Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O.[OH-].[Li+].C[O:5][C:6](=[O:37])[CH2:7][C:8]1[C:17]([CH3:18])=[C:16]([C:19]2[CH:24]=[CH:23][C:22]([S:25]([C:28]3[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:29]=3[Cl:35])(=[O:27])=[O:26])=[CH:21][CH:20]=2)[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Cl:36])[CH:14]=2)[CH:9]=1>C1COCC1.O>[Cl:36][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH2:7][C:6]([OH:37])=[O:5])[C:17]([CH3:18])=[C:16]2[C:19]1[CH:20]=[CH:21][C:22]([S:25]([C:28]2[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:29]=2[Cl:35])(=[O:26])=[O:27])=[CH:23][CH:24]=1
Reactant: COC(=O)Cc1cc2ccc(Cl)cc2c(-c2ccc(S(=O)(=O)c3cc(Cl)ccc3Cl)cc2)c1C
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Cc1c(CC(=O)O)cc2ccc(Cl)cc2c1-c1ccc(S(=O)(=O)c2cc(Cl)ccc2Cl)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 99.4 %

Procedure:
Lithium hydroxide monohydrate (0.012 g, 0.27 mmol) was added to a stirred solution of {6-chloro-4-[4-(2,5-dichloro-benzenesulfonyl)-phenyl]-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (0.037 g, 0.06 mmol) in a 3:1 THF—H2O mixture (4 mL). The reaction mixture was stirred for 16 hours at room temperature. The THF was distilled off under reduced pressure, and the crude residue was diluted with water, acidified [pH˜2] through the drop-wise addition of an aqueous solution of hydrochloric acid (6.0 N). The mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. Trituration with hexanes afforded {6-chloro-4-[4-(2,5-dichloro-benzenesulfonyl)-phenyl]-3-methyl-naphthalen-2-yl}-acetic acid (0.031 g, 86%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.52 (br. s, 1 H) 8.33 (s, 1 H) 8.16 (d, J=7.82 Hz, 2 H) 7.99 (s, 1 H) 7.85-7.93 (m, 2 H) 7.77 (d, J=8.80 Hz, 1 H) 7.55 (d, J=8.80 Hz, 2 H) 7.49 (d, J=8.80 Hz, 1 H) 6.95 (s, 1 H) 3.86 (s, 2 H) 2.05 (s, 3 H) MS calcd. for C25H16Cl3O4S [(M−H)−] 517, obsd. 517.3.
Reaction SMILES: C[N:2](C)[CH:3]=[CH:4][C:5]([C:7]1[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=2)[N:8]=1)=O.Cl.[Cl:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[NH:33]N.CCN(CC)CC>C(O)C>[Cl:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[N:33]1[C:5]([C:7]2[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=3)[N:8]=2)=[CH:4][CH:3]=[N:2]1
Reactant: NNc1ccccc1Cl
Reactant: CN(C)C=CC(=O)c1nn(-c2cccc(C(F)(F)F)c2)ccc1=O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: O=c1ccn(-c2cccc(C(F)(F)F)c2)nc1-c1ccnn1-c1ccccc1Cl
Temperature: 100 °C
Reaction time: 3 h
Yield: 33.6 %

Procedure:
To a solution of 3-[3-(dimethylamino)prop-2-enoyl]-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one (674 mg, 2.0 mmol) in ethanol (200 mL) were added 2-chlorophenylhydrazine hydrochloride (538 mg, 3.0 mmol) and Et3N (0.56 mL, 4.0 mmol). The mixture was stirred at 100° C. for 3 h and the solvent was removed under reduced pressure. Preparative HPLC chromatography provided 3-[1-(2-chlorophenyl)-1H-pyrazol-5-yl]-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one as a pale yellow solid (280 mg, 34%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=O)[C:6]([O:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)=[C:5]2O.CN(C)C=O.[ClH:27].[CH:28]([O:31][CH:32]1[CH2:35][NH:34][CH2:33]1)([CH3:30])[CH3:29]>C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([N:34]1[CH2:35][CH:32]([O:31][CH:28]([CH3:30])[CH3:29])[CH2:33]1)[C:6]([O:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)=[C:5]2[Cl:27]
Reactant: CC(C)OC1CNC1
Reactant: O=c1[nH]c2ccc(Br)cc2c(O)c1Oc1ccc(Cl)cc1
Reactant: Cl
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)OC1CN(c2nc3ccc(Br)cc3c(Cl)c2Oc2ccc(Cl)cc2)C1
Temperature: 60 °C

Procedure:
To 6-bromo-2,4-dichloro-3-(4-chlorophenoxy)quinoline (0.50 g, 1.24 mmol, Intermediate 7: step c) was added N,N-dimethylformamide (3 mL) and 3-isopropoxyazetidine-HCl (0.188 g, 1.24 mmol), and the reaction was heated at 60° C. overnight. The reaction was cooled, diluted with ethyl acetate and the organic layer was washed with water five times to remove the N,N-dimethylformamide. The organic layer was dried (MgSO4), filtered and concentrated, then purified over a silica gel column with ethyl acetate/heptane to afford the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](Cl)=[O:6].C(N(CC)CC)C.[CH:18]1([NH2:24])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([NH:24][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)=[O:6]
Reactant: NC1CCCCC1
Reactant: O=C(Cl)c1cccc(Br)c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(NC1CCCCC1)c1cccc(Br)c1
Reaction time: 2 h

Procedure:
A solution of 3-bromobenzoyl chloride (2.0 g, 9 1 mmol) in CH2Cl2 was added solution triethylamine (1.9 ml, 13.7 mmol) and cyclohexylamine (1.15 ml, 10 0 mmol) in CH2Cl2 at room temperature with stirring. After 2 h, the mixture was washed with HCl (4N), brine, dried over Na2SO4 and concentrated under reduced pressure to give 3-bromo-N-cyclohexylbenzamide as a white solid. Yield (2.43 g, 95%): 1H NMR (400 MHz, CD3OD) δ 8.29 (br s, 1H), 7.95 (t, J=2.0 Hz, 1H), 7.42-7.77 (m, 1H), 7.64-7.67 (m, 1H), 7.36(t, J=8.0 Hz, 1H), 3.78-3.84 (m, 1H), 1.92-1.94 (m, 2H), 1.78-1.81 (m, 2H), 1.65-1.69 (m, 1H), 1.16-1.46 (m, 5H).
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]1[CH:17]=[CH:16][C:6]([O:7][C:8]2[CH:9]=[C:10]([CH2:14]O)[CH:11]=[CH:12][CH:13]=2)=[CH:5][CH:4]=1.S(Cl)([Cl:22])=O>ClCCl>[Cl:22][CH2:14][C:10]1[CH:11]=[CH:12][CH:13]=[C:8]([O:7][C:6]2[CH:16]=[CH:17][C:3]([C:2]([F:19])([F:18])[F:1])=[CH:4][CH:5]=2)[CH:9]=1
Reactant: OCc1cccc(Oc2ccc(C(F)(F)F)cc2)c1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: FC(F)(F)c1ccc(Oc2cccc(CCl)c2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 96.4 %

Procedure:
(3-(4-(Trifluoromethyl)phenoxy)phenyl)methanol from Step 1 (1.3 g, 4.85 mmol), in dichloromethane (10 mL), was cooled to 0° C., and treated dropwise with thionyl chloride (0.39 mL, 5.33 mmol). The reaction mixture was allowed to warm to ambient temperature and was stirred for 16 h. The reaction was concentrated by evaporation and the residue was purified by silica gel chromatography (0-20%, EtOAc:heptane) to afford the title compound (1.34 g) as a thick oil.
Reaction SMILES: [N:1]12[CH2:8][CH2:7][C:4]([C:9]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[OH:10])([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.[Br:23][CH2:24][CH2:25][CH3:26]>CC#N>[Br-:23].[OH:10][C:9]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:4]12[CH2:5][CH2:6][N+:1]([CH2:24][CH2:25][CH3:26])([CH2:2][CH2:3]1)[CH2:8][CH2:7]2
Reactant: OC(c1ccccc1)(c1ccccc1)C12CCN(CC1)CC2
Reactant: CCCBr
Solvent: CC#N
Product: CCC[N+]12CCC(C(O)(c3ccccc3)c3ccccc3)(CC1)CC2
Product: [Br-]
Yield: 74.8 %

Procedure:
Following the general procedure outlined in Example 3, 1-azabicyclo[2.2.2]oct-4-yl(diphenyl)methanol (0.0518 g, 0.176 mmol) and 1-bromopropane (0.030 mL, 0.330 mmol) in 2 CH3CN/3 CHCl3 (4.0 mL) were reacted to give the desired product (0.0548 g, 75.1%). EI-MS m/z 336 (M+) Rt (1.97 min).
Reaction SMILES: [H-].[Na+].[CH2:3]([N:10]1[CH2:15][CH2:14][CH2:13][C:12](=[O:16])[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:17]S(C)=O>C1COCC1>[CH2:3]([N:10]1[CH2:15][CH2:14][CH2:13][C:12]2([O:16][CH2:17]2)[CH2:11]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: O=C1CCCN(Cc2ccccc2)C1
Reactant: CS(C)=O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: c1ccc(CN2CCCC3(CO3)C2)cc1
Reaction time: 1 h
Yield: 71 %

Procedure:
Sodium hydride (583 mg, 14.6 mmol) in DMSO (6 mL) was heated to 55 C. for 1 h. The reaction mixture is cooled to 0 C. and Me3SI (3 g, 14.62 mmol) dissolved in THF (9.8 mL) was added dropwise. 1-Benzyl-piperidine-3-one (1.5 g, 6.64 mmol) dissolved in DMSO (10 mL) was added 15 minutes later. After completion of addition the reaction proceded at RT. After 30 min. the reaction was quenched with water . The aqueous layer was extracted with hexanes. Combined organic layers were dried over Na2SO4 and concentrated. The crude material was purified using silica gel chromatography (9:1 DCM:hexanes in 2 M ammonia in EtOH) to yield 5-benzyl-1-oxa-5-aza-spiro[2.5]octane (960 mg, 71%). MH+ (204).
Reaction SMILES: [N:1]([C@H:4]1[C@@H:8]([O:9][CH3:10])[CH2:7][N:6]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[CH2:5]1)=[N+]=[N-].C(=O)=O>C(N(CC)CC)C.C(#N)C.CO>[NH2:1][C@H:4]1[C@@H:8]([O:9][CH3:10])[CH2:7][N:6]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[CH2:5]1
Reactant: CO[C@H]1CN(C(=O)OCc2ccccc2)C[C@H]1N=[N+]=[N-]
Agent: O=C=O
Solvent: CO
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CO[C@H]1CN(C(=O)OCc2ccccc2)C[C@H]1N

Procedure:
(+/−)-Cis-benzyl 3-azido-4-methoxypyrrolidine-1-carboxylate (8.0 g) was resolved using the following chiral SFC conditions: column: Chiralpak AD-H 25×3 cm, 5 μm, Column Temp. 48° C., Flow rate: 140 mL/min, Mobile Phase: 65/35=CO2/1:1 MeOH:ACN (v/v) with 0.1% triethylamine, Injection Volume: 3 mL (Conc. 59.3 mg/mL), detector wavelength: 215 nm. The isolated isomers were named “Pk1” and “Pk2” in the elution order. The Pkl was collected and concentrated to afford 3.82 g of the desired (3R,4S)-enantiomeric product. 1H NMR (400 MHz, CDCl3) δ ppm 7.36 (5H, m), 5.34 (2 H, m), 3.45-3.73 (5 H, m), 3.42 (3 H, s), 3.13-3.22 (1 H, d, m), 1.28-1.31 (2 H, br s). LCMS: M+1=251, t=1.54 min. Chiral purity: 99.9% ee (chiral HPLC conditions: column: Chiralpak AD-H (25×0.46 cm, 5 μm), 60/40=CO2/1:1 MeOH:ACN (v/v) with 0.1% triethylamine, 3 mL/min, 48° C., 215 nm, 100 bar).
Reaction SMILES: [CH2:1]([N:3]([CH2:18][CH3:19])[C:4]1[CH:9]=[C:8]([C:10]2[O:11][C:12]([N+:15]([O-])=O)=[CH:13][CH:14]=2)[N:7]=[CH:6][N:5]=1)[CH3:2].[Al].[C:21](OC(=O)C)(=[O:23])[CH3:22].[ClH:28]>C(OCC)(=O)C.O.C(OCC)C>[ClH:28].[CH2:1]([N:3]([CH2:18][CH3:19])[C:4]1[CH:9]=[C:8]([C:10]2[O:11][C:12]([NH:15][C:21](=[O:23])[CH3:22])=[CH:13][CH:14]=2)[N:7]=[CH:6][N:5]=1)[CH3:2]
Reactant: CCN(CC)c1cc(-c2ccc([N+](=O)[O-])o2)ncn1
Reactant: CC(=O)OC(C)=O
Agent: Cl
Agent: [Al]
Solvent: CCOC(C)=O
Solvent: CCOCC
Solvent: O
Product: CCN(CC)c1cc(-c2ccc(NC(C)=O)o2)ncn1

Procedure:
To a mixture of 2.62 g. (0.01 mole) of 4-diethylamino-6-(5-nitro-2-furyl)pyrimidine and aluminum amalgam, prepared from 4.0 g. of aluminum turnings, in 60 ml. of diethyl ether is added 4 ml. of water. Acetic anhydride (2.0 g.; 0.02 mole) is added dropwise during the ensuing reaction which is maintained by heating the reaction vessel in a warm water bath. The ether is filtered and the filtrate dried over sodium sulfate. Removal of the solvent under reduced pressure provides the crude product. The residue is dissolved in ethyl acetate and treated with gaseous hydrogen chloride until a precipitate no longer forms. The resulting hydrochloride salt is further purified by several recrystallizations form methanol/hexane.
Reaction SMILES: [C-]#N.[Na+].[N:4]12[CH2:11]CN(CC1)CC2.[O:12]([C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH:22]=[O:23])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[Cl:27][C:28]([Cl:38])=[CH:29][CH:30]1[CH:32]([C:33](Cl)=[O:34])[C:31]1([CH3:37])[CH3:36].C(=O)([O-])[O-].[Na+].[Na+]>O.CCCCCCCC>[Cl:27][C:28]([Cl:38])=[CH:29][CH:30]1[CH:32]([C:33]([O:23][CH:22]([C:11]#[N:4])[C:21]2[CH:24]=[CH:25][CH:26]=[C:19]([O:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:20]=2)=[O:34])[C:31]1([CH3:36])[CH3:37]
Reactant: CC1(C)C(C=C(Cl)Cl)C1C(=O)Cl
Reactant: C1CN2CCN1CC2
Reactant: O=Cc1cccc(Oc2ccccc2)c1
Agent: O=C([O-])[O-]
Agent: [C-]#N
Agent: [Na+]
Solvent: O
Solvent: CCCCCCCC
Product: CC1(C)C(C=C(Cl)Cl)C1C(=O)OC(C#N)c1cccc(Oc2ccccc2)c1
Temperature: 25 °C

Procedure:
Under a dry nitrogen atmosphere a mixture of sodium cyanide (5.9 g, 0.12 mole) and 1,4-diazabicyclo[2.2.2]octane (0.22 g, 0.002 mole) in 10 grams of water was stirred at room temperature. During a one hour period a solution of 3-phenoxybenzaldehyde (20.6 g, 0.1 mole) and 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarbonyl chloride (24.1 g, 0.105 mole) in 120 ml of n-octane was added to the reaction mixture. After complete addition, the reaction mixture was stirred for one hour. An aqueous solution containing 20% sodium carbonate was added to the reaction mixture and the total warmed to 60°. The organic phase was separated and washed with water, dried over anhydrous magnesium sulfate and filtered. The solvent was removed from the filtrate under reduced pressure to yield α-cyano-3-phenoxybenzyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate.
Reaction SMILES: [CH:1](O)=[O:2].[C:4]1([O:10][CH3:11])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[OH2:12]>>[O:2]=[CH:1][C:6]1[CH:7]=[CH:8][C:9]([OH:12])=[C:4]([O:10][CH3:11])[CH:5]=1
Reactant: COc1ccccc1
Reactant: O=CO
Reactant: O
Product: COc1cc(C=O)ccc1O
Temperature: 130 °C
Reaction time: 0.17 h

Procedure:
A reactant (2.0 mmol, 304 mg), a catalyst (20 mg), H2O (2 mL), formic acid (2.5 equivalents), and anisole (1.0 mmol) were filled in a decompression tube (4 mL) sealed with a Teflon lid. The reaction mixture was heated at 80° C. or 130° C. for 10 hours in an oil bath, and then cooled to room temperature. The reaction mixture was extracted by adding 10 mL CH2Cl2 and centrifuged for 10 minutes to separate a catalyst. The resulting organic layer was analyzed using gas chromatography-mass spectrophotometry (GC-MS).
Reaction SMILES: [CH2:1]([OH:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[C:16](O)(=[O:30])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>O>[C:1]([O:30][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])(=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCCCCCCCO
Reactant: CCCCCCCCCCCCCC(=O)O
Solvent: O
Product: CCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCC
Reaction time: 24 h

Procedure:
329 g of myristyl alcohol and 351 g of myristic acid were heated to 60° C. in a 1 L initial charge vessel and mixed by means of a magnetic stirrer. 2.72 g of Novozym 435 were added and the water of reaction formed was removed by applying a vacuum of 5 mbar, and the water was distilled off. The course of the reaction was monitored for ˜24 h by means of acid number titration (cf. Table 1).
Reaction SMILES: Cl[CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][N:9]([C:15]1[CH:16]=[C:17]([CH:24]=[CH:25][C:26]=1[CH3:27])[C:18]([NH:20][CH:21]1[CH2:23][CH2:22]1)=[O:19])[C:8]2=[O:28].[I-].[K+].Cl.[O:32]1[CH2:38][CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(N(CC)C(C)C)(C)C>CC(N(C)C)=O.C(OCC)(=O)C>[CH:21]1([NH:20][C:18](=[O:19])[C:17]2[CH:24]=[CH:25][C:26]([CH3:27])=[C:15]([N:9]3[C:8](=[O:28])[C:7]4[C:12](=[CH:13][CH:14]=[C:5]([O:4][CH2:3][CH2:2][N:35]5[CH2:36][CH2:37][CH2:38][O:32][CH2:33][CH2:34]5)[CH:6]=4)[N:11]=[CH:10]3)[CH:16]=2)[CH2:23][CH2:22]1
Reactant: C1CNCCOC1
Reactant: Cc1ccc(C(=O)NC2CC2)cc1-n1cnc2ccc(OCCCl)cc2c1=O
Agent: Cl
Agent: [I-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(C(=O)NC2CC2)cc1-n1cnc2ccc(OCCN3CCCOCC3)cc2c1=O
Temperature: 140 °C
Yield: 63.7 %

Procedure:
3-[6-(2-Chloroethoxy)-4-oxoquinazolin-3(4H)-yl]-N-cyclopropyl-4-methylbenzamide (0.15 g), potassium iodide (0.13 g), 1,4-oxazepane hydrochloride (0.32 g), and N,N-diisopropylethylamine (0.8 ml) were stirred in DMA (3 ml) and heated under microwave irradiation conditions (Personal Chemistry Emrys Optimizer with 300 W magnetron) at 140° C. for 1 hour. The reaction mixture was diluted with ethyl acetate and washed with water (5×), brine (2×), dried (magnesium sulfate) and concentrated. Purification by column chromatography on a silica column eluting with 10% methanol/ethyl acetate gave the title compound (0.111 g) as a white solid; NMR Spectrum: (DMSOd6) 0.55 (m, 2H), 0.70 (m, 2H), 1.80 (m, 2H), 2.13 (s, 3H), 2.76 (m, 4), 2.86 (m, 1H), 2.93 (t, 2H), 3.60 (t, 2H), 3.65 (t, 2H), 4.20 (m, 2H), 7.52 (m, 2H), 7.60 (s, 1H), 7.72 (d, 1H), 7.83 (s, 1H), 7.91 (d, 1H), 8.19 (s, 1H), 8.43 (d, 1H); Mass Spectrum: M+H+ 463.
Reaction SMILES: [CH2:1]([NH:4][C:5]([NH:7][C:8]1[CH:9]=[CH:10][C:11]2[N:15]=[C:14]([CH2:16][CH2:17][CH2:18][CH3:19])[N:13]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]4[C:28]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[CH:29][CH:30]=[CH:31][CH:32]=4)=[CH:23][CH:22]=3)[C:12]=2[CH:40]=1)=[O:6])[CH:2]=[CH2:3]>C(Cl)Cl.C(O)C>[CH2:16]([C:14]1[N:13]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[C:28]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:25][CH:26]=2)[C:12]2[CH:40]=[C:8]([NH:7][C:5]([NH:4][CH2:1][C:2]3[CH:12]=[CH:40][CH:8]=[CH:9][CH:3]=3)=[O:6])[CH:9]=[CH:10][C:11]=2[N:15]=1)[CH2:17][CH2:18][CH3:19]
Reactant: C=CCNC(=O)Nc1ccc2nc(CCCC)n(Cc3ccc(-c4ccccc4C(=O)OC(C)(C)C)cc3)c2c1
Solvent: ClCCl
Solvent: CCO
Product: CCCCc1nc2ccc(NC(=O)NCc3ccccc3)cc2n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1

Procedure:
tert.butyl 4'-[(6-allylaminocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylate oil, Rf value: 0.10 (Silica gel: methylene chloride/ethanol=19:1)
Reaction SMILES: B(F)(F)F.CCOCC.C([SiH](CC)CC)C.[Cl:17][C:18]1[C:23](=[O:24])[N:22]([CH3:25])[CH:21]=[C:20]2[C:26](=[O:42])[N:27]([CH2:30][CH2:31][C:32]3[CH:41]=[CH:40][C:39]4[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=4)[N:33]=3)[CH:28](O)[C:19]=12>C(Cl)Cl>[Cl:17][C:18]1[C:23](=[O:24])[N:22]([CH3:25])[CH:21]=[C:20]2[C:26](=[O:42])[N:27]([CH2:30][CH2:31][C:32]3[CH:41]=[CH:40][C:39]4[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=4)[N:33]=3)[CH2:28][C:19]=12
Reactant: Cn1cc2c(c(Cl)c1=O)C(O)N(CCc1ccc3ccccc3n1)C2=O
Agent: CC[SiH](CC)CC
Agent: FB(F)F
Solvent: CCOCC
Solvent: ClCCl
Product: Cn1cc2c(c(Cl)c1=O)CN(CCc1ccc3ccccc3n1)C2=O
Temperature: 0 °C
Reaction time: 3 h
Yield: 5.7 %

Procedure:
BF3.OEt2 (1.234 ml, 9.73 mmol) and triethylsilane (5.18 ml, 32.4 mmol) were added to a suspension of 7-Chloro-5-methyl-2-(2-quinolin-2-yl-ethyl)-1-hydroxyl-1,2-dihydro-5H-pyrrolo[3,4-c]pyridine-3,6-dione (1.2 g, 3.24 mmol, see Example c3.1)) in DCM (5 ml) at 0° C. and the reaction stirred at 0° C. for 3 h, which was then warmed to r.t. and stirred overnight. The solvent was removed and the resulting mixture was purified via preparative HPLC (Waters 2767 PHW003, eluent: MeCN/aqueous 0.05% solution of ammonium hydrogen carbonate (gradient: 20:80 to 40:60 over 14 min), column: Hanbon Benetnach C18, 10 μm, 20×250 mm) to afford the title compound (65 mg, 6.5% yield).
Reaction SMILES: [S:1](=[O:5])(=[O:4])([OH:3])O.[Fe:6].[CH:7]1[CH:8]=[CH:9][C:10]2[C:11](=[C:13]3[N:45]=[C:44]4[N:46]=[C:37]([C:38]5[CH:39]=[CH:40][CH:41]=[CH:42][C:43]=54)[N:36]=[C:34]4[NH:35][C:27]([C:28]5[CH:29]=[CH:30][CH:31]=[CH:32][C:33]=54)=[N:26][C:24]4=[N:25][C:17]([C:18]5[CH:19]=[CH:20][CH:21]=[CH:22][C:23]=54)=[N:16][C:15]=2[NH:14]3)[CH:12]=1>>[S:1]([Fe:6]([S:1]([OH:5])(=[O:4])=[O:3])([S:1]([OH:3])(=[O:5])=[O:4])[S:1]([OH:3])(=[O:5])=[O:4])([OH:3])(=[O:5])=[O:4].[CH:8]1[CH:7]=[CH:12][C:11]2[C:10](=[C:15]3[N:16]=[C:17]4[N:25]=[C:24]([C:23]5[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=54)[N:26]=[C:27]4[NH:35][C:34]([C:33]5[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=54)=[N:36][C:37]4=[N:46][C:44]([C:43]5[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=54)=[N:45][C:13]=2[NH:14]3)[CH:9]=1
Reactant: O=S(=O)(O)O
Reactant: [Fe]
Agent: c1ccc2c(c1)-c1nc-2nc2[nH]c(nc3nc(nc4[nH]c(n1)c1ccccc41)-c1ccccc1-3)c1ccccc21
Product: O=S(=O)(O)[Fe](S(=O)(=O)O)(S(=O)(=O)O)S(=O)(=O)O
Temperature: 50 °C

Procedure:
Under a nitrogen pad, about 55 g of 20 weight percent of fuming sulfuric acid is added slowly to about 10 g of iron-phthalocyanine. After the fuming sulfuric acid is completely added, the reaction mixture is heated to 50° C. for 2 hours. The reaction mixture is then cooled to room temperature and filtered. The filtrate is then washed with 500 mL of pH 8 water. The resulting solid is then removed and dried in a vacuum oven. The dried solid is then ground to a fine powder with a mortar and pestle. The final product is a dark gray powder having a tetra-sulfo iron-phthalocyanine yield of 70 percent. The material contains 12 percent sulfophthalimide, 25 percent phthalimide, 3 percent phthalic acid, and 0.8 percent sulfophthalic acid. A 1 percent solution of the material in 1:1 methyldiethanolamine:water yields excessive foaming characteristics and is non-filterable using standardized tests.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]([C:12]2[C:13]([CH3:25])([CH3:24])[C:14](=[O:23])[N:15]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[N:16]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11].[F:26][C:27]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:28]=1[C:29](Cl)=[O:30]>>[F:26][C:27]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:28]=1[C:29]([N:20]1[CH2:21][CH2:22][CH:17]([N:15]2[C:14](=[O:23])[C:13]([CH3:25])([CH3:24])[C:12]([C:6]3[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH3:2])[CH:5]=3)=[N:16]2)[CH2:18][CH2:19]1)=[O:30]
Reactant: COc1ccc(C2=NN(C3CCNCC3)C(=O)C2(C)C)cc1OC
Reactant: O=C(Cl)c1c(F)cccc1F
Agent: Cl
Product: COc1ccc(C2=NN(C3CCN(C(=O)c4c(F)cccc4F)CC3)C(=O)C2(C)C)cc1OC

Procedure:
The title compound is prepared analogously as described for GP1 using 5-(3,4-dimethoxyphenyl)-4,4-dimethyl-2-(piperidin-4-yl)-2,4-dihydro-3H-pyrazol-3-one hydrochloride (compound B1*HCl) and 2,6-difluorobenzoyl chloride as starting compounds. The crude product is purified by crystallization from EA and diethyl ether to yield the title compound.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH:11]=O)=[CH:3][CH:2]=1.[NH2:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20]C)=[O:19])=[CH:16][CH:15]=1.O.[BH4-].[Na+]>C1(C)C=CC=CC=1.C(O)C>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:11][NH:13][C:14]2[CH:23]=[CH:22][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=2)=[CH:3][CH:2]=1
Reactant: O=Cc1ccnc2ccccc12
Reactant: COC(=O)c1ccc(N)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Solvent: O
Product: O=C(O)c1ccc(NCc2ccnc3ccccc23)cc1
Temperature: 25 °C
Reaction time: 168 h
Yield: 87.9 %

Procedure:
4-Quinolinecarboxaldehyde (10.0 g, 63.8 mmol) and methyl 4-aminobenzoate (9.64 g, 63.8 mmol) were refluxed under nitrogen in 100 mL of toluene with azeotropic removal of water. After 7 days, the reaction mixture was allowed to cool to room temperature. The imine precipitated as a yellow solid and was collected by filtration. The material was dried under reduced pressure overnight affording 15.5 g (53.4 mmol) of crude product. This was stirred in 270 mL of ethanol and treated with sodium borohydride (2.22 g, 58.7 mmol). The reaction mixture was refluxed for 45 minutes then poured hot over 800 mL of crushed ice. After 45 minutes of stirring, the white solid was filtered and allowed to air dry in the funnel overnight giving 15.6 g of 4-[(4-quinolinylmethyl)amino]benzoic acid as a 5:1 mixture of methyl:ethyl esters. All of the material was refluxed for 18 hours in 180 mL of 1N KOH and then poured hot into a mixture of 180 mL of 1N HCl and 800 mL of water. After 3 hours of stirring, the white solid was filtered and washed successively with methanol and ether affording 13.5 g (48.5 mmol, 76% overall yield) of 4-[(4-quinolinylmethyl)amino]benzoic acid which was air dried in the funnel overnight.