Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O-].[Na+].C([O:7][C@@H:8]1[C@@H:17]([O:18]C(=O)C)[C@H:16]([O:22]C(=O)C)[C@@H:15]([CH2:26][O:27]C(=O)C)[O:14][C@H:9]1[O:10][CH2:11][CH2:12][Br:13])(=O)C>CO>[O:10]([CH2:11][CH2:12][Br:13])[C@@H:9]1[O:14][C@H:15]([CH2:26][OH:27])[C@@H:16]([OH:22])[C@H:17]([OH:18])[C@H:8]1[OH:7]
Reactant: CC(=O)OC[C@H]1O[C@@H](OCCBr)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: OC[C@H]1O[C@@H](OCCBr)[C@H](O)[C@@H](O)[C@@H]1O
Reaction time: 4 h
Yield: 92.9 %

Procedure:
A solution of NaOMe (0.1M, 0.3 mL) was added to a suspension of 4h (See FIG. 6) (300 mg, 0.66 mmol) in MeOH (3 mL) under N2 and stirred vigorously. After 4 hours, the resulting solution was passed through a Dowex 50W(H-) plug (2×1 cm, eluant MeOH) and the solvent removed to give 2-bromoethyl β-D-glucopyranoside 4c (See FIG. 6) (176 mg, 93%) as a white solid that was used directly in the next step. A sample was recrystallized from EtOH/EtOAc to give a colorless, crystalline solid; mp 74-78° C. (EtOH/EtOAc) [lit., (Helferich et al., Just. Lieb. Ann. Chem., 541:1-16 (1939), which is hereby incorporated by reference) mp 74-75° C. (EtOH/EtOAc)]; [α]26D=−22.4 (c 1.63, H2O) [lit., (Helferich et al., Just. Lieb. Ann. Chem., 541:1-16 (1939), which is hereby incorporated by reference) [α]19D=−26.1 (c 3.0, H2O)]; 1H NMR (400 MHz, CD3OD) δ 3.30 (t, J 8.4 Hz, 1H, H-2), 3.39-3.49 (m, 3H), 3.64-3.80 (m, 3H), 3.97 (br d, J6,6′ 11.7 Hz, 1H, H-6′), 4.02 (dt, Jt 6.5 Hz, Jd 11.3 Hz, 1H, —OCHH′—), 4.23 (dt, Jt 6.5 Hz, Jd 11.3 Hz, 1H, —OCHH′—), 4.44 (d, J1,2 7.9 Hz, 1H, H-1). NaSSO2CH3 (100 mg, 0.75 mmol) was added to a solution of 4c (See FIG. 6) (176 mg, 0.61 mmol) in DMF (7 mL) under N2 and warmed to 50° C. After 15 hours, the solution was cooled and the solvent removed. The residue was purified by flash chromatography (MeOH:EtOAc, 1:9) to give 1c (See FIG. 6) (144 mg, 74%) as a hygroscopic foam; [α]27 D=−15.8 (c 0.88, H2O); IR (KBr) 3400 cm−1 (OH), 1310, 1131 cm−1 (S—SO2); 1H NMR (500 MHz, D2O, COSY) δ 3.07 (dd, J1,2 8.1 Hz, J2,3 9.4 Hz, 1H, H-2), 3.16 (dd, J3,4 9.0 Hz, J4,5 9.8 Hz, 1H, H-4), 3.24 (ddd, J4,5 9.8 Hz, J5,6 6.0 Hz, J5,6′ 2.3 Hz, 1H, H-5), 3.27 (t, J 9.0 Hz, 1H, H-3), 3.30-3.33 (m, 2H, —CH2S—), 3.34 (s, 3H, CH3SO2—), 3.50 (dd, J5,6 6.0 Hz, J6,6′ 12.4 Hz, 1H, H-6), 3.69 (dd, J5,6′ 2.3 Hz, J6,6′ 12.4 Hz, 1H, H-6′), 3.81 (dt, Jt 5.8 Hz, Jd 11.5 Hz, 1H, —OCHH′—), 4.00 (dt, Jt 5.7 Hz, Jd 11.4 Hz, 1H, —OCHH′—), 4.30 (d, J1,2 8.1 Hz, 1H, H-1); 13C NMR (50 MHz, D2O) δ 36.9 (—CH2S—), 51.0 (CH3SO2—), 62.0 (—OCH2—), 69.5, 70.9, 74.3, 76.7, 77.3 (C-2, C-3, C-4, C-5, C-6), 103.7 (C-1): HRMS m/z (FAB+): Found 341.0351 (M+Na+); C9H18O8S2Na requires 341.0341.
Reaction SMILES: [CH:1]1[C:13]2[N:12]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][N:21]([CH3:26])[CH2:22][CH2:23][NH:24][CH3:25])[C:15]=3[OH:27])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.Br[CH2:29][C:30]1[CH:35]=[C:34]([Br:36])[CH:33]=[C:32]([Br:37])[C:31]=1[OH:38].C(N(CC)CC)C>C1COCC1>[CH:1]1[C:13]2[N:12]([C:14]3[C:15]([OH:27])=[C:16]([CH:17]=[CH:18][CH:19]=3)[CH2:20][N:21]([CH3:26])[CH2:22][CH2:23][N:24]([CH2:29][C:30]3[CH:35]=[C:34]([Br:36])[CH:33]=[C:32]([Br:37])[C:31]=3[OH:38])[CH3:25])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: Oc1c(Br)cc(Br)cc1CBr
Reactant: CNCCN(C)Cc1cccc(-n2c3ccccc3c3ccccc32)c1O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CN(CCN(C)Cc1cccc(-n2c3ccccc3c3ccccc32)c1O)Cc1cc(Br)cc(Br)c1O
Reaction time: 8 h
Yield: 56.9 %

Procedure:
8 (0.218 g, 0.606 mmol) and 2-bromomethyl-4,6-dibromophenol (0.209 g, 0.606 mmol) were dissolved in 20 mL of THF. Triethylamine (1.2 mL, 8.61 mmol) was added to the slightly pink solution. A white precipitate formed immediately. The reaction was allowed to stir overnight after which time the volatiles were removed and methanol added to make a slurry. The solids were filtered and dried under vacuum resulting in a white solid (0.215 g, 57% yield).
Reaction SMILES: [Br-:1].[Br-:2].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[C:22]([C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:32]=[C:33]3[C:38](=[CH:39][CH:40]=2)[N:37]=[C:36]([C:41](=[O:43])[CH3:42])[CH:35]=[CH:34]3)=[CH:27][CH:26]=1)(=[O:24])[CH3:23].Br>C(O)(=O)C>[Br:1][CH2:42][C:41]([C:36]1[CH:35]=[CH:34][C:33]2[C:38](=[CH:39][CH:40]=[C:31]([C:28]3[CH:27]=[CH:26][C:25]([C:22](=[O:24])[CH2:23][Br:2])=[CH:30][CH:29]=3)[CH:32]=2)[N:37]=1)=[O:43]
Reactant: CC(=O)c1ccc(-c2ccc3nc(C(C)=O)ccc3c2)cc1
Reactant: [Br-]
Agent: Br
Agent: c1cc[nH+]cc1
Solvent: CC(=O)O
Product: O=C(CBr)c1ccc(-c2ccc3nc(C(=O)CBr)ccc3c2)cc1
Temperature: 70 °C
Reaction time: 6 h
Yield: 77.6 %

Procedure:
Pyridinium tribromide (221 mg, 0.691 mmol) was added to a suspension of 1-(6-(4-acetylphenyl)quinolin-2-yl)ethanone (100 mg, 0.346 mmol) and HBr (0.061 mL, 0.35 mmol) in acetic acid (3 mL) the reaction mixture was stirred at 70° C.) for 6 h. The reaction was concentrated under vacuum and the residue was partitioned between aq NaHCO3 (15 mL) and EtOAc (30 mL+10 mL+10 mL). The organic layers were combined, washed with brine, dried, filtered and concentrated to yield crude 2-bromo-1-(6-(4-(2-bromoacetyl)phenyl)quinolin-2-yl)ethanone (120 mg) as white solid. LC-MS retention time 4.138 min; m/z 448.01 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 3u C18 2.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 0.8 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where Solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and Solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a MICROMASS® Platform for LC in electrospray mode.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]([CH3:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:5]=[C:4]([NH2:16])[N:3]=1.[C-:17]#[N:18].[K+]>CN(C=O)C.CCOC(C)=O>[NH2:16][C:4]1[N:5]=[C:6]([N:8]([CH3:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:7]=[C:2]([C:17]#[N:18])[N:3]=1
Reactant: CN(c1ccccc1)c1nc(N)nc(Cl)n1
Reactant: [C-]#N
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CN(c1ccccc1)c1nc(N)nc(C#N)n1
Reaction time: 2 h
Yield: 62.9 %

Procedure:
To a stirring solution of 6-chloro-N-methyl-N-phenyl-[1,3,5]triazine-2,4-diamine (Intermediate 41, 360 mg, 2.67 mmol) in DMF (25 ml) was added potassium cyanide (435 mg, 6.68 mmol). The reaction was stirred at 120 C under nitrogen for 2 h. The reaction mixture was diluted with EtOAc (80 ml); the solution was then extracted with 5% aq. sodium hydrogencarbonate solution (2×20 mL), and saturated brine (2×5 mL). After evaporation of the solvent, the crude residue was purified by FCC over silica gel eluting with heptane:EtOAc 1:0 to 8:2 to 6:4 to furnish the desired product (380 mg, 63%). Method C HPLC-MS: MH+ requires m/z=227. Found: m/z=227, Rt=1.24 min (95%).
Reaction SMILES: [C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:11]1[CH:12]=[C:13]2[N:19]=[C:18]([N:20]3[CH:26]4[CH2:27][CH2:28][N:23]([CH2:24][CH2:25]4)[CH2:22][CH2:21]3)[O:17][C:14]2=[N:15][CH:16]=1>>[C:1]1([C:11]2[CH:12]=[C:13]3[N:19]=[C:18]([N:20]4[CH:26]5[CH2:25][CH2:24][N:23]([CH2:28][CH2:27]5)[CH2:22][CH2:21]4)[O:17][C:14]3=[N:15][CH:16]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Brc1cnc2oc(N3CCN4CCC3CC4)nc2c1
Reactant: OB(O)c1ccccc1
Product: c1ccc(-c2cnc3oc(N4CCN5CCC4CC5)nc3c2)cc1
Yield: 50 %

Procedure:
The title compound was prepared according to the procedure in Example 44 using phenylboronic acid and 4-(6-bromo-oxazolo[5,4-b]pyridin-2-yl)-1,4-diaza-bicyclo[3.2.2]nonane (prepared in Example 23) in 50% yield as a colorless oil: 1H NMR (CDCl3, 400 MHz) δ 8.10 (d, 1H, J=2.1 Hz), 7.72 (d, 1H, J=2.1 Hz), 7.57-7.55 (m, 2H), 7.47-7.44 (m, 2H), 7.39-7.36 (m, 1H), 4.58 (br s, 1H), 3.98 (t, 2H, J=5.8 Hz), 3.22-3.14 (m, 4H), 3.11-3.01 (m, 2H), 2.22-2.15 (m, 2H), 1.89-1.82 (m, 2H); MS (Cl) m/z 321.2 (M+1).
Reaction SMILES: [CH3:1][N:2](C=O)C.C1COCC1.CN(C)[CH2:13][C:14]1[C:22]2[C:17](=[CH:18][C:19]([N+:23]([O-:25])=[O:24])=[CH:20][CH:21]=2)[NH:16][CH:15]=1.[C-]#N.[K+]>O>[N+:23]([C:19]1[CH:18]=[C:17]2[C:22]([C:14]([CH2:13][C:1]#[N:2])=[CH:15][NH:16]2)=[CH:21][CH:20]=1)([O-:25])=[O:24]
Reactant: CN(C)C=O
Reactant: CN(C)Cc1c[nH]c2cc([N+](=O)[O-])ccc12
Agent: [C-]#N
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: N#CCc1c[nH]c2cc([N+](=O)[O-])ccc12
Temperature: 25 °C
Yield: 36 %

Procedure:
To a mixture of DMF (35 mL) and Mel (74.6 g, 0.53 mol) in water (35 mL) and THF (400 mL) was added dimethyl-(6-nitro-1H-indol-3-ylmethyl)-amine (23 g, 0.105 mol). After the reaction mixture was refluxed for 10 min, potassium cyanide (54.6 g, 0.84 mol) was added and the mixture was kept refluxing overnight. The mixture was then cooled to room temperature and filtered. The filtrate was washed with brine (300 mL×3), dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give (6-nitro-1H-indol-3-yl)-acetonitrile (B-9-a) (7.5 g, 36%).
Reaction SMILES: Cl[C:2]1[N:7]=[N:6][C:5](Cl)=[C:4]2[C:9]([CH3:21])=[N:10][C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)=[CH:12][C:3]=12.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1>>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([C:11]2[N:10]=[C:9]([CH3:21])[C:4]3=[C:5]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[N:6]=[N:7][C:2]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[C:3]3[CH:12]=2)=[CH:14][CH:15]=1
Reactant: COc1ccc(-c2cc3c(Cl)nnc(Cl)c3c(C)n2)cc1
Reactant: C1COCCN1
Product: COc1ccc(-c2cc3c(N4CCOCC4)nnc(N4CCOCC4)c3c(C)n2)cc1
Temperature: 130 °C

Procedure:
1.0 part by weight of 1,4-dichloro-7-(p-methoxyphenyl)-5-methylpyrido(3,4-d)pyridazine is added to 10 parts by volume of morpholine, and the resulting mixture is heated at 130° C for 3 hours. The excess amount of morpholine is removed by evaporating under reduced pressure, and water is added to the residue. The crude crystals are collected by filtration and recrystallized from ethanol to obtain 7-(p-methoxyphenyl)-5-methyl-1,4-dimorpholinopyrido(3,4-d)-pyridazine as gray prisms melting at 206° to 209° C. Elementary analysis for C23H27O3N5
Reaction SMILES: [CH2:1]([O:3][C:4]([C@H:6]1[CH2:11][CH2:10][C@H:9]([O:12][C:13]2[N:14]=[N:15][C:16](Cl)=[CH:17][CH:18]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].C(N(CC)CC)C>C(OCC)(=O)C.[Pd]>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:11][CH2:10][C@H:9]([O:12][C:13]2[N:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)[C@H]1CC[C@H](Oc2ccc(Cl)nn2)CC1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CCOC(=O)[C@H]1CC[C@H](Oc2cccnn2)CC1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To an argon purged solution of cis/trans-4-(6-chloro-pyridazin-3-yloxy)-cyclohexanecarboxylic acid ethyl ester (1:1) (1.30 g, 4.57 mmol) and triethylamine (0.64 ml, 4.57 mmol) in ethyl acetate (46 ml) was added palladium on charcoal 10% (0.097 g). The reaction mixture was purged with hydrogen gas and stirred under an atmosphere of hydrogen gas for 4 h at room temperature. The catalyst and the ammonium salts were removed by filtration over Decalite. The filtrate was concentrated in vacuo to give the title compound (1.09 g, 95%) as light yellow oil.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[OH:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][C:17]=1[O:24][CH3:25].COC1C=C(OC)C=C2C=1C(=O)NC(C1C=CC=CN=1)=N2>>[OH:15][C:16]1[CH:23]=[CH:22][C:19]([C:20]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][C:9]([O:11][CH3:12])=[CH:8][C:7]=3[O:13][CH3:14])[N:1]=2)=[CH:18][C:17]=1[O:24][CH3:25]
Reactant: COc1cc(C=O)ccc1O
Reactant: COc1cc(N)c(C(N)=O)c(OC)c1
Agent: COc1cc(OC)c2c(=O)[nH]c(-c3ccccn3)nc2c1
Product: COc1cc(OC)c2c(=O)[nH]c(-c3ccc(O)c(OC)c3)nc2c1
Yield: 36 %

Procedure:
2-(4-Hydroxy-3-methoxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one was synthesized from 2-amino-4,6-dimethoxybenzamide and 4-hydroxy-3-methoxybenzaldehyde, using the method described for 5,7-dimethoxy-2-(pyridin-2-yl)quinazolin-4(3H)-one. 2-(4-Hydroxy-3-methoxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one (90 mg, 36%) was isolated as a white solid. Selected data: MS (m/z): 329.06; MP 294-296° C.
Reaction SMILES: [CH2:1](N=C=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].N1CCC[CH2:14][CH2:13]1>CC#N>[CH:2]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:8]=1[CH:13]=[CH2:14])=[CH2:1].[CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CCCCCCCCN=C=O
Reactant: C1CCNCC1
Solvent: CC#N
Product: C=Cc1ccccc1
Product: C=Cc1ccccc1C=C

Procedure:
(NaSO3-Fmoc)4-PBP-2, 10.1 mg, was prepared according to the procedure of Example 8. The protected peptide was dissolved in 0.20 mL DMF and 0.020 mL saturated NaHCO3 pH 8.7; 0.003 mL octyl isocyanate was added and stirred at RT to produce Compound 9P. Octyl isocyanate is commercially available, e.g., from Aldrich (Milwaukee, Wis.). After 45 min at RT 0.020 mL piperidine was added. After 40 min at RT the reaction mixture was diluted with 10 mL 20% CH3CN containing 0.014 mL H2SO4. Product was isolated on a 0.5 g styrene-divinylbenzene cartridge (EnviChrom-P®) using incrementally increasing concentrations of CH3CN about 0.05M in sodium sulfate at pH 2.3; product was eluted with 25% and 30% CH3CN. Product-containing fractions were pooled, solvent removed under vacuum, 2 mL 1.0 M ammonium acetate pH 5.0 buffer was added, pH adjusted to 5.0 by addition of ca. 0.6 mL 1.5 M NH4OH, and then diluted with an equal volume of MeOH. Product was isolated via CM-Sepharose® chromatography as described in Example 7. The product was further purified on a 0.5 g styrene-divinylbenzene cartridge as above but using eluents at pH 9.9 (0.10 M NH4OH-0.01 M (NH4)2SO4); product eluted with 30% CH3CN. Product-containing fractions were pooled, solvent removed under vacuum, and product was desalted and freeze dried using the procedure of Example 5. Yield: 2.7 mg of a white solid, C52H92N16O11. FABMS: calc. for C52H93N16O11, (M+H)+=1118.7. Found: 1119 (M+H)+, 1141 (M+Na)+, 1157 (M+K)+.
Reaction SMILES: C[NH:2][C:3]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:6]=[C:5]([C:15]2[CH:16]=[N:17][CH:18]=[C:19](C3C=CC(C(N4CCN(C)CC4)=O)=CC=3)[CH:20]=2)[CH:4]=1.[O:36]1[CH2:41][CH2:40][CH:39]([N:42]2[CH:46]=[C:45](B3OC(C)(C)C(C)(C)O3)[CH:44]=[N:43]2)[CH2:38][CH2:37]1.BrC1C=C(C2C=C(N)N=C(C3C=CC=CN=3)C=2)C=NC=1>>[O:36]1[CH2:37][CH2:38][CH:39]([N:42]2[CH:46]=[C:45]([C:19]3[CH:20]=[C:15]([C:5]4[CH:4]=[C:3]([NH2:2])[N:8]=[C:7]([C:9]5[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=5)[CH:6]=4)[CH:16]=[N:17][CH:18]=3)[CH:44]=[N:43]2)[CH2:40][CH2:41]1
Reactant: CC1(C)OB(c2cnn(C3CCOCC3)c2)OC1(C)C
Reactant: CNc1cc(-c2cncc(-c3ccc(C(=O)N4CCN(C)CC4)cc3)c2)cc(-c2ccccn2)n1
Agent: Nc1cc(-c2cncc(Br)c2)cc(-c2ccccn2)n1
Product: Nc1cc(-c2cncc(-c3cnn(C4CCOCC4)c3)c2)cc(-c2ccccn2)n1

Procedure:
This compound is prepared analogously to [4-(6′-Methylamino-[2,2′;4′,3″]terpyridin-5″-yl)-phenyl]-(4-methyl-piperazin-1-yl)-methanone (Example 2.1) by replacing (4-methyl-piperazin-1-yl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanone with 1-(tetrahydro-pyran-4-yl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (Intermediate B18) and by replacing (5″-Bromo-[2,2′;4′,3″]terpyridin-6′-yl)-methyl-amine with 5″-Bromo-[2,2′;4′,3″]terpyridin-6′-ylamine (Example 1.31).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1F)[N:8]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH:7]=[C:6]([C:17]([O:19]CC)=[O:18])[C:5]2=[O:22].[CH:23]1([NH:26][CH2:27][C@@H:28]2[C@H:32]([F:33])[CH2:31][NH:30][CH2:29]2)[CH2:25][CH2:24]1>>[CH:23]1([NH:26][CH2:27][C@@H:28]2[C@H:32]([F:33])[CH2:31][N:30]([C:11]3[CH:10]=[C:9]4[C:4]([C:5](=[O:22])[C:6]([C:17]([OH:19])=[O:18])=[CH:7][N:8]4[C:13]([CH3:14])([CH3:16])[CH3:15])=[CH:3][C:2]=3[F:1])[CH2:29]2)[CH2:25][CH2:24]1
Reactant: CCOC(=O)c1cn(C(C)(C)C)c2cc(F)c(F)cc2c1=O
Reactant: F[C@@H]1CNC[C@@H]1CNC1CC1
Product: CC(C)(C)n1cc(C(=O)O)c(=O)c2cc(F)c(N3C[C@H](CNC4CC4)[C@H](F)C3)cc21
Yield: 21.8 %

Procedure:
Using ethyl 6,7-difluoro-1,4-dihydro-1-(1,1-dimethylethyl)-4-oxo-3-quinolinecarboxylate (309 mg) and (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine (174 mg), the same procedure was followed as in Example 40 to give 7-[(3S,4S)-3-cyclopropylaminomethyl-4-fluoro-1-pyrrolidinyl]-6-fluoro-1,4-dihydro-1-(1,1-dimethylethyl)-4-oxo-3-quinolinecarboxylic acid as pale yellow crystals (91.3 mg).
Reaction SMILES: [CH:1](=[O:6])[CH2:2][CH2:3][CH2:4][CH3:5].[CH3:7][CH:8]([CH3:12])[CH2:9][CH:10]=O>>[CH:1](=[O:6])[CH:2]=[CH:3][CH2:4][CH2:5][CH2:10][CH2:9][CH:8]([CH3:12])[CH3:7]
Reactant: CCCCC=O
Reactant: CC(C)CC=O
Product: CC(C)CCCCC=CC=O

Procedure:
This example describes the process of the invention for the co-aldol condensation of n-pentanal and 3-methylbutanal (3-MBA) to give an isodecenal consisting of the isomers 2-propyl-5-methylhexenal and 2-isopropylheptenal (1+3) and also 2-propylheptenal (1+1) using the cosolvent diethylene glycol (DEG). 400kg/h of catalyst were passed through the reactor (as described in Example 3) at a temperature of 110° C. at the autogenous pressure of the reactants.
Reaction SMILES: C[C:2]1[CH:3]=[C:4]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].[CH2:17]([Br:20])[CH:18]=[CH2:19].C[C:22](C)=[O:23]>>[Br-:20].[CH3:22][O:23][C:2]1[CH:3]=[C:4]([C:11]2[CH:12]=[N+:13]([CH2:17][CH:18]=[CH2:19])[CH:14]=[CH:15][CH:16]=2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9]
Reactant: CC(C)=O
Reactant: C=CCBr
Reactant: Cc1cc(-c2cccnc2)ccc1[N+](=O)[O-]
Product: C=CC[n+]1cccc(-c2ccc([N+](=O)[O-])c(OC)c2)c1
Product: [Br-]
Temperature: 60 °C
Reaction time: 12 h
Yield: 99 %

Procedure:
To acetone (300 mL) was added 3-(3-methyl-4-nitrophenyl)pyridine (Intermediate B9, 20.25 g, 88.0 mmol)) and allyl bromide (42.6 g, 352.2 mmol, Aldrich), and the reaction was stirred at 60° C. for 12 h. Filtration removed the liquids and washing with MeOH (2×20 mL) afforded 3-[3-(methyloxy)-4-nitrophenyl]-1-(2-propen-1-yl)pyridinium bromide as a yellow solid (30.8 g, 99% yield).
Reaction SMILES: [CH3:1][N:2]1[C:6]([N+:7]([O-:9])=[O:8])=[CH:5][N:4]=[C:3]1[CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[C:14]([CH3:20])[CH:13]=1.ClC1C=CC=C(C(OO)=[O:29])C=1.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)(Cl)Cl>[CH3:1][N:2]1[C:6]([N+:7]([O-:9])=[O:8])=[CH:5][N:4]=[C:3]1[CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:19])=[O:29])=[C:14]([CH3:20])[CH:13]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSc1ccc(OCc2ncc([N+](=O)[O-])n2C)cc1C
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: Cc1cc(OCc2ncc([N+](=O)[O-])n2C)ccc1S(C)=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
29.3 g (0.1 mol) of 1-methyl-2-(3-methyl-4-methylthiophenyloxymethyl)-5-nitro-imidazole are dissolved in 200 ml of chloroform, and the solution is added dropwise while stirring at 25° C. to a solution of 17.25 g (0.1 mol) of 3-chloroperbenzoic acid in 70 ml of chloroform. The reaction mixture is stirred for 1 hour at 25° C., shaken with dilute sodium carbonate solution, the chloroform phase is separated, dried over sodium sulfate and concentrated by evaporation. The residue is recrystallized from ethanol with an addition of charcoal, to yield 21.0 g (68% of the theoretical yield) of 1-methyl-2-(3-methyl-4-methylsulfinylphenyl-oxymethyl)-5-nitro-imidazole in the form of yellow crystals, m.p. 121° C.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:8]2[N:12]=[CH:11][NH:10][N:9]=2)=[C:4]([NH2:7])[S:5][CH:6]=1.[Br:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH2:24][C:25](O)=[O:26])[C:19](=[O:28])[CH:18]=[CH:17]2>>[Br:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH2:24][C:25]([NH:7][C:4]1[S:5][CH:6]=[C:2]([Cl:1])[C:3]=1[C:8]1[N:12]=[CH:11][NH:10][N:9]=1)=[O:26])[C:19](=[O:28])[CH:18]=[CH:17]2
Reactant: O=C(O)Cn1c(=O)ccc2cc(Br)ccc21
Reactant: Nc1scc(Cl)c1-c1nc[nH]n1
Product: O=C(Cn1c(=O)ccc2cc(Br)ccc21)Nc1scc(Cl)c1-c1nc[nH]n1

Procedure:
The title compound was prepared from 4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-amine (115 mg, 573 umol) and 2-(6-bromo-2-oxoquinolin-1(2H)-yl)acetic acid (135 mg, 479 umol) according to protocol A. HPLC purification gave 2-(6-bromo-2-oxoquinolin-1(2H)-yl)-N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)acetamide. Method [7] Retention time 5.30 min by HPLC (M+=464, 466, and 468) are the major peak intensities. 1H NMR (300 MHz, CDCl3) δ 7.80 (m, 2H), 7.70 (s, 1H), 7.64 (dd, J=9.0 and 2.4 Hz, 1H), 7.19 (d, J=9.0 Hz, 1H), 6.94 (d, J=9.3 Hz, 1H), 6.82 (s, 1H), 5.30 (s, 2H).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2([C:14]3[CH:24]=[CH:23][C:17]4[O:18][C:19]([F:22])([F:21])[O:20][C:16]=4[CH:15]=3)[CH2:13][CH2:12]2)=[O:10])[CH:5]=[CH:4][C:3]=1[CH3:25].[CH3:26][O:27][C:28]1[C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][C:31]([CH3:43])=[CH:30][N:29]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(OCC)(=O)C.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>[F:21][C:19]1([F:22])[O:18][C:17]2[CH:23]=[CH:24][C:14]([C:11]3([C:9]([NH:8][C:6]4[N:7]=[C:2]([C:33]5[C:28]([O:27][CH3:26])=[N:29][CH:30]=[C:31]([CH3:43])[CH:32]=5)[C:3]([CH3:25])=[CH:4][CH:5]=4)=[O:10])[CH2:13][CH2:12]3)=[CH:15][C:16]=2[O:20]1
Reactant: Cc1ccc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)nc1Cl
Reactant: COc1ncc(C)cc1B1OC(C)(C)C(C)(C)O1
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: CCOC(C)=O
Solvent: COCCOC
Product: COc1ncc(C)cc1-c1nc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)ccc1C
Temperature: 120 °C
Yield: 54 %

Procedure:
N-(6-Chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (73 mg, 0.20 mmol) was dissolved in 2 mL of 1,2-dimethoxyethane in a reaction tube. 2-Methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (65 mg, 0.26 mmol), 0.2 mL of an aqueous 2 M sodium carbonate solution, and tetrakis(triphenylphosphine)palladium(0) (12 mg, 0.010 mmol) were added and the reaction mixture was heated at 120° C. for 20 minutes under microwave irradiation. The reaction was diluted with ethyl acetate (5 mL) and washed with water (5 mL). The organics were dried over sodium sulfate and evaporated to dryness. The resulting residue was purified by silica gel chromatography eluting with 0-100% ethyl acetate in hexane to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(2′-methoxy-3,5′-dimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (49 mg, 72%). ESI-MS m/z calc. 453.4. found 454.3 (M+1)+. Retention time 2.10 minutes.
Reaction SMILES: [Cl:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][CH:7]([CH2:11][CH3:12])[C:8](Cl)=[O:9])=[CH:4][CH:3]=1.[C:15]1(=[O:25])[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17](=[O:24])[CH2:16]1.N1CCCCC1.Cl>N1C=CC=CC=1.C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][CH:7]([CH2:11][CH3:12])[C:8]([CH:16]2[C:15](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]2=[O:24])=[O:9])=[CH:4][CH:3]=1
Reactant: O=C1CC(=O)c2ccccc21
Reactant: CCC(Oc1ccc(Cl)cc1)C(=O)Cl
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: C1CCNCC1
Solvent: c1ccncc1
Product: CCC(Oc1ccc(Cl)cc1)C(=O)C1C(=O)c2ccccc2C1=O
Temperature: 0 °C
Yield: 18.1 %

Procedure:
5.8 G of 2-(4-chlorophenoxy)butyryl chloride (0.025 mol) are added dropwise, with stirring and whilst cooling with an ice bath at 0°C and working under nitrogen, to 3.65 g (0.025 mol) of indane-1,3-dione in 20 ml of pyridine containing two drops of piperidine. After stirring the mixture for 18 hours, it is poured onto ice and acidified with hydrochloric acid, and the resulting mixture is ectracted with chloroform. After evaporating the solvent, the residue is crystallised from ethyl acetate to give 1.55 g of pure 2-[2'-(4"-chlorophenoxy)butyryl]indane-1,3-dione, melting point 132°C. Empirical formula: C19H15O4Cl; molecular Weight: 342.79; Elementary analysis: