Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:5][N:6]1[CH2:12][CH2:11][CH2:10][N:9]([CH3:13])[C@@H:8]([CH2:14][N:15]([S:33]([CH3:36])(=[O:35])=[O:34])[C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)=[CH:18][CH:17]=2)[C:7]1=[O:37])(C)(C)C.FC(F)(F)C(O)=O.CCCCCC>CCOCC>[OH:5][N:6]1[CH2:12][CH2:11][CH2:10][N:9]([CH3:13])[C@@H:8]([CH2:14][N:15]([S:33]([CH3:36])(=[O:35])=[O:34])[C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)=[CH:18][CH:17]=2)[C:7]1=[O:37]
Reactant: CN1CCCN(OC(C)(C)C)C(=O)[C@@H]1CN(c1ccc(Oc2ccc(C(F)(F)F)cc2)cc1)S(C)(=O)=O
Solvent: CCOCC
Solvent: O=C(O)C(F)(F)F
Solvent: CCCCCC
Product: CN1CCCN(O)C(=O)[C@@H]1CN(c1ccc(Oc2ccc(C(F)(F)F)cc2)cc1)S(C)(=O)=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 104.6 %

Procedure:
To a suspension of (3S)-1-t-butoxy-3-{N-methanesulfonyl-N-[4-(4-trifluoromethyl-phenoxy)phenyl]amino}methyl-4-methyl-1,4-diazepan-2-one (146 mg, 0.2 mmol) from Step G in Et2O (0.5 mL) at room temperature was added trifluoroacetic acid (1.5 mL) slowly. The mixture was stirred for 1 h at rt. The mixture was poured into Et2O/pure H2O (10 mL/30 mL) and hexane (20 mL) was then added. The organic layer was extracted with pure H2O (30 mL). The aqueous layers were collected and combined. After lyophilization gave 102 mg of the titled compound (85%) as a white trifluoroacetic acid salt. 1H NMR (300 MHz, d6-DMSO) δ 10.05-10.00 (br s, 1H), 7.77 (d, J=9.0 Hz, 2H), 7.56 (d, J=9.0 Hz, 2H), 7.21 (d, J=9.0 Hz, 2H), 7.18 (d, J=9.0 Hz, 2H), 4.5-4.0 (m, 5H), 3.37-3.31 (m, 1H), 3.09-3.06 (m, 4H), 2.51 (br s, 3H), 2.14-1.84 (m, 2H); MS (EI) 510 (M++Na), 488 (M++1, 100).
Reaction SMILES: [CH3:1][C:2]([CH3:16])([CH3:15])[CH:3]([OH:14])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N+:11]([O-])=O.S(=O)(=O)(O)O.[H][H]>C1COCC1.[Pd]>[NH2:11][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=1[CH2:4][CH:3]([OH:14])[C:2]([CH3:15])([CH3:1])[CH3:16]
Reactant: CC(C)(C)C(O)Cc1ccccc1[N+](=O)[O-]
Reactant: [H][H]
Agent: [Pd]
Agent: O=S(=O)(O)O
Solvent: C1CCOC1
Product: CC(C)(C)C(O)Cc1ccccc1N

Procedure:
3 g (13.4 mmol) of 3,3-dimethyl-1-(2-nitrophenyl)butan-2-ol are stirred in 50 ml of THF with 2.06 g of 65 percent sulfuric acid and 0.214 g of palladium/carbon (10%) at 90° C. under 10 bar of hydrogen pressure for 16 hours. Subsequently, the solution is filtered with suction through Celite and the filtrate is concentrated by rotary evaporation. After dissolution in ethyl acetate, washing with saturated sodium bicarbonate solution, and removal and concentration of the organic phase under reduced pressure, 2.2 g (75% of theory) of a solid are obtained. Purity (GC-MS): 88%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[CH:13]=[CH:14][C:15]3[N:16]([C:18]([C:21]4[S:29][C:28]5[CH:27]=CN=[CH:24][C:23]=5[CH:22]=4)=[CH:19][N:20]=3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[K+].[K+].COC1C=[C:82](C=CC=1OC)[NH2:83]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[CH:13]=[CH:14][C:15]3[N:16]([C:18]([C:21]4[S:29][C:28]5=[CH:27][N:83]=[CH:82][CH:24]=[C:23]5[CH:22]=4)=[CH:19][N:20]=3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COc1ccc(N)cc1OC
Reactant: COc1ccc(Nc2ccc3ncc(-c4cc5cnccc5s4)n3n2)cc1OC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Solvent: C1COCCO1
Product: COc1ccc(Nc2ccc3ncc(-c4cc5ccncc5s4)n3n2)cc1OC
Temperature: 110 °C

Procedure:
To a solution of N-(3,4-dimethoxyphenyl)-3-(thieno[3,2-c]pyridin-2-yl)imidazo[1,2-b]pyridazin-6-amine (44 mg, 0.153 mmol, 1.0 equiv), xantphos (18 mg, 0.0306 mmol, 0.2 equiv), palladium acetate (3 mg, 0.0153 mmol, 0.1 equiv), and potassium carbonate (424 mg, 3.07 mmol, 20 equiv) in dioxane (5.0 mL) was added 3,4-dimethoxyaniline (28 mg, 0.184 mmol, 1.2 equiv) and heated to 110° C. for 2 h. Purification by column chromatography using 2% methanol in dichloromethane elution gave 38 mg, of the yellow solid, 62%.
Reaction SMILES: C[O:2][C:3](=[O:34])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([CH3:33])=[C:9]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]3[CH:32]=[CH:31][CH:30]=[N:29]3)=[CH:24][CH:23]=1)[C:10]([O:17][CH:18]([F:20])[F:19])=[N:11]2.[OH-].[Na+].C(O)(=O)C>CO.O>[F:20][CH:18]([F:19])[O:17][C:10]1[C:9]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([N:28]3[CH:32]=[CH:31][CH:30]=[N:29]3)=[CH:24][CH:23]=2)=[C:8]([CH3:33])[C:7]2[C:12](=[C:13]([F:16])[CH:14]=[CH:15][C:6]=2[O:5][CH2:4][C:3]([OH:34])=[O:2])[N:11]=1
Reactant: COC(=O)COc1ccc(F)c2nc(OC(F)F)c(Cc3ccc(-n4cccn4)cc3)c(C)c12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Solvent: CO
Product: Cc1c(Cc2ccc(-n3cccn3)cc2)c(OC(F)F)nc2c(F)ccc(OCC(=O)O)c12
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 8.1 %

Procedure:
A solution of [2-difluoromethoxy-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-yloxy]acetic acid methyl ester (0.43 g) in methanol (7.0 mL) and water (0.7 mL) was treated with 5.0 M aqueous sodium hydroxide solution (0.36 mL), and the resulting mixture was stirred at room temperature for 1.5 hours. The mixture was acidified by the addition of glacial acetic acid, diluted with water and then extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate and then concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel gave title compound as a white solid (0.034 g).
Reaction SMILES: [F:1][CH:2]([F:23])[C:3]1[N:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:5]([CH3:18])[C:4]=1[S:19][CH:20]([CH3:22])[CH3:21].C1C=C(Cl)C=C(C(OO)=[O:32])C=1.C1C=C(Cl)C=C(C(O)=O)C=1>>[F:23][CH:2]([F:1])[C:3]1[N:8]=[C:7]([C:9]([F:12])([F:10])[F:11])[C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:5]([CH3:18])[C:4]=1[S:19]([CH:20]([CH3:22])[CH3:21])=[O:32]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCOC(=O)c1c(C(F)(F)F)nc(C(F)F)c(SC(C)C)c1C
Agent: O=C(O)c1cccc(Cl)c1
Product: CCOC(=O)c1c(C(F)(F)F)nc(C(F)F)c(S(=O)C(C)C)c1C

Procedure:
Prepared from product of Example 10 (6.06 g, 16.96 mmol) and MCPBA (3.44 g of an 85% mixture with MCBA, 16.96 mmol) as described above. Recrystallization (ether/petroleum ether) afforded the product as a white solid (4.65 g).
Reaction SMILES: C([O:3][C:4](=[O:23])[C:5]([CH2:20][CH:21]=[CH2:22])([S:9]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)(=[O:11])=[O:10])[CH2:6][CH:7]=[CH2:8])C>CO.[OH-].[Na+]>[CH2:20]([C:5]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)(=[O:11])=[O:10])([CH:6]=[CH:7][CH3:8])[C:4]([OH:23])=[O:3])[CH:21]=[CH2:22]
Reactant: C=CCC(CC=C)(C(=O)OCC)S(=O)(=O)c1ccc(OC)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: C=CCC(C=CC)(C(=O)O)S(=O)(=O)c1ccc(OC)cc1

Procedure:
2-Allyl-2-(4-methoxy-benzenesulfonyl)-pentenoic acid was prepared starting from 2-allyl-2-(4-methoxy-benzenesulfonyl)-pent-4-enoic acid ethyl ester (2.2 g, 6.5 mmol) dissolved in methanol (50 ml) and 10 N NaOH (30 ml). The resulting reaction mixture was worked up as outlined in Example 9. Yield 1.76 g, 87%; yellowish oil; MS: 311 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:5]([NH2:10])=[N:6][CH:7]=[CH:8][CH:9]=1)[CH3:2].Br[C:12]1[CH:25]=[C:24]2[C:15]([O:16][C:17]3[C:18]([F:34])=[CH:19][C:20]([O:32][CH3:33])=[CH:21][C:22]=3[C@@:23]32[CH2:30][CH2:29][O:28][C:27]([NH2:31])=[N:26]3)=[CH:14][CH:13]=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>C(OCC)(=O)C.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C:4]1[C:5]([NH:10][C:12]2[CH:25]=[C:24]3[C:15]([O:16][C:17]4[C:18]([F:34])=[CH:19][C:20]([O:32][CH3:33])=[CH:21][C:22]=4[C@:23]3([NH:26][C:27]#[N:31])[CH2:30][CH2:29][OH:28])=[CH:14][CH:13]=2)=[N:6][CH:7]=[CH:8][CH:9]=1)[CH3:2]
Reactant: CCOc1cccnc1N
Reactant: COc1cc(F)c2c(c1)[C@]1(CCOC(N)=N1)c1cc(Br)ccc1O2
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CCOC(C)=O
Solvent: O
Solvent: Cc1ccccc1
Product: CCOc1cccnc1Nc1ccc2c(c1)[C@](CCO)(NC#N)c1cc(OC)cc(F)c1O2
Temperature: 25 °C
Reaction time: 0.03 h
Yield: 55.8 %

Procedure:
A 20 mL resealable tube was charged with 3-ethoxypyridin-2-amine (176 mg, 1.272 mmol), (S)-7′-bromo-4′-fluoro-2′-methoxy-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-2-amine (250 mg, 0.636 mmol), Pd2 dba3 (29.1 mg, 0.032 mmol), t-BuXPhos (47.2 mg, 0.111 mmol) and sodium t-butoxide (244 mg, 2.54 mmol). Toluene (6 ml) was added, the mixture was stirred for 2 min at room temperature, then heated at 100° C. for 1.5 hr. The solution was diluted with ethyl acetate and water. The organic layer was separated and concentrated. The product was purified via silica gel column chromatography (RediSep 40 g column) using 20-80% ethyl acetate in heptane to afford (S)—N-(7-((3-ethoxypyridin-2-yl)amino)-4-fluoro-9-(2-hydroxyethyl)-2-methoxy-9H-xanthen-9-yl)cyanamide (160 mg, 0.355 mmol, 55.9% yield). MS m/z=451.0 [M+H].
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[CH2:9][OH:10].C(N(CC)CC)C.[C:18](Cl)(Cl)=[O:19].O>C1COCC1.CCOC(C)=O>[CH3:8][C:4]1[C:3]2[CH2:9][O:10][C:18](=[O:19])[NH:1][C:2]=2[CH:7]=[CH:6][CH:5]=1
Reactant: Cc1cccc(N)c1CO
Reactant: O=C(Cl)Cl
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: Cc1cccc2c1COC(=O)N2
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of (2-amino-6-methyl-phenyl)-methanol (2.74 g, 20 mmol) and triethylamine (4.04 g, 40 mmol) in THF (150 mL), phosgene (12.5% solution in toluene, 17.42 g, 22 mrnol) was added dropwise at 0° C. Reaction mixture was allowed to warm to room temperature and stirred for 16 hours. Water (150 mL) was added under stirring, followed by EtOAc (2×100 mL). EtOAc extracts were washed with water and brine and dried over MgSO4. The product (buff solid) was crystallized from EtOAc:pet. ether mixture. (Yield: 2.37=73%); mp 222-226° C.; MS (CI): M+1=163.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([F:21])([C:12]2[CH:17]=[CH:16][C:15]([CH:18]=[N:19][OH:20])=[CH:14][CH:13]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClN1C(=O)CCC1=O.[Cl:30][C:31]1[CH:32]=[C:33]([C:39](=[O:44])[C:40]([F:43])([F:42])[F:41])[CH:34]=[C:35]([Cl:38])[C:36]=1[F:37].C(=O)(O)[O-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[O:44][C:39]([C:33]4[CH:34]=[C:35]([Cl:38])[C:36]([F:37])=[C:31]([Cl:30])[CH:32]=4)([C:40]([F:43])([F:42])[F:41])[O:20][N:19]=3)=[CH:14][CH:13]=2)([F:21])[CH2:11]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CC(F)(c2ccc(C=NO)cc2)C1
Reactant: O=C(c1cc(Cl)c(F)c(Cl)c1)C(F)(F)F
Agent: O=C([O-])O
Agent: O=C1CCC(=O)N1Cl
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CC(F)(c2ccc(C3=NOC(c4cc(Cl)c(F)c(Cl)c4)(C(F)(F)F)O3)cc2)C1
Temperature: 55 °C
Reaction time: 1 h
Yield: 39.3 %

Procedure:
To a stirred solution of 3-fluoro-3-[4-(hydroxyimino-methyl)-phenyl]-azetidine-1-carboxylic acid tert-butyl ester (0.5 g, 1.7 mmol, 1 eq) in DMF (6.5 mL) was added N-chloro succinimide (0.227 g, 1.7 mmol, 1 eq). Reaction mixture was stirred at 55° C. for 1 hour. After 1 hour (chloro intermediate formation), 1-(3,5-dichloro-4-fluoro-phenyl)-2,2,2-trifluoro-ethanone (0.45 g, 1.73 mmol, 1.02 eq) was added followed by addition of sodium bicarbonate (0.146 g, 1.74 mmol, 1.02 eq) at room temperature. Resulting reaction mixture was stirred at 55° C. for 3 hours under nitrogen atmosphere. After complete consumption of starting material, reaction mixture was quenched by water (10 mL) and extracted with ethyl acetate (3×50 mL). Combined organic phase was washed with brine solution (20 mL), dried over anhydrous Na2SO4and concentrated under reduced pressure to get brown thick oil (0.6 g, Crude). Crude was purified by Combiflash using 40 g Redisep column. Desired compound was eluted in 25% ethyl acetate in hexane to afford title compound as colorless thick oil (0.37 g, 39.32%). 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 4.16-4.24 (m, 2H), 4.38-4.47 (m, 2H), 7.59 (d, J=8.44 Hz, 2H), 7.66 (d, J=5.88 Hz, 2H), 7.89 (d, J=8.2 Hz, 2H), LC-MS (m/z): No ionization.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].C(=O)([O-])[O-].[Na+].[Na+].[Cl:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1>O1CCOCC1.CCOCC.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:22][C:23]1[CH:28]=[C:27]([C:2]2[CH:3]=[C:4]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:11]=2)[CH:26]=[CH:25][CH:24]=1
Reactant: OB(O)c1cccc(Cl)c1
Reactant: COC(=O)c1cc(Br)cc(C(=O)OC)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: CCOCC
Solvent: C1COCCO1
Product: COC(=O)c1cc(C(=O)OC)cc(-c2cccc(Cl)c2)c1
Temperature: 90 °C

Procedure:
To dimethyl 5-bromoisophthalate (880 mg, 3.22 mmol) (commercial source: Matrix scientific) in 1,4-dioxane (15 ml), 3-chlorophenyl boronic acid) (756 mg, 4.83 mmol), sodium carbonate (2M aqueous solution) (1.38 gms in 6.5 ml water) and Pd(PPh3)4 (370 mg, 0.32 mmol) was added and heated at 90° C. for 5 h. Then reaction mixture was diluted with ether, washed with water, brine and dried. Volatiles were removed under vacuum and the crude residue was column chromatographed (10% ethylacetate/90% hexanes) to yield 700 mg of dimethyl 3′-chlorobiphenyl-3,5-dicarboxylate.
Reaction SMILES: [CH2:1](Br)[CH:2]=[CH2:3].[OH:5][C:6]1[CH:18]=[CH:17][C:9]([O:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:8][CH:7]=1.C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[CH2:1]([O:5][C:6]1[CH:7]=[CH:8][C:9]([O:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:17][CH:18]=1)[CH:2]=[CH2:3]
Reactant: CCOC(=O)COc1ccc(O)cc1
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: C=CCOc1ccc(OCC(=O)OCC)cc1
Temperature: 25 °C
Yield: 103.6 %

Procedure:
Allyl bromide (3.37 g) was added to a stirred suspension of ethyl 4-hydroxyphenoxyacetate (5.14 g) [prepared by method of Moser, J.A.C.S., (1950), 72, 1413) and potassium carbonate (3.90 g) in butan-2-one (50 ml). The reaction mixture was heated at reflux for 12 hours. The reaction mixture was cooled to ambient temperature and then filtered. The filtrate was evaporated to give an oil which was purified by column chromatography on silica gel (Merck. Art. No. 7734) using a 4:1 (v/v) mixture of hexane and ethylacetate as eluent to give ethyl 4-allyloxyphenoxyacetate (6.41 g) as a colourless oil; microanalysis, found: C, 65.8; H, 7.20%; C13H16O4 requires C, 66.1; H, 6.83%; NMR (CDCl3): 1.28 (3H, t), 4.25 (2H, q), 4.48 (2H, m), 4.57 (2H, s), 5.22-5.44 (2H, m), 5.92-6.12 (1H, m) and 6.84 (4H, s).
Reaction SMILES: [N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.FC(F)(F)S(O[C:72]1[CH:81]=[CH:80][CH:79]=[C:78]2[C:73]=1[CH:74]=[CH:75][C:76]([CH3:82])=[N:77]2)(=O)=O>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:82][C:76]1[CH:75]=[CH:74][C:73]2[C:78](=[CH:79][CH:80]=[CH:81][C:72]=2[N:4]2[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]2)[N:77]=1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: Cc1ccc2c(OS(=O)(=O)C(F)(F)F)cccc2n1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: Cc1ccc2c(N3CCN(C(=O)OC(C)(C)C)CC3)cccc2n1
Yield: 62 %

Procedure:
tert-Butyl 1-piperazine carboxylate (1.6 g; 1.2 eq), cesium carbonate (1.7 g; 1.5 eq), palladium acetate (0.33 g; 0.14 eq) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.97 mg; 0.15 eq) were added to a solution of 2-methyl-5-quinolinyl trifluoromethanesulfonate (D1) in toluene (20 mL) under an inert atmosphere. The reaction mixture was stirred at reflux under nitrogen for 8 hours. The reaction was quenched at room temperature using a saturated aqueous solution of ammonium chloride (15 mL) and extracted into ethyl acetate (3×20 mL). The organic layers were combined, dried over Na2SO4 and concentrated under reduced pressure. The crude was purified by flash chromatography, eluting with ethyl acetate/cyclohexane (3/7) affording the title compound in 62% yield (1.4 g).
Reaction SMILES: C([N:8]1[CH2:14][C:13]2[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=2[C:11](=[O:19])[C:10]2[CH:20]=[CH:21][CH:22]=[CH:23][C:9]1=2)C1C=CC=CC=1.[Cl-].[Al+3].[Cl-].[Cl-].[C:28](Cl)(=[O:30])[CH3:29]>C(Cl)Cl>[C:28]([C:21]1[CH:22]=[CH:23][C:9]2[NH:8][CH2:14][C:13]3[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=3[C:11](=[O:19])[C:10]=2[CH:20]=1)(=[O:30])[CH3:29]
Reactant: O=C1c2ccccc2CN(Cc2ccccc2)c2ccccc21
Reactant: CC(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CC(=O)c1ccc2c(c1)C(=O)c1ccccc1CN2
Yield: 47.2 %

Procedure:
5,6-Dihydro-5-benzyl-11-oxodibenz[b,e]azepine (10.1 g), anhydrous aluminum chloride (16 g), acetyl chloride (8 g) and methylene chloride (100 ml) were treated in the same manner as described in Example 25 to obtain the desired compound (4 g).
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[NH:16][S:15]2(=[O:25])=[O:24])[CH2:10][CH2:9]1)C1C=CC=CC=1.Cl.O.[H][H]>[C].[Pd].CO>[O:25]=[S:15]1(=[O:24])[N:14]([CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)[CH2:19][C:18]2[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=2[NH:16]1
Reactant: [H][H]
Reactant: O=S1(=O)Nc2ccccc2CN1C1CCN(Cc2ccccc2)CC1
Agent: [Pd]
Agent: Cl
Solvent: O
Solvent: CO
Product: O=S1(=O)Nc2ccccc2CN1C1CCNCC1
Temperature: 40 °C
Yield: 93.6 %

Procedure:
In this reference example, 7.14 g (20 m.mols) of 1-benzyl-4-(3,4-dihydro-2,2-dioxo-1H-2,1,3-benzothiadiazin-3-yl)-piperidine, 2 g of 10% palladium carbon, 20 ml of 1 N hydrochloric acid, 60 ml of water and 120 ml of methanol are mixed. While the mixture is stirred at 40° C., hydrogen gas is blown into the mixture at 40° C. for 20 hours. The reaction mixture is filtered to remove palladium carbon. The filtrate is concentrated to dryness to obtain 5.0 g of the desired product.
Reaction SMILES: ClS([N:5]=[C:6]=O)(=O)=O.[C:8]([C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][CH:16]=[CH:15]2)([CH3:11])([CH3:10])[CH3:9].CN(C)C=O>C(#N)C>[C:8]([C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][CH:16]=[C:15]2[C:6]#[N:5])([CH3:11])([CH3:9])[CH3:10]
Reactant: CC(C)(C)c1ccc2[nH]ccc2c1
Reactant: O=C=NS(=O)(=O)Cl
Solvent: CN(C)C=O
Solvent: CC#N
Product: CC(C)(C)c1ccc2[nH]cc(C#N)c2c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Chlorosulfonyl isocyanate (1 ml) was added dropwise to a suspension of 5-tert-butylindole (2.1 g) in acetonitrile (15 ml) over 10 minutes under ice-cooling. After being stirred for 1 hour at same temperature, a solution of N,N-dimethylformamide (1 ml) in acetonitrile (20 ml) was added to the mixture and then the mixture was stirred at 50° C. for 1 hour. The reaction mixture was poured into ice-water and extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The resulting residue was subjected to column chromatography on silica gel and eluted with a mixture of ethyl acetate and n-hexane. The fractions containing the objective compound were combined and concentrated under reduced pressure to give 5-tert-butyl-3-cyanoindole (1.20 g).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[CH2:24][CH:23]([C:28](O)=[O:29])[CH2:22][CH2:21]2)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]>CCOCC>[CH2:7]([O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[CH2:24][CH:23]([CH2:28][OH:29])[CH2:22][CH2:21]2)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCOc1ccc2c(c1)CCC(C(=O)O)C2
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: CCCCCCCCCCOc1ccc2c(c1)CCC(CO)C2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 94.9 %

Procedure:
0.34 g (8.95 mmol) of lithium aluminum hydride was added to 40 ml of ether. To this mixture was slowly added 2.54 g (7.65 mmol) of the 6-decyloxy-1,2,3,4-tetrahydro-2-naphthalenecarboxylic acid obtained in the first stage of Example 1. After the resulting mixture was stirred at room temperature for 30 minutes, it was heated under reflux for 6 hours. After cooling, the reaction mixture was caused to undergo hydrolysis and extraction with ether. The organic phase was concentrated and by purifying the concentrate using column chromatography there was obtained 2.31 g (7.26 mmol) of 6-decyloxy-1,2,3,4-tetrahydro-2-hydroxymethylnaphthalene as a white solid.
Reaction SMILES: [C:1]([O:4][CH:5]=[CH2:6])(=[O:3])[CH3:2]>[Ru].C(O)(=O)C>[C:1]([O:4][CH:5]([O:4][C:1](=[O:3])[CH3:2])[CH3:6])(=[O:3])[CH3:2]
Reactant: C=COC(C)=O
Agent: [Ru]
Solvent: CC(=O)O
Product: CC(=O)OC(C)OC(C)=O

Procedure:
The procedure of Example 17 was repeated except that 4.5 g of ruthenium (5%) supported on activated carbon was used in place of palladium supported on activated carbon. GC analysis showed that vinyl acetate was formed with considerable amount of acetic acid and 15.5 g of ethylidene diacetate.
Reaction SMILES: [CH3:1][S:2]([O:5][CH:6]([CH3:10])[C:7](Cl)=[O:8])(=[O:4])=[O:3].[C:11]([OH:14])(=[O:13])[CH3:12]>>[CH3:1][S:2]([O:5][CH:6]([CH3:10])[C:7]([O:14][C:11](=[O:13])[CH3:12])=[O:8])(=[O:4])=[O:3]
Reactant: CC(OS(C)(=O)=O)C(=O)Cl
Reactant: CC(=O)O
Product: CC(=O)OC(=O)C(C)OS(C)(=O)=O

Procedure:
The acyl halides can be converted to the symmetrical or mixed acid anhydrides corresponding to the compounds of formula II when Y is acyloxy, by contacting the acyl halide with an appropriate acid. For example, 2-methanesulfonyloxypropionyl chloride is allowed to react with acetic acid to afford the mixed anhydride, acetic 2-methanesulfonyloxypropionic anhydride. Additionally, for example, 2-methanesulfonyloxypropionyl chloride is allowed to react with 2-methanesulfonylotypropionic acid to afford bis(2-methanesulfonyloxypropionic)anhydride, a symmetrical anhydride. Alternatively, the acid precursors of the acyl halides of formula II can be contacted with an appropriate acyl halide to afford the symmetrical or mixed acid anhydrides. For example, 2-methanesulfonyloxypropionic acid is allowed to react with acetyl chloride to afford the mixed anhydride, acetic 2-methanesulfonyloxypropionic anhydride.
Reaction SMILES: [NH2:1][C:2]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].[C:17]([O-])([O-])([O:19][CH3:20])[CH3:18]>>[CH3:20][O:19][C:17](=[N:1][C:2]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5])[CH3:18]
Reactant: Cc1ccc(N)c(C(=O)c2ccccc2)c1
Reactant: COC(C)([O-])[O-]
Product: COC(C)=Nc1ccc(C)cc1C(=O)c1ccccc1

Procedure:
2-Amino-5-methylbenzophenone is reacted with methyl orthoacetate, whereby 2-(1-methoxyethylideneamino)-5-methylbenzophenone is obtained. The product is reacted with hydrazine hydrate, whereby 3-amino-3,4-dihydro-2, 6-dimethyl-4-hydroxy-4-phenylquinazoline (colorless peates melting at 192° to 196° C) is obtained. The product is reacted with chloroacetylchloride, followed by the same treatment as Example 1, whereby 3-chloroacetylamino-3, 4-dihydro-2, 6-dimethyl-4-hydroxy-4-phenylquinazoline having 1/2 mole of water of crystallization (colorless powdery crystals melting at 90° to 93° C) is obtained. The product is heated with acetic acid, whereby crystals of 2-(3-chloromethyl-1-methyl-s-triazol-4-yl)-5-methylbenzophenene are obtained. Recrystallization from benzene gives colorless needles melting at 167° to 168° C. Overall yield: 42%.