Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:12]([OH:14])=O)[C:10]=1[F:11])[NH:7][CH:6]=[CH:5]2.[Cl:15][C:16]1[CH:17]=[C:18]([CH2:23][CH2:24][NH:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([Si:33]([CH3:36])([CH3:35])[CH3:34])=[CH:29][CH:28]=2)[CH:19]=[CH:20][C:21]=1[Cl:22]>>[Cl:15][C:16]1[CH:17]=[C:18]([CH2:23][CH2:24][N:25]([CH2:26][C:27]2[CH:28]=[CH:29][C:30]([Si:33]([CH3:34])([CH3:36])[CH3:35])=[CH:31][CH:32]=2)[C:12]([C:9]2[C:10]([F:11])=[C:2]([Cl:1])[CH:3]=[C:4]3[C:8]=2[NH:7][CH:6]=[CH:5]3)=[O:14])[CH:19]=[CH:20][C:21]=1[Cl:22]
Reactant: O=C(O)c1c(F)c(Cl)cc2cc[nH]c12
Reactant: C[Si](C)(C)c1ccc(CNCCc2ccc(Cl)c(Cl)c2)cc1
Product: C[Si](C)(C)c1ccc(CN(CCc2ccc(Cl)c(Cl)c2)C(=O)c2c(F)c(Cl)cc3cc[nH]c23)cc1

Procedure:
5-Chloro-6-fluoro-1H-indole-7-carboxylic acid [2-(3,4-dichloro-phenyl)-ethyl]-(4-trimethylsilanyl-benzyl)-amide was prepared in analogy to example 1 from 5-chloro-6-fluoro-1H-indole-7-carboxylic acid and [2-(3,4-dichloro-phenyl)-ethyl]-(4-trimethylsilanyl-benzyl)-amine. MS (ISP) 547.2/549.3/551.3 (96/100/37) (M+H)+.
Reaction SMILES: [CH2:1]([O:4][C:5]([NH:7][CH2:8][C:9]([OH:11])=[O:10])=[O:6])[CH:2]=[CH2:3].Cl.[C:13](=O)(O)[O-].[Na+]>CO>[CH3:13][O:10][C:9](=[O:11])[CH2:8][NH:7][C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[O:6]
Reactant: C=CCOC(=O)NCC(=O)O
Reactant: O=C([O-])O
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: C=CCOC(=O)NCC(=O)OC

Procedure:
A solution of 0.06 mol of N-(allyloxycarbonyl)glycine, prepared as described by F. Guibe, O. Dangles, and G. Balavione in Tetrahedron Letters, 1986, 27, 2365-2368, and 0.066 mol of HCl in 100 mL of CH3OH is stirred at reflux for 8 hours. The solution is then cooled and treated with 0.066 mol of sodium bicarbonate. The solvent is removed by rotary evaporator, and the residue is dissolved in diethyl ether, filtered, dried over MgSO4, and filtered. The solvent is removed by rotary evaporator to give N-(allyloxycarbonyl)glycine methyl ester.
Reaction SMILES: C([Li])CCC.[CH2:6]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:13]=[CH:14][C:15]([CH3:18])=[N:16][CH:17]=1)[CH3:7].CN(C)[C:21](=[O:23])[CH3:22].Cl>CCCCCC.O1CCCC1>[CH2:6]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][C:21](=[O:23])[CH3:22])=[N:16][CH:17]=1)[CH3:7]
Reactant: CC(=O)N(C)C
Reactant: CCOCCOc1ccc(C)nc1
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCOCCOc1ccc(CC(C)=O)nc1
Reaction time: 0.17 h

Procedure:
2.5 ml of a 2.5 M solution of n-butyllithium in hexane are added dropwise at 5° C. to a solution of 1 g (5.5 mmol) of 5-(2-ethoxyethoxy)-2-methylpyridine in 20 ml of tetrahydrofuran. The mixture is stirred at 0°-5° C. for 10 minutes and then 530 mg (6 mmol) of N,N-dimethylacetamide dissolved in a little tetrahydrofuran are added. After stirring at room temperature for 90 minutes, the pH is adjusted to 5 with dilute hydrochloric acid and the tetrahydrofuran is stripped off. The residue is extracted with ethyl acetate, and the organic phase is dried with sodium sulphate and evaporated. Yield: 580 mg (47% of theory), content according to GC/MS:75%.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][OH:8])[CH2:3][CH2:2]1.[CH2:9]=[C:10]1[O:14][C:12](=[O:13])[CH2:11]1>O1CCCC1>[OH:8][CH2:7][CH:4]1[CH2:5][CH2:6][N:1]([C:12](=[O:13])[CH2:11][C:10](=[O:14])[CH3:9])[CH2:2][CH2:3]1
Reactant: OCC1CCNCC1
Reactant: C=C1CC(=O)O1
Solvent: C1CCOC1
Product: CC(=O)CC(=O)N1CCC(CO)CC1
Temperature: 0 °C
Reaction time: 1 h
Yield: 90 %

Procedure:
A solution of 25 g (0.22 mol) of 4-piperidine methanol in 200 ml tetrahydrofuran was added dropwise to a solution of 18 g of diketene (0.2 mol) in 200 ml tetrahydrofuran at −5 to 0° C. After 1 h stirring at 0° C. no more starting material was detected by thin layer chromatography. The reaction mixture was evaporated and the residue purified by column chromatography. This gave 35.40 g (0.18 mol, 83% yield) of a colorless oil.
Reaction SMILES: [NH2:1][C:2]1[C:10]2[CH2:9][CH2:8][O:7][C:6]=2[C:5]([C:11]([OH:13])=O)=[CH:4][C:3]=1[Cl:14].[NH2:15][CH2:16][CH2:17][C:18]12[CH2:25][CH2:24][CH2:23][N:22]1[CH2:21][CH2:20][CH2:19]2>O1CCCC1>[NH2:1][C:2]1[C:10]2[CH2:9][CH2:8][O:7][C:6]=2[C:5]([C:11]([NH:15][CH2:16][CH2:17][C:18]23[CH2:19][CH2:20][CH2:21][N:22]2[CH2:23][CH2:24][CH2:25]3)=[O:13])=[CH:4][C:3]=1[Cl:14]
Reactant: Nc1c(Cl)cc(C(=O)O)c2c1CCO2
Reactant: NCCC12CCCN1CCC2
Solvent: C1CCOC1
Product: Nc1c(Cl)cc(C(=O)NCCC23CCCN2CCC3)c2c1CCO2
Yield: 78.3 %

Procedure:
Into an agitating solution of 4-amino-5-chloro-2,3-dihydrobenzo[b]furan-7-carboxylic acid (3.21 g) in absolute tetrahydrofuran (50 ml), was added little by little 1,1-carbonylimidazole (2.43 g) and after lapsed 1 hour, a solution of 5-(2-aminoethyl)-1-azabicyclo[3.3.0]octane (2.31 g) in absolute tetrahydrofuran (2 ml) was added therein to reflux for 1 hour. After cooled, the solvent was distilled out in vacuo, a residue was dissolved into chloroform, washed with saturated sodium hydrogen carbonate solution and then water, and thereafter, the solvent was distilled out in vacuo. The resulting residue was refined by alumina column chromatography (developing solvent: chloroform) to afford 4.1 g of the titled compound.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH3:10])([O-:3])=[O:2].[C:11](#[N:14])[CH:12]=[CH2:13]>>[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][CH2:13][CH2:12][C:11]#[N:14])([O-:3])=[O:2]
Reactant: C=CC#N
Reactant: Cc1ccccc1[N+](=O)[O-]
Product: N#CCCCc1ccccc1[N+](=O)[O-]

Procedure:
reaction of ortho-nitrotoluene with acrylonitrile to give 4-(2-nitrophenyl)-butyronitrile,
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH2:7][NH2:8].F[C:15]1[CH:23]=[N:22][CH:21]=[CH:20][C:16]=1[C:17]([OH:19])=[O:18]>>[F:1][C:2]([F:12])([F:13])[O:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH2:7][NH:8][C:20]1[CH:21]=[N:22][CH:23]=[CH:15][C:16]=1[C:17]([OH:19])=[O:18]
Reactant: O=C(O)c1ccncc1F
Reactant: NCc1cccc(OC(F)(F)F)c1
Product: O=C(O)c1ccncc1NCc1cccc(OC(F)(F)F)c1
Yield: 4 %

Procedure:
The title compound was prepared in 4% yield from 3-trifluoromethoxy-benzylamine and 3-fluoroisonicotinic acid according to the procedure for the preparation of Example 3. 1H NMR (400 MHz, DMSO-d6): δ 13.47 (br s, 1H), 8.11 (br s, 1H), 7.84 (br s, 1H), 7.59 (s, 1H), 7.24-7.51 (m, 4H), 4.64 (s, 2H). [M+H] calc'd for C14H11F3N2O3, 313. found 313.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=3)[N:11]([C:20](Cl)=[O:21])[C:10]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([CH3:33])([CH3:32])[CH2:30][OH:31])=[CH:25][C:24]=3[O:34][CH2:35][CH3:36])=[N:9]2)=[CH:4][CH:3]=1.[NH:37]1[CH2:42][CH2:41][NH:40][CH2:39][C:38]1=[O:43]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@@H:12]([C:13]3[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=3)[N:11]([C:20]([N:40]3[CH2:41][CH2:42][NH:37][C:38](=[O:43])[CH2:39]3)=[O:21])[C:10]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([CH3:32])([CH3:33])[CH2:30][OH:31])=[CH:25][C:24]=3[O:34][CH2:35][CH3:36])=[N:9]2)=[CH:4][CH:3]=1
Reactant: CCOc1cc(C(C)(C)CO)ccc1C1=N[C@@H](c2ccc(Cl)cc2)[C@@H](c2ccc(Cl)cc2)N1C(=O)Cl
Reactant: O=C1CNCCN1
Product: CCOc1cc(C(C)(C)CO)ccc1C1=N[C@@H](c2ccc(Cl)cc2)[C@@H](c2ccc(Cl)cc2)N1C(=O)N1CCNC(=O)C1

Procedure:
4-{(4S,5R)-4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(2-hydroxy-1,1-dimethyl-ethyl)-phenyl]-4,5-dihydro-imidazole-1-carbonyl}-piperazin-2-one was prepared from (4S,5R)-4,5-bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(2-hydroxy-1,1-dimethyl-ethyl)-phenyl]-4,5-dihydro-imidazole-1-carbonyl chloride (example 12g) and 2-piperazinone (Avocado Organics) in an analogous manner as described in example 25. LR-MS: 609.4 [(M+H)+]
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[C:9]1(B(O)O)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>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.C(O)C>[Br:8][C:5]1[CH:4]=[N:3][C:2]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:7][CH:6]=1
Reactant: Brc1ccc(Br)nc1
Reactant: OB(O)c1ccccc1
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: c1ccccc1
Solvent: CCO
Product: Brc1ccc(-c2ccccc2)nc1

Procedure:
10 g (42.2 mmol) of 2,5-dibromopyridine, 5.2 g (42.2 mmol) of phenylboronic acid and 30 ml of benzene are placed in a 250 ml three-necked round-bottomed flask, 1.5 g (1.3 mmol) of tetrakis(triphenylphosphine)palladium, 30 ml of benzene and 30 ml of aqueous 2 M sodium carbonate solution and 1.4 ml of ethanol are added and the mixture is refluxed for 17 h.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9]#[N:10])[C:5](Cl)=[N:6][CH:7]=1.[NH2:11][NH2:12]>C(O)CCC>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH2:10])=[N:12][NH:11][C:5]2=[N:6][CH:7]=1
Reactant: NN
Reactant: N#Cc1cc(Br)cnc1Cl
Solvent: CCCCO
Product: Nc1n[nH]c2ncc(Br)cc12
Temperature: 25 °C

Procedure:
(Step 7-i) To a solution of 5-bromo-2-chloropyridine-3-carbonitrile (2 g, 9.22 mmol) in 30 mL n-butanol was added 2 mL anhydrous hydrazine. The reaction mixture was heated under reflux for 14 hrs and allowed to cool to room temperature. The solvent was removed by evaporation and the residue was poured into a saturated NaHCO3 solution. The resulting precipitate was collected and washed with water. After drying in vacuo, the product, 5-bromo-1H-pyrazolo[3,4-b]pyridin-3-amine, can be used directly without further purification.
Reaction SMILES: C(N(C(C)C)C(C)C)C.[C:10]1(=[O:17])[O:16][C:14](=[O:15])[CH2:13][CH2:12][CH2:11]1.[CH:18]1[C:28]2[CH:27]=[CH:26][C:25]3[CH:29]=[CH:30][CH:31]=[CH:32][C:24]=3[CH:23]([CH:33]3[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)[C:22]=2[CH:21]=[CH:20][CH:19]=1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH:29]1[C:25]2[CH:26]=[CH:27][C:28]3[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=3[CH:23]([CH:33]3[CH2:34][CH2:35][N:36]([C:14](=[O:15])[CH2:13][CH2:12][CH2:11][C:10]([OH:16])=[O:17])[CH2:37][CH2:38]3)[C:24]=2[CH:32]=[CH:31][CH:30]=1
Reactant: C1=Cc2ccccc2C(C2CCNCC2)c2ccccc21
Reactant: O=C1CCCC(=O)O1
Agent: CN(C)c1ccncc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(O)CCCC(=O)N1CCC(C2c3ccccc3C=Cc3ccccc32)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
0.04 gram (0.36 millimole) of 4-dimethylaminopyridine, 0.94 gram (7.26 millimoles) of ethyl diisopropylamine, and 0.41 gram (3.63 millimoles) of glutaric anhydride were added successively to a solution of 1.00 gram (3.63 millimoles) of 4-(5H-dibenzo[a,d]cyclohepten-5-yl)-piperidine and the resulting mixture stirred at ambient temperature for two hours. The reaction mixture was diluted with 100 milliliters of methylene chloride and washed with aqueous hydrochloric acid and then with brine. The washed solution was dried over magnesium sulfate, the drying agent filtered and the solution evaporated in vacuo whereupon a foam was produced which when triturated with hot acetonitrile produced white crystals. The crystals were recrystallized from hot acetic acid/acetonitrile to obtain 4-(5H-dibenzo[a,d]cyclohepten-5-yl)-δ-oxo-1-piperidinepentanoic acid product, m.p. 180°-186° C. The product had elemental analyses as follows:
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][CH:6]=1)=O.[F:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]([NH2:22])=[S:21])[CH:16]=[CH:17][CH:18]=1>>[Br:11][C:8]1[CH:9]=[CH:10][C:5]([C:3]2[N:22]=[C:20]([NH:19][C:15]3[CH:16]=[CH:17][CH:18]=[C:13]([F:12])[CH:14]=3)[S:21][CH:2]=2)=[CH:6][CH:7]=1
Reactant: NC(=S)Nc1cccc(F)c1
Reactant: O=C(CBr)c1ccc(Br)cc1
Product: Fc1cccc(Nc2nc(-c3ccc(Br)cc3)cs2)c1

Procedure:
The title compound is prepared analogously to Example 2-1 step B using 2-bromo-1-(4-bromophenyl)-ethanone and 3-fluorophenylthiourea: (M+H)+350.9.
Reaction SMILES: [C:1]1([CH2:14][OH:15])[C:13]2[CH2:12][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:16]1(=[O:22])[O:21][C:19](=[O:20])[CH2:18][CH2:17]1>ClCl>[C:1]1([CH2:14][O:15][C:16](=[O:22])[CH2:17][CH2:18][C:19]([OH:21])=[O:20])[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: O=C1CCC(=O)O1
Reactant: OCc1cccc2c1Cc1ccccc1-2
Agent: ClCl
Product: O=C(O)CCC(=O)OCc1cccc2c1Cc1ccccc1-2
Reaction time: 6 h

Procedure:
Fluorenemethanol (10.0 g, 51.0 mmol) was dissolved in 150 ml CH2 Cl2, and succinic anhydride (5.6 g, 56 mmol) was added. The solution was stirred for 6 h, and a further portion of succinic anhydride (2.5 g, 25 mmol) was added, and stirring continued overnight. The reaction appeared complete by TLC. The solvent was then removed, and the residue extracted with ethyl acetate, washed with 1% HCl, water, brine, dried (MgSO4) and evaporated to an oil which crystallized on standing. A quantitative yield of crude product was obtained which was used without further purification.
Reaction SMILES: [Cl:1][C:2]1[C:29]([Cl:30])=[CH:28][C:5]2[NH:6][C:7](=S)[CH2:8][C:9]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[C:25]5[CH:24]=[CH:23][N:22]=[CH:21][C:20]=5[N:19]=[C:18]4[CH3:26])=[CH:13][CH:12]=3)=[N:10][C:4]=2[CH:3]=1.[CH2:31]([CH2:33][NH2:34])[OH:32]>C(O)CCC.C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:29]([Cl:30])=[CH:28][C:5]2[N:6]=[C:7]([NH:34][CH2:33][CH2:31][OH:32])[CH2:8][C:9]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[C:25]5[CH:24]=[CH:23][N:22]=[CH:21][C:20]=5[N:19]=[C:18]4[CH3:26])=[CH:13][CH:12]=3)=[N:10][C:4]=2[CH:3]=1
Reactant: Cc1nc2cnccc2n1-c1ccc(C2=Nc3cc(Cl)c(Cl)cc3NC(=S)C2)cc1
Reactant: NCCO
Solvent: Cc1ccccc1
Solvent: CCCCO
Product: Cc1nc2cnccc2n1-c1ccc(C2=Nc3cc(Cl)c(Cl)cc3N=C(NCCO)C2)cc1

Procedure:
A mixture of 7,8-dichloro-2,3-dihydro-4-[4-(2-methylimidazo[4,5-c]pyrid-1-yl)phenyl]-1H-[1,5]benzodiazepin-2-thione (453 mg, 1.0 mmol), ethanolamine (122 mg, 2.0 mmol) and red mercuric oxide (216 mg, 1.0 mmol) was heated in n-butanol (5 ml) at reflux for 1 hour. The mixture was cooled, diluted with an equal volume of toluene and filtered through Arbocel filter aid. The filtrate was concentrated under reduced pressure, and the residue was purified by flash chromatography, eluting with ethyl acetate:methanol=4:1. Fractions containing product were evaporated yielding 7,8-dichloro-2-[2-hydroxyethylamino]-4-[4-(2-methylimidazo[4,5-c]pyrid-1-yl)phenyl]-3H-[1,5]-benzodiazepine as a yellow foam, (345 mg, 72%).
Reaction SMILES: [Br:1][C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)[NH:10][C:4]=2[CH:3]=1.Br[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O.C(OCC)(=O)C.[Cu]I>[Br:1][C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)[N:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[C:4]=2[CH:3]=1
Reactant: Cn1cc(-c2cc3cnc(Br)cc3[nH]2)cn1
Reactant: Brc1ccccn1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: CCOC(C)=O
Product: Cn1cc(-c2cc3cnc(Br)cc3n2-c2ccccn2)cn1
Temperature: 180 °C
Reaction time: 0.75 h
Yield: 48 %

Procedure:
6-Bromo-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine (Preparation 22, 27 mg 0.10 mmole) and 2-bromopyridine (24 mg, 15 uL, 0.15 mmole) were dissolved in DMA (0.7 ml) and potassium carbonate (20 mg, 0.14 mmole) and copper(I) iodide (4.0 mg, 0.022 mmole) were added. The reaction was placed under argon and heated by microwave at 180° C. for 60 minutes followed by 210° C. for 45 minutes. The reaction was taken up in ethyl acetate (25 mL) and the solution washed with water (3×7 mL) and brine. The aqueous solutions were backwashed with a single portion of ethyl acetate. The combined organic layers were dried (MgSO4) and concentrated in vacuo. The residue was purified using preparative TLC eluting with ethyl acetate to afford the title compound 17 mg (48%). 1H-NMR (CDCl3, 500 MHz): 3.88 (s, 3H), 6.72 (d, J=0.95 Hz, 1H), 7.18 (d of t, J=0.95, 7.88 Hz, 1H), 7.24 (s, 1H), 7.26 (d, J=0.63 Hz, 1H), 7.44 (ddd, J=0.95, 4.73, 7.57 Hz, 1H), 7.51 (t, J=0.95 Hz, 1H), 7.86 (t of d, J=1.89, 7.57 Hz, 1H), 8.66 (d, J=0.95 Hz, 1H), 8.73 (ddd, J=0.95, 1.89, 4.73 Hz, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][C:3]=1[C:4](Cl)=[O:5].CCN(CC)CC.[C:22]([C:24]1[C:25]([C:38]([F:41])([F:40])[F:39])=[C:26]2[C:30](=[CH:31][CH:32]=1)[N:29]([CH2:33][C:34](=[NH:37])[NH:35]O)[CH:28]=[CH:27]2)#[N:23]>CC#N>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][C:3]=1[C:4]1[O:5][N:37]=[C:34]([CH2:33][N:29]2[C:30]3[C:26](=[C:25]([C:38]([F:41])([F:39])[F:40])[C:24]([C:22]#[N:23])=[CH:32][CH:31]=3)[CH:27]=[CH:28]2)[N:35]=1
Reactant: O=C(Cl)c1cc(C(F)(F)F)ccc1Cl
Reactant: N#Cc1ccc2c(ccn2CC(=N)NO)c1C(F)(F)F
Solvent: CCN(CC)CC
Solvent: CC#N
Product: N#Cc1ccc2c(ccn2Cc2noc(-c3cc(C(F)(F)F)ccc3Cl)n2)c1C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h
Yield: 74.8 %

Procedure:
2-Chloro-5-(trifluoromethyl)benzoyl chloride (0.017 g, 0.071 mmol), Et3N (0.008 g. 0.078 mmol) and 2-[5-cyano-4-(trifluoromethyl)-1H-indol-1-yl]-N-hydroxyethanimidamide (0.020 g, 0.071 mmol) were combined in CH3CN (1.5 mL). After stirring at rt for 1 h, the mixture was heated to 150° C. in a microwave for 10 min. Purification (SiO2, EtOAc/hexanes) afforded the title compound (0.025 g): MS (ESI): m/z 469 (M−1).
Reaction SMILES: CC([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23]([CH2:25][NH2:26])[O:22][C:21]3=[O:27])=[CH:16][C:15]=2[F:28])[CH2:10][CH2:9]1)=[O:7])(C)C.N1C=CC=CC=1.[C:35](OC(=O)C)(=[O:37])[CH3:36]>C(Cl)Cl>[C:35]([NH:26][CH2:25][C@@H:23]1[O:22][C:21](=[O:27])[N:20]([C:17]2[CH:18]=[CH:19][C:14]([CH:11]3[CH2:10][CH2:9][N:8]([C:6]([OH:5])=[O:7])[CH2:13][CH2:12]3)=[C:15]([F:28])[CH:16]=2)[CH2:24]1)(=[O:37])[CH3:36]
Reactant: CC(=O)OC(C)=O
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(N3C[C@H](CN)OC3=O)cc2F)CC1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(=O)NC[C@H]1CN(c2ccc(C3CCN(C(=O)O)CC3)c(F)c2)C(=O)O1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A solution of (S)-(-)-4-[4-[5-(aminomethyl)-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester (EXAMPLE 20, Step 8, 9.45 g) in dry methylene chloride (96 mL) under N2 is treated with pyridine (5.82 mL) and acetic anhydride (3.40 mL), and the resulting mixture is stirred at ambient temperature for four hours, diluted with methylene chloride (25 mL), washed with water (25 mL), saturated aqueous sodium bicarbonate (25 mL) and saline (25 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product which is then chromatographed on silica gel (230-400 mesh, 350 g), eluting with a gradient of methanol/chloroform (2.5/97.5-7.5/92.5). Pooling and concentration of those fractions with an Rf =0.51 by TLC (methanol/chloroform, 10/90) gives the title compound, mp 144-146° C.
Reaction SMILES: Br[C:2]1[N:3]=[CH:4][N:5]([C:7]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[C:15]([CH3:23])[CH:14]=3)[CH:10]=[C:9]([C:24]([F:27])([F:26])[F:25])[N:8]=2)[CH:6]=1.[NH2:28][C:29]1[N:34]=[CH:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][N:30]=1>>[CH3:23][C:15]1[CH:14]=[C:13]([C:11]2[CH:10]=[C:9]([C:24]([F:27])([F:26])[F:25])[N:8]=[C:7]([N:5]3[CH:6]=[C:2]([C:32]4[CH:31]=[N:30][C:29]([NH2:28])=[N:34][CH:33]=4)[N:3]=[CH:4]3)[N:12]=2)[CH:18]=[CH:17][C:16]=1[C:19]([F:22])([F:21])[F:20]
Reactant: Cc1cc(-c2cc(C(F)(F)F)nc(-n3cnc(Br)c3)n2)ccc1C(F)(F)F
Reactant: CC1(C)OB(c2cnc(N)nc2)OC1(C)C
Product: Cc1cc(-c2cc(C(F)(F)F)nc(-n3cnc(-c4cnc(N)nc4)c3)n2)ccc1C(F)(F)F

Procedure:
The title compound was prepared from 2-(4-bromo-imidazol-1-yl)-4-(3-methyl-4-trifluoromethyl-phenyl)-6-trifluoromethyl-pyrimidine (example E.48) (0.23 g, 0.5 mmol) and commercially available 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (0.14 g, 0.65 mmol) according to the general procedure VI. Obtained as a yellow solid (0.168 g, 72%). MS (ISP) 466.1 [(M+H)+]; mp 297° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])[CH:10]=1)[C:5]([OH:7])=[O:6].C(Cl)(=O)C(Cl)=O.[CH2:25](O)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C(Cl)Cl.CN(C)C=O.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:13])[CH3:14])[CH:10]=1)[C:5]([O:7][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:6]
Reactant: OCc1ccccc1
Reactant: CC(C)(C)[Si](C)(C)Oc1cc(Cl)cc(C(=O)O)c1
Agent: CN(C)c1ccncc1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)Oc1cc(Cl)cc(C(=O)OCc2ccccc2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture of the acid 14 (3.80 g, 13.3 mmol) and oxalyl chloride (5.8 mL, 66 mmol) in methylene chloride (60 mL) was added ca. 0.05 mL of N,N-dimethylformamide as a catalyst. After stirring 1 hr at ambient temperature, the reaction was evaporated in vacuo, diluted with methylene chloride, and reacted with benzyl alcohol (1.38 mL, 13.3 mmol) and 4-(N,N-dimethylamino)pyridine (1.60 g, 13.3 mmol). After stirring 16 hrs at ambient temperature, the solution was washed with dilute aqueous HCl, dilute aqueous NaHCO3, and brine, dried over Na2SO4, and filtered. The filtrate was then evaporated in vacuo giving a quantitative yield of gold oil. 1H NMR (300 MHz, CDCl3) δ 7.64 (t, 1H, J=1.5 Hz), 7.45-7.28 (m, 6H), 7.02 (m, 1H), 5.35 (s, 2H), 0.98 (s, 9H), 0.22 (s, 6H).
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([C@@H:15]([CH3:25])[CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:11][CH:10]=2)O1.Br[C:28]1[C:29]2[C:30]3[CH:52]=[C:51]([CH3:53])[S:50][C:31]=3[C:32](=[O:49])[N:33]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[C:34]=2[C:35]([CH3:40])=[CH:36][C:37]=1[O:38][CH3:39]>>[CH3:39][O:38][C:37]1[CH:36]=[C:35]([CH3:40])[C:34]2[N:33]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:46])([CH3:47])[CH3:48])[C:32](=[O:49])[C:31]3[S:50][C:51]([CH3:53])=[CH:52][C:30]=3[C:29]=2[C:28]=1[C:9]1[CH:10]=[CH:11][C:12]([C@@H:15]([CH3:25])[CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[CH:13][CH:14]=1
Reactant: C[C@@H](CNC(=O)OC(C)(C)C)c1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Reactant: COc1cc(C)c2c(c1Br)c1cc(C)sc1c(=O)n2COCC[Si](C)(C)C
Product: COc1cc(C)c2c(c1-c1ccc([C@@H](C)CNC(=O)OC(C)(C)C)cc1)c1cc(C)sc1c(=O)n2COCC[Si](C)(C)C
Yield: 37.9 %

Procedure:
Following General Procedure B, (R)-tert-butyl 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propylcarbamate (0.12 g, 0.33 mmol) was reacted with 9-bromo-8-methoxy-2,6-dimethyl-5-((2-(trimethylsilyl)ethoxy)methyl)thieno[2,3-c]quinolin-4(5H)-one (0.12 g, 0.33 mmol) to afford the desired product (78 mg, 45%) as a solid: ESI MS m/z 623 [C34H46N2O5SSi+H]+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][C:11]=1[CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19].[CH:22]1([CH:25]([C:32]2[CH:37]=[CH:36][N:35]=[C:34]([CH2:38]O)[CH:33]=2)[CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:24][CH2:23]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1.C1(C)C=CC=CC=1>[CH:22]1([CH:25]([C:32]2[CH:37]=[CH:36][N:35]=[C:34]([CH2:38][O:16][C:13]3[CH:14]=[CH:15][C:10]([C:3]4[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=4[F:1])=[C:11]([CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH:12]=3)[CH:33]=2)[CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:24][CH2:23]1
Reactant: CCOC(=O)CC(c1ccnc(CO)c1)C1CC1
Reactant: COc1ccc(F)c(-c2ccc(O)cc2CC(C)(C)C)c1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CCOC(=O)CC(c1ccnc(COc2ccc(-c3cc(OC)ccc3F)c(CC(C)(C)C)c2)c1)C1CC1
Reaction time: 14 h
Yield: 39.4 %

Procedure:
Under a nitrogen atmosphere, to a solution of 2′-fluoro-5′-methoxy-2-neopentyl-[1,1′-biphenyl]-4-ol (100 mg), ethyl 3-cyclopropyl-3-(2-(hydroxymethyl)pyridin-4-yl)propanoate (94 mg) and triphenylphosphine (182 mg) in THF (3.0 mL) was added a 40% solution of diethyl azodicarboxylate in toluene (315 μL) at room temperature, and the mixture was stirred for 14 hr. Triphenylphosphine (182 mg) and a 40% solution of diethyl azodicarboxylate in toluene (315 μL) were added to the reaction mixture, and the mixture was further stirred at room temperature for 14 hr. The solvent of the reaction mixture was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (71 mg) as a pink oil.