Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C@@H:4]([CH2:11][CH2:12][CH2:13][CH2:14][O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:5][CH2:6][C:7]([O:9][CH3:10])=[O:8])[CH:2]=[CH2:3].C1(C2CCCCCCCC2)BCCCCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:50]1[CH:51]=[N:52][CH:53]=[CH:54][CH:55]=1.[OH-].[Na+].OO>O1CCCC1.CCOCC>[N:52]1[CH:53]=[CH:54][CH:55]=[C:50]([CH2:3][CH2:2][CH2:1][C@H:4]([CH2:11][CH2:12][CH2:13][CH2:14][O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:5][CH2:6][C:7]([O:9][CH3:10])=[O:8])[CH:51]=1
Reactant: C=CC[C@@H](CCCCOCc1ccccc1)CCC(=O)OC
Reactant: Brc1cccnc1
Agent: B1CCCCCCCC1C1CCCCCCCC1
Agent: O=P([O-])([O-])[O-]
Agent: OO
Solvent: CCOCC
Solvent: C1CCOC1
Product: COC(=O)CC[C@@H](CCCCOCc1ccccc1)CCCc1cccnc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of methyl 4(S)-allyl-8-(benzyloxy)octanoate (2.4 g, 7.9 mmol) in dry tetrahydrofuran (20 ml) under nitrogen is added a 0.5 M solution of 9-borabicyclononane in tetrahydrofuran (23.6 ml, 11.8 mmol) and the mixture is allowed to stir at room temperature for 18 hours. The reaction mixture is added to a solution of tetrakis-triphenylphosphine palladium (O) (0.13 g, 0.11 mmole as catalyst) and potassium phosphate (5.36 g, 23.3 mmole in tetrahydrofurane (4 ml). Then 3-bromopyridine (1.2 ml, 12.5 mmol) is added and the mixture is heated at reflux for 48 hours. The reaction mixture is cooled down to 0° C. and a 15% solution of sodium hydroxide (8.9 ml) is added followed by hydrogen peroxide (8.9 ml, 30% solution). The mixture is stirred at room temperature for 1.5 hour and then diluted with ether. The organic phase is washed with brine (3×30 ml) and saturated sodium sulfite solution (30 ml). The organic phase is dried, filtered and evaporated to give a dark oil which is purified by flash chromatography on silica gel using 3:2 ether/hexane as eluent to yield methyl 4(R)-[3-(3-pyridyl)propyl]-8-(benzyloxy)octanoate; IR (CH2Cl2): 1732, 1101, 896 cm- 1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[C:6]2=[N+:13]=[N-:14].[C:15]([O:19][CH2:20][CH3:21])(=[O:18])[C:16]#[CH:17]>C1C=CC=CC=1>[CH2:20]([O:19][C:15](=[O:18])[CH:16]=[CH:17][N:8]1[C:9]2[CH:10]=[CH:11][C:3]([O:2][CH3:1])=[CH:4][C:5]=2[C:6]2=[CH:17][C:16]([C:15]([O:19][CH2:20][CH3:21])=[O:18])=[N:14][N:13]2[C:7]1=[O:12])[CH3:21]
Reactant: C#CC(=O)OCC
Reactant: COc1ccc2c(c1)C(=[N+]=[N-])C(=O)N2
Solvent: c1ccccc1
Product: CCOC(=O)C=Cn1c(=O)n2nc(C(=O)OCC)cc2c2cc(OC)ccc21
Temperature: 25 °C

Procedure:
1.5 g (0.0079 mole) of 5-methoxy-3-diazooxindole and 0.99 g (0.01 mole of 1.3 equiv.) of 99% ethyl propiolate are refluxed in benzene (50 ml) under N2 for 24 hours. The reaction mixture is cooled down to room temperature and the precipitates that form are filtered off and washed well with ether, dried in a vacuum oven at 60° for 2 hours. Yield: 661.8 mg, m.p. 202°-204°, Rf 0.3. This crude product is taken up in 75 ml of absolute ethanol, treated with activated carbon, filtered through a celite pad and the clear filtrate is concentrated down to a volume of ~50 ml on the steam bath. After cooling, the precipitates that form are filtered off. The product is dried overnight in a vacuum oven at room temperature. Yield: 555.4 mg, m.p. 225°-227°.
Reaction SMILES: C(N(CC)CC)C.Cl.Cl.[NH2:10][C@H:11]1[CH:16]2[CH2:17][CH2:18][N:13]([CH2:14][CH2:15]2)[CH2:12]1.[F:19][C:20]([F:31])([F:30])[C:21]1[CH:26]=[CH:25][C:24]([C:27](O)=[O:28])=[CH:23][CH:22]=1.[I-].ClC1C=CC=C[N+]=1C>O.C(#N)C>[N:13]12[CH2:18][CH2:17][CH:16]([CH2:15][CH2:14]1)[C@H:11]([NH:10][C:27](=[O:28])[C:24]1[CH:25]=[CH:26][C:21]([C:20]([F:19])([F:30])[F:31])=[CH:22][CH:23]=1)[CH2:12]2
Reactant: O=C(O)c1ccc(C(F)(F)F)cc1
Reactant: N[C@@H]1CN2CCC1CC2
Agent: C[n+]1ccccc1Cl
Agent: Cl
Agent: [I-]
Solvent: CCN(CC)CC
Solvent: O
Solvent: CC#N
Product: O=C(N[C@@H]1CN2CCC1CC2)c1ccc(C(F)(F)F)cc1
Reaction time: 8 h
Yield: 93.2 %

Procedure:
1.5 ml of Acetonitrile and Triethylamine (700 uL, 5.0 mmol) was added to a flask charged with (S)-(−)-3-Aminoquinuclidine dihydrochloride (199 mg, 1.0 mmol) and α,α,α-Trifluoro-p-toluic acid (209 mg, 1.1 mmol), followed by addition of 2-Chloro-1-methyl pyridinium iodide (383 mg, 1.5 mmol) at room temperature. After stirring overnight, about 2 ml of water was added to reaction mixture to resolve a clear solution that was subsequently injected into a Preparative HPLC instrument for purification. Desired fractions were combined, concentrated under vacuum, and then recrystallized from 4 mL of Methanol/water (3:2) to isolate white crystalline solid of (S)—N-(quinuclidin-3-yl)-4-(trifluoromethyl)benzamide (278 mg, 93% yield). 1H NMR (400 MHz, Methanol-D4) δ (ppm): 8.05 (d, J=8.2 Hz, 1H), 7.82 (d, J=8.2 Hz, 1H), 4.47 (m, 1H), 3.87 (t, J=11.8, 11.8 Hz, 1H), 3.38 (m, 4H), 2.39 (m, 1H), 2.27 (m, 2H), 2.13 (t, J=8.2 Hz, 1H). LCMS (ESI): m/z 299.1 (M+H [C15H17F3N2O]=299.13).
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([C@@H:15]3[CH2:17][C@@H:16]3[F:18])=[O:14])[N:8]=[CH:9]2)=[CH:4][N:3]=1.[CH3:19][C:20]1[CH:25]=[CH:24][N:23]=[CH:22][C:21]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.C(OCC)(=O)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[F:18][C@H:16]1[CH2:17][C@H:15]1[C:13]([NH:12][C:7]1[N:8]=[CH:9][C:10]2[C:5]([CH:6]=1)=[CH:4][N:3]=[C:2]([C:21]1[CH:22]=[N:23][CH:24]=[CH:25][C:20]=1[CH3:19])[CH:11]=2)=[O:14]
Reactant: Cc1ccncc1B(O)O
Reactant: O=C(Nc1cc2cnc(Cl)cc2cn1)[C@@H]1C[C@@H]1F
Agent: Cl[Pd]Cl
Agent: CN(C)c1ccc(P(C(C)(C)C)C(C)(C)C)cc1
Agent: O=C([O-])[O-]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: Cc1ccncc1-c1cc2cnc(NC(=O)[C@@H]3C[C@@H]3F)cc2cn1
Temperature: 130 °C
Yield: 35.7 %

Procedure:
A mixture of (1S,2S)—N-(7-chloro-2,6-naphthyridin-3-yl)-2-fluorocyclopropanecarboxamide (40 mg, 0.2 mmol), 4-methylpyridine-3-boronic acid (62 mg, 0.45 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (11 mg, 0.015 mmol), and saturated aqueous sodium carbonate (0.1 mL) in acetonitrile (1 mL) was heated under microwave irradiation (Biotage, 200 watts) at 130° C. for 30 minutes. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min) to afford the title compound as an off-white solid (23 mg, 50%). 1H NMR (400 MHz, DMSO) δ 11.19 (s, 1H), 9.50 (s, 1H), 9.34 (s, 1H), 8.68 (s, 1H), 8.68 (s, 1H), 8.50 (d, J=5.0 Hz, 1H), 8.19 (s, 1H), 7.39 (d, J=5.0 Hz, 1H), 4.97 (m, 1H), 2.44 (s, 3H), 2.31 (m, 1H), 1.72 (m, 1H), 1.28-1.16 (m, 1H). LCMS (Method E): RT=2.980 min, M+H+=323.1.
Reaction SMILES: [F:1][C:2]1[C:21]([NH:22][S:23]([CH2:26][CH2:27][CH3:28])(=[O:25])=[O:24])=[CH:20][CH:19]=[C:18]([F:29])[C:3]=1[C:4]([C:6]1[C:14]2[C:9](=[N:10][CH:11]=[C:12]([C:15](O)=[O:16])[CH:13]=2)[NH:8][CH:7]=1)=[O:5].F[P-](F)(F)(F)(F)F.[N:37]1(OC(N(C)C)=[N+](C)C)[C:41]2[CH:42]=[CH:43][CH:44]=C[C:40]=2[N:39]=N1.C(N(CC)CC)C.N1C=CC=C(N)C=1>CN(C)C=O.O.C(OCC)(=O)C>[N:39]1[CH:44]=[CH:43][CH:42]=[C:41]([NH:37][C:15]([C:12]2[CH:13]=[C:14]3[C:6]([C:4](=[O:5])[C:3]4[C:18]([F:29])=[CH:19][CH:20]=[C:21]([NH:22][S:23]([CH2:26][CH2:27][CH3:28])(=[O:25])=[O:24])[C:2]=4[F:1])=[CH:7][NH:8][C:9]3=[N:10][CH:11]=2)=[O:16])[CH:40]=1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Reactant: CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(C(=O)O)cc23)c1F
Agent: F[P-](F)(F)(F)(F)F
Agent: Nc1cccnc1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(C(=O)Nc4cccnc4)cc23)c1F
Reaction time: 0.25 h

Procedure:
In a reaction vial, 3-[2,6-difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid (41, 13 mg, 0.031 mmol) is dissolved in 0.5 mL of N,N-dimethylformamide and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (17 mg, 0.046 mmol) is added followed by triethylamine (21 μL, 0.15 mmol). The mixture is stirred for 15 minutes, then pyridin-3-ylamine (42, 29 mg, 0.31 mmol) is added and the reaction is stirred at room temperature overnight. The reaction is diluted with water and ethyl acetate. The aqueous phase is separated and extracted with ethyl acetate. The organic layers are combined and dried with sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by reverse phase chromatography to provide the desired compound. MS (ESI) [M+H+]+=500.0.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:10]2([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[C:18]3[C:13](=[C:14]([F:19])[CH:15]=[CH:16][CH:17]=3)[C:12]([NH2:20])=[N:11]2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[N:31]1[CH:36]=[C:35](B(O)O)[CH:34]=[N:33][CH:32]=1.C(=O)([O-])[O-].[K+].[K+].CO>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:19][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:13]=1[C:12]([NH2:20])=[N:11][C:10]2([C:4]1[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([C:35]2[CH:36]=[N:31][CH:32]=[N:33][CH:34]=2)[CH:3]=1)[C:21]1[CH:26]=[CH:25][N:24]=[C:23]([C:27]([F:28])([F:29])[F:30])[CH:22]=1
Reactant: COc1ccc(C2(c3ccnc(C(F)(F)F)c3)N=C(N)c3c(F)cccc32)cc1Br
Reactant: OB(O)c1cncnc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CO
Solvent: CN(C)C=O
Product: COc1ccc(C2(c3ccnc(C(F)(F)F)c3)N=C(N)c3c(F)cccc32)cc1-c1cncnc1
Temperature: 150 °C
Yield: 43.3 %

Procedure:
1-(3-Bromo-4-methoxyphenyl)-4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-3-amine (1.5 g, 3.12 mmol), pyrimidin-5-ylboronic acid (0.542 g, 4.37 mmol), [1,1′-bis (diphenylphosphino)ferrocene]palladium(II) chloride (0.128 g, 0.16 mmol) and aqueous potassium carbonate (2M, 4.69 mL, 9.37 mmol) were dissolved in DMF (14 mL). The resulting mixture was heated to 150° C. for 20 mins by microwaves. Methanol (20 mL) was added and the mixture concentrated in vacuo. Dichloromethane (40 mL), water (20 mL) and brine (5 mL) were added and the organic phase separated and evaporated directly on silica. The crude product was purified by gradient column chromatography (40 g silica column eluted with 0-10% [0.1M ammonia in methanol] in dichloromethane). The desired fractions were combined and evaporated to give 648 mg (43%) of the title compound.
Reaction SMILES: [NH2:1][C@H:2]1[CH2:8][CH2:7][CH2:6][CH2:5][N:4]([CH:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)[C:3]1=[O:21].O=[C:23]([CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:24]([OH:26])=[O:25].C([BH3-])#N.[Na+]>>[C:18]([CH:9]([N:4]1[CH2:5][CH2:6][CH2:7][CH2:8][C@H:2]([NH:1][CH:23]([C:24]([OH:26])=[O:25])[CH2:27][CH2:28][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:3]1=[O:21])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)([OH:20])=[O:19]
Reactant: N[C@H]1CCCCN(C(Cc2ccc(O)cc2)C(=O)O)C1=O
Reactant: O=C(O)C(=O)CCc1ccccc1
Agent: [BH3-]C#N
Agent: [Na+]
Product: O=C(O)C(CCc1ccccc1)N[C@H]1CCCCN(C(Cc2ccc(O)cc2)C(=O)O)C1=O

Procedure:
Methyl 3-(p-phydroxyphenyl)-2-oxopropionate and α-t-Boc-L-lysine are condensed in the presence of sodium cyanoborohydride as described in Example 19. Subsequent ring closure, saponification of methyl ester, and removal of the t-butoxycarbonyl group with formic acid gives 3-(S)-amino-1-[1-carboxy-2-(4-hydroxyphenyl)ethyl]perhydroazepin-2-one. The caprolactam and 2-oxo-4-phenylbutyric acid are condensed in the presence of sodium cyanoborohydride to yield 1-[1-carboxy-2-(4-hydroxyphenyl)ethyl]-3-(S)-[(1-carboxy-3-phenylpropyl)amino]perhydroazepin-2-one.
Reaction SMILES: O[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]2[CH2:13][CH2:12][CH2:11][CH:10]2[C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)[CH:15]=2)[N:3]=1.[NH2:25][C:26]1[CH:30]=[C:29]([CH3:31])[NH:28][N:27]=1>>[CH3:31][C:29]1[NH:28][N:27]=[C:26]([NH:25][C:2]2[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]3[CH2:13][CH2:12][CH2:11][CH:10]3[C:14]3[O:18][N:17]=[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[CH:15]=3)[N:3]=2)[CH:30]=1
Reactant: Cc1cc(O)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1
Reactant: Cc1cc(N)n[nH]1
Product: Cc1cc(Nc2cc(C)[nH]n2)nc(N2CCCC2c2cc(-c3ccccn3)no2)n1

Procedure:
Starting materials: 4-hydroxy-6-methyl-2-[2-{3-(pyrid-2-yl)isoxazol-5-yl}pyrrolidin-1-yl]pyrimidine (Method 30) and 3-amino-5-methyl-1H-pyrazole.
Reaction SMILES: C([O-])(=O)C.[CH3:5][NH3+:6].[NH2:7][C:8]1[CH:15]=[CH:14][CH:13]=[C:12](F)[C:9]=1[C:10]#[N:11]>CNC=O>[NH2:7][C:8]1[CH:15]=[CH:14][CH:13]=[C:12]([NH:6][CH3:5])[C:9]=1[C:10]#[N:11]
Reactant: N#Cc1c(N)cccc1F
Reactant: C[NH3+]
Agent: CC(=O)[O-]
Solvent: CNC=O
Product: CNc1cccc(N)c1C#N

Procedure:
The title compound is prepared by heating a 10 molar excess of methylammonium acetate and 2-amino-6-fluorobenzonitrile in N-methyl formamide at 140° C. for 5 hrs.
Reaction SMILES: [CH:1]1([N:6]2[C:14]3[CH:13]=[C:12]([C:15]4[CH:20]=[CH:19][C:18]([CH2:21]O)=[CH:17][CH:16]=4)[CH:11]=[C:10]([C:23]([NH:25][CH2:26][C:27]4[C:28](=[O:35])[NH:29][C:30]([CH3:34])=[CH:31][C:32]=4[CH3:33])=[O:24])[C:9]=3[CH:8]=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:56].O>C(Cl)Cl>[Br:56][CH2:21][C:18]1[CH:17]=[CH:16][C:15]([C:12]2[CH:11]=[C:10]([C:23]([NH:25][CH2:26][C:27]3[C:28](=[O:35])[NH:29][C:30]([CH3:34])=[CH:31][C:32]=3[CH3:33])=[O:24])[C:9]3[CH:8]=[N:7][N:6]([CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)[C:14]=3[CH:13]=2)=[CH:20][CH:19]=1
Reactant: BrC(Br)(Br)Br
Reactant: Cc1cc(C)c(CNC(=O)c2cc(-c3ccc(CO)cc3)cc3c2cnn3C2CCCC2)c(=O)[nH]1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: O
Product: Cc1cc(C)c(CNC(=O)c2cc(-c3ccc(CBr)cc3)cc3c2cnn3C2CCCC2)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 58.6 %

Procedure:
To a stirred solution of 1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-(hydroxymethyl)phenyl)-1H-indazole-4-carboxamide (1.5 g, 3.2 mmol) in DCM (20 mL), triphenyl phosphine (1.33 g, 5.10 mmol) was added and stirred at room temperature for 10 min. CBr4 (1.69 g, 5.10 mmol) was then added portion-wise to it and the resulting solution stirred at room temperature overnight. After completion, water was added and extraction was carried out using DCM. The combined organic layers were washed with water, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford crude material which was purified by column chromatography to give 6-(4-(bromomethyl)phenyl)-1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide (1.0 g, 58.8%).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([CH2:22][C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)=[CH:18][N:17]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.O1C2C=CC(C3(C(NC4C=CC(Br)=CN=4)=O)CC3)=CC=2OC1.[Br-].C1(C[Zn+])CCCCC1>>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([CH2:22][CH:23]5[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]5)=[CH:18][N:17]=4)=[O:14])[CH2:11][CH2:12]3)=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: O=C(Nc1ccc(Cc2ccccc2)cn1)C1(c2ccc3c(c2)OCO3)CC1
Agent: O=C(Nc1ccc(Br)cn1)C1(c2ccc3c(c2)OCO3)CC1
Agent: [Br-]
Agent: [Zn+]CC1CCCCC1
Product: O=C(Nc1ccc(CC2CCCCC2)cn1)C1(c2ccc3c(c2)OCO3)CC1

Procedure:
1-(Benzo[d][1,3]dioxol-5-yl)-N-(5-(cyclohexylmethyl)pyridin-2-yl)cyclopropanecarboxamide was synthesized using the procedure of 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-benzylpyridin-2-yl)cyclopropanecarboxamide by reacting 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-bromopyridin-2-yl)cyclopropanecarboxamide with (cyclohexylmethyl)zinc(II) bromide.
Reaction SMILES: C(OP([CH:9]1[S:13][CH2:12][CH2:11][S:10]1)(OCC)=O)C.CCCCCC.C([Li])CCC.[CH:25]1[CH:30]=[CH:29][C:28]([C:31]([CH2:33][CH2:34][O:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=O)=[CH:27][CH:26]=1.[Cl-].[Na+]>O1CCCC1>[O:35]([C:34]1[CH:26]=[CH:27][C:28]([C:29](=[C:9]2[S:10][CH2:11][CH2:12][S:13]2)[CH2:30][CH3:25])=[CH:31][CH:33]=1)[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1
Reactant: O=C(CCOc1ccccc1)c1ccccc1
Reactant: CCOP(=O)(OCC)C1SCCS1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCC(=C1SCCS1)c1ccc(Oc2ccccc2)cc1
Temperature: 25 °C
Yield: 73 %

Procedure:
2-Diethoxyphosphoryl-1,3-dithiolan, 3.0 g, was dissolved in 30 ml of tetrahydrofuran and 7.75 ml of 1.6 mole hexane solution of n-butyl lithium was dropwise added to the solution in an argon flow at -65° C. The mixture was stirred at the same temperature for an hour. Then, a solution of 2.55 g of 4-phenoxypropiophenone in 9 ml of tetrahydrofuran was dropwise added to the mixture at the same temperature. The reaction mixture was gradually warmed to room temperature overnight. This suspension was poured onto saturated sodium chloride aqueous solution and the mixture was extracted with chloroform. After drying the chloroform phase over magnesium sulfate, the solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (chloroform : hexane =1 : 1) to give 2.60 g of the product.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[CH:18]=[C:17]3[C:13]([CH:14]=[CH:15][N:16]3[C:19]3[CH:24]=[CH:23][N:22]=[C:21]([NH2:25])[N:20]=3)=[CH:12][CH:11]=2)[CH:7]=[CH:8][CH:9]=1)([O-])=O.O.O.Cl[Sn]Cl.C(=O)(O)[O-].[Na+]>C(O)C>[NH2:1][C:4]1[CH:5]=[C:6]([C:10]2[CH:18]=[C:17]3[C:13]([CH:14]=[CH:15][N:16]3[C:19]3[CH:24]=[CH:23][N:22]=[C:21]([NH2:25])[N:20]=3)=[CH:12][CH:11]=2)[CH:7]=[CH:8][CH:9]=1
Reactant: Nc1nccc(-n2ccc3ccc(-c4cccc([N+](=O)[O-])c4)cc32)n1
Agent: Cl[Sn]Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Nc1cccc(-c2ccc3ccn(-c4ccnc(N)n4)c3c2)c1
Temperature: 100 °C
Reaction time: 3 h
Yield: 60.1 %

Procedure:
4-(6-(3-Nitrophenyl)-1H-indol-1-yl)pyrimidin-2-amine (76.8 mg, 0.232 mmol) was dissolved in ethanol and, after adding SnCl2.2H2O (262 mg, 1.159 mmol), the mixture was stirred at 100° C. for 3 hours. The reaction mixture was added to sodium bicarbonate aqueous solution and extracted with ethyl acetate. The combined organic layer was washed with brine, dried with magnesium sulfate, and concentrated under reduced pressure. Purification of the residue by column chromatography (silica gel, MC:MeOH=20:1) yielded 4-(6-(3-aminophenyl)-1H-indol-1-yl)pyrimidin-2-amine (42 mg).
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:4]=[C:5]([S:9]([NH2:12])(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1.ClN1C(=[O:19])CCC1=O>CO>[CH3:1][S:2]([C:3]1[CH:4]=[C:5]([S:9]([NH2:12])(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1)=[O:19]
Reactant: CSc1cccc(S(N)(=O)=O)c1
Reactant: O=C1CCC(=O)N1Cl
Solvent: CO
Product: CS(=O)c1cccc(S(N)(=O)=O)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 57 %

Procedure:
A mixture of 3-methylsulfanyl-benzenesulfonamide (406 mg, 2 mmol) and N-chlorosuccinimide (268 mg, 2 mmol) in methanol was stirred at room temperature for 8 hours. The methanol was evaporated and the residue was slurried with methylene chloride and filtered. The filtrate was evaporated to give 250 mg of the titled compound as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:14][OH:15])[C:11]3[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[CH3:28][O:29][C:30](=[O:39])[C:31]1[CH:36]=[C:35](Cl)[C:34](O)=[N:33][CH:32]=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>>[CH3:28][O:29][C:30](=[O:39])[C:31]1[CH:36]=[CH:35][C:34]([O:15][CH2:14][CH:13]([N:12]2[C:11]3[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:10]=3[N:9]=[C:8]2[C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)=[N:33][CH:32]=1
Reactant: OCC(C1CCCCC1)n1c(-c2ccc(Cl)cc2)nc2cc(F)c(F)cc21
Reactant: COC(=O)c1cnc(O)c(Cl)c1
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Product: COC(=O)c1ccc(OCC(C2CCCCC2)n2c(-c3ccc(Cl)cc3)nc3cc(F)c(F)cc32)nc1

Procedure:
The title compound was prepared in analogy to Example 4, intermediate, from 2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanol (Ex. 1, int. c) and 5-chloro-6-hydroxy-nicotinic acid methyl ester and replacing di-ethyl azodicarboxylate by di-tert-butyl azodicarboxylate. White solid (83%). MS (Turbo Spray): m/z=560.3 [M+H].
Reaction SMILES: [CH2:1]1[O:9][C:8]2[C:3](=[CH:4][C:5]([N+:22]([O-])=O)=[C:6]([C:10]3[CH:11]=[C:12]4[C:17](=[CH:18][CH:19]=3)[CH:16]=[C:15]([O:20][CH3:21])[CH:14]=[CH:13]4)[CH:7]=2)[O:2]1>C(OCC)(=O)C.[Pd]>[NH2:22][C:5]1[CH:4]=[C:3]2[O:2][CH2:1][O:9][C:8]2=[CH:7][C:6]=1[C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[CH:16]=[C:15]([O:20][CH3:21])[CH:14]=[CH:13]2
Reactant: COc1ccc2cc(-c3cc4c(cc3[N+](=O)[O-])OCO4)ccc2c1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COc1ccc2cc(-c3cc4c(cc3N)OCO4)ccc2c1
Yield: 75.8 %

Procedure:
6-(4,5-Methylenedioxy-2-nitrophenyl)-2-methoxynaphthalene 45 (260 mg, 0.81 mmol) was hydrogenated overnight in ethyl acetate (35 mL) at 40˜45 lb./sq. in. using 10% palladium on carbon (70 mg) as catalyst. The reaction solution was passed through a Celite bed and the catalyst was washed with ethyl acetate (10 mL×3). Concentration of the ethyl acetate solution in vacuo gave the crude product. The residue was chromatographed using a 75:25 mixture of hexanes:ethyl acetate to give 46 (180 mg) in 76% yield; mp 130-132° C.; IR (KBr) 3463, 3372, 2874, 1631, 1494, 1441, 1389, 1260, 1187cm−1; UV (MeOH) 234 nm (log ε=4.73); 1H NMR (CDCl3) δ3.56 (2H, s), 3.95 (3H, s), 5.92 (2H, s), 6.40 (1H, s), 6.75 (1H, s), 7.17-7.22 (2H, m), 7.51 (1H, dd, J1=8.5, J2=1.6), 7.73-7.82 (3H, m); 13C NMR δ55.84, 98.33, 101.25, 106.11, 110.71, 119.66, 120.30, 127.79, 128.27, 128.61, 129.60, 129.91, 133.95, 135.11, 138.95, 141.17, 148.05, 158.29; HRMS (EI) calcd for C18H15NO3 m/z: 293.1052; found: 293.1051.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:26])[C:7]=1[NH:8][C:9]1[NH:10][C:11]2[C:17]3[CH2:18][C:19]([CH3:22])([CH3:21])[O:20][C:16]=3[C:15]([C:23]([OH:25])=O)=[CH:14][C:12]=2[N:13]=1.F[B-](F)(F)F.[N:32]1(OC(N(C)C)=[N+](C)C)[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=2N=N1.CN1CCOCC1.C1(N)CCCCC1>C1COCC1.CN(C=O)C>[CH:36]1([NH:32][C:23]([C:15]2[C:16]3[O:20][C:19]([CH3:22])([CH3:21])[CH2:18][C:17]=3[C:11]3[NH:10][C:9]([NH:8][C:7]4[C:2]([Cl:1])=[CH:3][N:4]=[CH:5][C:6]=4[Cl:26])=[N:13][C:12]=3[CH:14]=2)=[O:25])[CH2:37][CH2:38][CH2:39][CH2:40][CH2:35]1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Reactant: CC1(C)Cc2c(c(C(=O)O)cc3nc(Nc4c(Cl)cncc4Cl)[nH]c23)O1
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: NC1CCCCC1
Solvent: C1CCOC1
Product: CC1(C)Cc2c(c(C(=O)NC3CCCCC3)cc3nc(Nc4c(Cl)cncc4Cl)[nH]c23)O1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 8.3 %

Procedure:
To a solution 2-[(3,5-dichloropyridin-4-yl)amino]-7,7-dimethyl-7,8-dihydro-1H-furo[3,2-e]benzimidazole-5-carboxylic acid (Intermediate-3, 0.050 g, 0.127 mmol) in mixture of DMF (0.5 mL) and THF (3.0 mL), were added O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (0.082 g, 0.255 mmol, TBTU), N-methyl morpholine (1.0 mL). The reaction mass was stirred at RT for 30 minutes. Then to the reaction mass added cyclohexyl amine (0.020 g, 0.202 mmol). The reaction mass was stirred at RT for 14-16 h. The reaction mass was quenched in water and extracted with ethyl acetate. The organic layer was washed with sodium bicarbonate and dilute HCl solution, and dried over anhydrous sodium sulphate and concentrated to afford 0.005 g of the desired product. 1HNMR (DMSO-d6): δ 1.15-1.35 (m, 7H), 1.48 (s, 3H), 1.58 (m, 2H), 1.79 (m, 2H), 3.00-3.07 (m, 4H), 3.80 (m, 1H), 7.20 (s, 1H), 7.66 (d, J=7.5 Hz, 1H), 8.41 (s, 2H), 10.89 (s, 1H), 11.39 (s, 1H); MS [M−H]−: 472.43.