Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: P(O)(O)(O)=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.[C:19]1([C:25]([CH3:30])([OH:29])[C:26]([OH:28])=[O:27])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[C:19]1([C@:25]([CH3:30])([OH:29])[C:26]([OH:28])=[O:27])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: CC(O)(C(=O)O)c1ccccc1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: O=P(O)(O)O
Product: C[C@@](O)(C(=O)O)c1ccccc1

Procedure:
We next examined the preparation of aryllactic acid derivatives 6 through hydrolysis of the corresponding cyanohydrins 5. Phenyllactic acid and derivatives serve as versatile building blocks for the preparation of numerous biologically active compounds. (Coppola, G. M.; Schuster, H. F. Chiral α-Hydroxy Acids in Enantioselective Synthesis; Wiley-VCH: Weinheim, Germany: 1997.) Upon screening our nitrilase library against the parent cyanohydrin 5a (Ar=phenyl), we found several enzymes that provided 6a with high enantiomeric excess. One enzyme, SEQ ID NOS: 103, 104, was further characterized. After optimization, SEQ ID NOS:103, 104, was shown to provide (S)-phenyllactic acid (6a) with complete conversion (50 mM) and very high enantioselectivity (98% ee) over 6 h. The highest enantioselectivity previously reported for biocatalytic conversion of 5 to 6 was 75% ee achieved through a whole cell transformation using a Pseudomonas strain. (Hashimoto, Y.; Kobayashi, E.; Endo, T.; Nishiyama, M.; Horinouchi, S. Biosci. Biotech. Biochem. 1996, 60, 1279.)
Reaction SMILES: [ClH:1].Cl.[NH2:3][CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:27]=[CH:26][C:17]3[C:18]4[CH2:25][CH2:24][CH2:23][C:19]=4[C:20](=[O:22])[O:21][C:16]=3[CH:15]=2)[CH2:6][CH2:5]1.[O-:28][C:29]#[N:30].[K+].Cl>O>[ClH:1].[NH:3]([CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:27]=[CH:26][C:17]3[C:18]4[CH2:25][CH2:24][CH2:23][C:19]=4[C:20](=[O:22])[O:21][C:16]=3[CH:15]=2)[CH2:6][CH2:5]1)[C:29]([NH2:30])=[O:28]
Reactant: N#C[O-]
Reactant: NC1CCN(CCCOc2ccc3c4c(c(=O)oc3c2)CCC4)CC1
Agent: Cl
Agent: [K+]
Solvent: O
Product: NC(=O)NC1CCN(CCCOc2ccc3c4c(c(=O)oc3c2)CCC4)CC1

Procedure:
A mixture of 4.15 g. (0.01 mole) 7-[3-(4-aminopiperidino)-propoxy]-2,3-dihydrocyclopenta[c][1]benzopyran-4(1H)-one dihydrochloride, 4.0 g. potassium cyanate, 50 ml. water and 30 ml. 2 N hydrochloric acid is stirred for 3 days at ambient temperature, filtered and the precipitate extracted with hot ethanol. There are thus obtained 2.4 g. (57% of theory) of the desired compound; m.p. 244°-245° C.
Reaction SMILES: C([NH:4][C:5]1[S:6][C:7]([S:10][C:11]2[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=2)=[CH:8][N:9]=1)(=O)C.Cl.[OH-].[Na+]>C(O)(=O)C>[NH2:4][C:5]1[S:6][C:7]([S:10][C:11]2[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=2)=[CH:8][N:9]=1
Reactant: CC(=O)Nc1ncc(Sc2ccc(N)cc2)s1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Product: Nc1ccc(Sc2cnc(N)s2)cc1
Temperature: 0 °C
Yield: 80.8 %

Procedure:
A solution of 2-acetylamino-5-(4-aminophenylthio)thiazole (2.5 g) in a mixture of acetic acid (20 ml) and 6N-aqueous hydrochloric acid (5 ml) was refluxed for 4 hours with stirring. The reaction mixture was poured into ice-water and the solution was adjusted to pH 10 using 1N-aqueous sodium hydroxide with stirring under ice cooling. The precipitates were collected by filtration, washed with water and dried in vacuo to give 2-amino-5-(4-aminophenylthio)thiazole (1.70 g, yield: 81.5%).
Reaction SMILES: [CH2:1]([N:4]1[CH2:7][CH:6]([C:8]2[CH:13]=[CH:12][C:11]([NH2:14])=[CH:10][CH:9]=2)[CH2:5]1)[CH2:2][CH3:3].[Br:15][C:16]1[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1>C(Cl)Cl.N1C=CC=CC=1>[Br:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([NH:14][C:11]2[CH:10]=[CH:9][C:8]([CH:6]3[CH2:5][N:4]([CH2:1][CH2:2][CH3:3])[CH2:7]3)=[CH:13][CH:12]=2)(=[O:24])=[O:23])=[CH:18][CH:17]=1
Reactant: CCCN1CC(c2ccc(N)cc2)C1
Reactant: O=S(=O)(Cl)c1ccc(Br)cc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCN1CC(c2ccc(NS(=O)(=O)c3ccc(Br)cc3)cc2)C1
Yield: 51.2 %

Procedure:
Following the same procedure as described in example 55, 4-(1-propyl-azetidin-3-yl)phenylamine (1 g, 5.25 mmol) in CH2Cl2/pyridine 9:1 (50 ml) was treated with 4-bromobenzenesulfonyl chloride (1.34 g, 5.25 mmol). Purification of the crude product by flash column chromatography (CH2Cl2:methanol, 95:5) provided the title compound (1.1 g, 51%) as a colourless gum.
Reaction SMILES: [H-].[Na+].[CH2:3]([C@H:10]1[CH2:14][O:13][C:12](=[O:15])[NH:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[CH2:17][C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=1[C:28]1[CH:33]=[C:32]([CH:34]([CH3:36])[CH3:35])[C:31]([F:37])=[CH:30][C:29]=1[O:38][CH3:39]>C1COCC1>[CH2:3]([C@H:10]1[CH2:14][O:13][C:12](=[O:15])[N:11]1[CH2:17][C:18]1[CH:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[CH:20][C:19]=1[C:28]1[CH:33]=[C:32]([CH:34]([CH3:36])[CH3:35])[C:31]([F:37])=[CH:30][C:29]=1[O:38][CH3:39])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: COc1cc(F)c(C(C)C)cc1-c1ccc(C(F)(F)F)cc1CBr
Reactant: O=C1N[C@@H](Cc2ccccc2)CO1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1cc(F)c(C(C)C)cc1-c1ccc(C(F)(F)F)cc1CN1C(=O)OC[C@@H]1Cc1ccccc1
Reaction time: 0.33 h

Procedure:
A stirred suspension of sodium hydride (60% in oil, 37 mg, 0.926 mmol) in THF (1 mL) was treated at 0° C. with (S)-4-benzyl-2-oxazolidinone (33 mg, 0.185 mmol) dissolved in THF (1 mL), under an atmosphere of N2. The reaction was stirred for 20 min and a solution of 2′-(bromomethyl)-4-fluoro-5-isopropyl-2-methoxy-4′-(trifluoromethyl)biphenyl (Intermediate 10, 50 mg, 0.124 mmol) in THF (1 mL) was added dropwise. The reaction was stirred at room temperature for 60 h. The reaction was quenched with H2O (1 mL) and partitioned between EtOAc (25 mL) and H2O (10 mL). The aqueous phase was re-extracted with EtOAc (3×15 mL) and the combined organic extracts were washed with brine (25 mL), dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash silica-gel chromatography (0-25% EtOAc/hexanes gradient) to afford (4S)-4-benzyl-3-{[4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-1,3-oxazolidin-2-one as a clear glass. LCMS=502.3 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers) δ 7.69-7.64 (m, 1H), 7.58 (s, 1H), 7.39-7.36 (m, 1 H), 7.29-7.24 (m, 3 H), 7.06 (d, J=8.5 Hz, 1H), 6.97-6.91 (m, 2 H), 6.73 (d, J=11.7, 1H), 4.79 (d, J=15.8 Hz, 1H), 4.30 (d, J=15.8 Hz, 1 H), 4.08-4.05 (m, 1H), 3.99-3.97 (m, 1H), 3.76 (s, 3H), 3.65-3.58 (m, 1H), 3.27-3.17 (m, 1 H), 2.81 (dd, J=13.5, 4.1 Hz, 1H), 2.45-2.40 (m, 1 H), 1.30-1.4 (m, 6 H).
Reaction SMILES: Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:15][C:14]=2[O:28][CH3:29])[N:3]=1.FC(F)(F)C(O)=O.[NH2:37][C:38]1[CH:39]=[CH:40][C:41]([CH:49]2[CH2:53][CH:52]([OH:54])[CH:51]([OH:55])[CH2:50]2)=[C:42]2[C:46]=1[C:45](=[O:47])[N:44]([CH3:48])[CH2:43]2>CCOC(C)=O>[CH2:20]([O:19][P:18]([CH2:17][C:16]1[CH:26]=[CH:27][C:13]([NH:12][C:4]2[N:3]=[C:2]([NH:37][C:38]3[CH:39]=[CH:40][C:41]([CH:49]4[CH2:50][CH:51]([OH:55])[CH:52]([OH:54])[CH2:53]4)=[C:42]4[C:46]=3[C:45](=[O:47])[N:44]([CH3:48])[CH2:43]4)[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=2)=[C:14]([O:28][CH3:29])[CH:15]=1)(=[O:25])[O:22][CH2:23][CH3:24])[CH3:21]
Reactant: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Cl)n2)c(OC)c1)OCC
Reactant: CN1Cc2c(C3CC(O)C(O)C3)ccc(N)c2C1=O
Solvent: O=C(O)C(F)(F)F
Solvent: CCOC(C)=O
Product: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(C4CC(O)C(O)C4)c4c3C(=O)N(C)C4)n2)c(OC)c1)OCC

Procedure:
The title compound was prepared according to the procedure for Example 102 using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (43 mg, 0.095 mmol) and 7-amino-4-(3,4-dihydroxycyclopentyl)-2-methyl-2,3-dihydro-1H-isoindol-1-one trifluoroacetate (salt) (Compound 243A, 36 mg, 0.096 mmol). The reaction mixture was diluted with EtOAc (30 mL), washed with sat. aq. NaHCO3 (2×10 mL), brine (10 mL), and dried over anhydrous sodium sulfate. The solvents were evaporated under reduced pressure, and the residue was purified by silica gel chromatography (ISCO Combi-flash system, eluting with 0-10% MeOH:DCM) to give the title compound as a white solid, 34 mg, 52% yield. 1H NMR (CDCl3): 1.26 (t, J=7.1 Hz, 6H), 1.95-2.01 (m, 2H), 2.23-2.29 (m, 2H), 3.17 (d, J=21.7 Hz, 2H), 3.21 (s, 3H), 3.53 (m, 1H), 3.91 (s, 3H), 3.97-4.07 (m, 4H), 4.35 (s, 2H), 4.39-4.43 (m, 2H), 6.84 (s, 1H), 6.94 (m, 1H), 7.32 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 8.26 (d, J=8.1 Hz, 1H), 8.38 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 10.31 (s, 1H). MS (ES+): m/z=680.14 [MH+]. HPLC: tR=3.60 min (ZQ3, polar—5 min).
Reaction SMILES: [CH3:1][NH:2][N:3]=[CH:4][C:5](=[O:7])[CH3:6].O=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=1)[CH:10]=[O:11].C(Cl)(Cl)Cl.CO>C(O)(=O)C>[OH:11][C:10]1[C:4]([C:5](=[O:7])[CH3:6])=[N:3][N:2]([CH3:1])[C:9]=1[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=1
Reactant: CNN=CC(C)=O
Reactant: O=CC(=O)c1cccc(C(F)(F)F)c1
Solvent: CO
Solvent: CC(=O)O
Solvent: ClC(Cl)Cl
Product: CC(=O)c1nn(C)c(-c2cccc(C(F)(F)F)c2)c1O
Temperature: 100 °C
Reaction time: 4 h
Yield: 11.1 %

Procedure:
2-Oxopropanal methylhydrazone (7.49 mmol, 750 mg) and (oxo)[3-trifluoromethylphenyl]acetaldehyde (7.0 mmol, 1.42 g) synthesized in Reference Synthetic Example 8 were dissolved in acetic acid (20 mL) and stirred at 100° C. for 4 hours. Then, the solvent was evaporated, and the residue was dried by means of a vacuum pump and purified by silica gel column chromatography (n-hexane/ethyl acetate=2/1) and then by silica gel thin layer chromatography (chloroform/methanol=30/1) to give the desired product as a reddish yellow liquid (221 mg, yield 11%).
Reaction SMILES: [Si](O[C@@H]1CCC[C@H](NC2C(F)=CN=C(C)C=2C2C3C(=NC=C(Cl)C=3)N(S(C3C=CC(C)=CC=3)(=O)=O)C=2)[C@H]1O)(C(C)(C)C)(C)C.[Si]([O:52][C@:53]1([CH3:88])[CH2:58][CH2:57][CH2:56][C@H:55]([NH:59][C:60]2[C:65]([F:66])=[CH:64][N:63]=[C:62]([C:67]3[C:75]4[C:70](=[N:71][CH:72]=[C:73]([Cl:76])[CH:74]=4)[N:69](S(C4C=CC(C)=CC=4)(=O)=O)[CH:68]=3)[N:61]=2)[C@H:54]1[OH:87])(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.C(OCC)(=O)C>[Cl:76][C:73]1[CH:74]=[C:75]2[C:67]([C:62]3[N:61]=[C:60]([NH:59][C@H:55]4[CH2:56][CH2:57][CH2:58][C@@:53]([CH3:88])([OH:52])[C@@H:54]4[OH:87])[C:65]([F:66])=[CH:64][N:63]=3)=[CH:68][NH:69][C:70]2=[N:71][CH:72]=1
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3ncc(F)c(N[C@H]4CCC[C@@](C)(O[Si](C)(C)C(C)(C)C)[C@@H]4O)n3)c3cc(Cl)cnc32)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: Cc1ccc(S(=O)(=O)n2cc(-c3c(C)ncc(F)c3N[C@H]3CCC[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H]3O)c3cc(Cl)cnc32)cc1
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: C[C@@]1(O)CCC[C@H](Nc2nc(-c3c[nH]c4ncc(Cl)cc34)ncc2F)[C@H]1O
Reaction time: 1.5 h

Procedure:
To a stirred solution of (1R,2R,6S)-2-[tert-butyl(dimethyl)silyl]oxy-6-[[2-methyl[5-chloro-1-(p-tolylsulfonyl)-pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyridin-4-yl]amino]cyclohexanol, 50f, (0.11 g; 0.16 mmol) in THF (2 mL) at room temperature, was added tetrabutylammonium fluoride (1.5 equiv) and the reaction mixture stirred for 1.5 h, at which point HPLC-analysis revealed no starting material but the de-tosylated product was observed with minor desilylation. An additional equivalent of TBAF was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was suspended in ethyl acetate (10 mL), washed with H2O (2×4 mL), aqueous saturated NH4Cl solution (2 mL) and brine (2 mL). The organic phase was dried (Na2SO4) and concentrated in vacuo to provide 139 mg of crude. The crude residue was purified by reverse phase HPLC (5-95% MeOH/water w/HCl buffer over 15 minutes). to afford 15 mg of desired product, 860. LCMS M+1=392.34
Reaction SMILES: Cl[C:2]1[S:3][C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:5]([CH3:7])[N:6]=1.[Cl:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[OH:21].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Cl:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[O:21][C:2]1[S:3][C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:5]([CH3:7])[N:6]=1
Reactant: CCOC(=O)c1sc(Cl)nc1C
Reactant: Oc1ccc(Cl)cc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)c1sc(Oc2ccc(Cl)cc2Cl)nc1C
Yield: 58.2 %

Procedure:
A mixture of 6.24 g (0.03 mole) of ethyl 2-chloro-4-methyl-5-thiazolecarboxylate, 4.89 g (0.03 mole) of 2,4-dichlorophenol, 4.14 g (0.03 mole) of potassium carbonate and 40 ml. of acetone was held at reflux for 89 hours. Acetone was removed under reduced pressure. The residue was treated with 50 ml. of water and extracted with ether. The ether solution was washed successively with saturated sodium bicarbonate, 30 ml. of 10% sodium hydroxide and 50 ml. of water. The ether solution was dried (MgSO4) and concentrated. The residue was recrystallized from hexane to give 5.8 g (58%) of ethyl 2-(2',4'-dichlorophenoxy)-4-methyl-5-thiazolecarboxylate as a white solid, m.p. 71°-73° C.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]([OH:9])=O)=[CH:3][CH:2]=1.[C:10]1([O:18][CH3:19])[C:11](=[CH:14][CH:15]=[CH:16][CH:17]=1)[O:12][CH3:13]>>[CH3:13][O:12][C:11]1[C:10]([O:18][CH3:19])=[CH:17][CH:16]=[CH:15][C:14]=1[C:7]([C:4]1[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=1)=[O:9]
Reactant: COc1ccccc1OC
Reactant: O=C(O)c1ccncc1
Product: COc1cccc(C(=O)c2ccncc2)c1OC

Procedure:
In Scheme H, step d, 4-pyridinecarboxylic acid (18) is reacted with lithiated veratrole to give 4-(2,3-dimethoxybenzoyl)pyridine (12).
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[C:4]([Cl:11])[C:3]=1[S:12](Cl)(=[O:14])=[O:13].[NH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(N(CC)CC)C>>[C:17]1([NH:16][S:12]([C:3]2[C:4]([Cl:11])=[CH:5][CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]=2[Cl:1])(=[O:14])=[O:13])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=[N+]([O-])c1ccc(Cl)c(S(=O)(=O)Cl)c1Cl
Reactant: Nc1ccccc1
Solvent: CCN(CC)CC
Product: O=[N+]([O-])c1ccc(Cl)c(S(=O)(=O)Nc2ccccc2)c1Cl
Yield: 4.7 %

Procedure:
Following the general procedure for sulfonamide formation outlined in example 15, 2,6-dichloro-3-nitrobenzenesulfonyl chloride (540 mg, 1.85 mmol), aniline (173 mg, 1.85 mmol) and triethylamine (0.61 mL, 5.55 mmol) were reacted to form the desired product (1 30 mg, 20%). 1NMR (MeOD-d4): δ7.65 (d, 1H), 7.58 (d, 1H), 7.40 (t, 2H), 7.15 (m, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6](Cl)[N:5]2[N:9]=[CH:10][CH:11]=[C:4]2[N:3]=1.[NH4+:12].[OH-]>>[Cl:1][C:2]1[CH:7]=[C:6]([NH2:12])[N:5]2[N:9]=[CH:10][CH:11]=[C:4]2[N:3]=1
Reactant: [NH4+]
Reactant: Clc1cc(Cl)n2nccc2n1
Agent: [OH-]
Product: Nc1cc(Cl)nc2ccnn12
Temperature: 85 °C

Procedure:
To 5,7-dichloropyrazolo[1,5-a]pyrimidine (7.6 g, 40.4 mmol) in a sealed vessel was added NH4OH (100 mL). The vessel was then sealed and heated at 85° C. for 2.5 hours, at which time the consistency of the white solid had changed (from foamy white solid to free-flowing white solid). The vessel was removed from the heat source and allowed to cool to room temperature overnight. On cooling, the contents of the vessel were collected and dried by vacuum filtration giving 5-chloropyrazolo[1,5-a]pyrimidin-7-amine as a yellow-tinged white solid (6.8 g).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1.[CH2:9]([NH2:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([NH:16][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:3][CH:4]=1
Reactant: Cc1ccc(Cl)cc1
Reactant: NCc1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)[O-]
Solvent: Cc1ccccc1
Product: Cc1ccc(NCc2ccccc2)cc1
Yield: 94.9 %

Procedure:
According to the general procedure A, 4-chlorotoluene (128 mg, 1.01 mmol) reacted with benzylamine (128 mg, 1.19 mmol) using 1 mol % of Pd(OAc)2, 2 mol % of Ph5FcP(t-Bu)2, and sodium tert-butoxide (122 mg, 1.27 mmol) in toluene at 100° C. to give the title compound (189 mg, 95%) as a colorless oil: 1H-NMR (400 MHz, CDCl3): δ 7.43-7.38 (m, 4H), 7.34-7.30 (m, 1H), 7.04 (d, 2H, J=8.26 Hz), 6.61 (d, 2H, J=8.37 Hz), 4.35 (s, 2H), 3.95 (bs, 1H), 2.29 (s, 3H). 13C{1H}-NMR (100 MHz, CDCl3): δ 145.85, 139.59, 129.70, 128.55, 127.45, 127.10, 126.68, 112.93, 48.56, 20.37. GC/MS(EI): m/z 197 (M+). Anal. Calcd for C14H15N. C, 85.24; H, 7.66; N, 7.10. Found C, 85.29; H, 7.68; N, 7.14.
Reaction SMILES: [NH2:1][C:2]1[C:11]([F:12])=[C:10](F)[CH:9]=[C:8]2[C:3]=1[C:4](=[O:20])[C:5]([C:17]([OH:19])=[O:18])=[CH:6][N:7]2[CH:14]1[CH2:16][CH2:15]1.[N:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[NH:27][CH2:28][CH2:29][NH2:30].C(N(CC)CC)C.[NH4+].[Cl-]>CS(C)=O>[NH2:1][C:2]1[C:11]([F:12])=[C:10]([NH:30][CH2:29][CH2:28][NH:27][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][N:21]=2)[CH:9]=[C:8]2[C:3]=1[C:4](=[O:20])[C:5]([C:17]([OH:19])=[O:18])=[CH:6][N:7]2[CH:14]1[CH2:16][CH2:15]1
Reactant: Nc1c(F)c(F)cc2c1c(=O)c(C(=O)O)cn2C1CC1
Reactant: NCCNc1ccccn1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: Nc1c(F)c(NCCNc2ccccn2)cc2c1c(=O)c(C(=O)O)cn2C1CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 90.5 %

Procedure:
A solution of 5-amino-1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (300 mg, 1.07 mmol), N-2-pyridyl-1,2-ethanediamine (221 mg, 1.61 mmol) and triethylamine (0.224 mL, 1.61 mmol) in DMSO (5 mL) was stirred at 100° C. for 3 h. After the reaction mixture was cooled to room temperature, 10% aq. NH4Cl was added to neutralize and the suspension was stirred for 30 min. The resulting precipitate was collected by filtration in vacuo, washed with water and hot EtOH, dried to yield 5-amino-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-[2-(2-pyridylamino)ethylamino]quinoline-3-carboxylic acid (385 mg, 91%) as a colorless solid.
Reaction SMILES: [OH:1][C:2]1[C:3]2[CH:18]=[C:17]3[C:12]([CH:13]=[CH:14][CH:15]=[CH:16]3)=[CH:11][C:4]=2[O:5][C:6]=1[C:7]([O:9][CH3:10])=[O:8].[C:19](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O>CC(C)=O>[CH3:19][O:1][C:2]1[C:3]2[CH:18]=[C:17]3[C:12]([CH:13]=[CH:14][CH:15]=[CH:16]3)=[CH:11][C:4]=2[O:5][C:6]=1[C:7]([O:9][CH3:10])=[O:8]
Reactant: COC(=O)c1oc2cc3ccccc3cc2c1O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: COS(=O)(=O)OC
Solvent: CC(C)=O
Product: COC(=O)c1oc2cc3ccccc3cc2c1OC
Reaction time: 24 h
Yield: 77 %

Procedure:
A mixture of 25.0 g (0.10 mole) of 3-hydroxynaphtho [2,3-b]furan-2-carboxylic acid, methyl ester, 15.3 g (0.11 mole) of anhydrous potassium carbonate, and 10.6 ml (14.1 g, 11 mole of dimethyl sulfate in 500 ml of acetone is stirred at refux for 24 hours. The mixture is cooled, filtered, and the filter cake is washed several times with fresh acetone. The combined filtrates are evaporated (vacuum), and the residue is recrystallized from methanol to yield 20.3 g (77% yield) of the analytically pure 3-methoxynaphtho[2,3-b]furan-2-carboxylic acid, methyl ester, mp 121°-124 ° C.
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:33])[NH:10][C@H:11]1[CH2:15][CH2:14][C@H:13]([O:16][CH2:17][C:18]([C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=2)=CC2C=CC=CC=2)[CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:34]=[O+][O-]>ClCCl>[CH2:1]([O:8][C:9](=[O:33])[NH:10][C@H:11]1[CH2:15][CH2:14][C@H:13]([O:16][CH2:17][C:18](=[O:34])[C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=2)[CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1ccc(C(=Cc2ccccc2)CO[C@H]2CC[C@H](NC(=O)OCc3ccccc3)C2)cc1
Reactant: O=[O+][O-]
Solvent: ClCCl
Product: Cc1ccc(C(=O)CO[C@H]2CC[C@H](NC(=O)OCc3ccccc3)C2)cc1
Temperature: 25 °C

Procedure:
To a stirred solution of 10 g of trans [3-(3-phenyl-2-p-tolyl-allyloxy)-cyclopentyl]-carbamic acid benzyl ester in 500 mL of dichloromethane cooled to −78° C. was dispersed a stream of ozone from an ozone generator until a blue color persisted. The excess ozone was purged with nitrogen until the blue color dissipated, and 20 mL of methyl sulfide was added. After warming to room temperature over 30 min, the solution was concentrated under reduced pressure. Chromatography over silica gel eluting with a gradient of 5%-45% ethyl acetate in hexane gave 6.5 g of product as a white crystalline solid: MS (m+1)=368.3; 1H NMR (400 MHz, CDCl3) 7.35 (m, 2H), 7.1 (m, 5H), 7.0 (m, 2H), 5.1 (s, 2H), 4.7 (m, 1H), 4.2 (s, 2H), 4.1 (m, 1H), 2.35 (s, 3H), 2.2 (m, 2H), 1.95 (m, 1H), 1.74 (m, 1H), 1.6 (m, 1H), 1.4 (m, 1H).
Reaction SMILES: Cl.[NH2:2][C@H:3]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].C(N(CC)CC)C.[N+:23]([C:26]1[CH:27]=[C:28]([CH:32]=[C:33]([N+:35]([O-:37])=[O:36])[CH:34]=1)[C:29](Cl)=[O:30])([O-:25])=[O:24]>O1CCCC1>[N+:23]([C:26]1[CH:27]=[C:28]([CH:32]=[C:33]([N+:35]([O-:37])=[O:36])[CH:34]=1)[C:29]([NH:2][C@H:3]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])=[O:30])([O-:25])=[O:24]
Reactant: O=C(Cl)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Reactant: CCOC(=O)C[C@H](N)c1ccccc1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCOC(=O)C[C@H](NC(=O)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1)c1ccccc1
Temperature: 5 °C
Reaction time: 0.33 h

Procedure:
11.49 g of ethyl (S)-3-amino-3-phenylpropionate hydrochloride were suspended in 100 ml of tetrahydrofuran and cooled to 0-10° C. in an icebath. After adding 14 ml of triethylamine, a solution of 11.52 g of 3,5-dinitrobenzoyl chloride in 40 ml of tetrahydrofuran was added with stirring and cooling over a period of 30 min. The cooling bath was removed, and the reaction mixture stirred for a further 120 min, in the course of which it warmed to room temperature. The reaction mixture was filtered, and the filtrate concentrated to dryness (product fraction 1). The filtercake—consisting of triethylamine hydrochloride and further product—was taken up in 100 ml of ethyl acetate and digested at 35° C. for 20 min. The suspension was filtered, and the filtercake discarded. The filtrate was concentrated to dryness under reduced pressure at 40° C. (product fraction 2). The product fractions were combined. Yield: 16.4 g; HPLC purity >97 area %. For further purification, the crude product was digested in 400 ml of water at room temperature for 2 h and then filtered. The moist yield was 15.4 g; HPLC purity 99.8 area %. The product was reacted further without further purification.
Reaction SMILES: [N:1]1([CH:7]2[CH2:12][CH2:11][CH:10]([NH:13][C:14](=[O:28])[C:15]3[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[C:17]([O:24][CH2:25][C:26]#[CH:27])[CH:16]=3)[CH2:9][CH2:8]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Sn](Cl)Cl.N>C(OCC)(=O)C.CO>[NH2:21][C:18]1[CH:19]=[CH:20][C:15]([C:14]([NH:13][CH:10]2[CH2:11][CH2:12][CH:7]([N:1]3[CH2:2][CH2:3][O:4][CH2:5][CH2:6]3)[CH2:8][CH2:9]2)=[O:28])=[CH:16][C:17]=1[O:24][CH2:25][C:26]#[CH:27]
Reactant: C#CCOc1cc(C(=O)NC2CCC(N3CCOCC3)CC2)ccc1[N+](=O)[O-]
Agent: Cl[Sn]Cl
Agent: N
Solvent: CCOC(C)=O
Solvent: CO
Product: C#CCOc1cc(C(=O)NC2CCC(N3CCOCC3)CC2)ccc1N
Temperature: 50 °C
Reaction time: 16 h

Procedure:
38.7 g (0.1 mol) N-(4-morpholin-4-yl-cyclohexyl)-4-nitro-3-prop-2-ynyloxy-benzamide are dissolved in 400 ml of ethyl acetate and 25 ml of methanol. To this solution are added 75 g tin (II)chloride.3H2O. The mixture is stirred for 16 h at 50° C. Then it is cooled to ambient temperature and 80 ml of conc. aqueous ammonia are added.