Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C@@H:2]([CH2:32]O)[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:31])[C@@H:11]([N:16]2[CH2:20][C:19]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=3)=[CH:18][C:17]2=[O:30])[CH2:12][CH:13]([CH3:15])[CH3:14])=[N:5]1.[CH3:34]N(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.Cl.O[C@@H](CO)CN1C=CC(NC(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=N1>ClCCl>[OH:1][C:2]([CH3:34])([CH3:32])[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:31])[C@@H:11]([N:16]2[CH2:20][C:19]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=3)=[CH:18][C:17]2=[O:30])[CH2:12][CH:13]([CH3:14])[CH3:15])=[N:5]1
Reactant: COc1cccc(OC2=CC(=O)N([C@@H](CC(C)C)C(=O)Nc3ccn(C[C@@H](O)CO)n3)C2)c1
Reactant: CCN=C=NCCCN(C)C
Agent: CC(C)C[C@@H](C(=O)Nc1ccn(C[C@@H](O)CO)n1)N1CC(Oc2cccc(Cl)c2Cl)=CC1=O
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: COc1cccc(OC2=CC(=O)N([C@@H](CC(C)C)C(=O)Nc3ccn(CC(C)(C)O)n3)C2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 79.2 %

Procedure:
A solution of (S)-2-[4-(3-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (prepared as in Example 160, 300 mg, 0.94 mmol) in dichloromethane (20 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (161 mg, 1.03 mmol) and 1-hydroxybenzotriazole (135 mg, 0.99 mmol). The reaction mixture was stirred at 25° C. for 1 h followed by the addition of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 175 mg, 1.13 mmol). The reaction mixture was stirred for 18 h at 25° C., under nitrogen. The reaction mixture was diluted with dichloromethane, washed with 2N hydrochloric acid, saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over magnesium sulfate. The crude product obtained after concentration, was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g; 0% to 10% methanol/dichloromethane) to afford (S)-2-[4-(3-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (340 mg, 79%) as a light brown powder: HR-ES-MS m/z calculated for C24H32N4O5 [M+H]+ 456, observed 457; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.3 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H), 1.04 (br. s., 3H), 1.06 (br. s., 3H), 1.39-1.64 (m, 2H), 1.67-1.82 (m, 1H), 3.77 (s, 3H), 3.89 (s, 2H), 4.16 (d, J=18.4 Hz, 1H), 4.57 (d, J=18.4 Hz, 1H), 4.68 (s, 1H), 4.84-4.93 (m 1H), 4.87 (s, 1H), 6.44 (d, J=2.1 Hz, 1H), 6.83-6.91 (m, 3H), 7.37 (t, J=8.2 Hz, 1H), 7.53 (d, J=2.1 Hz, 1H), 10.79 (s, 1H).
Reaction SMILES: C([O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[C:25]([CH2:26][O:27][C:28]3[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=3[CH3:35])=[C:24]3[C:19]([NH:20][C:21]([CH3:39])([CH3:38])[C:22](=[O:37])[N:23]3[CH3:36])=[CH:18][CH:17]=2)=[C:12]([O:40][CH3:41])[CH:11]=1)(=O)C1C=CC=CC=1.O.Cl>CO.O1CCCC1.[OH-].[Na+]>[F:34][C:32]1[CH:31]=[CH:30][C:29]([CH3:35])=[C:28]([CH:33]=1)[O:27][CH2:26][C:25]1[C:16]([C:13]2[CH:14]=[CH:15][C:10]([OH:9])=[CH:11][C:12]=2[O:40][CH3:41])=[CH:17][CH:18]=[C:19]2[C:24]=1[N:23]([CH3:36])[C:22](=[O:37])[C:21]([CH3:39])([CH3:38])[NH:20]2
Reactant: COc1cc(OC(=O)c2ccccc2)ccc1-c1ccc2c(c1COc1cc(F)ccc1C)N(C)C(=O)C(C)(C)N2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: COc1cc(O)ccc1-c1ccc2c(c1COc1cc(F)ccc1C)N(C)C(=O)C(C)(C)N2
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 85 %

Procedure:
7-(4-Benzoyloxy-2-methoxyphenyl)-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 6-31, 422 mg, 0.761 mmol) was dissolved in mixed solvent of methanol (2 mL) and tetrahydrofuran (2 mL), and 4N aqueous sodium hydroxide solution (0.761 mL, 3.04 mmoL) was added thereto. After the reaction mixture was stirred at room temperature for 40 minutes, water (100 mL) and 1N aqueous HCl solution (4 mL) were added thereto. After the mixture was extracted with ethyl acetate mL), the organic layer was washed with water mL) and saturated brine (50 mL) successively, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was filtered with a mixed solvent of hexane (10 mL) and ethyl acetate (10 mL) to give the titled compound (292 mg) as a colorless solid. (Yield 85%)
Reaction SMILES: Cl[C:2]1[CH:10]=[C:9]([NH:11][C:12]2([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:14][CH2:13]2)[C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][N:31]([C:34](=[O:37])[CH2:35][CH3:36])[CH2:30][CH2:29]2)=[CH:24][CH:23]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:15]1([C:12]2([NH:11][C:9]3[C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N:3]=[C:2]([NH:21][C:22]4[CH:23]=[CH:24][C:25]([N:28]5[CH2:29][CH2:30][N:31]([C:34](=[O:37])[CH2:35][CH3:36])[CH2:32][CH2:33]5)=[CH:26][CH:27]=4)[CH:10]=3)[CH2:14][CH2:13]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: NC(=O)c1cnc(Cl)cc1NC1(c2ccccc2)CC1
Reactant: CCC(=O)N1CCN(c2ccc(N)cc2)CC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: CCC(=O)N1CCN(c2ccc(Nc3cc(NC4(c5ccccc5)CC4)c(C(N)=O)cn3)cc2)CC1
Temperature: 80 °C
Yield: 19 %

Procedure:
To a solution of 6-chloro-4-(1-phenylcyclopropylamino)nicotinamide (50 mg, 0.174 mmol) in dioxane (1 mL) was added 1-(4-(4-aminophenyl)piperazin-1-yl)propan-1-one (61 mg, 0.261 mmol), BINAP (22 mg, 0.035 mmol), Pd(OAc)2 (8 mg, 0.035 mmol) and Cs2CO3 (170 mg, 0.52 mmol). After degassed with Argon, the mixture was heated at 80° C. for 15 h. The mixture was diluted with dioxane, precipitate was filtered off, filter cake was washed with AcCN, the filtrate was concentrated and purified by preparative HPLC to give of 4-(1-phenylcyclopropylamino)-6-(4-(4-propionylpiperazin-1-yl)phenylamino)nicotinamide (16 mg). MS found for C28H32N6O2 as (M+H)+ 485.5. λ=258.2.
Reaction SMILES: [Na].[CH3:2][N:3]1[C:11]2[N:10]=[CH:9][N:8]([CH3:12])[C:7]=2[C:6](=[O:13])[NH:5][C:4]1=[O:14].Cl[CH2:16][CH2:17][CH2:18][P:19](=[O:22])([CH3:21])[CH3:20]>>[CH3:2][N:3]1[C:11]2[N:10]=[CH:9][N:8]([CH3:12])[C:7]=2[C:6](=[O:13])[N:5]([CH2:16][CH2:17][CH2:18][P:19](=[O:22])([CH3:21])[CH3:20])[C:4]1=[O:14]
Reactant: CP(C)(=O)CCCCl
Reactant: Cn1cnc2c1c(=O)[nH]c(=O)n2C
Agent: [Na]
Product: Cn1cnc2c1c(=O)n(CCCP(C)(C)=O)c(=O)n2C

Procedure:
The title substance was prepared from 10.1 g (0.05 mol) of 3,7-di-methylxanthine sodium salt and 3-chloropropyldimethylphosphine oxide analogously to Example 59 and crystallized from ethyl acetate.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[CH2:14][N:15]([CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:16](=[O:18])[CH3:17])=[CH:4][CH:3]=1.[CH2:27]([O:29][C:30]([C:32]1([C:35]2[CH:40]=[CH:39][C:38](B3OC(C)(C)C(C)(C)O3)=[CH:37][CH:36]=2)[CH2:34][CH2:33]1)=[O:31])[CH3:28]>>[CH2:27]([O:29][C:30]([C:32]1([C:35]2[CH:40]=[CH:39][C:38]([C:2]3[CH:7]=[CH:6][C:5]([C:8]4[O:12][N:11]=[C:10]([CH3:13])[C:9]=4[CH2:14][N:15]([C:16](=[O:18])[CH3:17])[CH2:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[CH:4][CH:3]=3)=[CH:37][CH:36]=2)[CH2:33][CH2:34]1)=[O:31])[CH3:28]
Reactant: CC(=O)N(CCc1ccccc1)Cc1c(C)noc1-c1ccc(Br)cc1
Reactant: CCOC(=O)C1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4CN(CCc4ccccc4)C(C)=O)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 3, Step 5, using N-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-ylmethyl]-N-phenethyl-acetamide and 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarboxylic acid ethyl ester.
Reaction SMILES: [Si]([O:8][CH2:9][C@@H:10]([N:12]1[CH:16]=[C:15]([CH3:17])[N:14]=[CH:13]1)[CH3:11])(C(C)(C)C)(C)C.Cl>C(Cl)Cl.CCOCC>[CH3:17][C:15]1[N:14]=[CH:13][N:12]([C@@H:10]([CH3:11])[CH2:9][OH:8])[CH:16]=1
Reactant: Cc1cn([C@@H](C)CO[Si](C)(C)C(C)(C)C)cn1
Agent: Cl
Solvent: CCOCC
Solvent: ClCCl
Product: Cc1cn([C@@H](C)CO)cn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 90.6 %

Procedure:
To a solution (S)-1-(1-((tert-butyldimethylsilyl)oxy)propan-2-yl)-4-methyl-1H-imidazole (0.425 g, 1.67 mmol) in DCM (5 mL) was added 3M HCl in ether (10 mL) at room temperature. The resulting mixture was stirred at room temperature overnight. The mixture was concentrated under vacuum. The residue was dissolved in MeOH, and solid NaHCO3 was added. The mixture was stirred at room temperature for 1 h. The solid was filtered and washed with MeOH. The combined organic layers were concentrated to afford the title compound (0.212 g). 1H NMR (CDCl3): δ 7.33 (s, 1H), 6.63 (s, 1H), 4.18-4.12 (m, 1H), 3.78-3.47 (m, 2H), 2.10 (s, 3H), 1.42 (d, 3H); LCMS: 141 (M+H)+.
Reaction SMILES: [CH3:1][N:2]1[CH2:15][CH2:14][C:13]2[C:12]3[CH:11]=[C:10]([CH3:16])[CH:9]=[CH:8][C:7]=3[NH:6][C:5]=2[CH2:4][CH2:3]1.[F:17][C:18]([F:28])([F:27])[C:19]1[CH:24]=[CH:23][C:22]([CH:25]=[CH2:26])=[CH:21][N:20]=1>[OH-].[Na+].[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[CH3:1][N:2]1[CH2:15][CH2:14][C:13]2[C:12]3[CH:11]=[C:10]([CH3:16])[CH:9]=[CH:8][C:7]=3[N:6]([CH2:26][CH2:25][C:22]3[CH:21]=[N:20][C:19]([C:18]([F:28])([F:17])[F:27])=[CH:24][CH:23]=3)[C:5]=2[CH2:4][CH2:3]1
Reactant: Cc1ccc2[nH]c3c(c2c1)CCN(C)CC3
Reactant: C=Cc1ccc(C(F)(F)F)nc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Product: Cc1ccc2c(c1)c1c(n2CCc2ccc(C(F)(F)F)nc2)CCN(C)CC1
Temperature: 120 °C
Yield: 5.6 %

Procedure:
The title compound was prepared by following general procedure 4. To a solution of 3,9-dimethyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (150 mg, 0.69 mmol) in 50% aq. NaOH solution (3 mL) was added, tetra n-butyl ammonium chloride (9 mg, 0.034 mmol) followed by 2-(trifluoromethyl)-5-vinylpyridine (133 mg, 0.76 mmol). The reaction mixture was heated at 120° C. for 8 h and the reaction was monitored by TLC. After completion of reaction, the reaction mixture was diluted with water, extracted with ethyl acetate. The organic layer was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by reverse phase chromatography to afford 15 mg of 3,9-dimethyl-6-(2-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole as the TFA salt.
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O)=[O:2].Br[C:13]1[O:14][CH:15]=[CH:16][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(#N)C>[O:14]1[CH:15]=[CH:16][CH:17]=[C:13]1[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[CH:1]=[O:2]
Reactant: Brc1ccco1
Reactant: O=Cc1ccccc1B(O)O
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: O=Cc1ccccc1-c1ccco1
Temperature: 150 °C
Yield: 35.7 %

Procedure:
A microwave vial (20 ml) was charged with 2-formylphenylboronic acid (298 mg, 2.0 mmol), 2-bromo-furan (350 mg, 2.4 mmol) and 8 ml of acetonitrile. To this mixture was added 4 ml of aqueous sodium carbonate (1M), followed by 100 mg of dichlorobis-(triphenylphosphine)-palladium(II). The reaction vessel was sealed and heated at 150° C. for 5 minutes with microwave irradiation. After cooling, the reaction mixture was extracted with ethylacetate. The organic layer was evaporated to provide a crude material, which was purified by ISCO to give 123 mg of 2-furan-2-yl-benzaldehyde (34% yield).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:10][C:11]([OH:13])=O)=[CH:5][C:4]=1[C:18]([F:21])([F:20])[F:19])#[N:2].[F:22][C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1>>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:10][C:11]([NH:27][C:26]2[CH:28]=[CH:29][C:23]([F:22])=[CH:24][CH:25]=2)=[O:13])=[CH:5][C:4]=1[C:18]([F:21])([F:20])[F:19])#[N:2]
Reactant: CC(C)CN(CC(=O)O)c1ccc(C#N)c(C(F)(F)F)c1
Reactant: Nc1ccc(F)cc1
Product: CC(C)CN(CC(=O)Nc1ccc(F)cc1)c1ccc(C#N)c(C(F)(F)F)c1

Procedure:
Synthesized as described for Example 91C using N-[4-cyano-3-(trifluoromethyl)phenyl]-N-isobutylglycine and 4-fluoroaniline: MS (APCI) m/z 394 (M+1).
Reaction SMILES: [C:1]([C:6]([CH3:17])=[CH:7][CH2:8][CH:9]1[CH2:13][CH:12]=[C:11]([CH3:14])[C:10]1([CH3:16])[CH3:15])([O:3][CH2:4][CH3:5])=[O:2]>CO.[Ni]>[C:1]([CH:6]([CH3:17])[CH2:7][CH2:8][CH:9]1[CH2:13][CH:12]=[C:11]([CH3:14])[C:10]1([CH3:15])[CH3:16])([O:3][CH2:4][CH3:5])=[O:2]
Reactant: CCOC(=O)C(C)=CCC1CC=C(C)C1(C)C
Agent: [Ni]
Solvent: CO
Product: CCOC(=O)C(C)CCC1CC=C(C)C1(C)C
Yield: 93.9 %

Procedure:
A solution of 100 g (0.42 mole) of 2a in 300 mL of methanol was hydrogenated under standard conditions with 5 g of Raney nickel (ca. 10 hours). Filtration, distillation of the solvent, and fractionation yielded 94 g (94%) of 3a, b0.7 92°-95° C.
Reaction SMILES: C(OC([NH:11][C@H:12]1[CH2:17][CH2:16][N:15]([C:18]2[S:19][C:20]([CH3:28])=[C:21]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:22]=2)[CH2:14][C@H:13]1[O:29][CH3:30])=O)C1C=CC=CC=1.[H][H]>C(O)C.[C].[Pd]>[NH2:11][C@H:12]1[CH2:17][CH2:16][N:15]([C:18]2[S:19][C:20]([CH3:28])=[C:21]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:22]=2)[CH2:14][C@H:13]1[O:29][CH3:30]
Reactant: CCOC(=O)c1nc(N2CC[C@H](NC(=O)OCc3ccccc3)[C@H](OC)C2)sc1C
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)c1nc(N2CC[C@H](N)[C@H](OC)C2)sc1C
Yield: 88.2 %

Procedure:
Ethyl cis(±)-2-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)-5-methyl-1,3-thiazole-4-carboxylate obtained in Example (40d) (75 mg, 0.17 mmol) was dissolved in ethanol (3 mL). A 10% palladium-carbon catalyst (40 mg) was added, and the mixture was stirred in a hydrogen atmosphere for 21 hours. The reaction solution was filtered through celite and then concentrated under reduced pressure to obtain 44.9 mg of the title compound as a colorless oily substance. The resulting compound was used for the next reaction without purification.
Reaction SMILES: [N+:1]([C:4]1[CH:8]=[N:7][N:6]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[C:5]=1[CH2:17][OH:18])([O-:3])=[O:2]>C(Cl)(Cl)Cl.[O-2].[O-2].[Mn+4]>[N+:1]([C:4]1[CH:8]=[N:7][N:6]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:14])([CH3:15])[CH3:16])[C:5]=1[CH:17]=[O:18])([O-:3])=[O:2]
Reactant: C[Si](C)(C)CCOCn1ncc([N+](=O)[O-])c1CO
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClC(Cl)Cl
Product: C[Si](C)(C)CCOCn1ncc([N+](=O)[O-])c1C=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 20.1 %

Procedure:
To a solution of [4-nitro-2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazol-3-yl]methanol (7.776 g, 28.38 mmol) in chloroform (500 mL) was added manganese dioxide (29.18 g, 9 eq). The resulting mixture was heated at reflux for 4 hours, cooled to room temperature and stirred overnight. The reaction mixture was again heated to reflux for 3 hours, filtered through a 3 cm plug of celite using additional chloroform. The filtrate was concentrated to give 4.55 g of crude material and purified via silica gel chromatography with a 2-4% ethyl acetate in hexanes gradient to give the title compound as a colorless oil (1.55 g). M+=271
Reaction SMILES: [CH:1](=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[CH3:8][CH2:9][CH2:10]C(=O)CCCC>>[CH:8]#[C:9][CH2:10][CH:1]([OH:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCC(=O)CCC
Reactant: CCCCCC=O
Product: C#CCC(O)CCCCC

Procedure:
When 1-hexanal is substituted for 4-octanone in Example 27, there is obtained the title product.
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[C:10]3[CH:16]=[N:15][NH:14][C:11]3=[N:12][CH:13]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.Br[C:18]1[CH:19]=[C:20]2[N:26](C(OC(C)(C)C)=O)[N:25]=[CH:24][C:21]2=[N:22][CH:23]=1.[Cl:34][C:35]1[C:40](B2OC(C)(C)C(C)(C)O2)=[CH:39][CH:38]=[CH:37][N:36]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[C:10]3[CH:16]=[N:15][NH:14][C:11]3=[N:12][CH:13]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[Cl:34][C:35]1[C:40]([C:18]2[CH:19]=[C:20]3[NH:26][N:25]=[CH:24][C:21]3=[N:22][CH:23]=2)=[CH:39][CH:38]=[CH:37][N:36]=1
Reactant: CC(C)(C)OC(=O)n1ncc2ncc(Br)cc21
Reactant: CC1(C)OB(c2cccnc2Cl)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Clc1ncccc1-c1cnc2[nH]ncc2c1
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: Clc1ncccc1-c1cnc2cn[nH]c2c1

Procedure:
6-(2-Chloropyridin-3-yl)-1H-pyrazolo[4,3-b]pyridine was synthesized in the similar manner to the preparation of 5-(2-chloropyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine by heating the mixture of tert-butyl 6-bromo-1H-pyrazolo[4,3-b]pyridine-1-carboxylate (2.5 g, 8.4 mmol), 2-chloro-3-pyridine boronic acid pinacol ester (2.2 g, 9.2 mmol), Pd(PPh3)4 (610 mg, 0.52 mmol) and 2M aq.Na2CO3 (12 mL, 24 mmol) in 1,4-dioxane (40 mL). Upon work-up of the reaction mixture similar to 5-(2-chloropyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine provided 6-(2-chloropyridin-3-yl)-1H-pyrazolo[4,3-b]pyridine as an off-white crystalline solid. 1H NMR (DMSO-d6): δ 13.50 (s, 1H), 8.57 (app s, 1H), 8.48 (dd, 1H, J=1.7 and 4.7 Hz), 8.35 (s, 1H), 8.12 (s, 1H), 8.02 (dd, 1H, J=1.7 and 7.6 Hz), 7.60 (dd, 1H, J=4.7 and 7.7 Hz).LCMS: rt 4.50 min (A), purity 94%, MS (m/e) 231 (MH+).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=2[C:19]([C:21]2[CH:22]=[N:23][C:24]([CH3:27])=[CH:25][CH:26]=2)=[O:20])(=[O:10])=[O:9])=[CH:4][C:3]=1[F:28].O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:84][C@H:85]1[O:90][C@@H:89]([CH3:91])[CH2:88][NH:87][CH2:86]1>CN(C=O)C.[Pd]>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([NH:11][S:8]([C:5]2[CH:6]=[CH:7][C:2]([N:87]3[CH2:86][C@H:85]([CH3:84])[O:90][C@H:89]([CH3:91])[CH2:88]3)=[C:3]([F:28])[CH:4]=2)(=[O:10])=[O:9])=[C:13]([C:19]([C:21]2[CH:22]=[N:23][C:24]([CH3:27])=[CH:25][CH:26]=2)=[O:20])[CH:14]=1
Reactant: Cc1ccc(C(=O)c2cc(Cl)ccc2NS(=O)(=O)c2ccc(Br)c(F)c2)cn1
Reactant: C[C@@H]1CNC[C@H](C)O1
Agent: [Pd]
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(C(=O)c2cc(Cl)ccc2NS(=O)(=O)c2ccc(N3C[C@@H](C)O[C@@H](C)C3)c(F)c2)cn1

Procedure:
The title compound was prepared according to the general procedure for the synthesis of heterocyclyl and heteroaryl substituted phenylsulfonyl derivatives previously described, using 4-Bromo-N-[4-chloro-2-(6-methyl-pyridine-3-carbonyl)-phenyl]-3-fluoro-benzenesulfonamide 0.2 g (0.4 mmol), potassium phosphate tribasic monohydrate 0.570 g (2.4 mmol), rac-2,2′-bis (diphenylphosphino)-1,1′-binaphthyl 0.077 g (0.12 mmol), cis-2,6-dimethyl-morpholine 0.23 g (2 mmol) and Pd (dba)3 0.057 g (0.06 mmol) in 2 ml DMF. HPLC purification gave yellow compound.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1.[Cl:13][C:14]1[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][C:15]=1[S:21](Cl)(=[O:23])=[O:22]>>[Cl:13][C:14]1[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][C:15]=1[S:21]([NH:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1)(=[O:23])=[O:22]
Reactant: O=S(=O)(Cl)c1cccc(Cl)c1Cl
Reactant: CCOC(=O)Cc1csc(N)n1
Product: CCOC(=O)Cc1csc(NS(=O)(=O)c2cccc(Cl)c2Cl)n1

Procedure:
The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,3-dichlorobenzenesulfonyl chloride as described in the synthetic METHOD B to give a white solid (25.0 mg) with purity >90%. MS (pos) m/z 395.1, 397.1.
Reaction SMILES: Cl.[CH2:2]([O:14][C:15](=[O:22])[C@@H:16]1[CH2:20][C@@H:19]([OH:21])[CH2:18][NH:17]1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13].C(=O)([O-])O.[Na+].[C:28](Cl)(=[O:44])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]>O1CCOCC1.O>[CH2:2]([O:14][C:15](=[O:22])[C@@H:16]1[CH2:20][C@@H:19]([OH:21])[CH2:18][N:17]1[C:28](=[O:44])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: CCCCCCCCCCCCCCCC(=O)Cl
Reactant: CCCCCCCCCCCCOC(=O)[C@@H]1C[C@@H](O)CN1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: CCCCCCCCCCCCCCCC(=O)N1C[C@H](O)C[C@H]1C(=O)OCCCCCCCCCCCC

Procedure:
trans-4-Hydroxy-L-proline dodecyl ester hydrochloride (10 g, 29.8 mmol) was dissolved in 1,4-dioxane (125 ml) and water (125 ml); with stirring, sodium hydrogencarbonate (10.4 g, 123.8 mmol) was firstly added, followed by 1-hexadecanoyl chloride (9 ml, 8.19 g, 29.8 mmol). The reaction mixture was stirred for 1 hour at room temperature. The suspension was adjusted to pH 1 to 1.5 and then filtered. The residue was washed with water until neutral and dried under reduced pressure in the melt. Yield: 15.1 g (28 mmol, 94% of theory, 97 to 100% purity [HFLC]) of a white waxy crystalline mass, m.p.: 39 to 44° C. 1H-NMR (CDCl3)δ=0.89 (6H, t), 1.2 to 1.4 (40H, m), 1.5 to 1.7 (61-1, m), 2.05 to 2.40 (4H, dm), 3.79 (1H, dd), 4.12 (2H, m), 4.5 to 4.6 ppm (2H, m); 13C-NMR (CDCl3)δ=172.50 (s), 172.48 (s), 70.4 (d), 65.4 (t), 57.6 (d), 55.1 (t), 37.9 (t), 34.6 (t), 32.0, 29.72 (2C), 29.70 (2C), 29.68 (4C), 29.66, 29.62, 29.56 (2C), 29.48, 29.40, 29.38 (2C,), 29.28, 28.56, 25.85, 24.68, 22.70 (2C), 14.1 (2C, q,q). Elemental analysis: calc.: C 73.7%, H 11.8%, N 2.6%, O 11.9%; found: C 73.5%, H 11.8%, N 2.5%, O 12.2%.
Reaction SMILES: [CH3:1][N:2]([CH3:17])[CH2:3][CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([N+:14]([O-])=O)=[CH:11][CH:12]=2)[CH:7]=[N:6]1.[Cl-].[NH4+]>[Fe].C(O)C.O>[CH3:1][N:2]([CH3:17])[CH2:3][CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([NH2:14])=[CH:11][CH:12]=2)[CH:7]=[N:6]1
Reactant: CN(C)CCn1ncc2cc([N+](=O)[O-])ccc21
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: CN(C)CCn1ncc2cc(N)ccc21
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 91.1 %

Procedure:
A mixture of dimethyl-[2-(5-nitro-indazol-1-yl)-ethyl]-amine (1 g, 4.3 mmol), iron powder (1.9 g, 34 mmol), and ammonium chloride (120 mg, 2.2 mmol) in a 4:1 ethanol/H2O solution (20 mL) was heated to reflux for 3 hours, cooled to room temperature and concentrated under reduced pressure. The residue was stirred in triethylamine/ethyl acetate (1/4, 10 mL) for 15 minutes and then filtered through a plug of silica gel which was rinsed with triethylamine/ethyl acetate (1/4). The filtrate was concentrated under reduced pressure to provide the title compound (0.80 g, 92%). 1H NMR (300 MHz, DMSO-d6) ppm 2.15 (s, 6H), 2.64 (t, J=6.44, 2H), 4.34 (t, J=6.44, 2H), 4.77 (s, 2H), 6.72 (m, 1H), 6.79 (m, 1H), 7.35 (m, 1H), 7.67 (m, 1H); MS (DCI/NH3) m/z 205 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:21]=[CH:20][C:5]2[C:6]([C:9]3[CH:14]=[CH:13][C:12]([O:15][CH2:16][C@H:17]4[CH2:19][O:18]4)=[CH:11][CH:10]=3)=[N:7][O:8][C:4]=2[CH:3]=1.[N:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1>CN(C)C=O.C(O)C>[F:1][C:2]1[CH:21]=[CH:20][C:5]2[C:6]([C:9]3[CH:10]=[CH:11][C:12]([O:15][CH2:16][C@H:17]([OH:18])[CH2:19][N:31]4[CH2:32][CH2:33][N:28]([C:23]5[CH:24]=[CH:25][CH:26]=[CH:27][N:22]=5)[CH2:29][CH2:30]4)=[CH:13][CH:14]=3)=[N:7][O:8][C:4]=2[CH:3]=1
Reactant: c1ccc(N2CCNCC2)nc1
Reactant: Fc1ccc2c(-c3ccc(OC[C@H]4CO4)cc3)noc2c1
Solvent: CN(C)C=O
Solvent: CCO
Product: O[C@@H](COc1ccc(-c2noc3cc(F)ccc23)cc1)CN1CCN(c2ccccn2)CC1

Procedure:
The title compound is prepared from a mixture of (R)-6-fluoro-3-(4-oxiranylmethoxy-phenyl)-benzo[d]isoxazole in dimethylformamide and 1-pyridin-2-yl-piperazine in ethanol essentially as described above in Example 21. Purity by LC/MS=100%, [M+H]+=449.