Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH2:2][C:3]#[C:4][C:5]1[CH:13]=[CH:12][C:11]([C:14]2[N:15]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:16]3[C:21]([CH:22]=2)=[CH:20][C:19]([CH2:23][N:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[CH:18][CH:17]=3)=[C:10]2[C:6]=1[CH2:7][NH:8][C:9]2=[O:37]>CO.[Pd]>[OH:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:13]=[CH:12][C:11]([C:14]2[N:15]([C:30]([O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:31])[C:16]3[C:21]([CH:22]=2)=[CH:20][C:19]([CH2:23][N:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[CH:18][CH:17]=3)=[C:10]2[C:6]=1[CH2:7][NH:8][C:9]2=[O:37]
Reactant: CC(C)(C)OC(=O)n1c(-c2ccc(C#CCO)c3c2C(=O)NC3)cc2cc(CN3CCCCC3)ccc21
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)n1c(-c2ccc(CCCO)c3c2C(=O)NC3)cc2cc(CN3CCCCC3)ccc21
Temperature: 25 °C
Reaction time: 2.7 h
Yield: 93.3 %

Procedure:
4-(3-Hydroxy-1-propynyl)-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (89.7 mg, 0.180 mmol) was dissolved in methanol (5.4 mL), and the solution was added with 10% Pd—C (16.8 mg), followed by stirring at room temperature for 2.7 hours under hydrogen atmosphere at normal pressure. The mixture was added with 10% Pd—C (8.9 mg), and further stirred for 2.5 hours. The reaction mixture was filtered using Celite. The solvent of filtrate was evaporated under reduced pressure to obtain 4-(3-hydroxypropyl)-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (84.6 mg, yield 93%).
Reaction SMILES: [C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:19])OC2C=CC=CC=2)[N:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:26][O:27][C:28]1[CH:29]=[C:30]2[C:35](=[CH:36][C:37]=1[O:38][CH3:39])[N:34]=[CH:33][N:32]=[C:31]2[O:40][C:41]1[C:42]([F:48])=[C:43]([CH:45]=[CH:46][CH:47]=1)[NH2:44]>C1COCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:44][C:43]2[CH:45]=[CH:46][CH:47]=[C:41]([O:40][C:31]3[C:30]4[C:35](=[CH:36][C:37]([O:38][CH3:39])=[C:28]([O:27][CH3:26])[CH:29]=4)[N:34]=[CH:33][N:32]=3)[C:42]=2[F:48])=[O:19])[N:7]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:6]=1)([CH3:3])([CH3:2])[CH3:4]
Reactant: CC(C)(C)c1cc(NC(=O)Oc2ccccc2)n(-c2ccccc2)n1
Reactant: COc1cc2ncnc(Oc3cccc(N)c3F)c2cc1OC
Solvent: C1CCOC1
Product: COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)nn4-c4ccccc4)c3F)c2cc1OC
Temperature: 25 °C
Reaction time: 15 h
Yield: 63.2 %

Procedure:
A mixture of phenyl 3-tert-butyl-1-phenyl-1H-pyrazol-5-ylcarbamate (prepared as described in Example 153A) (239 mg, 0.71 mmol), 3-(6,7-dimethoxyquinazolin-4-yloxy)-2-fluoroaniline (prepared as described in Example 265A steps 1 through 3) (150 mg, 0.475 mmol) and N,N-4-(dimethylamino)pyridine (10 mg, 0.082 mmol) in THF (5 mL) was stirred at rt for 15 h. The reaction mixture was concentrated under reduced pressure to give the crude product. Purification via silica gel flash chromatography (eluting with a gradient of 20% ethyl acetate in hexanes to 100% ethyl acetate) afforded 1-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)-2-fluorophenyl)urea (167 mg, 63%) as a colorless solid. 1H NMR (300 MHz, DMSO-d6) δ 9.07 (brs, 1H), 8.85 (brs, 1H), 8.57 (s, 1H), 8.07 (m, 1H), 7.39-7.58 (m, 7H), 7.23 (m, 1H), 7.20 (m, 1H), 6.42 (s, 1H), 4.00 (s, 3H), 3.99 (s, 3H), 1.29 (s, 9H); LC-MS (ESI) m/z 557 (M+H)+.
Reaction SMILES: Br[C:2]1[C:7](=[O:8])[N:6]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:17]([C:22]#[N:23])=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:12][CH:11]=2)[C:5]([CH2:24][CH2:25][CH3:26])=[N:4][C:3]=1[CH2:27][CH3:28].[CH2:29]([O:31][C:32]1[N:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)[CH3:30].C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>C(OCC)(=O)C.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].ClCCl>[CH2:29]([O:31][C:32]1[N:37]=[CH:36][C:35]([C:2]2[C:7](=[O:8])[N:6]([CH2:9][C:10]3[CH:15]=[CH:14][C:13]([C:16]4[C:17]([C:22]#[N:23])=[CH:18][CH:19]=[CH:20][CH:21]=4)=[CH:12][CH:11]=3)[C:5]([CH2:24][CH2:25][CH3:26])=[N:4][C:3]=2[CH2:27][CH3:28])=[CH:34][CH:33]=1)[CH3:30]
Reactant: CCCc1nc(CC)c(Br)c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: CCOc1ccc(B(O)O)cn1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: C1COCCO1
Product: CCCc1nc(CC)c(-c2ccc(OCC)nc2)c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 100 °C
Reaction time: 12 h
Yield: 98.5 %

Procedure:
A mixture of 4′-[(5-bromo-4-ethyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl]biphenyl-2-carbonitrile (0.5 g), (6-ethoxypyridin-3-yl)boronic acid (0.23 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.05 g), 2 M aqueous cesium carbonate solution (5 mL) and 1,4-dioxane (5 mL) was stirred at 100° C. for 12 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a colorless amorphous solid (0.54 g, 98%).
Reaction SMILES: [C:1]([C:5](=[CH:10][NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19])[C:6]([O:8]C)=O)(=[O:4])[CH2:2][CH3:3]>C1(OC2C=CC=CC=2)C=CC=CC=1>[C:1]([C:5]1[C:6](=[O:8])[C:17]2[C:12](=[C:13]([O:18][CH3:19])[CH:14]=[CH:15][CH:16]=2)[NH:11][CH:10]=1)(=[O:4])[CH2:2][CH3:3]
Reactant: CCC(=O)C(=CNc1ccccc1OC)C(=O)OC
Solvent: c1ccc(Oc2ccccc2)cc1
Product: CCC(=O)c1c[nH]c2c(OC)cccc2c1=O
Yield: 53.1 %

Procedure:
Methyl 2-propanoyl-3-(2-methoxyphenylamino)acrylate (77.7 g, 0.29 mol) was added to boiling diphenyl ether (500 ml) then heated at reflux for 1 hour. The solution was partially cooled and poured into high-boiling petroleum ether, then the solid filtered off and washed with 40-60 petroleum ether to give 3-propanoyl-8-methoxy-4(1H)-quinolone (35.6 g, 52%), m.p. 260°-263°
Reaction SMILES: [C:1]([C:3]1[C:8]2[N:9]=[N:10][N:11]([CH3:12])[C:7]=2[CH:6]=[C:5]([C:13]2[CH:14]=[C:15]([C:35]([F:38])([F:37])[F:36])[C:16]([O:19][CH2:20][CH2:21][CH:22]3[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]3)=[N:17][CH:18]=2)[N:4]=1)#[N:2].[F:39][C:40]([F:45])([F:44])[C:41]([OH:43])=[O:42]>ClCCl.C(#N)C>[F:39][C:40]([F:45])([F:44])[C:41]([OH:43])=[O:42].[CH3:12][N:11]1[C:7]2[CH:6]=[C:5]([C:13]3[CH:18]=[N:17][C:16]([O:19][CH2:20][CH2:21][CH:22]4[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)=[C:15]([C:35]([F:36])([F:37])[F:38])[CH:14]=3)[N:4]=[C:3]([C:1]#[N:2])[C:8]=2[N:9]=[N:10]1
Reactant: Cn1nnc2c(C#N)nc(-c3cnc(OCCC4CCN(C(=O)OC(C)(C)C)CC4)c(C(F)(F)F)c3)cc21
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CC#N
Product: Cn1nnc2c(C#N)nc(-c3cnc(OCCC4CCNCC4)c(C(F)(F)F)c3)cc21
Temperature: 20 °C
Reaction time: 1 h
Yield: 78 %

Procedure:
To a solution of tert-butyl 4-(2-(5-(4-cyano-1-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-6-yl)-3-(trifluoromethyl)pyridin-2-yloxy)ethyl)piperidine-1-carboxylate (1.15 g) in dichloromethane (10 ml) and acetonitrile (5 ml), trifluoroacetic acid (2 ml) was added and the mixture stirred at 20° C. for 1 h then solvent evaporated under reduced pressure. The resulting residue was dissolved in ethyl acetate (10 ml) and diethyl ether added dropwise until the mixture turned cloudy. The solution was allowed to stand for two hours. The desired product was collected by filtration and washed with ether, dried in vacuum oven to give 920 mg 1-methyl-6-(6-(2-(piperidin-4-yl)ethoxy)-5-(trifluoromethyl)pyridin-3-yl)-1H-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrile trifluoroacetate (78%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]3[C:16]=2[CH2:17][C:18]2[NH:22][C:21]([C:23]3C=CC=CN=3)=[N:20][N:19]=2)=[CH:4][CH:3]=1.ClC1C=CC(C2N=C3C=CC=CN3C=2CC(NN)=O)=CC=1.Cl.C(=N)(N)C>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]3[C:16]=2[CH2:17][C:18]2[NH:22][C:21]([CH3:23])=[N:20][N:19]=2)=[CH:6][CH:7]=1
Reactant: Clc1ccc(-c2nc3ccccn3c2Cc2nnc(-c3ccccn3)[nH]2)cc1
Agent: CC(=N)N
Agent: Cl
Agent: NNC(=O)Cc1c(-c2ccc(Cl)cc2)nc2ccccn12
Product: Cc1nnc(Cc2c(-c3ccc(Cl)cc3)nc3ccccn23)[nH]1

Procedure:
The title compound was prepared according to the experimental described for compound 230 from 2-(2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)acetohydrazide and acetimidamide hydrochloride. M/e− 324 for C17H15ClN5 (M+H)+; 1H-NMR (400 MHz, CD3OD) δ 8.27 (d, J=6.6 Hz, 1H), 7.76 (d, J=8.4 Hz, 2H), 7.58 (d, J=9.1 Hz, 1H), 7.46 (d, J=8.4 Hz, 2H), 7.35 (t, J=6.9 Hz, 1H), 6.95 (t, J=6.2 Hz, 1H), 4.46 (s, 2H), 2.37 (s, 3H) ppm.
Reaction SMILES: C[O:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][C:13]([NH:15][CH:16]1[CH2:21][CH2:20][N:19](CC2C=CC=CC=2)[CH2:18][CH2:17]1)=O)=O.[H][H]>CO.[Pd]>[NH:19]1[CH2:20][CH2:21][CH:16]([N:15]2[CH2:13][CH2:12][C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=3[NH:5][C:3]2=[O:2])[CH2:17][CH2:18]1
Reactant: COC(=O)Nc1ccccc1CC(=O)NC1CCN(Cc2ccccc2)CC1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: O=C1Nc2ccccc2CCN1C1CCNCC1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
10.00 kg (29.81 mol, 1.0 eq) 3-[1-(phenylmethyl)-4-piperidinyl]-2,3,4,5-tetrahydro-1,3-benzodiazepin-2(1H)-one from Example 3 are dissolved in 100 L methanol, combined with 1.00 kg 10% Pd/C and hydrogenated in the pressurised reactor at 70° C. and 3 bar. After the hydrogen uptake has ended the catalyst is filtered off and washed with 30 L methanol. The filtrate is concentrated in vacuo and the residue is suspended in 100 L acetone. Then the mixture is refluxed, the suspension is stirred for 15 minutes at reflux temperature and half the acetone is distilled off at normal pressure. After the distillation has ended the mixture is cooled to 0° C. and stirred for a further hour. The product is suction filtered, washed with 20 L acetone and dried at 50° C.
Reaction SMILES: C(OC(=O)[NH:10][C@H:11]([CH2:23][C:24]([NH:26][CH2:27][C@@H:28]([NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:29][CH2:30][CH2:31][NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[O:25])[CH2:12][CH2:13][CH2:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])C1C=CC=CC=1>[Pd].C(O)C>[C:19]([O:18][C:16](=[O:17])[NH:15][CH2:14][CH2:13][CH2:12][C@H:11]([NH2:10])[CH2:23][C:24]([NH:26][CH2:27][C@@H:28]([NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:29][CH2:30][CH2:31][NH:32][C:33]([O:35][C:36]([CH3:37])([CH3:38])[CH3:39])=[O:34])=[O:25])([CH3:20])([CH3:21])[CH3:22]
Reactant: CC(C)(C)OC(=O)NCCC[C@@H](CC(=O)NC[C@H](CCCNC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)NC(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CCO
Product: CC(C)(C)OC(=O)NCCC[C@H](N)CC(=O)NC[C@H](CCCNC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C
Reaction time: 12 h

Procedure:
22 mg of palladium on activated carbon (10%) are added to a mixture of 0.146 g (0.22 mmol) of the compound from Example 234A in 10 ml of ethanol, and the mixture is then hydrogenated under atmospheric pressure for 12 h. The reaction mixture is filtered through kieselguhr, and the filtrate is concentrated in vacuo and dried under high vacuum. The crude product is reacted without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[N:6]=[C:5]([O:11][C:12]2[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:13]=2[C:14]([O:16]C)=[O:15])[N:4]=1.[OH-].[Na+].O>C(O)C>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[N:6]=[C:5]([O:11][C:12]2[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:13]=2[C:14]([OH:16])=[O:15])[N:4]=1
Reactant: COC(=O)c1ccc([N+](=O)[O-])cc1Oc1nc(OC)cc(OC)n1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: COc1cc(OC)nc(Oc2cc([N+](=O)[O-])ccc2C(=O)O)n1
Yield: 78.3 %

Procedure:
To a suspension in ethanol (20 ml) of methyl 2-(4,6-dimethoxypyrimidin-2-yl)oxy-4-nitrobenzoate (2.4 g), an equimolar amount of an aqueous sodium hydroxide solution (20 ml) was added, and the mixture was reacted at room temperature for 12 hours under stirring. The reaction mixture was poured into water, and extracted with ethyl ether, and non-reacted starting materials were removed. Then, the aqueous phase was acidified with a 10% hydrochloric acid aqueous solution. This was extracted with ethyl ether. The extract was washed with water and dried, and then the solvent was distilled off under reduced pressure to obtain 1.8 g of a yellow crystal. This crystal was further washed with a mixture of hexane and isopropyl ether to obtain the above identified compound as a yellow crystal (1.7 g). (Melting point: 93°-96° C.).
Reaction SMILES: O=C1C(=[C:11]([C:14]#[N:15])[C:12]#[N:13])C2C(=CC=C(S(N3CCCC3COC3C=CC=CC=3)(=O)=O)C=2)N1.[OH:32][C:33]1[CH:66]=[CH:65][C:36]([CH2:37][N:38]2[C:46]3[C:41](=[CH:42][C:43]([S:47]([N:50]4[CH2:54][CH2:53][CH2:52][CH:51]4[CH2:55][O:56][C:57]4[CH:58]=[N:59][CH:60]=[CH:61][CH:62]=4)(=[O:49])=[O:48])=[CH:44][CH:45]=3)[C:40](=O)[C:39]2=[O:64])=[CH:35][CH:34]=1>>[OH:32][C:33]1[CH:34]=[CH:35][C:36]([CH2:37][N:38]2[C:46]3[C:41](=[CH:42][C:43]([S:47]([N:50]4[CH2:54][CH2:53][CH2:52][CH:51]4[CH2:55][O:56][C:57]4[CH:58]=[N:59][CH:60]=[CH:61][CH:62]=4)(=[O:49])=[O:48])=[CH:44][CH:45]=3)[C:40](=[C:11]([C:14]#[N:15])[C:12]#[N:13])[C:39]2=[O:64])=[CH:65][CH:66]=1
Reactant: N#CC(C#N)=C1C(=O)Nc2ccc(S(=O)(=O)N3CCCC3COc3ccccc3)cc21
Reactant: O=C1C(=O)N(Cc2ccc(O)cc2)c2ccc(S(=O)(=O)N3CCCC3COc3cccnc3)cc21
Product: N#CC(C#N)=C1C(=O)N(Cc2ccc(O)cc2)c2ccc(S(=O)(=O)N3CCCC3COc3cccnc3)cc21
Yield: 85 %

Procedure:
2-{1-(4-Hydroxy-benzyl)-2-oxo-5-[2-(pyridine-3-yloxymethyl)-pyrrolidine-1-sulfonyl]-1,2-dihydro-indol-3-yl-idene}-malononitrile (30b) was prepared according to the same procedure for compound 26 except using 28b, to afford 46 mg (85%) of 30b as a purple solid, mp 203.3° C. (decomp). 1H NMR (300 MHz, DMSO) δ 9.50 (s, 1H), 8.31 (s, 1H), 8.25 (d, J=2.7 Hz, 1H), 8.17 (dd, J=4.5 Hz, J=1.5 Hz, 1H), 8.10 (d, J=8.1 Hz, 1H), 7.34 (m, 3H), 7.24 (d, J=8.4 Hz, 2H), 6.76 (d, J=8.7 Hz, 2H), 4.88 (s, 2H), 4.16 (m, 1H), 4.08 (m, 1H), 3.96 (m, 1H), 3.41 (m, 1H), 3.18 (m, 1H), 1.91 (m, 2H), 1.71 (m, 2H).
Reaction SMILES: [O:1]=[C:2]1[C:10](=[C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]([CH2:20][CH2:21]OS(C)(=O)=O)[O:12]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1.[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>O1CCOCC1>[N:27]1([CH2:21][CH2:20][CH:13]2[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:11](=[C:10]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[NH:3][C:2]3=[O:1])[O:12]2)[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1
Reactant: C1COCCN1
Reactant: CS(=O)(=O)OCCC1OC(=C2C(=O)Nc3ccccc32)c2ccccc21
Solvent: C1COCCO1
Product: O=C1Nc2ccccc2C1=C1OC(CCN2CCOCC2)c2ccccc21
Reaction time: 18 h
Yield: 75.6 %

Procedure:
A solution of methanesulfonic acid 2-[3-(2-oxo-1,2-dihydro-indol-3-ylidene)-1,3-dihydro-isobenzofuran-1-yl]-ethyl ester (50 mg, 0.135 mmol) and morpholine (118 μl, 1.35 mmol) in dioxane (0.8 ml) was heated at 70° C. for 40 minutes and then at 60° C. for 18 hours. The reaction was partitioned between EtOAc and water. The EtOAc layer was washed with water, brine, dried with anhydrous Na2SO4 and rotary evaporated to give a yellow film. The yellow film was chromatographed (CHCl3 to 2% MeOH/CHCl3 gradient) to give 3-[3-(2-morpholin-4-yl-ethyl)-3H-isobenzofuran-1-ylidene]-1,3-dihydro-indol-2-one as a yellow solid (37 mg, 76%).
Reaction SMILES: [CH2:1]([C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].[Cl:19][C:20]1[CH:21]=[CH:22][C:23]2[N:29](Cl)[C:28]3[CH:31]=[CH:32][CH:33]=[CH:34][C:27]=3[CH:26]=[N:25][C:24]=2[CH:35]=1>>[Cl:19][C:20]1[CH:21]=[CH:22][C:23]2[NH:29][C:28]3[CH:31]=[CH:32][CH:33]=[CH:34][C:27]=3[C:26]([C:13]3[CH:12]=[CH:11][C:10]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9])=[CH:15][CH:14]=3)=[N:25][C:24]=2[CH:35]=1
Reactant: Clc1ccc2c(c1)N=Cc1ccccc1N2Cl
Reactant: CCCCCCCCCc1ccc(B(O)O)cc1
Product: CCCCCCCCCc1ccc(C2=Nc3cc(Cl)ccc3Nc3ccccc32)cc1
Yield: 58 %

Procedure:
4-Nonylphenylboronic acid (30 mg, 0.12 mmol) and 8,5-dichloro-5H-dibenzo[b,e][1,4]diazepine (160FE64) (26 mg, 0.1 mmol) were reacted according GP11 to give 25 mg of the title compound (160FE63). MS (ESI) 431 (MH+). Purity for MH+ (UV/MS) 85/85.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([O:14][CH3:15])[CH:9]=2)[N:5]=[C:4]([O:16][CH3:17])[N:3]=1.Cl.[N+:19]([C:22]1[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][NH2:30])=[CH:24][CH:23]=1)([O-:21])=[O:20].C(N(C(C)C)CC)(C)C>CCO>[CH3:17][O:16][C:4]1[N:3]=[C:2]([NH:30][CH2:29][CH2:28][C:25]2[CH:24]=[CH:23][C:22]([N+:19]([O-:21])=[O:20])=[CH:27][CH:26]=2)[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([O:14][CH3:15])[CH:9]=2)[N:5]=1
Reactant: COc1cccc(-c2cc(Cl)nc(OC)n2)c1
Reactant: NCCc1ccc([N+](=O)[O-])cc1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CCO
Product: COc1cccc(-c2cc(NCCc3ccc([N+](=O)[O-])cc3)nc(OC)n2)c1
Temperature: 170 °C
Yield: 50.9 %

Procedure:
To a solution of 4-chloro-2-methoxy-6-(3-methoxy-phenyl)-pyrimidine [80 mg, 0.32 mmol, Intermediate (53)] and 2-(4-nitro-phenyl)-ethylamine hydrochloride (77.6 mg, 0.38 mmol) in EtOH (1.1 mL) is added diisopropyl-ethylamine (0.139 mL, 0.80 mmol). The reaction mixture is heated under microwave at 170° C. for 45 minutes. Solvent is removed and residue is subjected to flash column chromatography (silica gel: 10-50% ethyl acetate/heptane) to afford [2-methoxy-6-(3-methoxy-phenyl)-pyrimidin-4-yl]-[2-(4-nitro-phenyl)-ethyl]-amine [62 mg, 51%, Example 43(b)] as a solid. LC/MS: RT=2.57 minute, MS: 381 (M+H). 1H NMR (300 MHz, (CD3)2SO): □8.14 (2H, d, J=9.8 Hz), 7.53 (2H, d, J=9.8 Hz), 7.52 (3H, m), 7.38 (1H, t, J=8.6 Hz), 7.01 (1H, m), 6.58 (1H, s), 3.84 (3H, s), 3.79 (3H, s), 3.6 (2H, m), 2.99 (2H, m). IC50=0.9 nM
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[CH2:13][OH:14].[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][NH:26][C:25](=O)[CH:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][N:26]=[C:25]([O:14][CH2:13][C:3]2[C:4]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)=[N:5][O:6][C:2]=2[CH3:1])[CH:24]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: Cc1onc(-c2ccccc2)c1CO
Reactant: O=c1cc(OCc2ccccc2)cc[nH]1
Product: Cc1onc(-c2ccccc2)c1COc1cc(OCc2ccccc2)ccn1
Yield: 28 %

Procedure:
As described for example 4, (5-methyl-3-phenyl-isoxazol-4-yl)-methanol (95 mg, 0.50 mmol) was converted using 4-benzyloxy-2(1H)-pyridone instead of 2-hydroxy-5-trifluoromethylpyridine to the title compound (SiO2, heptane:ethyl acetate=95:5 to 0:100, 52 mg, 28%) which was obtained as a colourless oil. MS: m/e=373.1 [M+H]+.
Reaction SMILES: [C:1]([NH:3][C:4](=[N:12][C:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[C:15]([O:23][CH3:24])[CH:14]=1)OC1C=CC=CC=1)#[N:2].[CH:25]1([NH2:30])[CH2:29][CH2:28][CH2:27][CH2:26]1.C(N(CC)CC)C>C(#N)C>[C:1]([NH:3][C:4]([NH:30][CH:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)=[N:12][C:13]1[CH:18]=[C:17]([C:19]([F:20])([F:21])[F:22])[CH:16]=[C:15]([O:23][CH3:24])[CH:14]=1)#[N:2]
Reactant: NC1CCCC1
Reactant: COc1cc(N=C(NC#N)Oc2ccccc2)cc(C(F)(F)F)c1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: COc1cc(N=C(NC#N)NC2CCCC2)cc(C(F)(F)F)c1
Temperature: 75 °C
Reaction time: 19 h
Yield: 64.8 %

Procedure:
To a solution of N-Cyano-N'-(3-methoxy-5-trifluoromethyl-phenyl)-O-phenylisourea (0.52 mmol, 175 mg) in dry acetonitrile (1 ml), cyclopentylamine (1.04 mmol, 0.113 ml) and triethylamine (0.080 ml) were added. The mixture was stirred for 19 h at 75° C. under nitrogen. After concentration the residue was dissolved in dichloromethane, washed with 1 N aqueous HCl (2×), water, dried (Na2SO4) and concentrated. The residue was purified by flash chromatography (ethyl acetate/heptane 1:2) to give a syrup. Crystallisation from ethyl acetate/heptane 1:4 gave grey crystals (110 mg, 65%). Mp 101-102° C.; 1H-NMR (CDCl3): δ 1.40 (m, 2H), 1.65 (m, 4H), 2.02 (m, 2H), 4.13 (sextet, 1H), 5.05 (br, 1H), 6.96 (s, 1H), 7.00 (s, 1H), 7.03 (s, 1H), 8.15 ppm (br, 1H); EI SP/MS: 326 (M+).
Reaction SMILES: [CH2:1]1[CH2:23][O:22][C:3]2([CH2:8][CH2:7][C:6](O)([C:9]3[CH:14]=[C:13]([F:15])[C:12]([C:16]([F:19])([F:18])[F:17])=[C:11]([F:20])[CH:10]=3)[CH2:5][CH2:4]2)[O:2]1.CC1C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C=CC=CC=1>[CH2:23]1[CH2:1][O:2][C:3]2([CH2:8][CH2:7][C:6]([C:9]3[CH:14]=[C:13]([F:15])[C:12]([C:16]([F:17])([F:18])[F:19])=[C:11]([F:20])[CH:10]=3)=[CH:5][CH2:4]2)[O:22]1
Reactant: OC1(c2cc(F)c(C(F)(F)F)c(F)c2)CCC2(CC1)OCCO2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: Fc1cc(C2=CCC3(CC2)OCCO3)cc(F)c1C(F)(F)F
Yield: 79.4 %

Procedure:
1,1-Ethylenedioxy-4-hydroxy-4-(3',5'-difluoro-4'-trifluoromethylphenyl)cyclohexane (23 g) was dissolved in toluene (200 ml), followed by adding p-toluenesulfonic acidmonohydrate (5 g) to the solution, stirring the mixture under reflux for one hour, allowing the mixture to cool down, washing the reaction solution with water (200 ml), drying the organic layer over anhydrous MgSO4, and distilling off the solvent, to obtain 1,1-ethylenedioxy-4-(3',5'-difluoro-4'-trifluoromethylphenyl)-3-cyclohexene (17.3 g).
Reaction SMILES: [OH:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([CH2:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[C:15]([C:19]([OH:21])=O)=[CH:14][CH:13]=[CH:12]3)[CH:3]=1.[F:22][C:23]([F:32])([F:31])[C:24]1[CH:25]=[C:26]([CH:28]=[CH:29][CH:30]=1)[NH2:27]>C(Cl)Cl.CO>[F:22][C:23]([F:31])([F:32])[C:24]1[CH:25]=[C:26]([NH:27][C:19]([C:15]2[C:16]3[C:11](=[CH:10][C:9]([CH2:8][C:4]4[CH:3]=[C:2]([OH:1])[N:7]=[CH:6][N:5]=4)=[CH:18][CH:17]=3)[CH:12]=[CH:13][CH:14]=2)=[O:21])[CH:28]=[CH:29][CH:30]=1
Reactant: O=C(O)c1cccc2cc(Cc3cc(O)ncn3)ccc12
Reactant: Nc1cccc(C(F)(F)F)c1
Solvent: ClCCl
Solvent: CO
Product: O=C(Nc1cccc(C(F)(F)F)c1)c1cccc2cc(Cc3cc(O)ncn3)ccc12

Procedure:
Prepared from 6-(6-hydroxy-pyrimidin-4-ylmethyl)-naphthalene-1-carboxylic acid (Step 3.8) and 3-trifluoromethyl-aniline analogously to Ex. 3: MS: [M+1]+=424; TLC (CH2Cl2/MeOH 9:1): Rf=0.26.
Reaction SMILES: [N:1]([CH2:4][CH2:5][CH2:6][C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:16])[CH:14]=2)[N:9]([S:17]([C:20]2[N:27]3[C:23]([S:24][CH:25]=[CH:26]3)=[N:22][C:21]=2[Cl:28])(=[O:19])=[O:18])[CH:8]=1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>C1COCC1>[Cl:28][C:21]1[N:22]=[C:23]2[N:27]([C:20]=1[S:17]([N:9]1[C:10]3[C:15](=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)[C:7]([CH2:6][CH2:5][CH2:4][NH2:1])=[CH:8]1)(=[O:18])=[O:19])[CH:26]=[CH:25][S:24]2
Reactant: [N-]=[N+]=NCCCc1cn(S(=O)(=O)c2c(Cl)nc3sccn23)c2ccc(F)cc12
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: NCCCc1cn(S(=O)(=O)c2c(Cl)nc3sccn23)c2ccc(F)cc12
Yield: 78 %

Procedure:
A mixture of 3-(3-azidopropyl)-1-[(6-chloroimidazo-[2,1-b][1,3]thiazol-5-yl)sulfonyl]-5-fluoro-1H-indole (180 mg, 0.41 mmol) and triphenylphosphine (161 mg, 0.62 mmol in THF and water is stirred under nitrogen for 24 h at room temperature and concentrated in vacuo. The resultant residue is purified by flash chromatography (silica gel, EtOAc/2M NH3 in MeOH: 98/2) to afford the title product as an off-white solid, 132 mg (78% yield), mp 139–141° C., identified by NMR and mass spectral analyses.