Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:29])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[C:11]([CH:15]=[C:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)[CH:12]=[CH:13][CH:14]=2)[O:3]1.N#N.B([O-])[O-].B(O)O.B([O-])[O-]>C(O)C.[Pd]>[CH3:7][C:6]1([CH3:8])[C:2]([CH3:1])([CH3:29])[O:3][B:4]([C:9]2[CH:10]=[C:11]([CH2:15][CH:16]3[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH2:21]3)[CH:12]=[CH:13][CH:14]=2)[O:5]1
Reactant: CC(C)(C)OC(=O)N1CCC(=Cc2cccc(B3OC(C)(C)C(C)(C)O3)c2)CC1
Agent: [Pd]
Agent: N#N
Agent: OBO
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCC(Cc2cccc(B3OC(C)(C)C(C)(C)O3)c2)CC1

Procedure:
1,1-Dimethylethyl 4-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methylidene}-1-piperidinecarboxylate (92.48 g, 232 mmol) was dissolved in ethanol (1500 mL) and added to N2-purged 10% palladium on carbon (9 g, 4.25 mmol) in a 5 L hydrogenation flask. The resulting mixture was then deoxygenated by alternating N2 and vacuum supplies to the vessel. The flask was then placed under a hydrogen atmosphere with stirring. After 1 h the reaction had absorbed the theoretical volume of hydrogen and the hydrogen in the vessel was replaced by nitrogen by alternating the vacuum and nitrogen supplies. The mixture was then filtered through celite and the pad was washed well with ethanol. The filtrate was then concentrated to yield a straw coloured gum 87.6 g (94%). HPLC 3.11 min (ret time) (87.76% boronate) and 2.33 min (ret time) (6.66% boronic acid-boronate hydrolyses partially under HPLC conditions); LC-MS m/z 346 (M+H)+, 1.58 min (ret time) [product minus tBu group].
Reaction SMILES: [CH2:1]([CH:7]1[C:10](=[O:11])[O:9][CH:8]1[CH2:12][CH:13]([O:25]C(=O)C(NC=O)CC(C)C)[CH2:14][CH2:15][CH:16]=[CH:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]>[Pd].C1COCC1>[CH2:1]([C@H:7]1[C@H:8]([CH2:12][C@H:13]([OH:25])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[O:9][C:10]1=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCCCC=CCCC(CC1OC(=O)C1CCCCCC)OC(=O)C(CC(C)C)NC=O
Agent: [Pd]
Solvent: C1CCOC1
Product: CCCCCCCCCCC[C@@H](O)C[C@@H]1OC(=O)[C@H]1CCCCCC
Yield: 104 %

Procedure:
Prepared according to representative procedure described in Example 63, above. E/Z-mixture of β-lactone 20a (5.8 mg, 0.016 mmol) and 5 wt % palladium on carbon (5 mg) in 2 mL of THF was stirred at ambient temperature for 12 h under H2 atmosphere. Filtration gave the desired β-lactone 13d (5.9 mg, 99%) as a white solid.
Reaction SMILES: [CH3:1][C:2]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-])=O)=[CH:14][CH:13]=2)[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[CH2:21][C:22]([OH:24])=[O:23].[OH-].[Na+].COC(=O)CC1C2C(=NC=CC=2)N(CC2C=CC([N+]([O-])=O)=CC=2)C=1C>C1COCC1.CO>[NH2:18][C:15]1[CH:14]=[CH:13][C:12]([CH2:11][N:10]2[C:5]3=[N:6][CH:7]=[CH:8][CH:9]=[C:4]3[C:3]([CH2:21][C:22]([OH:24])=[O:23])=[C:2]2[CH3:1])=[CH:17][CH:16]=1
Reactant: Cc1c(CC(=O)O)c2cccnc2n1Cc1ccc([N+](=O)[O-])cc1
Agent: COC(=O)Cc1c(C)n(Cc2ccc([N+](=O)[O-])cc2)c2ncccc12
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: Cc1c(CC(=O)O)c2cccnc2n1Cc1ccc(N)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
[2-Methyl-1-(4-nitro-benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid: 1M Aqueous NaOH (1.18 ml) is added to a stirring suspension of [2-methyl-1-(4-nitro-benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid methyl ester (0.2 g, 0.54 mmol) in 4:1 THF/MeOH (5 ml). The reaction mixture is allowed to stir at room temperature for 4 hours and then the solvent is removed in vacuo. The crude residue is dissolved in 1:1 THF/water and acidified to pH 3-4 using 6M HCl. After stirring for 30 minutes the resulting suspension is filtered and dried in vacuo at 110° C. to yield the titled product as a yellow solid. (MH+326)
Reaction SMILES: [Cl:1][C:2]1[C:7]([NH2:8])=[C:6]([CH3:9])[CH:5]=[CH:4][N:3]=1.[N:10]([O-])=O.[Na+]>C(O)(=O)C.O>[Cl:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[CH:9]=[N:10][NH:8][C:7]=12
Reactant: O=N[O-]
Reactant: Cc1ccnc(Cl)c1N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: Clc1nccc2cn[nH]c12
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A solution of 2-chloro-4-methylpyridin-3-amine [133627-45-9] (3.0 g, 21.0 mmol) in acetic acid (300 mL) was treated with a solution of sodium nitrite (1.45 g, 21.0 mmol) in water (2.5 mL). The reaction mixture was stirred at rt for 15 min then allowed to stand at ambient temperature for 24 h. An additional solution of sodium nitrite (500 mg, 7.25 mmol) in water (1 mL) was added to the mixture which was allowed to stand at rt for 3 h. Acetic acid was evaporated under reduced pressure and the residual aqueous solution was partitioned between EtOAc and sat. aq. NaHCO3. The insoluble solid was filtered off (dried under vacuum; batch 1) and the organic filtrate was washed with water and brine, then dried (Phase separator) and concentrated under vacuum (batch 2). The two batches were combined to give 7-chloro-1H-pyrazolo[3,4-c]pyridine as a solid. MS (LC-MS): 153 [M+H]+, tR (HPLC conditions k): 0.9 min.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C:3]1=[O:8].[CH2:9]([O:16][CH:17](O)[CH3:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C(C)=CC=CC=1>[CH2:9]([O:16][CH2:17][CH2:18][O:8][CH:3]1[CH2:4][CH2:5][CH2:6][CH2:7][C:2]1=[O:1])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=C1CCCCC1O
Reactant: CC(O)OCc1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1C
Product: O=C1CCCCC1OCCOCc1ccccc1
Reaction time: 10 h
Yield: 67.1 %

Procedure:
A mixture of dimeric 2-hydroxycyclohexanone (13.7 g), 2 benzyloxyethanol (20 g) and p-toluensulphonic acid (2 g) were dissolved in xylene (500 ml) in a round bottom flask fitted with a Dean Stark apparatus and reluxed for 10 hrs. The resulting solution was cooled, washed with sodium hydrogen carbonate (3×50 ml) dried and concentrated under reduced pressure. The crude oil was then purified by flash chromatography using cyclohexane/ethyl acetate 60/40 as eluant yielding 20 g of the title compound (Rf=0.5).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[NH:12][C:11]([C:13]3[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=3[CH2:20][CH3:21])=[C:10]([C:22]([O:24]CC)=[O:23])[CH:9]=2)[C:5]([Br:27])=[CH:4][N:3]=1.[OH-].[K+].CCO>>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[NH:12][C:11]([C:13]3[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=3[CH2:20][CH3:21])=[C:10]([C:22]([OH:24])=[O:23])[CH:9]=2)[C:5]([Br:27])=[CH:4][N:3]=1
Reactant: CCOC(=O)c1cc(-c2nc(N)ncc2Br)[nH]c1-c1cc(Cl)ccc1CC
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CCc1ccc(Cl)cc1-c1[nH]c(-c2nc(N)ncc2Br)cc1C(=O)O
Temperature: 5 °C
Yield: 94.9 %

Procedure:
Ethyl 5-(2-amino-5-bromopyrimidin-4-yl)-2-(5-chloro-2-ethylphenyl)-1H-pyrrole-3-carboxylate (400 mg, 0.89 mmol) was treated with a 1.5 M solution of potassium hydroxide in 95% EtOH (11.86 mL, 20 eq) under reflux overnight. After cooling, the residue was concentrated, dissolved in water and washed with DCM. To the aqueous phase cooled to 5° C., a solution of 2 N HCl was added, under agitation. The resultant precipitate was collected by filtration to give the title compound (356 mg, 95%).
Reaction SMILES: CO[C:3]([NH2:7])([CH3:6])[CH2:4][OH:5].[C:8](=[O:15])([O-])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11].[C:16](=O)([O-])OC(C)(C)C>C([O-])(O)=O.[Na+].C(O)(C)(C)C>[C:8]([NH:7][C:3]([CH3:6])([CH3:16])[CH2:4][OH:5])([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:15]
Reactant: CC(C)(C)OC(=O)[O-]
Reactant: COC(C)(N)CO
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)(C)O
Product: CC(C)(CO)NC(=O)OC(C)(C)C
Reaction time: 8 h

Procedure:
2-Methoxy-2-amino-1-propanol is dissolved in saturated aqueous NaHCO3 at room temperature. Di-tert-butyl di-carbonate is added in tert-butanol. The contents are stirred overnight and then extracted with ethyl acetate. The organic layer is dried over MgSO4 and filtered. The filtrate is evaporated to give N-Boc-2-amino-2-methyl-1-propanol.
Reaction SMILES: [N+](C1C=CC(COC([N:12]2[CH2:17][CH2:16][CH:15]([NH:18][C:19]([C:21]3[N:22]=[C:23]([N:26]4[CH2:29][CH:28]([S:30][C:31]5[C@H:32]([CH3:55])[C@@H:33]6[C@@H:50]([C@H:51]([OH:53])[CH3:52])[C:49](=[O:54])[N:34]6[C:35]=5[C:36]([O:38]CC5C=CC([N+]([O-])=O)=CC=5)=[O:37])[CH2:27]4)[S:24][CH:25]=3)=[O:20])[CH2:14][CH2:13]2)=O)=CC=1)([O-])=O>O1CCCC1>[NH:12]1[CH2:13][CH2:14][CH:15]([NH:18][C:19]([C:21]2[N:22]=[C:23]([N:26]3[CH2:27][CH:28]([S:30][C:31]4[C@H:32]([CH3:55])[C@@H:33]5[C@@H:50]([C@H:51]([OH:53])[CH3:52])[C:49](=[O:54])[N:34]5[C:35]=4[C:36]([OH:38])=[O:37])[CH2:29]3)[S:24][CH:25]=2)=[O:20])[CH2:16][CH2:17]1
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(SC3CN(c4nc(C(=O)NC5CCN(C(=O)OCc6ccc([N+](=O)[O-])cc6)CC5)cs4)C3)[C@H](C)[C@H]12
Solvent: C1CCOC1
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(SC3CN(c4nc(C(=O)NC5CCNCC5)cs4)C3)[C@H](C)[C@H]12
Reaction time: 4.5 h
Yield: 33.3 %

Procedure:
p-Nitrobenzyl (1R,5S,6S)-2-(1-{4-[1-(p-nitrobenzyloxycarbonyl)-piperidin-4-ylcarbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (340 mg, 0.414 mmol) (obtained as described in Example 56(1)) in a mixture of tetrahydrofuran (17 ml) and distilled water (17 ml) was subjected to catalytic hydrogenation in the presence of 10% palladium on charcoal (340 mg) at room temperature for 4.5 hours. After checking the completion of the reaction, the reaction mixture was filtered and to the filtrate were added ethyl acetate and distilled water. The mixture was shaken in a separatory funnel. The aqueous layer was separated and concentrated under reduced pressure. The residue was purified by chromatography on a Cosmosil column (eluant: distilled water→distilled water:acetonitrile (8:2)) and the eluate was lyophilized to afford the desired compound (1R,5S,6S)-2-{1-[4-(piperidin-4-ylcarbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid (70 mg, yield 33%) as a white solid.
Reaction SMILES: Cl.C([N:9]1[C:13]([C:14]([C:24]2[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[CH:26][CH:25]=2)=[CH:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:12][N:11]=[CH:10]1)C1C=CC=CC=1>C(O)C.[H][H].[Pd]>[C:30]([C:27]1[CH:26]=[CH:25][C:24]([CH:14]([C:13]2[N:9]=[CH:10][NH:11][CH:12]=2)[CH2:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:29][CH:28]=1)#[N:31]
Reactant: N#Cc1ccc(C(=CCCc2ccccc2)c2cncn2Cc2ccccc2)cc1
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CCO
Product: N#Cc1ccc(C(CCCc2ccccc2)c2c[nH]cn2)cc1

Procedure:
1-benzyl-5-[1-(4-cyanophenyl)-4-phenyl-1-butenyl]-1H-imidazole hydrochloride (1,77 g) is dissolved in ethanol and a catalytic amount of 10% Pd/C is added. The reaction mixture is agitated vigorously at room temperature in hydrogen atmosphere until the reduction of the double bond and the debenzylation are complete. The reaction mixture is filtered and evaporated to dryness. The product is purified by flash chromatography.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[N:10]=[N:9][N:8]([CH:11]3[CH:15]4[O:16][C:17]([CH3:20])([CH3:19])[O:18][CH:14]4[CH:13]([CH2:21][OH:22])[O:12]3)[C:4]=2[N:5]=[CH:6][N:7]=1.C[Si](Cl)(C)C.[C:28](Cl)([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:29].[NH4+].[OH-]>N1C=CC=CC=1>[OH:22][CH2:21][CH:13]1[CH:14]2[O:18][C:17]([CH3:19])([CH3:20])[O:16][CH:15]2[CH:11]([N:8]2[C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH:1][C:28](=[O:29])[C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[C:3]=3[N:10]=[N:9]2)[O:12]1
Reactant: O=C(Cl)c1ccccc1
Reactant: CC1(C)OC2C(CO)OC(n3nnc4c(N)ncnc43)C2O1
Agent: C[Si](C)(C)Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: c1ccncc1
Product: CC1(C)OC2C(CO)OC(n3nnc4c(NC(=O)c5ccccc5)ncnc43)C2O1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 62.5 %

Procedure:
Compound 6.2 (2.2 g, 7.14 mmol) was dissolved in 30 mL pyridine and cooled to 0° C. To this was added TMSCl (2.7 mL, 21.4 mmol). The mixture was stirred at 0° C. for 30 min and then treated with BzCl (4.95 mL, 35.7 mmol). The mixture was stirred at 0° C. for 3 h and then treated with NH4OH (7.3 mL), stirred at 0° C. for another 30 min. The mixture was concentrated under reduced pressure and the residue was partitioned between CH2Cl2 and 1N HCl. The water layer was extracted three times with CH2Cl2. The organic layer was combined, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was subjected to a silica gel column chromatography eluting with 80% EtOAc in Hexane to yield compound 6.3 (1.84 g, 63% yield). 1HNMR (300 MHz, CDCl3) δ 1.42 (s, 3H), 1.70 (s, 3H), 3.79-4.01 (m, 2H), 4.63 (s, 1H), 5.14-5.16 (m, 1H), 5.31-5.35 (m, 1H), 6.68 (d, 1H, J=4.2), 7.55-7.61 (m, 2H), 7.61-7.69 (m, 1H), 8.08 (d, 2H, J=7.2), 8.90 (s, 1H). LRMS (ESI) MH+ C19H20N6O5 requires 413.2. Found 412.9.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].C1COCC1.[C:12]1([C@@H:18]2[NH:23][C:22](=O)[CH2:21][O:20][CH2:19]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C1COCC1>[C:12]1([C@H:18]2[CH2:19][O:20][CH2:21][CH2:22][NH:23]2)[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: O=C1COC[C@H](c2ccccc2)N1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: c1ccc([C@H]2COCCN2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 96 %

Procedure:
To a LiAlH4/THF slurry (0.47 g/2 mL) was added dropwise (S)-5-phenylmorpholin-3-one in THF solution (481 mg in 6 mL) at room temperature over 5 min. The resulting mixture was stirred at room temperature thereafter for 1 hour, then was heated with 72° C. oil bath overnight, then was cooled down to 0° C., quenched by sequential addition of H2O (0.47 mL), 3M aqueous solutionueous NaOH (0.47 mL) and H2O (1.4 mL), and the quenched residue was diluted with Et2O (30 mL), stirred for 10 min and the ethereal solution was separated by filtration. The filtrate was concentrated, further dried under vacuum and (S)-3-phenylmorpholine (424 mg, 96% yield) was obtained as colorless solid. LCMS (m/z): 164.2 (MH+), 0.33 min.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:22](OS(C1C=CC=C([N+]([O-])=O)C=1)(=O)=O)[C@H:23]1[O:25][CH2:24]1>CC(C)=O>[CH2:22]([C:14]1[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:10]([OH:15])[CH:11]=[CH:12][CH:13]=1)[C@@H:23]1[O:25][CH2:24]1
Reactant: Oc1ccccc1OCc1ccccc1
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)OC[C@@H]2CO2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: Oc1cccc(C[C@H]2CO2)c1OCc1ccccc1

Procedure:
A mixture of 2-benzyloxyphenol (900 mg, 4.5 mMol) and potassium carbonate (1.87 g, 13.5 mMol) in acetone (45 ml) was heated under reflux for 15 mins. (S)-Glycidyl-3-nitrobenzenesulphonate (1.0 g, 4.5 mMol) was added and the reaction mixture was heated under reflux for 23 hours. After cooling, the reaction mixture was filtered and the solvent was evaporated. The residue was partitioned between ethyl acetate and water. The organic fractions were combined, washed with water and brine, dried and evaporated to give the title compound as an oil.
Reaction SMILES: [CH2:1]([NH:7][C:8]1[N:13]=[C:12]([OH:14])[C:11]([C:15]([O:17]CC)=[O:16])=[CH:10][N:9]=1)[C:2]1[O:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>O>[CH2:1]([NH:7][C:8]1[N:13]=[C:12]([OH:14])[C:11]([C:15]([OH:17])=[O:16])=[CH:10][N:9]=1)[C:2]1[O:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)c1cnc(NCc2ccco2)nc1O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)c1cnc(NCc2ccco2)nc1O
Yield: 93 %

Procedure:
2-Furfurylamino-5-ethoxycarbonyl-4-hydroxypyrimidine (526 mg, 2 mmol) was hydrolysed in water (10 ml) with NaOH (5 mmol, 200 mg) by refluxing for 3 h. Cooling and acidification to pH 2 yielded the named product as a precipitate. (435 mg, 93% yield).
Reaction SMILES: [CH3:1][N:2]([CH3:15])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[CH:9]=O.[CH2:16]([NH2:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1(C)C=CC=CC=1>[CH3:1][N:2]([CH3:15])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[CH:9]=[N:23][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: CN(C)CCCOc1ccccc1C=O
Reactant: NCc1ccccc1
Solvent: Cc1ccccc1
Product: CN(C)CCCOc1ccccc1C=NCc1ccccc1

Procedure:
A solution of 20.0 g of 2-(3-dimethylaminopropoxy)benzaldehyde and 10.3 g of benzylamine in 100 ml of toluene is heated at reflux for one hour in a procedure described for Example 1. The yield of product is 22.1 g, boiling point 175°-178° C./0.05 mm of Hg.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]=1[C:12]([O:14][CH3:15])=[O:13].FC(F)(F)C(O)=O.[Br:23]N1C(C)(C)C(=O)N(Br)C1=O.S(=O)(=O)(O)O.C([O-])(=O)C.[Na+]>C(O)(=O)C>[Br:23][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[C:3]([C:12]([O:14][CH3:15])=[O:13])=[C:2]([CH3:1])[CH:11]=[CH:10]2
Reactant: COC(=O)c1c(C)ccc2ccccc12
Reactant: CC1(C)C(=O)N(Br)C(=O)N1Br
Agent: CC(=O)[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)c1c(C)ccc2cccc(Br)c12
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 69.8 %

Procedure:
Methyl 2-methylnaphthalene-1-carboxylate (5.6 g) was dissolved in acetic acid (12 ml) and trifluoroacetic acid (12 ml) and cooled in an ice bath. 1,3-Dibromo-5,5-dimethylhydantoin (4.8 g) was added in one portion then concentrated sulphuric acid was added dropwise. The mixture was then stirred at 0° C. for 30 minutes. Sodium acetate (6.12 g) was added and the mixture was partitioned between DCM and water. The organic layer was separated, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of DCM and pentane with a gradient of 20-70% to give methyl 8-bromo-2-methylnaphthalene-1-carboxylate (3.27 g) as a colourless oil.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[N:10]([C:11]3[C:20]4[C:15](=[CH:16][C:17]([F:21])=[CH:18][CH:19]=4)[N:14]=[C:13]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[S:28]([CH3:31])(=[O:30])=[O:29])[C:12]=3[CH3:32])[CH2:9][C:8]([CH3:34])([CH3:33])[C:5]2=[N:6][CH:7]=1.[B:35]1(B2OC(C)(C)C(C)(C)O2)[O:39]C(C)(C)C(C)(C)[O:36]1.C([O-])(=O)C.[K+]>O1CCOCC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.[Pd]>[F:21][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([N:10]3[C:4]4[C:5](=[N:6][CH:7]=[C:2]([B:35]([OH:39])[OH:36])[CH:3]=4)[C:8]([CH3:33])([CH3:34])[CH2:9]3)=[C:12]([CH3:32])[C:13]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[S:28]([CH3:31])(=[O:29])=[O:30])=[N:14]2)=[CH:19][CH:18]=1
Reactant: Cc1c(-c2ccccc2S(C)(=O)=O)nc2cc(F)ccc2c1N1CC(C)(C)c2ncc(Br)cc21
Reactant: CC1(C)OB(B2OC(C)(C)C(C)(C)O2)OC1(C)C
Agent: [Pd]
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Agent: CC(=O)[O-]
Solvent: C1COCCO1
Product: Cc1c(-c2ccccc2S(C)(=O)=O)nc2cc(F)ccc2c1N1CC(C)(C)c2ncc(B(O)O)cc21
Temperature: 100 °C

Procedure:
A stirred solution of 4-(6-bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]-pyridin-1-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinoline (93 mg, 0.17 mmol) (described herein) in 1,4-dioxane (2.5 mL) was sparged with N2 for 10 min. After this time bis(pinacolato)diboron (48.1 mg, 0.19 mmol), potassium acetate (25.3 mg, 0.26 mmol), and bis(tricyclohexylphosphine)palladium(o) (11.5 mg, 0.017 mmol) were added and the reaction heated at 100° C. for 16 h. The reaction was cooled to rt and partitioned between EtOAc and water. The organic layer was dried (MgSO4) and concentrated, affording crude 1-(7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinolin-4-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-ylboronic acid. No further purification was attempted. Mass Spectrum (ESI) m/e=506 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:12]([NH2:18])=[CH:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C([O-])(=O)C.[NH4+].C(O)(=O)C.C([BH3-])#N.[Na+]>CO.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH:12]([NH2:18])[CH2:13][S:14]([CH3:17])(=[O:15])=[O:16])[CH2:11][CH2:10][CH2:9]2)=[CH:6][CH:7]=1
Reactant: CS(=O)(=O)C=C(N)C1(c2ccc(Cl)cc2)CCC1
Agent: CC(=O)[O-]
Agent: [BH3-]C#N
Agent: [NH4+]
Solvent: O
Solvent: CO
Solvent: CC(=O)O
Product: CS(=O)(=O)CC(N)C1(c2ccc(Cl)cc2)CCC1

Procedure:
A solution of 1-[1(4-chlorophenyl)cyclobutyl]-2-methylsulphonylvinylamine (10 g), ammonium acetate (5 g), glacial acetic acid (7 ml) and sodium cyanoborohydride (5 g) in methanol (250 ml) was kept at room temperature for 12 days. The mixture was poured into water (750 ml) basified to pH 11 and extracted with dichloromethane. The organic extracts were washed with brine, dried and evaporated to give 1-[1-(4-chlorophenyl)cyclobutyl]-2-methylsulphonylethylamine (m.p. 134°-135°).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:31]=[C:32]([F:34])[CH:33]=1)[CH2:5][NH:6][C:7]1[CH:12]=[C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]3)=[CH:16][CH:15]=2)[N:10]=[CH:9][C:8]=1[CH2:27][C:28]([NH2:30])=[O:29].C[N+]1([O-])CCOCC1.O>CN(C)C=O.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[F:1][C:2]1[CH:3]=[C:4]([CH:31]=[C:32]([F:34])[CH:33]=1)[CH2:5][NH:6][C:7]1[CH:12]=[C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([N:20]3[CH2:21][CH2:22][C:23](=[O:26])[CH2:24][CH2:25]3)=[CH:18][CH:19]=2)[N:10]=[CH:9][C:8]=1[CH2:27][C:28]([NH2:30])=[O:29]
Reactant: NC(=O)Cc1cnc(Nc2ccc(N3CCC(O)CC3)cc2)cc1NCc1cc(F)cc(F)c1
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Agent: C[N+]1([O-])CCOCC1
Solvent: CN(C)C=O
Solvent: O
Product: NC(=O)Cc1cnc(Nc2ccc(N3CCC(=O)CC3)cc2)cc1NCc1cc(F)cc(F)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 10 %

Procedure:
120 mg of 4-[(3,5-difluorobenzyl)amino]-6-{[4-(4-hydroxypiperidino)phenyl]amino}pyridine-3-carboxyamide (the compound of Example 191) was dissolved in 1.5 mL of N,N-dimethylformamide, to which 78 mg of 4-methylmorpholine N-oxide, 120 mg of molecular sieve 4A powder and 2.8 mg of tetrapropylammonium perruthenate were added, and stirred at room temperature for 30 minutes. Water was added to the reaction mixture, extracted with ethyl acetate, and the extract was washed with saturated saline. After drying on anhydrous sodium sulfate, the solvent was evaporated, and the residue was purified by silica gel column chromatography (chloroform:methanol=20:1), recrystallized in methanol-ether-hexane to obtain 12 mg (10%) of the title compound as a light brown crystalline powder.
Reaction SMILES: [C:1](O)(=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[O:10]1[CH:14]=[CH:13][CH:12]=[CH:11]1.ClC(Cl)C(OC(=O)C(Cl)Cl)=O.[B]>C1(C)C=CC=CC=1>[C:1]([C:11]1[O:10][CH:14]=[CH:13][CH:12]=1)(=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: c1ccoc1
Reactant: CCCCCCC(=O)O
Agent: O=C(OC(=O)C(Cl)Cl)C(Cl)Cl
Agent: [B]
Solvent: Cc1ccccc1
Product: CCCCCCC(=O)c1ccco1
Temperature: 50 °C
Reaction time: 3 h
Yield: 99.3 %

Procedure:
In 50 ml of toluene were dissolved 6.51 g (0.05 mole) of heptanoic acid, 4.43 g (0.065 mole) of furan and 14.39 g (0.06 mole) of dichloroacetic anhydride. To the resulting solution was added 0.71 g of boron trifluoridediethyl ether coplex and the resulting mixture was then stirred at 50° C. for 3 hours. After completion of the reaction, the reaction solution was cooled and washed successively with 5% aqueous sodium carbonate solution and water. The organic layer was concentrated under reduced pressure and the resulting concentrated residue was then purified by silica gel-filled column chromatography to obtain 8.95 g of 2-heptanoylfuran.