Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:20]Br.[CH3:22][O:23][C:24]1[CH:32]=[C:31]2[C:27]([C:28]([CH2:33][CH2:34]O)=[CH:29][NH:30]2)=[CH:26][CH:25]=1>C(#N)C.C(OCC)C>[CH3:22][O:23][C:24]1[CH:32]=[C:31]2[C:27]([C:28]([CH2:33][CH2:34][Br:20])=[CH:29][NH:30]2)=[CH:26][CH:25]=1
Reactant: BrBr
Reactant: COc1ccc2c(CCO)c[nH]c2c1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Solvent: CCOCC
Product: COc1ccc2c(CCBr)c[nH]c2c1
Reaction time: 0.33 h

Procedure:
To a mechanically stirred mixture of 18.3 g (69.7 mmol) triphenylphosphine and 200 ml acetonitrile, 11.15 g (69.7 mmol) bromine is added dropwise over 20 minutes. The mixture is stirred 20 minutes at 0° and the ice bath is removed. A solution of 12.1 g (63.4 mmol) 6-methoxy-3-(2-hydroxyethyl)indole in 60 ml acetonitrile is added over 30 minutes. After stirring 2 hours at room temperature the mixture is diluted with 250 ml diethyl ether. The liquid is decanted from precipitated tar. The residue is washed with an additional 250 ml diethyl ether. The volume of the ethereal extracts is reduced to about 60 ml and the solution is filtered through 75 g silica gel with diethyl ether. The solvent is removed to yield 6-methoxy-3-(2-bromoethyl)indole, 4.1 g, yellow waxy solid, mp 98°-101°, which turns green on standing.
Reaction SMILES: [C:1]1([CH3:19])[CH:6]=[CH:5][C:4]([S:7]([N:10]2[CH2:15][CH2:14][S:13][CH2:12][C@H:11]2[C:16]([OH:18])=[O:17])(=[O:9])=[O:8])=[CH:3][CH:2]=1.[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][CH2:27][CH2:28]O)[CH:21]=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][CH2:27][CH2:28][O:17][C:16]([C@@H:11]2[CH2:12][S:13][CH2:14][CH2:15][N:10]2[S:7]([C:4]2[CH:3]=[CH:2][C:1]([CH3:19])=[CH:6][CH:5]=2)(=[O:9])=[O:8])=[O:18])[CH:21]=1
Reactant: OCCCc1cccnc1
Reactant: Cc1ccc(S(=O)(=O)N2CCSC[C@H]2C(=O)O)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)N2CCSC[C@H]2C(=O)OCCCc2cccnc2)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 92.7 %

Procedure:
0.301 g (1 mmol) of (3R)-4-(4-toluenesulfonyl)thiomorpholine-3-carboxylic acid, 0.206 g (1.5 mmol) of 3-(pyridin-3-yl)-propanol, 0.088 g (0.33 mmol) of CAS, 0.227 g (1.2 mmol) of DCC and 0.04 g (0.33 mmol) of DMAP were dissolved in 15 mL of CH2Cl2. The mixture was stirred for 24 h at room temperature. The solid was filtrated and the solvent was evaporated. The residual was dissolved in a suitable amount of ethyl acetate (20 ml) and then the mixture was filtered to remove insoluble substance. The ethyl acetate was added to 60 ml and then the liquid was washed with 10% NaHCO3 solution, saturated NaCl solution and dried over Na2SO4. After the drying agent was removed and part of ethyl acetate was evaporated, the crude product was purified by flash column chromatography (eluent: ethyl acetate:cyclohexane=1:1) to obtain the product as a oil (0.39 g).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH2:7])[C:2]=1[NH2:8].[C:9](=S)=[S:10]>CCO>[NH:7]1[C:3]2[C:2](=[N:1][CH:6]=[CH:5][CH:4]=2)[N:8]=[C:9]1[SH:10]
Reactant: Nc1cccnc1N
Reactant: S=C=S
Solvent: CCO
Product: Sc1nc2ncccc2[nH]1
Temperature: 40 °C
Reaction time: 10 h

Procedure:
To a solution of pyridine-2,3-diamine (5 g) in EtOH (150 mL) was added carbon disulfide (23 mL) at room temperature. The mixture was stirred at 40° C. under Ar for 10 h. The mixture was cooled to room temperature. The resulting white solid was filtered and washed with ether to give 1H-imidazo[4,5-b]pyridine-2-thiol (5.61 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([CH3:34])=[C:5]([C:25]([O:32][CH3:33])=[C:26]([O:30][CH3:31])[C:27]=1[O:28][CH3:29])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[O:23][CH3:24])=[C:11]([CH:16]=1)[C:12]([O:14]C)=[O:13]>[OH-].[Na+].O1CCOCC1.O>[CH3:1][O:2][C:3]1[C:4]([CH3:34])=[C:5]([C:25]([O:32][CH3:33])=[C:26]([O:30][CH3:31])[C:27]=1[O:28][CH3:29])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[O:23][CH3:24])=[C:11]([CH:16]=1)[C:12]([OH:14])=[O:13]
Reactant: COC(=O)c1cc(Cc2c(C)c(OC)c(OC)c(OC)c2OC)ccc1-c1ccccc1OC
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: COc1ccccc1-c1ccc(Cc2c(C)c(OC)c(OC)c(OC)c2OC)cc1C(=O)O
Temperature: 25 °C
Reaction time: 16 h
Yield: 93.1 %

Procedure:
Methyl 5-(3,4,5,6-tetramethoxy-2-methylbenzyl)-2-(2-methoxyphenyl)benzoate (1.34 g, 2.8755 mmol) was dissolved in a mixed solution of a 1N aqueous solution of sodium hydroxide (20 ml) and 1,4-dioxane (40 ml) followed by stirring at room temperature for 16 hours. The reaction solution was diluted with water (200 ml), washed with ether, acidified with concentrated hydrochloric acid and extracted with ether. The extract was washed with water and dried and the solvent was evaporated therefrom to give the title compound (1.21 g, 2.6769 mmol, 93%).
Reaction SMILES: C(O[C:6]([N:8]1[CH2:17][C:16]2[N:12]([N:13]=[N:14][C:15]=2[C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[C:11]2[CH:25]=[CH:26][CH:27]=[CH:28][C:10]=2[CH2:9]1)=[O:7])(C)(C)C.FC(F)(F)C(O)=O.[C:36]([O:40][C:41]([NH:43][C@H:44]([CH2:49][C:50]1[CH:55]=[C:54]([F:56])[C:53]([F:57])=[CH:52][C:51]=1[F:58])[CH2:45]C(O)=O)=[O:42])([CH3:39])([CH3:38])[CH3:37].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)CCl>[C:36]([O:40][C:41](=[O:42])[NH:43][CH:44]([CH2:49][C:50]1[CH:55]=[C:54]([F:56])[C:53]([F:57])=[CH:52][C:51]=1[F:58])[CH2:45][C:6]([N:8]1[CH2:17][C:16]2[N:12]([N:13]=[N:14][C:15]=2[C:18]2[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=2)[C:11]2[CH:25]=[CH:26][CH:27]=[CH:28][C:10]=2[CH2:9]1)=[O:7])([CH3:37])([CH3:38])[CH3:39]
Reactant: CC(C)(C)OC(=O)N1Cc2ccccc2-n2nnc(-c3ccc(F)cc3)c2C1
Reactant: CC(C)(C)OC(=O)N[C@@H](CC(=O)O)Cc1cc(F)c(F)cc1F
Agent: On1nnc2ccccc21
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)NC(CC(=O)N1Cc2ccccc2-n2nnc(-c3ccc(F)cc3)c2C1)Cc1cc(F)c(F)cc1F

Procedure:
3-(4-Fluoro-phenyl)-4H,6H-1,2,5,10b-tetraaza-benzo[e]azulene-5-carboxylic acid tert-butyl ester was deprotected using trifluoroacetic acid and the resulting salt was coupled with (R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid using HOBT, EDC and DIPEA. The desired compound was obtained as a viscous oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11](=[O:26])[NH:12][C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[CH:14]=1)[C:5](O)=[O:6].[NH2:27][C:28]1[S:29][CH2:30][CH2:31][N:32]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]([NH:27][C:28]2[S:29][CH2:30][CH2:31][N:32]=2)=[O:6])[CH:8]=[CH:9][C:10]=1[C:11]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[CH:14]=1)=[O:26]
Reactant: NC1=NCCS1
Reactant: O=C(O)c1ccc(C(=O)Nc2ccc(Cl)c(-c3ccccn3)c2)c(Cl)c1
Product: O=C(NC1=NCCS1)c1ccc(C(=O)Nc2ccc(Cl)c(-c3ccccn3)c2)c(Cl)c1

Procedure:
50 mg of 3-chloro-4-(4-chloro-3-(pyridin-2-yl)phenylcarbamoyl)benzoic acid was coupled to 2-amino-4,5-dihydrothiazole via Procedure G. The product was purified on reverse phase HPLC to yield 2-chloro-N1-(4-chloro-3-(pyridin-2-yl)phenyl)-N4-(4,5-dihydrothiazol-2-yl)terephthalamide. MS (Q1) 471 (M)+.
Reaction SMILES: [CH2:1]([C:7]1[CH:14]=[CH:13][C:10]([CH:11]=O)=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C(O)(=O)[CH2:16][C:17]([OH:19])=[O:18].Cl>N1CCCCC1.N1C=CC=CC=1>[CH2:1]([C:7]1[CH:14]=[CH:13][C:10]([CH:11]=[CH:16][C:17]([OH:19])=[O:18])=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: O=C(O)CC(=O)O
Reactant: CCCCCCc1ccc(C=O)cc1
Agent: Cl
Solvent: C1CCNCC1
Solvent: c1ccncc1
Product: CCCCCCc1ccc(C=CC(=O)O)cc1
Temperature: 100 °C

Procedure:
9.4 G. of p-n-hexylbenzaldehyde in 5 ml. of absolute pyridine are treated with 5.15 g. of malonic acid and 5 drops of piperidine. Then, the mixture is heated at 100° C. for 11 hours, and, subsequently, poured on to cold aqueous hydrochloric acid and extracted with ether. The p-n-hexylcinnamic acid obtained after recrystallization of the crude product from hexane/ether has a melting point of 107°-109° C.
Reaction SMILES: [CH3:1][N:2]([CH3:6])[C:3](Cl)=[S:4].[OH:7][C:8]1[C:15]([O:16][CH3:17])=[CH:14][C:13]([CH3:18])=[CH:12][C:9]=1[CH:10]=[O:11].[OH-].[K+]>O1CCCC1.O>[CH3:1][N:2]([CH3:6])[C:3]([O:7][C:8]1[C:15]([O:16][CH3:17])=[CH:14][C:13]([CH3:18])=[CH:12][C:9]=1[CH:10]=[O:11])=[S:4]
Reactant: COc1cc(C)cc(C=O)c1O
Reactant: CN(C)C(=S)Cl
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: COc1cc(C)cc(C=O)c1OC(=S)N(C)C
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
100 ml (0.8 mol) of dimethylthiocarbamoyl chloride in 150 ml of tetrahydrofuran are added at 5°-10° C. to 100 g (0.6 mol) of 2-hydroxy-3-methoxy-5-methylbenzaldehyde and 33.6 g (0.6 mol) of potassium hydroxide in 400 ml of water. The mixture is stirred at 25° C. for 15 min and, after adding 200 ml of 10% strength aqueous potassium hydroxide solution, extracted with ethyl acetate, the organic phase is washed with water and dried with sodium sulphate and, after concentrating in vacuo, the residue is recrystallised from ethanol.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][CH:9]([NH2:11])[CH3:10])[CH:5]=[CH:6][CH:7]=1.[ClH:12].[CH3:13][OH:14]>>[ClH:12].[CH:13]([NH:1][C:2]1[CH:3]=[C:4]([CH2:8][CH:9]([NH2:11])[CH3:10])[CH:5]=[CH:6][CH:7]=1)=[O:14]
Reactant: CO
Reactant: CC(N)Cc1cccc(N)c1
Agent: Cl
Product: CC(N)Cc1cccc(NC=O)c1

Procedure:
255 gm of 1-(3'-amino-phenyl)-2-amino-propane were dissolved in methanol, and the solution was acidified with ethereal hydrochloric acid. The monohydrochloride thus obtained was refluxed for 2 hours in 225 ml of formic acid, and the reaction mixture was then evaporated in a water aspirator vacuum, leaving a yellow oil which solidified upon being digested with ether. The solidified product was recrystallized from ethanol by addition of ether, yielding the compound of the formula ##STR15## which had a melting point of 150°-153° C.
Reaction SMILES: [CH3:1][O:2][C:3]1([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][C:9]=2[CH2:18]O)[CH2:7][CH2:6][CH2:5][CH2:4]1.C(Br)(Br)(Br)[Br:21].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Br:21][CH2:18][C:9]1[CH:10]=[C:11]([C:14]([F:17])([F:16])[F:15])[CH:12]=[CH:13][C:8]=1[C:3]1([O:2][CH3:1])[CH2:7][CH2:6][CH2:5][CH2:4]1
Reactant: COC1(c2ccc(C(F)(F)F)cc2CO)CCCC1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COC1(c2ccc(C(F)(F)F)cc2CBr)CCCC1
Temperature: 25 °C
Reaction time: 72 h
Yield: 98.9 %

Procedure:
To a solution of (2-(1-methoxycyclopentyl)-5-(trifluoromethyl)phenyl)methanol (10 mg, 0.036 mmol) in anhydrous dichloromethane (5 mL) was added carbon tetrabromide (14.5 mg, 0.043 mmol) followed by triphenylphosphine (11.47 mg, 0.043 mmol). The mixture was stirred at room temperature for 72 hours then the solvent was removed under reduced pressure. The residue was diluted with dichloromethane and hexanes, placed on 1 g of silica gel (Bakerbond spe disposable extraction columns, Mallinkrodt Baker Inc. Phillipsburg, N.J.) and eluted with hexanes to give the title compound (12 mg, 97.6%). 1H NMR (400 MHz, CDCl3) δ 7.78 (s, 1H) 7.46 (d, J=9.1 Hz, 1H) 7.40 (d, J=8.3 Hz, 1H) 4.97 (s, 2H) 2.94 (s, 3H) 2.30 (m, 2H) 2.0 (m, 2H) 1.85 (m, 2H) 1.74 (m, 2H).
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[CH3:10][C:11]1([CH3:19])[O:16][C:15](=[O:17])[CH2:14][C:13](=[O:18])[O:12]1>[Br-].C[N+](C)(C)CCCCCCCCCCCCCCCC>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[C:14]2[C:15](=[O:17])[O:16][C:11]([CH3:19])([CH3:10])[O:12][C:13]2=[O:18])=[CH:4][CH:3]=1
Reactant: CC1(C)OC(=O)CC(=O)O1
Reactant: O=Cc1ccc(Br)cc1
Agent: CCCCCCCCCCCCCCCC[N+](C)(C)C
Agent: [Br-]
Product: CC1(C)OC(=O)C(=Cc2ccc(Br)cc2)C(=O)O1
Temperature: 60 °C
Reaction time: 1 h
Yield: 80.3 %

Procedure:
A mixture of N,N,N-trimethylhexadecan-1-aminium bromide (15.76 g), 4-bromobenzaldehyde (80 g) and 2,2-dimethyl-1,3-dioxane-4,6-dione (68.6 g) was heated and stirred at 60° C. for 1 h, during which time a solid precipitated from solution. The mixture was allowed to cool to room temperature. The solid was collected by filtration and washed with cold water (600 mL). dried in vacuo at 50° C. to give 5-(4-bromobenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (108 g) as a colourless solid.
Reaction SMILES: I[C:2]1[C:10]2[CH2:9][C:8]([CH3:12])([CH3:11])[CH2:7][CH2:6][C:5]=2[N:4]([CH3:13])[N:3]=1.C([Mg]Cl)(C)C.[CH2:19]([Sn:23]([CH2:29][CH2:30][CH2:31][CH3:32])([CH2:25][CH2:26][CH2:27][CH3:28])Cl)[CH2:20][CH2:21][CH3:22]>C1COCC1>[CH3:13][N:4]1[C:5]2[CH2:6][CH2:7][C:8]([CH3:12])([CH3:11])[CH2:9][C:10]=2[C:2]([Sn:23]([CH2:25][CH2:26][CH2:27][CH3:28])([CH2:29][CH2:30][CH2:31][CH3:32])[CH2:19][CH2:20][CH2:21][CH3:22])=[N:3]1
Reactant: Cn1nc(I)c2c1CCC(C)(C)C2
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Agent: CC(C)[Mg]Cl
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)c1nn(C)c2c1CC(C)(C)CC2
Temperature: -16 °C
Reaction time: 0.33 h

Procedure:
In a round-bottomed flask, 3-iodo-1,5,5-trimethyl-4,5,6,7-tetrahydro-1H-indazole (140 mg, 0.48 mmol) was dissolved in THF (3 ml). The colorless solution was cooled to −16° C. (NaCl/ice bath) and isopropylmagnesium chloride (2.0M in THF, 0.27 ml, 0.54 mmol) was added dropwise. The reaction mixture was stirred at −16° C. for 20 min then tributylchlorostannane (0.15 ml, 0.55 mmol) was slowly added. The reaction mixture was allowed to warm to room temperature over 1.5 h then quenched with saturated NH4Cl, diluted with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated to afford 1,5,5-trimethyl-3-tributylstannanyl-4,5,6,7-tetrahydro-1H-indazole as a colorless oil which was used without further purification.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:37]=[CH:38][CH:39]=1)[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([O:15][CH2:16][C:17]3[CH:26]=[CH:25][C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[N:18]=3)=[CH:14][C:9]=2[N:8]=[C:7]1[CH2:27][C:28]1([C:33]([O:35][CH3:36])=[O:34])[CH2:32][CH2:31][CH2:30][CH2:29]1.[CH3:40][Si:41]([CH3:55])([CH3:54])[CH2:42][CH2:43][O:44][CH2:45][N:46]1[C:50](B(O)O)=[CH:49][CH:48]=[N:47]1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[N:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:25]=[CH:26][C:17]=1[CH2:16][O:15][C:13]1[CH:12]=[CH:11][C:10]2[N:6]([CH2:5][C:4]3[CH:37]=[CH:38][CH:39]=[C:2]([C:50]4[N:46]([CH2:45][O:44][CH2:43][CH2:42][Si:41]([CH3:55])([CH3:54])[CH3:40])[N:47]=[CH:48][CH:49]=4)[CH:3]=3)[C:7]([CH2:27][C:28]3([C:33]([O:35][CH3:36])=[O:34])[CH2:32][CH2:31][CH2:30][CH2:29]3)=[N:8][C:9]=2[CH:14]=1
Reactant: C[Si](C)(C)CCOCn1nccc1B(O)O
Reactant: COC(=O)C1(Cc2nc3cc(OCc4ccc5ccccc5n4)ccc3n2Cc2cccc(Br)c2)CCCC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: COC(=O)C1(Cc2nc3cc(OCc4ccc5ccccc5n4)ccc3n2Cc2cccc(-c3ccnn3COCC[Si](C)(C)C)c2)CCCC1
Temperature: 25 °C

Procedure:
To a 5 mL microwave vial were added methyl 1-{[1-(3-bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]methyl}cyclopentane carboxylate (59 mg, 0.1 mmol), Pd(Ph3)4 (10 mg, 0.008 mmol), (1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)boronic acid (65 mg, 0.26 mmol), Na2CO3 (0.15 mL, 2 M) and 1,4-dioxane (1.5 mL). The vial was flushed with N2 then capped and placed in a heating block at 100° C. After 16 h the mixture was cooled to RT, transferred to a round-bottomed flask and concentrated to dryness. The residue was purified using FCC to provide the title compound. MS (ESI): mass calcd. for C41H47N5O4Si, 701.94; m/z found 702.0 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[C:7]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3F)[N:12]=[CH:11][N:10]=2)=[C:6]2[O:20][CH2:21][O:22][C:5]2=[CH:4][CH:3]=1.[C:23]1([OH:29])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+].Cl>C(OCC)C.CN(C=O)C>[ClH:1].[Cl:1][C:2]1[C:7]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[O:29][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:12]=[CH:11][N:10]=2)=[C:6]2[O:20][CH2:21][O:22][C:5]2=[CH:4][CH:3]=1
Reactant: Fc1cccc2ncnc(Nc3c(Cl)ccc4c3OCO4)c12
Reactant: Oc1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: Clc1ccc2c(c1Nc1ncnc3cccc(Oc4ccccc4)c13)OCO2
Temperature: 90 °C
Yield: 34.8 %

Procedure:
A mixture of 4-(6-chloro-2,3-methylenedioxyanilino)-5-fluoroquinazoline (0.213 g), phenol (0.45 g), potassium carbonate (0.828 g) and DMF (3 ml) was stirred and heated to 90° C. for 30 hours. The mixture was evaporated and the residue was partitioned between ethyl acetate and a 2N aqueous sodium hydroxide solution. The organic layer was washed with brine, dried over magnesium sulphate and evaporated. The residue was purified by column chromatography on silica using a 99:1 mixture of methylene chloride and methanol as eluent. The material so obtained was dissolved in diethyl ether and a 6M solution of hydrogen chloride in diethyl ether (1 equivalent) was added. The resultant solid was isolated, washed with diethyl ether and dried under vacuum. There was thus obtained the title compound (0.05 g); NMR Spectrum: (DMSOd6 and CF3CO2D) 6.18 (s, 2H), 6.95 (d, 1H), 7.05 (d, 1H), 7.1 (d, 1H), 7.35 (d, 1H), 7.42 (m, 1H), 7.52–7.62 (m, 3H), 8.0 (m, 1H), 9.0 (s, 1H); Mass Spectrum: M+H+ 392 and 394.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]#[CH:8])[CH:2]=1.C[Si]([N:13]=[N+:14]=[N-:15])(C)C>O>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[N:13]=[N:14][NH:15][CH:8]=2)[CH:2]=1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Reactant: C#Cc1cccnc1
Solvent: O
Product: c1cncc(-c2c[nH]nn2)c1
Temperature: 150 °C

Procedure:
In a glass-coated bomb tube 6.5 g (0.063 mol) of 3-pyridyl acetylene (T. Sakamoto et al., Synthesis (1983) 312) and 8.7 g (0.075 mol) of trimethylsilyl azide were mixed and heated to 150° C. for 20 h. After cooling the mixture was poured into water. A colorless solid, 68, formed, which was isolated by filtration and dried. Yield: 4.0 g (0.028 mol, 44%).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:6]([S:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)=[N:7][S:8][C:9]=1[NH:10]C(OC(C)(C)C)=O)=[O:4].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[C:6]([S:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)=[N:7][S:8][C:9]=1[NH2:10])=[O:4]
Reactant: COC(=O)c1c(SCc2ccc(Cl)cc2)nsc1NC(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC(=O)c1c(SCc2ccc(Cl)cc2)nsc1N
Reaction time: 16 h
Yield: 82.3 %

Procedure:
Compound 19 (6.5 g, 15.67 mmol) is dissolved in methylene chloride (65 mL) and TFA is added (65 mL). After 16 hrs., the reaction is filtered and the solids are washed with ethyl ether. The solids are further dried in vacuo to provide 20 (4.06 g, 82%). 1H NMR (d6 DMSO): δ 7.88 (2H, br. s), 7.38 (2H, d, J=8.6 Hz), 7.32 (2H, d, J=8.6 Hz), 4.24 (2H, s), 3.69 (3H, s).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([NH:11]C(=O)C)[S:8][C:5]2=[N:6][CH:7]=1.[CH3:15][C:16]1([CH3:40])[CH2:25][CH2:24][C:23]2[N:22]=[CH:21][N:20]=[C:19]([N:26]3[CH2:32][C:31]4[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][C:30]=4[O:29][CH2:28][CH2:27]3)[C:18]=2[CH2:17]1>>[CH3:15][C:16]1([CH3:40])[CH2:25][CH2:24][C:23]2[N:22]=[CH:21][N:20]=[C:19]([N:26]3[CH2:32][C:31]4[CH:33]=[C:34]([C:2]5[CH:3]=[C:4]6[N:10]=[C:9]([NH2:11])[S:8][C:5]6=[N:6][CH:7]=5)[CH:35]=[CH:36][C:30]=4[O:29][CH2:28][CH2:27]3)[C:18]=2[CH2:17]1
Reactant: CC(=O)Nc1nc2cc(Br)cnc2s1
Reactant: CC1(C)CCc2ncnc(N3CCOc4ccc(B(O)O)cc4C3)c2C1
Product: CC1(C)CCc2ncnc(N3CCOc4ccc(-c5cnc6sc(N)nc6c5)cc4C3)c2C1

Procedure:
Prepared according to the method of example 5 by using N-(6-bromo[1,3]thiazolo[5,4-b]pyridin-2-yl)acetamide (Journal of Heterocyclic Chemistry (2003), 40, 261-268) and [4-(6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]boronic acid (reagent preparation 23) in step 1. 1H NMR (400 MHz, d6-DMSO): 8.38 (m, 2H), 7.88 (brs, 2H), 7.83 (d, 1H), 7.72 (d, 1H), 7.76 (dd, 1H), 7.05 (d, 1H), 4.63 (s, 2H), 4.33 (m, 2H), 3.83 (m, 2H), 2.72 (m, 2H), 2.46 (s, 2H), 1.61 (m, 2H), 0.83 (s, 6H); MS (EI) for C25H26N6OS: 459 (MH+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=O)=[CH:5]2.N1C=CC=CC=1.N1C(F)=NC(F)=NC=1[F:22]>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([F:22])=[O:13])=[CH:5]2
Reactant: O=C(O)c1cc2cc(Cl)ccc2[nH]1
Reactant: Fc1nc(F)nc(F)n1
Solvent: CC#N
Solvent: c1ccncc1
Product: O=C(F)c1cc2cc(Cl)ccc2[nH]1
Reaction time: 1 h

Procedure:
A solution of 5-chloro-1H-indole-2-carboxylic acid (10.0 g, 51.1 mmol) and pyridine (33.1 mmol) in acetonitrile was added to a solution of cyanuric fluoride (2.76 g, 20.4 mmol) in acetonitrile (total 340 mL) at 25° C. The reaction was followed by TLC on aliquots quenched with butylamine and appeared nearly complete at 1 hour. The mixture was poured onto ice, extracted with ether, dried (Na2SO4), and concentrated giving a solid which was used without purification (10.0 g, 99%). TLC of a butylamine-quenched aliquot showed some 5-chloroindole-2-carboxylic acid and the less polar N-butylamide. A sample was purified by chromatography on silica gel eluting with ethyl acetate-hexanes (50-100%) for characterization (16368-130-1).
Reaction SMILES: [F:1][C:2]([F:51])([F:50])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:31]=[C:32]([C:38]4[CH:43]=[CH:42][C:41]([C:44]([O:46]C)=[O:45])=[CH:40][C:39]=4[CH3:48])[CH:33]=[CH:34][C:35]=3[O:36][CH3:37])[C@H:14]2[CH3:49])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[K+].C(O)C>C(O)(=O)C>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:31]=[C:32]([C:38]4[CH:43]=[CH:42][C:41]([C:44]([OH:46])=[O:45])=[CH:40][C:39]=4[CH3:48])[CH:33]=[CH:34][C:35]=3[O:36][CH3:37])[C@H:14]2[CH3:49])[CH:4]=[C:3]([C:2]([F:1])([F:51])[F:50])[CH:8]=1
Reactant: COC(=O)c1ccc(-c2ccc(OC)c(-c3ccc(C(F)(F)F)cc3CN3C(=O)O[C@H](c4cc(C(F)(F)F)cc(C(F)(F)F)c4)[C@@H]3C)c2)c(C)c1
Agent: [K+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CCO
Product: COc1ccc(-c2ccc(C(=O)O)cc2C)cc1-c1ccc(C(F)(F)F)cc1CN1C(=O)O[C@H](c2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@@H]1C

Procedure:
methyl 2″-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (20 mg, 0.0276 mmol), aqueous potassium hydroxide (300 μL, 3M, 0.90 mmol) and ethanol (2 mL) were stirred at 20° C. for 2 hours and 20 minutes to complete the hydrolysis. The reaction mixture was acidified by acetic acid. The mixture was purified by preparative TLC on silica gel, (eluted with AcOH/EtOAc/hexanes=5/25/70, v/v) to afford 2″-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid. LCMS calc.=711.17; found=712.10 (M+1)+. 1H NMR signals are doubled because of atropoisomerism. 1H NMR (CDCl3, 500 MHz) δ 7.99 (d, J=8.0 Hz, 1H), 7.92 (d, J=8.5 Hz, 1H), 7.85 (d, J=5 Hz, 1H), 7.72-7.68 (m, 1.5H), 7.67-7.60 (m, 2.5H), 7.47-7.36 (m, 2H), 7.32 (d, J=8.0 Hz, 0.5H), 7.28 (d, J=8.0 Hz, 0.5H), 7.15 (s, 1H), 7.08 (d, J=8.5, 7.0 Hz, 1H), 5.58 (d, J=8.0 Hz, 0.5H), 5.29 (d, J=6.5 Hz, 0.5H), 4.97 (d, J=15.5 Hz, 0.5H), 4.94 (d, J=14 Hz, 0.5H), 4.16 (d, J=16 Hz, 0.5H), 3.96 (d, J=15.5 Hz, 0.5H), 3.87 (s, 3H), 3.83-3.74 (m, 1H), 2.38, 2.33 (s, 3H), 0.55 (d, J=6.5 Hz, 1.5H), 0.42 (d, J=7 Hz, 1.5H).