Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([OH:15])[CH:8]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C(O[CH:20]([NH:22]C(=O)C)[CH3:21])(C)C>FC(F)(F)C(O)=O>[NH2:22][CH:20]([C:8]1[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:10][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][C:7]=1[OH:15])[CH3:21]
Reactant: CC(C)(C)c1cc(O)cc(C(C)(C)C)c1
Reactant: CC(=O)NC(C)OC(C)C
Solvent: O=C(O)C(F)(F)F
Product: CC(N)c1c(O)cc(C(C)(C)C)cc1C(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 2.06 g (10.0 mmol) of 3,5-di-tert-butylphenol in 10 mL of trifluoroacetic acid was added 1.6 g (11.0 mmol) of N-(1-isopropoxyethyl)acetamide and the resulting mixture was stirred overnight at room temperature. The reaction mixture was concentrated in vacuo, and the residue was partitioned between EtOAc and saturated aqueous NaHCO3. The aqueous layers were separated and then extracted with EtOAc. The organic layers were combined, dried (Na2SO4), filtered and evaporated in vacuo. The product was purified on a silica gel flash chromatogrohy column eluted with 0-25% EtOAc in CH2Cl2. Evaporation of the purified fraction and drying in vacuo afforded the title compound.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:26])[CH2:4][C@H:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][C@H:15]3[C:23]4[C:18](=[C:19]([OH:25])[CH:20]=[CH:21][C:22]=4[F:24])[CH2:17][CH2:16]3)=[CH:13][C:8]=2[O:7][CH2:6]1.[CH3:27][N:28]1[C:32]2[CH:33]=[CH:34][C:35](B(O)O)=[CH:36][C:31]=2[N:30]=[CH:29]1>>[CH3:1][O:2][C:3](=[O:26])[CH2:4][C@H:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][C@H:15]3[C:23]4[C:18](=[C:19]([O:25][C:35]5[CH:34]=[CH:33][C:32]6[N:28]([CH3:27])[CH:29]=[N:30][C:31]=6[CH:36]=5)[CH:20]=[CH:21][C:22]=4[F:24])[CH2:17][CH2:16]3)=[CH:13][C:8]=2[O:7][CH2:6]1
Reactant: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c(O)ccc(F)c43)ccc21
Reactant: Cn1cnc2cc(B(O)O)ccc21
Product: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c(Oc5ccc6c(c5)ncn6C)ccc(F)c43)ccc21

Procedure:
The title compound is prepared from {(S)-6-[(R)-7-fluoro-4-hydroxy-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester and (1-methyl-1H-benzimidazol-5-yl)boronic acid following a procedure analogous to that described for Intermediate 6. LC (method 7): tR=0.36 min; Mass spectrum (ESI+): m/z=489 [M+H]+.
Reaction SMILES: [C:1]([OH:6])(=[O:5])[C:2]([NH2:4])=[O:3].[CH3:7][N:8]([CH3:40])[CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][N:20]([CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[C:21](=[O:33])[CH:22]=[CH:23][C:24]1[CH:29]=[CH:28][C:27]([N+:30]([O-])=O)=[CH:26][CH:25]=1.[H][H]>C(O)C.[Pd]>[C:1]([OH:6])(=[O:5])[C:2]([NH2:4])=[O:3].[CH3:40][N:8]([CH3:7])[CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][N:20]([CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[C:21](=[O:33])[CH:22]=[CH:23][C:24]1[CH:25]=[CH:26][C:27]([NH2:30])=[CH:28][CH:29]=1
Reactant: [H][H]
Reactant: CCOC(=O)CN(Cc1ccccc1OCCCN(C)C)C(=O)C=Cc1ccc([N+](=O)[O-])cc1
Agent: [Pd]
Agent: NC(=O)C(=O)O
Solvent: CCO
Product: CCOC(=O)CN(Cc1ccccc1OCCCN(C)C)C(=O)C=Cc1ccc(N)cc1

Procedure:
A suspension of 10 parts of [[[2-[3-(dimethylamino)propoxy]-phenyl]methyl][1-oxo-3-(4-nitrophenyl)-2-propenyl]amino]acetic acid, ethyl ester, oxamate salt (1:2) in 100 ml of ethanol is treated with 1 part of 5% palladium on carbon and placed under 3 atmospheres of gaseous hydrogen. The mixture is shaken until one equivalent of hydrogen is consumed, filtered and the solvent evaporated under reduced pressure to give the title compound.
Reaction SMILES: Br[C:2]1[S:6][C:5]([C:7]([NH:9][C:10]2[O:11][C:12]([C:15]3[O:16][CH:17]=[CH:18][CH:19]=3)=[N:13][N:14]=2)=[O:8])=[CH:4][CH:3]=1.O1C=CC=C1C1OC([NH:30][C:31]([C:33]2[CH:38]=[CH:37][CH:36]=[C:35](I)[CH:34]=2)=O)=NN=1.C(C1C=CC(B(O)O)=CC=1)#N>>[C:31]([C:33]1[CH:38]=[CH:37][C:36]([C:2]2[S:6][C:5]([C:7]([NH:9][C:10]3[O:11][C:12]([C:15]4[O:16][CH:17]=[CH:18][CH:19]=4)=[N:13][N:14]=3)=[O:8])=[CH:4][CH:3]=2)=[CH:35][CH:34]=1)#[N:30]
Reactant: O=C(Nc1nnc(-c2ccco2)o1)c1cccc(I)c1
Reactant: O=C(Nc1nnc(-c2ccco2)o1)c1ccc(Br)s1
Agent: N#Cc1ccc(B(O)O)cc1
Product: N#Cc1ccc(-c2ccc(C(=O)Nc3nnc(-c4ccco4)o3)s2)cc1

Procedure:
The title compound was synthesized in accordance with the synthesis method of compound Ia-50, using 5-bromo-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-thiophenecarboxamide prepared in Reference Example 4 instead of N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-iodobenzenecarboxamide and using commercially available 4-cyanophenylboronic acid instead of 1-methyl-5-indoleboronic acid pinacol ester.
Reaction SMILES: C([O:3][C:4](=[O:17])[CH:5]([C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[C:9]([OH:16])[CH:8]=1)[CH3:6])C.[OH-].[Na+].C(O)(=O)C>CCO.O>[OH:16][C:9]1[CH:8]=[C:7]([CH:5]([CH3:6])[C:4]([OH:17])=[O:3])[CH:12]=[CH:11][C:10]=1[N+:13]([O-:15])=[O:14]
Reactant: CCOC(=O)C(C)c1ccc([N+](=O)[O-])c(O)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Solvent: CCO
Product: CC(C(=O)O)c1ccc([N+](=O)[O-])c(O)c1
Temperature: 45 °C
Reaction time: 14 h

Procedure:
To a stirred solution of 2-(3-Hydroxy-4-nitro-phenyl)-propionic acid ethyl ester (1.48 g) in 90% aq. EtOH was added NaOH (1.24 g) at room temperature. After stirred for 14 h at 45° C., the reaction mixture was cooled to room temperature, diluted with water. The resulting aqueous layer was acidified with acetic acid and then extracted with dichloromethane. The combined organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. (1.30 mg, 99.5%, yellow solid)
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[O:5][C:6]1[C:15]2[NH:14][C:13](=[O:16])[CH:12]=[N:11][C:10]=2[N:9]=[CH:8][CH:7]=1.[C:20]([C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27](Cl)=[O:28])([CH3:23])([CH3:22])[CH3:21]>>[C:20]([C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27]([NH:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:4]([O:5][C:6]2[C:15]3[NH:14][C:13](=[O:16])[CH:12]=[N:11][C:10]=3[N:9]=[CH:8][CH:7]=2)[CH:3]=1)=[O:28])([CH3:23])([CH3:21])[CH3:22]
Reactant: Nc1cccc(Oc2ccnc3ncc(=O)[nH]c23)c1
Reactant: CC(C)(C)c1cccc(C(=O)Cl)c1
Product: CC(C)(C)c1cccc(C(=O)Nc2cccc(Oc3ccnc4ncc(=O)[nH]c34)c2)c1
Yield: 22 %

Procedure:
Method G1 was used with 8-(3-aminophenoxy)pyrido[2,3-b]pyrazin-2(1H)-one and 3-tertbutylbenzoyl chloride to afford the title compound as a white solid (14 mg, 22%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[C:14](=[O:15])[NH:13][C:12]3[N:16]=[CH:17][CH:18]=[CH:19][C:11]=3[S:10]2(=[O:21])=[O:20])[CH:6]=[C:5]([O:22][CH3:23])[N:4]=1.[Cl:24][C:25]1[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[C:26]=1[CH2:27]O.CN(C(/N=N/C(N(C)C)=O)=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.COC1C=C(N2C(=O)N(CC3C(C)=CC(F)=CN=3)C3C=CC=CC=3S2(=O)=O)C=C(OC)N=1>C(Cl)Cl>[Cl:24][C:25]1[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[C:26]=1[CH2:27][N:13]1[C:12]2[N:16]=[CH:17][CH:18]=[CH:19][C:11]=2[S:10](=[O:21])(=[O:20])[N:9]([C:7]2[CH:6]=[C:5]([O:22][CH3:23])[N:4]=[C:3]([O:2][CH3:1])[CH:8]=2)[C:14]1=[O:15]
Reactant: COc1cc(N2C(=O)Nc3ncccc3S2(=O)=O)cc(OC)n1
Reactant: OCc1c(F)cc(F)cc1Cl
Agent: CN(C)C(=O)/N=N/C(=O)N(C)C
Agent: COc1cc(N2C(=O)N(Cc3ncc(F)cc3C)c3ccccc3S2(=O)=O)cc(OC)n1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COc1cc(N2C(=O)N(Cc3c(F)cc(F)cc3Cl)c3ncccc3S2(=O)=O)cc(OC)n1
Yield: 50 %

Procedure:
The title compound (74 mg, 0.15 mmol) was prepared from 2-(2,6-dimethoxypyridin-4-yl)-2H-pyrido[2,3-e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxide (IntF3) (101 mg, 0.30 mmol), 2-chloro-4,6-difluorobenzyl alcohol (IntA22) (59 mg, 0.33 mmol), TMAD (57 mg, 0.33 mmol) and triphenyl phosphine (86 mg, 0.33 mmol) in DCM (3 mL) using the methods of (162).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH:11]=[C:12]([C:19]([O:21]CC)=[O:20])[CH:13]=[N:14]2)C1C=CC=CC=1.[Li+].[OH-]>C1COCC1.O>[CH3:1][O:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH:11]=[C:12]([C:19]([OH:21])=[O:20])[CH:13]=[N:14]2
Reactant: CCOC(=O)c1cnc2cccc(OCc3ccccc3)c2c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: COc1cccc2ncc(C(=O)O)cc12

Procedure:
A solution of ethyl 5-methoxyquinoline-3-carboxylate (2.31 g, 10 mmol) prepared in stage B of example 2 and LiOH (0.4 g, 20 mmol) in THF (20 mL) and water (0.5 mL) was refluxed for 2 hours. After cooling, the solvents were evaporated under vacuum. The solid residue was used in the next step without further purification.
Reaction SMILES: [CH2:1]([C:9]1[CH:10]=[N:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)=[N:13][CH:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[F:22][C:23]([F:47])([C:43]([F:46])([F:45])[F:44])[C:24]([F:42])([F:41])[C:25]([F:40])([F:39])[O:26][C:27]([F:38])([F:37])[CH2:28][O:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]Br>>[CH2:1]([C:9]1[CH:14]=[N:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][O:29][CH2:28][C:27]([O:26][C:25]([F:39])([F:40])[C:24]([F:41])([F:42])[C:23]([F:22])([F:47])[C:43]([F:44])([F:45])[F:46])([F:38])[F:37])=[CH:17][CH:16]=2)=[N:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: FC(F)(COCCCCCCBr)OC(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Reactant: CCCCCCCCc1cnc(-c2ccc(O)cc2)nc1
Product: CCCCCCCCc1cnc(-c2ccc(OCCCCCCOCC(F)(F)OC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)cc2)nc1

Procedure:
The title compound was prepared essentially as in Example 1 by combining 5-octyl-2-(4-hydroxyphenyl)pyrimidine (8.0 g, 28.13 mmol) and 6-(2-(nonafluorobutoxy)-2,2-difluoroethoxy)-1-bromohexane (14.15 g, 29.54 mmol; prepared by combining 1,6-dibromohexane with 2-(nonafluorobutoxy)-2,2-difluoroethanol). After refluxing overnight, the resulting crude product was isolated by filtration and further purified by recrystallization from ethanol, followed by Kugelrohr distillation (b.p. 200° C. at 0.25 torr).
Reaction SMILES: C([O:5][C:6]([C:8]1[N:13]2[C:14](=[O:19])[C@:15]([NH2:18])([O:16][CH3:17])[C@H:12]2[S:11][CH2:10][C:9]=1[CH:20]([S:27][C:28]1[NH:32][N:31]=[N:30][N:29]=1)[CH2:21][CH2:22][S:23](=[O:26])(=[O:25])[NH2:24])=[O:7])(C)(C)C.C(N(CC)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)C>C(Cl)Cl>[C:15]([NH:18][C@:15]1([O:16][CH3:17])[C:14](=[O:19])[N:13]2[C:8]([C:6]([OH:5])=[O:7])=[C:9]([CH:20]([S:27][C:28]3[NH:32][N:31]=[N:30][N:29]=3)[CH2:21][CH2:22][S:23](=[O:25])(=[O:26])[NH2:24])[CH2:10][S:11][C@H:12]12)(=[O:16])[C@@H:14]([C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)[OH:19]
Reactant: CCN(CC)c1ccccc1
Reactant: CO[C@@]1(N)C(=O)N2C(C(=O)OC(C)(C)C)=C(C(CCS(N)(=O)=O)Sc3nnn[nH]3)CS[C@@H]21
Solvent: ClCCl
Product: CO[C@@]1(NC(=O)[C@H](O)c2ccccc2)C(=O)N2C(C(=O)O)=C(C(CCS(N)(=O)=O)Sc3nnn[nH]3)CS[C@@H]21
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of 0.95 g. (2 mmol.) of 7β-amino-7α-methoxy-3-[1-(2-sulfamoylethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid t-butyl ester and 0.30 g. (2 mmol.) of N,N-diethylaniline in 100 ml. of dry methylene chloride is stirred at 0°-5° while 0.56 g. (2 mmol.) of D-O-dichloroacetylmandeloyl chloride in 10 ml. of methylene chloride is added dropwise over a 10 minute period. The mixture is stirred in the cold for 30 minutes then warmed to room temperature and stirred for an additional 30 minutes. The solution is washed with 50 ml. of cold dilute hydrochloric acid and 50 ml. of cold 5% aqueous sodium bicarbonate, dried (MgSO4) and evaporated to dryness. The residue is dissolved in a mixture of 10 ml. of trifluoroacetic acid and 2 ml. of m-dimethoxybenzene and stirred at ambient temperature for 2 hours. The excess trifluoroacetic acid is evaporated under vacuum and the residue is partitioned between 50 ml. of ether and 50 ml. of water. The pH is adjusted to 9.3-9.5 with 5% aqueous sodium carbonate and the organic phase is separated and discarded. The aqueous phase is stirred at pH 9.3-9.5 for 30 minutes, extracted with 50 ml. of ethyl acetate which is discarded, layered with fresh ethyl acetate and adjusted to pH 1.5 with dilute hydrochloric acid. The aqueous layer is extracted with three 50 ml. portions of ethyl acetate and the combined extracts are dried and evaporated to a small volume. Petroleum ether is added dropwise to precipitate the title compound which is collected and dried.
Reaction SMILES: [C:1]([CH:3]([CH:9]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)[CH2:10][C:11](OCC)=[O:12])[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].[H][H]>[Ni].C(O)C>[F:22][C:19]1[CH:20]=[CH:21][C:16]([C@@H:9]2[CH2:10][C:11](=[O:12])[NH:2][CH2:1][C@H:3]2[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[CH:17][CH:18]=1
Reactant: CCOC(=O)CC(c1ccc(F)cc1)C(C#N)C(=O)OCC
Reactant: [H][H]
Agent: [Ni]
Solvent: CCO
Product: CCOC(=O)[C@@H]1CNC(=O)C[C@H]1c1ccc(F)cc1
Yield: 46.3 %

Procedure:
5 g of diethyl 2-cyano-3-(p-fluorophenyl)glutarate obtained in Examples 1 to 3 was added to a mixture of 1.4 g of a commercially available developed Raney nickel and 120 mL of ethanol, and the reaction mixture was allowed to react at 27° C. for 6 hours under a hydrogen pressure of 2.5 atm (gauge pressure) of hydrogen. The reaction mixture was filtered through Celite, and the filtrate was concentrated. The resulting oily substance was recrystallized to obtain 2 g of ethyl trans-4-(p-fluorophenyl)-6-oxo-3-piperidinecarboxylate as a crystalline white powder.
Reaction SMILES: [CH:1]([Si:4]([CH3:14])([CH3:13])[C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1)([CH3:3])[CH3:2].[F:15][C:16]([F:27])([F:26])[C:17]1[CH:18]=[C:19]([CH2:23][CH2:24][NH2:25])[CH:20]=[CH:21][CH:22]=1>>[CH:1]([Si:4]([CH3:14])([CH3:13])[C:5]1[CH:12]=[CH:11][C:8]([CH2:9][NH:25][CH2:24][CH2:23][C:19]2[CH:20]=[CH:21][CH:22]=[C:17]([C:16]([F:15])([F:26])[F:27])[CH:18]=2)=[CH:7][CH:6]=1)([CH3:3])[CH3:2]
Reactant: CC(C)[Si](C)(C)c1ccc(C=O)cc1
Reactant: NCCc1cccc(C(F)(F)F)c1
Product: CC(C)[Si](C)(C)c1ccc(CNCCc2cccc(C(F)(F)F)c2)cc1

Procedure:
[4-(Isopropyl-dimethyl-silanyl)-benzyl]-[2-(3-trifluoromethyl-phenyl)-ethyl]-amine was prepared in analogy to example 1 from 4-(isopropyl-dimethyl-silanyl)-benzaldehyde and 2-(3-trifluoromethyl-phenyl)-ethylamine. MS (ISP): 380.2 (100) (M+H)+. 1HNMR (CDCl3, 300 MHz): δ 7.52-7.42 (m, 6H), 7.26 (d, J=7.8 Hz, 2H), 3.81 (s, 2H), 2.88-2.96 (m, 4H), 0.95 (m, 7H), 0.23 (s, 6H).
Reaction SMILES: [Br:1]Br.CO[C:5]1[CH:6]=[C:7]([C:15](=[O:17])[CH3:16])[CH:8]=[C:9](OC)[C:10]=1OC.C1(C2SC=C(C(C3C=C(OC)C(OC)=C(OC)C=3)=O)N=2)C=CC=CC=1.O>C(O)C>[Br:1][CH2:16][C:15]([C:7]1[CH:8]=[CH:9][CH:10]=[CH:5][CH:6]=1)=[O:17]
Reactant: COc1cc(C(C)=O)cc(OC)c1OC
Reactant: BrBr
Agent: COc1cc(C(=O)c2csc(-c3ccccc3)n2)cc(OC)c1OC
Solvent: CCO
Solvent: O
Product: O=C(CBr)c1ccccc1
Yield: 70 %

Procedure:
Bromine (160 mg, 1 mmol) was added dropwise to a stirred solution of an 1-(3,4,5-trimethoxyphenyl)ethanone (210 mg, 1 mmol) in ethanol (30 mL) and the solution was stirred at 0° C. for 1h and then poured into water to form a precipitate. This was recrystallized from ethanol to give bromoacetophenone (70%) and used directly for next step. A mixture of bromoacetophenone (288 mg, 1 mmol) and benzothioamide (137 mg, 1 mmol) in ethanol was refluxed for 1h. The reaction mixture was concentrated in vacuo and purified with flash column to give 2i (167 mg, 51.1%). 1H NMR (500 MHz, CDCl3) δ 8.05-8.03 (m, 2H), 7.48-7.44 (m, 3H), 7.41 (s, 1H), 7.22 (s, 2H), 3.97 (s, 6H), 3.89 (s, 3H). MS (ESI) m/z 350.1 (M+Na)+.
Reaction SMILES: [CH3:1][C:2]1[CH:16]=[CH:15][C:5]([CH:6](O)[C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[NH:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[C:18]1[C:26]([O:28][CH2:29][CH3:30])=[O:27]>>[CH3:1][C:2]1[CH:16]=[CH:15][C:5]([CH:6]([C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=2)[C:19]2[C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[NH:17][C:18]=2[C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:4][CH:3]=1
Reactant: Cc1ccc(C(O)c2ccc(C)cc2)cc1
Reactant: CCOC(=O)c1cc2ccccc2[nH]1
Product: CCOC(=O)c1[nH]c2ccccc2c1C(c1ccc(C)cc1)c1ccc(C)cc1
Yield: 97.6 %

Procedure:
Substantially the same procedure as in Reference Example 4 was repeated using 4,4'-dimethylbenzhydrol (11.8 g, 55.5 mmol) and ethyl indole-2-carboxylate (10.0 g, 52.9 mmol) to give 19.8 g (yield: 97%) of the title compound.
Reaction SMILES: [CH3:1][C:2]([CH3:12])=[CH:3][CH2:4][CH2:5][C:6]#[C:7][C:8]([O:10][CH3:11])=[O:9].[CH3:13][Cu]>>[CH3:13]/[C:6](/[CH2:5][CH2:4][CH:3]=[C:2]([CH3:12])[CH3:1])=[CH:7]/[C:8]([O:10][CH3:11])=[O:9]
Reactant: C[Cu]
Reactant: COC(=O)C#CCCC=C(C)C
Product: COC(=O)/C=C(/C)CCC=C(C)C

Procedure:
contacting the isolated product of step c with lithium dimethyl cuprate and methyl copper to produce methyl (Z)-3,7-dimethylocta-2,6-dienoate; and
Reaction SMILES: [C:1]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[S:8][C:9]([CH3:15])=[C:10]([CH2:12][CH2:13][OH:14])[N:11]=2)[CH:2]=1.[CH2:22]([O:24][C:25](=[O:37])[C:26]([O:29][C:30]1[CH:35]=[CH:34][C:33](O)=[CH:32][CH:31]=1)([CH3:28])[CH3:27])[CH3:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1.C(OCC)(=O)C>[CH2:22]([O:24][C:25](=[O:37])[C:26]([O:29][C:30]1[CH:35]=[CH:34][C:33]([O:14][CH2:13][CH2:12][C:10]2[N:11]=[C:7]([C:3]3[CH:2]=[C:1]([C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH:6]=[CH:5][CH:4]=3)[S:8][C:9]=2[CH3:15])=[CH:32][CH:31]=1)([CH3:28])[CH3:27])[CH3:23]
Reactant: CCOC(=O)C(C)(C)Oc1ccc(O)cc1
Reactant: Cc1sc(-c2cccc(-c3ccccc3)c2)nc1CCO
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCOC(=O)C(C)(C)Oc1ccc(OCCc2nc(-c3cccc(-c4ccccc4)c3)sc2C)cc1
Reaction time: 24 h
Yield: 10.7 %

Procedure:
To a solution of 2-(2-biphenyl-3-yl-5-methyl-thiazol-4-yl)-ethanol (2.58 g, 8.73 mmol), 2-(4-hydroxy-phenoxy)-2-methyl-propionic acid ethyl ester (1.9 6 g, 8.73 mmol), and triphenylphosphine (2.2 9 g, 8.73 mmol) in 90 mL tetrahydrofuran was added diisopropylazodicarboxylate (1.76 g, 8.73 mmol) dropwise over 30 min. After stirring 24 h, the solution was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered and concentrated to an orange oil. Silica gel chromatography (100 g silica gel, 15% ethyl acetate/hexanes) afforded 470 mg (11% yield) of 2-{4-[2-(2-biphenyl-3-yl-5-methyl-thiazol-4-yl)-ethoxy]-phenoxy}-2-methyl-propionic acid ethyl ester as a colorless oil. 1H NMR (400MHz, CDCl3) δ8.06 (s, 1H), 7.81 (d, 1H), 7.62 (d, 2H), 7.57 (d, 1H), 7.46-7.42 (m, 3H), 7.37-7.34 (m, 1H), 6.80-6.74 (m, 4H), 4.235 (t, 2H), 4.20 (q, 2H), 3.15 (t, 2H), 2.44 (s, 3H), 1.49 (s, 6H), 1.24 (t, 3H). MS EI+(m/e) 502.1
Reaction SMILES: Cl[C:2]1[N:24]=[C:5]2[C:6]([NH:10][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N:18]([CH3:23])[S:19]([CH3:22])(=[O:21])=[O:20])=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[N:25]1([CH2:30][CH2:31][O:32][C:33]2[CH:38]=[CH:37][C:36]([NH2:39])=[CH:35][CH:34]=2)[CH2:29][CH2:28][CH2:27][CH2:26]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:23][N:18]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[CH2:11][NH:10][C:6]1[C:5]2[N:4]([N:3]=[C:2]([NH:39][C:36]3[CH:37]=[CH:38][C:33]([O:32][CH2:31][CH2:30][N:25]4[CH2:29][CH2:28][CH2:27][CH2:26]4)=[CH:34][CH:35]=3)[N:24]=2)[CH:9]=[CH:8][CH:7]=1)[S:19]([CH3:22])(=[O:21])=[O:20]
Reactant: Nc1ccc(OCCN2CCCC2)cc1
Reactant: CN(c1ccccc1CNc1cccn2nc(Cl)nc12)S(C)(=O)=O
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: CN(c1ccccc1CNc1cccn2nc(Nc3ccc(OCCN4CCCC4)cc3)nc12)S(C)(=O)=O

Procedure:
N-Methyl-N-[2-({2-[4-(2-pyrrolidin-1-yl-ethoxy)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino}-methyl)-phenyl]-methanesulfonamide was prepared from N-{2-[(2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-methyl]-phenyl}-N-methyl-methanesulfonamide (75.0 mg, 0.205 mmol) and 4-(2-pyrrolidin-1-yl-ethoxy)-phenylamine (48.0 mg, 0.233 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (23.0 mg, 0.0421 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a tan foam (0.026 g, 24%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.79 (d, J=6.7 Hz, 1H), 7.55-7.45 (m, 3H), 7.38-7.28 (m, 3H), 6.92 (d, J=8.9 Hz, 2H), 6.65 (t, J=7.5 Hz, 1H), 6.51 (s, 1H), 6.36 (d, J=7.7 Hz, 1H), 5.21 (t, J=5.7 Hz, 1H), 4.72 (d, J=6.1 Hz, 2H), 4.10 (t, J=6.0 Hz, 2H), 3.31 (s, 3H), 3.00 (s, 3H), 2.90 (t, J=5.9 Hz, 2H), 2.66-2.59 (m, 4H), 1.85-1.77 (m, 4H). MS=536 (MH)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]([C:17]2[C:18]3[CH:39]=[CH:38][C:37]([OH:40])=[CH:36][C:19]=3[S:20][C:21]=2[C:22]2[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]3[CH2:35][CH2:34][CH2:33][CH2:32]3)=[CH:24][CH:23]=2)=O)[CH:6]=[CH:7][C:8]=1[CH2:9][N:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C1COCC1.ClCCl>[OH:40][C:37]1[CH:38]=[CH:39][C:18]2[C:17]([CH2:15][C:5]3[CH:6]=[CH:7][C:8]([CH2:9][N:10]4[CH2:14][CH2:13][CH2:12][CH2:11]4)=[C:3]([O:2][CH3:1])[CH:4]=3)=[C:21]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]4[CH2:35][CH2:34][CH2:33][CH2:32]4)=[CH:24][CH:23]=3)[S:20][C:19]=2[CH:36]=1
Reactant: COc1cc(C(=O)c2c(-c3ccc(OCCN4CCCC4)cc3)sc3cc(O)ccc23)ccc1CN1CCCC1
Agent: CC[SiH](CC)CC
Agent: [Al+3]
Agent: [H-]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Solvent: C1CCOC1
Product: COc1cc(Cc2c(-c3ccc(OCCN4CCCC4)cc3)sc3cc(O)ccc23)ccc1CN1CCCC1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 76.3 %

Procedure:
6-Hydroxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo-[b]thiophen-3-yl 3-methoxy-4-[(1-pyrrolidinyl)methyl]phenyl ketone (368006, 1.17 g, 2.10 mmol) in dry THF (40 mL) at 0° C. under argon was treated with lithium aluminum hydride (164 mg) for 1 h, then quenched with water(1 mL) and sodium hydroxide (1.0M, 3 mL). Stirring continued for 30 min. The reaction mixture was diluted with brine (100 mL) and extracted with dichloromethane (100 mL×3). The combined organic layers were dried with sodium sulfate and concentrated in vacuo to give a white foam-like material. This material was dissolved in dichloromethane (30 mL), treated with triethylsilane (3.0 mL), cooled to 0° C. under argon, and followed by slow addition of trifluroacetic acid (2.5 mL). The resulting mixture was stirred at 0° C. for 2 h and then concentrated under reduced pressure. The residue was extracted with dichloromethane (50 mL×3) which extracts were washed with saturated aqueous sodium bicarbonate (100 mL). The combined organic layers were dried with sodium sulfate and concentrated. Chromatography with Et3N:MeOH:EtOAc (5:10:85) afforded the product as a white solid (0.87 g, 76%).
Reaction SMILES: Cl[C:2]1[S:6][C:5]([C:7](=[O:9])[CH3:8])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11].[Na].[Cl:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19]([Cl:22])[C:20]=1[SH:21].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1>[Cl:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19]([Cl:22])[C:20]=1[S:21][C:2]1[S:6][C:5]([C:7](=[O:9])[CH3:8])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11]
Reactant: Sc1c(Cl)cncc1Cl
Reactant: CC(=O)c1cc([N+](=O)[O-])c(Cl)s1
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na]
Solvent: Cc1ccccc1
Product: CC(=O)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1
Temperature: 25 °C
Reaction time: 18 h
Yield: 11.5 %

Procedure:
To a solution of 1-(5-chloro-4-nitro-2-thienyl)ethanone (113 mg, 0.55 mmol) in toluene (2 mL), was added 3,5-dichloropyridine-4-thiol sodium salt (100 mg, 0.55 mmol) and potassium carbonate (113 mg, 0.825 mmol). The resulting reaction mixture was stirred at ambient temperature for 18 hours. After this time, the reaction mixture was filtered to remove the solid residues. The organic solution was diluted with ethyl acetate (15 mL) and was washed with water (2 mL×2) and brine (1 mL×2), dried (Na2SO4) and concentrated under vacuum. The residue was purified by silica gel chromatography using a mixture of 96:4 hexane and ethyl acetate as eluent to afford the title product as a solid (22 mg, 12% yield). 1H NMR (400 MHz, MeOD) δ: 8.85 (2H, m) 8.36 (1H, s), 2.52 (3H, s). MS m/z: 348.8 [M+H]+.