Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:11])=[CH:4][C:5]([OH:10])=[C:6]([CH:9]=1)[CH:7]=O.C([O-])([O-])=O.[K+].[K+].[F:18][C:19]([F:28])([F:27])/[CH:20]=[CH:21]/[C:22]([O:24][CH2:25][CH3:26])=[O:23].C([O-])(=O)/C=C/C.Cl>CN(C=O)C>[Cl:1][C:2]1[CH:9]=[C:6]2[C:5](=[CH:4][C:3]=1[F:11])[O:10][CH:20]([C:19]([F:18])([F:28])[F:27])[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:7]2
Reactant: O=Cc1cc(Cl)c(F)cc1O
Reactant: CCOC(=O)/C=C/C(F)(F)F
Agent: C/C=C/C(=O)[O-]
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Product: CCOC(=O)C1=Cc2cc(Cl)c(F)cc2OC1C(F)(F)F
Temperature: 70 °C
Reaction time: 2 h
Yield: 58.8 %

Procedure:
To the aldehyde (17.46 g, 100 mmole) from Step 1 in DMF (25 mL) was added K2CO3 (15.2 g, 110 mmole). The mixture was stirred, heated to 70° C. and treated with ethyl trifluorocrotonate (22.4 mL, 150 mmole). After 2 h, the mixture was heated to 95° C. After a total of 4 h, an additional 16 mL of crotonate was added and the mixture allowed to stir for 4 h at 95° C. and an additional 12 h at r.t. The reaction was complete by LCMS. This mixture was treated with 300 mL of 1N HCl and extracted 4× with CH2Cl2. The combined extracts were filtered through silica (4.5×6 cm) and the silica plug washed with additional CH2Cl2. The extracts were concd, the crude solid triturated with cold methanol, the solid collected and air dried to afford 19.1 g of a tan solid. The mother liquors were concd, dissolved in CH2Cl2 and filtered through a new silica plug following the same approach as above to give a second crop of 4.1 g of solid. The mother liquors were diluted with H2O and the solid collected to give a third crop of 3.16 g of solid. Total yield was 26.36 g (81.2%). The first and second crop were >95% by 1H NMR. The third crop was >90% pure: 1HNMR (CDCl3) 1.35 (t, 3H, J=7.1 Hz), 4.33 (m, 2H), 5.71 (q, 1H, J=6.7 Hz), 6.82 (d, 1H, J=9.4 Hz), 7.28 (d, 1H, 7.9 Hz), 7.63 (s, 1H). 19FNMR (CDCl3) −78.9 (d, 3F, J=6.7 Hz), −106.7 (t, 1F, J=8.7 Hz). 13CNMR (CDC13) 14.2, 61.7, 70.9 (q, C2, J=33.3 Hz), 105.5 (d, C8,J=25.5 Hz), 114.9 (d, J=18.7 Hz), 116.4, 117.1, 123.1 (q,CF3,J=287.2 Hz), 130.4 (d, J=1.5 Hz), 134.9 (d, J=1.9 Hz), 152.9 (d, J=11.4 Hz), 160.1 (d, C7, J=255.2 Hz), 163.4 (C═O)
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)[CH:12]=[CH:11][C:10]=1[N+:26]([O-])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[Ca+2].[Cl-].O>[Fe].C(O)C>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)[CH:12]=[CH:11][C:10]=1[NH2:26])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CS(=O)(=O)c1ccc(Oc2ccc([N+](=O)[O-])c(OCc3ccccc3)c2)cc1
Agent: [Fe]
Agent: [Ca+2]
Agent: [Cl-]
Solvent: CCO
Solvent: O
Product: CS(=O)(=O)c1ccc(Oc2ccc(N)c(OCc3ccccc3)c2)cc1
Temperature: 80 °C
Reaction time: 2 h
Yield: 91.4 %

Procedure:
A mixture of 2-(benzyloxy)-4-[4-(methylsulfonyl)phenoxy]-1-nitrobenzene (11.0 g), iron powder (7.6 g), calcium chloride (0.3 g), water (30 mL), and ethanol (120 mL) was stirred at 80° C. for 2 hr. The reaction solution was filtered through celite, and the filtrate was concentrated. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The obtained crude product was crystallized from toluene and the obtained crystals were washed with diethyl ether to give the title compound (9.3 g, yield 92%) as pale-brown crystals.
Reaction SMILES: NC1N=C(OCCCC)N=C2C=1N=C(OC)N2CCCC1CCCCN1C(OCC1C=CC=CC=1)=O.FC(F)(F)C(O)=O.[CH3:44][C@H:45]([O:49][C:50]1[N:58]=[C:57]2[C:53]([N:54]=[C:55]([O:59][CH3:60])[NH:56]2)=[C:52]([NH2:61])[N:51]=1)[CH2:46][CH2:47][CH3:48].Br[CH2:63][CH2:64][CH2:65][CH:66]1[CH2:71][CH2:70][CH2:69][N:68]([C:72]([O:74][CH2:75][C:76]2[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=2)=[O:73])[CH2:67]1>>[NH2:61][C:52]1[N:51]=[C:50]([O:49][C@@H:45]([CH3:44])[CH2:46][CH2:47][CH3:48])[N:58]=[C:57]2[C:53]=1[N:54]=[C:55]([O:59][CH3:60])[N:56]2[CH2:63][CH2:64][CH2:65][CH:66]1[CH2:71][CH2:70][CH2:69][N:68]([C:72]([O:74][CH2:75][C:76]2[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=2)=[O:73])[CH2:67]1
Reactant: CCC[C@H](C)Oc1nc(N)c2nc(OC)[nH]c2n1
Reactant: O=C(OCc1ccccc1)N1CCCC(CCCBr)C1
Agent: CCCCOc1nc(N)c2nc(OC)n(CCCC3CCCCN3C(=O)OCc3ccccc3)c2n1
Solvent: O=C(O)C(F)(F)F
Product: CCC[C@H](C)Oc1nc(N)c2nc(OC)n(CCCC3CCCN(C(=O)OCc4ccccc4)C3)c2n1

Procedure:
Prepared similarly to Intermediate 31 from 2-{[(1S)-1-methylbutyl]oxy}-8-(methyloxy)-9H-purin-6-amine trifluoroacetate salt and phenylmethyl 3-(3-bromopropyl)-1-piperidinecarboxylate.
Reaction SMILES: Cl[O-].[Na+].[CH3:4][O:5][C:6]1[C:7]([CH:20]=[N:21][OH:22])=[CH:8][C:9]2[C:10]([CH3:19])([CH3:18])[CH2:11][CH2:12][C:13]([CH3:17])([CH3:16])[C:14]=2[CH:15]=1>>[C:20]([C:7]1[CH:8]=[CH:9][C:14]([C:13]2[O:22][N:21]=[C:20]([C:7]3[C:6]([O:5][CH3:4])=[CH:15][C:14]4[C:13]([CH3:16])([CH3:17])[CH2:12][CH2:11][C:10]([CH3:18])([CH3:19])[C:9]=4[CH:8]=3)[CH:12]=2)=[CH:15][CH:6]=1)#[N:21]
Reactant: COc1cc2c(cc1C=NO)C(C)(C)CCC2(C)C
Agent: [Na+]
Agent: [O-]Cl
Product: COc1cc2c(cc1-c1cc(-c3ccc(C#N)cc3)on1)C(C)(C)CCC2(C)C
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 147.1 %

Procedure:
17.2 g of a 10% strength aqueous sodium hypochlorite solution were added dropwise at 10°-15° C. to a solution of 5.0 g (19 millimoles) of 5,6,7,8-tetrahydro-3-methoxy-5,5,8,8-tetramethyl-2-naphthaldoxime and 2.4 g (19 millimoles) of 4-ethnylbenzonitrile. The mixture was stirred for 1.5 hours at room temperature. Thereafter, the reaction mixture was poured onto water, the phases were separated and the aqueous phase was extracted again with methylene chloride. The combined organic extracts were washed with sodium bisulfite solution, dried over sodium sulfate and evaporated down. The residue was digested in hot methanol, the mixture was allowed to cool and the crystals were filtered off under suction and dried to give 5.4 g of the title compound of melting point 202°-203° C.
Reaction SMILES: Br[C:2]1[C:3]([N:20]2[CH2:25][CH2:24][N:23]([CH2:26][C:27]([NH:29][C:30]3[S:31][CH:32]=[CH:33][N:34]=3)=[O:28])[CH2:22][CH2:21]2)=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([N:17]([CH3:19])[CH3:18])=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1.[CH3:35][N:36](C=O)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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.[Fe+2].[C-]#N.[C-]#N.[Zn+2]>[C:35]([C:2]1[C:3]([N:20]2[CH2:25][CH2:24][N:23]([CH2:26][C:27]([NH:29][C:30]3[S:31][CH:32]=[CH:33][N:34]=3)=[O:28])[CH2:22][CH2:21]2)=[C:4]2[N:10]=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([N:17]([CH3:19])[CH3:18])=[CH:15][CH:16]=3)[NH:8][C:5]2=[N:6][CH:7]=1)#[N:36]
Reactant: CN(C)c1ccc(-c2nc3c(N4CCN(CC(=O)Nc5nccs5)CC4)c(Br)cnc3[nH]2)cc1
Reactant: CN(C)C=O
Agent: [Fe+2]
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Product: CN(C)c1ccc(-c2nc3c(N4CCN(CC(=O)Nc5nccs5)CC4)c(C#N)cnc3[nH]2)cc1
Temperature: 180 °C

Procedure:
A solution of 2-(4-(6-bromo-2-(4-(dimethylamino)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide (75 mg, 0.14 mmol) in degassed DMF (1 mL) containing Pd2 dba3 (0.05 eq, 0.0069 mmol, 6 mg), dppf (0.1 eq, 0.014 mmol, 8 mg) and Zn(CN)2 (1.5 eq, 0.21 mmol, 24 mg) was stirred with microwave heating at 180° C. for 30 minutes. After this time, further Pd2(dba)3 (6 mg), dppf (8 mg) and Zn(CN)2 (24 mg) were added and the mixture stirred under the same conditions for a further 30 minutes. hplc then showed partial conversion to the desired compound. Concentration in vacuo and purification of a small sample by semi-preparative hplc gave the pure product as a colourless solid; 1H-NMR (500 MHz, DMSO-d6) 2.80 (t, br, J=4.7 Hz, 4H, piperazine N(CH2)2), 3.00 (s, 6H, N(CH3)2), 3.42 (s, 2H, NCH2CO), 4.11 (s, br, 4H, piperazine N(CH2)2), 6.82 (d, J=9.0 Hz, 2H, N,N-dimethylaminophenyl), 7.24 (d, J=3.5 Hz, 1H, thiazole H-4 or H-5), 7.50 (d, J=3.5 Hz, 1H, thiazole H-4 or H-5), 7.99 (d, J=9.0 Hz, 2H, N,N-dimethylaminophenyl), 8.23 (s, 1H, imidazo[4,5-b]pyridine H-5), 11.91 (br s, 1H, CONH), 13.46 (br s, 1H, imidazo[4,5-b]pyridine NH);
Reaction SMILES: [C:1]([NH:4][CH2:5][CH2:6][CH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([NH:17][C:18](=O)[CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:14]=2[OH:16])[CH2:9][CH2:8]1)(=[O:3])[CH3:2].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C1(C)C(C)=CC=CC=1>[CH2:19]([C:18]1[O:16][C:14]2[C:15]3[CH:7]([CH2:6][CH2:5][NH:4][C:1](=[O:3])[CH3:2])[CH2:8][CH2:9][C:10]=3[CH:11]=[CH:12][C:13]=2[N:17]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: CC(=O)NCCC1CCc2ccc(NC(=O)Cc3ccccc3)c(O)c21
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: Cc1ccccc1C
Product: CC(=O)NCCC1CCc2ccc3nc(Cc4ccccc4)oc3c21
Yield: 28 %

Procedure:
N-{3-[2-(Acetylamino)ethyl]-4-hydroxy-2,3-dihydro-1H-inden-5-yl}-2-phenylacetamide (29.0 mg, 0.0823 mmol) and pyridinium p-toluenesulfonate (4.1 mg, 0.0164 mmol) were heated under reflux in xylene (2 mL) for 2.5 hr. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane=30/70→60/40) to give the title compound (7.7 mg, yield 28%).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[C:11]([CH2:26][CH3:27])=[N:12][CH:13]=[CH:14][C:15]=2[C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[C:18]([Cl:25])[CH:17]=2)=[CH:4][CH:3]=1.[CH3:28][N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.O.C(#N)C>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[C:11]([CH2:26][CH3:27])=[N:12][CH:13]=[CH:14][C:15]=2[C:16]2[CH:24]=[CH:23][C:19]([C:20]([N:32]3[CH2:33][CH2:34][N:29]([CH3:28])[CH2:30][CH2:31]3)=[O:21])=[C:18]([Cl:25])[CH:17]=2)=[CH:4][CH:3]=1
Reactant: CN1CCNCC1
Reactant: CCc1nccc(-c2ccc(C(=O)O)c(Cl)c2)c1C#Cc1ccc(N)nc1
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: ClCCCl
Product: CCc1nccc(-c2ccc(C(=O)N3CCN(C)CC3)c(Cl)c2)c1C#Cc1ccc(N)nc1

Procedure:
The title compound is synthesized according to general procedure GP5 starting from 100 mg (0.27 mmol) 4-[3-(6-Amino-pyridin-3-ylethynyl)-2-ethyl-pyridin-4-yl]-2-chloro-benzoic acid (A-40) using 40 mg (0.40 mmoL) N-methyl piperazine, 102 mg (0.53 mmol) EDC, 72 mg (0.53 mmol) HOBt and 68 mg (0.53 mmol) DIPEA in 1.2 mL DMF. After completion of the reaction, the reaction mixture is filtered and the product is isolated from the obtained solution by RP-HPLC using a H2O/ACN-gradient. Yield: 66 mg (54%).
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([C:9]#[C:10][Si](C)(C)C)[CH:3]=1.CO.CCOCC.C([O-])([O-])=O.[K+].[K+]>O>[C:9]([C:4]1[CH:3]=[C:2]([CH3:1])[CH:8]=[CH:7][C:5]=1[NH2:6])#[CH:10]
Reactant: Cc1ccc(N)c(C#C[Si](C)(C)C)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CO
Solvent: CCOCC
Product: C#Cc1cc(C)ccc1N
Reaction time: 1 h

Procedure:
To a stirred solution of 22 (11.32 g, 55.6 mmol) in 2:1 MeOH/Et2O (250 mL) was added K2CO3 (15.38 g, 111 mmol) at room temperature. After stirring for 1 h at this temperature, the reaction mixture was diluted with water and extracted with CH2Cl2. The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure to give 23 as a light brown solid without the need for purification (6.79 g, 93%): 1H NMR (300 MHz, CDCl3) δ 7.14 (d, J=1.5 Hz, 1H), 6.96 (dd, J=8.2, 1.5 Hz, 1H), 6.62 (d, J=8.2 Hz, 1H), 4.11 (s, 2H), 3.36 (s, 1H), 2.21 (s, 3H).
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])[CH3:2].[NH2:8][C:9]1[CH:10]=[C:11]([CH:33]=[CH:34][C:35]=1[O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH:12]([OH:32])[CH2:13][N:14]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH:15]([CH3:24])[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=1>>[CH2:37]([O:36][C:35]1[CH:34]=[CH:33][C:11]([CH:12]([OH:32])[CH2:13][N:14]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:15]([CH3:24])[CH2:16][C:17]2[CH:18]=[CH:19][C:20]([OH:23])=[CH:21][CH:22]=2)=[CH:10][C:9]=1[NH:8][C:1](=[O:3])[CH3:2])[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1
Reactant: CC(=O)OC(C)=O
Reactant: CC(Cc1ccc(O)cc1)N(Cc1ccccc1)CC(O)c1ccc(OCc2ccccc2)c(N)c1
Product: CC(=O)Nc1cc(C(O)CN(Cc2ccccc2)C(C)Cc2ccc(O)cc2)ccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
In 20 ml. of acetic anhydride there was dissolved 4.0 g. of 3-amino-4-benzyloxy-α-[N-benzyl-N-(1-methyl-2-p-hydroxyphenylethyl)aminomethyl] benzyl alcohol [A] prepared above and after heating the mixture to 65°-80° C for one hour and 30 minutes, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in a mixture of 15 ml. of methanol and 2.0 g. of potassium hydroxide and the solution was stirred for one hour at room temperature. Then, methanol was distilled off under reduced pressure and after water was added to the residue, the residue was extracted with benzene. The extract was washed with water, dried over anhydrous magnesium sulfate, and dried. Thereafter, by distilling off the solvent, 3.8 g. of a crystalline powder of 4-benzyloxy-3-acetylamino-α-[N-benzyl-N-(1-methyl-2-p-hydroxyphenylethyl)aminomethyl] benzyl alcohol [A] was obtained. By recrystallizing 2.0 g. of the product thus obtained from 20 ml. of ethanol 1.6 g. of the crystalline pure product was obtained, melting at 141°-143° C.______________________________________Elemental analysis for C32H36N2O4 : C(%) H(%) N(%)______________________________________Calculated: 75.55 6.92 5.34Found: 75.62 7.03 5.21______________________________________
Reaction SMILES: [Cl:1][C:2]1[C:10]2[O:9][C:8]([C:16]([O:18][CH2:19][CH3:20])=[O:17])([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:7](O)[C:6]=2[CH:5]=[CH:4][C:3]=1[O:22][CH3:23].[H][H]>S(=O)(=O)(O)O.[Pd].C(O)(=O)C>[Cl:1][C:2]1[C:10]2[O:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:7][C:6]=2[CH:5]=[CH:4][C:3]=1[O:22][CH3:23]
Reactant: CCOC(=O)C1(C(=O)OCC)Oc2c(ccc(OC)c2Cl)C1O
Reactant: [H][H]
Agent: [Pd]
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Product: CCOC(=O)C1(C(=O)OCC)Cc2ccc(OC)c(Cl)c2O1
Yield: 82.5 %

Procedure:
A solution of (15h) (2.67 g., 0.008 mol) and 3 drops of concentrated sulfuric acid in 100 ml. of glacial acetic acid was treated with 0.3 g. of 20% palladium on carbon in a Parr apparatus under 3 atmospheres of hydrogen for 2 hours at room temperature. The solvent was evaporated under reduced pressure and the residue was dissolved in chloroform. This solution was washed with aqueous sodium bicarbonate and brine solutions, dried over anhydrous sodium sulfate, and evaporated. There resulted an 82.5% yield of diethyl 7-chloro-2,3-dihydro-6-methoxybenzofuran-2,2-dicarboxylate, m.p. 97°-99° C. Analysis (C15H17ClO6) C,H.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1([CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[C:20]([C:31]([F:34])([F:33])[F:32])[CH:19]=2)[CH2:13][O:12]C(C)(C)[O:10][CH2:9]1)(C)(C)C.[ClH:36]>C(O)C>[ClH:36].[NH2:7][C:8]([CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[C:20]([C:31]([F:32])([F:33])[F:34])[CH:19]=1)([CH2:9][OH:10])[CH2:13][OH:12]
Reactant: CCCCCCOc1ccc(CCC2(NC(=O)OC(C)(C)C)COC(C)(C)OC2)cc1C(F)(F)F
Agent: Cl
Solvent: CCO
Product: CCCCCCOc1ccc(CCC(N)(CO)CO)cc1C(F)(F)F
Temperature: 80 °C
Reaction time: 3 h

Procedure:
Compound 11-1 (620 mg) was dissolved in ethanol (15 ml), concentrated hydrochloric acid (2.5 ml) was added, and the mixture was stirred at 80° C. for 3 hr. The reaction mixture was concentrated, and the residue was washed with diethyl ether to give the object product (465 mg) as a white powder.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH:4]=[CH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[CH:14][N:13]=2)=[CH:8][CH:7]=1.[H][H]>O1CCCC1.[Pd]>[OH:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[N:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[CH:14][N:13]=2)=[CH:10][CH:11]=1
Reactant: CCCCCCCCCCOc1cnc(-c2ccc(C=CCCO)cc2)nc1
Reactant: [H][H]
Agent: [Pd]
Solvent: C1CCOC1
Product: CCCCCCCCCCOc1cnc(-c2ccc(CCCCO)cc2)nc1
Yield: 99 %

Procedure:
0.38 g (1 mmol) of the thus obtained 2-(4-(4-hydroxy-1-butenyl)phenyl)-5-decyloxypyrimidine was dissolved in 20 ml of tetrahydrofuran, added with 0.05 g of 10% Pd/C and subjected to a hydrogenation reaction in a hydrogen atmosphere under normal pressure. The reaction was stopped when about 25 ml of hydrogen was consumed. Then 10% Pd/C was filtered out and the filtrate was concentrated to obtain 0.38 g of 2-(4-(4-hydroxybutyl)-phenyl)-5-decyloxypyrimidine (yield: 99%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][NH:11][C:10](=[O:14])[CH:9]=2)=[N:6][CH:7]=1.Br[C:16]1[CH:24]=[C:23]2[C:19]([C:20]3[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][C:21]=3[N:22]2[CH3:25])=[CH:18][CH:17]=1>>[CH3:25][N:22]1[C:23]2[C:19](=[CH:18][CH:17]=[C:16]([N:11]3[CH:12]=[CH:13][C:8]([C:5]4[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=4)=[CH:9][C:10]3=[O:14])[CH:24]=2)[C:20]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][C:21]1=2
Reactant: Cc1ccc(-c2cc[nH]c(=O)c2)nc1
Reactant: Cn1c2c(c3ccc(Br)cc31)CCN(C(=O)OC(C)(C)C)C2
Product: Cc1ccc(-c2ccn(-c3ccc4c5c(n(C)c4c3)CN(C(=O)OC(C)(C)C)CC5)c(=O)c2)nc1
Yield: 36.4 %

Procedure:
4-(5-methylpyridin-2-yl)pyridin-2(1H)-one (150 mg, 0.81 mmol) and tert-butyl 7-bromo-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (294 mg, 0.805 mmol) were reacted following the procedure of Example 30 (step g) to provide the title compound (138 mg, 36%) as a yellow/green solid: 1H NMR (500 MHz, CDCl3) δ 8.56 (s, 1H), 7.71 (d, J=8.2 Hz, 1H), 7.63-7.61 (m, 1H), 7.56 (d, J=8.3 Hz, 1H), 7.52 (d, J=7.2 Hz, 1H), 7.37 (s, 1H), 7.17 (d, J=1.6 Hz, 1H), 7.09 (dd, J=8.3, 1.7 Hz, 1H), 7.04 (dd, J=7.2, 1.9 Hz, 1H), 4.65 (br m, 2H), 3.76 (br m, 2H), 3.65 (s, 3H), 2.82 (br m, 2H), 2.42 (s, 3H), 1.51 (s, 9H).
Reaction SMILES: [C:1]1([CH:7]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8]#[N:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:17][CH2:18][CH2:19][NH:20]N.[S]>>[C:1]1([CH:7]([C:8]2[NH:20][CH2:19][CH2:18][NH:17][N:9]=2)[CH2:10][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: NCCNN
Reactant: N#CC(Cc1ccccc1)c1ccccc1
Agent: [S]
Product: c1ccc(CC(C2=NNCCN2)c2ccccc2)cc1

Procedure:
A process for preparing 3-(1,2-diphenylethyl)-1,4,5,6-tetrahydro-1,2,4-triazine which comprises reacting benzyl cyanide with benzyl chloride to produce 2,3-diphenylpropionitrile and cyclizing the 2,3-diphenylpropionitrile with 2-aminoethylhydrazine in the presence of a catalytic amount of elemental sulfur to give 3-(1,2-diphenylethyl)-1,4,5,6-tetrahydro-1,2,4-triazine.
Reaction SMILES: [C:1]1([NH:7][C:8]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([NH:19]S(C4C=C(Cl)C=C(Cl)C=4)(=O)=O)=[CH:16][CH:17]=3)[CH2:12][CH2:11]2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>CO>[C:1]1([NH:7][C:8]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([NH2:19])=[CH:16][CH:17]=3)[CH2:12][CH2:11]2)=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(Nc1ccccc1)N1CCc2cc(NS(=O)(=O)c3cc(Cl)cc(Cl)c3)ccc21
Solvent: CO
Product: Nc1ccc2c(c1)CCN2C(=O)Nc1ccccc1

Procedure:
The reaction is carried out in methanol. The crude product is further reacted directly in V (9).
Reaction SMILES: CON(C)[C:4]([C:6]1[N:7]=[CH:8][N:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]3[C:18]([F:24])=[N:19][CH:20]=[CH:21][C:22]=3[F:23])[CH:12]=2)[CH:10]=1)=[O:5].Br[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1>>[F:24][C:18]1[C:17]([C:13]2[CH:12]=[C:11]([N:9]3[CH:10]=[C:6]([C:4]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=4)=[O:5])[N:7]=[CH:8]3)[CH:16]=[CH:15][CH:14]=2)=[C:22]([F:23])[CH:21]=[CH:20][N:19]=1
Reactant: Brc1ccccn1
Reactant: CON(C)C(=O)c1cn(-c2cccc(-c3c(F)ccnc3F)c2)cn1
Product: O=C(c1ccccn1)c1cn(-c2cccc(-c3c(F)ccnc3F)c2)cn1

Procedure:
This compound is prepared by method C using compound 12j and 2-bromopyridine
Reaction SMILES: O[CH:2]1[C:10]2[CH:9]=[CH:8][S:7][C:6]=2[CH2:5][CH2:4][CH2:3]1.ClC1C2C=CSC=2CCC1.[NH2:21][C:22]([NH2:24])=[O:23]>S(Cl)(Cl)=O.CN(C)C=O.C(N(C(C)C)CC)(C)C>[S:7]1[CH:8]=[CH:9][C:10]2[CH:2]([NH:21][C:22]([NH2:24])=[O:23])[CH2:3][CH2:4][CH2:5][C:6]1=2
Reactant: OC1CCCc2sccc21
Reactant: NC(N)=O
Agent: ClC1CCCc2sccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O=S(Cl)Cl
Product: NC(=O)NC1CCCc2sccc21
Temperature: 50 °C

Procedure:
A 1 gram sample of 4-hydroxy-4,5,6,7-tetrahydrobenzo[b]thiophene is stirred in the cold for several hours in thionyl chloride (5 ml.) and the mixture is evaporated to dryness. The crude 4-chloro-4,5,6,7-tetrahydrobenzo[b]thiophene is then added to a mixture of urea (1- 5 mole-equivalents) in dimethylformamide and diisopropyl ethylamine. The mixture is warmed, after several hours, to 50° C. and after 4 hours is poured on ice and the product, 4,5,6,7-tetrahydrobenzo[b]thien-4-ylurea, is collected by filtration.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6](Cl)[C:5]([N+:9]([O-:11])=[O:10])=[C:4]([NH:12][CH:13]([CH3:15])[CH3:14])[N:3]=1.[CH:16]([NH2:20])([CH2:18][CH3:19])[CH3:17]>C(N(CC)CC)C>[CH3:1][C:2]1[N:3]=[C:4]([NH:12][CH:13]([CH3:15])[CH3:14])[C:5]([N+:9]([O-:11])=[O:10])=[C:6]([NH:20][CH:16]([CH2:18][CH3:19])[CH3:17])[N:7]=1
Reactant: CCC(C)N
Reactant: Cc1nc(Cl)c([N+](=O)[O-])c(NC(C)C)n1
Solvent: CCN(CC)CC
Product: CCC(C)Nc1nc(C)nc(NC(C)C)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 16 h
Yield: 96.2 %

Procedure:
10 ml of triethylamine are added to 8.05 g (0.035 mol) of 2-methyl-4-chloro-5-nitro-6-isopropylamino-pyrimidine. While cooling with ice, 7.3 g (0.1 mol) of sec- butylamine are slowly added dropwise and the mixture is stirred for 16 hours at room temperature. The reaction solution is evaporated, the residue suspended in 500 ml of water and extracted 3 times with ether, to yield 9.0 g of 2-methyl-4-isopropylamino-6-sec.butylamino-5-nitro-pyrimidine (36.5 %) as an oil.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]3([CH2:22][O:23][P:24]([C:30]([CH3:33])([CH3:32])[CH3:31])([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])[CH2:20][O:19][C:18]([CH3:21])=[N:17]3)=[CH:10][CH:9]=2)=[C:4]([F:34])[CH:3]=1.[C:35]1([SH:41])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(N(C(C)C)CC)(C)C.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd].O>[F:34][C:4]1[CH:3]=[C:2]([S:41][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:7]=[CH:6][C:5]=1[C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]2([CH2:22][O:23][P:24]([C:30]([CH3:33])([CH3:32])[CH3:31])([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])[CH2:20][O:19][C:18]([CH3:21])=[N:17]2)=[CH:10][CH:9]=1
Reactant: Sc1ccccc1
Reactant: CC1=NC(CCc2ccc(-c3ccc(Br)cc3F)cc2)(COP(=O)(C(C)(C)C)C(C)(C)C)CO1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: ClC(Cl)Cl
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: CC1=NC(CCc2ccc(-c3ccc(Sc4ccccc4)cc3F)cc2)(COP(=O)(C(C)(C)C)C(C)(C)C)CO1
Yield: 48.7 %

Procedure:
A solution of 4-[2-(4′-bromo-2′-fluorobiphenyl-4-yl)ethyl]-4-di(tert-butyl)phosphoryloxymethyl-2-methyl-2-oxazoline (201 mg), benzenethiol (42 mg), diisopropylethylamine (89 mg), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (17.8 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (19.9 mg) in 1,4-dioxane (2 mL) was heated under reflux for 15 hr under a nitrogen atmosphere. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound (103 mg) as a yellow oil.