Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[C@H:16]([NH:17][C:18](=[O:25])[CH2:19][C:20]3[S:21][CH:22]=[CH:23][CH:24]=3)[C:15](=[O:26])[N:10]2[C:11]=1[C:12]([OH:14])=[O:13])(=[O:3])[CH3:2].C(OC(=O)C)(=O)C>N1C=CC=CC=1>[C:1]([O:4][CH2:5][C:6]1[CH:11]([C:12]([OH:14])=[O:13])[N:10]2[C:15](=[O:26])[C@@H:16]([NH:17][C:18](=[O:25])[CH2:19][C:20]3[S:21][CH:22]=[CH:23][CH:24]=3)[C@H:9]2[S:8][CH:7]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](NC(=O)Cc3cccs3)[C@H]2SC1
Solvent: c1ccncc1
Solvent: CC(=O)OC(C)=O
Product: CC(=O)OCC1=CS[C@@H]2[C@H](NC(=O)Cc3cccs3)C(=O)N2C1C(=O)O
Reaction time: 0.75 h
Yield: 64.9 %

Procedure:
A solution of 3-acetoxymethyl-7β-(2-thienylacetamido)ceph-3-em-4-carboxylic acid (146.5 g.) in pyridine (600 ml.) was treated with acetic anhydride (45 ml.) and the mixture stirred vigorously at 22° for 45 minutes. The material which crystallised out was isolated by filtration washed with pyridine and ethyl acetate, and dried in vacuo to give the pyridinium salt of the title compound (95.15 g., 54.5%). This pyridinium salt was stirred with water (350 ml.) and ethyl acetate (700 ml.) and 2N-hydrochloric acid (ca 120 ml.) added until all the solid had dissolved. The organic phase was separated, washed with water, dried and evaporated in vacuo to give the title compound (77 g.) as a white solid, m.p. 151°-152.5°, [α]D + 480° 5% sodium carbonate), λmax. 235 nm. (ε 15,200), νmax. 3293 (NH), 1746 (β-lactam), 1722 and 2600 (CO2H), 1722 and 1208 (CH2OCOCH3) and 1660 and 1528 cm.-1 (CONH), τ (D2O - sodium bicarbonate) 2.7 and 3.0 (thienyl, 1-proton t and 2-proton d), 3.62 (C(2) -H, broad s), 4.58 (C(7) -H, d, J 4.5 Hz), 4.69 (C(6) -H, d, J 4.5 Hz), 5.18 (C(4) -H, broad s), 6.15 (CH2CONH, s) and 7.9 (-OCOCH3, s) (CH2OAc obscured by H2O band). (Found: C, 48.3; H, 4.1; N, 7.0; S, 16.2. Calc. for C16H16N2O6S2 : C, 48.4; H, 4.05; N, 7.05; S, 16.15%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[C:11](=O)[CH2:12][N:13]1[CH2:17][CH2:16][CH2:15][CH:14]1[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH2:25][CH2:26][CH2:27][N:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)[CH:19]=1.N>CO.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[C@H:11]1[C:23]2[C:18](=[CH:19][C:20]([O:24][CH2:25][CH2:26][CH2:27][N:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)=[CH:21][CH:22]=2)[C@@H:14]2[CH2:15][CH2:16][CH2:17][N:13]2[CH2:12]1
Reactant: COc1ccc(C(=O)CN2CCCC2c2cccc(OCCCN3CCCCC3)c2)c(OC)c1
Agent: N
Solvent: CO
Solvent: ClCCl
Product: COc1ccc([C@@H]2CN3CCC[C@H]3c3cc(OCCCN4CCCCC4)ccc32)c(OC)c1
Yield: 78 %

Procedure:
1. 1-(2,4-Dimethoxy-phenyl)-2-{2-[3-(3-piperidin-1-yl-propoxy)-phenyl]-pyrrolidin-1-yl}-ethanone. Prepared as described in Example 8, Step 1, on a 3.47 mmol scale, to give 1.28 g (78%) of the desired product as a pale yellow oil after chromatography (NH3 in MeOH/CH2Cl2). MS: exact mass calcd for C28H38N2O4, 466.3; m/z found, 467.5 [M+H]+. 1H NMR (MeOH-d4): 7.16 (m, 1H), 7.10 (d, J=3.2, 1H), 6.97 (dd, J=3.2, 9.0, 1H), 6.93 (d, J=1.6, 1H), 6.87 (m, 2H), 6.76 (m, 1H), 4.04 (m, 1H), 3.91 (m, 2H), 3.69 (s, 3H), 3.63 (s, 3H), 3.43 (m, 3H), 2.39 (m, 6H), 2.30 (m, 1H), 2.11 (m, 1H), 1.92 (m, 3H), 1.82 (m, 1H), 1.75 (m, 1H), 1.55 (m, 4H), 1.42 (m, 2H).
Reaction SMILES: [Si]([O:8][CH:9]([C:19]1[CH:20]=[CH:21][C:22]([C:25](=O)[CH2:26][CH2:27][C:28](=O)[CH:29]([C:36]2[CH:41]=[CH:40][C:39]([S:42][CH3:43])=[CH:38][N:37]=2)[CH2:30][CH:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)=[N:23][CH:24]=1)[CH2:10][O:11][Si](C(C)(C)C)(C)C)(C(C)(C)C)(C)C.C([O-])(=O)C.[NH4+:50].C(=O)([O-])O.[Na+]>C(O)(=O)C.C(OCC)(=O)C>[CH:31]1([CH2:30][CH:29]([C:28]2[NH:50][C:25]([C:22]3[N:23]=[CH:24][C:19]([CH:9]([OH:8])[CH2:10][OH:11])=[CH:20][CH:21]=3)=[CH:26][CH:27]=2)[C:36]2[CH:41]=[CH:40][C:39]([S:42][CH3:43])=[CH:38][N:37]=2)[CH2:35][CH2:34][CH2:33][CH2:32]1
Reactant: CSc1ccc(C(CC2CCCC2)C(=O)CCC(=O)c2ccc(C(CO[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C)cn2)nc1
Reactant: [NH4+]
Agent: CC(=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CSc1ccc(C(CC2CCCC2)c2ccc(-c3ccc(C(O)CO)cn3)[nH]2)nc1
Temperature: 110 °C
Reaction time: 0.75 h
Yield: 53.4 %

Procedure:
To a solution of 1-[5-(1,2-bis{[tert-butyl(dimethyl)silyl]oxy}ethyl)pyridin-2-yl]-6-cyclopentyl-5-[5-(methylsulfanyl)pyridin-2-yl]hexane-1,4-dione (682 mg) in acetic acid (7 mL) was added ammonium acetate (1.26 g), and the mixture was stirred at 110° C. for 45 min. After cooling to room temperature, the mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution. The reaction mixture was diluted with ethyl acetate and washed with water. The ethyl acetate layer was dried (MgSO4) and concentrated. To a solution of the obtained residue in tetrahydrofuran (4 mL) was added tetrabutylammonium fluoride (1M tetrahydrofuran solution, 8.16 mL), and the mixture was stirred at room temperature for 1.5 hr. The reaction mixture was diluted with ethyl acetate, and washed with saturated brine. The ethyl acetate layer was dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (230 mg, yield 53%) was obtained as a colorless amorphous solid from a fraction eluted with ethyl acetate-hexane (99:1, volume ratio). MS: 424 (MH+).
Reaction SMILES: [S:1]([NH:11][C:12]1[N:17]2[C:18]3[N:24]=[CH:23][CH:22]=[CH:21][C:19]=3[CH:20]=[C:16]2[CH:15]=[CH:14][N:13]=1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[I:25]N1C(=O)CCC1=O>C(Cl)Cl>[I:25][C:20]1[C:19]2[CH:21]=[CH:22][CH:23]=[N:24][C:18]=2[N:17]2[C:16]=1[CH:15]=[CH:14][N:13]=[C:12]2[NH:11][S:1]([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:2])=[O:3]
Reactant: Cc1ccc(S(=O)(=O)Nc2nccc3cc4cccnc4n23)cc1
Reactant: O=C1CCC(=O)N1I
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)Nc2nccc3c(I)c4cccnc4n23)cc1
Reaction time: 0.25 h
Yield: 100.5 %

Procedure:
To a solution of 23a (10 mg, 0.03 mmol) in CH2Cl2 (5 ml) at −30° C. N-iodosuccinimide (7 mg mg, 0.03 mmol) was portionwise added and the mixture was stirred for 15 min. The solution was washed with water and the organic solutions was dried, filtered and evaporated to obtain 24a (14 mg, 95%) as a yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:7])[C@@H:4]([CH3:6])[NH2:5].[CH2:8]1[CH2:14][S:11](=[O:13])(=[O:12])[O:10][CH2:9]1>C(#N)C>[CH3:1][O:2][C:3](=[O:7])[C@H:4]([NH:5][CH2:9][CH2:8][CH2:14][S:11]([OH:13])(=[O:12])=[O:10])[CH3:6]
Reactant: O=S1(=O)CCCO1
Reactant: COC(=O)[C@@H](C)N
Solvent: CC#N
Product: COC(=O)[C@@H](C)NCCCS(=O)(=O)O
Temperature: 25 °C
Yield: 57.7 %

Procedure:
To a solution of D-Alanine methylester (1.33 g, 12.9 mmol) in acetonitrile (15 mL was added 1,3-propane sultone (1.42 g, 11.7 mmol). The solution was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was filtered and washed with acetonitrile (2×15 mL). The solid was dissolved in water (30 mL). Dowex Marathon C ion exchange resin (strongly acidic) was added to the solution. The suspension was stirred for 15 minutes before the resin was removed by filtration. The filtrate was evaporated under reduced pressure and dried in vacuo, affording the title compound (1.52 g, 42%). 1H NMR (D2O, 500 MHz) δ ppm 4.07 (m, 1H), 3.72 (s, 3H), 3.14 (m, 2H), 2.89 (t, 2H, J=7.3 Hz), 2.03 (m, 2H), 1.46 (dd, 3H, J=1.95 Hz, 7.3 Hz). 13C (DMSO, 125 MHz) δ ppm 170.74, 55.62, 53.82, 47.96, 44.76, 21.53, 14.03. [α]D=+1.4° (c=0.0088 in water), ES-MS 224 (M−1).
Reaction SMILES: [C:1]([C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][CH:10]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[CH3:22]O>>[C:2]1([C:1]([C:9]2[CH:10]=[CH:11][C:12]([C:13]([O:15][CH3:22])=[O:14])=[CH:16][CH:17]=2)=[O:8])[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1ccc(C(=O)c2ccccc2)cc1
Reactant: CO
Solvent: O=S(Cl)Cl
Product: COC(=O)c1ccc(C(=O)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 64 %

Procedure:
A stirring solution of MeOH, 4-benzoylbenzoic acid and thionyl chloride was refluxed for 7 h under a nitrogen atmosphere. The reaction was cooled to RT and a white solid precipitated. The mixture was refrigerated overnight then filtered, rinsed with ice chilled MeOH and air-dried to yield 6.10 g (64%) of the title compound 19 as a white solid. 1H NMR (400 MHz, DMSO-d6): δ8.09 (d, J=8.2 Hz, 2H), 7.85 (d, J=8.1 Hz, 2H), 7.54-7.74 (m, 5H), 3.88 (s, 3H).
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:10]=[C:11]([CH2:15][S:16]([NH2:19])(=[O:18])=[O:17])[CH:12]=[CH:13][CH:14]=2)[N:3]=1.[NH:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:22][CH2:21]1>>[N:20]1([C:2]2[N:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]3[CH:10]=[C:11]([CH2:15][S:16]([NH2:19])(=[O:18])=[O:17])[CH:12]=[CH:13][CH:14]=3)[N:3]=2)[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:22][CH2:21]1
Reactant: c1ccc2c(c1)CCN2
Reactant: NS(=O)(=O)Cc1cccc(Nc2ncnc(Cl)n2)c1
Product: NS(=O)(=O)Cc1cccc(Nc2ncnc(N3CCc4ccccc43)n2)c1

Procedure:
B52 was prepared following the general procedure reported for B10 using A1 and indoline; yield: 76.2 mg (20%), pale yellow solid. 1H NMR (400 MHz, d6-DMSO, 300K) δ 3.11-3.18 (m, 2H), 4.14-4.26 (m, 2H), 4.23 (s, 2H), 6.84 (s, 2H), 6.97 (t, J=7.1 Hz, 1H), 7.01-7.09 (bm, 1H), 7.13-7.21 (bm, 1H), 7.25 (d, J=7.0 Hz, 1H), 7.33 (t, J=7.7 Hz, 1H), 7.64-7.90 (bm, 2H), 8.29-8.41 (bm, 1H), 8.43 (s, 1H), 9.90 (s, 1H). MS (ES) C18H18N6O2S requires: 382. found: 383 (M+H)+.
Reaction SMILES: [OH-].[K+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[C:10](=[O:14])[CH2:9][CH2:8]2.[CH:15](=O)[CH2:16][CH2:17][CH3:18]>[Pd].C(O)C>[CH2:15]([CH:9]1[CH2:8][C:7]2[C:11](=[CH:12][CH:13]=[C:5]([O:4][CH3:3])[CH:6]=2)[C:10]1=[O:14])[CH2:16][CH2:17][CH3:18]
Reactant: CCCC=O
Reactant: COc1ccc2c(c1)CCC2=O
Agent: [Pd]
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CCCCC1Cc2cc(OC)ccc2C1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 104.1 %

Procedure:
Potassium hydroxide (0.44 g, 85% weight pure, 6.67 mmol) and 10% palladium on activated carbon (0.42 g) were added to a mixture of 5-methoxy-1-indanone (5.0 g, 30.8 mmol) and butyraldehyde (3.3 mL, 37 mmol) in ethanol (30 mL). The resulting mixture was stirred under an atmosphere of hydrogen at room temperature for 2 hours. The mixture was filtered and the filtrate evaporated under vacuum. The residue was partitioned between EtOAc (200 mL) and water (200 mL) containing 2N HCl (5 mL). The organic phase was washed with brine (100 mL), dried over MgSO4, filtered, and evaporated under vacuum to afford crude 2-butyl-5-methoxy-1-indanone (7.0 g) as an oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]2[CH2:12][O:11][C:10](=[O:13])[NH:9]2)=[N:6][CH:7]=1.[H-].[Na+].[Br:16][C:17]1[CH:18]=[N:19][N:20]2[CH:25]=[CH:24][C:23](Cl)=[N:22][C:21]=12.O>CN(C=O)C>[Br:16][C:17]1[CH:18]=[N:19][N:20]2[CH:25]=[CH:24][C:23]([N:9]3[C@@H:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=4)[CH2:12][O:11][C:10]3=[O:13])=[N:22][C:21]=12
Reactant: O=C1N[C@@H](c2ccc(F)cn2)CO1
Reactant: Clc1ccn2ncc(Br)c2n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C1OC[C@H](c2ccc(F)cn2)N1c1ccn2ncc(Br)c2n1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 75 %

Procedure:
To a solution of (S)-4-(5-fluoropyridin-2-yl)oxazolidin-2-one (4.3 g, 24 mmol) in DMF (75 mL) was added sodium hydride (0.94 g, 24 mmol) in portions and the reaction stirred for 15 minutes at room temperature, followed by the addition of 3-bromo-5-chloropyrazolo[1,5-a]pyrimidine (5.5 g, 24 mmol) in a solution of DMF (50 mL) and the reaction was stirred for an additional 1 hour. The reaction was poured into water (400 mL) and extracted into ether (400 mL). The water layer was separated and washed with ether (200 mL). The combined organic layers were washed with water (100 mL) and brine (200 mL), dried over MgSO4 and concentrated in vacuo. The crude material was chromatographed using 15% EtOAc/DCM as eluent to yield (S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-(5-fluoropyridin-2-yl)oxazolidin-2-one (6.7 g, 18 mmol, 75% yield).
Reaction SMILES: Cl.C([NH:4][C:5]1[S:6][C:7]([Br:31])=[C:8]([C:10](=[N:28][O:29][CH3:30])[C:11]([NH:13][CH:14]2[C:26](=[O:27])[N:16]3[C:17]([C:23]([OH:25])=[O:24])=[CH:18][CH:19]([O:21][CH3:22])[S:20][C@H:15]23)=[O:12])[N:9]=1)=O.C.[OH-].[Na+]>CO.O>[NH2:4][C:5]1[S:6][C:7]([Br:31])=[C:8]([C:10](=[N:28][O:29][CH3:30])[C:11]([NH:13][CH:14]2[C:26](=[O:27])[N:16]3[C:17]([C:23]([OH:25])=[O:24])=[CH:18][CH:19]([O:21][CH3:22])[S:20][C@H:15]23)=[O:12])[N:9]=1
Reactant: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=CC(OC)S[C@H]12)c1nc(NC=O)sc1Br
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=CC(OC)S[C@H]12)c1nc(N)sc1Br
Temperature: 25 °C
Reaction time: 2 h
Yield: 90.6 %

Procedure:
Conc. hydrochloric acid (0.7 ml.) was added to a solution of 7-[2-(2-formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetamido]-2-methoxy-3-cephem-4-carboxylic acid (syn isomer, 1.4 g.) in methanol (45 ml.) and stirred at room temperature for 2 hrs. and further for 3.5 hrs. under ice-cooling. The reaction mixture was treated with activated charcoal. Water (30 ml.) was added to the solution and adjusted to pH 6.5 with 1N-aqueous sodium hydroxide, and methanol was distilled off. Ethyl acetate was added to the residue and adjusted to pH 2.5 with 1N-hydrochloric acid. The ethyl acetate layer was separated and the aqueous layer was washed with ethyl acetate. The ethyl acetate solution obtained above and the washings were combined, dried over magnesium sulfate, treated with activated charcoal and evaporated in vacuo. The residue was pulverized with diethyl ether, and the precipitates were collected by filtration and dried to give 7-[2-(2-amino-5-bromothiazol-4-yl)-2-methoxyiminoacetamido]-2-methoxy-3 -cephem-4-carboxylic acid (syn isomer, 1.2 g.).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][NH:11][C:12](=[O:33])[C:13]1[CH:18]=[C:17]([N:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[N:16]=[C:15]([C:25]2[CH:30]=[CH:29][C:28]([CH:31]=O)=[CH:27][CH:26]=2)[CH:14]=1.[CH3:34][NH:35][CH3:36].C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][NH:11][C:12](=[O:33])[C:13]1[CH:18]=[C:17]([N:19]2[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]2)[N:16]=[C:15]([C:25]2[CH:30]=[CH:29][C:28]([CH2:31][N:35]([CH3:36])[CH3:34])=[CH:27][CH:26]=2)[CH:14]=1
Reactant: CNC
Reactant: Cc1cc(C)c(CNC(=O)c2cc(-c3ccc(C=O)cc3)nc(N3CCCCC3)c2)c(=O)[nH]1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: Cc1cc(C)c(CNC(=O)c2cc(-c3ccc(CN(C)C)cc3)nc(N3CCCCC3)c2)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 81.2 %

Procedure:
To a solution of N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-(4-formylphenyl)-6-(piperidin-1-yl)isonicotinamide (0.2 g, 0.45 mmol) in methanol (12 mL), dimethyl amine (2.6 mL, 4.5 mmol, 2M solution in THF) and acetic acid (0.02 g, 0.45 mmol) were added and reaction mass stirred at rt for 90 min. Then reaction mass was cooled to 0° C. and sodium cyanoborohydride (0.056 g, 0.9 mmol) was added. Reaction stirred at 0° C. for 2 h and then stirred at rt for overnight. On completion, solvent was removed under reduced pressure, residue treated with water and extracted with ethyl acetate. Combined ethyl acetate layers were dried over sodium sulfate and concentrated under reduced pressure to afford crude material which was purified by column chromatography over silica gel obtaining N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-(4-((dimethylamino)methyl)phenyl)-6-(piperidin-1-yl)isonicotinamide as light green solid (0.173 g, 79%).
Reaction SMILES: [C:1]1(=[O:17])[N:5]([CH2:6][CH2:7][S:8](Cl)(=[O:10])=[O:9])[C:4](=[O:12])[C:3]2=[CH:13][CH:14]=[CH:15][CH:16]=[C:2]12.[NH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1>>[O:21]1[CH2:22][CH2:23][N:18]([S:8]([CH2:7][CH2:6][N:5]2[C:4](=[O:12])[C:3]3[C:2](=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:1]2=[O:17])(=[O:10])=[O:9])[CH2:19][CH2:20]1
Reactant: C1COCCN1
Reactant: O=C1c2ccccc2C(=O)N1CCS(=O)(=O)Cl
Product: O=C1c2ccccc2C(=O)N1CCS(=O)(=O)N1CCOCC1

Procedure:
Prepared according to general method A from 2-phthalimidoethanesulfonyl chloride (2.0 g) and morpholine (2.14 ml). Yield: 1.28 g (48%). 1H-NMR (CDCl3) δ (ppm) 7.94-7.84 (m, 4H), 3.99 (t, J=6.8 Hz, 2H), 3.62 (t, J=4.7 Hz, 4H), 3.45 (t, J=6.8 Hz, 4H), 3.15 (t, J=4.6 Hz, 4H).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([O:24][C:25]([NH:27][CH:28]1[CH2:33][CH2:32][CH2:31][N:30]([C:34]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[O:35])[CH:29]1[CH2:44][CH2:45]O)=[O:26])([CH3:23])([CH3:22])[CH3:21].C1(P([N:61]=[N+:62]=[N-:63])(C2C=CC=CC=2)=O)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1(C)C=CC=CC=1.O1CCCC1>[N:61]([CH2:45][CH2:44][CH:29]1[CH:28]([NH:27][C:25]([O:24][C:20]([CH3:22])([CH3:23])[CH3:21])=[O:26])[CH2:33][CH2:32][CH2:31][N:30]1[C:34]([O:36][CH2:37][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)=[O:35])=[N+:62]=[N-:63]
Reactant: CC(C)(C)OC(=O)NC1CCCN(C(=O)OCc2ccccc2)C1CCO
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)NC1CCCN(C(=O)OCc2ccccc2)C1CCN=[N+]=[N-]
Temperature: 0 °C

Procedure:
Triphenylphosphine (202 mg) was added to the compound 14 (146 mg), tetrahydrofuran (1 mL), diphenylphosphoryl azide (0.17 mL) and 2.2 mol/L of a solution (0.35 mL) of diethyl azodicarboxylate in toluene with stirring at 0° C. The reaction solution was stirred at room temperature for 1 hour and then concentrated. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:3) to obtain the title compound (136 mg) having the following physical properties.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[CH:12]=[CH:11][S:10][C:9]=2[CH:13]=O)[CH:3]=1.O.[CH3:16][NH:17][CH3:18].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[CH:12]=[CH:11][S:10][C:9]=2[CH2:13][N:17]([CH3:18])[CH3:16])[CH:3]=1
Reactant: O=Cc1sccc1-c1cc(Cl)ccn1
Reactant: CNC
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: CN(C)Cc1sccc1-c1cc(Cl)ccn1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 3-(4-chloro-pyridin-2-yl)-thiophene-2-carbaldehyde (20 mg, 0.1 mmol) in dichloromethane (3 mL) was added dimethylamine water solution (40%, 0.6 mL) and sodium triacetoxyborohydride (42 mg, 0.2 mmol). The resulting mixture was stirred at room temperature for 16 hours, then washed with NaHCO3 solution and water and concentrated. The resulting residue was purified by preparative TLC to yield [3-(4-Chloro-pyridin-2-yl)-thiophen-2-ylmethyl]-dimethyl-amine.
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:8]2[S:22][CH2:21][CH2:20][C:9]=2[N:10]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[N:12]=1)(=O)=O.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][OH:34])=[CH:28][CH:27]=1>>[Cl:19][C:15]1[CH:14]=[C:13]([C:11]2[N:12]=[C:7]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][OH:34])=[CH:28][CH:27]=3)[C:8]3[S:22][CH2:21][CH2:20][C:9]=3[N:10]=2)[CH:18]=[CH:17][CH:16]=1
Reactant: Nc1ccc(CCO)cc1
Reactant: O=S(=O)(Oc1nc(-c2cccc(Cl)c2)nc2c1SCC2)C(F)(F)F
Product: OCCc1ccc(Nc2nc(-c3cccc(Cl)c3)nc3c2SCC3)cc1
Yield: 67.3 %

Procedure:
Following general procedure H, 2-(3-chlorophenyl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl trifluoromethanesulfonate (0.094 g, 0.24 mmol) was reacted with 2-(4-aminophenyl)ethanol (0.033 g, 0.24 mmol) to afford the title compound (0.062 g, 68%) as a white solid. MW=383.89. 1H NMR (DMSO-d6, 500 MHz) δ 8.81 (s, 1H), 8.24-8.15 (m, 2H), 7.60 (d, J=8.5 Hz, 2H), 7.53-7.48 (m, 2H), 7.21 (d, J=8.5 Hz, 2H), 4.63 (t, J=5.5 Hz, 1H), 3.66-3.59 (m, 2H), 3.46-3.40 (m, 2H), 3.35-3.32 (m, 2H), 2.72 (t, J=7.0 Hz, 2H); APCI MS m/z 384 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1([CH3:13])[CH2:11][C:10]2[NH:9][CH2:8][CH2:7][CH2:6][C:5]=2[C:4](=[O:12])[CH2:3]1.[CH3:14][O:15][C:16]1[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=1)[C:19](Cl)=[O:20]>>[CH3:1][C:2]1([CH3:13])[CH2:11][C:10]2[N:9]([C:19](=[O:20])[C:18]3[CH:22]=[CH:23][CH:24]=[C:16]([O:15][CH3:14])[CH:17]=3)[CH2:8][CH2:7][CH2:6][C:5]=2[C:4](=[O:12])[CH2:3]1
Reactant: CC1(C)CC(=O)C2=C(C1)NCCC2
Reactant: COc1cccc(C(=O)Cl)c1
Product: COc1cccc(C(=O)N2CCCC3=C2CC(C)(C)CC3=O)c1

Procedure:
7,7-Dimethyl-1,2,3,4,7,8-hexahydro-quinolin-5(6H)-one was reacted with 3-methoxybenzoyl chloride according to the procedure of Part b) of Example 1 to give 7,7-dimethyl-1,2,3,4,7,8-hexahydro-1-(3-methoxybenzoyl)-quinolin-5(6H)-one (20) as a pale yellow solid.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7]2.[CH3:16][C:17]1[CH:22]=[CH:21][C:20]([S:23](Cl)(=[O:25])=[O:24])=[CH:19][CH:18]=1>N1C=CC=CC=1>[CH3:16][C:17]1[CH:22]=[CH:21][C:20]([S:23]([NH:1][C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:10]=2[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7]3)(=[O:25])=[O:24])=[CH:19][CH:18]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CCOC(=O)c1cc2cccc(N)c2[nH]1
Solvent: c1ccncc1
Product: CCOC(=O)c1cc2cccc(NS(=O)(=O)c3ccc(C)cc3)c2[nH]1
Temperature: 25 °C
Reaction time: 18 h
Yield: 88.3 %

Procedure:
To a mixture of ethyl 7-amino-1H-indole-2-carboxylate (0.30 g) and pyridine (8 mL) was added 4-methylphenylsulfonyl chloride (0.34 g) at 4° C., and the mixture was stirred at room temperature for 18 hr. The reaction mixture was concentrated, diluted with ethyl acetate, washed with aqueous citric acid solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained crystals were recrystallized from ethyl acetate-hexane to give the title compound (465 mg, yield 88%) as pale-yellow prism crystals. MS:359 (MH+).
Reaction SMILES: [CH2:1](Br)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[OH:12][C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([OH:23])[CH:19]=2)[CH:14]=1.C(=O)([O-])[O-].[K+].[K+].Cl>O.CN(C)C=O>[CH2:1]([O:12][C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([OH:23])[CH:19]=2)[CH:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCCCCCCBr
Reactant: Oc1ccc2cc(O)ccc2c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCCCCCCCCOc1ccc2cc(O)ccc2c1
Temperature: 130 °C
Reaction time: 2 h

Procedure:
Decyl monobromide (7.0 g), 2,6-dihydroxynaphthalene (5.0 g) and anhydrous potassium carbonate (4.0 g) were added to 100 ml of dimethylformamide. After stirring at 130° C. for 2 hours, the reaction solution was poured into water. Dilute hydrochloric acid was added to neutralize the solution, which was extracted with diethyl ether. The extract was distilled to remove the solvent to obtain the titled compound as residue (8.0 g).
Reaction SMILES: [F:1][C:2]([F:29])([F:28])[S:3][C:4]1[CH:5]=[C:6]([CH2:22][C:23]([O:25]CC)=[O:24])[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]=1.[OH-].[Na+]>O1CCOCC1.O>[F:28][C:2]([F:1])([F:29])[S:3][C:4]1[CH:5]=[C:6]([CH2:22][C:23]([OH:25])=[O:24])[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]=1
Reactant: CCOC(=O)Cc1ccc(OCc2ccc3ccccc3n2)c(SC(F)(F)F)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: O=C(O)Cc1ccc(OCc2ccc3ccccc3n2)c(SC(F)(F)F)c1

Procedure:
In analogy to the procedure of Example XV, the title compound is prepared from 2.1 g (5 mmol) of the compound from Example XXV and 0.4 g (0.01 mol) of sodium hydroxide in dioxane/water.