Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]=1.[ClH]1C=CC=C1[S:15]([N:18]=[C:19]=[O:20])(=[O:17])=[O:16].[NH:21]1[CH:25]=[CH:24][CH:23]=[C:22]1[C:26]([O:28][CH3:29])=[O:27].[Cl-].[Al+3].[Cl-].[Cl-]>[N+](C)([O-])=O.O>[CH3:9][C:4]1[CH:5]=[C:6]([CH3:8])[N:7]=[C:2]([NH:1][C:19]([NH:18][S:15]([C:24]2[CH:23]=[C:22]([C:26]([O:28][CH3:29])=[O:27])[NH:21][CH:25]=2)(=[O:17])=[O:16])=[O:20])[N:3]=1
Reactant: Cc1cc(C)nc(N)n1
Reactant: COC(=O)c1ccc[nH]1
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: C[N+](=O)[O-]
Product: COC(=O)c1cc(S(=O)(=O)NC(=O)Nc2nc(C)cc(C)n2)c[nH]1
Reaction time: 0.5 h

Procedure:
To a stirred suspension of 2.58 g (0.021 mol) of 2-amino-4,6-dimethylpyrimidine in 75 ml dry nitromethane at -10° was added dropwise, via syringe, under nitrogen, 2.0 ml (0.023 mol) of chlorolsulfonyl isocyanate at such a rate to maintain the temperature below 0°. The resulting clear solution was stirred 0.5 hour at -5° to -10°, then treated dropwise with a solution of 2.29 g (0.021 mole) of methyl pyrrole-2-carboxylate in 25 ml dry nitromethane. Upon completion of the addition, 2.95 gm (0.022 mole) of aluminum (III) chloride was added in one portion. The reaction mixture was heated at reflux for 2 hours, then allowed to stand overnight at ambient temperatures. The mixture was poured into 300 ml H2O and the two phase system extracted with three portions of CH2Cl2. The organic solutions were washed with water, dried over MgSO4 and evaporated to a tan foam which was triturated with minimal CH2Cl2 to afford the product as a white solid, m.p. 202°-204°.
Reaction SMILES: [C:1]([N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH3:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH:17]=[CH2:18])[N:12]=1.C(O)(=O)C>CO>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:18][CH2:17][C:13]2[CH:14]=[CH:15][CH:16]=[C:11]([CH3:10])[N:12]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]
Reactant: C=Cc1cccc(C)n1
Reactant: CC(=O)N1CCNCC1
Solvent: CC(=O)O
Solvent: CO
Product: CC(=O)N1CCN(CCc2cccc(C)n2)CC1
Temperature: 80 °C
Reaction time: 24 h
Yield: 72.8 %

Procedure:
To a stirring solution of N-acetylpiperazine (2.50 g, 20 mmol) in methanol (40 mL) at 0° C. under nitrogen was added 2-methyl-6-vinyl-pyridine (2.39 g, 20 mmol) and acetic acid (1.28 mL). The mixture was stirred for 24 hours at 80° C. and was then concentrated. The residue was partitioned between 10% aqueous K2CO3 /CH2Cl2. The organic phase was dried and concentrated to afford 3.60 g (73%) of 1-acetyl-4-[2-(6-methyl-2-pyridyl)ethyl]piperazine as a brown solid which was used directly in the next step: 1H NMR (CDCl3): δ7.48 (m, 1H), 7.0 (d, 1H), 3.63 (t, 2H), 3.45 (t, 2H), 2.95-2.60 (m, 4H), 2.50 (m, s, 9H), 2.08 (s, 3H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=O)[CH2:6][CH2:5]2.[Cl-].[OH:13][NH3+:14].C([O-])(=O)C.[Na+]>CO.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[N:14][OH:13])[CH2:6][CH2:5]2
Reactant: [NH3+]O
Reactant: O=C1CCc2cc(Br)ccc21
Agent: CC(=O)[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: ON=C1CCc2cc(Br)ccc21
Reaction time: 8 h
Yield: 95.2 %

Procedure:
5-Bromoindan-1-one (5.0 g) was dissolved in methanol. Hydroxylammonium chloride (2.5 g) and sodium acetate (2.9 g) were added to the solution at room temperature, and then stirred overnight. The reaction solution was diluted with water and extracted twice with ethyl acetate. The organic layers were combined, washed with water, and dried over anhydrous magnesium sulfate. The desiccant was filtered and separated, and then the solvent was evaporated off under reduced pressure to obtain 5-bromo-N-hydroxyindan-1-imine (5.1 g).
Reaction SMILES: C(NC(C)C)(C)C.[Li]CCCC.[C:13]([CH:15]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]1)#[N:14].Br[CH2:27][F:28]>C1COCC1>[C:13]([C:15]1([CH2:27][F:28])[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]1)#[N:14]
Reactant: CC(C)(C)OC(=O)N1CC(C#N)C1
Reactant: FCBr
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CC(C#N)(CF)C1
Temperature: 0 °C
Yield: 88.6 %

Procedure:
To an oven-dried 25 mL round bottom flask equipped for stirring was added diisopropylamine (0.659 mL, 4.66 mmol) under nitrogen. THF (5 mL) was added and the colorless solution was cooled to 0° C. To this solution was added n-BuLi (2.92 mL, 4.66 mmol) and the solution was stirred at 0° C. for 30 min. The solution was cooled to -78° C. and a solution of tert-butyl 3-cyanoazetidine-1-carboxylate (0.5 g, 2.74 mmol) in THF (3 mL) was added and the solution was stirred at −78° C. for 30 min. Bromofluoromethane (0.403 g, 3.57 mmol) was added at −78° C. dropwise. The reaction mixture was stirred for 30 min and then allowed to warm to 25° C. and stirred for 16 h. The reaction mixture was quenched at 0° C. with aqueous NH4Cl (5 mL) and extracted with DCM (3×). The extracts were dried over Na2SO4. Purification by silica column chromatography (MeOH/DCM, 0-5%) afforded the title compound as a yellow oil (0.52 g, 94%).
Reaction SMILES: CC1C2N=[C:9]([C:11]3[CH:16]=[C:15]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[C:14]([CH2:24][OH:25])=[CH:13][C:12]=3[O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[O:10]C=2C=CC=1.C1C=CC(N=NC2C=CC(N)=NC=2N)=CC=1.Cl.[Cr](Cl)([O-])(=O)=O.CCOCC>C(Cl)Cl>[CH2:27]([O:26][C:12]1[CH:13]=[C:14]([CH2:24][OH:25])[C:15]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[CH:16][C:11]=1[CH:9]=[O:10])[CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]
Reactant: CCCCCCOc1cc(-c2nc3c(C)cccc3o2)c(OCCCCCC)cc1CO
Agent: O=[Cr](=O)([O-])Cl
Agent: Cl
Agent: Nc1ccc(N=Nc2ccccc2)c(N)n1
Solvent: CCOCC
Solvent: ClCCl
Product: CCCCCCOc1cc(CO)c(OCCCCCC)cc1C=O
Reaction time: 2 h

Procedure:
A solution of 2-(4-methylbenzoxazolyl)-5-(hydroxylmethyl)-1,4-bis(hexyloxy)benzene (1.99 g, 4.53 mmol) in CH2Cl2 (10 mL) was added dropwise to a stirred solution of freshly prepared pyridium chlorochromate (PCC) (1.46 g, 6.80 mmol) in CH2Cl2 (100 mL) at room temperature. Anhydrous Et2O (100 mL) was added, and the mixture was stirred for an additional 2 h. The reaction mixture was then directly transferred onto the top of a short silica gel column. The yellow and highly fluorescent product was then washed off the column with CH2Cl2, giving 2,5-bis(hexyloxy)-4-(hydroxymethyl)benzaldehyde in 86.9% (1.72 g). The product (mp. 48-50° C.) had the following spectral properties. 1H NMR (CDCl3, 300 MHz, δ): 10.53 (s, 1H, —CHO), 7.78 (s, 1H), 7.48 (s, 1H), 7.40 (d, J=8.4 Hz, 1H), 7.26 (dd, J=7.8 Hz, J=7.8 Hz, 1H), 7.17 (d, J=7.2 Hz, 1H), 4.18 (t, J=6.6 Hz, 2H), 4.12 (t, J=6.0 Hz, 2H), 2.68 (s, 3H), 1.87 (q, J=6.3 Hz, 4H), 1.54 (m, 4H), 1.35 (m, 8H), 0.90 (m, 6H). IR(KBr): 1684 cm−1, 1609.5 cm−1, 1534.6 cm−1.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][N:6]([CH2:16][C:17]1[C:22]([C:23]([OH:26])([CH3:25])[CH3:24])=[CH:21][CH:20]=[CH:19][N:18]=1)[CH2:7][C:8]1[C:13]([CH3:14])=[CH:12][C:11]([CH3:15])=[CH:10][N:9]=1.Cl.N1C=CC([C:33]([NH2:35])=[NH:34])=N1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:14][C:13]1[C:8]([CH2:7][N:6]([CH2:16][C:17]2[C:22]([C:23]([OH:26])([CH3:24])[CH3:25])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:5][CH2:4][CH2:3][CH2:2][NH:1][C:33]([NH2:35])=[NH:34])=[N:9][CH:10]=[C:11]([CH3:15])[CH:12]=1
Reactant: Cc1cnc(CN(CCCCN)Cc2ncccc2C(C)(C)O)c(C)c1
Reactant: N=C(N)c1cc[nH]n1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cnc(CN(CCCCNC(=N)N)Cc2ncccc2C(C)(C)O)c(C)c1
Temperature: 25 °C
Reaction time: 20 h
Yield: 122.5 %

Procedure:
To a solution of 2-(2-{[(4-Amino-butyl)-(3,5-dimethyl-pyridin-2-ylmethyl)-amino]-methyl}-pyridin-3-yl)-propan-2-ol (0.1423 g, 0.28 mmol) in DMF (3 mL) was adde 1H-pyrazole-carboxamidine hydrochloride (0.0440 g, 0.28 mmol) and DIPEA (0.29 mL, 1.68 mmol) and stirred at room temperature for 20 hours. The reaction mixture was concentrated, and purification of the crude material by column chromatography on silica gel (5:1:1 CH2Cl2-MeOH—NH4OH) followed by radial chromatography on silica gel (10:2:1 CH2Cl2-MeOH—NH4OH) provided 0.1367 g (41%) of COMPOUND 197 as a white solid. 1H NMR (CDCl3) δ 1.43-1.48 (m, 8H), 1.68-1.70 (m, 2H), 2.21 (s, 3H), 2.25 (s, 3H), 2.71-2.73 (m, 4H), 3.15-3.17 (m, 3H), 3.47 (s, 2H), 3.91 (s, 2H), 4.32 (s, 2H), 7.18-7.21 (m, 1H), 7.59-7.63 (m, 1H), 7.92-7.93 (m, 1H), 8.17 (s, 1H), 8.37-8.39 (m, 1H). 13C NMR (CDCl3) δ 18.31, 18.65, 22.77, 26.67, 31.59, 41.57, 54.09, 56.32, 61.95, 72.43, 123.57, 132.52, 132.92, 135.02, 139.67, 144.31, 146.94, 147.10, 150.68, 153.40, 158.00. ES-MS m/z 400 (M+H). Anal. Calcd. for C22H34N6O.1.9CH2Cl2O.1.5H2O: C, 48.91; H, 7.01; N, 14.32. Found: C, 48.68; H, 6.83; N, 14.68.
Reaction SMILES: [OH:1][C@@H:2]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:12]=[C:13]([NH:17][C:18](=[O:22])[CH:19]([CH3:21])[CH3:20])[CH:14]=[CH:15][CH:16]=2)[CH2:7][CH2:6]1.[CH3:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([C:37](=[O:39])[CH3:38])=[CH:33][C:32]=1O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.N>C1COCC1.C(Cl)(Cl)Cl>[C:37]([C:34]1[CH:33]=[CH:32][C:31]([O:30][CH3:29])=[C:36]([CH:35]=1)[O:1][C@H:2]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:12]=[C:13]([NH:17][C:18](=[O:22])[CH:19]([CH3:21])[CH3:20])[CH:14]=[CH:15][CH:16]=2)[CH2:7][CH2:6]1)(=[O:39])[CH3:38]
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CC[C@@H](O)c3ccccc3)CC2)c1
Reactant: COc1ccc(C(C)=O)cc1O
Agent: CCOC(=O)N=NC(=O)OCC
Agent: N
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Product: COc1ccc(C(C)=O)cc1O[C@@H](CCN1CCC(c2cccc(NC(=O)C(C)C)c2)CC1)c1ccccc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 22.1 %

Procedure:
A mixture of N-(3-{1-[(3R)-3-hydroxy-3-phenylpropyl]-4-piperidinyl}phenyl)-2-methylpropanamide (5.20 mg, 0.0137 mmol), 2-methoxy-5-acetylphenol (100 mg), triphenylphosphine (30.0 mg, 0.115 mmol) and diethyl azodicarboxylate (7.42 mg, 0.0426 mmol) in THF (0.50 mL) was stirred at room temperature for 3 days. Chromatography using silica preparative TLC plates [2.5% of NH3 (2.0 M in methanol) in CHCl3] gave the desired product (1.60 mg, 22.2% yield) as a thick oil: 1H NMR (400 MHz, CDCl3) δ 7.52 (d, 2H, J=2.4 Hz), 7.3-7.2 (m, 5H), 7.20 (m, 3H), 6.97 (apparent d, 1H, J=6.7 Hz), 6.69 (apparent d, 1H, J=8.0 Hz), 5.47 (apparent dd, 1H, J=4.3, 7.8 Hz), 3.95 (s, 3H), 3.38 (m, 2H), 2.93 (m, 2H), 2.61 (s, 1H), 2.53 (apparent sept, partially hidden, 1H, J=7.6 Hz), 2.50 (s, 3H), 2.30-2.10 (m, 6H), 1.82 (m, 2H), 1.25 (d, 6H, J=6.8 Hz); ESMS m/e: 529.6 (M+H)+.
Reaction SMILES: [CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([CH2:49][CH2:50][CH2:51][OH:52])[C:20]([O:22][C@H:23]([C:34]3[CH:39]=[CH:38][C:37]([O:40][CH:41]([F:43])[F:42])=[C:36]([O:44][CH2:45][CH:46]4[CH2:48][CH2:47]4)[CH:35]=3)[CH2:24][C:25]3[C:30]([Cl:31])=[CH:29][N+:28]([O-:32])=[CH:27][C:26]=3[Cl:33])=[O:21])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:53](Cl)(=[O:55])[CH3:54]>C(Cl)Cl>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([CH2:49][CH2:50][CH2:51][O:52][C:53](=[O:55])[CH3:54])[C:20]([O:22][C@H:23]([C:34]3[CH:39]=[CH:38][C:37]([O:40][CH:41]([F:43])[F:42])=[C:36]([O:44][CH2:45][CH:46]4[CH2:47][CH2:48]4)[CH:35]=3)[CH2:24][C:25]3[C:26]([Cl:33])=[CH:27][N+:28]([O-:32])=[CH:29][C:30]=3[Cl:31])=[O:21])=[O:17])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1
Reactant: O=C(N[C@H](CCCO)C(=O)O[C@@H](Cc1c(Cl)c[n+]([O-])cc1Cl)c1ccc(OC(F)F)c(OCC2CC2)c1)OCC1c2ccccc2-c2ccccc21
Reactant: CC(=O)Cl
Solvent: ClCCl
Product: CC(=O)OCCC[C@@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O[C@@H](Cc1c(Cl)c[n+]([O-])cc1Cl)c1ccc(OC(F)F)c(OCC2CC2)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 100.3 %

Procedure:
To a solution of 4-((S)-2-((R)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-hydroxypentanoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-ethyl)-3,5-dichloropyridine 1-oxide (268 mg, 0.354 mmol) in DCM (5 mL), acetyl chloride (54 μl, 0.757 mmol) and TEA (108 μl, 0.775 mmol) were added. The mixture was stirred at RT for 3 hours. The mixture was then diluted with DCM and washed with NaHCO3 sat. sol., HCl 0.1 M and brine. The organic phase was dried over Na2SO4 and the solvent was evaporated, to yield 284 mg of the title compound.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([S:10]([OH:12])=[O:11])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].Br[CH2:14][C:15]#[CH:16].C1COCC1>O>[N+:1]([C:4]1[CH:5]=[C:6]([S:10]([CH2:16][C:15]#[CH:14])(=[O:12])=[O:11])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1cccc(S(=O)O)c1
Reactant: C#CCBr
Solvent: C1CCOC1
Solvent: O
Product: C#CCS(=O)(=O)c1cccc([N+](=O)[O-])c1
Yield: 53.3 %

Procedure:
93.5 g (0.5 mol) of 3-nitrobenzenesulfinic acid were dissolved in 500 ml of water at pH 6.5 and the solution was added to a solution of 65.5 g of 3-bromo-prop-1-yne and 70 ml of THF. The reaction mixture was heated at 40°-50° C. until the reaction had ended (check by TLC). The reaction product was extracted with about 1.5 l of ethyl acetate, and the organic phase was neutralized and dried over sodium sulfate. The solvent was evaporated off to leave 60 g of 3-nitro-1-(prop-1-yn-3-ylsulfonyl)benzene (melting point 250°-255° C.). ##STR29##
Reaction SMILES: [H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Br:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:20]=1[N:19]=[C:18](Cl)[CH:17]=[CH:16]2>C1COCC1>[Br:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:20]=1[N:19]=[C:18]([O:9][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[CH:17]=[CH:16]2
Reactant: Clc1ccc2cccc(Br)c2n1
Reactant: Oc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Brc1cccc2ccc(Oc3ccccc3)nc12
Temperature: 0 °C
Reaction time: 1 h
Yield: 41 %

Procedure:
NaH (60% w/w in mineral oil; 1.311 g, 32.8 mmol) was added to a solution of phenol (3.09 g, 32.8 mmol, Aldrich) in THF (219 ml) at 0° C.; the resulting mixture was stirred for 10 min before 8-bromo-2-chloroquinoline (178a, 5.30 g, 21.86 mmol, Biofine International, Inc., Vancouver, BC) in THF (100 ml) was added. The reaction was stirred at 0° C. for 1 h before it was warmed to RT and stirred for 3 h, then heated at reflux for 24 h. Purification by silica gel chromatography (100% hexanes to 10% EtOAc/hexanes) provided 8-bromo-2-phenoxyquinoline (178b, 41% yield) as a light yellow oil. MS (ESI, pos. ion) m/z: 300.0/302 (M+1).
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][N:4]=1.[CH3:13][C:14]([S@@:17]([NH2:19])=[O:18])([CH3:16])[CH3:15]>ClC(Cl)C.S([O-])([O-])(=O)=O.[Cu+2]>[CH3:13][C:14]([S:17](/[N:19]=[CH:7]/[C:6]1[CH:5]=[N:4][C:3]([C:2]([F:12])([F:11])[F:1])=[CH:10][CH:9]=1)=[O:18])([CH3:16])[CH3:15]
Reactant: O=Cc1ccc(C(F)(F)F)nc1
Reactant: CC(C)(C)[S@@](N)=O
Agent: [Cu+2]
Agent: O=S(=O)([O-])[O-]
Solvent: CC(Cl)Cl
Product: CC(C)(C)S(=O)/N=C/c1ccc(C(F)(F)F)nc1
Temperature: 50 °C
Reaction time: 48 h
Yield: 107.4 %

Procedure:
To a solution of 6-(trifluoromethyl)nicotinaldehyde (45.0 g, 257 mmol) in dichloroethane (640 mL) were added (S)-(−)-2-methyl-2-propanesulfinamide (34.3 g, 283 mmol) and anhydrous copper(II) sulfate (82 g, 514 mmol). The mixture was stirred at 50° C. After 48 h, the mixture cooled to ambient temperature. The reaction mixture was filtered through Celite. The filtered cake was washed with dichloromethane and the filtrate was concentrated to give the title compound (76.8 g). MS 223.1 (M-tert-butyl+1)
Reaction SMILES: [N:1]1[N:2]([C:14]2[CH:23]=[C:22]3[C:17]([CH:18]=[C:19](Br)[C:20](=[O:24])[O:21]3)=[CH:16][CH:15]=2)[N:3]=[C:4]2[CH:13]=[CH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=12.[CH3:26][Si:27]([C:30]#[CH:31])([CH3:29])[CH3:28].C(N(CC)CC)C>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu](I)I>[N:1]1[N:2]([C:14]2[CH:23]=[C:22]3[C:17]([CH:18]=[C:19]([C:31]#[C:30][Si:27]([CH3:29])([CH3:28])[CH3:26])[C:20](=[O:24])[O:21]3)=[CH:16][CH:15]=2)[N:3]=[C:4]2[CH:13]=[CH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=12
Reactant: O=c1oc2cc(-n3nc4ccc5ccccc5c4n3)ccc2cc1Br
Reactant: C#C[Si](C)(C)C
Agent: I[Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: C[Si](C)(C)C#Cc1cc2ccc(-n3nc4ccc5ccccc5c4n3)cc2oc1=O

Procedure:
After charging 7.8 parts of 7-(naphtho[1,2]triazol-2-yl)-3-bromocoumarin synthesized by a known method, 2.4 parts of trimethylsilylacetylene, 0.46 parts of tetrakis(triphenylphosphine)palladium(0), 0.038 parts of copper iodide and 20 ml of triethylamine in 40 ml of THF, the mixture was refluxed for 9 hours. The reaction mixture was filtered and washed with THF, and the obtained filtrate was concentrated and then diluted with water and filtered. The obtained cake was recrystallized from methanol. Upon drying under reduced pressure there was obtained 4 parts of 7-(naphtho[1,2]triazol-2-yl)-3-trimethylsilylethynylcoumarin having a melting point of 250-252° C.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:6][OH:7])[C@H:3]([CH3:5])[OH:4].N1C=CN=C1.[Si:13](Cl)([C:26]([CH3:29])([CH3:28])[CH3:27])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CN(C=O)C.CCOC(C)=O>[NH2:1][C@@H:2]([CH2:6][O:7][Si:13]([C:26]([CH3:29])([CH3:28])[CH3:27])([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C@@H:3]([OH:4])[CH3:5]
Reactant: C[C@H](O)[C@@H](N)CO
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C[C@H](O)[C@@H](N)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 49.1 %

Procedure:
D-threoninol (2 g, 19.02 mmol) was dissolved in DMF (15 ml), treated with imidazole (3.89 g, 57.1 mmol) and stirred at RT for 5 min. Then, TBDPS-Cl (5.13 ml, 19.97 mmol) was added dropwise to the reaction solution under argon. The reaction solution was stirred for 16H at RT. Then it was diluted in EtOAc and washed twice with saturated NaHCO3 solution and once with brine. Organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (heptane/EtOAc: 100%→0% heptane.) to give the title compound (3.21 g, 47%). tR: 0.98 min (LC-MS 1); ESI-MS: 344.3 [M+H]+ (LC-MS 1).
Reaction SMILES: [CH2:1]([CH:4]1[C:9](=[O:10])[CH2:8][CH2:7][CH2:6][C:5]1=[O:11])[CH2:2][CH3:3].N1C=CC=CC=1.[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH2:26][CH2:27][CH2:28][C:29](=[O:32])[CH:30]=[CH2:31])[CH:23]=[CH:24][CH:25]=1>C1C=CC=CC=1>[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH2:26][CH2:27][CH2:28][C:29](=[O:32])[CH2:30][CH2:31][C:4]2([CH2:1][CH2:2][CH3:3])[C:5](=[O:11])[CH2:6][CH2:7][CH2:8][C:9]2=[O:10])[CH:23]=[CH:24][CH:25]=1
Reactant: C=CC(=O)CCCc1cccc(OC)c1
Reactant: CCCC1C(=O)CCCC1=O
Solvent: c1ccccc1
Solvent: c1ccncc1
Product: CCCC1(CCC(=O)CCCc2cccc(OC)c2)C(=O)CCCC1=O

Procedure:
Dissolve 2-propylcyclohexane-1,3-dione (36.3 g) in benzene (400 cc) containing pyridine (21.2 cc). Add 6-m-methoxyphenylhex-1-en-3-one (43.2 g) and reflux the solution over night. Cool the reaction mixture, wash with water, aqueous sodium carbonate, and 10% aqueous sulfuric acid, dry and remove the solvents under reduced pressure to obtain 2-(6-m-methoxyphenyl-3-oxohexyl)-2-propylcyclohexane-1,3-dione.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:13])[C:5]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:6]=1[OH:12])[CH3:2].[C:14]([Si:18](Cl)([CH3:20])[CH3:19])([CH3:17])([CH3:16])[CH3:15].C(N(C(C)C)CC)(C)C>ClCCl>[CH2:1]([O:3][C:4](=[O:13])[C:5]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:6]=1[O:12][Si:18]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:20])[CH3:19])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CCOC(=O)c1c(C)cccc1O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCOC(=O)c1c(C)cccc1O[Si](C)(C)C(C)(C)C
Temperature: 50 °C
Reaction time: 24 h
Yield: 92.8 %

Procedure:
To a solution of 2-hydroxy-6-methyl-benzoic acid ethyl ester (5.00 g, 27.8 mmol) and t-butyl-di-methylsilyl chloride (6.27 g, 41.6 mmol) in dichloromethane (100 ml) was added diisopropyl ethylamine. The solution was stirred at 50° C. for 24 hours, washed with water, brine, dried (MgSO4), filtered and the solvent evaporated in vacuo, which afforded 7.6 g (93%) of 2-(tert-butyl-dimethyl-silanyloxy)-6-methyl-benzoic acid ethyl ester as an oil.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH2:8])[N:5]=[C:4]2[N:9]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])[N:10]=[CH:11][C:3]=12.[S:20]1[CH:24]=[CH:23][CH:22]=[C:21]1B(O)O.C([O-])(O)=O.[Na+]>C1COCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[CH2:12][N:9]1[C:4]2=[N:5][C:6]([NH2:8])=[N:7][C:2]([C:21]3[S:20][CH:24]=[CH:23][CH:22]=3)=[C:3]2[CH:11]=[N:10]1
Reactant: Nc1nc(Cl)c2cnn(Cc3ccccc3F)c2n1
Reactant: OB(O)c1cccs1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: Nc1nc(-c2cccs2)c2cnn(Cc3ccccc3F)c2n1
Yield: 19.7 %

Procedure:
A stirred solution of 4-chloro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidine-6-amine (139 mg, 0.5 mmol) in dry THF (10 mL) was treated with 2-thiopheneboronic acid (128 mg, 1.0 mmol), Pd(PPh3)4 (50 mg, 10 mol %) and saturated aqueous NaHCO3 solution (2 mL), refluxed for 30 min, diluted with H2O, extracted with EtOAc, dried (MgSO4) and concentrated in vacuo. The resulting dark brown oil was purified by chromatography [SiO2; heptane:EtOAc (1:1) then (1:3)] to give the title compound (32 mg, 20%) as a cream solid.
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([NH:9][C:10](=[O:21])[CH:11]([NH:18][CH2:19][CH3:20])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:7][CH:8]=1.C=O.[C:26](=O)([O-])[O-].[K+].[K+]>CCCCCC.C(OCC)(=O)C>[CH2:19]([N:18]1[CH:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:10](=[O:21])[N:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:22])([F:23])[F:1])[CH:4]=2)[CH2:26]1)[CH3:20]
Reactant: O=C([O-])[O-]
Reactant: CCNC(C(=O)Nc1cccc(C(F)(F)F)c1)c1ccccc1
Agent: C=O
Agent: [K+]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CCN1CN(c2cccc(C(F)(F)F)c2)C(=O)C1c1ccccc1
Yield: 203.4 %

Procedure:
An ethanolic (50 mL) solution of the above N-aryl-2-ethylamino-2-phenylacetamide prepared in Example II (6.8 grams, 0.02 mol) and paraformaldehyde (0.65 grams, 0.02 mol) and potassium carbonate (1.5 grams, 0.01 mol) was heated under reflux for 2 hours. The reaction was followed by thin layer chromatography (3:1 hexane-ethyl acetate). The mixture was concentrated in a rotary evaporator. The product was extracted into ethyl acetate and washed with water and isolated to give the desired 1-ethyl-5-phenyl-3-(3-trifluoromethylphenyl) imidazolidine-4-one (6.8 grams, 97% yield) whose structure was confirmed by nuclear magnetic resonance, infra-red spectroscopy, and mass spectroscopy analysis.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH2:11][C:10]2[CH:13]=[C:14](N)[CH:15]=[CH:16][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2].[OH:18]S(O)(=O)=O.N([O-])=O.[Na+].C1COCC1>O>[CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH2:11][C:10]2[CH:13]=[C:14]([OH:18])[CH:15]=[CH:16][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)N1CCc2ccc(N)cc2CC1
Reactant: O=S(=O)(O)O
Agent: O=N[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)N1CCc2ccc(O)cc2CC1
Temperature: 70 °C
Reaction time: 0.25 h
Yield: 66.3 %

Procedure:
Into a 250 ml flask, the product from step (b) (3 g, 12.82 mmol) dissolved in water (15 ml) and concentrated H2SO4 (1.02 ml, 19.23 mmol) was added The reaction mixture was heated to 70° C. and stirred for 15 minutes. A solution of NaNO2 (1.01 g, 14.74 mmol) in water (30 ml) was quickly added, followed by addition of THF (45 ml). The reaction mixture was stirred at 70° C. for 30 minutes and then allowed to cool to room temperature. The reaction mixture was extracted with EtOAc (3×). The combined EtOAc extracts were washed with brine, dried over Na2SO4, and solvent evaporated in vacuo to give the sub-title compound as a yellow solid (2.0 g) that was used without further purification. MS: ESI (positive): 236 (M+H).