Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2](=[CH2:14])[CH2:3][C@H:4]([C@H:9]([OH:13])[CH2:10][CH2:11][CH3:12])[C:5]([O:7][CH3:8])=[O:6]>[Pd].CO>[CH3:14][CH:2]([CH3:1])[CH2:3][C@H:4]([C@H:9]([OH:13])[CH2:10][CH2:11][CH3:12])[C:5]([O:7][CH3:8])=[O:6]
Reactant: C=C(C)C[C@@H](C(=O)OC)[C@H](O)CCC
Agent: [Pd]
Solvent: CO
Product: CCC[C@@H](O)[C@@H](CC(C)C)C(=O)OC
Reaction time: 8 h
Yield: 92.9 %

Procedure:
A mixture of methyl (2R,3R)-2-(2-methyl-2-propene-1-yl)-3-hydroxyhexanoate (7 g, 34.6 mmol) and 1.7 g of 5% palladium on carbon (50 wt. % water content) in 50 mL of MeOH is stirred overnight under hydrogen gas at 1 atmosphere pressure. Filtration and concentration of the filtrate under reduced pressure affords 6.5 g (93%) of methyl (2R,3R)-2-(2-methyl-1-propyl)-3-hydroxyhexanoate as an oil.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:6]=[C:5]2[CH2:17][C:18]#[N:19].[C:20]1(B(O)O)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C([O-])([O-])=O.[Na+].[Na+].O>COCCOC.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:18]([CH2:17][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:3]=2)[N:7]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:6]=1)#[N:19]
Reactant: OB(O)c1ccccc1
Reactant: CCOC(=O)Cn1cc(CC#N)c2cc(Br)ccc21
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: COCCOC
Product: CCOC(=O)Cn1cc(CC#N)c2cc(-c3ccccc3)ccc21
Temperature: 25 °C
Reaction time: 12 h
Yield: 45.1 %

Procedure:
5-Bromo-3-cyanomethyl-indole-N-acetic acid, ethyl ester (1.0 g, 3.1 mmol) and phenylboronic acid (0.418 g, 3.4 mmol) were dissolved in anhydrous DME at room temperature under a nitrogen atmosphere and treated with Pd(OAc)2 (2.1 mg, 0.0093 mmol) and PPh3 (7.4 mg, 0.028 mmol). This mixture was heated to reflux and 2 M Na2CO3 (3.11 mL, 6.2 mmol) was added via syringe. After 12 h, the mixture was cooled to room temperature and added to H2O (50 mL). The resultant mixture was extracted with EtOAc (2×, 100 mL) and the organics were combined and washed with a sat'd aqueous NaCl solution, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by SiO2 flash chromatography (heptane to 1:1 heptane/EtOAc) to give the desired material as a white solid (445 mg, 45%); 1H NMR (DMSO-d6, 300 MHz) δ 7.64-7.74 (m, 4H), 7.39-7.44 (m, 4H), 7.29-7.34 (m, 1H), 5.20 (s, 2H), 4.15 (q, J=7.2 Hz, 2H), 4.08 (s, 2H), 1.20 (t, J=7.2 Hz, 3H).
Reaction SMILES: [CH3:1][C:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[C:5]([CH:10]=[O:11])=[CH:4][CH:3]=1>[Pd].C(OCC)(=O)C>[CH3:9][C:6]1([CH3:8])[CH2:7][CH:2]([CH3:1])[CH2:3][CH2:4][CH:5]1[CH:10]=[O:11]
Reactant: CC1=CC=C(C=O)C(C)(C)C1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CC1CCC(C=O)C(C)(C)C1
Reaction time: 72 h
Yield: 67.6 %

Procedure:
4,6,6-Trimethyl-1,3-cyclohexadiene-1-carbaldehyde (100.0 g, 0.66 mole), 11 of ethyl acetate and 0.3 g of palladium on charcoal (0.3 g) were hydrogenated as described in Example 1, over 3 days. The H2-consumption was 35 1. The mixture was then heated with pyridin chlorochromate to oxidize the amounts of alcohol formed. After filtration and concentration, the product was distilled at 65-73°/18 hPa, to obtain 68.8 g (67%) of the desired product in the form of a mixture of 2 isomers in a ratio of 1:3.
Reaction SMILES: C1(O[C:8](=[O:25])[NH:9][C:10]2[CH:15]=[CH:14][C:13]([B:16]3[O:20][C:19]([CH3:22])([CH3:21])[C:18]([CH3:24])([CH3:23])[O:17]3)=[CH:12][CH:11]=2)C=CC=CC=1.[F:26][CH:27]([F:30])[CH2:28][NH2:29]>>[F:26][CH:27]([F:30])[CH2:28][NH:29][C:8]([NH:9][C:10]1[CH:11]=[CH:12][C:13]([B:16]2[O:17][C:18]([CH3:24])([CH3:23])[C:19]([CH3:21])([CH3:22])[O:20]2)=[CH:14][CH:15]=1)=[O:25]
Reactant: CC1(C)OB(c2ccc(NC(=O)Oc3ccccc3)cc2)OC1(C)C
Reactant: NCC(F)F
Product: CC1(C)OB(c2ccc(NC(=O)NCC(F)F)cc2)OC1(C)C
Yield: 48 %

Procedure:
Method as described for intermediate 13 using phenyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (intermediate 17) and 2,2-difluoroethylamine to afford a pink oil (505 mg, 48%).
Reaction SMILES: [CH2:1]([NH:8][C:9]1[N:10]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)[N:11]=[C:12]2[C:17]=1[CH:16]=[CH:15][CH:14]=[CH:13]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:25][O:26][C:27](=[O:38])[C:28]1[CH:33]=[CH:32][C:31]([N:34]=[C:35]=[O:36])=[C:30]([Cl:37])[CH:29]=1>C1(C)C=CC=CC=1>[CH3:25][O:26][C:27](=[O:38])[C:28]1[CH:33]=[CH:32][C:31]([NH:34][C:35]([N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:9]2[N:10]([C:18]3[CH:19]=[CH:20][C:21]([Cl:24])=[CH:22][CH:23]=3)[N:11]=[C:12]3[C:17]=2[CH:16]=[CH:15][CH:14]=[CH:13]3)=[O:36])=[C:30]([Cl:37])[CH:29]=1
Reactant: COC(=O)c1ccc(N=C=O)c(Cl)c1
Reactant: Clc1ccc(-n2nc3ccccc3c2NCc2ccccc2)cc1
Solvent: Cc1ccccc1
Product: COC(=O)c1ccc(NC(=O)N(Cc2ccccc2)c2c3ccccc3nn2-c2ccc(Cl)cc2)c(Cl)c1

Procedure:
In analogy to the procedure described in example 1.2, benzyl-[2-(4-chloro-phenyl)-2H-indazol-3-yl]-amine (example 7.1) was reacted with 3-chloro-4-isocyanato-benzoic acid methyl ester in toluene for 72 h under reflux conditions to give the title compound as yellow oil. MS: m/e=547.0 [M+H+].
Reaction SMILES: [Cl:1]([O-:5])(=[O:4])(=[O:3])=[O:2].[CH:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9][CH2:8][NH+:7]=1.[C:16](=[C:19]1[CH2:24][CH2:23][CH2:22][CH2:21][C:20]1=O)([CH3:18])[CH3:17]>CN(C)C=O.C(O)C>[Cl:1]([O-:5])(=[O:4])(=[O:3])=[O:2].[CH3:18][C:16]1[C:19]2[CH2:24][CH2:23][CH2:22][CH2:21][C:20]=2[N+:7]2[CH2:8][CH2:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=3[C:6]=2[CH:17]=1
Reactant: C1=[NH+]CCc2ccccc21
Reactant: CC(C)=C1CCCCC1=O
Agent: [O-][Cl+3]([O-])([O-])[O-]
Solvent: CCO
Solvent: CN(C)C=O
Product: Cc1cc2[n+](c3c1CCCC3)CCc1ccccc1-2

Procedure:
3,4-Dihydroisoquinolinium perchlorate (4.6 g) and 2-isopropylidenecyclohexanone (3 g) were dissolved in dimethylforamide (12 ml) and refluxed for 12 hours. The reaction mixture was cooled, diluted with ethanol, and filtered. The product was purified by recrystallization from methanol. Yield 3 g; m.p. 205°.
Reaction SMILES: [Cl:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N:15]=[C:16]=S)=[CH:11][CH:10]=2)=[N:6][CH:5]=[CH:4][N:3]=1.[C:18]1([NH2:25])[C:19]([NH2:24])=[CH:20][CH:21]=[CH:22][CH:23]=1.C1(N=C=NC2CCCCC2)CCCCC1>C1COCC1.C(Cl)Cl>[Cl:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[NH:25][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[N:24]=3)=[CH:11][CH:10]=2)=[N:6][CH:5]=[CH:4][N:3]=1
Reactant: Nc1ccccc1N
Reactant: S=C=Nc1ccc(Oc2nccnc2Cl)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Solvent: C1CCOC1
Product: Clc1nccnc1Oc1ccc(Nc2nc3ccccc3[nH]2)cc1
Temperature: 75 °C

Procedure:
The mixture of 2-chloro-3-(4-isothiocyanatophenoxy)pyrazine (190 mg, 721 mmol), benzene-1,2-diamine (93.5 mg, 865 μmol) and N,N′-dicyclohexylcarbodiimide (223 mg, 1081 μmol) in THF (1.5 ml) was heated at 75° C. for 1.5 hrs. The mixture was cooled to room temperature, diluted with DCM and absorbed onto silica for purification using a 20-100% EtOAc/hexanes gradient to give the desired product.
Reaction SMILES: [CH2:1]([NH:17][C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][CH2:25][CH:26]2[O:28][CH2:27]2)=[O:23])=[CH:20][CH:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].S(=O)(=O)(O)[OH:32].COCCOC>O>[CH2:1]([NH:17][C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][CH2:25][CH:26]([OH:28])[CH2:27][OH:32])=[O:23])=[CH:20][CH:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCCCCCNc1ccc(C(=O)OCC2CO2)cc1
Reactant: O=S(=O)(O)O
Solvent: COCCOC
Solvent: O
Product: CCCCCCCCCCCCCCCCNc1ccc(C(=O)OCC(O)CO)cc1

Procedure:
A mixture of 100 mg of 2,3-epoxypropyl 4-(n-hexadecylamino)benzoate, 0.2 ml of 1N sulfuric acid, and 1.0 ml of 1,2-dimethoxyethane is heated under reflux for one hour, diluted with water, and filtered to yield 2,3-dihydroxypropyl 4-(n-hexadecylamino)benzoate as a white solid, mp 112°C.
Reaction SMILES: [CH3:1][CH:2]1[C:7]2[NH:8][C:9]3[C:14]([C:6]=2[CH2:5][CH2:4][N:3]1[CH3:16])=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=3.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[C:40]#[C:41][C:42]1[CH:47]=[CH:46][C:45]([Cl:48])=[CH:44][CH:43]=1>C1(C)C=CC=CC=1>[Cl:48][C:45]1[CH:46]=[CH:47][C:42]([C:41]#[C:40][N:8]2[C:9]3[C:14](=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=3)[C:6]3[CH2:5][CH2:4][N:3]([CH3:16])[CH:2]([CH3:1])[C:7]2=3)=[CH:43][CH:44]=1
Reactant: Cc1ccc2[nH]c3c(c2c1)CCN(C)C3C
Reactant: Clc1ccc(C#CBr)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Agent: c1cnc2c(c1)ccc1cccnc12
Solvent: Cc1ccccc1
Product: Cc1ccc2c(c1)c1c(n2C#Cc2ccc(Cl)cc2)C(C)N(C)CC1
Temperature: 80 °C
Yield: 19.2 %

Procedure:
1,2,6-trimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (214 mg, μmol) was mixed with CuSO4.5H2O (50 mg, 0.2 mmol), 1,10-phenanthroline (72 mg, 0.4 mmol), K3PO4 (425 mg, 2 mmol) and 1-(bromoethynyl)-4-chlorobenzene (237 mg, 1.1 mmol) in toluene (8-10 ml). The reaction mixture was flushed with nitrogen and heated at 80° C. for 16 h. The reaction mixture was filtered through Celite, and the Celite bed was rinsed with dichloromethane. Combined organic layer was concentrated under reduced pressure and the residue was purified by silica gel chromatography (100-200 mesh) eluting with 60-80% ethyl acetate in hexane to obtain 9-((4-chlorophenyl)ethynyl)-1,2,6-trimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (67 mg) as brown semi solid. 1H NMR (CDCl3) FREE BASE 7.42 (d, 2H), 7.38 (d, 2H), 7.30 (m, 2H), 7.10 (d, 1H), 3.90 (m, 1H), 3.20 (m, 1H), 2.90 (m, 2H), 2.62 (m, 1H), 2.58 (s, 3H), 2.42 (s, 3H), 1.30 (d, 3H).
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=1.Br[CH2:11][C:12]#[N:13].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.CN(C)C=O>[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][CH:8]=1)[O:9][CH2:11][C:12]#[N:13]
Reactant: N#CCBr
Reactant: OCc1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CN(C)C=O
Product: N#CCOc1cccc(CO)c1

Procedure:
A mixture of 3-hydroxymethyl phenol (0.081 mol), bromacetonitrile (0.081 mol) and anhydrous potassium carbonate (0.081 mol) in acetone (160 ml) and dimethylformamide (20 ml) are heated at reflux for 48 hrs. The reaction mixture is filtered and evaporated. The residue is diluted with ethyl acetate (150 ml), washed with 10% aqueous sodium hydroxide solution (3×100 ml) and then with brine (3×100 ml). The ethyl acetate solution is dried (magnesium sulfate) and chromatographed using a silica gel column (ca. 100 g) and eluted with 1:1 petroleum ether: ethylacetate (2l). The resultant oil is used directly in the next step.
Reaction SMILES: [CH3:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[N:8]1[C:12]2=[C:13]3[CH:19]=[CH:18][NH:17][C:14]3=[N:15][CH:16]=[C:11]2[NH:10][C:9]1=[O:20].[Br:21]N1C(=O)CCC1=O.C(Cl)(Cl)Cl.O>CN(C)C=O>[Br:21][C:19]1[C:13]2[C:14](=[N:15][CH:16]=[C:11]3[NH:10][C:9](=[O:20])[N:8]([C@H:3]4[CH2:4][CH2:5][CH2:6][CH2:7][C@H:2]4[CH3:1])[C:12]3=2)[NH:17][CH:18]=1
Reactant: C[C@@H]1CCCC[C@@H]1n1c(=O)[nH]c2cnc3[nH]ccc3c21
Reactant: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)Cl
Solvent: CN(C)C=O
Solvent: O
Product: C[C@@H]1CCCC[C@@H]1n1c(=O)[nH]c2cnc3[nH]cc(Br)c3c21
Temperature: 25 °C
Reaction time: 2 h
Yield: 9.3 %

Procedure:
To a solution of 1-[(1S,2R)-2-methylcyclohexyl]-3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2(1H)-one (100 mg) in N,N-dimethylformamide (1 mL) was added N-bromosuccinimide (66 mg). The mixture was stirred at ambient temperature for 2 hours. To the mixture were added chloroform and water. The mixture was extracted with chloroform. The extract was washed saturated aqueous sodium hydrogencarbonate and brine, dried over MgSO4 and filtrated. The filtrate was concentrated under reduced pressure. The residue was dissolved in a small-amount of methanol and to the solution was added EtOAc. The precipitate was filtrated and washed with EtOAc to give 8-bromo-1-[(1S,2R)-2-methylcyclohexyl]-3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2(1H)-one (12 mg) as a white powder.
Reaction SMILES: Br[C:2]1[C:10]2[NH:9][C:8]3[CH:11]4[CH2:17][CH2:16][N:14]([CH2:15][C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1)[CH2:13][CH2:12]4.[N:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[C:20](B(O)O)[CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>CC(O)C.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>[N:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[C:20]([C:2]2[C:10]3[NH:9][C:8]4[CH:11]5[CH2:17][CH2:16][N:14]([CH2:15][C:7]=4[C:6]=3[CH:5]=[CH:4][CH:3]=2)[CH2:13][CH2:12]5)[CH:19]=1
Reactant: OB(O)c1cnc2ccccc2c1
Reactant: Brc1cccc2c3c([nH]c12)C1CCN(CC1)C3
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(C)O
Product: c1ccc2ncc(-c3cccc4c5c([nH]c34)C3CCN(CC3)C5)cc2c1
Temperature: 80 °C
Reaction time: 1 h

Procedure:
A suspension of the product of Example 1B (150 mg, 0.52 mmol), 3-quinolineboronic acid (102 mg, 0.59 mmol; Aldrich), dichlorobis(triphenylphosphine)palladium (II) (18 mg, 0.026 mmol; Aldrich) and 1.0 M sodium carbonate (1.3 mL) in 2-propanol (3.8 mL) was purged with nitrogen and then stirred at 80° C. for 1 hour in a sealed tube. The reaction mixture was cooled and partitioned between CHCl3 (2×30 mL) and 1.0 M sodium carbonate (50 mL). The combined organic extracts were dried (sodium sulfate) and concentrated under vacuum. The resulting residue was purified by reverse-phase HPLC [Waters XBridge™RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 40-100% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound: 1H NMR (400 MHz, methanol-d4) δ ppm 1.98-2.16 (m, 4 H), 3.02-3.14 (m, 3 H), 3.25 (ddd, J=14.1, 8.8, 5.5 Hz, 2 H), 4.28 (s, 2 H), 7.12-7.22 (m, 2 H), 7.39 (dd, J=7.3, 1.5 Hz, 1 H), 7.66 (ddd, J=8.1, 7.0, 1.1 Hz, 1 H), 7.79 (ddd, J=8.5, 6.9, 1.4 Hz, 1 H), 8.03 (dd, J=8.2, 0.9 Hz, 1 H), 8.09 (d, J=8.5 Hz, 1 H), 8.57 (d, J=2.1 Hz, 1 H), 9.09 (d, J=2.1 Hz, 1 H); MS (ESI+) m/z 340 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[OH:9])=[CH:4][CH:3]=1.Cl[CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:38]=[CH:37][C:31]2[CH:32]=[CH:33][C:34](=[O:36])[O:35][C:30]=2[CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+]>C(O)CCC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)([OH:9])[CH:10]2[CH2:11][CH2:12][N:13]([CH2:24][CH2:25][CH2:26][O:27][C:28]3[CH:38]=[CH:37][C:31]4[CH:32]=[CH:33][C:34](=[O:36])[O:35][C:30]=4[CH:29]=3)[CH2:14][CH2:15]2)=[CH:4][CH:3]=1
Reactant: O=c1ccc2ccc(OCCCCl)cc2o1
Reactant: OC(c1ccc(F)cc1)(c1ccc(F)cc1)C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCCCO
Product: O=c1ccc2ccc(OCCCN3CCC(C(O)(c4ccc(F)cc4)c4ccc(F)cc4)CC3)cc2o1
Yield: 71.2 %

Procedure:
This compound was prepared according to the procedure of Example 1. A mixture of 3.0 g (0.01 mole) of α,α-bis(p-fluorophenyl)-4-piperidinemethanol, 2.4 g (0.01 mole of 7-(3-chloropropoxy)2H-1-benzopyran-2-one, 5.3 g (0.05 mole) of anhydrous sodium carbonate and 0.3 g of potassium iodide in 100 ml of 1-butanol gave 3.6 g (71%) of pale yellow crystals, m.p. 99°-120° C. with decomposition.
Reaction SMILES: C[Si]([C:5]#[C:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]#[C:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH2:23][CH3:24])=[CH:17][CH:16]=2)=[CH:9][CH:8]=1)(C)C.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CO>[C:6]([C:7]1[CH:12]=[CH:11][C:10]([C:13]#[C:14][C:15]2[CH:16]=[CH:17][C:18]([CH2:21][CH2:22][CH2:23][CH3:24])=[CH:19][CH:20]=2)=[CH:9][CH:8]=1)#[CH:5]
Reactant: CCCCc1ccc(C#Cc2ccc(C#C[Si](C)(C)C)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CO
Product: C#Cc1ccc(C#Cc2ccc(CCCC)cc2)cc1
Temperature: 25 °C
Reaction time: 19 h
Yield: 8.2 %

Procedure:
1-(trimethylsilylethynyl)-4-(4-n-butylphenylethynyl)benzene (192 g, 11.86 mmol) was dissolved in CH2Cl2 (100 nit) diluted with MeOH (40 mL) and then treated with powdered K2CO3 (2.1 g, 15 mmol) and allowed to stir at ambient temperature for 19 h under N2. The reaction mixture was filtered to remove solids, concentrated, redissolved in CHCl3, washed with water (2×), brine, dried over MgSO4, filtered and concentrated to dryness to give a brown solid. The solid was chromatographed on silica gel, eluting with 15:1 hexanes/EtOAc to give several fractions rich in product. These fractions were combined and chromatographed again with 95:5 hexanes/EtOAc to give 0.25 g (7%) product as a waxy solid. 1H NMR (CDCl3) δ: 7.50 (s, 4H), 7.47 (d, 8.2 Hz, 2H); 7.21 (d, J=8.2 Hz, 2H); 3.20 (s, 1H); 2.63 (t, J=7.8 Hz, 2H); 1.64 (m, 2H); 1.41 (m, 2H); 0.97 (t, J=7.5 Hz, 3H). 13C{1H} NMR (CDCl3): 143.8, 132.1, 11.6, 131.4, 1128.6, 124.1, 121.6, 120.0, 911.7, 88.2, 83.4, 78.8, 35.6, 33.4, 22.2, 14.0 ppm.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([CH3:27])=[C:5]([C:18]([O:25][CH3:26])=[C:19]([O:23][CH3:24])[C:20]=1[O:21][CH3:22])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([OH:17])=[C:11]([CH:16]=1)[C:12]([O:14][CH3:15])=[O:13].[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(N(CC)CC)C.N1C=CC=CC=1>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:1][O:2][C:3]1[C:4]([CH3:27])=[C:5]([C:18]([O:25][CH3:26])=[C:19]([O:23][CH3:24])[C:20]=1[O:21][CH3:22])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:17][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[C:11]([CH:16]=1)[C:12]([O:14][CH3:15])=[O:13]
Reactant: OB(O)c1ccccc1
Reactant: COC(=O)c1cc(Cc2c(C)c(OC)c(OC)c(OC)c2OC)ccc1O
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)c1cc(Cc2c(C)c(OC)c(OC)c(OC)c2OC)ccc1Oc1ccccc1
Yield: 41.3 %

Procedure:
Methyl 5-(3,4,5,6-tetramethoxy-2-methylbenzyl)-2-hydroxybenzoate (0.510 g, 1.18 mmol) was dissolved in methylene chloride (12 ml) and after adding thereto in sequence copper acetate (0.215 g, 1.18 mmol), phenylboronic acid (0.289 g, 2.37 mmol), Molecular Sieves 4A (0.300 g), triethylamine (0.299 g, 2.96 mmol) and pyridine (0.234 g, 2.96 mmol), the solution was stirred at room temperature for 12 hours. The reaction solution was filtered and the filtrate was poured into water and then extracted with methylene chloride. The extract was washed with saturated brine, then dried and concentrated. The obtained residue was purified by silica gel column chromatography (hexand:ethyl acetate=3:1) to obtain the titled compound (0.220 g, 0.487 mmol, 41%).
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH:32][C:33]1[CH:34]=[CH:35][C:36]2[C:37]3[N:45]=[C:44]([C:46]4[CH:51]=[CH:50][C:49]([O:52][CH3:53])=[CH:48][CH:47]=4)[CH:43]=[C:42]([C:54]([NH2:56])=[O:55])[C:38]=3[NH:39][C:40]=2[CH:41]=1.[CH3:57][N:58]([CH3:62])[CH2:59][CH2:60]O>C1COCC1>[CH3:57][N:58]([CH3:62])[CH2:59][CH2:60][O:32][C:33]1[CH:34]=[CH:35][C:36]2[C:37]3[N:45]=[C:44]([C:46]4[CH:47]=[CH:48][C:49]([O:52][CH3:53])=[CH:50][CH:51]=4)[CH:43]=[C:42]([C:54]([NH2:56])=[O:55])[C:38]=3[NH:39][C:40]=2[CH:41]=1
Reactant: COc1ccc(-c2cc(C(N)=O)c3[nH]c4cc(O)ccc4c3n2)cc1
Reactant: CN(C)CCO
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COc1ccc(-c2cc(C(N)=O)c3[nH]c4cc(OCCN(C)C)ccc4c3n2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 16.5 %

Procedure:
Diethyl azodicarboxylate (0.057 mL, 0.360 mmol) was added to an ice-cooled solution of triphenylphosphine (94 mg, 0.360 mmol) in dry THF (1 mL). The bath was removed and a solution of 7-hydroxy-2-(4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxamide (Example 207, 60 mg, 0.180 mmol) and 2-(dimethylamino)ethanol (24 mg, 0.270 mmol) in dry THF (1 mL) was added after 15 minutes. After stirring for 2 hr at room temperature, the reaction was quenched with brine and extracted with EtOAc. The extracts were dried with sodium sulfate and the solvent was removed. Radial silica gel chromatography of the residue (step gradient elution with methylene chloride containing 10 to 60% methanol) followed by SCX cartridge purification gave 7-(2-(dimethylamino)ethoxy)-2-(4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxamide (12 mg) as a yellow glass. MS (ESI) m/z 405.1 (M+H). 1H NMR (DMSO-d6) δ ppm 11.34 (1H, br. s.), 8.56 (1H, s), 8.28 (1H, s), 8.23 (2H, d, J=8.85 Hz), 8.10 (1H, d, J=8.55 Hz), 7.83 (1H, s), 7.28 (1H, d, J=2.14 Hz), 7.10 (2H, d, J=8.85 Hz), 6.89 (1H, dd, J=8.55, 2.44 Hz), 4.15 (2H, t, J=5.95 Hz), 3.85 (3H, s), 2.70 (2H, t, J=5.80 Hz), 2.27 (6H, s).
Reaction SMILES: Cl[C:2]1[C:19]([O:20][CH3:21])=[CH:18][C:5]2[C@H:6]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:7][N:8]([CH3:11])[CH2:9][CH2:10][C:4]=2[CH:3]=1.[OH-].[Na+].[H][H]>C(O)C.O.[Pd]>[CH3:21][O:20][C:19]1[CH:2]=[CH:3][C:4]2[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][C@@H:6]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:5]=2[CH:18]=1
Reactant: [H][H]
Reactant: COc1cc2c(cc1Cl)CCN(C)C[C@H]2c1ccccc1
Agent: [Pd]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: COc1ccc2c(c1)[C@H](c1ccccc1)CN(C)CC2

Procedure:
Hydrogenate a solution of 21.10 g (0.07 moles) of (S)-7-chloro-8-methoxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1-H-3-benzazepine (e.g. obtained as described in Example 1, step D) 3.30 g (0.0825 moles) of sodium hydroxide in 300 ml of 95% ethanol at room temperature and at 4.2 kg/cm2 (=60 psi), with 1.70 g of 20% palladium hydroxide-on-carbon until the theoretical amount of hydrogen is consumed. Remove the catalyst and concentrate the filtrate to dryness on a steam bath at about 100 mm. Stir the residue with a mixture of 100 ml of water and 150 ml of ethyl ether to total dissolution. Separate the ether layer, dry over anhydrous sodium sulfate, and evaporate to dryness. Crystallize the residue from hexane to obtain analytically pure (S)-8-methoxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine, m.p. 50°-51° C., [α]D26 =+51.8° (c=1, ethanol).
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][N:27]=1)[C:5]([NH:7][C:8]1[S:9][C:10]2[C:16]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:15][CH:14]=[C:13]([O:23][CH3:24])[C:11]=2[N:12]=1)=[O:6].[H-].[Na+].[F:30][C:31]([F:35])([F:34])[CH2:32][OH:33]>O1CCOCC1.CN(C=O)C>[CH3:24][O:23][C:13]1[C:11]2[N:12]=[C:8]([NH:7][C:5](=[O:6])[C:4]3[CH:25]=[CH:26][N:27]=[C:2]([O:33][CH2:32][C:31]([F:35])([F:34])[F:30])[CH:3]=3)[S:9][C:10]=2[C:16]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[CH:15][CH:14]=1
Reactant: COc1ccc(N2CCOCC2)c2sc(NC(=O)c3ccnc(Cl)c3)nc12
Reactant: OCC(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CN(C)C=O
Product: COc1ccc(N2CCOCC2)c2sc(NC(=O)c3ccnc(OCC(F)(F)F)c3)nc12

Procedure:
From 2-chloro-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-isonicotinamide with sodium hydride and 2,2,2-trifluoroethanol in dioxane and DMF. ES-MS m/e (%): 491 (M+Na+, 81), 469 (M+H+, 100).
Reaction SMILES: [H-].[Na+].[C:3](Cl)(=[O:5])[CH3:4].[Cl:7][C:8]1[CH:9]=[C:10]([CH:13]=[C:14]([O:16][C:17]2[C:18]([CH3:23])=[N:19][NH:20][C:21]=2[CH3:22])[CH:15]=1)[C:11]#[N:12]>CN(C)C=O>[C:3]([N:20]1[C:21]([CH3:22])=[C:17]([O:16][C:14]2[CH:13]=[C:10]([CH:9]=[C:8]([Cl:7])[CH:15]=2)[C:11]#[N:12])[C:18]([CH3:23])=[N:19]1)(=[O:5])[CH3:4]
Reactant: CC(=O)Cl
Reactant: Cc1n[nH]c(C)c1Oc1cc(Cl)cc(C#N)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(=O)n1nc(C)c(Oc2cc(Cl)cc(C#N)c2)c1C
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 89 %

Procedure:
Sodium hydride (60% dispersion in oil, 840 mg, 21.0 mmol) was added to a stirred solution of acetyl chloride (1.50 ml, 21.0 mmol) and the pyrazole of Example 76 (4.80 g, 19.4 mmol) in N,N-dimethylformamide (20 ml) at 0° C. under nitrogen. The reaction was stirred at 0° C. for 15 minutes and then quenched by the addition of water (200 ml). The reaction mixture was extracted with ethyl acetate (3×120 ml). The combined organic phases were washed with water (50 ml) and brine (50 ml), dried over magnesium sulphate, filtered and concentrated under reduced pressure to leave a yellow solid. The crude product was purified by flash column chromatography on silica gel eluting with dichloromethane to provide the title compound (5.00 g) as a white solid, m.p. <60° C.