Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C@:2]12[C@@H:19]([OH:20])[CH2:18][C@@:16]3([CH3:17])[C@@H:12]([CH2:13][CH2:14][C@@H:15]3[SH:21])[C@@H:11]1[CH2:10][CH2:9][C:8]1[C@:3]2([CH3:23])[CH:4]=[CH:5][C:6](=[O:22])[CH:7]=1.[OH-].[Na+].[CH2:26](Br)[CH:27]=[CH2:28]>CO>[F:1][C@:2]12[C@@H:19]([OH:20])[CH2:18][C@@:16]3([CH3:17])[C@@H:12]([CH2:13][CH2:14][C@@H:15]3[S:21][CH2:28][CH:27]=[CH2:26])[C@@H:11]1[CH2:10][CH2:9][C:8]1[C@:3]2([CH3:23])[CH:4]=[CH:5][C:6](=[O:22])[CH:7]=1
Reactant: C[C@]12C[C@H](O)[C@@]3(F)[C@@H](CCC4=CC(=O)C=C[C@@]43C)[C@@H]1CC[C@@H]2S
Reactant: C=CCBr
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: C=CCS[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]12C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution of 1.7 g of (11β,17β)-9-Fluoro-11-hydroxy-17-mercaptoandrosta-1,4-dien-3-one dissolved in 100 ml of methanol, there was added 1 g of sodium hydroxide followed by 2.5 ml of allyl bromide (nitrogen atmosphere). The alkylation was complete after 1 hour of stirring at room temperature. The solution was partly evaporated, water was added and the resulting solid filtered and washed with water. Crystallization of the solid from ethyl acetate-petroleum ether furnished 1.08 g of the analytical sample, melting point 173°-175° C.
Reaction SMILES: Br[C:2]1[S:3][C:4]2[CH:10]=[C:9]([OH:11])[CH:8]=[CH:7][C:5]=2[N:6]=1.[CH3:12][CH:13]1[CH2:18][CH2:17][N:16]([C:19]([C:21]2[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=2)=[O:20])[CH2:15][CH2:14]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(OCCO)C.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>[OH:11][C:9]1[CH:8]=[CH:7][C:5]2[N:6]=[C:2]([C:24]3[CH:23]=[CH:22][C:21]([C:19]([N:16]4[CH2:15][CH2:14][CH:13]([CH3:12])[CH2:18][CH2:17]4)=[O:20])=[CH:26][CH:25]=3)[S:3][C:4]=2[CH:10]=1
Reactant: Oc1ccc2nc(Br)sc2c1
Reactant: CC1CCN(C(=O)c2ccc(B(O)O)cc2)CC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CCOCCO
Solvent: O
Product: CC1CCN(C(=O)c2ccc(-c3nc4ccc(O)cc4s3)cc2)CC1
Temperature: 115 °C
Reaction time: 2 h
Yield: 20.1 %

Procedure:
2-Bromo-6-hydroxybenzothiazole (400 mg, 1.74 mmol), 4-(4-methylpiperidine-1-carbonyl)phenylboronic acid (472 mg, 1.91 mmol), potassium phosphate (848 mg, 6.96 mmol) and tetrakis(triphenylphosphine)palladium (60 mg, 0.05 mmol) were dissolved in a mixture of 1.3.5 mL 2-ethoxyethanol and 1.5 mL water. The mixture was stirred at 115° C. under argon for 2 h. The reaction mixture was let to reach room temperature then activated-carbon was added and stirred for 20 min. The mixture was filtered, the solid was washed with ethanol and the combined filtrates were evaporated. The residue was purified by column chromatography (Kieselgel 60) with chloroform as the eluent. The crude product was triturated with Et2O, collected and air dried, affording the title compound (122 mg, 0.35 mmol, 20%).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][C@@H:11]([CH3:14])[C@@H:10]([N:15]3[C:19]4=[C:20]5[CH:26]=[CH:25][NH:24][C:21]5=[N:22][CH:23]=[C:18]4[NH:17][C:16]3=[O:27])[CH2:9]2)[CH:5]=[CH:4][N:3]=1.[C-]#N.[Na+].[N:31]12CCN(CC1)C[CH2:32]2.O>CS(C)=O>[CH3:14][C@@H:11]1[CH2:12][CH2:13][N:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:32]#[N:31])[N:7]=2)[CH2:9][C@@H:10]1[N:15]1[C:19]2=[C:20]3[CH:26]=[CH:25][NH:24][C:21]3=[N:22][CH:23]=[C:18]2[NH:17][C:16]1=[O:27]
Reactant: C1CN2CCN1CC2
Reactant: C[C@@H]1CCN(c2ccnc(Cl)n2)C[C@@H]1n1c(=O)[nH]c2cnc3[nH]ccc3c21
Agent: [C-]#N
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: C[C@@H]1CCN(c2ccnc(C#N)n2)C[C@@H]1n1c(=O)[nH]c2cnc3[nH]ccc3c21
Temperature: 80 °C
Reaction time: 7 h
Yield: 245.7 %

Procedure:
To a solution of rel-1-[(3R,4R)-1-(2-chloro-4-pyrimidinyl)-4-methyl-3-piperidinyl]-3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]-pyridin-2(1H)-one (60 mg) and sodium cyanide (38 mg) in DMSO (1 mL), 1,4-diazabicyclo[2.2.2]octane (5 mg) was added at ambient temperature. The temperature was raised to 80° C. and stirred for 7 hours. After cooling down to ambient temperature, water (15 mL) was added to the mixture and resulting precipitate was collected by filtration. The filtrate was purified by pre-packed column (chloroform:methanol=95:1 to 80:20) to afford rel-4-[(3R,4R)-4-methyl-3-(2-oxo-3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(2H)-yl)-1-piperidinyl]-2-pyrimidinecarbonitrile (41 mg) as white powder.
Reaction SMILES: [CH3:1][C:2]1[C:3]2[C:8]([C:9]([CH3:16])=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2>[Cr]([O-])([O-])=O.[Cu+2].C1(C)C=CC=CC=1>[CH3:1][CH:2]1[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:8]=2[CH:9]([CH3:16])[C:10]2[C:15]1=[CH:14][CH:13]=[CH:12][CH:11]=2
Reactant: Cc1c2ccccc2c(C)c2ccccc12
Agent: O=[Cr]([O-])[O-]
Agent: [Cu+2]
Solvent: Cc1ccccc1
Product: CC1c2ccccc2C(C)c2ccccc21
Reaction time: 1 h
Yield: 8 %

Procedure:
9,10-Dihydro-9,10-dimethylanthracene was prepared by hydrogenation of 9,10-dimethylanthracene with Girdler G-22 copper chromite catalyst in toluene at 120° C. and 1500 psi for 1 hour. The mixtures resulting from five such runs were combined and filtered, and the off-white solid product was isolated by evaporating the solvent. It was characterized by nmr spectroscopy.
Reaction SMILES: Br[C:2]1[C:3]2[N:4]([N:8]=[C:9]([NH2:11])[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[CH:12]([S:15]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)(=[O:17])=[O:16])([CH3:14])[CH3:13]>>[CH3:14][CH:12]([S:15]([C:18]1[CH:23]=[CH:22][C:21]([C:2]2[C:3]3[N:4]([N:8]=[C:9]([NH2:11])[N:10]=3)[CH:5]=[CH:6][CH:7]=2)=[CH:20][CH:19]=1)(=[O:16])=[O:17])[CH3:13]
Reactant: Nc1nc2c(Br)cccn2n1
Reactant: CC(C)S(=O)(=O)c1ccc(B(O)O)cc1
Product: CC(C)S(=O)(=O)c1ccc(-c2cccn3nc(N)nc23)cc1

Procedure:
8-[4-(Propane-2-sulfonyl)-phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine was prepared from 8-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (500.0 mg, 2.347 mmol) and 4-isopropylsulfonylbenzeneboronic acid (650.0 mg, 2.850 mmol) in a manner analogous to Step 2c. The reaction product was isolated as an off-white solid (0.317 g, 42%). MP=175-177° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.64 (d, J=6.6 Hz, 1H), 8.39 (d, J=7.4 Hz, 2H), 7.96 (d, J=7.5 Hz, 2H), 7.85 (d, J=7.4 Hz, 1H), 7.06-7.00 (m, 1H), 6.21 (br s, 2H), 3.54-3.42 (m, 1H), 1.19 (d, J=6.5 Hz, 6H). MS=317 (MH)+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:16]3[C:11]([CH:12]=[N:13][C:14](S(C)=O)=[N:15]3)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)C(C)C)(C)C.[CH3:29][N:30]([CH3:38])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([NH2:37])[CH:32]=1.COCCO>>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:16]3[C:11]([CH:12]=[N:13][C:14]([NH:37][C:33]4[CH:34]=[CH:35][CH:36]=[C:31]([N:30]([CH3:38])[CH3:29])[CH:32]=4)=[N:15]3)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CN(C)c1cccc(N)c1
Reactant: CS(=O)c1ncc2ccc(-c3cccc(Cl)c3)n2n1
Solvent: COCCO
Solvent: CCN(C(C)C)C(C)C
Product: CN(C)c1cccc(Nc2ncc3ccc(-c4cccc(Cl)c4)n3n2)c1
Temperature: 180 °C
Yield: 3.9 %

Procedure:
7-(3-Chloro-phenyl)-2-methanesulfinyl-pyrrolo[2,1-f][1,2,4]triazine (76.2 mg, 0.000261 mol), N,N-Diisopropylethylamine (0.0682 mL, 0.000392 mol) and N,N-Dimethyl-benzene-1,3-diamine (71.1 mg, 0.000522 mol) were dissolved in 2-Methoxyethanol (1.83 mL, 0.0232 mol) and the reaction was heated at 180° C. until HPLC showed consumption of starting material. The reaction mixture was then reduced en vacuo and the product was isolated and purified by Gilson prep HPLC to afford 3.73 mg of N-[7-(3-Chloro-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N′,N′-dimethyl-benzene-1,3-diamine as a lyophilated powder. (M+H)=364.11. 1H NMR (400 MHz, CDCl3) δ 9.08 (s, 1H), 8.37 (d, 1H, J=9.60 Hz), 8.10 (s, 1H), 7.89 (d, 1H, J=7.58 Hz), 7.44 (m, 3H), 7.20 (d, 1H, J=4.80 Hz), 7.03 (d, 1H, J=4.54 Hz), 6.61 (m, 2H), 3.11 (s, 6H).
Reaction SMILES: C(OC([N:6]1[CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][OH:15])[CH2:8][CH2:7]1)=O)C.[OH-].[Na+]>C(O)C>[OH:15][CH2:14][CH2:13][CH2:12][N:9]1[CH2:10][CH2:11][NH:6][CH2:7][CH2:8]1
Reactant: CCOC(=O)N1CCN(CCCO)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: OCCCN1CCNCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 80.7 %

Procedure:
4-(3-hydroxypropyl)piperazinylcarboxylic acid ethyl ester (14.06 g, 65.09 mmol), 10% sodium hydroxide aqueous solution (150 mL) and ethanol (150 mL) were placed in a 500 mL round bottom flask, heated for refluxing and stirred overnight. The reaction was cooled down to room temperature, distilled under a reduced pressure to remove the solvent to obtain a light yellow oily substance, which was added with 200 mL saturated saline, and the resulting mixture was extracted with dichloromethane (5×200 mL), dried (Na2SO4), filtered, concentrated to obtain a light yellow oily substance, 7.56 g, yield 80.7%, which was directly used in the next step of reaction.
Reaction SMILES: [Br:1][C:2]1[S:3][C:4]([Br:35])=[C:5]2[CH2:9][N:8]([CH2:10][C:11]3[N:12]=[CH:13][N:14](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[CH:15]=3)[CH2:7][C:6]=12.[ClH:36]>>[ClH:36].[ClH:36].[Br:1][C:2]1[S:3][C:4]([Br:35])=[C:5]2[CH2:9][N:8]([CH2:10][C:11]3[N:12]=[CH:13][NH:14][CH:15]=3)[CH2:7][C:6]=12
Reactant: Brc1sc(Br)c2c1CN(Cc1cn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cn1)C2
Agent: Cl
Product: Brc1sc(Br)c2c1CN(Cc1c[nH]cn1)C2

Procedure:
A suspension of 0.7 g (1.15 mmol) of 1,3-dibromo-5[(1-triphenylmethyl-1H-imidazol-4-yl) methyl]-5,6-dihydro-4H-thieno[3,4-c]pyrrole in 14 ml of 2M hydrochloric acid is heated at reflux for 1 hour. The precipitate formed is filtered and washed with water. The combined aqueous phases are washed with ethyl acetate and then evaporated to dryness to provide 0.45 g of a chestnut-brown solid which is crystallized from isopropanol. 0.082 g of a cream solid is obtained. Yield 17%. Melting point: 221° C. (with decomposition).
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[C:6]([CH3:11])[CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:12][N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16](=[O:23])[N:15]([C@H:24]([CH2:28][CH2:29][CH3:30])[C:25](O)=[O:26])[C:14]2=[O:31])=[CH:3]1.N.C1C=CC2N(O)N=[N:39]C=2C=1.C(Cl)CCl>C1COCC1.O1CCOCC1.O.CN(C=O)C>[CH3:1][N:2]1[C:10]2[C:5](=[C:6]([CH3:11])[CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:12][N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16](=[O:23])[N:15]([C@H:24]([CH2:28][CH2:29][CH3:30])[C:25]([NH2:39])=[O:26])[C:14]2=[O:31])=[CH:3]1
Reactant: CCC[C@H](C(=O)O)n1c(=O)c2ccccc2n(Cc2cn(C)c3cccc(C)c23)c1=O
Reactant: On1nnc2ccccc21
Agent: N
Solvent: ClCCCl
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CCC[C@H](C(N)=O)n1c(=O)c2ccccc2n(Cc2cn(C)c3cccc(C)c23)c1=O
Reaction time: 16 h

Procedure:
To the suspension of (R)-2-[1-(1,4-Dimethyl-1H-indol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-pentanoic acid (95 mg, 0.23 mmol), (prepared according to example 4) in THF (2.5 mL) at room temperature are added 0.5 M NH3 in 1,4-dioxane solution (0.91 mL, 0.45 mmol) and HOBt (15 mg, 0.11 mmol). Then EDC (87 mg, 0.45 mmol) is added in small portions. The reaction mixture is stirred for 16 hours and then DMF (1.0 mL) along with another 0.5 M NH3 (1.0 mL) in 1,4-dioxane solution and EDC (87 mg, 0.45 mmol) are added. The reaction is continued for another 60 hours. Then water (55 mL) is added and the mixture is extracted with EtOAc (3×30 mL). The organic layers are combined, dried over Na2SO4 and are concentrated to give crude product. Purification by flash column chromatography using 6% MeOH in DCM followed by washing using Methanol affords the title compound. LCMS (ESMS): m/z 419.77 (M+H+).
Reaction SMILES: O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][CH2:13][N:14]1[C:23]2[C:18](=[N:19][CH:20]=[C:21]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[CH:22]=2)[C:17]([OH:32])=[C:16]([C:33]([NH:35][CH2:36][CH2:37][OH:38])=[O:34])[C:15]1=[O:39].NN>CCO>[NH2:3][CH2:12][CH2:13][N:14]1[C:23]2[C:18](=[N:19][CH:20]=[C:21]([CH2:24][C:25]3[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=3)[CH:22]=2)[C:17]([OH:32])=[C:16]([C:33]([NH:35][CH2:36][CH2:37][OH:38])=[O:34])[C:15]1=[O:39]
Reactant: O=C(NCCO)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2n(CCN2C(=O)c3ccccc3C2=O)c1=O
Agent: NN
Solvent: CCO
Product: NCCn1c(=O)c(C(=O)NCCO)c(O)c2ncc(Cc3ccc(F)cc3)cc21
Temperature: 50 °C
Reaction time: 8 h

Procedure:
A solution of 1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-7-[(4-fluorophenyl)methyl]-4-hydroxy-N-(2-hydroxyethyl)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide (0.255 g, 0.48 mmol) in EtOH (80 mL) under nitrogen was treated with hydrazine (0.151 mL, 4.81 mmol) for 1 h@50° C. Additional hydrazine was added (0.075 mL @1 h) after 1 and 4 hours (0.15 mL @ 4 h) and the reaction was stirred for a total of 8 h@50° C. The reaction was then capped and cooled in a refrigerator overnight. The resulting suspension was filtered then thoroughly dried under high vacuum to provide the title compound as an off-white solid: 1H NMR (300 MHz, DMSO-D6) δ ppm 2.8 (m, 1 H), 3.4 (m, 2 H), 3.6 (m, 2 H), 4.1 (s, 2 H), 4.2 (m, 2 H), 4.9 (bs, 1 H), 7.1 (t, J=8.7 Hz, 2 H), 7.4 (m, 2 H), 8.1 (s, 1 H), 8.5 (s, 1 H), 10.5 (m, 1 H); ES+ MS: 401 (M+H+).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N:8]1[CH2:12][CH2:11][NH:10][C:9]1=[O:13].Br[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.N[C@@H]1CCCC[C@H]1N.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu](I)I.O1CCOCC1>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N:8]1[CH2:12][CH2:11][N:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]1=[O:13]
Reactant: Cc1ccncc1N1CCNC1=O
Reactant: Brc1ccccc1
Agent: I[Cu]I
Agent: N[C@@H]1CCCC[C@H]1N
Agent: O=P([O-])([O-])[O-]
Solvent: C1COCCO1
Product: Cc1ccncc1N1CCN(c2ccccc2)C1=O
Yield: 92.3 %

Procedure:
Using the same reaction conditions as in Example 14, 1-(4-methyl-pyridin-3-yl)-imidazolidin-2-one (I-14b: 100 mg, 0.5643 mmol) was reacted with bromo-benzene (89 mg, 0.5643 mmol), 1,4-dioxane (20 mL), copper iodide (10 mg), trans-1,2-diamino cyclohexane (20 mg) and potassium phosphate (359 mg, 1.693 mmol) to afford the crude product. Purification by column chromatography on silica gel (1.2-1.4% MeOH in CHCl3) afforded 132 mg of the product (92.30% yield).
Reaction SMILES: [NH:1]([C:14]([O:16][CH2:17][CH:18]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]2[C:19]1=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:15])[C@H:2]([C:4](ON1C(=O)CCC1=O)=[O:5])[CH3:3].[NH2:31][C@H:32]([C:52]([OH:54])=[O:53])[CH2:33][CH2:34][CH2:35][CH2:36][NH:37][S:38]([C:41]1[C:50]([CH3:51])=[C:48]([CH3:49])[C:45]([O:46][CH3:47])=[CH:44][C:42]=1[CH3:43])(=[O:40])=[O:39].C(=O)(O)[O-].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>COCCOC.O.O.COCCOC>[NH:1]([C:14]([O:16][CH2:17][CH:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:25]2[C:30]1=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:15])[C@H:2]([C:4]([NH:31][C@H:32]([C:52]([OH:54])=[O:53])[CH2:33][CH2:34][CH2:35][CH2:36][NH:37][S:38]([C:41]1[C:50]([CH3:51])=[C:48]([CH3:49])[C:45]([O:46][CH3:47])=[CH:44][C:42]=1[CH3:43])(=[O:40])=[O:39])=[O:5])[CH3:3]
Reactant: C[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)ON1C(=O)CCC1=O
Reactant: COc1cc(C)c(S(=O)(=O)NCCCC[C@H](N)C(=O)O)c(C)c1C
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: O=C([O-])O
Agent: [K+]
Solvent: O
Solvent: COCCOC
Product: COc1cc(C)c(S(=O)(=O)NCCCC[C@H](NC(=O)[C@H](C)NC(=O)OCC2c3ccccc3-c3ccccc32)C(=O)O)c(C)c1C

Procedure:
A solution of Fmoc-Ala-OSu 7c (15.31 mmol) in DME (100 mL) was added to a stirred solution of Lys(Mtr) 2 (6.4080 g, 1 equiv) and potassium bicarbonate (1.5331 mg, 1 equiv) in 2:1 water/DME (150 mL). After 16 h the DME was removed in vacuo and the resulting suspension was treated with citric acid (3.22 g, 1.1 equiv) in water (25 mL). The mixture was extracted with ethyl acetate. The organic phase was washed with water (2×) and brine, dried over sodium sulfate, and concentrated in vacuo, giving a yellow foam which was carried on without further purification. 1H-NMR (CDCl3/CD3OD) δ 1.25 (m, 2H), 1.32 (d, 3H), 1.57 (m, 3H), 1.73 (m, 1H), 2.41 (brt, 2H), 3.72 (s, 3H), 4.14 (m, 1H), 4.29 (m, 4H), 6.79 (d, 2H), 7.22 (m, 16H), 7.38 (d, 4H), 7.52 (m, 2H), 7.72 (d, 2H). MS (FAB) 712.2 (MH)+, 750.2 (M+K)+.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[NH:6][C:7]3[C:12]([C:13]=2[CH:14]=1)=[CH:11][C:10](Br)=[CH:9][CH:8]=3.[C:16]1(B(O)O)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C([O-])([O-])=O.[K+].[K+]>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.C1(C)C=CC=CC=1>[C:16]1([C:2]2[CH:3]=[CH:4][C:5]3[NH:6][C:7]4[C:12]([C:13]=3[CH:14]=2)=[CH:11][C:10]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:13][CH:14]=2)=[CH:9][CH:8]=4)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: OB(O)c1ccccc1
Reactant: Brc1ccc2[nH]c3ccc(Br)cc3c2c1
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: [K+]
Solvent: Cc1ccccc1
Product: c1ccc(-c2ccc3[nH]c4ccc(-c5ccccc5)cc4c3c2)cc1
Yield: 73 %

Procedure:
As depicted in Reaction 5, 15 g (46 mmol) of 3,6-dibromocarbazole, 14 g (92 mmol) of phenylboronic acid, K2CO3 (2 mol), Pd(PPh3)4 and toluene were refluxed for 10 hours. The reaction mixture was extracted with methylene chloride. The solvent was removed, and then the residue was purified by column chromatography (eluent:hexane) to give the title compound. Yield: 73%. MS (EI) (Calcd. for C24H17N, 319.14. Found: 319).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)C=[CH:11][C:10]=1CC(O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O[C:32]([NH:34][C@H:35]([C:40]([N:42]1[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]1)=[O:41])[CH2:36][C:37](=[O:39])[NH2:38])=O)(C)(C)C>>[CH2:16]([O:15][C:13]1[CH:14]=[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:10]=[CH:11][C:32]=1[NH:34][C@H:35]([C:40]([N:42]1[CH2:43][CH2:44][N:45]([CH3:48])[CH2:46][CH2:47]1)=[O:41])[CH2:36][C:37](=[O:39])[NH2:38])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: CN1CCN(C(=O)[C@H](CC(N)=O)NC(=O)OC(C)(C)C)CC1
Reactant: O=C(O)Cc1ccc(OCc2ccccc2)cc1OCc1ccccc1
Product: CN1CCN(C(=O)[C@H](CC(N)=O)Nc2ccc(OCc3ccccc3)cc2OCc2ccccc2)CC1
Yield: 88.6 %

Procedure:
Condensation of 2,4-dibenzyloxyphenylacetic acid (923 mg) and 1-(N-tert-butoxycarbonyl-L-asparaginyl)-4-methylpiperazine (1.0 g) was carried out in the same manner as in Example 12 (i) to obtain colorless crystalline powder 1-(2,4-dibenzyloxyphenyl-L-asparaginyl)-4-methylpiperazine (1.18 g). Melting point: 83°-85° C.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[Cl:7][C:8]1[C:9]2[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:10]=2[S:11][C:12]=1[CH:13]([O:19][CH3:20])[CH:14]([N+:16]([O-])=O)[CH3:15].O>C(OCC)C>[Cl:7][C:8]1[C:9]2[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:10]=2[S:11][C:12]=1[CH:13]([O:19][CH3:20])[CH:14]([NH2:16])[CH3:15]
Reactant: COC(c1sc2ccc(Cl)cc2c1Cl)C(C)[N+](=O)[O-]
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: CCOCC
Product: COC(c1sc2ccc(Cl)cc2c1Cl)C(C)N
Reaction time: 5 h

Procedure:
In a sulfonation flask 15 ml (0.015 mol) of an etheral 1 molar LiAlH4 solution is diluted with 40 ml of diethylether. A solution of 0.97 g (0.003 mol) 3,5-dichloro-2-(1-methoxy-2-nitropropyl)benzo[b]thiophene and 30 ml diethylether is added under stirring in such a manner that the internal temperature remains constant at 0-5° C. Then the mixture is warmed up to it and stirring continued for 5 h. Then the reaction mixture is cooled again and water added slowly. After quenching sodium sulphate is added. Filtration and distilling off the solvent in a water jet vacuum, the raw material is obtained. Purification is achieved by column chromatography (eluent: tert. butylmethylether/EtOH 3:1). Yield: 0.62 g (87% of theory) yellowish oil consisting of a diastereoisomeric mixture (ratio:ca. 2:1). 1H-NMR: 1.05/d/3H-DS1 (minor isomer), 1.13/d/3H, DS2 (major isomer), 3.2/m/1H-DS1, 3.35/s/6H-DS1+DS2, 3.39/m/1H-DS2, 4.45/d/1H-DS1, 4.52/d/1H-DS2, 7.38/m/2H-DS1+DS2, 7.72/d/2H-DS1+DS2, 7.8/2 s/DS1+DS2.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=O)[NH:12][N:11]=2)=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:23])=O.Cl.N>C(#N)C.O1CCOCC1.O>[Cl:23][C:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:10]([CH2:9][CH2:8][C:5]2[CH:6]=[N:7][C:2]([CH3:1])=[CH:3][CH:4]=2)=[N:11][N:12]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1ccc(CCc2n[nH]c(=O)c3ccccc23)cn1
Agent: Cl
Agent: N
Solvent: C1COCCO1
Solvent: O
Solvent: CC#N
Product: Cc1ccc(CCc2nnc(Cl)c3ccccc23)cn1
Temperature: 60 °C
Reaction time: 9 h

Procedure:
Under N2-atmosphere, 217 mg (0.818 mmol) 4-[2-(6-methylpyridin-3-yl)ethyl]phthalazin-1(2H)-one in 3.3 ml acetonitrile is mixed with 187 μl (2.04 mmol) phosphoryl chloride and 0.41 ml 4 N HCl in dioxane and stirred for 9 h at 60° C. After cooling to RT, 2.6 ml H2O, followed by a solution of 0.5 ml sat. NH3 and 5 ml H2O is added. Immediate extraction with 3 portions of EtOAc, washing of the organic layers with water and brine, drying (Na2SO4) and evaporation yield the title compound; FAB-MS (M+H)+=284.
Reaction SMILES: [CH:1]([C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([NH2:15])=[O:14])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)=[O:2].[CH2:18]([Mg]Br)[CH3:19]>C1COCC1.C(OCC)(=O)C>[OH:2][CH:1]([C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([NH2:15])=[O:14])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)[CH2:18][CH3:19]
Reactant: NC(=O)c1ccc(-c2ccc(C=O)nc2)cc1
Reactant: CC[Mg]Br
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCC(O)c1ccc(-c2ccc(C(N)=O)cc2)cn1
Reaction time: 3 h
Yield: 50.2 %

Procedure:
To a solution of 4-(6-formylpyridin-3-yl)benzamide (0.30 g, 1.32 mmol), in THF (30 mL) was added ethyl magnesium bromide (0.53 g, 3.97 mmol, 3M in diethyl ether) under nitrogen at 0° C. and the contents were stirred for 3 h at the same temperature. The contents were diluted with ethyl acetate (150 mL), quenched with ammonium chloride solution (100 mL), the organic layer washed with brine solution (2×100 mL), the layers separated, the organic layer dried over sodium sulphate and distilled off to get the crude product. The compound was purified by flash chromatography (100-200 micron; 60% ethyl acetate in hexane) to give 4-(6-(1-hydroxypropyl)pyridin-3-yl)benzamide (0.17 g, 51% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.83 (s, 1H), 8.10 (dd, 1H), 8.00 (s, 1H), 7.97 (d, 2H), 7.79 (d, 2H), 7.55 (d, 1H), 7.36 (s, 1H), 5.30 (d, 1H), 4.53 (q, 1H), 1.17 (m, 1H), 1.65 (m, 1H), 0.86 (t, 3H); LC-MS m/z calcd for [M+H]+ 257.31. found 257.4.