Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[O:3]=[C:4]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:5]P(=O)(OC)OC.[CH3:19][O:20][C:21](=[O:37])[CH2:22][O:23][CH2:24][CH2:25][CH2:26][CH2:27][N:28]1[C:33](=[O:34])[CH2:32][CH2:31][CH2:30][C@@H:29]1[CH:35]=O>C1COCC1>[CH3:19][O:20][C:21](=[O:37])[CH2:22][O:23][CH2:24][CH2:25][CH2:26][CH2:27][N:28]1[C@@H:29](/[CH:35]=[CH:5]/[C:4](=[O:3])[CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:30][CH2:31][CH2:32][C:33]1=[O:34]
Reactant: COC(=O)COCCCCN1C(=O)CCC[C@@H]1C=O
Reactant: COP(=O)(CC(=O)Cc1ccccc1)OC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)COCCCCN1C(=O)CCC[C@@H]1/C=C/C(=O)Cc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 31.9 %

Procedure:
Sodium hydride (60% dispersion in oil, 14 mg, 0.35 mmol) was added to a solution of dimethyl 2-oxo-3-phenylpropylphosphonate (83 mg, 0.34 mmol) in THF (1.0 mL) at 0° C. After 1 h at 0° C., [4-((R)-2-formyl-6-oxo-piperidin-1-yl)-butoxy]-acetic acid methyl ester (94 mg, 0.35 mmol) in THF (1 mL) was added via cannula. The reaction was allowed to warm to rt. After 22 h at rt, the reaction was quenched with saturated aqueous NH4Cl (10 mL) and extracted with EtOAc (3×15 mL). The combined organic phase was washed with brine (20 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (30% →50% EtOAc/CH2Cl2, gradient) afforded 42 mg (31%) of the title compound.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[N:20](COCC[Si](C)(C)C)[C:19](=[O:29])[C:18]3[C:13](=[CH:14][CH:15]=[C:16](I)[CH:17]=3)[N:12]=2)[CH:10]=1)=[O:5])C.[F:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1>>[F:31][C:32]1[CH:37]=[CH:36][C:35]([C:16]2[CH:17]=[C:18]3[C:13](=[CH:14][CH:15]=2)[N:12]=[C:11]([N:9]2[CH:10]=[C:6]([C:4]([OH:3])=[O:5])[CH:7]=[N:8]2)[NH:20][C:19]3=[O:29])=[CH:34][CH:33]=1
Reactant: OB(O)c1ccc(F)cc1
Reactant: CCOC(=O)c1cnn(-c2nc3ccc(I)cc3c(=O)n2COCC[Si](C)(C)C)c1
Product: O=C(O)c1cnn(-c2nc3ccc(-c4ccc(F)cc4)cc3c(=O)[nH]2)c1

Procedure:
The titled compound was prepared in a manner analogous to Example 69, steps C-E, using 1-[6-iodo-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (Example 69 product from step B) and 4-fluorophenylboronic acid in step C. MS (ESI): mass calcd. for C18H11FN4O3, 350.1; m/z found, 351.1 [M+H]+. 1H NMR (600 MHz, DMSO-d6): 13.01 (br s, 1H), 12.92 (br s, 1H), 8.98 (s, 1H), 8.32 (s, 1H), 8.28 (s, 1H), 8.16 (dd, J=8.5, 2.2 Hz, 1H), 7.88-7.82 (m, 2H), 7.79 (s, 1H), 7.37-7.32 (m, 2H).
Reaction SMILES: [CH2:1]([C:3]1[C:8](=[O:9])[NH:7][C:6]([CH3:10])=[C:5]([C:11]2[S:15][C:14]([S:16](Cl)(=[O:18])=[O:17])=[CH:13][CH:12]=2)[CH:4]=1)[CH3:2].[OH:20][CH:21]1[CH2:25][CH2:24][NH:23][CH2:22]1>>[CH2:1]([C:3]1[C:8](=[O:9])[NH:7][C:6]([CH3:10])=[C:5]([C:11]2[S:15][C:14]([S:16]([N:23]3[CH2:24][CH2:25][CH:21]([OH:20])[CH2:22]3)(=[O:18])=[O:17])=[CH:13][CH:12]=2)[CH:4]=1)[CH3:2]
Reactant: OC1CCNC1
Reactant: CCc1cc(-c2ccc(S(=O)(=O)Cl)s2)c(C)[nH]c1=O
Product: CCc1cc(-c2ccc(S(=O)(=O)N3CCC(O)C3)s2)c(C)[nH]c1=O
Yield: 48.8 %

Procedure:
5-(5-Ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonyl chloride is reacted with 3-hydroxypyrrolidine as described in Step 5, Example 24 to give the title compound as a solid (48.8% yield). LC/MS: RT 2.42 min; m/e 369 (M+H); 1H NMR (δ, ppm): 11.8 (1H, s), 7.6 (1H, d); 7.38 (1H, d); 7.2 (1H, d), 4.92 (1H, br s), 4.2 (1H, s), 3.38 (4H, m), 3.07 (1H, d), 2.4 (2H, q), 2.32 (3H, s), 1.8 (2H, m), 1.08 (3H, t).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=O)[NH:7][CH2:6][CH2:5]2.CO>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][NH:7][CH2:6][CH2:5]2
Reactant: O=C1NCCc2cc(Br)ccc21
Solvent: C1CCOC1
Solvent: CO
Product: Brc1ccc2c(c1)CCNC2

Procedure:
A solution of 6-bromo-3,4-dihydro-1(1H)-isoquinolinone (Example 31, Step 1; 5.5 g, 1.0 mmol) in THF (25 mL) was treated with 1M BH3 in THF (5 mL, 5 mmol) and heated at reflux for 20 h. To the mixture was added MeOH (5 mL), the solvent removed and the residue heated with 2N HCl for 3 h. The reaction was cooled, made basic with aqueous NH4OH and extracted with CH2Cl2, dried and evaporated to give the title compound as a gum which was used as such.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10]O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Br)(Br)[Br:13]>C(OCC)(=O)C>[Br:13][CH2:10][CH2:9][CH2:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OCCCCc1ccccc1
Reactant: BrP(Br)Br
Solvent: CCOC(C)=O
Product: BrCCCCc1ccccc1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To 1.50 g of 4-phenylbutanol was added 385 μl of phosphorus tribromide with ice cooling, and the mixture was stirred at a room temperature for 5 minutes and then at 80° C. for one hour. To the reaction mixture were added 20 ml of ice water and 30 ml of ethyl acetate. The separated organic layer was, successively washed with water, 5% sodium bicarbonate aqueous solution and a saturated sodium chloride aqueous solution, dried over magnesium sulfate, and evaporated under a reduced pressure to obtain an oily residue. The residue was applied to a silica gel column and eluted with hexane/benzene (6:1) to obtain 1.94 g of (4-bromobutyl)benzene as a colorless liquid.
Reaction SMILES: Br[C:2]1[CH:15]=[CH:14][C:5]([O:6][CH2:7][CH2:8][N:9]([CH2:12][CH3:13])[CH2:10][CH3:11])=[CH:4][CH:3]=1.[CH3:16][C:17]1([CH3:38])[C:21]([CH3:23])([CH3:22])[O:20][B:19](C2C=CC(OC3C=CC=CC=3)=CC=2C)[O:18]1>>[CH2:10]([N:9]([CH2:12][CH3:13])[CH2:8][CH2:7][O:6][C:5]1[CH:14]=[CH:15][C:2]([B:19]2[O:20][C:21]([CH3:23])([CH3:22])[C:17]([CH3:38])([CH3:16])[O:18]2)=[CH:3][CH:4]=1)[CH3:11]
Reactant: Cc1cc(Oc2ccccc2)ccc1B1OC(C)(C)C(C)(C)O1
Reactant: CCN(CC)CCOc1ccc(Br)cc1
Product: CCN(CC)CCOc1ccc(B2OC(C)(C)C(C)(C)O2)cc1

Procedure:
Prepared from [2-(4-bromo-phenoxy)-ethyl]-diethyl-amine according to general Method I for borylation described above for preparation of 4,4,5,5-tetramethyl-2-(2-methyl-4-phenoxy-phenyl)-[1,3,2]dioxaborolane.
Reaction SMILES: [CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:26](O)=[O:27])=[C:21]5[C:25]=4[O:24][CH2:23][CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:29])[C:8](=[O:30])[C@H:7]2[CH2:31][CH3:32])[CH2:5][CH2:4][CH2:3][CH2:2]1.F[B-](F)(F)F.[N:38]1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>ClCCl>[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:26]([NH2:38])=[O:27])=[C:21]5[C:25]=4[O:24][CH2:23][CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:29])[C:8](=[O:30])[C@H:7]2[CH2:31][CH3:32])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Reactant: CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)O)c4c3OCC4)nc2N1C1CCCC1
Agent: F[B-](F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(N)=O)c4c3OCC4)nc2N1C1CCCC1
Yield: 90.6 %

Procedure:
7-[[(7R)-8-Cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 1q (187 mg, 0.43 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (138 mg, 0.43 mmol) were dissolved in 40 mL of anhydrous dichloromethane followed by the addition of diisopropylethylamine (0.2 mL, 0.95 mmol), stirred until the solution became clear, followed by the addition of 5 mL of a solution of (cis-exo)-2-methyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-amine 5k (60 mg, 0.43 mmol) in dichloromethane, and stirred for another 2 hours. The resulting solution was added with 30 mL of dichloromethane, washed with dilute aqueous ammonia (20 mL), water (20 mL) and saturated sodium chloride solution (20 mL) successively, then dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (cis-exo)-N-2-methyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]-7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxamide 5 (170 mg, yield: 71.0%) as a white solid.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:12]=2[CH2:13][CH:14]([CH2:21][C:22]2([CH2:28][CH3:29])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[C:15]3=O)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].C1(C)C=CC=CC=1.OS(O)(=O)=O>CO>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:12]=2[CH2:13][C:14]([CH2:21][C:22]2([CH2:28][CH3:29])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]2)=[CH:15]3)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CCC1(CC2Cc3c(cccc3-c3ccc(C(C)(C)C)cc3)C2=O)CCCCC1
Agent: O=S(=O)(O)O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: Cc1ccccc1
Product: CCC1(CC2=Cc3cccc(-c4ccc(C(C)(C)C)cc4)c3C2)CCCCC1
Temperature: 50 °C
Reaction time: 2.5 h
Yield: 97.3 %

Procedure:
24.0 g of crude 4-(4-tert-butyl-phenyl)-2-[(1-ethylcyclohexyl)methyl]indan-1-one (˜82% purity), 2.4 g (63.4 mmol) of NaBH4 and 60 ml of toluene are charged in a flask equipped with reflux condenser, dropping funnel and magnetic stirring bar. The mixture is warmed to 50° C. and 12 ml of methanol are slowly added with stirring and stirring is continued for 2.5 h to ensure a complete reaction. Excess NaBH4 is carefully hydrolyzed with approx. 35 ml of 2n H2SO4. The organic phase is separated and the water phase is washed with another 30 ml of toluene. The combined organic phases are twice extracted with 2n H2SO4 and dried over anhydrous MgSO4. Most of the solvent is removed in a vacuum and replaced by fresh toluene up to a total volume of 90 ml and 0.26 g of p-toluenesulfonic acid are added. The reaction flask is fitted with a water separator and the reaction mixture is heated to reflux for 1.5 h. The conversion can be monitored by TLC. Once the dehydration is complete, the solution is washed with a saturated NaHCO3 solution and dried over anhydrous MgSO4. The solvent is thoroughly removed in a vacuum and 22.4 g of a brown oil is obtained. Purification of the indene is carried out via a column chromatography. Yield: 15.3 g (˜81%) of 7-(4-tert-Butyl-phenyl)-2-[(1-ethylcyclohexyl)methyl]-1H-indene.
Reaction SMILES: [C:1]([C:3]1[S:4][C:5]2[C:11]([C:12]#[N:13])=[C:10](/[N:14]=[CH:15]/[N:16](C)C)[CH:9]=[CH:8][C:6]=2[N:7]=1)#[N:2].[CH3:19][O:20][C:21]1[CH:22]=[C:23]([CH:25]=[C:26]([O:30][CH3:31])[C:27]=1[O:28][CH3:29])N.[K+].[Br-]>C(Cl)Cl.CCOC(C)=O>[CH3:31][O:30][C:26]1[CH:25]=[C:23]([NH:13][C:12]2[C:11]3[C:10](=[CH:9][CH:8]=[C:6]4[N:7]=[C:3]([C:1]#[N:2])[S:4][C:5]4=3)[N:14]=[CH:15][N:16]=2)[CH:22]=[C:21]([O:20][CH3:19])[C:27]=1[O:28][CH3:29]
Reactant: COc1cc(N)cc(OC)c1OC
Reactant: CN(C)/C=N/c1ccc2nc(C#N)sc2c1C#N
Agent: [Br-]
Agent: [K+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: COc1cc(Nc2ncnc3ccc4nc(C#N)sc4c23)cc(OC)c1OC
Yield: 94 %

Procedure:
Prepared from VII and 3,4,5-trimethoxyaniline. Flash chromatography eluent (DCM-EtOAc, 5:5). Yield: 94%; pale yellow solid, mp 230° C.; IR (KBr) νmax/cm−1 3255, 3089, 3001, 2947, 2837, 2230, 1735, 1637, 1613, 1581, 1498, 1458, 1412, 1381, 1352, 1307, 1270, 1229, 1193, 1165, 1122, 1037, 1002, 991, 970, 952, 852, 830; 1H NMR (300 MHz, DMSO-d6) δ 8.51 (d, 1H, J=9.0 Hz), 8.05 (s, 1H), 7.80 (d, 1H, J=9.0 Hz), 6.46 (s, 2H), 3.77 (s, 6H), 3.67 (s, 3H); HRMS calcd for C19H16N5O3S (M+H+): 394.0974, found 394.0987.
Reaction SMILES: [Si]([O:8][C@:9]1([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([S:22][C:23]3[CH:24]=[C:25]4[C:30](=[CH:31][CH:32]=3)[NH:29][C:28](=[O:33])[CH2:27][CH2:26]4)[CH:17]=2)[CH2:14][CH2:13][O:12][C@@H:11]([CH3:15])[CH2:10]1)(C(C)(C)C)(C)C.[CH2:34](Cl)[CH:35]=[CH2:36].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>>[CH2:36]([N:29]1[C:30]2[C:25](=[CH:24][C:23]([S:22][C:18]3[CH:17]=[C:16]([C@@:9]4([OH:8])[CH2:14][CH2:13][O:12][C@@H:11]([CH3:15])[CH2:10]4)[CH:21]=[CH:20][CH:19]=3)=[CH:32][CH:31]=2)[CH2:26][CH2:27][C:28]1=[O:33])[CH:35]=[CH2:34]
Reactant: C=CCCl
Reactant: C[C@H]1C[C@@](O[Si](C)(C)C(C)(C)C)(c2cccc(Sc3ccc4c(c3)CCC(=O)N4)c2)CCO1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Product: C=CCN1C(=O)CCc2cc(Sc3cccc([C@@]4(O)CCO[C@@H](C)C4)c3)ccc21
Yield: 86 %

Procedure:
Using an analogous procedure to that described in Example 18, (2S,4R)-4-(tert-butyldimethylsilyloxy)-2-methyl-4-[3-(2-oxo-1,2,3,4-tetrahydroquinolin-6-ylthio)phenyl]tetrahydropyran was reacted with allyl chloride and the resultant product was treated with tetrabutylammonium fluoride to give (2S,4R)-4-[3-(1-allyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-ylthio)phenyl]-4-hydroxy-2-methyltetrahydropyran in 86% yield, m.p. 107°-109° C. (recrystallised from diethyl ether);
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[CH3:10].CCN(CC)CC.[CH3:18][O:19][CH2:20]Cl>C(Cl)Cl.CCOC(C)=O>[CH3:18][O:19][CH2:20][O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[CH3:10]
Reactant: COCCl
Reactant: Cc1cc(C=O)ccc1O
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: COCOc1ccc(C=O)cc1C
Temperature: 25 °C
Reaction time: 16 h
Yield: 52.9 %

Procedure:
To a solution of 4-hydroxy-3-methylbenzaldehyde (900 mg, 6.61 mmol) in CH2Cl2 (19 mL) was added Et3N (5.90 mL, 42.3 mmol) and chloromethyl methyl ether (2.00 mL, 26.3 mmol). The reaction was stirred at 25° C. for 16 h. The reaction mixture was diluted with EtOAc and was successively washed with aqueous 1 N HCl solution, aqueous saturated NaHCO3 solution, water and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (Hexane:EtOAc, 4:1) to give the title compound (630 mg, 53% yield) as a clear oil.
Reaction SMILES: [N+](=C)=[N-].[CH3:4][O:5][C:6]([CH:8]1[CH2:12][S:11][CH2:10][C:9]1=[O:13])=[O:7].[CH:14](Cl)(Cl)Cl>CCOCC>[CH3:4][O:5][C:6]([C:8]1[CH:9]([O:13][CH3:14])[CH2:10][S:11][CH:12]=1)=[O:7]
Reactant: COC(=O)C1CSCC1=O
Reactant: ClC(Cl)Cl
Agent: C=[N+]=[N-]
Solvent: CCOCC
Product: COC(=O)C1=CSCC1OC
Temperature: 0 °C
Reaction time: 21 h
Yield: 86 %

Procedure:
15 Parts by volume of an 0.5 molar solution of diazomethane in ether are added in the course of about 10 minutes to a solution, cooled to 0° C., of 1.6 parts of 3-oxo-tetrahydrothiophene-4-carboxylic acid methyl ester in 10 parts by volume of dry chloroform. The solution is stirred for 21 hours at 0° C., flushed with nitrogen to remove excess diazomethane and concentrated under reduced pressure. The residue is recrystallized from methylene chloride/petroleum ether. 1.5 parts (86% of theory) of 3-methoxy-dihydrothiophene-4-carboxylic acid methyl ester of melting point 79°-81° C. are obtained.
Reaction SMILES: [C:1]1([S:7]([CH2:10][C:11](O)=O)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[C:1]1([S:7](/[CH:10]=[CH:11]/[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(O)CS(=O)(=O)c1ccccc1
Reactant: O=Cc1ccccc1
Product: O=S(=O)(/C=C/c1ccccc1)c1ccccc1
Yield: 68 %

Procedure:
A solution of phenyl sulfonylacetic acid (0.01 mol) and benzaldehyde (0.01 mol) was subjected to the Procedure 1, Part B. The title compound was obtained in 68-72% yield.
Reaction SMILES: [CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([C:16](=[NH:21])[O:17][CH2:18][CH2:19][CH3:20])[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:22](Cl)(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>>[C:22]([N:21]=[C:16]([N:7]1[CH2:6][C:5]2[CH:4]=[CH:3][CH:2]=[CH:1][C:11]=2[C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[CH2:8]1)[O:17][CH2:18][CH2:19][CH3:20])(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: CCCOC(=N)N1Cc2ccccc2-c2ccccc2C1
Product: CCCOC(=NC(=O)c1ccccc1)N1Cc2ccccc2-c2ccccc2C1

Procedure:
starting from propyl 5,7-dihydro-6H-dibenz[c,e]-azepine-6-carboximidate and benzoyl chloride, there is obtained propyl N-benzoyl-5,7-dihydro-6H-dibenz[c,e]-azepine-6-carboximidate as a resin, mass spectrum m/e: M+ 384 (7), 341 (13), 194 (100), 179 (23), 105 (59);
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:13])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][CH:7]=1)[CH3:2].C=O.[C:16]([O-])([O-])=O.[K+].[K+]>[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].CN(C=O)C.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:13])[C:5]([C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][CH:7]=1)=[CH2:16])[CH3:2]
Reactant: O=C([O-])[O-]
Reactant: CCOC(=O)Cc1ccc(Br)cc1
Agent: C=O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C=C(C(=O)OCC)c1ccc(Br)cc1
Yield: 72.5 %

Procedure:
To a solution of (4-bromo-phenyl)-acetic acid ethyl ester (972.4 mg, 4 mmol), paraformaldehyde (240 mg, 8 mmol), and Bu4NCl (22 mg, 0.08 mmol) in DMF (10 mL) was added K2CO3 (1.32 g, 9.6 mmol). This mixture was heated at 60 degrees Celsius for 2 h. Then the mixture was cooled and diluted with EtOAc (30 mL) and washed with water (20 mL×3), brine, dried over Na2SO4, filtered and evaporated. The residue was purified by flash column chromatography on silica gel to give a white solid (0.74 g, 73%). MS: calc'd 255 (MH+), exp 255 (MH+).
Reaction SMILES: [CH2:1]([O:10][C:11]1[CH:12]=[N:13][C:14]([C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]C)=[CH:19][CH:18]=2)=[N:15][CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].C(OC1C=NC(C2C=CC(CCCCCCCCCCCC)=CC=2)=NC=1)CCCCCCCC.C(OC1C=NC(C2C=CC(CCCCCCCCCCC)=CC=2)=NC=1)CCCCCCCC>>[CH2:1]([O:10][C:11]1[CH:12]=[N:13][C:14]([C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[CH:19][CH:18]=2)=[N:15][CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCCCCCCOc1cnc(-c2ccc(CCCCCC)cc2)nc1
Agent: CCCCCCCCCCCCc1ccc(-c2ncc(OCCCCCCCCC)cn2)cc1
Agent: CCCCCCCCCCCc1ccc(-c2ncc(OCCCCCCCCC)cn2)cc1
Product: CCCCCCCCCOc1cnc(-c2ccc(CCCCC)cc2)nc1

Procedure:
5-nonyloxy-2-(4-hexylphenyl)pyrimdine ##STR15## 5-nonyloxy-2-(4-heptylphenyl)pyrimidine ##STR16## 5-nonyloxy-2-(4-octylphenyl)pyrimidine ##STR17## 5-nonyloxy-2-(4-nonylphenyl)pyrimidine ##STR18## 5-nonyloxy-2-(4-decylphenyl)pyrimidine ##STR19## 5-nonyloxy-2-(4-undecylphenyl)pyrimidine 5-nonyloxy-2-(4-dodecylphenyl)pyrimidine
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4].[P:12]12(SP3(SP(SP(S3)(S1)=S)(=S)[S:14]2)=S)=[S:13]>CCCCCC>[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([P:12](=[S:14])=[S:13])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOc1ccccc1
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: CCCCCC
Product: CCCCOc1ccc(P(=S)=S)cc1
Reaction time: 48 h

Procedure:
n-Butyloxybenzene (Ic) and P4S10 (in a molar ratio of 10:1) were stirred for six hours at 150° C. under anhydrous conditions. The mixture was cooled, hexane was added, and the reaction flask was left for two days at 5° C. The resulting precipitate was recovered by filtration, washed with anhydrous hexane and dried. The yield of product was 37% of theory; after recrystallization from chloroform/petroleum ether it melted at 142°-4° C. Its solubility in tetrahydrofuran was found to be 5 gms/100 ml at room temperature.
Reaction SMILES: [NH2:1][C:2]1[C:11]([N+:12]([O-])=O)=[CH:10][C:9]2[C:4](=[CH:5][C:6]([S:15][CH2:16][CH:17]([CH3:19])[CH3:18])=[CH:7][CH:8]=2)[CH:3]=1.S(S([O-])=O)([O-])=O.[Na+].[Na+].O>C(O)C>[CH2:16]([S:15][C:6]1[CH:5]=[C:4]2[C:9]([CH:10]=[C:11]([NH2:12])[C:2]([NH2:1])=[CH:3]2)=[CH:8][CH:7]=1)[CH:17]([CH3:19])[CH3:18]
Reactant: CC(C)CSc1ccc2cc([N+](=O)[O-])c(N)cc2c1
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CC(C)CSc1ccc2cc(N)c(N)cc2c1

Procedure:
To 0.025 mole of the 2-amino-7-isobutylthio-3-nitronaphthalene (prepared in Example 5) in 100 ml of 95% ethanol is added a solution of 3.4 equivalents of sodium hydrosulfite (Na2S2O4) in a solution of 100 ml of water and 15 ml concentrated (28%) ammonium hydroxide. The mixture is refluxed for 5 minutes and an amount of hydrosulfite solution equal to 10% of the original is added to the refluxing mixture. TLC (silica gel, ether) indicates consumption of starting material. The mixture is concentrated to one-half its original volume under vacuum and the residual mixture extracted with two 150 ml portions of chloroform. The combined chloroform extracts are dried (Na2SO4), filtered, and evaporated to dryness to yield the crude title compound which is used without further purification in Example 7.
Reaction SMILES: Br[C:2]1[C:3]([C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[O:29])=[CH:4][C:5]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[C:6]([CH:18]=1)[C:7]([O:9]CC1C=CC(F)=CC=1)=[O:8].[CH3:36][N:37]1[CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH:39]=[N:38]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Li+].Cl>COCCOC.O.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.O1CCCC1>[F:27][C:24]1[CH:23]=[CH:22][C:21]([CH2:20][O:19][C:5]2[CH:4]=[C:3]([C:28]([N:30]3[CH2:31][CH2:32][O:33][CH2:34][CH2:35]3)=[O:29])[C:2]([C:40]3[CH:39]=[N:38][N:37]([CH3:36])[CH:41]=3)=[CH:18][C:6]=2[C:7]([OH:9])=[O:8])=[CH:26][CH:25]=1
Reactant: O=C(OCc1ccc(F)cc1)c1cc(Br)c(C(=O)N2CCOCC2)cc1OCc1ccc(F)cc1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cl
Agent: O=P([O-])([O-])[O-]
Solvent: O
Solvent: COCCOC
Solvent: C1CCOC1
Product: Cn1cc(-c2cc(C(=O)O)c(OCc3ccc(F)cc3)cc2C(=O)N2CCOCC2)cn1
Temperature: 130 °C

Procedure:
To a solution of 4-fluorobenzyl 5-bromo-2-((4-fluorobenzyl)oxy)-4-(morpholine-4-carbonyl)benzoate (380 mg, 0.696 mmol) (may be prepared as described in description D19) in 1,2-Dimethoxyethane (DME) (10 mL)/Water (1.00 mL) was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (217 mg, 1.043 mmol), Tetrakis (48.2 mg, 0.042 mmol), tripotassium phosphate (295 mg, 1.391 mmol). The vial was sealed and heated to 130° C. for 25 min. Mixture was diluted with water (50 ml) and extracted with ethyl acetate (3×50 ml), the organics were combined, dried (MgSO4) and evaporated on a buchi under reduced pressure. No attempt was made to purify this intermediate it was taken up into a mixture of Tetrahydrofuran (THF) (10.00 mL)/Water (1.00 mL) and lithium hydroxide (33.3 mg, 1.391 mmol) was added. The mixture was then heated to 80° C. for 3 hrs. The mixture on cooling was diluted with water (50 ml) and acidified to pH2 using 2M aqueous HCl. The solid formed was filtered off, washed with water (2×20 ml) and dried in air under vacuum to give the title compound as an off white solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:27])[NH:4][C@@H:5]1[C@@H:9]([NH:10][C:11](=[O:19])[CH2:12][CH2:13][C:14]([F:18])([F:17])[CH2:15]Cl)[CH2:8][N:7]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:6]1.CC(C)([O-])C.[Na+]>CN(C)C=O>[CH3:1][O:2][C:3](=[O:27])[NH:4][C@@H:5]1[C@@H:9]([N:10]2[CH2:15][C:14]([F:18])([F:17])[CH2:13][CH2:12][C:11]2=[O:19])[CH2:8][N:7]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:6]1
Reactant: COC(=O)N[C@H]1CN(Cc2ccccc2)C[C@@H]1NC(=O)CCC(F)(F)CCl
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)N[C@H]1CN(Cc2ccccc2)C[C@@H]1N1CC(F)(F)CCC1=O
Temperature: 25 °C
Yield: 68 %

Procedure:
A solution of the product from Step 4 (0.50 g, 1.24 mmol) in N,N-dimethylformamide (3.0 mL) was cooled to 0° C. and sodium tert-butoxide (0.24 g, 2.54 mol) was added. The reaction was stirred and warmed to room temperature over 1.5 hours. The reaction was quenched by the addition of ice (50 g) and the resulting mixture was diluted with H2O (20 mL), methyl tert-butyl ether (30 mL) and ethyl acetate (100 mL). The organic layer was separated, washed with a 2% lithium chloride solution (20 mL) and then saturated sodium chloride solution (20 mL). The organic layer was dried over sodium sulfate and concentrated to afford a solid that was triturated with a 1:1 cyclohexan/heptane mixture to provide 0.31 g (68%) of the product as a light-yellow solid. 1H NMR (400 MHz, Methanol-d4) δ 7.38-7.18 (m, 5H), 4.87-4.51 (m, 1H), 4.22-4.11 (m, 1H), 3.94-3.48 (m, 4H), 3.59 (s, 3H), 3.22-3.07 (m, 1H), 2.78-2.64 (m, 2H), 2.61-2.43 (m, 2H), 2.40-2.13 (m, 3H). MS 368.2 (AP+, 100).