Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N1[CH2:12][CH2:11][CH:10]([C:13](=[O:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)C1)C1C=CC=CC=1.C([CH:23]1CCC[N:24]1[CH2:28][CH2:29][CH2:30][O:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)#N.[F:38]C1C=CC([Mg]Br)=CC=1>>[F:38][C:17]1[CH:16]=[CH:15][C:14]([C:13]([CH:10]2[CH2:11][CH2:12][CH2:23][N:24]2[CH2:28][CH2:29][CH2:30][O:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:20])=[CH:19][CH:18]=1
Reactant: Fc1ccc([Mg]Br)cc1
Reactant: O=C(c1ccccc1)C1CCN(Cc2ccccc2)C1
Reactant: N#CC1CCCN1CCCOc1ccccc1
Product: O=C(c1ccc(F)cc1)C1CCCN1CCCOc1ccccc1

Procedure:
Following the procedure for the preparation of 1-benzyl-3-benzoylpyrrolidine (U.S. Pat. No. 3,479,370) the title compound is prepared from 2-cyano-1-(3-phenoxypropyl)pyrrolidine and 4-fluorophenylmagnesium bromide.
Reaction SMILES: CC1C=CC(S(O[C:12]2[C:13]3[CH2:23][CH2:22][CH2:21][CH2:20][C:19]([CH3:25])([CH3:24])[C:14]=3[N:15]=[C:16]([NH2:18])[N:17]=2)(=O)=O)=CC=1.[N:26]1(C(OC(C)(C)C)=O)[CH2:31][CH2:30][CH2:29][C@@H:28]2[CH2:32][NH:33][CH2:34][C@H:27]12.N1C[CH2:45][C@@H:44](NC(=O)OC(C)(C)C)[CH2:43]1>>[C:19]1([CH:20]2[C:12]3[N:17]=[C:16]([NH2:18])[N:15]=[C:14]([N:33]4[CH2:32][C@@H:28]5[C@@H:27]([NH:26][CH2:31][CH2:30][CH2:29]5)[CH2:34]4)[C:13]=3[CH2:23][CH2:22][CH2:21]2)[CH:24]=[CH:45][CH:44]=[CH:43][CH:25]=1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]2CNC[C@@H]21
Reactant: Cc1ccc(S(=O)(=O)Oc2nc(N)nc3c2CCCCC3(C)C)cc1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCNC1
Product: Nc1nc2c(c(N3C[C@H]4CCCN[C@H]4C3)n1)CCCC2c1ccccc1

Procedure:
The title compound was prepared according to the procedures of Examples 1E and 1F, substituting the product from Example 9C for the product from Example 1D and substituting (4aR,7aR)-tert-butyl octahydro-1H-pyrrolo[3,4-b]pyridine-1-carboxylate for (R)-tert-butyl pyrrolidin-3-ylcarbamate. 1H NMR (300 MHz, CDCl3) δ 7.22 (m, J=4.36 Hz, 2H), 7.16 (m, 1H), 7.09 (d, J=8.33 Hz, 1H), 7.02 (d, J=8.72 Hz, 1H), 4.40 (s, 2H), 3.89 (m, 3H), 3.52 (m, 3H), 3.03 (m, 1H), 2.72 (m, 3H), 2.26 (m, 3H), 1.74 (m, 6H); MS (ESI+) m/z 350 (M+H)+.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[C:8](=[O:9])[C:7]2=[CH:10][CH:11]=[CH:12][CH:13]=[C:6]2[C:5]1=[O:14].B.[H][H].[CH3:18][C:19]1[C:33](=[O:34])[N:32]=[C:31]2[N:21]([C@@H:22]3[O:26][C@H:25]([CH2:27][OH:28])[C@@H:24]([OH:29])[C@@H:23]3[O:30]2)[CH:20]=1.C(=O)(O)[O-].[Na+]>O1CCCC1>[C:8]1(=[O:9])[N:4]([CH2:3][CH2:2][O:1][C@@H:23]2[C@H:24]([OH:29])[C@@H:25]([CH2:27][OH:28])[O:26][C@H:22]2[N:21]2[CH:20]=[C:19]([CH3:18])[C:33](=[O:34])[NH:32][C:31]2=[O:30])[C:5](=[O:14])[C:6]2=[CH:13][CH:12]=[CH:11][CH:10]=[C:7]12
Reactant: [H][H]
Reactant: O=C1c2ccccc2C(=O)N1CCO
Reactant: Cc1cn2c(nc1=O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]12
Agent: B
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1cn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2OCCN2C(=O)c3ccccc3C2=O)c(=O)[nH]c1=O
Temperature: 150 °C
Reaction time: 0.5 h
Yield: 90 %

Procedure:
N-(2-Hydroxyethyl)phthalimide (277 g, 1.45 mol) was slowly added to a solution of borane in tetrahydrofuran (1 M, 600 mL) with stirring. Hydrogen gas evolved as the solid dissolved. Once the rate of bubbling subsided, the solution was placed in a 2 L stainless steel bomb. 2,2′-anhydro-5-methyluridine (60 g, 0.25 mol) and sodium bicarbonate (120 mg) were added and the bomb was sealed. After 30 minutes, the bomb was vented for the last time and then placed in an oil bath and heated to 150° C. internal temperature for 24 hours. The bomb was cooled to room temperature and opened. TLC revealed all the starting material was gone. The crude solution was concentrated and the residue was columned on silica gel starting with straight ethyl acetate to remove the excess phthalimide reagent followed by ethyl acetate-methanol 95/5 to elute the product to give 22.2 g (20.6%) of ca 90% pure product.
Reaction SMILES: [O:1]([C:8]1[S:9][C:10]([CH2:13][OH:14])=[CH:11][N:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:15][C:16]1([CH3:29])[C@H:18]([CH:19]=[C:20]2[CH2:24][CH2:23][S:22][C:21]2=[O:25])[C@H:17]1[C:26](Cl)=[O:27].Cl>C1C=CC=CC=1.N1C=CC=CC=1>[CH3:15][C:16]1([CH3:29])[C@H:18]([CH:19]=[C:20]2[CH2:24][CH2:23][S:22][C:21]2=[O:25])[C@H:17]1[C:26]([O:14][CH2:13][C:10]1[S:9][C:8]([O:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[N:12][CH:11]=1)=[O:27]
Reactant: CC1(C)[C@H](C=C2CCSC2=O)[C@H]1C(=O)Cl
Reactant: OCc1cnc(Oc2ccccc2)s1
Agent: Cl
Solvent: c1ccncc1
Solvent: c1ccccc1
Product: CC1(C)[C@H](C=C2CCSC2=O)[C@H]1C(=O)OCc1cnc(Oc2ccccc2)s1
Temperature: 20 °C
Reaction time: 17 h

Procedure:
2 g of (2-phenoxy-5-thiazolyl)-methanol were added to a solution of (1R,3R)2,2-dimethyl-3-[(dihydro-2-oxo-3-(2H)-thienylidene)-methyl]-cyclopropane-1-carboxylic acid chloride [described in French Pat. No. 70-21682 published under No. 2.097.244] prepared from 2.2 g of the corresponding acid in 30 ml of benzene and 0.81 ml of pyridine were added thereto at -10° C.The reaction mixture was stirred at 20° C. for 17 hours and was poured into aqueous dilute hydrochloric acid. The decanted aqueous phase was extracted with ether and the combined organic phases were washed with water, dried and evaporated to dryness under reduced pressure. The residuewas chromatographed over silica gel and was eluted with an 8-2 cyclohexane-ethyl acetate mixture to obtain 2.9 g of (2-phenoxy-5-thiazolyl)-methyl (1R,3R) 2,2-dimethyl-3[(dihydro-2-oxo-3-(2H)-thienylidene)-methyl]-cyclopropane-1-carboxylate.
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=3)[O:12][CH:13]=2)O1.Br[C:22]1[N:27]=[C:26]([C:28]2[N:33]=[CH:32][CH:31]=[CH:30][N:29]=2)[CH:25]=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+].O>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>[N:16]1[CH:17]=[CH:18][CH:19]=[C:14]([C:11]2[O:12][CH:13]=[C:9]([C:22]3[N:27]=[C:26]([C:28]4[N:29]=[CH:30][CH:31]=[CH:32][N:33]=4)[CH:25]=[CH:24][CH:23]=3)[CH:10]=2)[CH:15]=1
Reactant: Brc1cccc(-c2ncccn2)n1
Reactant: CC1(C)OB(c2coc(-c3cccnc3)c2)OC1(C)C
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
Solvent: O
Product: c1cnc(-c2cccc(-c3coc(-c4cccnc4)c3)n2)nc1
Yield: 49.7 %

Procedure:
400 mg (1.38 mmol) of 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-furyl]pyridine and 347 mg (1.38 mmol) of 2-(6-bromopyridin-2-yl)pyrimidine were initially charged in 20 ml of dioxane, and 3.46 ml of a 2 molar aqueous sodium carbonate solution were added. The reaction mixture was degassed in an ultrasonic bath under argon and then heated to reflux temperature, and, at 80° C., 48.0 mg (42.0 μmol) of tetrakis(triphenylphosphine)palladium(0) were added. The reaction mixture was stirred under reflux for 8 hours and then at room temperature overnight. The mixture was then poured into 100 ml of water and extracted with dichloromethane. The light-yellow organic phases were combined, washed with 100 ml of water and then dried over MgSO4. The mixture was then filtered and concentrated under reduced pressure on a rotary evaporator. Chromatographic purification gave 206 mg (50% of theory) of 2-{6-[5-(pyridin-3-yl)-3-furyl]pyridin-2-yl}pyrimidine.
Reaction SMILES: [OH-:1].[Na+].[F:3][C:4]([P:10](C(F)(F)C(F)(F)F)[C:11]([F:17])([F:16])[C:12]([F:15])([F:14])[F:13])([F:9])[C:5]([F:8])([F:7])[F:6].Br>C(OCC)C>[F:3][C:4]([P:10]([C:11]([F:17])([F:16])[C:12]([F:15])([F:14])[F:13])[OH:1])([F:9])[C:5]([F:8])([F:7])[F:6]
Reactant: [OH-]
Reactant: FC(F)(F)C(F)(F)P(C(F)(F)C(F)(F)F)C(F)(F)C(F)(F)F
Agent: Br
Agent: [Na+]
Solvent: CCOCC
Product: OP(C(F)(F)C(F)(F)F)C(F)(F)C(F)(F)F
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
29 mmol of a 1.5 molar aqueous sodium hydroxide solution are added to a solution of 5.2 g (13.3 mmol) of tris(pentafluoroethyl)phosphine in 50 ml of diethyl ether, and the mixture is stirred at room temperature for 15 minutes. After removal of the aqueous phase, 50 ml of 1,6-dibromohexane are added, and all volatile constituents are removed overnight in vacuo. The reaction mixture is reacted with 13 mmol of HBr, and the product is separated off from the reaction mixture by means of fractional condensation (3 cold traps at −30° C., −78° C. and −196° C.). The compound is stable at room temperature under inert-gas conditions.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]([C:7]([NH:9][C:10]2[C:11]([NH2:16])=[CH:12][CH:13]=[CH:14][CH:15]=2)=[O:8])=[CH:5][CH:4]=1.[C:19]1(=[O:26])[O:25][C:23](=[O:24])[CH2:22][CH2:21][CH2:20]1.N1C=CC=CC=1>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([NH:9][C:10]2[C:11]([NH:16][C:19](=[O:26])[CH2:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])=[CH:12][CH:13]=[CH:14][CH:15]=2)=[O:8])=[CH:17][CH:18]=1
Reactant: COc1ccc(C(=O)Nc2ccccc2N)cc1
Reactant: O=C1CCCC(=O)O1
Solvent: ClCCl
Solvent: c1ccncc1
Product: COc1ccc(C(=O)Nc2ccccc2NC(=O)CCCC(=O)O)cc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 90.7 %

Procedure:
N1-(4-Methoxybenzoyl)-1,2-benzenediamine (3.0 g, 12 mmol), glutaric anhydride (1.7 g, 15 mmol), and pyridine (7 mL) were dissolved in methylene chloride (2 mL) and allowed to stir at ambient temperature for 5 h. The reaction mixture was quenched with water (2 mL) and concentrated in vacuo. The resultant residue was acidified with aqueous sulfuric acid. The resulting white solid was collected and dried at 60° C. in vacuo to yield 3.88 g (88%) of the title compound.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](=[O:16])[CH2:7][C:8]1[CH:9]=[N:10][C:11]([O:14]C)=[CH:12][CH:13]=1.I[CH3:18]>CC(OC)(C)C>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](=[O:16])[CH2:7][C:8]1[CH:13]=[CH:12][C:11](=[O:14])[N:10]([CH3:18])[CH:9]=1
Reactant: CI
Reactant: COc1ccc(CC(=O)c2ccco2)cn1
Solvent: COC(C)(C)C
Product: Cn1cc(CC(=O)c2ccco2)ccc1=O
Temperature: 100 °C
Reaction time: 3 h
Yield: 287.1 %

Procedure:
To a solution of 1-furan-2-yl-2-(6-methoxy-pyridin-3-yl)ethanone (7) (800.0 g, content 625.6 g, 2.88 mol) obtained in Example 1 in N-methyl-2-pyrrolidine (NMP) (1.88 L) was added iodomethane (122.6 g, 0.86 mol), and the reaction mixture was stirred at 100° C. for 3 hours and then at room temperature for 17.5 hours. To the reaction mixture was added dropwise MTBE (6.6 L) over a period of 77 minutes, followed by stirring for 1 hour while cooling in an ice bath. The precipitated crystals were collected by filtration and washed with MTBE (2.0 L), and then dried under reduced pressure at 50° C. for 3 hours to give 692.0 g of a crude product of the title compound as a dark brown powder (content 536.4 g, yield 85.7%).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([CH:9]=[O:10])=[C:4](Cl)[N:3]=1.CCN(C(C)C)C(C)C.[N:21]1([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>CN(C=O)C>[NH2:1][C:2]1[N:3]=[C:4]([N:24]2[CH2:23][CH2:22][N:21]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:26][CH2:25]2)[C:5]([CH:9]=[O:10])=[C:6]([Cl:8])[N:7]=1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: Nc1nc(Cl)c(C=O)c(Cl)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCN(c2nc(N)nc(Cl)c2C=O)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of 2-amino-4,6-dichloropyrimidine-5-carboxaldehyde (3.84 g, 20 mmol) and DIPEA (5.2 mL, 30 mmol) in DMF was added tert-butyl piperazine-1-carboxylate (3.73 g, 20 mmol) portionwise. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated and the residue obtained was precipitated with H2O. The precipitate was collected, washed with water and dried in vacuo, to provide the title compound as a white solid in quantitative yield. MS (m/z) 342 [M+H]+.
Reaction SMILES: [O:1]=[C:2]1[O:6][C:5]([CH2:7][CH2:8][C:9]([OH:11])=O)=[N:4][N:3]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[B-](F)(F)(F)F.CCOC(C(C#N)=NOC(N(C)C)=[N+](C)C)=O.[NH:40]1[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1>CN(C=O)C>[O:11]=[C:9]([N:40]1[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1)[CH2:8][CH2:7][C:5]1[O:6][C:2](=[O:1])[N:3]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:4]=1
Reactant: O=C(O)CCc1nn(-c2ccccc2)c(=O)o1
Reactant: C1CCNCC1
Agent: CCOC(=O)C(C#N)=NOC(N(C)C)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Product: O=C(CCc1nn(-c2ccccc2)c(=O)o1)N1CCCCC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
50 mg (0.21 mmol) of 3-(5-oxo-4-phenyl-4,5-dihydro-[1,3,4]oxadiazol-2-yl)-propionic acid, 245 mg (2.13 mmol) of NEM and 77 mg (0.23 mmol) of TOTU were dissolved in 2 ml of DMF and stirred at room temperature for 15 min. 20 mg (0.23 mmol) of piperidine were added, and the reaction mixture was stirred at room temperature for 16 h. After evaporation, the product was purified by silica gel chromatography. Yield: 45 mg.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([C:20]4[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=4)[C:14]=3[CH:13]=[CH:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C([Li])CCC.[I:31]I>O1CCCC1.CCCCCC>[I:31][C:12]1[N:11]([S:8]([C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=2)(=[O:9])=[O:10])[C:15]2[N:16]=[CH:17][N:18]=[C:19]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)[C:14]=2[CH:13]=1
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c(-c4cccnc4)ncnc32)cc1
Reactant: II
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)n2c(I)cc3c(-c4cccnc4)ncnc32)cc1
Reaction time: 1.5 h
Yield: 19.1 %

Procedure:
To a solution of 7-[(4-methylphenyl)sulfonyl]4-pyridin-3-yl-7H-pyrrolo[2,3-d]pyrimidine [1 g, Reference Example 2] in tetrahydrofuran (20 mL) at −78° C. was added drop wise a solution of butyl lithium in hexane (2 mL, 1.6M) under inert atmosphere. The solution was stirred at that temperature for 1.5 hour and iodine (796 mg) was added. The reaction mixture was stirred at −78° C. for another 1 hour and allowed to reach room temperature. The reaction mixture was partitioned between ethyl acetate and aqueous sodium sulfite solution. The organic phase was separated, then dried over magnesium sulfate and then evaporated under reduced pressure. The residue was subjected to flash column chromatography on silica eluting with a gradient of ethyl acetate and cyclohexane (50:50, to 100, v/v) to give the title compound (260 mg) as an amorphous solid. MS: 477 [MH]+. LCMS (Method B) RT=3.26 minutes.
Reaction SMILES: COC(=O)CNC(=O)C=CC1C=CC=CC=1.[C:17]([O:21][C:22](=[O:25])[CH2:23][NH2:24])([CH3:20])([CH3:19])[CH3:18].CN1CCOCC1.[C:33](O)(=[O:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.ClC(OCC(C)C)=O>CN(C)C=O.C(OCC)(=O)C>[C:17]([O:21][C:22](=[O:25])[CH2:23][NH:24][C:33](=[O:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([CH3:20])([CH3:19])[CH3:18]
Reactant: CC(C)(C)OC(=O)CN
Reactant: O=C(O)c1ccccc1
Agent: CC(C)COC(=O)Cl
Agent: COC(=O)CNC(=O)C=Cc1ccccc1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: CC(C)(C)OC(=O)CNC(=O)c1ccccc1
Temperature: 0 °C

Procedure:
Following the same general procedure described previously for cinnamoyl-glycine-methyl ester, glycine-t-butyl ester. MCl (10.88 grams) was dissolved in dimethyl formamide (approximately 100 ml), cooled to 0° C. and treated with N-methylmorpholine (9.04 ml, 1 equivalent) followed immediately by a pre-cooled solution of benzoic acid (7.94 grams) in ethyl acetate (approximately 75 ml) which had been pre-activated by treatment with N-methylmorpholine (9.04 ml) followed by isobutyl chloroformate (8.4 ml) at -20° C. After work-up, benzoyl-glycine-t-butyl ester was obtained as a white solid which was used for the next step without further purification.
Reaction SMILES: ClC1C=[C:4]([NH:8][C:9]([NH:11][S:12]([CH:15]=[CH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)(=[O:14])=[O:13])=[O:10])[CH:5]=[CH:6][CH:7]=1.N1CCCC1>C(O)C>[N:8]1([C:9]([NH:11][S:12]([CH:15]=[CH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)(=[O:14])=[O:13])=[O:10])[CH2:4][CH2:5][CH2:6][CH2:7]1
Reactant: O=C(Nc1cccc(Cl)c1)NS(=O)(=O)C=Cc1ccccc1
Solvent: C1CCNC1
Solvent: CCO
Product: O=C(NS(=O)(=O)C=Cc1ccccc1)N1CCCC1

Procedure:
A mixture of 3.4 g. of N-(N-[m-chlorophenyl]carbamoyl)-2-phenylethenesulfonamide and 2.15 g. of pyrrolidine in 100 ml. of ethanol is heated under reflux for 20 hours. The solution is cooled, and then it is concentrated in vacuo to ca. 25 ml. A small amount of starting material precipitates and it is filtered off. To the ethanol filtrate is then added 75 ml. of ether and 75 ml. of water. The layers are separated, and the aqueous layer is acidified using concentrated hydrochloric acid. This causes the crude product to precipitate. It is filtered off, and when dry it weighs 1.5 g. The ether layer is washed with 50 ml. of 1N hydrochloric acid, followed by 25 ml. of water. After being dried using anhydrous sodium sulfate, the ether is evaporated in vacuo to give a second crop of product (0.70 g.). The first crop of product is recrystallized from acetone to 0.60 g. of pure N-(pyrrolidinocarbonyl)-2-phenylethenesulfonamide, m.p. 201°-204° C.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1.[F:19][C@@H:20]1[CH2:24][CH2:23][NH:22][CH2:21]1>>[Cl:1][C:2]1[N:3]=[C:4]([N:22]2[CH2:23][CH2:24][C@@H:20]([F:19])[CH2:21]2)[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1
Reactant: F[C@@H]1CCNC1
Reactant: Fc1ccc(C2CCc3c(Cl)nc(Cl)nc32)cc1
Product: Fc1ccc(C2CCc3c2nc(Cl)nc3N2CC[C@@H](F)C2)cc1

Procedure:
2,4-dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (Preparation H) was reacted as described in Preparation Hp1 and Hp2 with (R)-3-fluoropyrrolidine. The solvent was removed and the residue applied to Silica gel and eluted with an EtOAc/Hex gradient to afford the combined two diasteriomers (Hq).
Reaction SMILES: [C:1]([CH:5]1[CH2:10][C:9]([CH3:12])([CH3:11])[CH2:8][CH2:7][CH:6]1[O:13]C(C)OCC)([O:3]C)=O.[CH:19]([Mg]Br)=[CH2:20].[CH:23](Br)=[CH2:24].Cl>C1COCC1.C(Cl)Cl.CCOC(C)=O>[OH:13][CH:6]1[CH2:7][CH2:8][C:9]([CH3:11])([CH3:12])[CH2:10][CH:5]1[C:1](=[O:3])[CH2:23][CH2:24][CH:19]=[CH2:20]
Reactant: C=CBr
Reactant: C=C[Mg]Br
Reactant: CCOC(C)OC1CCC(C)(C)CC1C(=O)OC
Agent: Cl
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: C=CCCC(=O)C1CC(C)(C)CCC1O
Yield: 60 %

Procedure:
A solution of 2-carbomethoxy-4,4-dimethyl-1-(2-methyl-1,3-dioxapent-1-yl) cyclohexane (5.16 g) in 10 ml of THF was added dropwise, over 15 minutes, to a solution of vinylmagnesium bromide (1.2 g) and vinyl bromide (5.35 g) in 20 ml of THF at 65° C. After 4 hours the mixture was cooled and poured into cold 20% aqueous HCl (40 ml). Extraction of the mixture with Et2O, removal of the solvents and a SiO2 chromatography (CH2Cl2/AcOEt) provide pure 1-(2-hydroxy-5,5-dimethyl-1-cyclohexyl)-4-penten-1-one (yield 60%).
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:10][C:11]1[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=1>ClCCl>[N:14]1[CH:15]=[CH:16][C:11]([CH2:10][C:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:8])=[CH:12][CH:13]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Cc1ccncc1
Solvent: ClCCl
Product: O=C(Cc1ccncc1)c1ccccc1
Temperature: 10 °C
Reaction time: 16 h

Procedure:
30.2 g of benzoyl chloride dissolved in 30 cc of dichloromethane was added dropwise over 1 hour to 10 g of 4-methylpyridine dissolved in 60 cc dichloromethane and maintained at 10° C. during the addition. The reaction was brought to room temperature and stirred 16 hours. The reaction was brought to reflux for 1 hour, then cooled and quenched into saturated sodium carbonate solution. The organic layer was separated, solvent removed under reduced pressure and alcohol added. The mixture was refluxed 16 hours, then the solvent removed under reduced pressure. The residue was taken up in dichloromethane and washed two times with 3N HCl. The organic layer was separated and the aqueous acid layer first neutralized, then saturated with sodium carbonate. Dichloromethane extraction of the product, solvent removal and azeotropic removal of excess unreacted 4-methylpyridine using toluene gave 4.85 g of desired product.
Reaction SMILES: COC1C=CC=CC=1[C:9]1[CH:14]=[C:13]([N+]([O-])=O)[CH:12]=[CH:11][C:10]=1[S:18]([C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-])=O)=[CH:23][C:22]=1C1C=CC=CC=1OC)(=[O:20])=[O:19].[OH-].[Na+].[CH2:40]([OH:42])C>>[CH3:40][O:42][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[S:18]([C:21]1[CH:22]=[CH:23][C:24]([NH2:27])=[CH:25][CH:26]=1)(=[O:19])=[O:20]
Reactant: COc1ccccc1-c1cc([N+](=O)[O-])ccc1S(=O)(=O)c1ccc([N+](=O)[O-])cc1-c1ccccc1OC
Reactant: CCO
Agent: [Na+]
Agent: [OH-]
Product: COc1ccccc1S(=O)(=O)c1ccc(N)cc1
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 49 %

Procedure:
To a stirred slurry of 2-methoxyphenyl-4-nitrophenyl sulfone (12.36 g, 4.2 mmol) and 90 mL of absolute ethanol was added stannous chloride dehydrate (47.4 g, 21 mmol) in one portion. The mixture was heated to 50° C. where an exothermic reaction caused the solution to strongly reflux. The mixture was allowed to stir at ambient temperature for 30 min., poured onto ice-water and made strongly basic by the addition of 350 mL of 15% NaOH. The mixture was extracted with methylene chloride (3×275 mL, the extracts dried (MgSO4), filtered, and the solvent removed in vacuo to yield a white solid which was recrystallized from ethyl acetate-hexane. After cooling the solid was filtered to yield the title benzenamine (5.38 g, 49%) as a white solid; mp 206°-208° C. 1H--NMR (300 MHz, d6 --DMSO): 3.75 (s, 3H, OCH3), 6.10 (s, 2H, NH2), 6.56-6.61 (m, 2H, aromatic), 7.07-7.13 (m, 2H, aromatic), 7.49-7.61 (m, 3H, aromatic), 7.90 (dd, 1H, J=8.1 & 1.7 Hz, aromatic). MS (CI, CH4): 264 (M+1).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[C:6]([CH3:8])[CH:7]=1.[Cl:10][CH:11](O)[CH2:12][CH2:13][CH2:14]Cl.[OH-:17].[Na+]>>[Cl:10][CH2:11][CH2:12][CH:13]([OH:17])[CH2:14][O:9][C:4]1[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([CH3:1])[CH:3]=1
Reactant: [OH-]
Reactant: Cc1cc(C)cc(O)c1
Reactant: OC(Cl)CCCCl
Agent: [Na+]
Product: Cc1cc(C)cc(OCC(O)CCCl)c1
Temperature: 65 °C
Reaction time: 8 h

Procedure:
To a mixture of 245 g. (2 moles) of 3,5-dimethylphenol and 2 liters of 2 N sodium hydroxide was added 2.5 moles of 1,4-dichlorobutanol with stirring at 65° C. overnight. The solid precipitate which separated on cooling was filtered and washed with water to neutrality. Recrystallization with isopropyl ether yielded 375 g. of white crystalline solid which melted at 74°-76° C.
Reaction SMILES: [C:1]1([NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH2:7].Cl[C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=1>>[CH:4]1[C:3]2=[C:2]3[C:3]([C:10]4[C:19]5[C:14](=[CH:15][CH:16]=[CH:17][C:18]2=5)[CH:13]=[CH:12][CH:11]=4)=[CH:2][CH:1]=[CH:6][C:1]3=[CH:6][CH:5]=1.[N:7]1[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[NH:8][CH:10]=1.[N:7]1[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[NH:8][CH:10]=1
Reactant: Nc1ccccc1N
Reactant: Clc1cccc2ccccc12
Product: c1cc2cccc3c4cccc5cccc(c(c1)c23)c54
Product: c1ccc2[nH]cnc2c1
Temperature: 25 °C

Procedure:
In a 20 liter stainless steel reaction vessel were mixed 817 g (2.08 mols) of perylene-3,4,9,10-tetracarboxylic acid dianhydride, 1169 g (10.4 mols) of o-phenylenediamine, and 9.36 liters of 1-chloronaphthalene. The mixture obtained was heated to a temperature of from 240° C. to 250° C. for 3 hours with stirring and then cooled to room temperature. Then, a solid product formed was obtained by filtering the reaction mixture with a filter cloth and then washed thrice with N,N-dimethylformamide. Thereafter, the solid product was mixed with an alcohol solution of sodium hydroxide to provide a slurry. After filtering the slurry, the solid product collected was washed with N,N-dimethylformamide and then methanol, and then dried overnight in an oven at 95° C. to provide 1100 g of a bisbenzimidazole perylene pigment (a mixture of the cis form and the trans form). Furthermore, the pigment was purified by sublimation. The powder X-ray diffraction pattern of the pigment after the purification by sublimation is shown in FIG. 1 (showing strong peaks at 0.8°, 10.2°, and 12.5°).