Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH:5]=[C:4]([C:6]([OH:8])=O)[N:3]=[CH:2]1.C(Cl)(=O)C(Cl)=O.[NH2:15][C:16]1[N:45]=[C:19]2[CH:20]=[CH:21][C:22]([O:24][C:25]3[CH:26]=[C:27]([NH:31][C:32](=[O:44])[C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([C:42]#[N:43])([CH3:41])[CH3:40])[CH:34]=4)[CH:28]=[CH:29][CH:30]=3)=[CH:23][N:18]2[N:17]=1.C(=O)([O-])O.[Na+]>O1CCCC1.N1C=CC=CC=1.CN(C)C=O>[C:42]([C:39]([C:35]1[CH:34]=[C:33]([C:32]([NH:31][C:27]2[CH:26]=[C:25]([CH:30]=[CH:29][CH:28]=2)[O:24][C:22]2[CH:21]=[CH:20][C:19]3[N:18]([N:17]=[C:16]([NH:15][C:6]([C:4]4[N:3]=[CH:2][O:1][CH:5]=4)=[O:8])[N:45]=3)[CH:23]=2)=[O:44])[CH:38]=[CH:37][CH:36]=1)([CH3:41])[CH3:40])#[N:43]
Reactant: CC(C)(C#N)c1cccc(C(=O)Nc2cccc(Oc3ccc4nc(N)nn4c3)c2)c1
Reactant: O=C(O)c1cocn1
Agent: O=C(Cl)C(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: c1ccncc1
Solvent: CN(C)C=O
Product: CC(C)(C#N)c1cccc(C(=O)Nc2cccc(Oc3ccc4nc(NC(=O)c5cocn5)nn4c3)c2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 80.6 %

Procedure:
To a solution of 1,3-oxazole-4-carboxylic acid (145 mg, 1.29 mmol) in tetrahydrofuran (3 mL) were added oxalyl chloride (157 μL, 1.80 mmol) and N,N-dimethylformamide (20 μL), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure. The obtained residue and the above-mentioned N-{3-[(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide (213 mg, 516 μmol) were dissolved in pyridine (8 mL), and the mixture was stirred at room temperature for 25 hr. A saturated aqueous sodium hydrogen carbonate solution (10 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20 mL, 2×10 mL). The combined organic layer was washed with saturated brine (5 mL) and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/methanol=100/0→97/3), and fractions containing the desired product were concentrated under reduced pressure. Diisopropyl ether was added to the obtained residue. The obtained precipitate was collected by filtration and dried to give the title compound (211 mg, 81%) as a colorless powder.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[CH2:11][CH2:12][C:13]([N:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1)=[O:14].[C:20](=O)([O-])[O-].[K+].[K+].IC>CN(C)C=O>[CH3:20][O:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[CH2:11][CH2:12][C:13]([N:15]1[CH2:16][CH2:17][CH2:18][CH2:19]1)=[O:14]
Reactant: O=C(CCc1ccc([N+](=O)[O-])cc1O)N1CCCC1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: COc1cc([N+](=O)[O-])ccc1CCC(=O)N1CCCC1
Reaction time: 5 h
Yield: 94.1 %

Procedure:
This amide (900 mg, 3.4 mmol) was dissolved in dimethylformamide (100 ml) and potassium carbonate (516 mg) added, followed by iodomethane (0.6 ml, 3.7 mmol). The solution was stirred for 5 hours, then concentrated in vacuo. The residual oil was partitioned between ethyl acetate (50 ml) and H2O (50 ml), the aqueous layer extracted with ethyl acetate (3×50 ml), the combined organic phases washed with brine (20 ml), dried (MgSO4) and evaporated to yield 3-(2-methoxy-4-nitrophenyl)-1-pyrrolidin-1-yl-propan-1-one as a black oil (900 mg, 3.2 mmol);
Reaction SMILES: I[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:9]=1[NH:10][C:11]1[C:12]([CH3:20])=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[CH:14]2)[C:7]#[N:8].[CH3:21][O:22][CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][C:29](B2OC(C)(C)C(C)(C)O2)=[CH:28][CH:27]=1.O>COCCOC.C([O-])(O)=O.[Na+].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>[CH3:21][O:22][CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([C:9]=2[NH:10][C:11]2[C:12]([CH3:20])=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[CH:14]3)[C:7]#[N:8])=[CH:28][CH:27]=1
Reactant: COCCOc1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Reactant: Cc1c(Nc2c(I)cncc2C#N)ccc2[nH]ccc12
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
Solvent: O
Product: COCCOc1ccc(-c2cncc(C#N)c2Nc2ccc3[nH]ccc3c2C)cc1
Temperature: 95 °C
Yield: 69.7 %

Procedure:
A mixture of 5-iodo-4[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile (100 mg, 0.27 mmol), 2-[4-(2-methoxyethoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (98 mg, 0.35 mmol), and tetrakis(triphenylphosphine)palladium(0) (16 mg, 0.014 mmol) in DME (6 mL) and saturated aqueous NaHCO3 (4 mL) was heated at 95° C. for 3 h, cooled to room temperature, and treated with water. The precipitate was filtered, washed with water, dried in vacuo, and purified by flash column chromatography (MeOH/CH2Cl2, 2% to 4%) to provide 75 mg (70%) of 5-[4-(2-methoxyethoxy)phenyl]-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile as a tan solid. HPLC retention time: 8.2 min.(g); MS: 399.3 (M+H); melting range: 208-210° C.; and HRMS: 399.18056.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[CH2:4][C:5](=O)[CH2:6][S:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][CH3:15])[CH:9]=1.[CH3:18]S(O)(=O)=O>ClCCl>[CH3:1][O:2][C:3](=[O:17])[CH2:4][C:5]1[C:13]2[CH:12]=[C:11]([CH3:18])[C:10]([O:14][CH3:15])=[CH:9][C:8]=2[S:7][CH:6]=1
Reactant: COC(=O)CC(=O)CSc1cccc(OC)c1
Reactant: CS(=O)(=O)O
Solvent: ClCCl
Product: COC(=O)Cc1csc2cc(OC)c(C)cc12

Procedure:
A solution of compound 78A from the preceding step (8.6 g, 32 mmol) in 30 mL of dichloromethane was added dropwise to 30 mL of methanesulfonic acid stirred under N2 at icebath temperature. The mixture was allowed to warn gradually to room temperature. After an hour 200 mL of icewater was cautiously added (vigorous reaction!), then the mixture was partitioned between a total of 300 mL of water and 350–400 mL of dichloro-methane. The organic layer was drawn off and washed with water, then 0.5M aq NaHCO3, and dried over MgSO4. The solvent was removed in vacuo, and the residue dissolved in a minimum of CHCl3/EtOAc (24:1) and passed slowly through a column of silica gel, eluting with several column volumes of the same solvent. The effluent was stripped of solvent in vacuo to leave the title compound as a clear amber syrup, contaminated with the other possible regio-isomer, but of sufficient purity for the next step.
Reaction SMILES: [NH2:1][C:2]1[C:3]([Cl:9])=[N:4][CH:5]=[CH:6][C:7]=1[NH2:8].[C:10](N1C=CN=C1)(N1C=CN=C1)=[O:11]>C1COCC1>[Cl:9][C:3]1[C:2]2[NH:1][C:10]([OH:11])=[N:8][C:7]=2[CH:6]=[CH:5][N:4]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: Nc1ccnc(Cl)c1N
Solvent: C1CCOC1
Product: Oc1nc2ccnc(Cl)c2[nH]1
Yield: 86.5 %

Procedure:
1.1 A solution of 17.23 g of 3,4-diamino-2-chloropyridine and 19.46 g of 1,1′-carbonyldiimidazole in THF is stirred at room temperature for 16 hours. The product is separated off and dried, giving 17.6 g of 4-chloro-3H-imidazo[4,5-c]pyridin-2-ol (“1”).
Reaction SMILES: C(OC([N:8]1[C:17]2[C:12](=[CH:13][C:14](B(O)O)=[CH:15][CH:16]=2)[C:11]([CH3:21])=[CH:10][C:9]1([CH3:23])[CH3:22])=O)(C)(C)C.[F:24][C:25]1[CH:26]=[C:27]([N+:32]([O-:34])=[O:33])[CH:28]=[C:29](I)[CH:30]=1>>[F:24][C:25]1[CH:26]=[C:27]([N+:32]([O-:34])=[O:33])[CH:28]=[C:29]([C:14]2[CH:13]=[C:12]3[C:17](=[CH:16][CH:15]=2)[NH:8][C:9]([CH3:22])([CH3:23])[CH:10]=[C:11]3[CH3:21])[CH:30]=1
Reactant: CC1=CC(C)(C)N(C(=O)OC(C)(C)C)c2ccc(B(O)O)cc21
Reactant: O=[N+]([O-])c1cc(F)cc(I)c1
Product: CC1=CC(C)(C)Nc2ccc(-c3cc(F)cc([N+](=O)[O-])c3)cc21
Yield: 69.1 %

Procedure:
This compound was prepared according to General Method 2 (EXAMPLE 9 ) from Compound 9 (140.2 mg, 0.44 mmol) and 5-fluoro-3-nitroiodobenzene (117.6 mg, 0.44 mmol). The crude material was purified by flash column chromatography (150 ml silica, hexane to 20% acetone/hexane) followed by a second flash column chromatography (100 mL silica, hexane to 20% acetone/hexane) to afford 95 mg (69%) of Compound 280. Data for Compound 280: 1H NMR (400 MHz, acetone-d6) 8.22 (app t, J=3.0, 1.5, 1H), 7.78 (m, 1H), 7.43 (d, J=2.2, 1H), 7.38 (dd, J=8.4, 2.3, 1H), 6.61 (d, J=8.3, 1H), 5.58 (s, 1H), 5.40 (s, 1H), 2.05 (s, 3H), 1.29 (s, 6H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([NH:12][C:13]([C:15]2[CH:16]=[C:17]([CH:21]3[C:30]([CH3:32])([CH3:31])[CH2:29][C:28]4[C:23](=[CH:24][CH:25]=[C:26]([C:33]([O:35]C)=[O:34])[CH:27]=4)[NH:22]3)[CH:18]=[CH:19][CH:20]=2)=[O:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]([NH:12][C:13]([C:15]2[CH:16]=[C:17]([CH:21]3[C:30]([CH3:32])([CH3:31])[CH2:29][C:28]4[C:23](=[CH:24][CH:25]=[C:26]([C:33]([OH:35])=[O:34])[CH:27]=4)[NH:22]3)[CH:18]=[CH:19][CH:20]=2)=[O:14])[CH2:11]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)c1ccc2c(c1)CC(C)(C)C(c1cccc(C(=O)NC3CN(C(=O)OC(C)(C)C)C3)c1)N2
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CC(NC(=O)c2cccc(C3Nc4ccc(C(=O)O)cc4CC3(C)C)c2)C1

Procedure:
A mixture of methyl 2-(3-(1-(tert-butoxycarbonyl)azetidin-3-ylcarbamoyl)phenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate (234 mg, 0.44 mmol of theory) in methanol (6.8 mL) and 1 M sodium hydroxide aqueous solution (5.3 mL, 5.3 mmol, 12.0 eq.) was heated to reflux for 60 min, LC-MS showed the reaction was complete and only the desired product formed. The solvent was concentrate in vacuo and the residue was dissolved in water and acidified with 1 M hydrochloric acid solution to pH=6. The white precipitated solid was extracted with tetrahydrofuran (twice). The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate. Removal of the solvent gave 209 mg product as a white solid, which was purified by column chromatography (Pure ethyl acetate) to afford 78 mg of 2-(3-(1-(tert-butoxycarbonyl)azetidin-3-ylcarbamoyl)phenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylic acid as a white solid. Yield: 37.2%. MS (ESI+APCI) M+1=480.2.
Reaction SMILES: C([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11][CH2:12][CH2:13][O:14][CH3:15])=[CH:7][C:6]=1[N+:16]([O-:18])=[O:17])(=O)C.[OH-].[Na+]>CO>[NH2:4][C:5]1[CH:10]=[CH:9][C:8]([S:11][CH2:12][CH2:13][O:14][CH3:15])=[CH:7][C:6]=1[N+:16]([O-:18])=[O:17]
Reactant: COCCSc1ccc(NC(C)=O)c([N+](=O)[O-])c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: COCCSc1ccc(N)c([N+](=O)[O-])c1

Procedure:
1.4 G. of 1-acetamido-2-nitro-4-methoxyethylthiobenzene is treated with 3 ml. 5N sodium hydroxide and 6 ml. methanol in the steam bath for about 15 minutes. The mixture is stripped under vacuum and the residue extracted with chloroform. The dried extracts are evaporated giving 1-amino-2-nitro-4-methoxyethylthiobenzene as a red crystalline solid.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]=[C:17]([NH:20][CH2:21][C:22]([OH:24])=O)[S:18][CH:19]=2)=[CH:11][CH:10]=1.[NH:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[N:16]=[C:17]([NH:20][CH2:21][C:22]([N:25]3[CH2:29][CH2:28][CH2:27][CH2:26]3)=[O:24])[S:18][CH:19]=2)=[CH:13][CH:14]=1
Reactant: C1CCNC1
Reactant: O=C(O)CNc1nc(-c2ccc(F)cc2)cs1
Solvent: O=C(O)C(F)(F)F
Product: O=C(CNc1nc(-c2ccc(F)cc2)cs1)N1CCCC1

Procedure:
The title compound was prepared analogously as described in Example 30(d) from 100 mg (0.27 mmol) of [4-(4-fluoro-phenyl)-thiazol-2-ylamino]-acetic acid trifluoroacetic acid salt and 38.8 mg (0.54 mmol) of pyrrolidine. Yield: 17 mg.
Reaction SMILES: [CH2:1]([N:3]1[CH2:8][CH2:7][CH2:6][CH:5]([OH:9])[CH2:4]1)[CH3:2].[OH-].[Na+].Cl[C:13]1[N:18]=[C:17]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([Cl:28])[CH:21]=2)[N:16]=[C:15]([NH:29][CH:30]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[N:14]=1>C1C=CC=CC=1>[Cl:28][C:22]1[CH:21]=[C:20]([NH:19][C:17]2[N:16]=[C:15]([NH:29][CH:30]3[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]3)[N:14]=[C:13]([O:9][CH:5]3[CH2:6][CH2:7][CH2:8][N:3]([CH2:1][CH3:2])[CH2:4]3)[N:18]=2)[CH:25]=[CH:24][C:23]=1[O:26][CH3:27]
Reactant: COc1ccc(Nc2nc(Cl)nc(NC3CCCCCC3)n2)cc1Cl
Reactant: CCN1CCCC(O)C1
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccccc1
Product: CCN1CCCC(Oc2nc(Nc3ccc(OC)c(Cl)c3)nc(NC3CCCCCC3)n2)C1
Temperature: 25 °C

Procedure:
A mixture of N-ethyl-3-hydroxypiperidine (0.3 g, 2.3 mmol) and NaOH (94 mg, 2.3 mmol) in benzene (10 ml) was heated to reflux for 2 hr with stirring under nitrogen atmosphere and then cooled to 25° C. followed by the addition of compound 133 (0.3 g, 0.78 mmol) at same temperature. The mixture was heated to reflux for 12 hrs., concentrated under vacuum and diluted with water (10 ml). The solid precipitated was filtered off and washed with petroleum ether to afford the title compound as a off white solid (0.3 g, 81%). mp 62-64° C.; HPLC: HICHROM RPB (250×4.6 mm) 5 microns [solvent A=0.01 M KH2PO4 (pH 6.0); solvent B=CH3CN], Gradient elution program: T/% B=0/40, 5/40, 25/80, 35/80, 40/40, 45/40; 270 nm, Rt 26.83 min, 93.65% purity; MS (CI): m/z 447 (M+, 100).
Reaction SMILES: [Cl:1][C:2]1[C:10]([C:11]2[CH:12]=[N:13][CH:14]=[C:15]([CH:17]=[CH2:18])[CH:16]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][C:5](=[O:20])[N:6]2[CH3:19]>C(O)C.[Pd]>[Cl:1][C:2]1[C:10]([C:11]2[CH:12]=[N:13][CH:14]=[C:15]([CH2:17][CH3:18])[CH:16]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][C:5](=[O:20])[N:6]2[CH3:19]
Reactant: C=Cc1cncc(-c2ccc3c(c2Cl)CC(=O)N3C)c1
Agent: [Pd]
Solvent: CCO
Product: CCc1cncc(-c2ccc3c(c2Cl)CC(=O)N3C)c1
Reaction time: 0.42 h

Procedure:
To a solution of 4-chloro-1-methyl-5-(5-vinyl-pyridin-3-yl)-1,3-dihydro-indol-2-one (70 mg, 0.246 mmol) in ethanol (5 mL) was added 10% palladium on carbon (39 mg, 0.037 mmol). The atmosphere over the reaction mixture was evacuated and the reaction was placed under an atmosphere of hydrogen gas via a balloon. The reaction was stirred for 25 minutes. The reaction mixture was then filtered through a plug of Celite® and the filtrate was then concentrated to dryness. The resulting residue was purified by silica gel flash chromatography (ethanol-dichloromethane, 0 to 5%) to afford 4-chloro-5-(5-ethyl-pyridin-3-yl)-1-methyl-1,3-dihydro-indol-2-one. HRMS: (ESI) m/z 287.0946 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 1.33 (t, J=7.6 Hz, 3H), 2.76 (q, J=7.6 Hz, 2H), 3.27 (s 3H), 3.61 (s, 2H), 6.85 (d, J=8.0 Hz, 1H), 7.30 (d, J=8.0 Hz, 1H), 7.68 (s, 1H), 8.45-8.57 (m, 2H).
Reaction SMILES: C([O-])([O-])OCC.[C:7]([C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[C:16]([CH3:21])([CH3:20])[CH2:15][CH2:14][C:13]2([CH3:23])[CH3:22])(=[O:9])[CH3:8].[CH2:24](O)[CH:25]([OH:27])[CH3:26]>C(Cl)(=O)C.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O)C.C1(C)C=CC=CC=1>[CH3:8][C:7]1([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[C:16]([CH3:21])([CH3:20])[CH2:15][CH2:14][C:13]3([CH3:23])[CH3:22])[O:27][CH:25]([CH3:26])[CH2:24][O:9]1
Reactant: CC(=O)c1ccc2c(c1)C(C)(C)CCC2(C)C
Reactant: CC(O)CO
Agent: CCOC([O-])[O-]
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC(=O)Cl
Solvent: Cc1ccccc1
Solvent: CCO
Product: CC1COC(C)(c2ccc3c(c2)C(C)(C)CCC3(C)C)O1
Reaction time: 2 h
Yield: 63.2 %

Procedure:
Acetyl chloride (0.15 g) is added dropwise at room temperature to a mixture of 52.5 g (0.35 mol) of ethyl orthoformate, 30 g (0.13 mol) of 6-acetyl-1,1,4,4-tetra-methyl-tetralin and 18 ml of ethanol. The reaction is slightly exothermic, which results in a temperature increase from 20° C. to 28° C. The mixture is stirred at this temperature for 2 hours. The excess ethyl orthoformate and ethanol are removed by vacuum distillation (120° C./ 100 mm Hg). After this time the reaction mixture is cooled and 50 ml of toluene, 22.5 g (0.29 mol) of propylene glycol and 0.3 g of p-toluenesulphonic acid are added rapidly. The mixture is stirred at 85° C. to 90° C. for 2 1/2 hours. The ethanol which is formed is removed by distillation. Thereupon, the residual mixture is neutralized by the addition of a 10% solution of potassium hydroxide in ethanol, filtered and the filtrate is evaporated. Crude 2-dimethyl-2-(1,1,4,4-tetramethyl-tetralin-6-yl)-1,3-dioxolane is obtained. The product is purified by vacuum distillation and there are obtained 23.7 g of pure product. The boiling point of the pure product is 112° C. at 0.45 mmHg.
Reaction SMILES: C(O)(CC)C.[N+:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N:15]=[N:16][C:17]1[CH:22]=[C:21]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:20]=[CH:19][C:18]=1[OH:27])([O-:8])=O.[N+](C1C=CC=CC=1N=NC1C=C(C(C)(C)C)[CH:42]=[C:41]([C:49](C)(C)C)[C:40]=1O)([O-])=O>C(O)CCCCCCC>[OH:27][C:18]1[C:19]([C:41]([CH3:49])([CH3:42])[CH3:40])=[CH:20][C:21]([C:23]([CH3:26])([CH3:24])[CH3:25])=[CH:22][C:17]=1[N:16]1[N+:6]([O-:8])=[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]2=[N:15]1
Reactant: CC(C)(C)c1ccc(O)c(N=Nc2ccccc2[N+](=O)[O-])c1
Reactant: CC(C)(C)c1cc(N=Nc2ccccc2[N+](=O)[O-])c(O)c(C(C)(C)C)c1
Solvent: CCC(C)O
Solvent: CCCCCCCCO
Product: CC(C)(C)c1cc(-n2nc3ccccc3[n+]2[O-])c(O)c(C(C)(C)C)c1
Yield: 82.9 %

Procedure:
The same procedure as in Example 7 was repeated, except that secondary butanol 80 g was replaced by n-octanol 50 g, and that 2-nitro-2'-hydroxy-5'-t-butylazobenzene 19.9 g was replaced by 2-nitro-2'-hydroxy-3',5'-di-t-butylazobenzene 23.7 g, thus producing 18.7 g of 2-(2-hydroxy-3,5-di-t-butylphenyl)benzotriazole-N-oxide having a melting point of 168° to 171° C. at the yield of 83.0%.
Reaction SMILES: FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[C:16]1[N:21]=[C:20]([NH:22][CH:23]([CH3:26])[CH2:24][NH2:25])[N:19]2[CH:27]=[CH:28][N:29]=[C:18]2[CH:17]=1.[NH2:30][C:31]1[C:36]([N+:37]([O-:39])=[O:38])=[CH:35][CH:34]=[C:33](Cl)[N:32]=1.C(N(CC)C(C)C)(C)C>>[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[C:16]1[N:21]=[C:20]([NH:22][CH:23]([CH3:26])[CH2:24][NH:25][C:33]2[N:32]=[C:31]([NH2:30])[C:36]([N+:37]([O-:39])=[O:38])=[CH:35][CH:34]=2)[N:19]2[CH:27]=[CH:28][N:29]=[C:18]2[CH:17]=1
Reactant: CC(CN)Nc1nc(-c2ccc(Cl)cc2Cl)cc2nccn12
Reactant: Nc1nc(Cl)ccc1[N+](=O)[O-]
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: CC(CNc1ccc([N+](=O)[O-])c(N)n1)Nc1nc(-c2ccc(Cl)cc2Cl)cc2nccn12

Procedure:
N6-(2-{[7-(2,4-Dichlorophenyl)imidazo[1,2-c]pyrimidin-5-yl]amino}propyl)-3-nitropyridine-2,6-diamine (Example 83) is prepared in analogy to Example 82 from Example 37A (300 mg, 0.47 mmol), 2-amino-6-chloro-3-nitropyridine (161 mg, 0.93 mmol) and N,N-diisopropylethylamine (600 mg, 4.6 mmol). The crude product is reprecipitated from N,N-dimethylformamide and acetonitrile. The product is filtered off and washed with acetonitrile and dried. 99 mg (45% of theory) of the product are obtained as a solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C@H:11]([CH2:20][NH:21][CH3:22])[CH2:12][C:13]([O:15][C:16](C)(C)C)=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]>CO.Cl.O1CCOCC1>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C@H:11]([CH2:20][NH:21][CH3:22])[CH2:12][C:13]([O:15][CH3:16])=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]
Reactant: CNC[C@H](CC(=O)OC(C)(C)C)Nc1ccc(C#N)c(Cl)c1
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Product: CNC[C@H](CC(=O)OC)Nc1ccc(C#N)c(Cl)c1
Temperature: 60 °C

Procedure:
The 1,1-dimethylethyl (3S)-3-[(3-chloro-4-cyanophenyl)amino]-4-(methylamino)butanoate from the previous step (31.4 g) was dissolved in a mixture of MeOH (100 mL) and 4N HCl/dioxane (30 mL) and heated to 60° C. for 1.25 h. The solvents were concentrated to a slurry, Et2O (200 mL) was added, the solid filtered, washed well with Et2O to give the titled compound (15.6 g).
Reaction SMILES: [SH:1][C:2]1[S:3][C:4]2[CH2:14][CH2:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][C:11]=3[O:15][CH2:16][C:17]([O:19]CC)=[O:18])[C:5]=2[N:6]=1.[C:22]1([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C.O>[C:22]1([CH:28]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[S:1][C:2]2[S:3][C:4]3[CH2:14][CH2:13][C:12]4[C:7](=[CH:8][CH:9]=[CH:10][C:11]=4[O:15][CH2:16][C:17]([OH:19])=[O:18])[C:5]=3[N:6]=2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: CCOC(=O)COc1cccc2c1CCc1sc(S)nc1-2
Reactant: c1ccc(Cc2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: O=C(O)COc1cccc2c1CCc1sc(SC(c3ccccc3)c3ccccc3)nc1-2
Temperature: 60 °C
Reaction time: 3 h
Yield: 37 %

Procedure:
To a solution of ethyl [(2-mercapto-4,5-dihydronaphtho[1,2-d]thiazol-6-yl)oxy]acetate (1.10 g, 3.42 mmol) in N,N-dimethylformamide (20 mL) were added diphenylmethane hromide (0.93 g, 3.76 mmol) and potassium carbonate (0.52 g, 3.76 mmol), and the mixture was stirred at 60° C. for 3 hours. This reaction mixture was diluted with ethyl acetate and water and, after phase separation, the aqueous layer was extracted with ethyl acetate. The pooled organic solution was washed with water, dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure and the residue was dissolved in acetic acid (20 mL). To this solution was added concentrated sulfuric acid (10 ml), and the mixture was refluxed for 1 hour. After cooling, the reaction mixture was diluted with water and extracted with 2 portions of ethyl acetate. The pooled extract was washed with water, dried over MsGO4, and filtered. The filtrate was concentrated under reduced pressure and the residue was crystallized from hexane-ethyl acetate to provide 0.58 g of the title compound. Yield 37%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:10])=[C:6]([CH:9]=1)[CH:7]=[O:8].[C:11]([O:15][C:16](=[O:21])[C:17](Br)([CH3:19])[CH3:18])([CH3:14])([CH3:13])[CH3:12].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:11]([O:15][C:16](=[O:21])[C:17]([O:10][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:9][C:6]=1[CH:7]=[O:8])([CH3:19])[CH3:18])([CH3:14])([CH3:13])[CH3:12]
Reactant: CC(C)(C)OC(=O)C(C)(C)Br
Reactant: O=Cc1cc(Cl)ccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)C(C)(C)Oc1ccc(Cl)cc1C=O
Temperature: 110 °C
Yield: 53.6 %

Procedure:
5-Chloro-2-hydroxy-benzaldehyde (15.6 g, 100 mmol), 2-bromo-2-methyl-propionic acid tert-butyl ester (33.4 g, 150 mmol), K2CO3 (27.6 g, 200 mmol) and KI (3 g, 19 mmol) were mixed in DMF (100 mL). Then the reaction mixture was heated at 110° C. for 3 h. The mixture was filtered and the filtrate was concentrated. The residue was dissolved in ethyl acetate and washed with 1N NaOH. Then the organic layer was separated, dried over Na2SO4 and concentrated to give title compound (16 g)
Reaction SMILES: [I-].[OH:2][C@@H:3]([C@H:5]1[C:33](=[O:34])[N:7]2[C:8]([C:20]([O:22]CC3C=CC([N+]([O-])=O)=CC=3)=[O:21])=[C:9]([C:11]3[S:15][C:14]4=[CH:16][N:17]([CH3:19])[CH:18]=[N+:13]4[CH:12]=3)[CH2:10][C@H:6]12)[CH3:4].P([O-])([O-])([O-])=O>C1COCC1.[Pd]>[OH:2][C@@H:3]([C@H:5]1[C:33](=[O:34])[N:7]2[C:8]([C:20]([O-:22])=[O:21])=[C:9]([C:11]3[S:15][C:14]4=[CH:16][N:17]([CH3:19])[CH:18]=[N+:13]4[CH:12]=3)[CH2:10][C@H:6]12)[CH3:4]
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(c3c[n+]4cn(C)cc4s3)C[C@H]12
Agent: [Pd]
Agent: O=P([O-])([O-])[O-]
Agent: [I-]
Solvent: C1CCOC1
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)[O-])=C(c3c[n+]4cn(C)cc4s3)C[C@H]12
Temperature: 25 °C
Reaction time: 4 h
Yield: 16.7 %

Procedure:
To a solution of 58 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(6-methylimidazo[5,1-b]thiazolium-2-yl)-1-carbapen-2-em-3-carboxylate iodide in 2 ml of THF and 2 ml of 1/15 M phosphate buffer (pH 6.8) was added 68 mg of 10% Pd-C. The reactor was purged with hydrogen, and the reaction mixture was stirred at room temperature for 4 hours. The catalyst was collected by filtration on Celite, and washed with water. The filtrate was washed with ethyl acetate, the aqueous layer was purified by column chromatography on DIAION HP-20 to give 5.4 mg of the title compound.