Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][C@H:6]([C:20]([NH:22][CH2:23][CH2:24][CH:25]([F:34])[CH2:26][C@@H:27]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[NH2:28])=[O:21])[CH:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4].[N+:35]([C:38]1[CH:43]=[CH:42][C:41]([S:44](Cl)(=[O:46])=[O:45])=[CH:40][CH:39]=1)([O-:37])=[O:36]>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:20]([NH:22][CH2:23][CH2:24][CH:25]([F:34])[CH2:26][C@@H:27]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[NH:28][S:44]([C:41]1[CH:40]=[CH:39][C:38]([N+:35]([O-:37])=[O:36])=[CH:43][CH:42]=1)(=[O:45])=[O:46])=[O:21])[CH:7]([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4]
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)Cl)cc1
Reactant: CCOC(=O)[C@@H](N)CC(F)CCNC(=O)[C@@H](NC(=O)OC)C(c1ccccc1)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: CCOC(=O)[C@H](CC(F)CCNC(=O)[C@@H](NC(=O)OC)C(c1ccccc1)c1ccccc1)NS(=O)(=O)c1ccc([N+](=O)[O-])cc1
Temperature: 85 °C
Reaction time: 8 h
Yield: 21.1 %

Procedure:
To a solution of the material from Step 4 (170 mg, 0.359 mmol) in pyridine (1.5 mL) at room temperature were added 4-nitrobenzenesulfonyl chloride (119 mg, 0.539 mmol) and DMAP (8.77 mg, 0.072 mmol). The reaction mixture was stirred at 85° C. overnight. Upon cooling to rt, the reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography on silica gel using ethyl acetate-hexanes (0:100 to 90:10) to afford 50 mg of the title compound as a yellow foam. LCMS (M+1)=659.
Reaction SMILES: [CH3:1][O:2]C1C=CC(C#CC(OCC)=O)=C(OC)C=1C1C(C)=CC2C(C)(C)CCC(C)(C)C=2C=1.[CH3:33][O:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]#[C:42][C:43]([OH:45])=[O:44])=[C:37](OC)[C:36]=1[C:48]1[C:57]([CH3:58])=[CH:56][C:55]2[C:54]([CH3:60])([CH3:59])[CH2:53][CH2:52][C:51]([CH3:62])([CH3:61])[C:50]=2[CH:49]=1>>[CH3:1][O:2][CH2:33][O:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]#[C:42][C:43]([OH:45])=[O:44])=[CH:37][C:36]=1[C:48]1[C:57]([CH3:58])=[CH:56][C:55]2[C:54]([CH3:59])([CH3:60])[CH2:53][CH2:52][C:51]([CH3:62])([CH3:61])[C:50]=2[CH:49]=1
Reactant: CCOC(=O)C#Cc1ccc(OC)c(-c2cc3c(cc2C)C(C)(C)CCC3(C)C)c1OC
Reactant: COc1ccc(C#CC(=O)O)c(OC)c1-c1cc2c(cc1C)C(C)(C)CCC2(C)C
Product: COCOc1ccc(C#CC(=O)O)cc1-c1cc2c(cc1C)C(C)(C)CCC2(C)C

Procedure:
In a manner similar to that of Example 2(h), starting from 439 mg (1 mmol) of ethyl [4-methoxy-methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]propynoate, 375 mg (91%) of [4-methoxy-methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]propynoic acid having a melting point of 168°-170° C. were obtained.
Reaction SMILES: [C:1]1(P(C2C=CC=CC=2)C2C=CC=CC=2CN[C@@H]2CCCC[C@H]2NCC2C=CC=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:49][C:50]([F:89])([F:88])[C:51]1[CH:52]=[C:53]([CH:81]=[C:82]([C:84]([F:87])([F:86])[F:85])[CH:83]=1)[CH2:54][N:55]([CH2:62][C:63]1[CH:68]=[C:67]([C:69]([F:72])([F:71])[F:70])[CH:66]=[CH:65][C:64]=1[C:73]([CH:75]1[CH2:80][CH2:79][CH2:78][CH2:77][CH2:76]1)=[O:74])[C:56]1[N:57]=[N:58][N:59]([CH3:61])[N:60]=1.[OH-].[K+]>C(O)(C)C>[F:89][C:50]([F:49])([F:88])[C:51]1[CH:52]=[C:53]([CH:81]=[C:82]([C:84]([F:85])([F:86])[F:87])[CH:83]=1)[CH2:54][N:55]([CH2:62][C:63]1[CH:68]=[C:67]([C:69]([F:72])([F:71])[F:70])[CH:66]=[CH:65][C:64]=1[C@H:73]([CH:75]1[CH2:80][CH2:79][CH2:78][CH2:77][CH2:76]1)[O:74][CH3:1])[C:56]1[N:57]=[N:58][N:59]([CH3:61])[N:60]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2CN[C@@H]2CCCC[C@H]2NCc2ccccc2P(c2ccccc2)c2ccccc2)cc1
Reactant: Cn1nnc(N(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)Cc2cc(C(F)(F)F)ccc2C(=O)C2CCCCC2)n1
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)O
Product: CO[C@H](c1ccc(C(F)(F)F)cc1CN(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1nnn(C)n1)C1CCCCC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 92 %

Procedure:
A mixture of [IrHCl2(COD)]2 (54.4 mg, 0.073 mmol) and (1R,2R)—N,N′-bis[2-(diphenylphosphino)benzyl]cyclohexane-1,2-diamine (44.8 mg, 0.067 mmol) in isopropanol was stirred at room temperature for 30 minutes. A solution of (2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-cyclohexyl-methanone in isopropanol was added to mixture followed by potassium hydroxide (44.8 mg, 0.799 mmol) and stirred at room temperature for 18 hours. Isopropanol was removed in vacuo and the crude product was purified on Biotage 40+M silica column, eluted with 0-30% ethyl acetate in heptane, to afford 3.7 g (92%) of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 0.92-1.17 (m, 5H) 1.24 (d, J=15.77 Hz, 1H) 1.54-1.60 (m, 1H) 1.61-1.67 (m, J=2.07 Hz, 2H) 1.73-1.79 (m, 1H) 1.93 (d, J=12.86 Hz, 1H) 2.25 (s, 1H) 4.20 (s, 3H) 4.65 (d, J=7.05 Hz, 1H) 4.70 (d, J=15.77 Hz, 1H) 4.76 (t, J=15.35 Hz, 2H) 4.86 (d, J=15.77 Hz, 1H) 7.34 (s, 1H) 7.50-7.59 (m, 2H) 7.65 (s, 2H) 7.77 (s, 1H). MS (ES+) Calc: 595.2, Found: 596.5 (M+1). 95.9% ee determined by chiral HPLC on Chiralpak AD-H (4.6 mm×25 cm) eluted at 6.912 min using 90/10 heptane/IPO (1 mL/min).
Reaction SMILES: [Li+].C[Si]([N-][Si](C)(C)C)(C)C.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([NH2:17])[CH:12]=1.F[C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[N+:26]([O-:28])=[O:27]>C1COCC1>[F:25][C:23]1[CH:22]=[CH:21][C:20]([N+:26]([O-:28])=[O:27])=[C:19]([NH:17][C:13]2[CH:12]=[N:11][CH:16]=[CH:15][CH:14]=2)[CH:24]=1
Reactant: O=[N+]([O-])c1ccc(F)cc1F
Reactant: Nc1cccnc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccc(F)cc1Nc1cccnc1
Temperature: -78 °C
Reaction time: 0.17 h

Procedure:
LiHMDS (1.0M in THF, 50 mL, 50 mmol) was added dropwise to a stirred solution of pyridin-3-ylamine (2.5 g, 26.4 mmol) in anhydrous THF (20 mL) under a nitrogen atmosphere at −70° C. After 10 min stirring at −78° C., a solution of 2,4-difluoro-1-nitrobenzene (4.0 g, 25.1 mmol) in THF (40 mL) was added dropwise at −78° C. The reaction mixture was slowly warmed to RT. After 4 h stirring at RT, the crude mixture was quenched by addition of an aqueous solution of NH4Cl and the aqueous fraction extracted with EtOAc. The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo to afford the title compound as a red solid (quantitative). 1H NMR (CDCl3, 300 MHz): δ 9.58 (1H, br s), 8.61 (1H, d, J=2.64 Hz), 8.55 (1H, d, J=4.76 Hz), 8.29 (1H, dd, J=9.47, 5.92 Hz), 7.66-7.61 (1H, m), 7.40 (1H, dd, J=8.19, 4.75 Hz), 6.74 (1H, dd, J=10.95, 2.62 Hz), 6.60-6.51 (1H, m).
Reaction SMILES: [Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[C:10]([CH:11]=[O:12])=[C:6]2[CH:5]=[CH:4][CH:3]=1.[C:20]([Mg]Br)#[CH:21]>>[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[C:10]([CH:11]([OH:12])[C:20]#[CH:21])=[C:6]2[CH:5]=[CH:4][CH:3]=1
Reactant: C#C[Mg]Br
Reactant: O=Cc1c(-c2ccc(F)cc2)nn2c(Cl)cccc12
Product: C#CC(O)c1c(-c2ccc(F)cc2)nn2c(Cl)cccc12
Yield: 88.1 %

Procedure:
In a similar manner as described in Example 34 from 7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridine-3-carbaldehyde (5.49 g, 20.0 mmol) and ethynylmagnesium bromide (100 mL, 0.5 M in tetrahydrofuran, 50.0 mmol) at 0° C., recrystallized from dichloromethane, was obtained 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]-2-propyn-1-ol (5.3 g, 88%) as a pale yellow crystalline solid. 1H NMR (CDCl3): δ 8.04 (d, 1H), 7.79 (m, 2H), 7.20 (m, 3H), 7.01 (d, 1H), 5.77 (m, 1H), 2.69 (d, 1H), 2.32 (d, 1H); MS m/z 301 (M+1).
Reaction SMILES: [OH:1][CH2:2][CH2:3][C@@H:4]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[C:5]([N:7]1[CH2:24][CH2:23][CH2:22][C@:9]2([C:13](=[O:14])[N:12]([CH3:15])[CH2:11][C@H:10]2[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:8]1)=[O:6].[C:33]1(O)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[CH3:15][N:12]1[CH2:11][C@@H:10]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C@@:9]2([CH2:22][CH2:23][CH2:24][N:7]([C:5](=[O:6])[C@H:4]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:29])([CH3:31])[CH3:30])[CH2:3][CH2:2][O:1][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:8]2)[C:13]1=[O:14]
Reactant: CN1C[C@@H](c2ccccc2)[C@@]2(CCCN(C(=O)[C@@H](CCO)NC(=O)OC(C)(C)C)C2)C1=O
Reactant: Oc1ccccc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CN1C[C@@H](c2ccccc2)[C@@]2(CCCN(C(=O)[C@@H](CCOc3ccccc3)NC(=O)OC(C)(C)C)C2)C1=O
Temperature: 0 °C
Reaction time: 8 h

Procedure:
Tert-butyl (R)-4-hydroxy-1-((4S,5R)-2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxobutan-2-ylcarbamate (111 mg; 0.249 mmol) was solubilised in THF (2.5 ml). Phenol (24 mg; 0.249 mmol) was added followed by triphenylphosphine (98 mg; 0.374 mmol). The solution was cooled to 0° C. and diisopropyl azodicarboxylate (0.073 ml; 0.374 mmol) was added. The reaction mixture was warmed to RT slowly and stirred overnight. The solution was concentrated in vacuo and purified by chromatography on silica eluting with 0-10% MeOH in DCM with ammonia. The compound eluted with triphenylphospine oxide and was used crude in the next step.
Reaction SMILES: [O:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:18]=[C:17]([C:19]([OH:21])=O)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)=[CH:5][CH:4]=1)[CH3:2].Cl.[CH3:23][O:24][C:25]1[C:34]([O:35][CH3:36])=[CH:33][CH:32]=[C:31]2[C:26]=1[CH2:27][CH2:28][NH:29][CH2:30]2>>[O:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:18]=[C:17]([C:19]([N:29]3[CH2:28][CH2:27][C:26]4[C:31](=[CH:32][CH:33]=[C:34]([O:35][CH3:36])[C:25]=4[O:24][CH3:23])[CH2:30]3)=[O:21])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)=[CH:5][CH:4]=1)[CH3:2]
Reactant: COc1ccc(-c2nc(C(=O)O)c3ccccc3n2)cc1
Reactant: COc1ccc2c(c1OC)CCNC2
Agent: Cl
Product: COc1ccc(-c2nc(C(=O)N3CCc4c(ccc(OC)c4OC)C3)c3ccccc3n2)cc1
Yield: 13 %

Procedure:
Reaction of 2-(4-methoxylphenyl)quinazoline-4-carboxylic acid with 5,6-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride gave compound 24 (13% yield) as a light yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 2.72 and 2.98 (2t, 2H), 3.48 and 4.03 (2t, 2H), 3.69-3.87 (5s, 9H), 4.41 and 4.93 (2s, 2H), 6.63 and 7.01 (2d, 1H), 6.80 and 7.08 (2d, 1H), 7.11-7.14 (m, 2H), 7.71-7.74 (m, 1H), 7.83-7.95 (2d, 1H), 8.03-8.10 (m, 2H), 8.45-8.51 (m, 2H); MS (ESI) m/z 456 ([M+H]+).
Reaction SMILES: [C:1]1([C:7]2[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:10]([SH:18])[NH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:20][CH2:21][O:22][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][O:24]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:1]1([C:7]2[C:11]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[C:10]([S:18][CH2:20][CH2:21][O:22][CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][O:24]3)[NH:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: BrCCOC1CCCCO1
Reactant: Sc1[nH]nc(-c2ccccc2)c1-c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: c1ccc(-c2n[nH]c(SCCOC3CCCCO3)c2-c2ccccc2)cc1
Temperature: 60 °C
Reaction time: 2 h
Yield: 93.9 %

Procedure:
To a solution of 3,4-diphenyl-1H-pyrazole-5-thiol (1.2 g, 4.76 mmol) and 2-(2-bromoethoxy)tetrahydro-2H-pyran (0.994 g, 4.76 mmol) in DMF (5 mL) was added K2CO3 (1.0 g, 7.23 mmol). The reaction was stirred at 60° C. for 2 h, cooled to room temperature, and quenched with H2O (5 mL). The mixture was extracted with EtOAc, dried over MgSO4, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a colorless oil (1.7 g). LCMS m/z=381.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.32-1.50 (m, 4H), 1.50-1.73 (m, 2H), 2.99-3.13 (m, 1H), 3.21-3.44 (m, 2H), 3.46-3.59 (m, 1H), 3.61-3.82 (m, 2H), 4.44-4.59 (m, 1H), 7.16-7.40 (m, 10H), 13.32 (bs, 1H).
Reaction SMILES: C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([C:18](=[O:38])[NH:19][CH:20]3[C:26]4=[N:27][C:28]([C:32]5[CH:37]=[CH:36][N:35]=[CH:34][N:33]=5)=[CH:29][C:30](=[O:31])[N:25]4[CH2:24][CH2:23][O:22][CH2:21]3)=[CH:13][CH:14]=2)[CH2:9]1)=O)(C)(C)C.[ClH:39]>ClCCl>[ClH:39].[O:31]=[C:30]1[N:25]2[C:26]([CH:20]([NH:19][C:18]([C:12]3[CH:11]=[C:10]4[C:15]([CH2:16][CH2:17][NH:8][CH2:9]4)=[CH:14][CH:13]=3)=[O:38])[CH2:21][O:22][CH2:23][CH2:24]2)=[N:27][C:28]([C:32]2[CH:37]=[CH:36][N:35]=[CH:34][N:33]=2)=[CH:29]1
Reactant: CC(C)(C)OC(=O)N1CCc2ccc(C(=O)NC3COCCn4c3nc(-c3ccncn3)cc4=O)cc2C1
Agent: Cl
Solvent: ClCCl
Product: O=C(NC1COCCn2c1nc(-c1ccncn1)cc2=O)c1ccc2c(c1)CNCC2
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 68.1 %

Procedure:
To a solution of 0.049 g (0.10 mmol) of (+/−)-7-(4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-7-oxa-1,4-a-diaza-benzocyclohepten-9-ylcarbamoyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (example 1) dissolved in 0.5 mL of dichloromethane was added 0.24 mL (0.96 mmol) of hydrochloric acid (4M in dioxane). The resulting mixture was stirred at room temperature for 2.5 hours. The resulting residue was filtered, washed with dichloromethane and isopropylether to afford 0.031 g (70%) of the pure product as a yellow powder.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:24])[CH2:4][O:5][C:6]1[CH:10]=[C:9]([C:11]2[S:12][C:13](Br)=[CH:14][CH:15]=2)[N:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:23])[N:7]=1.[CH3:25][S:26]([C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)(=[O:28])=[O:27].C([O-])([O-])=O.[Na+].[Na+].O>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>[Cl:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[N:8]1[C:9]([C:11]2[S:12][C:13]([C:33]3[CH:32]=[CH:31][CH:30]=[C:29]([S:26]([CH3:25])(=[O:28])=[O:27])[CH:34]=3)=[CH:14][CH:15]=2)=[CH:10][C:6]([O:5][CH2:4][C:3]([O:2][CH3:1])=[O:24])=[N:7]1
Reactant: COC(=O)COc1cc(-c2ccc(Br)s2)n(-c2ccccc2Cl)n1
Reactant: CS(=O)(=O)c1cccc(B(O)O)c1
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: O
Solvent: C1CCOC1
Product: COC(=O)COc1cc(-c2ccc(-c3cccc(S(C)(=O)=O)c3)s2)n(-c2ccccc2Cl)n1
Temperature: 70 °C
Yield: 44.5 %

Procedure:
To a solution of [5-(5-bromo-thiophen-2-yl)-1-(2-chloro-phenyl)-1H-pyrazol-3-yloxy]-acetic acid methyl ester (1.43 g, 3.33 mmol) in anhydrous THF (13.0 mL) was added sequentially 3-methylsulfonylphenylboronic acid (0.80 g, 4.0 mmol), Pd(PPh3)4 (192 mg, 0.17 mmol), Na2CO3 (1.06 g, 10.0 mmol) and water (1.0 mL). The reaction mixture was heated to reflux at 70° C. for overnight. The solvent was evaporated and the crude residue was purified by flash column chromatography with 50% ethyl acetate in hexane, resulting the product methyl {1-(2-chloro-phenyl)-5-[5-(3-methanesulfonyl-phenyl)-thiophen-2-yl]-1H-pyrazol-3-yloxy}acetate (0.746 g, 45% yield). 1H-NMR (CDCl3): δ 8.17 (m, 1H), 7.83 (m, 2H), 7.55 (m, 3H), 7.40 (m, 3H), 7.33 (m, 1H), 5.91 (s, 1H), 4.70 (s, 2H), 3.81 (s, 3H), 3.09 (s, 3H). MS (ES): 503 [M+H]+.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:28]=[CH:29][CH:30]=1)[C:6]([NH:8][C:9]1[C:10]([NH:16][C:17](=[O:27])[C:18]2[CH:23]=[CH:22][C:21]([CH:24]([CH3:26])[CH3:25])=[CH:20][CH:19]=2)=[CH:11][C:12]([OH:15])=[CH:13][CH:14]=1)=[O:7])#[N:2].Cl.[NH2:32][OH:33].C(N(CC)CC)C>CCO>[NH2:2][C:1](=[N:32][OH:33])[C:3]1[CH:4]=[C:5]([CH:28]=[CH:29][CH:30]=1)[C:6]([NH:8][C:9]1[C:10]([NH:16][C:17](=[O:27])[C:18]2[CH:23]=[CH:22][C:21]([CH:24]([CH3:26])[CH3:25])=[CH:20][CH:19]=2)=[CH:11][C:12]([OH:15])=[CH:13][CH:14]=1)=[O:7]
Reactant: CC(C)c1ccc(C(=O)Nc2cc(O)ccc2NC(=O)c2cccc(C#N)c2)cc1
Reactant: NO
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: CC(C)c1ccc(C(=O)Nc2cc(O)ccc2NC(=O)c2cccc(C(N)=NO)c2)cc1
Temperature: 80 °C
Yield: 49.5 %

Procedure:
To a mixture of N1-(3-cyanobenzoyl)-N2-(4-isopropylbenzoyl)-4-hydroxy-1,2-benzenediamine (445 mg, 1.11 mmol) and absolute EtOH (30 mL) was added hydroxylamine hydrochloride (125 mg, 1.80 mmol) followed by triethylamine (0.3 mL, 2.15 mmol). The resulting mixture was heated to 80° C. for 2 h, cooled to room temperature, and filtered to give the title compound as a solid (238 mg, 0.55 mmol, 50%); NMR(300 MHz, d6-DMSO): δ9.92 (s, 1H), 9.76 (s, 1H), 9.69 (s, 1H), 9.53 (s, 1H), 8.23 (s, 1H), 7.84 (m, 4H), 7.49 (m, 1H), 7.29 (m, 4H), 6.65 (d, J=9.0, 1H), 5.85 (s, 2H), 2.92 (m, 1H), 1.19 (s, 3H), 1.17 (s, 3H); MS(FD): 432.2.
Reaction SMILES: Cl[CH2:2][CH:3]1[O:7][C:6](=[O:8])[N:5]([C:9]2[CH:14]=[CH:13][C:12]([S:15][C:16](F)(F)F)=[CH:11][CH:10]=2)[CH2:4]1.[C:20]([O-:23])(=[O:22])[CH3:21].[K+].C1OCCOCCOCCOCCOCCOC1>CN(C)C=O>[C:20]([O:23][CH2:2][CH:3]1[O:7][C:6](=[O:8])[N:5]([C:9]2[CH:14]=[CH:13][C:12]([S:15][CH3:16])=[CH:11][CH:10]=2)[CH2:4]1)(=[O:22])[CH3:21]
Reactant: O=C1OC(CCl)CN1c1ccc(SC(F)(F)F)cc1
Reactant: CC(=O)[O-]
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [K+]
Solvent: CN(C)C=O
Product: CSc1ccc(N2CC(COC(C)=O)OC2=O)cc1
Temperature: 0 °C
Yield: 81.3 %

Procedure:
A mixture of 15 g of II (R1 =CH3, X=Cl), 50 g of potassium acetate, a catalytic amount of 18-crown-6, and 60 ml of dimethylformamide was heated under nitrogen atmosphere at 130° C. for 5 hours. The mixture was poured into ice water and the solid precipitate was collected by filtration. The solid was recrystallized from 1-chlorobutane to give 11 g of 5-acetoxymethyl-3-(4-methylthiophenyl)-2-oxazolidinone (XV, R1 =CH3).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([NH:13][C:14](=[O:22])OC2C=CC=CC=2)[C:7]([O:11][CH3:12])=[N:8][C:9]=1[CH3:10])(=[O:3])[CH3:2].[Cl:23][C:24]1[CH:25]=[C:26]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH:27]=[C:28]([Cl:30])[CH:29]=1>>[C:1]([C:4]1[CH:5]=[C:6]([NH:13][C:14]([N:34]2[CH2:33][CH2:32][N:31]([C:26]3[CH:25]=[C:24]([Cl:23])[CH:29]=[C:28]([Cl:30])[CH:27]=3)[CH2:36][CH2:35]2)=[O:22])[C:7]([O:11][CH3:12])=[N:8][C:9]=1[CH3:10])(=[O:3])[CH3:2]
Reactant: COc1nc(C)c(C(C)=O)cc1NC(=O)Oc1ccccc1
Reactant: Clc1cc(Cl)cc(N2CCNCC2)c1
Product: COc1nc(C)c(C(C)=O)cc1NC(=O)N1CCN(c2cc(Cl)cc(Cl)c2)CC1
Yield: 81 %

Procedure:
Phenyl N-(5-acetyl-2-methoxy-6-methylpyridin-3-yl)carbamate and 1-(3,5-dichlorophenyl)piperazine were reacted by the same way with the example 46 to obtain the titled compound.
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[N:12]=[C:11]([CH2:13][CH2:14][CH3:15])[C:10]([CH2:16][OH:17])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.C[N+]1([O-])CCOCC1>ClCCl.C(OCC)C.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[Cl:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]([CH:16]=[O:17])=[C:11]([CH2:13][CH2:14][CH3:15])[N:12]=2)=[CH:4][CH:3]=1
Reactant: CCCc1nc(Oc2ccc(Cl)cc2)ccc1CO
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Agent: C[N+]1([O-])CCOCC1
Solvent: CCOCC
Solvent: ClCCl
Product: CCCc1nc(Oc2ccc(Cl)cc2)ccc1C=O
Temperature: 20 °C
Reaction time: 1 h

Procedure:
A mixture of the product from Step 4 (30.5 g, 110 mmol), N-methylmorpholine-N-oxide (19.3 g, 165 mmol), tetrapropylammonium perruthenate (1.9 g, 5.5 mmol) and 4 Å molecular sieves (55 g) in dichloromethane (500 mL) was cooled with a water bath at 20° C. and stirred for 1 h. The reaction mixture was diluted with diethyl ether (1.5 L), stirred for 15 min and filtered through a short path of silica gel. Removal of the solvent gave the title product as a light yellow oil.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][CH2:7][NH2:8].[C:9](Cl)(=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=1.C(N(CC)CC)C>C1COCC1>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([C:9]([NH:8][CH2:7][CH2:6][C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)=[O:18])=[CH:11][CH:12]=1
Reactant: NCCc1cccs1
Reactant: COc1ccc(C(=O)Cl)cc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COc1ccc(C(=O)NCCc2cccs2)cc1
Yield: 95.2 %

Procedure:
Reaction of 2-thiopheneethylamine (50 μL, 0.42 mmol) in THF (2.5 mL) with p-anisoyl chloride(74 μL, 0.57 mmol) in presence of triethylamine (78 μL, 0.55 mmol) according to method A gave 4-methoxy-N-(2-thiophen-2-yl-ethyl)-benzamid (105 mg,0.40 mmol, 95% yield) as a white powder after purification by chromatography on silica gel (eluent: EtOAc/hexane 5/95 to 20/80).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][CH3:9])[C:3]=1[CH:10]([C:12]1[N:13]=[CH:14][N:15](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:16]=1)[OH:11].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][CH3:9])[C:3]=1[CH:10]([C:12]1[N:13]=[CH:14][NH:15][CH:16]=1)[OH:11]
Reactant: CCc1cccc(Cl)c1C(O)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCc1cccc(Cl)c1C(O)c1c[nH]cn1

Procedure:
Prepared in analogy to Example 57(e) from rac-(2-chloro-6-ethyl-phenyl)-(1-trityl-1H-imidazol-4-yl)-methanol, triethylsilane and trifluoroacetic acid in dichloromethane at room temperature, with the title compound being obtained as a by-product resulting from deprotection of trityl group without concomitant reduction of the benzylic alcohol moiety. Yellow oil. MS (ISP): 238.9 ([{37Cl}M+H]+), 236.8 ([{35Cl}M+H]+).
Reaction SMILES: [CH2:1]([NH:8][C:9]([C:11]1([CH3:25])[CH2:20][CH2:19][C:18]2[C:13](=[C:14]([CH3:24])[C:15]([CH3:23])=[C:16]([OH:22])[C:17]=2[CH3:21])[O:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:26]=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+]>>[CH2:1]([NH:8][C:9](=[O:10])[C:11]([OH:26])([CH3:25])[CH2:20][CH2:19][C:18]1[C:13](=[O:12])[C:14]([CH3:24])=[C:15]([CH3:23])[C:16](=[O:22])[C:17]=1[CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1c(C)c2c(c(C)c1O)CCC(C)(C(=O)NCc1ccccc1)O2
Reactant: O=[N+]([O-])[O-]
Agent: [Ce+4]
Agent: [NH4+]
Product: CC1=C(C)C(=O)C(CCC(C)(O)C(=O)NCc2ccccc2)=C(C)C1=O
Yield: 87.9 %

Procedure:
Oxidation as described in protocol B, using 130 mg (0.383 mmol) of N-benzyl-6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamide and 441 mg CAN (0.805 mmol) yielded 119.7 mg of N-benzyl-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide as a yellow foam.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([S:8]([OH:11])(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[C:12]([C:16]1[CH:24]=[CH:23][C:19]([C:20](Cl)=[O:21])=[CH:18][CH:17]=1)([CH3:15])([CH3:14])[CH3:13]>N1C=CC=CC=1>[C:12]([C:16]1[CH:17]=[CH:18][C:19]([C:20]([NH:1][C:2]2[CH:3]=[C:4]([S:8]([OH:11])(=[O:9])=[O:10])[CH:5]=[CH:6][CH:7]=2)=[O:21])=[CH:23][CH:24]=1)([CH3:15])([CH3:13])[CH3:14]
Reactant: Nc1cccc(S(=O)(=O)O)c1
Reactant: CC(C)(C)c1ccc(C(=O)Cl)cc1
Solvent: c1ccncc1
Product: CC(C)(C)c1ccc(C(=O)Nc2cccc(S(=O)(=O)O)c2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 63 %

Procedure:
To a solution of 3-amino benzenesulfonic acid (1.7 g, 10 mmol) in pyridine (100 mL) was added 4-tert-butyl benzoyl chloride (2.0 mL, 10 mmol). The reaction was stirred at room temperature 16 h and the solvent was evaporated under vacuum. The residue was dissolved in EtOAc and washed with 1 M aqueous hydrochloric acid. The aqueous washes were extracted with EtOAc. The combined organic extracts were dried over Na2SO4 and concentrated under vacuum. The residue was purified by silica gel chromatography (10%-20% MeOH—CH2Cl2) to obtain 3-(4-tert-butylbenzamido)benzenesulfonic acid (2.1 g, 63% yield). LC/MS: m/z 334.3 (M+H)+ at 2.79 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).