Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[S:19][C:20]4[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[CH:23][C:21]=4[N:22]=3)=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)([O-])=O.O.O.[Sn](Cl)Cl.CCCCCC.CCOC(C)=O>CCO>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([CH:10]=[CH:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]3[S:19][C:20]4[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[CH:23][C:21]=4[N:22]=3)=[CH:16][CH:17]=2)=[CH:8][CH:9]=1
Reactant: COc1ccc2nc(-c3ccc(C=Cc4ccc([N+](=O)[O-])cc4)cc3)sc2c1
Agent: Cl[Sn]Cl
Solvent: O
Solvent: CCOC(C)=O
Solvent: CCO
Product: COc1ccc2nc(-c3ccc(C=Cc4ccc(N)cc4)cc3)sc2c1
Yield: 39.9 %

Procedure:
Prepared as described in the Nitro Reduction section using 2-{4-[2-(4-nitrophenyl)-vinyl]-phenyl}-6-methoxybenzothiazole (0.10 g, 0.28 mmol) and tin (II) chloride dihydrate (0.5 g, 2.23 mmol) in EtOH (7 ml) to give the title compound (0.04 g, 43%) as a yellow solid after work-up and flash chromatography (2:1 Hexane/EtOAc).
Reaction SMILES: C[N:2]([CH:4]=[N:5][C:6]([C:8]1[S:9][C:10]([CH2:25][CH3:26])=[C:11]([C:23]#[N:24])[C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=1)=O)C.O.[NH2:28]N>C(O)(=O)C>[C:19]([C:16]1[CH:17]=[CH:18][C:13]([C:12]2[C:11]([C:23]#[N:24])=[C:10]([CH2:25][CH3:26])[S:9][C:8]=2[C:6]2[NH:28][N:2]=[CH:4][N:5]=2)=[CH:14][CH:15]=1)([CH3:20])([CH3:22])[CH3:21]
Reactant: NN
Reactant: CCc1sc(C(=O)N=CN(C)C)c(-c2ccc(C(C)(C)C)cc2)c1C#N
Solvent: O
Solvent: CC(=O)O
Product: CCc1sc(-c2ncn[nH]2)c(-c2ccc(C(C)(C)C)cc2)c1C#N
Temperature: 90 °C

Procedure:
Dissolve 3-(4-tert-butyl-phenyl)-4-cyano-5-ethyl-thiophene-2-carboxylic acid dimethylaminomethyleneamide (261 mg, 0.71 mmol) in 2 mL of glacial acetic acid, add hydrazine monohydrate (50 μL, 1.03 mmol) and heat to 90° C. under nitrogen. After 90 minutes cool the reaction slightly, pour into 50 mL of ice-water and stir for twenty minutes. Filter off the resulting solid and rinse with 10 mL of water. Vacuum-dry overnight to give the title compound, 206 mg (86%). MS(ES+, m/e)=337 (M++1); HPLC=00%.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[S:12][C:13]3[CH2:14][N:15]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:17][C:18]=3[N:19]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:27]([O:30][CH2:31][C:32]1[C:33]([N:41]2[CH2:52][CH2:51][N:50]3[C:43](=[CH:44][C:45]4[CH2:46][C:47]([CH3:54])([CH3:53])[CH2:48][C:49]=43)[C:42]2=[O:55])=[N:34][CH:35]=[CH:36][C:37]=1B(O)O)(=[O:29])[CH3:28].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>O.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].C(#N)C>[C:27]([O:30][CH2:31][C:32]1[C:33]([N:41]2[CH2:52][CH2:51][N:50]3[C:43](=[CH:44][C:45]4[CH2:46][C:47]([CH3:54])([CH3:53])[CH2:48][C:49]=43)[C:42]2=[O:55])=[N:34][CH:35]=[CH:36][C:37]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[S:12][C:13]3[CH2:14][N:15]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:17][C:18]=3[N:19]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:29])[CH3:28]
Reactant: CC(=O)OCc1c(B(O)O)ccnc1N1CCn2c(cc3c2CC(C)(C)C3)C1=O
Reactant: Cn1cc(Br)cc(Nc2nc3c(s2)CN(C(=O)OC(C)(C)C)CC3)c1=O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: CC(=O)[O-]
Solvent: CC#N
Solvent: O
Product: CC(=O)OCc1c(-c2cc(Nc3nc4c(s3)CN(C(=O)OC(C)(C)C)CC4)c(=O)n(C)c2)ccnc1N1CCn2c(cc3c2CC(C)(C)C3)C1=O
Temperature: 100 °C

Procedure:
A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 233a (300 mg, 0.68 mmol), (3-(acetoxymethyl)-2-(7,7-dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta[4,5]pyrrolo-[1,2-a]pyrazin-2(6H)-yl)pyridin-4-yl)boronic acid 199e (1.8 g, 2.72 mmol), Pd(dppf)Cl2 (27.7 mg, 0.034 mmol), K3PO4 (288.3 mg, 1.36 mmol), sodium acetate (111.5 mg, 1.36 mmol), water (10 drops), and acetonitrile (10 mL). After bubbling nitrogen through the mixture for 30 minutes, it was heated at 100° C. under N2 protection for 1 h. Analysis of reaction mixture by LCMS showed complete conversion to the desired product. The mixture was filtered and the filtrate was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 100:1 dichloromethane/methanol to afford 233b (220 mg, 45%) as a yellow solid. MS-ESI: [M+H]+ 714.3
Reaction SMILES: [CH:1]1[CH:2]=C[C:4]2[N:9](O)N=[N:7][C:5]=2[CH:6]=1.[C:11]1([CH2:17][O:18][C:19]2[CH:27]=[CH:26][C:25]([C:28]([N:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)=[O:29])=[CH:24][C:20]=2[C:21](O)=[O:22])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.N1C=CC=C(N)C=1.C(Cl)CCl>CN(C)C=O.O>[C:11]1([CH2:17][O:18][C:19]2[CH:27]=[CH:26][C:25]([C:28]([N:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)=[O:29])=[CH:24][C:20]=2[C:21]([NH:7][C:5]2[CH:4]=[N:9][CH:2]=[CH:1][CH:6]=2)=[O:22])[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: On1nnc2ccccc21
Reactant: O=C(O)c1cc(C(=O)N2CCCCC2)ccc1OCc1ccccc1
Agent: Nc1cccnc1
Solvent: CN(C)C=O
Solvent: O
Solvent: ClCCCl
Product: O=C(Nc1cccnc1)c1cc(C(=O)N2CCCCC2)ccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Neat HOBT (90 mg, 0.59 mmol) was added in one charge to a stirred solution of 2-[(phenylmethyl)oxy]-5-(1-piperidinylcarbonyl)benzoic acid (may be prepared as described in Description 53; 200 mg, 0.59 mmol), 3-pyridinamine (55.5 mg, 0.59 mmol), and EDC (113 mg, 0.59 mmol) in N,N-dimethylformamide (5 ml) under nitrogen at room temperature. The reaction mixture was stirred at room temperature for 4 h. The mixture was diluted with water (50 ml). The precipitate was collected by filtration, washed with ether (5 ml), and dried to yield the title compound as a white solid. 65 mg.
Reaction SMILES: CO[C:3]([C@H:5]1[NH:18][C:17](=[S:19])[CH2:16][CH2:15][CH2:14][CH2:13][O:12][C:11](=[O:20])[C:10]2[C:21]([CH3:28])=[C:22]([O:26][CH3:27])[CH:23]=[C:24]([OH:25])[C:9]=2[CH2:8][S:7][CH2:6]1)=[O:4].[NH2:29][CH2:30][CH2:31][CH2:32][OH:33]>CO.C(OCC)(=O)C>[OH:33][CH2:32][CH2:31][CH2:30][NH:29][C:3]([C@H:5]1[NH:18][C:17](=[S:19])[CH2:16][CH2:15][CH2:14][CH2:13][O:12][C:11](=[O:20])[C:10]2[C:21]([CH3:28])=[C:22]([O:26][CH3:27])[CH:23]=[C:24]([OH:25])[C:9]=2[CH2:8][S:7][CH2:6]1)=[O:4]
Reactant: COC(=O)[C@@H]1CSCc2c(O)cc(OC)c(C)c2C(=O)OCCCCC(=S)N1
Reactant: NCCCO
Solvent: CO
Solvent: CCOC(C)=O
Product: COc1cc(O)c2c(c1C)C(=O)OCCCCC(=S)N[C@H](C(=O)NCCCO)CSC2
Temperature: 50 °C

Procedure:
A solution of 43 mg of the product of Example 23 in a mixture of 0.5 ml of methanol and 0.5 ml of 3-amino-propanol was heated to 50° C. 20 min. The mixture was diluted with ethyl acetate and washed with 1N hydrochloric acid and water. The organic layer was dried over sodium sulfate and evaporated in vacuo and the solid residue was recrystallized from ethyl acetate/hexane to afford 12 mg (R)-16-hydroxy-14-methoxy-13-methyl-12-oxo-6-thioxo-1,3,4,5,6,7,8,9,10,12-decahydro-11,2,5-benzoxathiaazacyclotetradecine-4-carboxylic acid 3-hydroxy-propylamide as a white solid.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:5]=[C:6]([OH:8])[CH:7]=1.[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[CH2:15]([O:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:5]=[C:6]([O:8][CH2:9][C:4]2[CH:5]=[CH:6][CH:7]=[CH:2][CH:3]=2)[CH:7]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: BrCc1ccccc1
Reactant: CCOC(=O)Cc1cc(O)cc(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)Cc1cc(OCc2ccccc2)cc(OCc2ccccc2)c1

Procedure:
A solution of ethyl 3,5-dihydroxyphenylacetate (4.0 g, 20.39 mmol), benzyl bromide (4.85 ml, 6.97 g, 40.77 mmol, 2 eq) and 5.64 g (40.77 mmol, 2 eq) of K2CO3 in 100 ml of acetone is refluxed overnight. The mixture is concentrated in vacuo, then partitioned between EtOAc and H2O. The organics are dried (MgSO4) and concentrated in vacuo. This is then passed through a flash silica gel column that is slurry packed with hexanes and eluted with 10% EtOAc in hexanes. Concentration of desired fractions gives ethyl 3,5-dibenzyloxyphenylacetate which is confirmed by NMR and used directly in the next step.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]([Cl:12])=[C:4]([NH2:13])[N:3]=1.Br[CH2:15][C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=O.[I-].[Na+]>>[NH2:13][C:4]1[N:3]2[CH:15]=[C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[N:1]=[C:2]2[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]=1[Cl:12]
Reactant: COC(=O)c1cc(Cl)c(N)nc1N
Reactant: O=C(CBr)c1ccccc1
Agent: [I-]
Agent: [Na+]
Product: COC(=O)c1cc(Cl)c(N)n2cc(-c3ccccc3)nc12

Procedure:
The title compounds were prepared according to the procedure described in the step 2 in EXAMPLE 1 (METHOD B) using methyl 2,6-diamino-5-chloro-3-pyridinecarboxylate (EXAMPLE 1, METHOD B, Step 1), 2-bromoacetophenone and sodium iodide.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[O:13][CH:14]=[CH:15][CH:16]=1)[CH:6]=[C:5]2[C:17]([NH:19][C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)=[O:18]>CN(C=O)C.C(OCC)(=O)C>[O:13]1[CH:14]=[CH:15][CH:16]=[C:12]1[C:7]1[CH:6]=[C:5]([C:17]([NH:19][C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)=[O:18])[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:2]3[CH:3]=[CH:4][CH:9]=[CH:10][CH:11]=3)[CH:3]=2)[N:8]=1
Reactant: O=C(Nc1cccnc1)c1cc(-c2ccco2)nc2ccc(Br)cc12
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C(Nc1cccnc1)c1cc(-c2ccco2)nc2ccc(-c3ccccc3)cc12
Temperature: 90 °C
Reaction time: 0.08 h
Yield: 124.1 %

Procedure:
To a sealed tube under argon atmosphere was added 6-bromo-2-(furan-2-yl)-N-(pyridin-3-yl)quinoline-4-carboxamide (0.250 g) in DMF (5 ml), and the vessel was purged with argon under stirring for 5 minutes. After 5 minutes, 2N solution of sodium carbonate in water (3.3 ml) was added and the tube was purged with argon under stirring for 5 minutes. Phenylboronic acid (0.115 g) was then added and the tube was purged with argon under stirring for 15 minutes. Finally, palladium(0)tetrakis triphenylphosphine (0.034 g) was added under argon and the tube was sealed and heated to 90° C. for 16 hours. The completion of the reaction was monitored by TLC using ethyl acetate:hexanes (5:5) as a mobile phase. After completion of the reaction, the reaction mixture was diluted with ethyl acetate (100 ml) and then washed with water (5*100 ml). The ethyl acetate layer was dried over anhydrous sodium sulphate, and the solvent was removed by distillation and the crude product was subjected to purification by silica gel column chromatography, eluting with 1-2% methanol in methylene chloride to provide 0.154 g of 2-(furan-2-yl)-6-phenyl-N-(pyridin-3-yl)quinoline-4-carboxamide (1). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.13 (s, 1H), 8.59 (m, 1H), 8.39 (m, 1H), 8.37 (s, 1H), 8.30 (m, 1H), 8.25 (s, 1H), 8.19 (m, 2H), 8.02 (s, 1H), 7.79 (m, 2H), 7.55 (m, 3H), 7.46 (m, 2H), 6.79 (m, 1H); m/z 392.2 (MH+).
Reaction SMILES: [NH:1]([C:8]([C@H:10]1[N:14]2[C:15](=[O:41])[C:16]([N:19]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=3)C(=O)OCC3C=CC=CC=3)=[CH:17][N:18]=[C:13]2[CH:12]([CH3:42])[CH2:11]1)=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH2:54][C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56]>C1COCC1>[NH:1]([C:8]([C@H:10]1[N:14]2[C:15](=[O:41])[C:16]([NH:19][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:39])([F:40])[F:38])[CH:32]=3)=[CH:17][N:18]=[C:13]2[C@:12]([CH2:54][C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])([CH3:42])[CH2:11]1)=[O:9])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC1C[C@@H](C(=O)Nc2ccccc2)n2c1ncc(N(Cc1cccc(C(F)(F)F)c1)C(=O)OCc1ccccc1)c2=O
Reactant: CC(C)(C)OC(=O)CBr
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)C[C@@]1(C)C[C@@H](C(=O)Nc2ccccc2)n2c1ncc(NCc1cccc(C(F)(F)F)c1)c2=O
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 45.4 %

Procedure:
To a solution of 12c (0.987 g, 1.71 mmol) in 8.6 mL THF at −78° C., was added LiHMDS (1M in THF, 3.59 mL, 3.59 mmol). The red solution was stirred at −78° C. for 10 min, then a solution of t-butyl bromoacetate (0.278 mL, 1.88 mmol) was added. The reaction was allowed to slowly warm to −50° C. over 1 h, then was quenched with the addition of sat. NH4Cl. The mixture was poured into 50 mL H2O and extracted with 100 mL EtOAc. The organic phase was washed with 0.1N HCl and brine, dried (Na2SO4), and concentrated. The product was purified by flash chromatography (50% EtOAc/hexanes) to afford 432 mg (37%) of 92a. 1H NMR (300 MHz, CDCl3) δ8.94 (br s, 1H), 7.51-7.26 (m, 15H), 7.09 (t, J=7.5, 1H), 5.25-5.13 (m, 3H), 5.06 (dd, J=9.4, 6.0, 1H), 4.85 (br s, 2H), 2.89 (dd, J=13.9, 5.8, 1H), 2.80 (ABq, JAB=16.8, δνAB=91.9, 2H), 2.44 (dd, J=13.5, 9.1, 1H), 1.38 (s, 12H); MS (ESI) 713.2 (M+Na+), 689.4 (M−H+).
Reaction SMILES: [C:1]1([C:7]2([C:10]3[CH:11]=[N:12][C:13]([N:16]4[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]4)=[N:14][CH:15]=3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.O1CCOCC1>O1CCOCC1>[C:1]1([C:7]2([C:10]3[CH:15]=[N:14][C:13]([N:16]4[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]4)=[N:12][CH:11]=3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ncc(C3(c4ccccc4)CC3)cn2)CC1
Agent: Cl
Solvent: C1COCCO1
Product: c1ccc(C2(c3cnc(N4CCNCC4)nc3)CC2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of tert-butyl 4-(5-(1-phenylcyclopropyl)pyrimidin-2-yl)piperazine-1-carboxylate (30 mg, 0.08 mmol) in dioxane (2 mL) was added 4 M HCl-dioxane (2 mL). The reaction mixture was stirred at room temperature overnight and then concentrated to afford crude 5-(1-phenylcyclopropyl)-2-(piperazin-1-yl)pyrimidin. MS (ES+) C17H20N4 requires: 280, found: 281 [M+H]+.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([CH2:6][O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[C:10]([O:17][CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=2)=[CH:2]1.Cl.[NH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30].ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O>[CH3:32][O:31][C:29]([CH2:28][NH:27][C:12]([C:11]1[CH:15]=[CH:16][C:8]([O:7][CH2:6][C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)=[CH:9][C:10]=1[O:17][CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])=[O:14])=[O:30]
Reactant: C[Si](C)(C)CCOCOc1cc(OCc2ccsc2)ccc1C(=O)O
Reactant: COC(=O)CN
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COC(=O)CNC(=O)c1ccc(OCc2ccsc2)cc1OCOCC[Si](C)(C)C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A mixture of 4-(3-thienylmethoxy)-2-[2-(trimethylsilyl)ethoxy]methoxybenzoic acid (3.09 g), methyl aminoacetate hydrochloride (0.99 g), 1-hydroxybenzotriazole (1.28 g), triethylamine (0.8 g) and dimethylformamide (50 mL) is stirred at ambient temperature for 16 hours. It is then concentrated in vacuo and the resulting residue is dissolved in ethyl acetate (100 mL), washed quickly with hydrochloric acid (2×50 mL; 1 N), and then washed with saturated aqueous sodium bicarbonate solution (50 mL) and with water (50 mL), then dried over magnesium sulphate, filtered and concentrated in vacuo, to give 1-[N-(methoxycarbonylmethyl)carbamoyl]-4-(3-thienylmethoxy)-2-[2-(trimethylsilyl)ethoxy]methoxybenzene, in the form of a yellow oil.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:19]=[CH:18][C:7]([CH2:8][CH:9]([C:14]([O:16][CH3:17])=[O:15])[C:10]([O:12][CH3:13])=[O:11])=[CH:6][C:5]=1[CH2:20][OH:21])[CH3:2].[Cl:22][C:23]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=1[N:30]=[C:31]=[O:32]>>[Cl:22][C:23]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=1[NH:30][C:31]([O:21][CH2:20][C:5]1[CH:6]=[C:7]([CH:18]=[CH:19][C:4]=1[O:3][CH2:1][CH3:2])[CH2:8][CH:9]([C:14]([O:16][CH3:17])=[O:15])[C:10]([O:12][CH3:13])=[O:11])=[O:32]
Reactant: O=C=Nc1ccc(Cl)cc1Cl
Reactant: CCOc1ccc(CC(C(=O)OC)C(=O)OC)cc1CO
Product: CCOc1ccc(CC(C(=O)OC)C(=O)OC)cc1COC(=O)Nc1ccc(Cl)cc1Cl

Procedure:
Using dimethyl 2-[4-ethoxy-3-(hydroxymethyl)benzyl]-malonate and 2,4-dichlorophenylisocyanate, the title compound was obtained in the same manner as described in Example 192b)
Reaction SMILES: CO[N:3]=[C:4]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][CH:7]=1.B.O1CCCC1.O>C1COCC1>[NH2:3][CH:4]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][CH:7]=1
Reactant: CON=C(Cc1ccc(Br)cc1)c1ccccc1
Agent: B
Solvent: C1CCOC1
Solvent: O
Product: NC(Cc1ccc(Br)cc1)c1ccccc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of the mixture of oxime isomers 8 (4.92 g, 16.2 mmol) in 75 ml THF (freshly distilled from sodium benzophenone ketyl) under nitrogen was added borane-tetrahydrofuran complex (1.0M in THF, 55.0 ml, 55.0 mmol) by syringe at room temperature. The resulting pale orange solution was brought to reflux and held there for 16 hours. With cooling by an ice bath, water (125 ml) was carefully added to quench, followed by 20% NaOH (125 ml).The resulting biphasic solution was refluxed with vigorous magnetic stirring overnight. After cooling to room temperature, hexanes (60 ml) were added and the layers were separated. The aqueous portion was extracted with hexanes (2×50 ml). The combined organic portions were dried over potassium carbonate and concentrated in vacuo to a cloudy, colorless syrup. This syrup was purified by column chromatography on 20 g neutral alumina (activity I) using a 20% ethyl acetate-hexanes to 4% diethylamine-chloroform elution gradient. The amine 13 was isolated as 3.985 g of a clear, colorless syrup (89% yield): Rf 0.18 (2% diethylamine in CHCl3); 1H NMR (CDCl3) δ7.41 (d, J=8.2 Hz, 2H), 7.35-7.28 (m, 5H), 7.03 (d, J=8.2 Hz, 2H), 4.18 (dd, J=8.2, 5.3 Hz, 1H), 2.97 (dd, J=13.3, 53 Hz, 1H), 2.83 (dd, J=13.3, 8.3 Hz, 1H), 1.45 br s, 2H); low resolution mass Spec. 277 (M+, 1.5), 275 (M+, 1.5), 261 (2.2), 259 (2.2), 171, (4.5), 169 (4.5), 106 (100), 79 (45).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:21]3[C:22]4=[C:23]5[C:18](=[CH:19][CH:20]=3)[CH:17]=[CH:16][CH:15]=[C:14]5[CH:13]=[CH:12][C:11]4=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:24][C:25]1([CH3:59])[C:49]2[C:29]([CH:30]=[C:31]3[CH:48]=[C:47]4[C:34]([C:35]5[C:40]([C:41]6[C:46]4=[CH:45][CH:44]=[CH:43][CH:42]=6)=[CH:39][CH:38]=[CH:37][CH:36]=5)=[CH:33][C:32]3=2)=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26]1.C([O-])([O-])=O.[Na+].[Na+].CCO>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.CO.C1(C)C=CC=CC=1>[CH3:59][C:25]1([CH3:24])[C:49]2[C:29]([CH:30]=[C:31]3[CH:48]=[C:47]4[C:34]([C:35]5[C:40]([C:41]6[C:46]4=[CH:45][CH:44]=[CH:43][CH:42]=6)=[CH:39][CH:38]=[CH:37][CH:36]=5)=[CH:33][C:32]3=2)=[CH:28][C:27]([C:2]2[CH:3]=[CH:4][C:5]([C:8]3[C:21]4[C:22]5=[C:23]6[C:18](=[CH:19][CH:20]=4)[CH:17]=[CH:16][CH:15]=[C:14]6[CH:13]=[CH:12][C:11]5=[CH:10][CH:9]=3)=[CH:6][CH:7]=2)=[CH:26]1
Reactant: CC1(C)C=C(B2OC(C)(C)C(C)(C)O2)C=C2C=c3cc4c5ccccc5c5ccccc5c4cc3=C21
Reactant: Brc1ccc(-c2ccc3ccc4cccc5ccc2c3c45)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: CO
Product: CC1(C)C=C(c2ccc(-c3ccc4ccc5cccc6ccc3c4c56)cc2)C=C2C=c3cc4c5ccccc5c5ccccc5c4cc3=C21
Temperature: 90 °C
Yield: 57 %

Procedure:
A mixture of 5 g (14 mmol) of 1-(4-bromophenyl)pyrene, of 7.53 (16 mmol) 2-(10,10-dimethyl-10H-indeno[1,2-b]triphenylen-12-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, 0.16 g (0.14 mmol) of Tetrakis(triphenylphosphine)palladium, 11 ml of 2M Na2CO3, 30 ml of EtOH and 65 ml toluene was degassed and placed under nitrogen, and then heated at 90° C. for 12 h. After the reaction finish, the mixture was allowed to cool to room temperature. Than 500 ml MeOH was added, while stirring and the precipitated product was filtered off with suction. To give 4.95 g (yield 57%) of yellow product which was recrystallized from toluene. MS(m/z,FAB+): 620.2; 1H NMR (CDCl3, 400 MHz): chemical shift(ppm) 9.06 (s, 1H), 8.86 (d, J=8.00 Hz, 1H), 8.80 (d, J=8.00 Hz, 1H), 8.75 (s, 1H), 8.71 (d, J=8.00 Hz, 2H), 8.33˜8.27 (m, 2H), 8.22˜8.20 (m, 2H), 8.14˜8.05 (m, 6H), 7.94 (d, J=8.00 Hz, 2H), 7.89 (s, 1H), 7.85˜7.69 (m, 7H), 1.77 (s, 6H).
Reaction SMILES: [IH:1].CS[C:4](=[NH:19])[NH:5][CH:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[NH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>CC(O)(C)C>[IH:1].[C:7]1([CH:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[NH:5][C:4]([N:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[NH:19])[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: CSC(=N)NC(c1ccccc1)c1ccccc1
Reactant: C1CCNCC1
Agent: I
Solvent: CC(C)(C)O
Product: N=C(NC(c1ccccc1)c1ccccc1)N1CCCCC1

Procedure:
To a suspension of 9.61 g (0.025 mole) of methyl-N-(diphenylmethyl)-carbamimidothioate hydroiodide in 20 ml of t-BuOH is added 4.26 g (0.05 mole) of piperidine. The mixture is heated under reflux over night. The resulting crystals after cooling in ice, are filtered; mp 200°-213° C. One recrystallization from methanol-t-BuOH yields the pure product, N-(diphenylmethyl)-1-piperidinecarboximidamide monohydroiodide as a white crystalline solid; mp 207°-210° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH3:21])[C:10](=[N:13][C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=3)[S:11][CH:12]=2)=[CH:4][C:3]=1[S:22](=[O:27])(=[O:26])[N:23]([CH3:25])[CH3:24].[C:28](Cl)(=[O:31])[CH2:29][CH3:30].N1C=CC=CC=1>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH3:21])[C:10](=[N:13][C:14]3[CH:15]=[CH:16][C:17]([O:20][C:28](=[O:31])[CH2:29][CH3:30])=[CH:18][CH:19]=3)[S:11][CH:12]=2)=[CH:4][C:3]=1[S:22](=[O:27])(=[O:26])[N:23]([CH3:24])[CH3:25]
Reactant: CCC(=O)Cl
Reactant: CN(C)S(=O)(=O)c1cc(-c2csc(=Nc3ccc(O)cc3)n2C)ccc1Cl
Solvent: c1ccncc1
Solvent: ClC(Cl)Cl
Product: CCC(=O)Oc1ccc(N=c2scc(-c3ccc(Cl)c(S(=O)(=O)N(C)C)c3)n2C)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
2 g (4.7 mmoles) of 4-(4-chloro-3-dimethylsulfamoylphenyl)-2-(4-hydroxyphenylimino)-3-methyl-4-thiazoline is suspended in 40 ml of dry chloroform. 0.4 g (4.7 mmoles) of propionyl chloride (dissolved in 10 ml of chloroform) and 1.4 g (18 mmoles) of pyridine are added in that order. A slightly exothermic reaction produces, temporarily, a solution from which a yellow solid precipitates. After stirring for 3 hours at room temperature, a further 0.4 ml of propionyl chloride is added. The resulting yellow solution is allowed to stand for 3 days at room temperature and then evaporated to dryness in vacuo, the residue is distributed between water and ethyl acetate, the organic phase is dried and evaporated and the residue is recrystallized from isopropanol. Colorless crystals of m.p. 155°-159° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([F:11])[C:3]=1[N:12]1[CH2:17][CH:16]2[CH:14]([O:15]2)[CH2:13]1.[H][H]>[Pd].C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[C:4]([F:11])[C:3]=1[N:12]1[CH2:17][CH:16]2[CH:14]([O:15]2)[CH2:13]1
Reactant: O=[N+]([O-])c1cc(F)c(N2CC3OC3C2)c(F)c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: Nc1cc(F)c(N2CC3OC3C2)c(F)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
10% Palladium on carbon (0.02 g) was added to 3-(2,6-difluoro-4-nitro-phenyl)-6-oxa-3-aza-bicyclo[3.1.0]hexane (0.2 g, 0.83 mmol) dissolved in ethyl acetate (8.0 mL). The flask was charged with hydrogen gas and the mixture was stirred at room temperature for 3 h. The reaction mixture was filtered through celite and the solvent removed to get the title compound which was used directly in the next reaction.