Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[O:2]([CH2:9][C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[S:15]([C:18]1[CH:26]=[CH:25][C:24]2[N:23]3[CH2:27][CH2:28][CH2:29][N:30]=[C:22]3[C:21]3(OCCC[O:31]3)[C:20]=2[CH:19]=1)(=[O:17])=[O:16])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[NH4+].[OH-]>O1CCOCC1>[O:2]([CH2:9][C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[S:15]([C:18]1[CH:26]=[CH:25][C:24]2[N:23]3[CH2:27][CH2:28][CH2:29][N:30]=[C:22]3[C:21](=[O:31])[C:20]=2[CH:19]=1)(=[O:17])=[O:16])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: O=S(=O)(c1ccc2c(c1)C1(OCCCO1)C1=NCCCN12)N1CCC[C@H]1COc1ccccc1
Agent: Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: C1COCCO1
Product: O=C1C2=NCCCN2c2ccc(S(=O)(=O)N3CCC[C@H]3COc3ccccc3)cc21
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To cold concentrated HCl (8.5 mL) was added a solution of 8′-{[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonyl}-3′,4′-dihydro-2′H-spiro[1,3-dioxane-2,10′-pyrimido[1,2-a]indole] (0.430 g, 0.889 mmol) in 1,4 dioxane (2 mL) drop-wise over a period of 20 minutes with cooling in an ice bath. The mixture was stirred at room temperature (16 hours) then heated at 53° C. (36 hours). The mixture was cooled in an ice bath, poured into ice, and basified with concentrated NH4OH to pH 11 keeping the temperature below 5° C. The organics were extracted with EtOAc (2×). The combined organic extracts were dried over MgSO4, filtered and concentrated. The crude product was flash chromatographed on Biotage KP silica gel eluting with 95/5 (EtOAc/CH3OH) to give the title compound which was dried in vacuo at 61° C. to give the analytically pure sample as an orange-brown solid (0.074 g, 19.5% yield). Anal. Calc'd for C22H23N3O4S: C, 62.10; H, 5.45; N, 9.88. Found: C, 61.89; H, 5.50; N, 9.65. NMR (400 MHz, DMSO-d6): consistent. MS: (ES+) m/z 426 [M+H]. MS: (ES−) m/z 424 [M−H]. m.p.: 159-160° C.
Reaction SMILES: CN1CCOCC1.[O:8]=[C:9]1[CH2:13][CH2:12][CH2:11][N:10]1[CH2:14][CH2:15][C:16]([OH:18])=O.[CH:19]1([Mg]Br)[CH2:23][CH2:22][CH2:21][CH2:20]1>C1COCC1.[Cu](I)I>[CH:19]1([C:16](=[O:18])[CH2:15][CH2:14][N:10]2[CH2:11][CH2:12][CH2:13][C:9]2=[O:8])[CH2:23][CH2:22][CH2:21][CH2:20]1
Reactant: Br[Mg]C1CCCC1
Reactant: O=C(O)CCN1CCCC1=O
Agent: I[Cu]I
Solvent: CN1CCOCC1
Solvent: C1CCOC1
Product: O=C(CCN1CCCC1=O)C1CCCC1
Temperature: 0 °C
Yield: 15 %

Procedure:
2-Chloro-4-6-dimethoxy-1,3,5-triazine (2.68 g, 15.2 mmol) and N-methylmorpholine (4.2 mL, 38.1 mmol) were added to a solution of 3-(2-Oxo-pyrrolidin-1-yl)-propionic acid (2 g, 12.7 mmol, from Step 1) in THF (35 mL). After 1 h the reaction mixture was filtered through a glass frit to remove a white precipitate. The filtrate was treated with copper iodide (2.4 g, 12.7 mmol), cooled to 0° C. and then cyclopentyl magnesium bromide (6.35 mL, 12.7 mmol, 2M in ether) was added. After 4 h the resulting black mixture was quenched with saturated NH4Cl and extracted with CH2Cl2. The organic layers were washed with 1N HCl, saturated NaHCO3, brine, dried over Na2SO4 and concentrated. The residue was purifed by silica gel chromatography (75% EtOAc in hexanes then 5% MeOH in CH2Cl2) to give the title compound as a yellow oil. (0.4 g, 15% yield). 1H NMR (CDCl3): δ 1.55-1.83 (br m, 8H), 1.99 (m, 3H), 2.35 (t, 2H, J=8.3 Hz), 2.74 (t, 2H, J=6.8 Hz), 3.41 (d, 2H, J=7.2 Hz), 3.53 (t, 2H, J=6.6 Hz).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C:9]1=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.Cl.[NH2:23][C@H:24]([C:29]([NH2:31])=[O:30])[CH2:25][CH2:26][S:27][CH3:28].O>CCO.C(Cl)Cl>[CH3:28][S:27][CH2:26][CH2:25][CH:24]1[NH:23][C:11]2([CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[NH:31][C:29]1=[O:30]
Reactant: CSCC[C@H](N)C(N)=O
Reactant: CC(C)(C)OC(=O)N1CCCCC1=O
Agent: Cl
Solvent: ClCCl
Solvent: CCO
Solvent: O
Product: CSCCC1NC2(CCN(C(=O)OC(C)(C)C)CC2)NC1=O

Procedure:
N-tert-Butyloxycarbonylpiperidone (5.9 g, 29.8 mmol) and triethylamine (3.02 g, 29.8 mmol) were added to a solution of methioninamide hydrochloride (5.5 g, 29.8 mmol) in dry EtOH (66 ml), and the mixture was heated under reflux for 2.5 h. After addition of water (50 ml) and CH2Cl2 (200 ml), the organic phase was separated off, and the aqueous phase was extracted with CH2Cl2 (3×20 ml). The combined organic phases were dried over Na2SO4. After filtration, the solvent was removed by distillation. tert-Butyl 3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4,5]decane-8-carboxylate was obtained in a yield of 8.0 g (82% of theory).
Reaction SMILES: Cl[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=[C:6]2[CH:5]=[CH:4][N:3]=1.[CH:19]1([C:22]2[N:27]=[CH:26][N:25]=[C:24]([NH2:28])[CH:23]=2)[CH2:21][CH2:20]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:19]1([C:22]2[N:27]=[CH:26][N:25]=[C:24]([NH:28][C:2]3[C:7]4=[CH:8][N:9]([C:11]5[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=5[Cl:18])[N:10]=[C:6]4[CH:5]=[CH:4][N:3]=3)[CH:23]=2)[CH2:21][CH2:20]1
Reactant: Clc1cccc(Cl)c1-n1cc2c(Cl)nccc2n1
Reactant: Nc1cc(C2CC2)ncn1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: Clc1cccc(Cl)c1-n1cc2c(Nc3cc(C4CC4)ncn3)nccc2n1
Temperature: 120 °C
Yield: 43.2 %

Procedure:
A mixture of 4-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine (52 mg, 0.175 mmol), 6-cyclopropylpyrimidin-4-ylamine (26 mg, 0.193 mmol), Pd2(dba)3 (8 mg, 0.0088 mmol), Xantphos (10.1 mg, 0.0175 mmol) and cesium carbonate (114 mg, 0.35 mmol) in dioxane (1.5 mL) was de-gassed and purged with nitrogen and the reaction mixture was heated at 120° C. in the microwave for 1 hour. The resultant mixture was filtered and washed with dioxane. The filtrate was concentrated under reduced pressure and the resultant residue was purified by silica gel flash chromatography (0-100% ethyl acetate in cyclohexane) to afford the title compound as a yellow solid (30 mg, 43% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.56 (d, J=0.9 Hz, 1H), 8.94 (d, J=1.0 Hz, 1H), 8.05 (d, J=7.3 Hz, 1H), 7.87-7.83 (m, 2H), 7.79-7.74 (m, 1H), 7.62 (dd, J=7.3, 0.9 Hz, 1H), 7.39 (s, 1H), 2.34-2.26 (m, 1H), 1.19-1.12 (m, 4H). LCMS (Method B): RT=3.17 min, m/z: 397 [M+H+].
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[NH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.CN(C)C=O.Cl[CH2:19][CH2:20][CH2:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([CH:29]2[CH2:34][CH2:33][C:32](=[O:35])[CH2:31][CH2:30]2)=[CH:25][CH:24]=1>>[O:35]=[C:32]1[CH2:33][CH2:34][CH:29]([C:26]2[CH:25]=[CH:24][C:23]([O:22][CH2:21][CH2:20][CH2:19][N:7]3[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]3)=[CH:28][CH:27]=2)[CH2:30][CH2:31]1
Reactant: C1CCNCC1
Reactant: O=C1CCC(c2ccc(OCCCCl)cc2)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C1CCC(c2ccc(OCCCN3CCCCC3)cc2)CC1
Temperature: 25 °C

Procedure:
A suspension of potassium carbonate (3.11 g) in a mixture of 4-[4-(3-chloropropoxy)phenyl]cyclohexanone (2 g), piperidine (2.22 mL) and N,N-dimethylformamide (40 mL) is heated for three hour at a temperature close to 110° C., then stirred for twenty hour at room temperature. The mixture is concentrated under reduced pressure and dissolved in ethyl acetate (150 mL) and water (150 mL). The organic phase is washed twice with water (100 mL), dried over magnesium sulphate, concentrated under reduced pressure and purified by chromatography over silica gel with a gradient dichloromethane/methanol from 95/5 to 90/10. Fractions containing the product are pooled and concentrated under reduced pressure affording 1.94 g of 1-{3-[4-(4-oxocyclohexyl)phenoxy]propyl}-piperidine as a yellow solid used without further purification.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[N:10]1[C:14]([C:15](=O)[CH:16]([CH3:20])[CH2:17][CH:18]=O)=[C:13]([C:22]#[N:23])[C:12]([CH3:24])=[N:11]1.[CH3:25][NH2:26]>C(Cl)Cl>[CH3:25][N:26]1[CH:18]=[CH:17][C:16]([CH3:20])=[C:15]1[C:14]1[N:10]([C:3]2[CH:4]=[CH:5][C:6]([O:8][CH3:9])=[CH:7][C:2]=2[F:1])[N:11]=[C:12]([CH3:24])[C:13]=1[C:22]#[N:23]
Reactant: CN
Reactant: COc1ccc(-n2nc(C)c(C#N)c2C(=O)C(C)CC=O)c(F)c1
Solvent: ClCCl
Product: COc1ccc(-n2nc(C)c(C#N)c2-c2c(C)ccn2C)c(F)c1
Temperature: 25 °C
Reaction time: 14 h
Yield: 68.5 %

Procedure:
To a stirred solution of 1-(2-fluoro-4-methoxyphenyl)-3-methyl-5-(2-methyl-4-oxobutanoyl)-1H-pyrazole-4-carbonitrile (29 mg, 0.09 mmol) in CH2Cl2 (2 mL) was added methylamine (2.0 M solution in methanol, 0.61 mL, 1.2 mmol) at ambient temperature in a closed microwave tube. The reaction mixture was stirred at ambient temperature for 14 h and concentrated under reduced pressure. Purification using a silica plug (heptane/CH2Cl2/Et2O-1:0:0-1:1:0-0:1:0-0:1:1) yielded 5-(1,3-dimethyl-1H-pyrrol-2-yl)-1-(2-fluoro-4-methoxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile (20 mg, 62%).
Reaction SMILES: Br[C:2]1[N:3]([CH:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])[C:4]2[C:9]([C:10]=1[C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.[Br-].[CH:24]1([Zn+])[CH2:26][CH2:25]1>O1CCCC1.O.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>[CH:24]1([C:2]2[N:3]([CH:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])[C:4]3[C:9]([C:10]=2[C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=3)[CH2:26][CH2:25]1
Reactant: COC(=O)c1c(Br)n(C(C)c2ccccc2)c2ccccc12
Reactant: [Zn+]C1CC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Br-]
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)c1c(C2CC2)n(C(C)c2ccccc2)c2ccccc12
Temperature: 25 °C
Yield: 82 %

Procedure:
To a solution of methyl 2-bromo-1-(1-phenylethyl)-1H-indole-3-carboxylate (0.30 g, 0.84 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.09 g, 0.08 mmol) in tetrahydrofuran (20 mL) was added cyclopropylzinc(II) bromide (6.0 mL, 0.5 mol/L in tetrahydrofuran). The reaction mixture was stirred at reflux for 12 hours. After the reaction, it was cooled to room temperature and diluted with water (100 mL). The product was extracted with ethyl acetate (100 mL), dried over anhydrous sodium sulfate, concentrated and purified by column chromatography (silica gel: ethyl acetate:petroleum ether=1:10) to give the crude product methyl 2-cyclopropyl-1-(1-phenylethyl)-1H-indole-3-carboxylate (0.22 g, 82%) as a yellow oil.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19]C)[N:3]=1.B(Br)(Br)Br>C(Cl)Cl>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:19])[N:3]=1
Reactant: COc1ccccc1-c1nc(Cl)c2cc(F)ccc2n1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: Oc1ccccc1-c1nc(Cl)c2cc(F)ccc2n1
Temperature: 25 °C
Yield: 56.9 %

Procedure:
A solution of 4-chloro-6-fluoro-2-(2-methoxyphenyl)quinazoline (3.0 g, 10.3 mmol) in CH2Cl2 (15 mL) was cooled to −78° C. Then, 1 M BBr3 (51.95 mL, 59.95 mmol) was added dropwise. The reaction was warmed to room temperature and was quenched with NaHCO3 and extracted twice with CH2Cl2. The organic layer was dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 5-20% CH2Cl2 in hexanes gave 2-(4-chloro-6-fluoroquinazolin-2-yl)phenol (1.61 g, 57%). LC/MS: m/z 275.1 (M+H)+ at 3.8 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[C:8](=O)([O:16]C1C=CC([N+]([O-])=O)=CC=1)[O:9][CH2:10][CH2:11][Si:12]([CH3:15])([CH3:14])[CH3:13].C(N(CC)C(C)C)(C)C>C1COCC1>[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:9][CH2:10][CH2:11][Si:12]([CH3:15])([CH3:14])[CH3:13])=[O:16])[CH2:4][CH2:3]1
Reactant: C[Si](C)(C)CCOC(=O)Oc1ccc([N+](=O)[O-])cc1
Reactant: OC1CCNCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: C[Si](C)(C)CCOC(=O)N1CCC(O)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
6.9 g of 4-hydroxypiperidine were dissolved in 150 ml of THF. 19.4 g of 2-(trimethylsilyl)ethyl 4-nitrophenyl carbonate and 11.9 ml of N,N-diisopropylethylamine were successively added thereto. The mixture was stirred at room temperature for 1 h and then the solvent was removed in vacuo. The residue was taken up in 400 ml of ethyl acetate and washed once with 200 ml of 0.5 N HCl and twice with 200 ml of 1 N NaOH each time. The organic phase was dried with MgSO4, the solvent was removed in vacuo, and the residue was purified by chromatography on silica gel.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:26])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[N:22][C:21]([C:24]#[N:25])=[CH:20][N:19]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2].Cl.[NH2:28][OH:29].C(N(CC)CC)C>CO>[CH2:1]([O:3][C:4](=[O:26])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[N:22][C:21]([C:24](=[NH:25])[NH:28][OH:29])=[CH:20][N:19]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2]
Reactant: CCOC(=O)CC1OB(O)c2cc(Oc3cnc(C#N)cn3)cc(C)c21
Reactant: NO
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CO
Product: CCOC(=O)CC1OB(O)c2cc(Oc3cnc(C(=N)NO)cn3)cc(C)c21
Temperature: 25 °C
Reaction time: 8 h
Yield: 79 %

Procedure:
[6-(5-Cyano-pyrazin-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester (200 mg, 0.57 mmol) and hydroxylamine hydrochloride (99 mg, 1.4 mmol) were mixed in methanol (5.4 mL). To this was added triethylamine (0.28 mL, 2 mmol). The reaction was stirred at room temperature overnight. The solvent was removed. The residue was dissolved in dichloromethane and washed with water. The organic layer was separated and the solvent was removed to give a residue. The residue was dried under high vacuum to give the title compound (174 mg, 79%) as a white solid. MS found (electrospray): (M+H)+=387.1.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[N:4]([C:8]([CH3:12])=[C:9]([CH3:11])[N:10]=2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+].[CH3:21][C:22]1[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[C:23]=1[CH2:24]Cl>CC(C)=O>[CH3:11][C:9]1[N:10]=[C:3]2[C:2]([NH:1][CH2:24][C:23]3[C:26]([CH3:30])=[CH:27][CH:28]=[CH:29][C:22]=3[CH3:21])=[CH:7][CH:6]=[CH:5][N:4]2[C:8]=1[CH3:12]
Reactant: Cc1cccc(C)c1CCl
Reactant: Cc1nc2c(N)cccn2c1C
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: Cc1cccc(C)c1CNc1cccn2c(C)c(C)nc12
Reaction time: 8 h
Yield: 57.7 %

Procedure:
A mixture of 8-amino-2,3-dimethylimidazo[1,2-a]pyridine (0.7 g, 4.34 mmol), sodium carbonate (2.0 g), sodium iodide (0.3 g), 2,6-dimethylbenzylchloride (0.671 g, 4.34 mmol) and acetone (30 ml) was stirred overnight. The reaction mixture was filtered and the solvent was removed in vacuo. The residue was dissolved in methylene chloride and washed with aqueous NaHCO3. The organic layer was separated and the solvent was evaporated. The crude product was purified by flash chromatography eluting with CH2Cl2/MeOH to give 0.7 g of the title compound.
Reaction SMILES: [OH:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=2)[CH:4]=[N:3]1.[CH3:15][N:16]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:17](Cl)=[O:18]>>[CH3:14][O:13][C:10]1[CH:9]=[CH:8][C:7]([C:5]2[CH:4]=[N:3][N:2]([O:1][C:17](=[O:18])[N:16]([CH3:15])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:6]=2)=[CH:12][CH:11]=1
Reactant: COc1ccc(-c2cnn(O)c2)cc1
Reactant: CN(C(=O)Cl)c1ccccc1
Product: COc1ccc(-c2cnn(OC(=O)N(C)c3ccccc3)c2)cc1

Procedure:
The title compound was prepared from 1-hydroxy-4-(4-methoxyphenyl)pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (6%, oil).
Reaction SMILES: [N+:1]([C:4]1[CH:10]=[CH:9][C:7]([NH2:8])=[C:6]([Cl:11])[CH:5]=1)([O-:3])=[O:2].[C:12](Cl)(=[O:22])[C:13]1[CH:21]=[CH:20][C:16]([C:17](Cl)=[O:18])=[CH:15][CH:14]=1>CN(C)P(N(C)C)(N(C)C)=O>[N+:1]([C:4]1[CH:10]=[CH:9][C:7]([NH:8][C:12](=[O:22])[C:13]2[CH:21]=[CH:20][C:16]([C:17]([NH:8][C:7]3[CH:9]=[CH:10][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][C:6]=3[Cl:11])=[O:18])=[CH:15][CH:14]=2)=[C:6]([Cl:11])[CH:5]=1)([O-:3])=[O:2]
Reactant: Nc1ccc([N+](=O)[O-])cc1Cl
Reactant: O=C(Cl)c1ccc(C(=O)Cl)cc1
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: O=C(Nc1ccc([N+](=O)[O-])cc1Cl)c1ccc(C(=O)Nc2ccc([N+](=O)[O-])cc2Cl)cc1
Reaction time: 4 h

Procedure:
In a 1 l. three-neck round bottom flask provided with a stirrer, nitrogen inlet and drying tube, a solution of 52.56 g. (0.3 mole) 4-nitro-2-chloroaniline (recrystallized from water) in 250 ml. of distilled hexamethylphosphoramide is prepared. The solution is cooled with an ice bath, and 30.45 g. (0.15 mole) terephthaloyl chloride is added in small portions over a period of 11/2 hours. After the addition is completed, the ice-bath is removed. A precipitate forms in four hours and the resulting suspension is stirred for 20 hours. After this period 1 l, of water is added to precipitate the product. The pale yellow powder is filtered, and washed two times with hot water in a blender. After being dried at 80° C. in a vacuum oven, 68.2 g. (95 percent of theoretical) of product is obtained; m.p. 339° C. (determined by Differential Thermal Analysis).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Cl:12])[CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:19][C:18]3[CH:20]=[C:21]([F:24])[CH:22]=[CH:23][C:17]=3[S:16](=[O:26])(=[O:25])[CH2:15][CH2:14]2)[CH:3]=1.[NH2:27][CH2:28][C:29]1([NH2:33])[CH2:32][O:31][CH2:30]1>>[NH2:33][C:29]1([CH2:28][NH:27][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([Cl:12])[CH:10]=3)[N:5]=[C:4]([N:13]3[CH2:19][C:18]4[CH:20]=[C:21]([F:24])[CH:22]=[CH:23][C:17]=4[S:16](=[O:26])(=[O:25])[CH2:15][CH2:14]3)[CH:3]=2)[CH2:32][O:31][CH2:30]1
Reactant: O=S1(=O)CCN(c2cc(Cl)c3cc(Cl)ccc3n2)Cc2cc(F)ccc21
Reactant: NCC1(N)COC1
Product: NC1(CNc2cc(N3CCS(=O)(=O)c4ccc(F)cc4C3)nc3ccc(Cl)cc23)COC1

Procedure:
The title compound was prepared in analogy to Example 3-1 in Scheme 5 by using 4-(4,6-dichloroquinolin-2-yl)-7-fluoro-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (prepared in analogy to the one in Example 3-2) and 3-(aminomethyl)oxetan-3-amine. MS obsd. (ESI+) [(M+H)+] 477, 1H NMR (400 MHz, CD3OD) δ ppm 8.07-7.94 (m, 2 H), 7.72 (dd, J=8.97, 2.65 Hz, 1 H), 7.53 (d, J=8.84 Hz, 1 H), 7.43 (dd, J=8.84, 2.27 Hz, 1 H), 7.15 (td, J=8.46, 2.53 Hz, 1 H), 6.23 (s, 1 H), 5.18 (brs, 2 H), 4.73-4.60 (m, 4 H), 4.51 (brs, 2 H), 3.75 (s, 2 H), 3.59 (t, J=4.67 Hz, 2 H).
Reaction SMILES: [Li]CCCC.CCCCCC.[CH3:12][C:13]1[CH2:14][C:15]2[C:20]([CH:21]=1)=[C:19]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH:18]=[CH:17][CH:16]=2.[Cl:28][Si:29](Cl)([CH3:31])[CH3:30]>CCOCC>[Cl:28][Si:29]([CH:14]1[C:15]2[C:20](=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:18]=[CH:17][CH:16]=2)[CH:21]=[C:13]1[CH3:12])([CH3:31])[CH3:30]
Reactant: C[Si](C)(Cl)Cl
Reactant: CC1=Cc2c(cccc2-c2ccccc2)C1
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: CCCCCC
Product: CC1=Cc2c(-c3ccccc3)cccc2C1[Si](C)(C)Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 92.8 %

Procedure:
A 2.5 M solution of n-BuLi in hexane (4.85 mL, 12.12 mmol) was added at 0° C. to a solution of 2.50 g of 2-methyl-4-phenyl-indene (Boulder Scientific Company, Mw=206.29, 12.12 mmol, n-BuLi:2-Me-4-Ph-Ind=1:1) in 30 mL of ether. The resulting mixture was stirred for additional 2 h at room temperature with final formation of an orange solution. This solution was cooled again to 0° C. and added slowly of a solution of 1.58 mL of dichlorodimethylsilane (Aldrich, Mw=129.06, d=1.064, 13.03 mmol, Me2SiCl2:2-Me-4-Ph-Ind=1.08:1) in 20 mL of ether. The reaction mixture was then allowed to warm to room temperature and stirred for 1 h. The final straw yellow suspension was concentrated under vacuum and the residue was extracted with 50 mL of toluene. The extract was dried under vacuum to give 3.36 g of a straw yellow solid, which was characterized by GC-MS analysis and 1H-NMR spectroscopy. Yield=92.8%.
Reaction SMILES: C([Li])CCC.[CH3:6][N:7]([CH3:15])[C:8]1[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=1.I[CH2:17][C:18](=[O:39])[CH:19]=[P:20]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CCCCCC.C(COC)OC.C1C=CC=CC=1.C1(C)C=CC=CC=1>[CH3:6][N:7]([CH3:15])[C:8]1[CH:9]=[C:10]([CH:11]=[CH:12][CH:13]=1)[O:14][CH2:17][C:18](=[O:39])[CH:19]=[P:20]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: O=C(C=P(c1ccccc1)(c1ccccc1)c1ccccc1)CI
Reactant: CN(C)c1cccc(O)c1
Agent: [Li]CCCC
Solvent: c1ccccc1
Solvent: Cc1ccccc1
Solvent: CCCCCC
Product: CN(C)c1cccc(OCC(=O)C=P(c2ccccc2)(c2ccccc2)c2ccccc2)c1
Temperature: 25 °C

Procedure:
n-Butyl-lithium (3.85 ml. of a 1.3 M solution in hexane) was added to a solution of 3-dimethylaminophenol (685 mg.) in dimethoxyethane (20 ml.) at -70° C. under an atmosphere of nitrogen. The solution was allowed to warm to room temperature, a solution of 3-iodoacetonylidene-triphenylphosphorane (2.22 g.) in benzene (100 ml.) was added, and the mixture was heated under reflux for 2 hours. The mixture was then diluted with toluene (100 ml.), washed with water (2×50 ml.) and dried, the solvents were evaporated and the residue was triturated with ether to give [3-(3-dimethylaminophenoxy)acetonylidene]triphenylphosphorane, m.p. 110°-115° C.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([NH:10][C:11]2[CH:16]=[C:15]([NH:17][C:18]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)[CH:21]=3)=[O:19])[CH:14]=[CH:13][C:12]=2[Cl:32])=[O:9])=[CH:4][CH:3]=1.[CH3:33][N:34]([CH3:40])[CH2:35][CH2:36][CH2:37][NH:38][CH3:39]>>[Cl:32][C:12]1[CH:13]=[CH:14][C:15]([NH:17][C:18]([C:20]2[CH:25]=[CH:24][N:23]=[C:22]([N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[CH:21]=2)=[O:19])=[CH:16][C:11]=1[NH:10][C:8]([C:5]1[CH:6]=[N:7][C:2]([N:38]([CH2:37][CH2:36][CH2:35][N:34]([CH3:40])[CH3:33])[CH3:39])=[CH:3][CH:4]=1)=[O:9]
Reactant: O=C(Nc1ccc(Cl)c(NC(=O)c2ccc(Cl)nc2)c1)c1ccnc(N2CCOCC2)c1
Reactant: CNCCCN(C)C
Product: CN(C)CCCN(C)c1ccc(C(=O)Nc2cc(NC(=O)c3ccnc(N4CCOCC4)c3)ccc2Cl)cn1
Yield: 73 %

Procedure:
Using an analogous procedure to that described in Example 21, 6-chloro-N-[2-chloro-5-(2-morpholinopyrid-4-ylcarbonylamino)phenyl]pyridine-3-carboxamide was reacted with N-(3-dimethylaminopropyl)-N-methylamine to give the title compound in 73% yield; NMR Spectrum: (DMSOd6) 1.67 (m, 2H), 2.12 (s, 6H), 2.21 (t, 2H), 3.07 (s, 3H), 3.51 (m, 4H), 3.58 (m, 2H), 3.71 (m, 4H), 6.69 (d, 1H), 7.1 (d, 1H), 7.23 (s, 1H), 7.5 (d, 1H), 7.68 (d, 1H), 8.04 (m, 2H), 8.28 (d, 1H), 8.72 (s, 1H), 9.7 (s, 1H), 10.44 (s, 1H); Mass Spectrum: M+H+ 552 and 554.
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([CH2:11][CH2:12][NH:13]C(OCC3C=CC=CC=3)=O)=[CH:10][C:5]=2[N:4]=[C:3]1[CH2:24][CH2:25][NH:26]C(OCC1C=CC=CC=1)=O>[Pd]>[NH2:13][CH2:12][CH2:11][C:9]1[CH:8]=[CH:7][C:6]2[N:2]([CH3:1])[C:3]([CH2:24][CH2:25][NH2:26])=[N:4][C:5]=2[CH:10]=1
Reactant: Cn1c(CCNC(=O)OCc2ccccc2)nc2cc(CCNC(=O)OCc3ccccc3)ccc21
Agent: [Pd]
Product: Cn1c(CCN)nc2cc(CCN)ccc21
Yield: 55 %

Procedure:
N-[2-(1-Methyl-5-{2-[(phenylmethoxy)carbonylamino]ethyl}benzimidazol-2-yl)ethyl](phenylmethoxy)carboxamide (3.6 mmol) and 10% palladium on carbon (1.0 g, 62 mole %) were combined and hydrogenation was carried out in a manner analogous to the procedure described in example 6 to provide the intermediate title compound, 2-[5-(2-aminoethyl)-1-methylbenzimidazol-2-yl]ethylamine, (55%) as a colorless oil.