Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7](O)=[O:8])=[CH:5][CH:4]=1)#[N:2].C(Cl)([Cl:14])=O>C(#N)C>[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([Cl:14])=[O:8])=[CH:5][CH:4]=1)#[N:2]
Reactant: O=C(Cl)Cl
Reactant: N#Cc1ccc(C(=O)O)cc1
Solvent: CC#N
Product: N#Cc1ccc(C(=O)Cl)cc1
Yield: 97.9 %

Procedure:
p-Cyanobenzoic acid (14.7 g) and acetonitrile (300 ml) were mixed and stirred vigorously while the solvent was refluxed, and phosgene gas (30 g) was introduced to the mixture over four hours. After dry nitrogen gas was introduced to the reaction mixture for one hour, acetonitrile was removed under ambient pressure, and was further removed under reduced pressure through distillation, to thereby obtain 16.2 g of p-cyanobenzoyl chloride (yield 98%, based on p-cyanobenzoic acid). The p-cyanobenzoyl chloride obtained had a purity of 99%.
Reaction SMILES: C([N:5]1[C:14]2[C:9](=[CH:10][C:11]([F:18])=[C:12]([F:17])[C:13]=2[O:15][CH3:16])[C:8](=[O:19])[C:7]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:6]1)(C)(C)C.[N+:25]([O-])([O-:27])=[O:26].[K+]>OS(O)(=O)=O>[F:18][C:11]1[C:10]([N+:25]([O-:27])=[O:26])=[C:9]2[C:14](=[C:13]([O:15][CH3:16])[C:12]=1[F:17])[NH:5][CH:6]=[C:7]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:8]2=[O:19]
Reactant: O=[N+]([O-])[O-]
Reactant: CCOC(=O)c1cn(C(C)(C)C)c2c(OC)c(F)c(F)cc2c1=O
Agent: O=S(=O)(O)O
Agent: [K+]
Product: CCOC(=O)c1c[nH]c2c(OC)c(F)c(F)c([N+](=O)[O-])c2c1=O
Temperature: 0 °C
Reaction time: 1 h
Yield: 66.1 %

Procedure:
A solution of ethyl 1-tert-butyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylate (20.0 g, 58.9 mmol) in concentrated H2SO4 (120 mL) was treated portionwise at 0° C. with solid KNO3 (8.90 g, 88.0 mmol). After stirring at 0° C. for 1 h, the reaction mixture was poured into 500 mL of ice-water and the resulting precipitate was removed by filtration. The resulting solid washed with EtOH, dried to yield ethyl 6,7-difluoro-1,4-dihydro-8-methoxy-5-nitro-4-oxoquinoline-3-carboxylate (12.77 g, 66%) as a pale yellow solid.
Reaction SMILES: [N:1]1([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH3:10])=[O:8])[CH2:3][CH2:2]1.[Li+].[CH3:19][CH:20]([N-:22]C(C)C)C.BrCC#N>C1COCC1>[C:20]([CH2:19][C:4]1([C:7]([O:9][CH3:10])=[O:8])[CH2:3][CH2:2][N:1]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6][CH2:5]1)#[N:22]
Reactant: CC(C)[N-]C(C)C
Reactant: COC(=O)C1CCN(C(=O)OC(C)(C)C)CC1
Agent: N#CCBr
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(=O)C1(CC#N)CCN(C(=O)OC(C)(C)C)CC1
Temperature: -65 °C
Reaction time: 1.5 h

Procedure:
To a solution of commercially available 1-tert-butyl 4-methyl piperidine-1,4-dicarboxylate (200 g, 0.82 mol) in anhydrous THF (2 L) was added LDA (2M in THF, 575 mL, 1.15 mol) drop-wise at −65° C. under N2. The mixture was stirred at −65° C. for 1.5 h. To the mixture was added bromoacetonitrile (148 g, 1.23 mol) in anhydrous THF (500 mL) at −65° C. The mixture was stirred at −65° C. for 1 h, then warmed up to room temperature and stirred overnight. The reaction was quenched with water (800 mL) at 0° C. and the combined reaction mixture was concentrated in vacuum to give a crude product, which was extracted with ethyl acetate (1 L three times). The combined organic phases were washed with brine (1 L) and dried over Na2SO4. The organic layer was filtered and the filtrate was concentrated under vacuum to give a crude product, which was purified by column chromatography on silica gel eluting with petroleum ether/ethyl acetate (from petroleum ether to 2/1) to give the title compound. 1H-NMR (400 MHz, CDCl3) δ 3.900-3.750 (m, 5H), 3.120-3.000 (m, 2H), 2.612-2.562 (m, 2H), 2.190-2.111 (m, 2H), 1.590-1.502 (m, 2H), 1.402 (s, 9H).
Reaction SMILES: Cl[C:2]1[C:14]2[C:13]3[CH:12]=[CH:11][C:10]([C:15]([O:17][CH3:18])=[O:16])=[CH:9][C:8]=3[NH:7][C:6]=2[C:5]([C:19]#[N:20])=[CH:4][N:3]=1.[CH3:21][C:22]1[C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:25]=[CH:24][C:23]=1[N:37]1[C:46](=[O:47])[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[N:39]=[CH:38]1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.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>[CH3:18][O:17][C:15]([C:10]1[CH:11]=[CH:12][C:13]2[C:14]3[C:2]([C:27]4[CH:26]=[CH:25][CH:24]=[C:23]([N:37]5[C:46](=[O:47])[C:45]6[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=6)[N:39]=[CH:38]5)[C:22]=4[CH3:21])=[N:3][CH:4]=[C:5]([C:19]#[N:20])[C:6]=3[NH:7][C:8]=2[CH:9]=1)=[O:16]
Reactant: COC(=O)c1ccc2c(c1)[nH]c1c(C#N)cnc(Cl)c12
Reactant: Cc1c(B2OC(C)(C)C(C)(C)O2)cccc1-n1cnc2ccccc2c1=O
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: C1COCCO1
Product: COC(=O)c1ccc2c(c1)[nH]c1c(C#N)cnc(-c3cccc(-n4cnc5ccccc5c4=O)c3C)c12
Temperature: 110 °C
Yield: 39 %

Procedure:
A stirred mixture of methyl 1-chloro-4-cyano-5H-pyrido[4,3-b]indole-7-carboxylate (0.285 g, 0.998 mmol), 3-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)quinazolin-4(3H)-one (0.361 g, 0.998 mmol), Tetrakis(triphenylphosphine)palladium(0) (0.058 g, 0.050 mmol) and Sodium carbonate[2M] (0.499 mL, 0.998 mmol) in Dioxane (2 mL) was heated at 110° C. for 16 hours overnight. LC-MS showed complete conversion to the desired product mass plus residual starting material[boronic ester] and a byproduct. The reaction mixture was concentrated. The residue was taken up in 10 ml DMF, stirred and filtered. The filtrate was concentrated; the residue triturated with methanol and filtered. The solid residue was dried overnight. LC-MS showed the solid residue to be the desired product methyl-4-cyano-1-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-5H-pyrido[4,3-b]indole-7-carboxylate as a tan solid [0.192 g, 0.395 mmol, 39% yield]. The product had an HPLC Retention Time=3.521 min [mixture of rotamers][4 min grad, 10% MeOH/water to 90% MeOH/water, 0.1% TFA, YMC COMBISCREEN® ODS-A, 4.6×50 mm, 220 nM]; LC/MS+1 486.2
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:22])[CH2:11][C:12]23[CH2:21][CH:16]4[CH2:17][CH:18]([CH2:20][CH:14]([CH2:15]4)[CH2:13]2)[CH2:19]3)=[C:5]([CH3:23])[CH:4]=1.B(Br)(Br)Br>ClCCl>[OH:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]([C:10](=[O:22])[CH2:11][C:12]23[CH2:21][CH:16]4[CH2:15][CH:14]([CH2:20][CH:18]([CH2:17]4)[CH2:19]2)[CH2:13]3)[C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)=[C:5]([CH3:23])[CH:4]=1
Reactant: COc1ccc(NC(=O)CC23CC4CC(CC(C4)C2)C3)c(C)c1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: Cc1cc(O)ccc1N(C(=O)CC12CC3CC(CC(C3)C1)C2)c1ccccc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of N-(4-Methoxy-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-acetamide from Example 20 (1.20 g) in dichloromethane (50 ml) at −78° C. was added boron tribromide (4 ml of a 1.0M solution in dichloromethane) under an inert atmosphere. The reaction mixture was stirred for 24 hours and then warmed to ambient temperature and washed with brine. The organic layer was then dried over magnesium sulphate (MgSO4) and concentrated under reduced pressure to yield a residue which was purified by silica gel chromatography eluting with iso-hexane/diethyl ether (1:1) to give the ititle compound as a white solid. (0.54 g).
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]2[CH:13]=[C:12]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[CH:22][S:23][C:16]=34)[CH:11]=[CH:10][C:5]=2[C:6]=1[C:7](Cl)=[O:8].[CH:24]([O:27][CH2:28][CH2:29][NH2:30])([CH3:26])[CH3:25]>>[CH:24]([O:27][CH2:28][CH2:29][NH:30][C:7]([C:6]1[C:5]2[CH:10]=[CH:11][C:12]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[CH:22][S:23][C:16]=34)=[CH:13][C:4]=2[O:3][C:2]=1[CH3:1])=[O:8])([CH3:26])[CH3:25]
Reactant: Cc1oc2cc(Oc3ccnc4ccsc34)ccc2c1C(=O)Cl
Reactant: CC(C)OCCN
Product: Cc1oc2cc(Oc3ccnc4ccsc34)ccc2c1C(=O)NCCOC(C)C

Procedure:
This material was prepared from 2-methyl-6-[thieno[3,2-b]pyridin-7-yloxy]benzofuran-3-carbonyl chloride 101 and 2-(isopropoxy)ethylamine in a similar manner as that described for example 108. 1H NMR (CD3CN) δ 8.49 (1H, d, J=5.6 Hz), 7.91 (1H, d, J=5.6 Hz), 7.82 (1H, d, J=8.6 Hz), 7.54 (1H, d, J=5.6 Hz), 7.41 (1H, d, J=2.3 Hz), 7.20 (1H, dd, J=8:6, 2.3 Hz), 6.67 (1H, bm), 6.63 (1H, d, J=5.3 Hz), 3.8–3.51 (5H, m), 2.66 (3H, s), 1.15 (6H, d, J=6.1 Hz). Anal. Calcd for C22H22N2O4S: C, 64.37; H, 5.40; N, 6.82; S, 7.81. Found: C, 64.35; H, 5.51; N, 6.76; S, 7.74.
Reaction SMILES: [OH:1][C:2]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][C:3]=1[C:4]([CH2:6][CH2:7][C:8]([O:10][CH3:11])=[O:9])=[O:5].[CH2:18]([CH:20]1[O:22][CH2:21]1)Br>>[O:22]1[CH2:21][CH:20]1[CH2:18][O:1][C:2]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][C:3]=1[C:4]([CH2:6][CH2:7][C:8]([O:10][CH3:11])=[O:9])=[O:5]
Reactant: COC(=O)CCC(=O)c1cc(OC)ccc1O
Reactant: BrCC1CO1
Product: COC(=O)CCC(=O)c1cc(OC)ccc1OCC1CO1

Procedure:
Methyl 3-(2-hydroxy-5-methoxybenzoyl)propionate was reacted with epibromohydrin in a similar manner to that described in Example 1 (ii) to give methyl 3-[2-(2,3-epoxypropoxy)-5-methoxybenzoyl]propionate which, recrystallised from ether-petroleum ether (b.p. 60°-80°), had m.p. 50° - 51.5° C). (Found: C, 60.91; H, 6.07; C15H18O6 requires: C, 61.21; H, 6.17%).
Reaction SMILES: Br[C:2]1[C:3]([Cl:18])=[C:4]([CH:8]([CH:15]2[CH2:17][CH2:16]2)[N:9]([CH3:14])[S:10]([CH3:13])(=[O:12])=[O:11])[CH:5]=[N:6][CH:7]=1.[Cl:19][C:20]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:25]=[CH:24][C:21]=1[C:22]#[N:23].C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[Cl:18][C:3]1[C:2]([C:26]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[C:20]([Cl:19])[CH:27]=2)=[CH:7][N:6]=[CH:5][C:4]=1[CH:8]([CH:15]1[CH2:17][CH2:16]1)[N:9]([CH3:14])[S:10]([CH3:13])(=[O:12])=[O:11]
Reactant: CC1(C)OB(c2ccc(C#N)c(Cl)c2)OC1(C)C
Reactant: CN(C(c1cncc(Br)c1Cl)C1CC1)S(C)(=O)=O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: O
Product: CN(C(c1cncc(-c2ccc(C#N)c(Cl)c2)c1Cl)C1CC1)S(C)(=O)=O
Temperature: 25 °C

Procedure:
To a solution of N-((5-bromo-4-chloropyridin-3-yl)(cyclopropyl)methyl)-N-methylmethanesulfonamide (1.03 g, 2.9 mmol) and 2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (2.29 g, 8.7 mmol) in DMF (20 mL) was added PdCl2(dppf).CH2Cl2 (118 mg, 0.145 mmol) and 2M Na2CO3 in water (2.9 mL, 5.8 mmol), and the mixture was heated to 85° C. for 7 h. The mixture was cooled to room temperature, poured into water (100 mL), extracted with EtOAc (200 mL*3), washed with water (20 mL*3) and dried over Na2SO4. The mixture was purified by silica gel chromatography eluting with a 0-50% EtOAc-heptane gradient to give N-((4-chloro-5-(3-chloro-4-cyanophenyl)pyridin-3-yl)(cyclopropyl)methyl)-N-methylmethanesulfonamide. MS (ESI): m/z 410.1, 412.1 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([OH:13])=O)[CH:10]=2)[CH:7]=1.[F:14][C:15]1[CH:24]=[CH:23][C:22]([F:25])=[C:21]2[C:16]=1[CH2:17][CH2:18][NH:19][CH:20]2[CH3:26]>>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([N:19]3[CH2:18][CH2:17][C:16]4[C:21](=[C:22]([F:25])[CH:23]=[CH:24][C:15]=4[F:14])[CH:20]3[CH3:26])=[O:13])[CH:10]=2)[CH:7]=1
Reactant: O=C(O)c1cc2ncc(Br)cn2n1
Reactant: CC1NCCc2c(F)ccc(F)c21
Product: CC1c2c(F)ccc(F)c2CCN1C(=O)c1cc2ncc(Br)cn2n1

Procedure:
In close analogy to the procedure described in Example 1, 6-bromo-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 5,8-Difluoro-1-methyl-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]([CH:13]([CH:27]1[CH2:31][CH2:30][CH:29]([CH2:32]O)[CH2:28]1)[C:14]1[NH:15][C:16](=[O:26])[C:17]([OH:25])=[C:18]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[N:19]=1)[CH3:12])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.C(OC(N(C(C1CCC(COS(C)(=O)=O)C1)C1N(S(C)(=O)=O)C(=O)C(OS(C)(=O)=O)=C(C(OCC)=O)N=1)C)=O)C1C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].Cl>C1COCC1.CN(C=O)C.O>[CH2:1]([O:8][C:9]([N:11]([CH3:12])[C:13]12[CH2:32][CH:29]([CH2:30][CH2:31][CH2:27]1)[CH2:28][N:15]1[C:16](=[O:26])[C:17]([OH:25])=[C:18]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[N:19]=[C:14]21)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)c1nc(C(C2CCC(CO)C2)N(C)C(=O)OCc2ccccc2)[nH]c(=O)c1O
Agent: CCOC(=O)c1nc(C(C2CCC(COS(C)(=O)=O)C2)N(C)C(=O)OCc2ccccc2)n(S(C)(=O)=O)c(=O)c1OS(C)(=O)=O
Agent: CS(=O)(=O)Cl
Agent: Cl
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(CC)CC
Product: CCOC(=O)c1nc2n(c(=O)c1O)CC1CCCC2(N(C)C(=O)OCc2ccccc2)C1
Temperature: 80 °C
Reaction time: 12 h

Procedure:
To ethyl 2-(((benzyloxycarbonyl)(methyl)amino)(3-(hydroxymethyl)cyclopentyl)methyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate (0.235 g, 0.511 mmol)in THF (30 mL) at 0° C. was added triethylamine (0.214 mL, 1.53 mmol) and methanesulfonyl chloride (0.119 mL, 1.53 mmol). The reaction mixture was stirrer at 23° C. for 3 hours. H2O (50 mL) was then added and the reaction mixture extracted with ethyl acetate (3×50 mL). The combined organic fractions were dried (MgSO4) and concentrated in vacuo. LCMS (+ESI, M+H+) m/z 694. To the crude ethyl 2-(((benzyloxycarbonyl)(methyl)amino)(3-((methylsulfonyloxy)methyl)cyclopentyl)methyl)-1-(methylsulfonyl)-5-(methylsulfonyloxy)-6-oxo-1,6-dihydropyrimidine-4-carboxylate (0.252 g, 0.363 mmol) dissolved in DMF (40 mL) was added Cs2CO3 (0.590 g, 1.816 mmol). The reaction mixture was stirred at 80° C. for 12 hours. HCl (1N, 40 ml) was added and the organic material was extracted with ethyl acetate (3×30 mL). The combined organic fractions were dried (MgSO4) and concentrated in vacuo to afford the title compound. LCMS (+ESI, M+H+) m/z 442.
Reaction SMILES: [CH3:1][NH:2][CH:3]=[O:4].[OH-].[Na+].C(=O)([O-])[O-].[K+].[K+].Br[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][OH:25]>S(=O)(=O)(O)[O-].C([N+](CCCC)(CCCC)CCCC)CCC.CN1C(=O)N(C)CCC1.O>[CH3:1][N:2]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][OH:25])[CH:3]=[O:4]
Reactant: CNC=O
Reactant: OCCCCCCCCCCCBr
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: O=S(=O)([O-])O
Solvent: O
Solvent: CN1CCCN(C)C1=O
Product: CN(C=O)CCCCCCCCCCCO
Temperature: 25 °C
Reaction time: 1 h
Yield: 91 %

Procedure:
A mixture of 5.8 g of N-methylformamide, 13.6 g of sodium hydroxide solution powder [sic], 5.8 g of potassium carbonate powder, 3.2 g of tetrabutylammonium bisulfate and 90 ml of dimethylpropyleneurea was stirred for 1 hour at room temperature. Thereafter, the resulting mixture was heated at 40° C. for 20 minutes and then to 70° C. At this temperature, a solution of 25 g of 11-bromoundecan-1-ol in 70 ml of dimethylpropyleneurea was added dropwise to the mixture. The resulting reaction mixture was then stirred for a further 12 hours at 70° C. and then poured onto 1.6 1 of water. The aqueous phase obtained was extracted with four times 180 ml of a solvent mixture of ether and ethyl acetate in a volume ratio of 1 1. The resulting organic phases were combined, and the combined organic phase was washed with three times 50 ml of water and then dried with sodium sulfate. After the sodium sulfate had been separated off and the organic solvent evaporated off, 20.5 g of N-methyl-N-(11-hydroxyundecyl)-formamide were obtained, which corresponded to a yield of 91%.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([OH:11])[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH2:19]([S:21](Cl)(=[O:23])=[O:22])[CH3:20]>C1(C)C=CC=CC=1.O>[CH2:19]([S:21]([O:11][C:7]1[CH:8]=[CH:9][CH:10]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:6]=1)(=[O:23])=[O:22])[CH3:20]
Reactant: CCS(=O)(=O)Cl
Reactant: CC(C)(C)c1cccc(O)c1
Solvent: CCN(CC)CC
Solvent: O
Solvent: Cc1ccccc1
Product: CCS(=O)(=O)Oc1cccc(C(C)(C)C)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 0.1 %

Procedure:
8.00 g (53.3 mol) of 3-tert-butylphenol and 5.93 g (58.6 mol) of triethylamine were dissolved in 80 mL of toluene followed by dropping in 7.53 g (58.6 mol) of ethanesulfonyl chloride over the course of 10 minutes at 10° C. followed by stirring for 10 minutes at 25° C. and confirming the 3-tert-butylphenol to no longer be present by gas chromatography. The reaction liquid was placed in water and following separation of the organic layer, was washed three times with water, once with saturated aqueous NaHCO3 solution and once with saturated brine followed by drying with MgSO4, concentrating and purifying the resulting residue by vacuum distillation to obtain 12.02 g (yield: 93%) of 3-tert-butylphenyl ethanesulfonate.
Reaction SMILES: [C:1]1([CH2:7][N:8]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:9]2[CH:16]=[CH:15][C:12]([CH:13]=O)=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:24]([CH2:26][C:27]([O:29][CH3:30])=[O:28])#[N:25]>N1CCCCC1.CO>[C:18]1([CH2:17][N:8]([CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:9]2[CH:10]=[CH:11][C:12]([CH:13]=[C:26]([C:24]#[N:25])[C:27]([O:29][CH3:30])=[O:28])=[CH:15][CH:16]=2)[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: COC(=O)CC#N
Reactant: O=Cc1ccc(N(Cc2ccccc2)Cc2ccccc2)cc1
Solvent: C1CCNCC1
Solvent: CO
Product: COC(=O)C(C#N)=Cc1ccc(N(Cc2ccccc2)Cc2ccccc2)cc1

Procedure:
A mixture of 4-(bis(phenylmethyl)amino]benzaldehyde (60.2 g, 0.20 mol), methyl cyanoacetate (21.8 g, 0.22 mol), methanol (300 mL), and piperidine (10 drops) is heated at reflux for 1.5 hours. After cooling, the yellow product is collected by filtration, washed with methanol, and dried in air. The yellow colorant, methyl 3-[4-[bis(phenylmethyl)amino]phenyl]-2-cyano-propenoate, is obtained in a yield of 53.5 g (70.0% of theory).
Reaction SMILES: FC1C=C(CN)C=NC=1.[F:10][C:11]1[C:12]([CH2:17][NH2:18])=[N:13][CH:14]=[CH:15][CH:16]=1.[CH:19]1([CH2:22][N:23]2[CH2:27][CH2:26][N:25]([C:28]3[S:29][C:30]([C:34](O)=[O:35])=[C:31]([CH3:33])[N:32]=3)[C:24]2=[O:37])[CH2:21][CH2:20]1>>[CH:19]1([CH2:22][N:23]2[CH2:27][CH2:26][N:25]([C:28]3[S:29][C:30]([C:34]([NH:18][CH2:17][C:12]4[C:11]([F:10])=[CH:16][CH:15]=[CH:14][N:13]=4)=[O:35])=[C:31]([CH3:33])[N:32]=3)[C:24]2=[O:37])[CH2:20][CH2:21]1
Reactant: Cc1nc(N2CCN(CC3CC3)C2=O)sc1C(=O)O
Reactant: NCc1ncccc1F
Agent: NCc1cncc(F)c1
Product: Cc1nc(N2CCN(CC3CC3)C2=O)sc1C(=O)NCc1ncccc1F
Yield: 60 %

Procedure:
Following the procedure as describe in Example 12, making variations as required to replace (5-fluoropyridin-3-yl)methanamine with (3-fluoropyridin-2-yl)methanamine to react with 2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid, the title compound was obtained as a white solid in 60% yield: mp 142-144° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.38-8.31 (m, 2H), 7.69-7.62 (m, 1H), 7.39-7.33 (m, 1H), 4.51-4.54 (m, 2H), 4.00-3.95 (m, 2H), 3.64-3.59 (m, 2H), 3.06 (d, J=6.0 Hz, 2H), 2.44 (s, 3H), 0.96-0.87 (m, 1H), 0.49-0.42 (m, 2H), 0.21-0.16 (m, 2H); 13C NMR (75 MHZ, DMSO-d6) δ 162.2, 159.1, 157.9, 155.7, 151.2, 146.2, 145.4, 124.5, 123.6, 118.2, 48.2, 42.5, 42.3, 40.8, 17.5, 9.3, 3.6; MS (ES+) m/z 389.9 (M+1).
Reaction SMILES: Br[CH2:2][C:3]1[CH:7]=[CH:6][S:5][C:4]=1[C:8]([CH3:10])=[O:9].CC(C)=O.[N-:15]=[N+:16]=[N-:17].[Na+]>O>[N:15]([CH2:2][C:3]1[CH:7]=[CH:6][S:5][C:4]=1[C:8]([CH3:10])=[O:9])=[N+:16]=[N-:17]
Reactant: CC(=O)c1sccc1CBr
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: CC(=O)c1sccc1CN=[N+]=[N-]
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
To a solution of methyl 3-bromomethyl-2-thienyl ketone (5 g., 0.023 mole) in 42 ml. of acetone and 4 ml. of water was added sodium azide (1.56 g., 0.024 mole) with caution (exothermic!). The resulting solution was stirred at room temperature for 2.5 hours, the acetone evaporated, the residue diluted with water and extracted with diethyl ether. The combined extracts were washed with water, saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over magnesium sulfate and the dried extracts evaporated to dryness to obtain 4.0 g. (97%) of yellow oil. 1H--NMR (CDCl3), ppm. (δ): 7.5 (d, J=5, aromatic-H), 7.2 (d, J=5, aromatic-H), 4.75 (s, CH2N3), 2.5 (s, CH3); IR spectrum (film, cm.-1 : 3100, 2100 (N3), 1660, 1525 and 1420.
Reaction SMILES: [Si:1]([O:8][CH2:9][CH:10](O)[CH2:11][C:12]1[CH:20]=[CH:19][C:18]2[CH2:17][CH2:16][CH2:15][C:14]=2[C:13]=1[OH:21])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[C:4]([Si:1]([CH3:2])([CH3:3])[O:8][CH2:9][CH:10]1[O:21][C:13]2[C:14]3[CH2:15][CH2:16][CH2:17][C:18]=3[CH:19]=[CH:20][C:12]=2[CH2:11]1)([CH3:5])([CH3:7])[CH3:6]
Reactant: CC(C)(C)[Si](C)(C)OCC(O)Cc1ccc2c(c1O)CCC2
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OCC1Cc2ccc3c(c2O1)CCC3
Temperature: 25 °C
Reaction time: 8 h
Yield: 45.8 %

Procedure:
To a solution of (±)-5-(3-{[tert-butyl(dimethyl)silyl]oxy}-2-hydroxypropyl)indan-4-ol (6.78 g, 21.02 mmol) in tetrahydrofuran (210 mL) cooled to 0° C. was added triphenylphosphine (5.79 g, 22.07 mmol) followed by diethylazodicarboxylate (3.84 g, 22.07 mmol) and the reaction mixture was allowed to stir at room temperature overnight. The reaction mixture was quenched by the addition of water (10 mL) and the solvent was removed in vacuo to give a crude solid. Purification by flash column chromatography (silica, ethyl acetate:hexanes 1:7) provided 2.93 g (46%) of (±)-tert-butyl(dimethyl)(3,6,7,8-tetrahydro-2H-indeno[4,5-b]furan-2-ylmethoxy)silane as a colorless oil. Rf=0.86 (silica, ethyl acetate:hexanes 1:5); Anal. calcd. for C18H28O2Si: C, 71.0; H, 9.27. Found: C, 69.77; H, 9.21.
Reaction SMILES: O[C:2]1([C:17]2[C:26]([OH:27])=[CH:25][C:20]3[N:21]=[C:22]([CH3:24])[S:23][C:19]=3[CH:18]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:3]1=[O:16]>I>[OH:27][C:26]1[C:17]([CH:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[N:4]([CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:3]2=[O:16])=[CH:18][C:19]2[S:23][C:22]([CH3:24])=[N:21][C:20]=2[CH:25]=1
Reactant: CCCCCN1C(=O)C(O)(c2cc3sc(C)nc3cc2O)c2ccccc21
Agent: I
Product: CCCCCN1C(=O)C(c2cc3sc(C)nc3cc2O)c2ccccc21

Procedure:
A suspension of 3-hydroxy-3-(5-hydroxy-2-methyl-1,3-benzothiazol-6-yl)-1-pentyl-1,3-dihydro-2H-indol-2-one (0.50 g, 1.31 mmol) in hydroiodic acid (10.0 mL) was refluxed for 1.5 days. The reaction mixture was concentrated in vacuo to dryness.
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH2:7][C:6]([CH3:14])=[CH:5][CH2:4][C:3]1=2.[OH2:16].[OH2:17].C[N+]([O-])(C)C>C(O)(C)(C)C.O.[Os](=O)(=O)(=O)=O>[CH3:1][C:2]1([CH3:15])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH2:7][C:6]([CH3:14])([OH:16])[CH:5]([OH:17])[CH2:4][C:3]1=2
Reactant: CC1=CCC2=C(C1)C(C)(C)CCC2(C)C
Reactant: O
Agent: O=[Os](=O)(=O)=O
Agent: C[N+](C)(C)[O-]
Solvent: CC(C)(C)O
Product: CC1(C)CCC(C)(C)C2=C1CC(O)C(C)(O)C2
Reaction time: 48 h

Procedure:
253.3 g of hydrocarbon mixture containing about 60% of 2,2,5,5,8-pentamethyl-bicyclo[4.4.0]deca-1(6),8-diene are dissolved in 1050 ml of tert.butanol and treated with a solution of 91.65 g of trimethylamine N-oxide dihydrate in 375 ml of water. Thereto there is added a solution of 40 mg of osmium tetroxide in 75 ml of tert.butanol and the mixture is held for 48 hours at 95° C. with good stirring at reflux temperature. The solution is extracted with 2 l of dichloromethane, 1 l of water and 412.5 ml of 2N hydrochloric acid and ice. The organic phase is washed neutral twice with 1 l of water each time and the aqueous phases are extracted with dichloromethane. After drying over magnesium sulphate and concentration on a rotary evaporator, there are obtained 269 g of crude crystals. These are recrystallized from 150 ml of hexane and 80 ml of dichloromethane. There are obtained 167.0 g of crystalline 2,2,5,5,8-pentamethyl-bicyclo[4.4.0]dec-1(6)-ene-8,9-diol of melting point 98°-99.5° C.