Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: F[C:2]1[CH:28]=[CH:27][C:5]2[N:6]=[C:7]([C:9]3[C:10]([NH2:26])=[N:11][CH:12]=[C:13]([C:15]4[CH:16]=[N:17][N:18]([CH:20]5[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]5)[CH:19]=4)[CH:14]=3)[S:8][C:4]=2[CH:3]=1.[Cl:29]C1SC2C(Cl)=CC=CC=2N=1>>[Cl:29][C:3]1[C:4]2[S:8][C:7]([C:9]3[C:10]([NH2:26])=[N:11][CH:12]=[C:13]([C:15]4[CH:16]=[N:17][N:18]([CH:20]5[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]5)[CH:19]=4)[CH:14]=3)=[N:6][C:5]=2[CH:27]=[CH:28][CH:2]=1
Reactant: Nc1ncc(-c2cnn(C3CCNCC3)c2)cc1-c1nc2ccc(F)cc2s1
Reactant: Clc1nc2cccc(Cl)c2s1
Product: Nc1ncc(-c2cnn(C3CCNCC3)c2)cc1-c1nc2cccc(Cl)c2s1

Procedure:
Same procedure as 3-(6-fluorobenzothiazol-2-yl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine except using 2,7-dichloro-1,3-benzothiazole in place of 2-chloro-6-fluorobenzothiazole to afford the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ=2.10-2.22 (m, 2H), 2.23-2.31 (m, 2H), 3.12 (q, J=11.1 Hz, 2H), 3.42 (d, J=12.4 Hz, 2H), 4.46-4.56 (m, 1H), 7.60-7.66 (m, 2H), 8.09 (s, 1H), 8.12 (dd, J=6.2, 2.9 Hz, 1H), 8.44 (s, 2H), 8.56 (d, J=1.8 Hz, 1H). MS (ES+): m/z=411.09/413.06 (3:1) [MH+]. HPLC: tR=2.16 min (ZQ2, polar—5 min).
Reaction SMILES: [C:1]([C-:3]1[CH:7]=[CH:6][CH:5]=[CH:4]1)#[CH:2].[CH-:8]1[CH:12]=[CH:11][CH:10]=[CH:9]1.[Fe+2:13].[I:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17](I)[CH:16]=1>>[C-:3]1([C:1]#[C:2][C:17]2[CH:18]=[CH:19][CH:20]=[C:15]([I:14])[CH:16]=2)[CH:7]=[CH:6][CH:5]=[CH:4]1.[CH-:8]1[CH:12]=[CH:11][CH:10]=[CH:9]1.[Fe+2:13]
Reactant: C#C[c-]1cccc1
Reactant: Ic1cccc(I)c1
Agent: [Fe+2]
Agent: c1cc[cH-]c1
Product: Ic1cccc(C#C[c-]2cccc2)c1

Procedure:
Ethynylferrocene 500 was reacted with 1,3-diiodobenzene 502 to form 1-(ferrocenylethynyl)-3-iodobenzene 504. Sufficient ethynylferrocene 500 was present such that the second step of the reaction immediately proceeded. 1-(Ferrocenylethynyl)-3-iodobenzene 504 reacted with ethynylferrocene 514 to form 1,3-bis(ferrocenylethynyl) benzene 516. The reaction procedure is shown in FIG. 5.
Reaction SMILES: [F:1][C:2]([F:15])=[CH:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH:12]([OH:14])[CH3:13].CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O>[F:1][C:2]([F:15])=[CH:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([CH3:13])=[O:14]
Reactant: CC(O)CCCCCCCCC=C(F)F
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)=O
Product: CC(=O)CCCCCCCCC=C(F)F
Yield: 66.2 %

Procedure:
To a stirred solution of 1.0 gram (0.0045 mole) of 12,12-difluoro-11-dodecen-2-ol (prepared in Example 3) in 10 ml of acetone was added 1.68 ml (0.0045 mole) of Jones reagent (2.7 Molar in acetone) while maintaining the reaction mixture temperature at 20°-25° C. Excess Jones reagent was destroyed by the addition of 1-methylethanol. The reaction mixture was passed through silica gel with the aid of additional acetone. The eluate was concentrated under reduced pressure, and the residue was dissolved in 50 ml of pentane. The resultant solution was washed with two 20 ml portions of water and then with one 20 ml portion of an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure yielding 0.65 gram of methyl 10,10-difluoro-9-decenyl ketone. The nmr spectrum was consistent with the proposed structure. The reaction was repeated several times.
Reaction SMILES: [CH2:1]([N:19]([CH2:87][CH2:88][CH2:89][CH2:90][CH2:91][CH2:92][CH2:93][CH2:94][CH2:95][CH2:96][CH2:97][CH2:98][CH2:99][CH2:100][CH2:101][CH2:102][CH2:103][CH3:104])[C:20]([CH2:22][CH2:23][CH:24]([CH:26]1[C:42]2([CH3:43])[CH:29]([CH:30]3[CH:39]([CH2:40][CH2:41]2)[C:38]2([CH3:44])[CH:33]([CH2:34][CH:35]([O:45][C:46](=[O:86])[NH:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][C:53]([N:55]4[CH2:59][CH:58]([OH:60])[CH2:57][CH:56]4[CH:61]([C:80]4[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=4)[O:62][CH:63]([C:72]4[CH:77]=[CH:76][C:75]([O:78][CH3:79])=[CH:74][CH:73]=4)[C:64]4[CH:69]=[CH:68][C:67]([O:70][CH3:71])=[CH:66][CH:65]=4)=[O:54])[CH2:36][CH2:37]2)[CH2:32][CH2:31]3)[CH2:28][CH2:27]1)[CH3:25])=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[C:105]1(=[O:111])[O:110][C:108](=[O:109])[CH2:107][CH2:106]1.C(N(CC)CC)C>CN(C1C=CN=CC=1)C.ClCCl>[CH3:71][O:70][C:67]1[CH:68]=[CH:69][C:64]([CH:63]([C:72]2[CH:77]=[CH:76][C:75]([O:78][CH3:79])=[CH:74][CH:73]=2)[O:62][CH:61]([C:80]2[CH:81]=[CH:82][CH:83]=[CH:84][CH:85]=2)[CH:56]2[N:55]([C:53](=[O:54])[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48][NH:47][C:46]([O:45][CH:35]3[CH2:34][CH:33]4[C:38]([CH3:44])([CH:39]5[CH:30]([CH2:31][CH2:32]4)[CH:29]4[C:42]([CH3:43])([CH:26]([CH:24]([CH3:25])[CH2:23][CH2:22][C:20](=[O:21])[N:19]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:87][CH2:88][CH2:89][CH2:90][CH2:91][CH2:92][CH2:93][CH2:94][CH2:95][CH2:96][CH2:97][CH2:98][CH2:99][CH2:100][CH2:101][CH2:102][CH2:103][CH3:104])[CH2:27][CH2:28]4)[CH2:41][CH2:40]5)[CH2:37][CH2:36]3)=[O:86])[CH2:59][CH:58]([O:60][C:105](=[O:111])[CH2:106][CH2:107][C:108]([OH:110])=[O:109])[CH2:57]2)=[CH:65][CH:66]=1
Reactant: CCCCCCCCCCCCCCCCCCN(CCCCCCCCCCCCCCCCCC)C(=O)CCC(C)C1CCC2C3CCC4CC(OC(=O)NCCCCCC(=O)N5CC(O)CC5C(OC(c5ccc(OC)cc5)c5ccc(OC)cc5)c5ccccc5)CCC4(C)C3CCC12C
Reactant: O=C1CCC(=O)O1
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCCCCN(CCCCCCCCCCCCCCCCCC)C(=O)CCC(C)C1CCC2C3CCC4CC(OC(=O)NCCCCCC(=O)N5CC(OC(=O)CCC(=O)O)CC5C(OC(c5ccc(OC)cc5)c5ccc(OC)cc5)c5ccccc5)CCC4(C)C3CCC12C
Temperature: 25 °C
Reaction time: 16 h
Yield: 71.5 %

Procedure:
Referring to scheme 21, Compound 84 (1.44 g, 1 mmol) was mixed with succinic anhydride (0.15 g, 1.5 mmol) and DMAP (0.0122 g, 0.1 mmol) and dried in a vacuum at 40° C. overnight. The mixture was dissolved in anhydrous dichloromethane (5 mL), triethylamine (0.101 g, 0.14 mL, 1 mmol) was added and the solution was stirred at room temperature under argon atmosphere for 16 h. It was then diluted with dichloromethane (50 mL) and washed with ice cold aqueous citric acid (5% wt., 25 mL) and water (2×25 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated to dryness. The crude product was purified by column chromatography to afford compound 86 as white solid (1.1 g, 71% yield; Rf=0.5 in 10% MeOH/CHCl3).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[Cl:12])[C:8]([OH:13])=[C:7]([C:14](=[O:19])[CH2:15][CH2:16][CH:17]=[O:18])[C:6](=[O:20])[C:5]2([CH3:22])[CH3:21].[OH:23]OS([O-])=O.[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[Cl:12])[C:8](=[O:13])[C:7]([C:14](=[O:19])[CH2:15][CH2:16][C:17]([OH:23])=[O:18])=[C:6]([OH:20])[C:5]2([CH3:22])[CH3:21]
Reactant: CC1(C)C(=O)C(C(=O)CCC=O)=C(O)c2cc(Cl)c(Cl)cc21
Reactant: O=S([O-])OO
Agent: [K+]
Solvent: CN(C)C=O
Product: CC1(C)C(O)=C(C(=O)CCC(=O)O)C(=O)c2cc(Cl)c(Cl)cc21
Temperature: 25 °C
Yield: 100.6 %

Procedure:
A mixture of 4-(6,7-dichloro-1-hydroxy-4,4-dimethyl-3-oxo-3,4-dihydronaphthalen-2-yl)-4-oxobutanal (0.22 g, 0.64 mmol) in 6 mL DMF was stirred at room temperature and treated with oxone (0.36 mL, 0.64 mmol). The mixture was stirred at room temperature for 2 hours. The mixture was quenched with 50 mL H2O and adjusted to pH=5 with concentrated HCl. The solid was collected by filtration and washed with 20 mL H2O. The crude was dried under high vacuum to give 0.23 g white solid. MS m/e: 357 (M+H)+. Calculated for C16H14Cl2O5: 356.
Reaction SMILES: [CH3:1][C:2]([C:4]([O:6]CCN(C)C)=[O:5])=[CH2:3].C1C=[C:16](C2N=CC=CC=2)[N:15]=[CH:14]C=1>O.Cl[Cu]>[C:4]([O:6][N:15]([CH3:16])[CH3:14])(=[O:5])[C:2]([CH3:1])=[CH2:3]
Reactant: C=C(C)C(=O)OCCN(C)C
Reactant: c1ccc(-c2ccccn2)nc1
Agent: Cl[Cu]
Solvent: O
Product: C=C(C)C(=O)ON(C)C
Temperature: 55 °C
Reaction time: 0.17 h

Procedure:
7 ml DMAEMA (6.531 g; 41.5 mmol), 0.0206 g CuCl (0.208 mmol) and 0.0658 g BiPy (0.421 mmol) were mixed and stirred for 10 minutes. A clear brown solution was formed. To this solution, a solution of 0.1355 g (0.205 mmol) azo-initiator 2 in 7 ml water was added. The temperature of the experiment was maintained at 55° C. The progress of the polymerization is shown in Table 7.
Reaction SMILES: [CH3:1][N:2]([CH3:21])[C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:12]2[CH:17]=[CH:16][C:15]([N:18]([CH3:20])[CH3:19])=[CH:14][CH:13]=2)=[CH:10][CH3:11])=[CH:5][CH:4]=1.ClCCCl.[Br:26]Br.N1C=CC=CC=1>C1(C)C=CC=CC=1>[CH3:20][N:18]([CH3:19])[C:15]1[CH:14]=[CH:13][C:12]([C:9]([C:6]2[CH:5]=[CH:4][C:3]([N:2]([CH3:1])[CH3:21])=[CH:8][CH:7]=2)=[C:10]([Br:26])[CH3:11])=[CH:17][CH:16]=1
Reactant: CC=C(c1ccc(N(C)C)cc1)c1ccc(N(C)C)cc1
Reactant: BrBr
Solvent: ClCCCl
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CC(Br)=C(c1ccc(N(C)C)cc1)c1ccc(N(C)C)cc1
Temperature: 0 °C
Reaction time: 3 h
Yield: 68.9 %

Procedure:
Into a reactor were introduced 13.6 g (48.5 mmol) of the 1,1-bis(4-dimethylaminophenyl)propene and 54 mL of 1,2-dichloroethane under a nitrogen atmosphere. The contents were cooled to 0° C. Thereto was gradually added dropwise 7.76 g (48.5 mmol) of bromine. The resultant mixture was stirred at room temperature for 2.5 hours. Thereafter, 15.7 mL (194 mmol) of pyridine and 109 mL of toluene were added thereto and this mixture was stirred at 80° C. for 3 hours. After being cooled, the reaction mixture was washed with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution, subsequently dried with anhydrous magnesium sulfate, and then concentrated under reduced pressure. The concentrate was purified by column chromatography and then crystallized from methanol to obtain 12.0 g (69%) of the target compound as green-yellow crystals.
Reaction SMILES: C(OC[N:10]1[C:18]2[C:17](=[O:19])[N:16]([CH3:20])[CH2:15][N:14]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=3[Cl:28])[C:13]=2[N:12]=[C:11]1[CH2:29][CH3:30])C1C=CC=CC=1.FC(F)(F)C(O)=O>C(Cl)(Cl)Cl>[Cl:28][C:22]1[CH:23]=[C:24]([Cl:27])[CH:25]=[CH:26][C:21]=1[N:14]1[C:13]2[N:12]=[C:11]([CH2:29][CH3:30])[NH:10][C:18]=2[C:17](=[O:19])[N:16]([CH3:20])[CH2:15]1
Reactant: CCc1nc2c(n1COCc1ccccc1)C(=O)N(C)CN2c1ccc(Cl)cc1Cl
Solvent: O=C(O)C(F)(F)F
Solvent: ClC(Cl)Cl
Product: CCc1nc2c([nH]1)C(=O)N(C)CN2c1ccc(Cl)cc1Cl
Temperature: 80 °C
Yield: 94.8 %

Procedure:
A solution of 7-benzyloxymethyl-3-(2,4-dichlorophenyl)-8-ethyl-1-methyl-1,2,3,7-tetrahydro-6H-purin-6-one (1.3 g, 2.92 mmol), prepared by the method described in example 7, in CHCl3 (2 mL) was treated with trifluoroacetic acid (15 mL). The solution was heated at 80° C. in a pressure tube for 5 h. The mixture was then cooled to rt and was concentrated. The residue was concentrated from heptane (2×), transferred into a separatory funnel containing saturated aqueous NaHCO3 (75 mL), and the aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel (3% methanol in CH2Cl2) to furnish 3-(2,4-dichlorophenyl)-8-ethyl-1-methyl-1,2,3,7-tetrahydro-6H-purin-6-one (900 mg, 95% yield) as a colorless solid: mp 200-201° C.; 1H NMR (300 MHz, CDCl3) δ 12.05 (s, 1H), 7.47 (d, J=2.2 Hz, 1H), 7.20 (dd, J=8.8, 2.6 Hz, 1H), 7.12 (d, J=8.4 Hz, 1H), 4.90 (s, 2H), 3.02 (s, 3H), 2.79 (q, J=7.7 Hz, 2H), 1.34 (t, J=7.7 Hz, 3H); LRMS (APCI) m/e 325.0 [(M+H)+, calcd for C14H15N15OCl2 325.1].
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][CH:17]=[C:18](I)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][N:30]([C:33]2[C:38]([C:39]([F:42])([F:41])[F:40])=[CH:37][C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][N:34]=2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[C:20]([O:24][C:25]([N:27]1[CH2:28][CH2:29][N:30]([C:33]2[C:38]([C:39]([F:42])([F:40])[F:41])=[CH:37][C:36]([C:18]3[N:13]4[C:14]([S:15][C:11]([C:5]5[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=5)=[N:12]4)=[N:16][CH:17]=3)=[CH:35][N:34]=2)[CH2:31][CH2:32]1)=[O:26])([CH3:23])([CH3:21])[CH3:22]
Reactant: CC(C)(C)OC(=O)N1CCN(c2ncc(B3OC(C)(C)C(C)(C)O3)cc2C(F)(F)F)CC1
Reactant: COc1ccc(-c2nn3c(I)cnc3s2)cc1OC
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: COc1ccc(-c2nn3c(-c4cnc(N5CCN(C(=O)OC(C)(C)C)CC5)c(C(F)(F)F)c4)cnc3s2)cc1OC
Temperature: 110 °C
Yield: 55.7 %

Procedure:
A mixture of 2-(3,4-dimethoxy-phenyl)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole (0.2 g, 0.517 mmol, 1 eq), PdCl2(Ph3P)2 (73 mg, 0.103 mmol, 0.2 eq), 4-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-pyridin-2-yl]-piperazine-1-carboxylic acid tert-butyl ester (0.354 g, 0.775 mmol, 1.5 eq) and Na2CO3 (2M aqueous solution, 1 mL) in dioxane (4 mL) was heated at 110° C. for 2.5 h. The reaction was cooled down to rt and solvents were removed under reduced pressure. The residue was treated with water, sonicated and filtered. The solid was washed with water and purified by column chromatography (Biotage, cHex/EtOac 10 to 100%) to afford the desired product (170 mg, 56%): HPLC-MS: (5-100% B in 8 min, 0.8 mL/min, 50° C.): tR=7.36 min, [M+H]+ m/z 591.2; 1H NMR (300 MHz, CDCl3) δ 8.98 (d, J=2.0 Hz, 1H), 8.56 (d, J=2.2 Hz, 1H), 7.62 (s, 1H), 7.42 (m, 2H), 6.95 (m, 1H), 3.98 (s, 3H), 3.96 (s, 3H), 3.57 (m, 4H), 3.31 (m, 4H), 1.50 (s, 9H).
Reaction SMILES: [OH:1][CH:2]([C:4]1[O:8][N:7]=[C:6]([C:9]([OH:11])=O)[CH:5]=1)[CH3:3].[NH2:12][C@@H:13]([CH3:29])[CH2:14][N:15]1[CH:19]=[CH:18][C:17]([C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([Cl:28])[CH:21]=2)=[N:16]1>>[Cl:28][C:22]1[CH:21]=[C:20]([C:17]2[CH:18]=[CH:19][N:15]([CH2:14][C@@H:13]([NH:12][C:9]([C:6]3[CH:5]=[C:4]([CH:2]([OH:1])[CH3:3])[O:8][N:7]=3)=[O:11])[CH3:29])[N:16]=2)[CH:27]=[CH:26][C:23]=1[C:24]#[N:25]
Reactant: C[C@H](N)Cn1ccc(-c2ccc(C#N)c(Cl)c2)n1
Reactant: CC(O)c1cc(C(=O)O)no1
Product: CC(O)c1cc(C(=O)N[C@@H](C)Cn2ccc(-c3ccc(C#N)c(Cl)c3)n2)no1
Yield: 46.1 %

Procedure:
N—((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)isoxazole-3-carboxamide was prepared using the method of Example 34(d) starting from 5-(1-hydroxyethyl)isoxazole-3-carboxylic acid (2.170 g, 13.81 mmol) and (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile (3 g, 11.51 mmol). The product was purified by Flash-chromatography with yield of 46.1%. 1H-NMR (400 MHz; CDCl3): δ 1.23 (d, 3H), 1.62 (d, MI), 2.30 (s, 1H), 4.26 (dd, 1H), 4.43 (dd, 1H), 4.53-4.64 (m, 1H), 5.06 (q, 1H), 6.63 (d, 1H), 6.64 (d, 1H), 7.48 (d, 1H), 7.69 (d, 1H), 7.84 (dd, 1H), 7.87 (d, 1H), 8.05 (d, 1H).
Reaction SMILES: [CH3:1][C:2]1([CH3:27])[CH2:7][CH:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([OH:24])[CH3:23])=[CH:17][CH:16]=3)[CH:12]=[CH:11][N:10]=2)[CH2:5][C:4]([CH3:26])([CH3:25])[NH:3]1.[C:28]1([CH3:38])[CH:33]=[CH:32][C:31]([S:34](Cl)(=[O:36])=[O:35])=[CH:30][CH:29]=1>N1C=CC=CC=1>[CH3:23][CH:22]([O:24][S:34]([C:31]1[CH:32]=[CH:33][C:28]([CH3:38])=[CH:29][CH:30]=1)(=[O:36])=[O:35])[CH2:21][C:18]1[CH:19]=[CH:20][C:15]([C:13]2[CH:12]=[CH:11][N:10]=[C:9]([NH:8][CH:6]3[CH2:5][C:4]([CH3:26])([CH3:25])[NH:3][C:2]([CH3:1])([CH3:27])[CH2:7]3)[N:14]=2)=[CH:16][CH:17]=1
Reactant: CC(O)Cc1ccc(-c2ccnc(NC3CC(C)(C)NC(C)(C)C3)n2)cc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OC(C)Cc2ccc(-c3ccnc(NC4CC(C)(C)NC(C)(C)C4)n3)cc2)cc1

Procedure:
The title compound was prepared from 1-{4-[2-(2,2,6,6-tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-phenyl}-propan-2-ol and p-toluenesulfonyl chloride in pyridine. Yield: 177 mg (100%).
Reaction SMILES: [CH3:1][N:2]([S:25]([CH3:28])(=[O:27])=[O:26])[C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([N:13]2[CH2:17][CH:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:15][C:14]2=O)[CH:12]=1)[C:6]([O:8]C)=[O:7].O1CCCC1.O1CCCC1.CO>O1CCCC1>[CH3:1][N:2]([S:25]([CH3:28])(=[O:27])=[O:26])[C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([N:13]2[CH2:14][CH2:15][CH:16]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH2:17]2)[CH:12]=1)[C:6]([OH:8])=[O:7]
Reactant: COC(=O)c1cc(N2CC(c3ccccc3)CC2=O)cc(N(C)S(C)(=O)=O)c1
Solvent: CO
Solvent: C1CCOC1
Product: CN(c1cc(C(=O)O)cc(N2CCC(c3ccccc3)C2)c1)S(C)(=O)=O
Temperature: 25 °C
Reaction time: 16 h
Yield: 88 %

Procedure:
To a solution of methyl 3-[methyl(methylsulfonyl)amino]-5-(2-oxo-4-phenylpyrrolidin-1-yl)benzoate obtained in Reference Example 18 0.20 g (0.50 mmol) in tetrahydrofuran (3 mL) was added 1.0 M BH3.tetrahydrofuran/tetrahydrofuran solution (1.5 mL) dropwise under ice-cooling and the mixture was stirred at room temperature for 16 hours. To the reaction solution was added methanol (3 mL) under ice-cooling, and the solvent was evaporated. The residue was dissolved in methanol (10 mL), and the mixture was stirred at 80° C. for 7 hours and the solvent was evaporated. The resulting solid was dissolved in a mixture of 2N aqueous sodium hydroxide solution (0.5 mL), methanol (0.5 mL) and tetrahydrofuran (0.5 mL) and the mixture was stirred at room temperature for 15 hours. The solvent was concentrated and the residue was adjusted by adding 1N hydrochloric acid to pH=3 and the mixture was extracted with ethyl acetate. After drying of the mixture on magnesium sulfate, the solvent was evaporated to give 165 mg (0.176 mmol) of the title compound (yield: 88%).
Reaction SMILES: Br[C:2]1[CH:14]=[CH:13][C:5]2[S:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[C:4]=2[CH:3]=1.[C:15]1(B(O)O)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+].C(O)C>C1(C)C=CC=CC=1.O>[C:15]1([C:2]2[CH:14]=[CH:13][C:5]3[S:6][C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=4[C:4]=3[CH:3]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: Brc1ccc2sc3ccccc3c2c1
Reactant: OB(O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCO
Solvent: Cc1ccccc1
Product: c1ccc(-c2ccc3sc4ccccc4c3c2)cc1
Yield: 52.6 %

Procedure:
2-bromo-dibenzo[b,d]thiophene (10 g), phenylboronic acid (5.1 g) tetrakis(triphenylphosphine)palladium (2.2 g) and potassium carbonate (18.38 g) were refluxed in a mixture of toluene (110 mL), ethanol (20 mL) and water (90 mL) overnight. The reaction was quenched with water and the toluene layer was removed and passed through a celite column and the toluene layer was evaporated in a rotary evaporator to yield 5.2 g 2-phenyl-dibenzo[b,d]thiophene. 2-phenyldibenzo[b,d]thiophene (5.2 g) was dissolved in anhydrous tetrahydrofuran (50 mL) under nitrogen atmosphere, and the solution was then cooled to −78° C. 20.0 mL of n-butyl lithium (1.6 M solution) was added dropwise into the reaction mixture, and continuously stirred to equilibriate to room temperature. The reaction mixture was then cool to −60° C., and trimethyborate (5.67 mL) was added and the reaction was allowed to stir overnight. The reaction was then quenched with 20% aqueous hydrochloric acid, and extracted the organic layer with ethyl acetate; ethyl acetate layer was then washed thoroughly with water and dried over anhydrous sodium sulfate, and was evaporated to dryness to yield 4.2 g of 8-phenyldibenzo[b,d]thiophene-4-boronic acid.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[OH:11])=[O:3].CC(C)([O-])C.[K+].[C:18](OCC)(=O)[C:19]([O:21]CC)=[O:20]>>[F:10][C:8]1[CH:7]=[CH:6][C:5]2[O:11][C:18]([C:19]([OH:21])=[O:20])=[CH:1][C:2](=[O:3])[C:4]=2[CH:9]=1
Reactant: CC(=O)c1cc(F)ccc1O
Reactant: CCOC(=O)C(=O)OCC
Agent: CC(C)(C)[O-]
Agent: [K+]
Product: O=C(O)c1cc(=O)c2cc(F)ccc2o1

Procedure:
5-Fluoro-2-hydroxyacetophenone (II) was treated with potassium tertiary butoxide and diethyl oxalate to give 6-fluoro-4-oxo-4H-1-benzopyran-2-carboxylic acid (III) according to Reaction 1 as given below by a known process (JP 2218675).
Reaction SMILES: Br[C:2]1[CH:20]=[CH:19][C:5]([CH2:6][O:7][CH:8]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:9]([NH:11][CH2:12][C:13]#[N:14])=[O:10])=[CH:4][CH:3]=1.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=2)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].C(=O)([O-])[O-].[Na+].[Na+].ClCCl>CN(C=O)C.C(OC(=O)C)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]>[C:13]([CH2:12][NH:11][C:9]([CH:8]([O:7][CH2:6][C:5]1[CH:19]=[CH:20][C:2]([C:37]2[CH:36]=[CH:35][C:34]([N:31]3[CH2:30][CH2:29][N:28]([C:26]([O:25][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:27])[CH2:33][CH2:32]3)=[CH:39][CH:38]=2)=[CH:3][CH:4]=1)[CH2:15][CH:16]([CH3:18])[CH3:17])=[O:10])#[N:14]
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(B(O)O)cc2)CC1
Reactant: CC(C)CC(OCc1ccc(Br)cc1)C(=O)NCC#N
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(C)CC(OCc1ccc(-c2ccc(N3CCN(C(=O)OC(C)(C)C)CC3)cc2)cc1)C(=O)NCC#N
Temperature: 85 °C
Reaction time: 8 h

Procedure:
To 2-[(4-bromobenzyl)oxy]-N-(cyanomethyl)-4-methylpentanamide (646 mg, 1.9 mmoles) in DMF (12.5 mL) was added 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (640 mg, 2.1 mmoles) followed by 2 M aqueous sodium carbonate (2.85 mL, 5.7 mmoles) and finally [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (78 mg, 0.1 mmoles). The reaction was stirred overnight at 85° C. and cooled to room temperature prior to taking it up in ethylacetate. The organic phase was washed three times with 1.2 N hydrochloric acid, washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography (10% EtOAc, 90% Hexanes) to give tert-butyl 4-{4′-[(1-{[(cyanomethyl)amino]carbonyl}-3-methylbutoxy)-methyl][1,1 ′-biphenyl]-4-yl}-1-piperazinecarboxylate.
Reaction SMILES: [Cl:1][C:2]1[C:10]([Cl:11])=[C:9]2[C:5]([C:6]([CH:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[O:18]1[CH2:20][C@H:19]1[CH2:21][O:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]2[C:24]=1[CH:25]=[CH:26][NH:27]2>CO.CS(C)=O>[Cl:1][C:2]1[C:10]([Cl:11])=[C:9]2[C:5]([C:6]([CH:12]3[CH2:17][CH2:16][N:15]([CH2:20][C@H:19]([OH:18])[CH2:21][O:22][C:23]4[CH:31]=[CH:30][CH:29]=[C:28]5[C:24]=4[CH:25]=[CH:26][NH:27]5)[CH2:14][CH2:13]3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1
Reactant: c1cc(OC[C@@H]2CO2)c2cc[nH]c2c1
Reactant: Clc1ccc2c(C3CCNCC3)c[nH]c2c1Cl
Solvent: CO
Solvent: CS(C)=O
Product: O[C@H](COc1cccc2[nH]ccc12)CN1CCC(c2c[nH]c3c(Cl)c(Cl)ccc23)CC1

Procedure:
The title compound was prepared in a fashion similar to that described in Example 193 from 6,7-dichloro-3-(piperidin-4-yl)-1H-indole (0.80 g, 3.0 mmol) and (S)-(+)-4-(oxiranylmethoxy)-1H-indole (0.58 g, 3.1 mmol). The product was isolated as a white solid. Yield 0.64 g (47%). mp 192°-197° C. FDMS m/e=457 (M+ of free base). α[D]589 =+6.46 (c=0.99, methanol/dimethylsulfoxide).
Reaction SMILES: [CH2:1]([NH:8][C:9]1[N:14]2[N:15]=[CH:16][C:17]([C:18]([OH:20])=O)=[C:13]2[N:12]=[CH:11][C:10]=1[C:21]([N:23]1[CH2:28][CH2:27][C:26]2([C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:30]=[CH:29]2)[CH:25]([CH3:37])[CH2:24]1)=[O:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:38][S:39]([NH2:42])(=[O:41])=[O:40]>>[CH2:1]([NH:8][C:9]1[N:14]2[N:15]=[CH:16][C:17]([C:18]([NH:42][S:39]([CH3:38])(=[O:41])=[O:40])=[O:20])=[C:13]2[N:12]=[CH:11][C:10]=1[C:21]([N:23]1[CH2:28][CH2:27][C:26]2([C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:30]=[CH:29]2)[CH:25]([CH3:37])[CH2:24]1)=[O:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC1CN(C(=O)c2cnc3c(C(=O)O)cnn3c2NCc2ccccc2)CCC12C=Cc1ccccc12
Reactant: CS(N)(=O)=O
Product: CC1CN(C(=O)c2cnc3c(C(=O)NS(C)(=O)=O)cnn3c2NCc2ccccc2)CCC12C=Cc1ccccc12
Yield: 78.6 %

Procedure:
In the same manner as in Example 1, step 6 and using 7-benzylamino-6-(3′-methylspiro[inden-1,4′-piperidine]-1′-ylcarbonyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (0.049 g, 0.0825 mmol) obtained in step 2 and methanesulfonamide (0.039 g, 0.413 mmol), the title compound (0.037 g, 79%) was obtained.