Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[O:6][CH:5]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH2:15])[CH:10]=2)[CH2:4][O:3]1.C(O)C.Cl[CH:21]([CH:27]=O)[C:22]([O:24][CH2:25][CH3:26])=[O:23].C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[CH3:1][C:2]1([CH3:16])[O:6][CH:5]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][N:12]3[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:27][N:15]=[C:11]3[CH:10]=2)[CH2:4][O:3]1
Reactant: CCOC(=O)C(Cl)C=O
Reactant: CC1(C)OCC(COc2ccnc(N)c2)O1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCO
Product: CCOC(=O)c1cnc2cc(OCC3COC(C)(C)O3)ccn12
Temperature: 60 °C

Procedure:
4-((2,2-Dimethyl-1,3-dioxolan-4-yl)methoxy)pyridin-2-amine (5.6 g, 0.025 mol) was mixed with ethanol (60 mL) in a reaction flask, under an atmosphere of dry nitrogen. A solution of ethyl 2-chloro-3-oxopropanoate (5% in benzene; 93 mL; Commercial solution from Toronto Research Chemicals Inc.) was added. The mixture was heated to 60° C. under nitrogen for 2 hours. After allowing the mixture to cool the solvent was removed under vacuum to give a brown solid. The solid was mixed with ethyl acetate (200 mL) and sodium bicarbonate solution (100 mL) and stirred to dissolve. The phases were separated and the bicarbonate solution was extracted further with ethyl acetate (50 mL). The combined ethyl acetate extracts were dried over sodium sulfate, filtered and concentrated under vacuum to give a solid. The crude material was dissolved in ethyl acetate and passed through a short column of silica, eluting with ethyl acetate. Fractions containing the product were concentrated to give ethyl 7-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)imidazo[1,2-a]pyridine-3-carboxylate as a pale yellow solid (5.76 g).
Reaction SMILES: [C:1]([SiH2:5][O:6][C:7]([CH3:28])([CH3:27])[C:8]1[CH:9]=[C:10]([C:14]2[N:22]3[C:17]([CH:18]=[N:19][C:20](S(C)(=O)=O)=[N:21]3)=[CH:16][CH:15]=2)[CH:11]=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].[OH-:29].[Na+].O.Cl>O1CCOCC1>[C:1]([SiH2:5][O:6][C:7]([CH3:28])([CH3:27])[C:8]1[CH:9]=[C:10]([C:14]2[N:22]3[C:17]([CH:18]=[N:19][C:20]([OH:29])=[N:21]3)=[CH:16][CH:15]=2)[CH:11]=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: [OH-]
Reactant: CC(C)(C)[SiH2]OC(C)(C)c1cccc(-c2ccc3cnc(S(C)(=O)=O)nn23)c1
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: CC(C)(C)[SiH2]OC(C)(C)c1cccc(-c2ccc3cnc(O)nn23)c1
Temperature: 80 °C
Yield: 37 %

Procedure:
7-[3-(tert-Butyl-dimethyl-silanyloxymethyl)-phenyl]-2-methanesulfonyl-pyrrolo[2,1-f][1,2,4]triazine (800 mg, 1.92 mmol) was dissolved in 1,4-dioxane (5.00 mL) and 5.00 M sodium hydroxide in water (5.00 mL, 25.0 mmol) was added. The reaction was heated at 80° C. for 2 hours and then acidified to pH 6 with conc. HCl. The product was then extracted with DCM (100 mL) and the organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by silica gel chromatography using a gradient of 0-100% EtOAc/hex as the eluting solvent to obtain 7-[3-(tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol as a yellow solid (252 mg, 37%). m.p.=194-195° C.; LCMS (m/e) 356 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.48 (s, 1H), 8.27 (d, 1H, J=7.7 Hz), 8.07 (s, 1H), 7.52-7.44 (m, 1H), 7.40 (d, 1H, J=7.6 Hz), 7.17 (d, 1H, J=5.1 Hz), 7.05 (d, 1H, J=5.1 Hz), 4.84 (s, 2H), 0.97 (s, 9H), 0.13 (s, 6H).
Reaction SMILES: F[C:2]1C=C(F)C=C[C:3]=1[O:4][C:5]1[N:10]2[N:11]=[C:12]([CH3:14])[CH:13]=[C:9]2[N:8]=[C:7]([CH3:15])[C:6]=1[C:16]1[C:17]2[CH:26]=[CH:25][N:24](S(C3C=CC(C)=CC=3)(=O)=O)[C:18]=2[C:19](=[O:23])[N:20]([CH3:22])[CH:21]=1.[OH-].[Na+].O>C(O)C>[CH2:3]([O:4][C:5]1[N:10]2[N:11]=[C:12]([CH3:14])[CH:13]=[C:9]2[N:8]=[C:7]([CH3:15])[C:6]=1[C:16]1[C:17]2[CH:26]=[CH:25][NH:24][C:18]=2[C:19](=[O:23])[N:20]([CH3:22])[CH:21]=1)[CH3:2]
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c(-c4c(C)nc5cc(C)nn5c4Oc4ccc(F)cc4F)cn(C)c(=O)c32)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCOc1c(-c2cn(C)c(=O)c3[nH]ccc23)c(C)nc2cc(C)nn12
Temperature: 55 °C
Reaction time: 0.5 h
Yield: 35.1 %

Procedure:
A suspension of 4-[7-(2,4-difluorophenoxy)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl]-6-methyl-1-[(4-methylphenyl)sulfonyl]-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (29.1 mg, 50.6 μmol) in ethanol (1.0 mL) was treated with a 3.0 M solution of sodium hydroxide in water (0.254 mL, 0.762 mmol), then warmed to 55° C. and stirred at that temperature for 30 min. The reaction mixture was purified via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (6 mg, 14%). 1H NMR (300 MHz, DMSO-d6) δ 12.15 (br s, 1H), 7.28 (d, J=2.8 Hz, 1H), 7.24 (s, 1H), 6.39 (s, 1H), 6.03 (d, J=2.7 Hz, 1H), 4.45 (q, J=7.0 Hz, 2H), 3.55 (s, 3H), 2.42 (s, 3H), 2.24 (s, 3H), 1.07 (t, J=7.1 Hz, 3H); LCMS calculated for C18H20N5O2 (M+H)+: m/z=338.2. found: 338.1.
Reaction SMILES: [O:1]=[C:2]1[NH:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[CH2:5][CH2:4][N:3]1[CH2:13][C@H:14]1[CH2:19][CH2:18][C@H:17]([C:20]([OH:22])=O)[CH2:16][CH2:15]1.C1N=CN(C(N2C=NC=C2)=O)C=1.[N:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1>C(Cl)Cl>[N:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[N:41]1[CH2:42][CH2:43][N:44]([C:20]([C@H:17]2[CH2:18][CH2:19][C@H:14]([CH2:13][N:3]3[CH2:4][CH2:5][C:6]4[CH:12]=[CH:11][CH:10]=[CH:9][C:7]=4[NH:8][C:2]3=[O:1])[CH2:15][CH2:16]2)=[O:22])[CH2:45][CH2:46]1
Reactant: O=C1Nc2ccccc2CCN1C[C@H]1CC[C@H](C(=O)O)CC1
Reactant: c1ccc(N2CCNCC2)nc1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Product: O=C1Nc2ccccc2CCN1C[C@H]1CC[C@H](C(=O)N2CCN(c3ccccn3)CC2)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a suspension of trans-4-(2-oxo-1,2,4,5-tetrahydro-benzo[d][1,3]diazepin-3-ylmethyl)-cyclohexanecarboxylic acid (52 mg, 0.17 mmol) in dry DCM (2 mL) was added CDI (50 mg, 0.31 mmol). The resulting mixture was stirred at room temperature for 2 h, then 1-Pyridin-2-yl-piperazine (44 μL, 0.56 mmol) was added. The reaction mixture was stirred at room temperature for 1.5 h. Then solvent was removed under reduced pressure and crude was purified by crystallization from acetonitrile.
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[N:19]1([C:22]([C:24]2[C:32]3[CH:31]=[CH:30][C:29]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH2:28][C:27]=3[N:26](COCC[Si](C)(C)C)[N:25]=2)=[O:23])[CH2:21][CH2:20]1.O>O1CCCC1>[N:19]1([C:22]([C:24]2[C:32]3[CH:31]=[CH:30][C:29]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)([C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)[CH2:28][C:27]=3[NH:26][N:25]=2)=[O:23])[CH2:21][CH2:20]1
Reactant: C[Si](C)(C)CCOCn1nc(C(=O)N2CC2)c2c1CC(c1ccccc1)(c1ccccc1)C=C2
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(c1n[nH]c2c1C=CC(c1ccccc1)(c1ccccc1)C2)N1CC1
Temperature: 0 °C
Reaction time: 48 h
Yield: 470.3 %

Procedure:
6 cm3 of a commercial 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran are added to a solution of 0.235 g of aziridin-1-yl(6,6-diphenyl-1-(2-trimethylsilanylethoxymethyl)-6,7-dihydro-1H-indazol-3-yl)methanone in 2.5 cm3 of tetrahydrofuran cooled to a temperature in the region of 0° C. After stirring for about 48 hours at a temperature in the region of 20° C., the mixture is poured into 30 cm3 of an ice plus water mixture and extracted with three times 50 cm3 of diethyl ether. The combined organic phases are washed with three times 25 cm3 of water and 25 cm3 of saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (13 kPa). After flash chromatography on a column of silica [eluent: dichloromethane/methanol (90/10 by volume)], 0.80 g of aziridin-1-yl(6,6-diphenyl-6,7-dihydro-1H-indazol-3-yl)methanone is thus obtained in the form of a solid, the characteristics of which are as follows:
Reaction SMILES: [CH2:1]([N:5]1[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][NH:13][C:14]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]([CH2:25][CH2:26][CH3:27])[N:17]=2)=O)[CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:37])=CC=1>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl>[CH2:1]([N:5]1[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][NH:13][C:14]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]([CH2:25][CH2:26][CH3:27])[N:17]=2)=[S:37])[CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CCCCN1CCN(CCNC(=O)c2nn(CCC)c3ccccc23)CC1
Solvent: Cc1ccccc1
Solvent: ClC(Cl)Cl
Product: CCCCN1CCN(CCNC(=S)c2nn(CCC)c3ccccc23)CC1
Temperature: 25 °C
Yield: 88.5 %

Procedure:
To a solution of N-[2-(4-n-butyl-1-piperazinyl)-ethyl]-1-n-propylindazole-3-carboxamide (0.39 g) obtained in Example 3 in toluene (10 ml) was added Lawesson reagent (0.64 g) at room temperature, and the mixture was heated under reflux for one hour. The reaction solution was cooled to room temperature, diluted with chloroform (50 ml), and then washed with saturated aqueous sodium hydrogencarbonate (50 ml). The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by thin-layer chromatography on silica gel (chloroform:methanol:aqueous ammonia=8:2:0.2) to give the title compound (0.36 g) as a pale yellow oily substance. Yield=88%.
Reaction SMILES: C[N:2]([CH3:13])[C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[C:5]=1[CH3:11].[OH:14][CH:15]1[CH2:19][CH2:18][N:17]([CH2:20][CH2:21]C#N)[CH2:16]1>>[OH:14][CH:15]1[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][C:13]2[NH:2][C:3](=[O:12])[C:4]3[C:5]([CH:11]=2)=[C:6]([CH3:10])[CH:7]=[CH:8][CH:9]=3)[CH2:16]1
Reactant: Cc1cccc(C(=O)N(C)C)c1C
Reactant: N#CCCN1CCC(O)C1
Product: Cc1cccc2c(=O)[nH]c(CCN3CCC(O)C3)cc12
Yield: 5.4 %

Procedure:
By the reaction in the same manner as in Example 1a, using N,N-dimethyl-2,3-dimethylbenzamide (4.10 g) and 3-(3-hydroxypyrrolidin-1-yl)propionitrile (1.5 g), 3-[2-(3-hydroxypyrrolidin-1-yl)ethyl]-5-methyl-2H-isoquinolin-1-one (157.5 mg) was obtained.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH3:11][N:12]([CH3:23])[CH2:13][CH2:14][NH:15][S:16]([CH2:19][CH2:20][CH2:21][CH3:22])(=[O:18])=[O:17].[H-].[Na+]>>[CH3:11][N:12]([CH3:23])[CH2:13][CH2:14][N:15]([C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1)[S:16]([CH2:19][CH2:20][CH2:21][CH3:22])(=[O:18])=[O:17]
Reactant: CCCCS(=O)(=O)NCCN(C)C
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Product: CCCCS(=O)(=O)N(CCN(C)C)c1ccc([N+](=O)[O-])cc1

Procedure:
Prepared from 1-fluoro-4nitro-benzene, N-(2-dimethylamino-ethyl)-butanesulphonamide and sodium hydride as base
Reaction SMILES: Cl.[CH3:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[C:13]1[CH:18]=[C:17]([N:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[N:16]=[C:15]([NH2:26])[N:14]=1)[CH2:9][NH:8][CH2:7][CH2:6]2.[CH:27]1([N:33]=[C:34]=[O:35])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[NH2:26][C:15]1[N:14]=[C:13]([C:12]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][N:8]([C:34]([NH:33][CH:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)=[O:35])[CH2:9]3)=[CH:4][C:3]=2[CH3:2])[CH:18]=[C:17]([N:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)[N:16]=1
Reactant: O=C=NC1CCCCC1
Reactant: Cc1cc2c(cc1-c1cc(N3CCN(C)CC3)nc(N)n1)CNCC2
Agent: Cl
Product: Cc1cc2c(cc1-c1cc(N3CCN(C)CC3)nc(N)n1)CN(C(=O)NC1CCCCC1)CC2

Procedure:
This compound was prepared by using procedures analogous to those described for the synthesis of Example 77, Step 6 starting from 4-(6-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine HCl salt, and cyclohexylisocyanate. Analytic LCMS (M+H)+: m/z=464.2.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[N:12]=[C:11]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[CH:10]=2)=[CH:5][CH:4]=1.[N:27]([C:38]([C:45]#[N:46])([CH3:44])[CH2:39][CH2:40][C:41]([OH:43])=[O:42])=[N:28][C:29]([C:36]#[N:37])([CH3:35])[CH2:30][CH2:31][C:32]([OH:34])=[O:33].C([O-])([O-])=O.[Cs+].[Cs+].O>CC(C)=O>[N:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[C:11]1[CH:10]=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([CH2:2][O:42][C:41](=[O:43])[CH2:40][CH2:39][C:38]([N:27]=[N:28][C:29]([C:36]#[N:37])([CH3:35])[CH2:30][CH2:31][C:32]([O:34][CH2:2][C:3]3[CH:4]=[CH:5][C:6]([C:9]4[CH:10]=[C:11]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=5)[N:12]=[C:13]([C:15]5[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=5)[CH:14]=4)=[CH:7][CH:8]=3)=[O:33])([C:45]#[N:46])[CH3:44])=[CH:4][CH:5]=2)[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[N:12]=1
Reactant: BrCc1ccc(-c2cc(-c3ccccn3)nc(-c3ccccn3)c2)cc1
Reactant: CC(C#N)(CCC(=O)O)N=NC(C)(C#N)CCC(=O)O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(C)=O
Solvent: O
Product: CC(C#N)(CCC(=O)OCc1ccc(-c2cc(-c3ccccn3)nc(-c3ccccn3)c2)cc1)N=NC(C)(C#N)CCC(=O)OCc1ccc(-c2cc(-c3ccccn3)nc(-c3ccccn3)c2)cc1
Temperature: 25 °C
Reaction time: 120 h
Yield: 46.3 %

Procedure:
A reaction mixture of 4′-(4-bromomethylphenyl)-2,2′:6′,2″-terpyridine (1.500 g, 3.729 mmol), 4,4′-azobis(4-cyanopentanoic acid) (500 mg, 1.7839 mmol), Cs2CO3 (750 mg, 2.302 mmol), 1.0 ml of water and 100 ml of acetone was stirred vigorously at room temperature for 5 days. The solvents were removed under vacuum, and CH2Cl2 was added. The precipitate was filtered off. The filtrate was evaporated to dryness under vacuum, and then 300 ml of CH2Cl2-hexane mixture solvents (1:12, v/v) was added. The precipitate was filtered, and dried, and further purified by column chromatography (Al2O3) using ethyl acetate-hexane (3:2, v/v) as eluent to give pure product (0.763 g, 46%). 1H-NMR (CDCl3): δ=8.64 (m, 12H), 7.85 (m, 8H), 7.47 (m, 4H), 7.30 (m, 4H), 5.20 (s, 4H, —CH2—O—C(O)—), 2.65-2.48(m,8H, —OOC—CH2CH2—), 1.69(m, 6H, =N—C(CN)—CH3). HRMS (TOF): calculated for C56H47N10O4[(M+H)+] m/z=923.3782, found m/z=923.3759 Fluorescent Spectral Properties: λex=320 nm, λem=380 nm.
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][C:12]([C:14]([F:17])([F:16])[F:15])=[CH:13][C:8]=2[NH:7][C:6]1=[O:18].S(Cl)([Cl:21])=O>ClC(Cl)Cl>[Cl:21][CH2:2][CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][C:12]([C:14]([F:17])([F:16])[F:15])=[CH:13][C:8]=2[NH:7][C:6]1=[O:18]
Reactant: O=S(Cl)Cl
Reactant: O=c1[nH]c2cc(C(F)(F)F)ccc2n1CCCO
Solvent: ClC(Cl)Cl
Product: O=c1[nH]c2cc(C(F)(F)F)ccc2n1CCCCl
Reaction time: 1 h
Yield: 56 %

Procedure:
To a stirred mixture of 23 parts of 1,3-dihydro-1-(3-hydroxypropyl)-5-(trifluoromethyl)-2H-benzimidazol-2-one in 150 parts of trichloromethane are added dropwise 32 parts of sulfinyl chloride. Upon completion, the whole is heated to reflux and stirring is continued for 1 hour at reflux temperature. After cooling, the reaction mixture is evaporated and the residue is crystallized from 2,2'-oxybispropane, yielding 14 parts (56%) of 1-(3-chloropropyl)-1,3-dihydro-5-(trifluoromethyl)-2H-benzimidazol-2-one.
Reaction SMILES: [NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[CH:3][C:2]1=[O:11].[Br:12]Br>S(=O)(=O)(O)O.C(Cl)(Cl)(Cl)Cl.S([O-])([O-])(=O)=O.[Ag+2]>[Br:12][C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[NH:1][C:2](=[O:11])[CH:3]=[N:4]2
Reactant: BrBr
Reactant: O=c1cnc2ccccc2[nH]1
Agent: [Ag+2]
Agent: O=S(=O)(O)O
Agent: O=S(=O)([O-])[O-]
Solvent: ClC(Cl)(Cl)Cl
Product: O=c1cnc2cc(Br)ccc2[nH]1
Temperature: 50 °C
Reaction time: 24 h
Yield: 40 %

Procedure:
The quinoxalin-2(1H)-one (14.6 g, 0.1 mol, Aldrich, cat. no. 260517) and silver sulphate (15.6 g, 0.05 mol) were dissolved in conc. Sulfuric acid (100 ml) at 20° C. Bromine (5.2 ml, 0.1 mol) was added and the reaction mixture was stirred vigorously for 24 hours. The reaction mass was then diluted with carbon tetrachloride (100 mL), and this was heated at 50° C. The reaction mass was then filtered and the filtrate was poured into ice cold water and stirred for 30 minutes to obtain a precipitate. The precipitate was filtered and the solid material was dried in vacuo to afford the title product (9.0 g, 40%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([F:16])[CH:10]=2)[N:5]=[C:4]([C:17]([O:19][CH3:20])=[O:18])[CH:3]=1.[I:21](O)(=O)(=O)=O.II>CO.ClCCl>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([F:16])[CH:10]=2)[N:5]=[C:4]([C:17]([O:19][CH3:20])=[O:18])[C:3]=1[I:21]
Reactant: COC(=O)c1cc(N)c(F)c(-c2ccc(Cl)c(F)c2)n1
Reactant: [O-][I+3]([O-])([O-])O
Agent: II
Solvent: ClCCl
Solvent: CO
Product: COC(=O)c1nc(-c2ccc(Cl)c(F)c2)c(F)c(N)c1I
Yield: 236.6 %

Procedure:
Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoropicolinate (3.1 g, 10.38 mmol) was dissolved in methanol (40 mL). Periodic acid (0.946 g, 4.15 mmol) and iodine (2.371 g, 9.34 mmol) were added. The reaction mixture was heated at reflux overnight. The cooled reaction mixture was diluted with dichloromethane and washed with 1N sodium sulfite. The organic phase was washed with 1N sodium sulfite, washed with saturated sodium chloride, dried over magnesium sulfate, fitered, and concentrated onto celite. The product was purified by flash chromatography (SiO2, 100% dichloromethane) to provide the title compound 4.17 g, 9.82 mmol, 95% yield) as a pink solid: 1H NMR (400 MHz, DMSO-d6) d 3.88 (s, 3H), 6.80 (s, 2H), 7.65-7.77 (m, 2H), 7.77-7.84 (m, 1H); 19F NMR (376 MHz, DMSO-d6) d −140.15 , −115.85. ESIMS m/z 426 ([M+H]+).
Reaction SMILES: FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:20][CH2:19][N:18]([C:21]2[N:26]=[CH:25][CH:24]=[CH:23][N:22]=2)[CH2:17][CH:16]1[CH3:27])=O)(C)(C)C>ClCCl>[CH3:27][CH:16]1[NH:15][CH2:20][CH2:19][N:18]([C:21]2[N:22]=[CH:23][CH:24]=[CH:25][N:26]=2)[CH2:17]1
Reactant: CC1CN(c2ncccn2)CCN1C(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC1CN(c2ncccn2)CCN1
Temperature: 25 °C
Reaction time: 24 h
Yield: 97.6 %

Procedure:
5 mL trifluoro acetic acid was added to 240 mg of 2-methyl-4-pyrimidin-2-yl-piperazine-1-carboxylic acid tert-butyl ester in 10 mL dichlormethane. The mixture was stirred for 24 h at RT. The solvent of the mixture was evaporated and the residue was dissolved in dichlormethane and extracted with 10% aqueous potassium hydrogencarbonate. The organic layer was evaporated to yield 150 mg of the desired product. Rt: 0.50 min (method B), (M+H)+: 179
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-])=O)=[CH:5][CH:4]=1.O>C(OCC)(=O)C>[NH2:9][C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1
Reactant: COc1ccc([N+](=O)[O-])cc1
Solvent: CCOC(C)=O
Solvent: O
Product: COc1ccc(N)cc1
Reaction time: 0.5 h
Yield: 78 %

Procedure:
76.6 mg (0.50 mmol) of 1-methoxy-4-nitrobenzene (10), 270 μL (15 mmol) of distilled water and stainless steel balls (50 pieces) were placed in the vessel of the planetary ball mill, which was then closed, and agitated by operating the planetary ball mill for 12 hours at 800 rpm (reversed every 30 minutes). After the lapse of 12 hours, 10 mL of ethyl acetate was added to the vessel of the ball mill to provide a solution containing the reaction mixture, which was then filtered with celite. The operation was repeated 5 times to provide a filtrate, which was then concentrated, thereby providing 48.2 mg (0.39 mmol) of 4-amino-1-methoxybenzene (11). The yield was 78%. The reaction is expressed by the following scheme.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]2[C:6](=[O:9])[CH2:7][O:8][C:4]=2[CH:3]=1.[CH3:12][C:13]1[NH:14][C:15]2[C:20]([C:21]=1[CH:22]=O)=[CH:19][CH:18]=[CH:17][CH:16]=2.Cl>C(O)C>[OH:1][C:2]1[CH:11]=[CH:10][C:5]2[C:6](=[O:9])/[C:7](=[CH:22]/[C:21]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[NH:14][C:13]=3[CH3:12])/[O:8][C:4]=2[CH:3]=1
Reactant: Cc1[nH]c2ccccc2c1C=O
Reactant: O=C1COc2cc(O)ccc21
Agent: Cl
Solvent: CCO
Product: Cc1[nH]c2ccccc2c1/C=C1\Oc2cc(O)ccc2C1=O
Temperature: 75 °C
Reaction time: 2 h
Yield: 114.4 %

Procedure:
A solution of 6-hydroxybenzofuran-3(2H)-one (0.50 g, 3.3 mmol) and 2-methyl-1H-indole-3-carboxaldehyde (0.58 g, 3.6 mmol) in ethanol (10 mL) was added with concentrated hydrochloric acid (1.0 mL), and the mixture was stirred at 75° C. for 2 hours. The reaction mixture was cooled to room temperature, and then the solid was collected by filtration, and washed with methanol to obtain (Z)-6-hydroxy-2-[(2-methyl-1H-indol-3-yl)methylene]benzofuran-3(2H)-one (1.1 g, 95%).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:7][O:8][C:9]1[CH:19]=[CH:18][C:12]([CH:13]=[CH:14][C:15](Cl)=[O:16])=[CH:11][CH:10]=1>C1C=CC=CC=1>[CH3:7][O:8][C:9]1[CH:19]=[CH:18][C:12]([CH:13]=[CH:14][C:15]([N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:16])=[CH:11][CH:10]=1
Reactant: C1CCNCC1
Reactant: COc1ccc(C=CC(=O)Cl)cc1
Solvent: c1ccccc1
Product: COc1ccc(C=CC(=O)N2CCCCC2)cc1

Procedure:
In a conical flask, 1.96 g of the paramethoxycinnamoyl chloride are dissolved in 20 ml of benzene. 2 ml of piperidine are added. After evaporation to dryness in vacuo, the residue is taken up in N hydrochloric acid and extracted with chloroform. The chloroform solution is washed successively with a 10% aqueous solution of KHCO3 and with water. It is then collected, dried over magnesium sulfate and evaporated. The product obtained is precipitated in cyclohexane and filtered off. After recrystallization from a 95° ethanol/water mixture (1/3:2/3), 2.15 g of white crystals are isolated (yield=78%).
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.Br[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26].C(=O)([O-])[O-].[K+].[K+]>CN(C)P(N(C)C)(N(C)C)=O.O>[CH2:26]([NH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH3:11]
Reactant: N#Cc1ccc(N)cc1
Reactant: CCCCCCCCCCCCCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: CCCCCCCCCCCCCCCCNc1ccc(C#N)cc1

Procedure:
A sample of p-aminobenzonitrile is treated at 135° for 15 hours with equimolar quantities of 1-bromohexadecane and anhydrous potassium carbonate in hexamethylphosphoramide. Upon cooling the mixture is diluted with water and extracted with ether. Evaporation of the ether extracts and recrystallization of the residue yields p-(hexadecylamino)benzonitrile.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH:10][C:11]2[C:20]3[C:15](=[N:16][CH:17]=[CH:18][N:19]=3)[N:14]=[CH:13][N:12]=2)=[CH:4][CH:3]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][N:23]=1.C([O-])(O)=O.[Na+]>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.COCCOC>[F:21][C:22]1[N:23]=[CH:24][C:25]([C:2]2[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH:10][C:11]3[C:20]4[C:15](=[N:16][CH:17]=[CH:18][N:19]=4)[N:14]=[CH:13][N:12]=3)=[CH:4][CH:3]=2)=[CH:26][CH:27]=1
Reactant: Brc1ccc(CCNc2ncnc3nccnc23)cc1
Reactant: OB(O)c1ccc(F)nc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: COCCOC
Product: Fc1ccc(-c2ccc(CCNc3ncnc4nccnc34)cc2)cn1
Yield: 9.5 %

Procedure:
To a round bottom flask was added [2-(4-bromophenyl)-ethyl]-pteridin-4-yl-amine (200 mg, 0.61 mmol), 2-fluoro-5-pyridineboronic acid (102 mg, 0.73 mmol), NaHCO3 (102 mg, 1.21 mmol), PdCl2(PPh3)2 (213 mg) and 50% aqueous ethylene glycol dimethyl ether (DME; 3.0 mL). The reaction was heated to reflux for 4.5 h, after which the reaction was cooled and the resulting orange precipitate filtered. The filtered material was washed with EtOAc and the filtrate washed with H2O. The organic fractions were pooled and concentrated in vacuo. The residue (229 mg) was purified by preparative RP-HPLC to afford {2-[4-(6-fluoropyridin-3-yl)-phenyl]-ethyl}-pteridin-4-yl-amine (20 mg) as an orange solid: mp 184-186° C.; EIMS m/z 346 ([M]+).