Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1F)[O:8][CH:7]([C:13]([F:16])([F:15])[F:14])[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:5]2.[CH2:22]([NH2:26])[CH2:23][CH2:24][CH3:25].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[NH:26][CH2:22][CH2:23][CH2:24][CH3:25])[O:8][CH:7]([C:13]([F:16])([F:15])[F:14])[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:5]2
Reactant: CCCCN
Reactant: CCOC(=O)C1=Cc2cc(Cl)c(F)cc2OC1C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCNc1cc2c(cc1Cl)C=C(C(=O)OCC)C(C(F)(F)F)O2
Temperature: 90 °C
Yield: 79.1 %

Procedure:
A mixture of ethyl 6-chloro-7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate (Example 7a, Step 2) (0.5 g, 1.54 mmole) and butylamine (0.15 mL, 1.54 mmole) was dissolved in anhydrous DMF (5 mL), warmed to 90° C. and treated with K2CO3 (0.25 g, 1.84 mmole). The solution was maintained at 90° C. for 24 hrs, cooled to room temperature, filtered through celite and condensed to a viscous oil. The oil was purified by flash chromatography (silica gel) with 40% methylene chloride in hexane to give a light yellow oil (0.46g, 79%): GCMS m/z 377.00 (M+). 1H NMR (CDCl3/400 MHz) 7.58 (s, 1H), 7.08 (s, 1H), 6.23 (s, 1H), 5.63 (q, 1H, J=7.0 Hz), 4.70 (brs, 1H), 4.27 (m, 2H), 3.17 (m, 2H), 1.63 (m, 2H), 1.43 (m, 2H), 1.31 (m, 3H), 0.98 (m, 3H).
Reaction SMILES: CCOC(/N=N/C(OCC)=O)=O.[CH2:13]([O:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][C:22]=1[N+:28]([O-:30])=[O:29])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH3:31][C@H:32](OC1C=CC(C2C=CC=CC=2C([O-])=O)=CC=1[N+]([O-])=O)[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38]>>[CH3:31][C@H:32]([O:27][C:24]1[CH:25]=[CH:26][C:21]([O:20][CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[C:22]([N+:28]([O-:30])=[O:29])[CH:23]=1)[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38]
Reactant: CCCCCC[C@H](C)Oc1ccc(-c2ccccc2C(=O)[O-])cc1[N+](=O)[O-]
Reactant: O=[N+]([O-])c1cc(O)ccc1OCc1ccccc1
Agent: CCOC(=O)/N=N/C(=O)OCC
Product: CCCCCC[C@H](C)Oc1ccc(OCc2ccccc2)c([N+](=O)[O-])c1
Yield: 76 %

Procedure:
DEAD (777 mg, 4.46 mmol), TPP (1.171 g, 4.46 mmol), R-2-octanol (511 mg, 3.93 mmol), and compound 54 (875 mg, 3.57 mmol) were reacted according to the procedure for compound 32a. The crude product was purified via flash chromatography over silica gel with gradual elutions from 95/5-80/20 (Hex/EtOAc). Evaporation of solvent yielded 972 mg (76%) of a light yellow oil.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[CH:4][N:3]=1.[C:9]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=1)([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].C(N(C(C)C)CC)(C)C>C(O)CCC>[Cl:8][C:6]1[N:5]=[CH:4][N:3]=[C:2]([NH:23][C:20]2[CH:19]=[CH:18][C:17]([NH:16][C:9](=[O:10])[O:11][C:12]([CH3:14])([CH3:13])[CH3:15])=[CH:22][CH:21]=2)[CH:7]=1
Reactant: Clc1cc(Cl)ncn1
Reactant: CC(C)(C)OC(=O)Nc1ccc(N)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCCCO
Product: CC(C)(C)OC(=O)Nc1ccc(Nc2cc(Cl)ncn2)cc1

Procedure:
4,6-Dichloropyrimidine (14.89 g, 0.1 mol), N-Boc-1,4-phenylenediamine (20.83 g, 0.1 mol) and diisopropylethylamine (17.11 mL, 0.1 mol) are heated in n-butanol (160 mL) for 20 h at 90° C. After evaporation, the residue is extracted and purified by crystallization.
Reaction SMILES: [C:1]([Li])#[C:2][CH3:3].FC(F)(F)S(O[Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])(=O)=O>CCOCC>[CH3:13][CH:12]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[C:1]#[C:2][CH3:3])[CH3:14]
Reactant: CC(C)[Si](OS(=O)(=O)C(F)(F)F)(C(C)C)C(C)C
Reactant: [Li]C#CC
Solvent: CCOCC
Product: CC#C[Si](C(C)C)(C(C)C)C(C)C
Temperature: 25 °C
Yield: 83.9 %

Procedure:
1-Propynyllithium (7.18 g, 156 mmol) was stirred in 160 mL of anhydrous ether at -40° C. under nitrogen and treated dropwise with triisopropylsilyl trifluoromethanesulfonate (47.8 g, 41.93 mL, 156 mmol). The reaction was warmed to room temperature, washed with 2×100 mL of water and 1×100 mL of brine. The organic phase was dried over MgSO4 and concentrated in vacuo. Flash chromatography (95 mm column, petroleum ether eluent, 51/2 inches of silica gel) afforded 25.7 g (84%) of product as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:16]2[C:20]([CH3:21])=[CH:19][N:18]=[C:17]2[CH2:22]O)=[C:6]([CH:15]=1)[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:8].[C:24]1(=[O:34])[NH:28][C:27](=[O:29])[C:26]2=[CH:30][CH:31]=[CH:32][CH:33]=[C:25]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:16]2[C:20]([CH3:21])=[CH:19][N:18]=[C:17]2[CH2:22][N:28]2[C:24](=[O:34])[C:25]3=[CH:33][CH:32]=[CH:31][CH:30]=[C:26]3[C:27]2=[O:29])=[C:6]([CH:15]=1)[C:7]([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)=[O:8]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: Cc1cnc(CO)n1-c1ccc(Cl)cc1C(=O)c1ccccc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: Cc1cnc(CN2C(=O)c3ccccc3C2=O)n1-c1ccc(Cl)cc1C(=O)c1ccccc1

Procedure:
In the manner given in Example 17, 5-chloro-2-[5-methyl-2-(hydroxymethyl)imidazol-1-yl]benzophenone is treated with phthalimide and triphenylphosphine and finally with diethyl azodicarboxylate to give 5-chloro-2-[5-methyl-2-(phthalimidomethyl)imidazol-1-yl]benzophenone.
Reaction SMILES: [C:1]1([C:7]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[O:8][CH:9]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[C:10]#[CH:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(BC(C(C)C)C)(C(C)C)C.[Br-:41]>>[Br:41]/[CH:11]=[CH:10]/[CH:9]([O:8][C:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: [Br-]
Reactant: C#CC(CCCCCC)OC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CC(C)C(C)BC(C)C(C)C
Product: CCCCCCC(/C=C/Br)OC(c1ccccc1)(c1ccccc1)c1ccccc1

Procedure:
Treatment of 3-triphenylmethoxy-1-nonyne (Example 128) with disiamylborane and the bromide by the procedure described in Example 1173 is productive of the title compound.
Reaction SMILES: N1C=CC(N)=CC=1N.C([O:11][C:12]([C:14]1[NH:15][C:16]2[C:21]([CH:22]=1)=[CH:20][C:19]([NH:23][C:24]1[N:29]=[C:28]([NH:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([OH:37])[CH:32]=3)[C:27]([F:38])=[CH:26][N:25]=1)=[CH:18][CH:17]=2)=[O:13])C.[Li+].[OH-]>>[C:12]([C:14]1[NH:15][C:16]2[C:21]([CH:22]=1)=[CH:20][C:19]([NH:23][C:24]1[N:29]=[C:28]([NH:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([OH:37])[CH:32]=3)[C:27]([F:38])=[CH:26][N:25]=1)=[CH:18][CH:17]=2)([OH:13])=[O:11]
Reactant: CCOC(=O)c1cc2cc(Nc3ncc(F)c(Nc4cccc(O)c4)n3)ccc2[nH]1
Agent: Nc1ccnc(N)c1
Agent: [Li+]
Agent: [OH-]
Product: O=C(O)c1cc2cc(Nc3ncc(F)c(Nc4cccc(O)c4)n3)ccc2[nH]1

Procedure:
In a manner similar to the preparation of N4-(4-tert-butylphenyl)-5-fluoro-N2-[2,3-dihydro-2-carboxy)benzofuran-5-yl]-2,4-pyridinediamine, N2-(2-ethoxycarbonylindol-5-yl)-5-fluoro-N4-(3-hydroxyphenyl)-2,4-pyrimidinediamine upon LiOH treatment gave N2-(2-carboxyindol-5-yl)-5-fluoro-N4-(3-hydroxyphenyl)-2,4-pyrimidinediamine. 1H NMR (CD3OD): δ 7.83 (m, 1H), 7.73 (s, 1H), 7.50 (bd, 1H, J=8.7 Hz), 7.30–7.11 (m, 5H), 6.68 (bd, 1H); LCMS: ret. time: 16.50 min.; purity: 97%; MS (m/e): 380 (MH+).
Reaction SMILES: C(OC([NH:8][C@@H:9]([CH2:41][CH:42]([CH3:44])[CH3:43])[CH:10]([OH:40])[CH2:11][NH:12][C@H:13]([C:18]([NH:20][C@H:21]([C:25]([NH:27][C@H:28]([C:36]([O:38][CH3:39])=[O:37])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:26])[CH:22]([CH3:24])[CH3:23])=[O:19])[CH2:14][CH:15]([CH3:17])[CH3:16])=O)(C)(C)C.[Cl:45]CCl.[ClH:48].O>C(OCC)(=O)C>[ClH:45].[ClH:48].[NH2:8][C@@H:9]([CH2:41][CH:42]([CH3:44])[CH3:43])[CH:10]([OH:40])[CH2:11][NH:12][C@H:13]([C:18]([NH:20][C@H:21]([C:25]([NH:27][C@H:28]([C:36]([O:38][CH3:39])=[O:37])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:26])[CH:22]([CH3:24])[CH3:23])=[O:19])[CH2:14][CH:15]([CH3:16])[CH3:17]
Reactant: COC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NCC(O)[C@H](CC(C)C)NC(=O)OC(C)(C)C)C(C)C
Reactant: ClCCl
Agent: Cl
Solvent: O
Solvent: CCOC(C)=O
Product: COC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NCC(O)[C@@H](N)CC(C)C)C(C)C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 250 mg of N-[N-[N-[(3S)-3-[[(t-butyloxy)carbonyl]amino]-2-hydroxy-5-methylhexyl]-L-leucyl]-L-valyl]-L-phenylalanine, methyl ester (slower isomer) (see example 6C) in 3 ml of ethyl acetate and 1.5 ml of dichloromethane was cooled in an ice bath under nitrogen, and then treated with anhydrous hydrogen chloride gas to saturation. Once the reaction was saturated, the ice bath was removed, the reaction was stoppered, and stirred at ambient temperature. After one hour, the reaction was concentrated to dryness in vacuo, resuspended in 5 ml of ethyl acetate, cooled in an ice bath under nitrogen, resaturated with anhydrous hydrogen chloride and stoppered. After 30 minutes, the reaction was concentrated to dryness in vacuo, then recrystallized from methanol/ether at room temperature, and refrigerated overnight to afford 200 mg of the title compound as a hydrate with 0.4 mole of water, melting point 242°-252° C., dec. Analysis Calc'd. for C28H48N4O5.2HCl.0.4MH2O: C, 55.96; H, 8.52; N, 9.33; Cl, 11.80; Found: C, 55.96; H, 8.42; N, 9.31; Cl, 11.70.
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10](Cl)(=[O:12])=[O:11])=[CH:6][CH:5]=1)[CH2:2][CH3:3].N1C=CC=CC=1.N#N.[NH2:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[N:29]=[C:28]([CH3:33])[C:27]([CH3:34])=[N:26]2.C([O-])(O)=O.[Na+]>ClCCl>[CH3:33][C:28]1[C:27]([CH3:34])=[N:26][C:25]2[C:30](=[CH:31][CH:32]=[C:23]([NH:22][S:10]([C:7]3[CH:8]=[CH:9][C:4]([CH2:1][CH2:2][CH3:3])=[CH:5][CH:6]=3)(=[O:12])=[O:11])[CH:24]=2)[N:29]=1
Reactant: CCCc1ccc(S(=O)(=O)Cl)cc1
Reactant: Cc1nc2ccc(N)cc2nc1C
Agent: N#N
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCc1ccc(S(=O)(=O)Nc2ccc3nc(C)c(C)nc3c2)cc1
Yield: 89.9 %

Procedure:
To a solution of 0.4n-propylbenzenesulphonyl chloride (106 mg, 0.485 mmol) in dichloromethane (3 mL) was added pyridine (90 μL, 1.2 mmol) and the mixture was stirred under. N2 for 5 min, after which time 6-amino-2,3-dimethylquinoxaline (80 mg, 0.46 mmol) was added. The resulting mixture was stirred for 6 h at room temperature, then saturated NaHCO3 solution (8 mL) was added and the mixture was extracted into ethyl acetate (15 mL). The organic phase was washed with brine, dried (Na2SO4), filtered and evaporated to give a residue that was purified using flash chromatography to afford an off-white solid (147 mg, 90%), single spot at Rf 0.69 (ethyl acetate). mp 198.4-198.8° C., HPLC purity 99+% (tR 2.39 min in 10% water-acetonitrile). 1H NMR (CDCl3): δ 7.86 (1H, d, J=8.9 Hz), 7.72 (2H, d, Jz;8.4 Hz), 7.56 (1H, d, J=2.5 Hz), 7.48 (1H, dd, J9.2, 2.5 Hz), 7.20 (2H, d, J=7.9 Hz), 6.82 (1H, s, N—H, 2.67 (6H, s), 2.56 (2H, t, J=7.5 Hz), 1.57 (2H, sextet, J=7.4 Hz), 0.87 (3H, t, J=7.4 Hz). LCMS: 354.31 (M−). FAB-MS (MH+, C19H21N3O2S): calcd 356.1432, found 356.1433.
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8]Cl)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH2:12]([N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)[CH3:13].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:12]([N:14]1[CH2:19][CH2:18][N:17]([CH2:8][C:7]2[CH:10]=[CH:11][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[CH2:16][CH2:15]1)[CH3:13]
Reactant: CCN1CCNCC1
Reactant: O=[N+]([O-])c1ccc(CCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCN1CCN(Cc2ccc([N+](=O)[O-])cc2)CC1
Temperature: 25 °C
Reaction time: 15 h
Yield: 99.1 %

Procedure:
A mixture of 4-nitrobenzylchloride (5 g, 29.14 mmol), N-ethylpiperazine (4.4 ml, 34.97 mmol, 1.2 eq.), potassium carbonate (8 g, 58.28, 2 eq.), and acetone (100 ml) is stirred for 15 h at reflux. The reaction mixture is allowed to cool to RT, filtered and concentrated to afford 7.2 g of the title compound as a brow oil: ESI-MS: 250.1 [MH]+; TLC: Rf=0.31 (DCM/MeOH+1% NH3aq, 9:1).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:9])[CH2:5][C@@H:6]([OH:8])[CH3:7])[CH3:2].ClC(Cl)(Cl)C(=N)O[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(Cl)Cl.FC(F)(F)S(O)(=O)=O>[CH2:1]([O:3][C:4](=[O:9])[CH2:5][C@@H:6]([O:8][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH3:7])[CH3:2]
Reactant: CCOC(=O)C[C@H](C)O
Reactant: N=C(OCc1ccccc1)C(Cl)(Cl)Cl
Agent: O=S(=O)(O)C(F)(F)F
Solvent: ClCCl
Product: CCOC(=O)C[C@H](C)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 200.7 %

Procedure:
Under a nitrogen atmosphere, to a solution of (S)-(+)-3-hydroxybutyric acid ethyl ester (100 g, 0.76 mol) in methylene chloride (1.0 L), benzyl 2,2,2-trichloroacetoimidate (381 g, 1.5 mol) and trifluoromethanesulfonic acid (6.7 mL, 76 mmol) were gradually added, and the mixture was stirred at room temperature overnight. The precipitated solid was filtered, and after the mother liquid was successively washed with a saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, it was dried with sodium sulfate and the solvent was distilled off under reduced pressure. Hexane was added to the residue, and after the solid was filtered again, the solvent of the mother liquid was distilled off under reduced pressure to give (3S)-3-(benzyloxy)butanoic acid ethyl ester (339 g) as a mixture. The present compound was used for the subsequent reaction without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:9][C:10]([CH:12]2[C:17](=O)[CH2:16][CH2:15][N:14]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:13]2)=O)[CH:6]=[CH:7][CH:8]=1.[N+]([O-])(O)=O.[N+]([O-])(O)=O.[CH3:34][O:35][C:36]1[CH:37]=[C:38]([NH:48][C:49]([NH2:51])=[NH:50])[CH:39]=[CH:40][C:41]=1[N:42]1[CH:46]=[C:45]([CH3:47])[N:44]=[CH:43]1.C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>C(O)C.O>[CH3:34][O:35][C:36]1[CH:37]=[C:38]([NH:48][C:49]2[N:51]=[C:10]([CH2:9][C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=3)[C:12]3[CH2:13][N:14]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:16][C:17]=3[N:50]=2)[CH:39]=[CH:40][C:41]=1[N:42]1[CH:46]=[C:45]([CH3:47])[N:44]=[CH:43]1
Reactant: COc1cc(NC(=N)N)ccc1-n1cnc(C)c1
Reactant: COc1cccc(CC(=O)C2CN(C(=O)OC(C)(C)C)CCC2=O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: O
Solvent: ClCCl
Product: COc1cccc(Cc2nc(Nc3ccc(-n4cnc(C)c4)c(OC)c3)nc3c2CN(C(=O)OC(C)(C)C)CC3)c1
Yield: 2.9 %

Procedure:
tert-Butyl 3-(2-(3-methoxyphenyl)acetyl)-4-oxopiperidine-1-carboxylate (320 mg, 0.92 mmol), 1-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)guanidine dinitrate (342 mg, 0.92 mmol, example 43a) and potassium carbonate (382 mg, 2.76 mmol) in ethanol (4 mL) was heated in a microwave reactor to 130° C. for 3 hours. DCM and water was added and the organic phases were separated, dried with MgSO4, concentrated and purified by preparative HPLC to afford tert-butyl 2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-4-(3-methoxybenzyl)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (15.00 mg, 3%).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]([S:15]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)(=[O:17])=[O:16])[C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[C:9](Br)[CH:8]=2)=[O:4].[CH3:25][C:26](P(C(C)(C)C)C1C=CC=CC=1)([CH3:28])C.C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC=CC=1>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:1][O:2][C:3]([C:5]1[N:6]([S:15]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)(=[O:17])=[O:16])[C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[C:9]([CH:28]1[CH2:26][CH2:25]1)[CH:8]=2)=[O:4]
Reactant: CC(C)(C)P(c1ccccc1)C(C)(C)C
Reactant: COC(=O)c1cc2ccc(Br)cc2n1S(=O)(=O)c1ccc(C)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Solvent: O
Solvent: CCOC(C)=O
Product: COC(=O)c1cc2ccc(C3CC3)cc2n1S(=O)(=O)c1ccc(C)cc1
Temperature: 100 °C
Reaction time: 14 h

Procedure:
Predetermined amounts of 6-bromo-1-(toluene-4-sulfonyl)-1H-indole-2-carboxylic acid methyl ester (300 mg, 0.73 mmol), palladium acetate (16.5 mg, 0.07 mmol), bis(1,1-dimethylethyl)phenylphosphine (0.028 ml, 0.12 mmol), potassium cyclopropyl trifluoro borate (163 mg, 1.1 mmol), and cesium carbonate (718 mg, 2.2 mmol) were placed in a reaction container, and toluene (5 ml) and water (0.5 ml) were added thereto. The resulting mixture was then stirred at 100° C. for 14 hours. After cooling it to room temperature, the mixture was diluted with ethyl acetate, and washed twice with water, and then dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and concentration was performed. Then, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (hexane/ethyl acetate=97/3 to 7/3). Thus, a yellow solid was obtained (208 mg, 77%).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6]#[C:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=1.[C:14]1(=[O:24])[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[N:16][NH:15]1>>[N:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[C:7]#[C:6][CH2:5][CH2:4][CH2:3][CH2:2][N:15]1[N:16]=[CH:17][C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:14]1=[O:24]
Reactant: O=c1[nH]ncc2ccccc12
Reactant: BrCCCCC#Cc1ccccn1
Product: O=c1c2ccccc2cnn1CCCCC#Cc1ccccn1

Procedure:
The title compound was prepared in accordance with the general method of Example 242(B), from 2-(6-bromohex-1-ynyl)pyridine (138 mg, 0.578 mmol) and phthalazin-1(2H)-one (80 mg, 0.55 mmol).
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([C:15](Cl)=[O:16])=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:5][CH:4]=1.[NH2:20][C:21]1[CH:26]=[CH:25][C:24]([I:27])=[CH:23][CH:22]=1.C(N(CC)CC)C>C(Cl)Cl>[I:27][C:24]1[CH:25]=[CH:26][C:21]([NH:20][C:15]([C:10]2[C:9]([C:6]3[CH:7]=[CH:8][C:3]([C:2]([F:19])([F:18])[F:1])=[CH:4][CH:5]=3)=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:16])=[CH:22][CH:23]=1
Reactant: Nc1ccc(I)cc1
Reactant: O=C(Cl)c1ccccc1-c1ccc(C(F)(F)F)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(Nc1ccc(I)cc1)c1ccccc1-c1ccc(C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 76.8 %

Procedure:
A solution of 4′-(trifluoromethyl)-[1,1′-biphenyl]-2-carbonyl chloride (0.019 mol) in DCM (50 ml) was added slowly at 5° C. to a mixture of 1-amino-4-iodo-benzene (0.017 mol) and triethylamine (0.026 mol) in DCM (40 ml). The mixture was stirred at room temperature for 1 hour, then washed with HCl 1N, then with K2CO3 10%. The organic layer was separated, dried, filtered, and the solvent was evaporated. The residue was crystallized from DIPE. The precipitate was filtered off and dried, yielding 6.1 g of N-(4-iodophenyl)-4′-(trifluoromethyl)-[1,1′-biphenyl]-2-carboxamide (intermediate 1; mp. 147° C.).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[Mg]Br.Cl[Si:12]1([CH2:17][Cl:18])[CH2:16][CH2:15][CH2:14][CH2:13]1>C1COCC1>[Cl:18][CH2:17][Si:12]1([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])[CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: Fc1ccc([Mg]Br)c(F)c1
Reactant: ClC[Si]1(Cl)CCCC1
Solvent: C1CCOC1
Product: Fc1ccc([Si]2(CCl)CCCC2)c(F)c1

Procedure:
In the same apparatus and procedures as Example 4-ii) was prepared 15.3 g (0.079 mol) of 2,4-difluorophenylmagnesiumbromide solution in THF, and the followed by coupling with 1-chloro-1-chloromethyl-1-silacyclopentane prepared from the above procedure i) for 1hr at 60° C. In the same method as Example 1 was treated the reaction product to give 3.5 g of 1-chloromethyl -1-(2,4-difluorophenyl)-1-silacyclopentane (56°-7° C. /0.3 mmHg).
Reaction SMILES: Br[C:2]1[C:3]([O:16][CH:17]2[CH2:20][N:19]([S:21]([CH3:24])(=[O:23])=[O:22])[CH2:18]2)=[N:4][C:5]([NH:8][C@H:9]2[CH2:14][CH2:13][C@@H:12]([CH3:15])[CH2:11][CH2:10]2)=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:33]2[CH:38]=[CH:37][C:36]([O:39][C@@H:40]3[CH2:44][CH2:43][O:42][CH2:41]3)=[CH:35][CH:34]=2)O1>>[CH3:15][C@@H:12]1[CH2:13][CH2:14][C@H:9]([NH:8][C:5]2[N:4]=[C:3]([O:16][CH:17]3[CH2:20][N:19]([S:21]([CH3:24])(=[O:23])=[O:22])[CH2:18]3)[C:2]([C:33]3[CH:38]=[CH:37][C:36]([O:39][C@@H:40]4[CH2:44][CH2:43][O:42][CH2:41]4)=[CH:35][CH:34]=3)=[CH:7][N:6]=2)[CH2:10][CH2:11]1
Reactant: CS(=O)(=O)N1CC(Oc2nc(N[C@H]3CC[C@@H](C)CC3)ncc2Br)C1
Reactant: CC1(C)OB(c2ccc(O[C@@H]3CCOC3)cc2)OC1(C)C
Product: CS(=O)(=O)N1CC(Oc2nc(N[C@H]3CC[C@@H](C)CC3)ncc2-c2ccc(O[C@@H]3CCOC3)cc2)C1

Procedure:
Using the procedure of Example 1 Step 3, 5-bromo-N-(cis-4-methylcyclohexyl)-4-(1-(methylsulfonyl)azetidin-3-yloxy)pyrimidin-2-amine was reacted with (R)-4,4,5,5-tetramethyl-2-(4-(tetrahydrofuran-3-yloxy)phenyl)-1,3,2-dioxaborolane to provide the title compound (18 mg, 45% yield). 1H NMR (CDCl3, 400 MHz) 8.12 (s, 1H), 7.38 (m, 2H), 6.91 (m, 2H), 5.34 (m, 1H), 5.20 (sb, 1H), 4.95 (m, 1H), 4.31 (m, 2H), 4.09-3.92 (m, 6H), 2.90 (s, 3H), 2.22 (m, 2H), 1.80-1.57 (m, 6H), 1.23 (m, 2H), 0.94 (d, 3H). MS (ESI) m/z: Calc. 502.2 (M+). Found: 503.1 (M++1).
Reaction SMILES: [Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([N:9]2[N+:13]([O-:14])=[C:12]3[CH2:15][CH2:16][CH2:17][CH2:18][C:11]3=[N:10]2)=[C:4]([F:19])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.[CH2:31](Br)[C:32]#[CH:33]>O>[Cl:1][C:2]1[C:7]([O:8][CH2:33][C:32]#[CH:31])=[CH:6][C:5]([N:9]2[N+:13]([O-:14])=[C:12]3[CH2:15][CH2:16][CH2:17][CH2:18][C:11]3=[N:10]2)=[C:4]([F:19])[CH:3]=1
Reactant: [O-][n+]1c2c(nn1-c1cc(O)c(Cl)cc1F)CCCC2
Reactant: C#CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: C#CCOc1cc(-n2nc3c([n+]2[O-])CCCC3)c(F)cc1Cl
Yield: 13.2 %

Procedure:
To a mixture of 2-(4-chloro-2-fluoro-5-hydroxyphenyl)-4,5,6,7-tetrahydro-1,2,3-benzotriazol-1-oxide (1 g), potassium carbonate (0.3 g) and dimethylformamide (5 ml), propargyl bromide (0.6 g) was added, and the resultant mixture was stirred at 70° to 80° C. for 4 hours. After cooling, water was added to the mixture, which was then extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated. The residue was purified by silica gel thin layer chromatography using a mixture of n-hexane and ethyl acetate as a developing solvent to give 0.15 g of 2-(4-chloro-2-fluoro-5-propargyloxyphenyl)-4,5,6,7-tetrahydro-1,2,3-benzotriazol-1-oxide (Compound No. 12). M.P., 155°-156° C.
Reaction SMILES: [H][H].N[C:4]1[CH:19]=[CH:18][C:7]2=[N:8][N:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[OH:17])[N:10]=[C:6]2[CH:5]=1.[N+](C1C=CC(O)=C(N=NC2C=CC=CC=2O)C=1C1C=CC=CC=1)([O-])=O.C1(N)C=CC=CC=1N.NC1C=CC=CC=1O>>[OH:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[N:9]1[N:10]=[C:6]2[CH:5]=[CH:4][CH:19]=[CH:18][C:7]2=[N:8]1
Reactant: [H][H]
Reactant: Nc1ccc2nn(-c3ccccc3O)nc2c1
Agent: Nc1ccccc1N
Agent: Nc1ccccc1O
Agent: O=[N+]([O-])c1ccc(O)c(N=Nc2ccccc2O)c1-c1ccccc1
Product: Oc1ccccc1-n1nc2ccccc2n1

Procedure:
2-(2'-Hydroxyphenyl)benzotriazoles are known as light stabilizers for plastics (U.S. Pat. No. 3,004,896, Heller et al., Oct. 17, 1961). One method of making these compounds involves reducing an azo compound with powdered zinc (U.S. Pat. No. 3,214,436, Boyle et al., Oct. 26, 1965) but this method presents a problem of separation of large amounts of zinc oxide from the product. Another method involves oxidizing a diaminohydroxyazobenzene to form a 5-amino-2-(2'-hydroxyphenyl)benzotriazole which must then be subjected to an undesirable diazotization step. It would be desirable to use the cheapest and most convenient reducing agent, hydrogen gas, but, unfortunately, instead of the desired benzotriazole, the usual products of catalytic hydrogenation of a nitrophenylazophenol are the corresponding o-phenylenediamine and o-aminophenol in nearly quantitative yield [W. F. Whitmore and A. J. Revukus, J. Am. Chem. Soc., 62, 1687 (1940)]. The present invention is based on the surprising discovery that in an alkaline medium, the catalytic hydrogenation does not produce the previously observed cleavage of azobenzene N=N bond but instead yields the desired 2-(hydroxyphenyl)benzotriazole.