:25][O:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: [H][H]
Reactant: CC(CCOc1ccccc1)c1cc(OCc2ccccc2)ccc1OCc1ccccc1
Agent: [Pd]
Agent: Cl
Solvent: CCO
Solvent: CCOC(C)=O
Product: CC(CCOc1ccccc1)c1cc(O)ccc1O
Reaction time: 2 h

Procedure:
A solution of 3-(2,5-dibenzyloxyphenyl)-1-phenoxybutane (14.7 g., 133.5 mM) in a mixture of ethyl acetate (110 ml.), ethanol (110 ml.) and concentrated hydrochloric acid (0.7 ml.) is hydrogenated for 2 hours under 60 p.s.i. hydrogen in the presence of 10% palladium-on-carbon (1.5 g.). Removal of the catalyst by filtration and concentration of the filtrate gives an oil. The oil is purified by chromatography on silica gel (100 g.) and eluting with benzene-ethyl acetate consisting of 0-10% ethyl acetate. The middle fractions are combined and concentrated to give the title product.
Reaction SMILES: [O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)[N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:4][N:3]1[CH2:18][C:19]1[CH:20]=[C:21]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=1.[I-].[Na+].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:39][CH2:40][CH2:41][N:42]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH2:44][C:43]1=[O:51]>CC(=O)CC>[O:1]=[C:2]1[C:6]2([CH2:7][CH2:8][N:9]([CH2:39][CH2:40][CH2:41][N:42]3[C:50]4[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=4)[CH2:44][C:43]3=[O:51])[CH2:10][CH2:11]2)[N:5]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:4][N:3]1[CH2:18][C:19]1[CH:20]=[C:21]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=1
Reactant: O=C1Cc2ccccc2N1CCCCl
Reactant: CS(=O)(=O)Nc1cccc(CN2CN(c3ccccc3)C3(CCNCC3)C2=O)c1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCC(C)=O
Product: CS(=O)(=O)Nc1cccc(CN2CN(c3ccccc3)C3(CCN(CCCN4C(=O)Cc5ccccc54)CC3)C2=O)c1
Temperature: 78 °C
Reaction time: 3 h
Yield: 13.2 %

Procedure:
To a solution of N-(3((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)phenyl)methanesulfonamide (0.22 g, 0.53 mmol), sodium iodide (0.032 g, 0.21 mmol) and potassium carbonate (0.146 g, 1.06 mmol) in 2-butanone (5 mL), was added 1-(3-chloropropyl)indolin-2-one (0.11 g, 0.53 mmol). After stirring at 78° C. for 3 hours, the reaction mixture was filtered and isolated by preparatory TLC (10% methanol/dichloromethane) to obtain the title compound (0.041 g, 13%); 1H NMR (DMSO-d6): δ 1.66 (d, 2H, J=13.6 Hz), 1.78 (t, 2H, J=6.8 Hz), 2.33-2.47 (m, 2H), 2.50-2.56 (m, 2H), 2.76 (br, 4H), 2.96 (s, 3H), 3.54 (s, 2H), 3.73 (t, 2H, J=6.8 Hz), 4.52 (s, 2H), 4.58 (s, 2H), 6.77 (t, 1H, J=7.2 Hz), 6.85 (d, 2H, J=8.4 Hz), 6.97-7.02 (m, 2H), 7.08-7.13 (m, 3H), 7.20-7.26 (m, 4H), 7.32 (t, 1H, J=8 Hz), 9.80 (s, 1H); MS for C32H37N5O4S m/z 588.3 (M+H)+.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][CH:13]=1)[C:8]([OH:10])=[O:9])(=[O:4])=[O:3].[N+:14]([O-])([O-:16])=[O:15].[K+]>S(=O)(=O)(O)O>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([N+:14]([O-:16])=[O:15])[CH:13]=1)[C:8]([OH:10])=[O:9])(=[O:3])=[O:4]
Reactant: CS(=O)(=O)c1cccc(C(=O)O)c1
Reactant: O=[N+]([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Product: CS(=O)(=O)c1cc(C(=O)O)cc([N+](=O)[O-])c1
Temperature: 110 °C
Yield: 0.1 %

Procedure:
To a suspension of 3-(methylsulfonyl)-benzoic acid (32.5 g; 0.16 mol) in 130 mL 98% sulphuric acid at 0° C. was slowly added potassium nitrate (32.8 g; 0.32 mol). The reaction mixture was heated for 3 hours at 110° C., subsequently cooled to room temperature and poured onto ice and the precipitate collected. 28 g (0.114 mmol; 71% yield) of 3-(methylsulfonyl)-5-nitro-benzoic acid were obtained as a solid.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[O:5][CH2:6][C:7]([NH2:9])=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].CCOCC.[H-]>O>[NH2:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[O:5][CH2:6][CH2:7][NH2:9]
Reactant: NC(=O)COc1cccc(N)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: O
Product: NCCOc1cccc(N)c1
Temperature: 25 °C

Procedure:
A mixture of 3-aminophenoxyacetamide (10.0 g., 0.05 M), lithium aluminum hydride (6.8 g., 0.18 M) and ether (250 ml.) is refluxed under dry nitrogen for four days. It is then cooled to room temperature and water slowly added to decompose unreacted hydride. The precipitated salts are removed by filtration and the filtrate concentrated to an oil under reduced pressure. The crude oil is chromatographed on silica gel using 20% methanol/ethyl acetate as eluting agent. Concentration of appropriate fractions affords 4.83 g. (53%) of product as an oil. It is used without further purification.
Reaction SMILES: [OH-].[K+].[OH:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:12])[CH3:11])=[CH:6][CH:5]=1.O=[CH:14][C:15]1[CH:23]=[CH:22][C:20]([OH:21])=[C:17]([O:18][CH3:19])[CH:16]=1>C(OCCOCCOCC)C>[OH:21][C:20]1[CH:22]=[CH:23][C:15]([CH:14]=[CH:11][C:10]([C:7]2[CH:8]=[CH:9][C:4]([OH:3])=[CH:5][CH:6]=2)=[O:12])=[CH:16][C:17]=1[O:18][CH3:19]
Reactant: COc1cc(C=O)ccc1O
Reactant: CC(=O)c1ccc(O)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CCOCCOCCOCC
Product: COc1cc(C=CC(=O)c2ccc(O)cc2)ccc1O
Temperature: 120 °C
Reaction time: 0.33 h
Yield: 93.8 %

Procedure:
20 g of potassium hydroxide are initially introduced into 100 g of diethylene glycol diethyl ether, heated to 120° C. with stirring and combined with a mixture of 14 g of p-hydroxyacetophenone and 15 g of vanillin within 1 h. Once addition is complete, stirring is continued for a further 20 min, the mixture hydrolyzed and adjusted to pH 6-7. Once the phases have separated, the solvent is removed and 25 g of 3-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)-2-propen-1-one are obtained, yield: 93% of theoretical.
Reaction SMILES: [Si]([O:18][C:19]1[CH:20]=[C:21]([C:25]2[N:33]=[C:32]3[C:28]([NH:29][C:30](=[O:40])[N:31]3[CH:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[C:27]([C:41]([O:43]C)=O)[N:26]=2)[CH:22]=[CH:23][CH:24]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[NH2:45]C1C(C(OC)=O)=NC(C2C=CC=C(O[Si](C(C)(C)C)(C3C=CC=CC=3)C3C=CC=CC=3)C=2)=NC=1NC1CCOCC1>ClCCl>[OH:18][C:19]1[CH:20]=[C:21]([C:25]2[N:33]=[C:32]3[C:28]([NH:29][C:30](=[O:40])[N:31]3[CH:34]3[CH2:35][CH2:36][O:37][CH2:38][CH2:39]3)=[C:27]([C:41]([NH2:45])=[O:43])[N:26]=2)[CH:22]=[CH:23][CH:24]=1
Reactant: COC(=O)c1nc(-c2cccc(O[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)c2)nc(NC2CCOCC2)c1N
Reactant: COC(=O)c1nc(-c2cccc(O[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)c2)nc2c1[nH]c(=O)n2C1CCOCC1
Solvent: ClCCl
Product: NC(=O)c1nc(-c2cccc(O)c2)nc2c1[nH]c(=O)n2C1CCOCC1
Yield: 71 %

Procedure:
Methyl 2-(3-(tert-butyldiphenylsilyloxy)phenyl)-8-oxo-9-(tetrahydro-2H-pyran-4-yl)-8,9-dihydro-7H-purine-6-carboxylate. Methyl 5-amino-2-(3-(tert-butyldiphenylsilyloxy)phenyl)-6-(tetrahydro-2H-pyran-4-ylamino)pyrimidine-4-carboxylate (0.361 g, 0.722 mmol) and 1,1′-1,1′-carbonyldiimidazole (0.702 g, 4.33 mmol) in dichloromethane (15 mL) were reacted according to General Procedure F and purified via biotage chromatography (0 to 75% EtOAc in hexanes) to afford the title compound (0.270 g, 71%). 1H NMR (400 MHz, DMSO-d6) δ 11.80 (s, 1H), 7.96 (s, 2H), 7.41 (t, J=8.39, 1H), 7.00 (dd, J=7.99 2.39, 1H), 4.51 (m, 1H), 4.01 (dd, J=11.19, 3.59, 2H), 3.94 (s, 3H), 3.48 (t, J=11.99, 2H), 2.65 (m, 2H), 1.75 (d, 9.59, 2H), 1.33 (m, 3H), 1.10 (d, J=3.59, 18H).
Reaction SMILES: N[C@H](C(O)=O)CC[C:5](O)=[O:6].[O:11]=[CH:12][C@@H:13]([C@H:15]([C@@H:17]([CH2:19][OH:20])[OH:18])[OH:16])[OH:14]>>[O:11]=[CH:12][C@@H:13]([C@H:15]([C@@H:17]([C@@H:19]([CH2:5][OH:6])[OH:20])[OH:18])[OH:16])[OH:14]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)CO
Reactant: N[C@@H](CCC(=O)O)C(=O)O
Product: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
On the other hand, when the P. ananatis NA1 strain containing pTWVPtac_ccrNXA_Km was cultured with the mixed carbon source of glucose and xylose (MSII-GX medium), the glutamic acid yield was significantly higher as compared to the parent strain (yield: 69.9%). If it is taken into consideration that the parent strain hardly produces glutamic acid from xylose, and it is assumed that the glutamic acid yield from glucose of the strain containing pTWVPtac_ccrNXA_Km is equivalent to that of the parent strain, the yield of glutamic acid produced from xylose via the NXA pathway is about 86%. In fact, when the culture was performed with xylose as the sole carbon source (MSII-Xylose), the strain containing pTWVPtac_ccrNXA_Km produced Glu at a yield of 80% (Table 3).
Reaction SMILES: ClC1C=CC(CN2CCC(NC3C=CC(C#N)=CC=3)CC2)=CC=1OCC.[CH3:27][O:28][C:29](=[O:51])[C:30]1[CH:35]=[C:34]([Cl:36])[N:33]=[C:32]([NH:37][CH:38]2[CH2:43][CH2:42][N:41](C(OC(C)(C)C)=O)[CH2:40][CH2:39]2)[CH:31]=1.Cl>O1CCOCC1.C(O)C>[CH3:27][O:28][C:29](=[O:51])[C:30]1[CH:31]=[C:32]([NH:37][CH:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[N:33]=[C:34]([Cl:36])[CH:35]=1
Reactant: COC(=O)c1cc(Cl)nc(NC2CCN(C(=O)OC(C)(C)C)CC2)c1
Agent: CCOc1cc(CN2CCC(Nc3ccc(C#N)cc3)CC2)ccc1Cl
Agent: Cl
Solvent: C1COCCO1
Solvent: CCO
Product: COC(=O)c1cc(Cl)nc(NC2CCNCC2)c1

Procedure:
The title compound was prepared in analogy to the synthesis of (5-methanesulfonyl-pyridin-2-yl)-piperidin-4-yl-amine (intermediate B16/step 2) from 2-(1-tert-butoxycarbonyl-piperidin-4-ylamino)-6-chloro-isonicotinic acid methyl ester by cleavage of the BOC group with 4 M HCl in dioxane and ethanol at rt. MS (ISP): 270.1 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:27]=[C:26]([C:28]([O:30][CH3:31])=[O:29])[CH:25]=[CH:24][C:3]=1[O:4][C@H:5]1[CH2:9][CH2:8][N:7]([CH:10]2[CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11]2)[C:6]1=[O:23].[ClH:32].C(O)(C)C>CCOC(C)=O>[ClH:32].[F:1][C:2]1[CH:27]=[C:26]([CH:25]=[CH:24][C:3]=1[O:4][C@H:5]1[CH2:9][CH2:8][N:7]([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[C:6]1=[O:23])[C:28]([O:30][CH3:31])=[O:29]
Reactant: COC(=O)c1ccc(O[C@H]2CCN(C3CCN(C(=O)OC(C)(C)C)CC3)C2=O)c(F)c1
Agent: Cl
Solvent: CC(C)O
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(O[C@H]2CCN(C3CCNCC3)C2=O)c(F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
To a solution of (S)-tert-butyl 4-(3-(2-fluoro-4-(methoxycarbonyl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (2 g, 4.6 mmol) in EtOAc (20 mL) was added hydrogen chloride in isopropanol (5-6 M) (9.2 mL, 46 mmol) and the reaction was stirred overnight at ambient temperature. The reaction was concentrated under vacuum to give (S)-methyl 3-fluoro-4-(2-oxo-1-(piperidin-4-yl)pyrrolidin-3-yloxy)benzoate hydrochloride (1.5 g, 100%), which was used crude in the next reaction
Reaction SMILES: [CH:1]1([C:11](OC)=[O:12])[CH2:6][CH2:5][CH:4]([C:7](OC)=[O:8])[CH2:3][CH2:2]1.[H][H]>[Cr].[Cu]>[CH:1]1([CH2:11][OH:12])[CH2:6][CH2:5][CH:4]([CH2:7][OH:8])[CH2:3][CH2:2]1
Reactant: [H][H]
Reactant: COC(=O)C1CCC(C(=O)OC)CC1
Agent: [Cr]
Agent: [Cu]
Product: OCC1CCC(CO)CC1
Temperature: 260 °C

Procedure:
250 Parts of dimethyl 1,4-cyclohexanedicarboxylate and 25 parts of a copper-chromium catalyst were placed in an autoclave having a volume of 2 liters, and the mixture was stirred at 260° C. and reduced with hydrogen under a hydrogen pressure of 15 MPa. Then, the catalyst was removed by filtration, methanol formed as a side product was removed from an obtained filtrate by concentration, and the remaining filtrate was distilled under reduced pressure (160-175° C./1.33-2.00×103 Pa), to give 1,4-cyclohexanedimethanol (to be sometimes referred to as “CHDM” hereinafter). This product was subjected to 1H-NMR (JNM-AL400 supplied by JEOL) to show an isomer structure ratio of 71% of a trans-isomeric compound and 29% of a cis-isomeric compound (CHDM1).
Reaction SMILES: [CH2:1]([C@H:8]([NH:39]C(=O)OC(C)(C)C)[C@@H:9]([OH:38])[CH2:10][C@@H:11]([NH:25][C:26](=[O:37])[C@H:27]([C:33]([CH3:36])([CH3:35])[CH3:34])[NH:28][C:29]([O:31][CH3:32])=[O:30])[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=2)=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[NH2:39][C@@H:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@@H:9]([OH:38])[CH2:10][C@@H:11]([NH:25][C:26](=[O:37])[C@H:27]([C:33]([CH3:36])([CH3:35])[CH3:34])[NH:28][C:29]([O:31][CH3:32])=[O:30])[CH2:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]2[CH:20]=[CH:21][N:22]=[CH:23][CH:24]=2)=[CH:17][CH:18]=1
Reactant: COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(-c2ccncc2)cc1)C[C@H](O)[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C)C(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(-c2ccncc2)cc1)C[C@H](O)[C@@H](N)Cc1ccccc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of the product of Example 150D (0.138 g, 0.22 mmol) in dichloromethane (2.0 mL) was added trifluoroacetic acid (0.5 mL), and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated, and the reaction was partitioned between ethyl acetate and diluted NaHCO3 solution. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated.
Reaction SMILES: [CH3:1][CH:2]([CH3:11])[C:3]([P:5](=[O:10])([O:8]C)[O:6][CH3:7])=[O:4].[I-].[Na+:13]>CC(CC)=O>[CH3:1][CH:2]([CH3:11])[C:3]([P:5](=[O:8])([O-:10])[O:6][CH3:7])=[O:4].[Na+:13]
Reactant: COP(=O)(OC)C(=O)C(C)C
Agent: [I-]
Agent: [Na+]
Solvent: CCC(C)=O
Product: COP(=O)([O-])C(=O)C(C)C

Procedure:
Dimethyl (2-methyl-1-oxopropyl)phosphonate (10.8 g, 0.06 mol) and sodium iodide (9.0 g, 0.06 mol) were dissolved in ethyl methyl ketone (160 ml) and the solution stirred and refluxed for 16 hours. There was evidence of a precipitate after about 10 minutes refluxing.
Reaction SMILES: [CH3:1][CH:2]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].Br[CH2:16][CH2:17][CH3:18]>>[CH3:1][CH:2]([N:8]([CH2:16][CH2:17][CH3:18])[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCBr
Reactant: CCCCCC(C)Nc1ccccc1
Product: CCCCCC(C)N(CCC)c1ccccc1

Procedure:
N-(1-Methylhexyl)-N-propylaniline was prepared from N-(1-methylhexyl)aniline (as in Example 2i)) and 1-bromopropane using the same method as in Example 2ii).
Reaction SMILES: [CH:1]1[CH:10]=[C:9]([OH:11])[C:8]2[N:7]=[CH:6][C:5]([OH:12])=[CH:4][C:3]=2[CH:2]=1>C(OC(=O)C)(=O)C.N1C=CC=CC=1.C(OCC)(=O)C>[C:9]([O:12][C:5]1[CH:6]=[N:7][C:8]2[C:3]([CH:4]=1)=[CH:2][CH:1]=[CH:10][C:9]=2[O:11][C:5](=[O:12])[CH3:4])(=[O:11])[CH3:8]
Reactant: Oc1cnc2c(O)cccc2c1
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Solvent: CC(=O)OC(C)=O
Product: CC(=O)Oc1cnc2c(OC(C)=O)cccc2c1
Yield: 78 %

Procedure:
Jineol of 5.0 mg was dissolved in 0.5 ml of acetic acid anhydride and 0.5 ml of pyridine, and then the solution was agitated at room temperature for 9 hours. After the solution was diluted with ethyl acetate, it was washed with sodium dicarbonate solution and brine. The solution was dried with anhydrous magnesium sulfate anhydride. After the residue was removed, the solution was purified by silicagel chromatography to give 5.9 mg of 3,8-diacetoxy quinoline with 78% yield.
Reaction SMILES: [NH2:1][C:2]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:3]=1[N:4]=[C:5]1[C:10](=[N:11]2)[C:9]2[CH:16]=[CH:17][CH:18]=[CH:19][C:8]=2[C:7]2[CH:20]=[CH:21][CH:22]=[CH:23][C:6]1=2.F[C:25]1[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=1.CS(C)=O.C(O[K])(C)(C)C>O>[N+:31]([C:28]1[CH:29]=[CH:30][C:25]([N:4]2[C:3]3[C:12](=[CH:13][CH:14]=[CH:15][C:2]=3[NH2:1])[NH:11][C:10]3[C:9]4[CH:16]=[CH:17][CH:18]=[CH:19][C:8]=4[C:7]4[CH:20]=[CH:21][CH:22]=[CH:23][C:6]=4[C:5]2=3)=[CH:26][CH:27]=1)([O-:33])=[O:32]
Reactant: Nc1cccc2nc3c4ccccc4c4ccccc4c3nc12
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: CC(C)(C)O[K]
Solvent: CS(C)=O
Solvent: O
Product: Nc1cccc2c1N(c1ccc([N+](=O)[O-])cc1)c1c(c3ccccc3c3ccccc13)N2
Reaction time: 24 h

Procedure:
While agitating 10.0 g (34 mmol) of 10-aminodibenzo(A,C)phenazine, 4.8 g (34 mmol) of 4-fluoronitrobenzene and 500 ml of dimethylsulfoxide, 19.4 g (173 mmol) of t-butoxy potassium was gently added. After completion of the addition, the reaction container was charged with nitrogen, followed by agitation at room temperature for 24 hours. After completion of the reaction, 500 ml of water was added while cooling, after which the reaction solution was filtered to obtain a filtration residue. The thus obtained residue was washed with methanol to obtain the intended product.