Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])[CH:6]=[CH:7][CH:8]=1.[Li]CCCC.[Mg+2].[Br-].[Br-].CCOCC.[Cl:29][C:30]1[CH:35]=[CH:34][C:33]([S:36]([NH:39][C:40]2[C:41]([CH:47]=[O:48])=[N:42][CH:43]=[C:44]([Cl:46])[CH:45]=2)(=[O:38])=[O:37])=[CH:32][C:31]=1[C:49]([F:52])([F:51])[F:50]>C1COCC1>[Cl:46][C:44]1[CH:45]=[C:40]([NH:39][S:36]([C:33]2[CH:34]=[CH:35][C:30]([Cl:29])=[C:31]([C:49]([F:50])([F:52])[F:51])[CH:32]=2)(=[O:37])=[O:38])[C:41]([CH:47]([OH:48])[C:4]2[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][C:5]=2[NH:9][C:10](=[O:15])[C:11]([CH3:12])([CH3:14])[CH3:13])=[N:42][CH:43]=1
Reactant: COc1cccc(NC(=O)C(C)(C)C)c1
Reactant: O=Cc1ncc(Cl)cc1NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1
Agent: [Br-]
Agent: [Li]CCCC
Agent: [Mg+2]
Solvent: CCOCC
Solvent: C1CCOC1
Product: COc1cccc(NC(=O)C(C)(C)C)c1C(O)c1ncc(Cl)cc1NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1
Temperature: -78 °C
Reaction time: 0.75 h

Procedure:
To a stirred solution of N-(3-methoxy-phenyl)-2,2-dimethyl-propionamide (1.11 g, 4.8 mmol) in anhydrous THF at 0° C. was added a solution of n-BuLi (3.65 mL, 9.1 mmol) in hexanes. After 45 minutes, anhydrous MgBr2-Et2O (1.23 g, 4.8 mmol) was added in one portion and stirring was continued at the same temperature for 1 h. The mixture was then cooled to −78° C. and solid 4-chloro-N-(5-chloro-2-formyl-pyridin-3-yl)-3-trifluoromethyl-benzenesulfonamide (300 mg, 0.75 mmol) was added in one portion and slowly warmed to room temperature over 4 h. The mixture was then quenched with saturated aqueous NH4Cl (10 mL), and extracted with EtOAc (3×75 mL). The combined extracts were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel using ethyl acetate-hexane to provide N-(2-{[5-chloro-3-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-pyridin-2-yl]-hydroxy-methyl}-3-methoxy-phenyl)-2,2-dimethyl-propionamide: MS m/z 606.0 (M+H)+.
Reaction SMILES: [OH:1][CH:2]([CH3:6])[C:3]([OH:5])=[O:4].CC(C)([O-])C.[K+].[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19]Cl)=[CH:17][CH:16]=1>>[OH:1][CH:2]([CH3:6])[C:3]([O:5][CH2:19][C:18]1[CH:21]=[CH:22][C:15]([O:14][CH3:13])=[CH:16][CH:17]=1)=[O:4]
Reactant: CC(O)C(=O)O
Reactant: COc1ccc(CCl)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Product: COc1ccc(COC(=O)C(C)O)cc1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
To a stirred solution of DL-2 hydroxypropionic acid (9.0 g, 100 mmole) in 100 ml dry DMP was added potassium tert-butoxide (12.34 g, 110 mmole) and the mixture was stirred for one hour at 60° C. 4-methoxybenzyl chloride was (18.8 g 120 mmole) was added and the mixture was stirred for eight hours at 60° C. The mixture was evaporated under reduced pressure and 250 ml ethyl acatate was added The organic phase was washed four times with water. The organic phase was dried with sodium sulfate and concentrated in vacuo. Yield: 16.8 g
Reaction SMILES: [CH:1]1([C:4]2[CH:5]=[C:6]([C:25]([O:27]CC)=[O:26])[C:7](=[O:24])[N:8]3[C:13]=2[C:12]([CH3:14])=[C:11]([C:15]2[CH:20]=[C:19]([CH3:21])[C:18]([NH2:22])=[CH:17][C:16]=2[Cl:23])[CH:10]=[CH:9]3)[CH2:3][CH2:2]1.[Li+].[OH-].Cl.C(OCC)(=O)C>C1COCC1.O>[CH:1]1([C:4]2[CH:5]=[C:6]([C:25]([OH:27])=[O:26])[C:7](=[O:24])[N:8]3[C:13]=2[C:12]([CH3:14])=[C:11]([C:15]2[CH:20]=[C:19]([CH3:21])[C:18]([NH2:22])=[CH:17][C:16]=2[Cl:23])[CH:10]=[CH:9]3)[CH2:3][CH2:2]1
Reactant: CCOC(=O)c1cc(C2CC2)c2c(C)c(-c3cc(C)c(N)cc3Cl)ccn2c1=O
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1cc(-c2ccn3c(=O)c(C(=O)O)cc(C4CC4)c3c2C)c(Cl)cc1N
Temperature: 60 °C

Procedure:
A solution of ethyl 1-cyclopropyl-8-(4-amino-2-chloro-5-methyl-phenyl)-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (70 mg, 0.171 mmol) in THF (6 mL) and water (2 mL) was treated with LiOH (29 mg, 0.690 mmol). The reaction was heated to 60° C. overnight and acidified with 1N HCl to pH 4. The precipitate was dissolved with ethyl acetate (50 mL) and washed with brine (2×20 mL). The organic phase was separated, dried, and concentrated. The precipitate was filtered to afford the title compound EXAMPLE 30 as yellow solid (51 mg, 78%). ESI-MS m/z: 383 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ ppm: 9.28 (d, J=7.5 Hz, 1H), 8.24 (s, 1H), 7.43 (d, J=7.5 Hz, 1H), 6.99 (s, 1H), 6.81 (s, 1H), 5.55 (s, 2H), 2.75 (s, 3H), 2.54-2.52 (m, 1H), 2.07 (s, 3H), 1.03-1.01 (m, 2H), 0.74-0.70 (m, 2H).
Reaction SMILES: [CH2:1]([S:16][CH2:17][C@@H:18]([C:20]([OH:22])=[O:21])[NH2:19])[CH:2]=[C:3]([CH2:5][CH2:6][CH:7]=[C:8]([CH2:10][CH2:11][CH:12]=[C:13]([CH3:15])[CH3:14])[CH3:9])[CH3:4].[C:23](Cl)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.Cl.[OH-].[Na+]>C(OCC)(=O)C.C(N(CC)CC)C.CO>[C:23]([NH:19][C@H:18]([C:20]([OH:22])=[O:21])[CH2:17][S:16][CH2:1][CH:2]=[C:3]([CH2:5][CH2:6][CH:7]=[C:8]([CH2:10][CH2:11][CH:12]=[C:13]([CH3:15])[CH3:14])[CH3:9])[CH3:4])(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: CC(C)=CCCC(C)=CCCC(C)=CCSC[C@H](N)C(=O)O
Reactant: O=C(Cl)c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CC(C)=CCCC(C)=CCCC(C)=CCSC[C@H](NC(=O)c1ccccc1)C(=O)O

Procedure:
S-farnesylcysteine was dissolved in dry ethyl acetate/triethylamine in a dry flask under nitrogen. equivalents of benzoylchloride was added in the cold and the suspension was allowed to stir for an hour. The solution was neutralized with dilute HCl. After evaporation, the product was applied to a preparative thin layer chromatography plate and eluted with hexane/ethyl acetate. The pure product was removed from the plate and eluted with methanol. Yields were in the range of 50-75%. The product showed the anticipated nmr and infrared spectra. The parent acid was prepared from the ester by the addition of one equivalent of sodium hydroxide in methanol. The product showed the expected nmr and infrared spectra.
Reaction SMILES: B([C:4]1[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][C:5]=1[O:6][C@@H:7]([CH3:11])[C:8]([OH:10])=[O:9])(O)O.C(=O)([O-])[O-].[Na+].[Na+].Br[C:24]1[CH:29]=[CH:28][C:27]([S:30]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)(=[O:32])=[O:31])=[CH:26][CH:25]=1>O1CCOCC1.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]>[Cl:16][C:14]1[CH:13]=[CH:12][C:5]([O:6][C@@H:7]([CH3:11])[C:8]([OH:10])=[O:9])=[C:4]([C:24]2[CH:29]=[CH:28][C:27]([S:30]([N:33]3[CH2:34][CH2:35][O:36][CH2:37][CH2:38]3)(=[O:31])=[O:32])=[CH:26][CH:25]=2)[CH:15]=1
Reactant: O=S(=O)(c1ccc(Br)cc1)N1CCOCC1
Reactant: C[C@H](Oc1ccc(Cl)cc1B(O)O)C(=O)O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: C[C@H](Oc1ccc(Cl)cc1-c1ccc(S(=O)(=O)N2CCOCC2)cc1)C(=O)O

Procedure:
A mixture of the product from example 151 step (iv) (0.126 g), sodium carbonate (0.22 g), 4-[(4-bromophenyl)sulfonyl]morpholine (0.16 g) and Pd(dppf)Cl2 (0.03 g) in dioxane (10 ml) was heated under reflux for 4 h. The mixture was evaporated and purified by RVHPLC (MeCN/aqNH4Cl). Yield 0.09 g.
Reaction SMILES: C(OC(=O)[NH:7][C@H:8]([C:33](=[O:40])[NH:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:20][C:19](=[O:21])[N:18]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[S:17]2(=[O:32])=[O:31])=[CH:12][CH:11]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][C@@H:8]([CH2:9][C:10]1[CH:11]=[CH:12][C:13]([N:16]2[CH2:20][C:19](=[O:21])[N:18]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[S:17]2(=[O:31])=[O:32])=[CH:14][CH:15]=1)[C:33]([NH:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])=[O:40]
Reactant: CCCCCNC(=O)[C@H](Cc1ccc(N2CC(=O)N(Cc3ccc(OC)cc3)S2(=O)=O)cc1)NC(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCCCCNC(=O)[C@@H](N)Cc1ccc(N2CC(=O)N(Cc3ccc(OC)cc3)S2(=O)=O)cc1
Reaction time: 0.33 h

Procedure:
A solution of the title A compond, ((S)-2-(4-[5-{4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl]-phenyl}-1-pentylcarbamoyl-ethyl)-carbamic acid t-butyl ester (64 mg, 0.108 mmol) in CH2Cl2 (1 mL) is treated with TFA (1 mL). After 20 min, the solvent is evaporated under stream of nitrogen. The residue is partitioned between EtOAc and saturated aqueous NaHCO3, and the organic solution is washed with brine, dried over anhydrous MgSO4, filtered and concentrated to yield (S)-2-amino-3-{4-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl]-phenyl}-N-pentyl-propionamide as a white solid: [M+1]+=489.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:13]=[C:14]([NH2:16])[CH:15]=1)[C:7]([NH:9][CH2:10][CH2:11][OH:12])=[O:8])([O-:3])=[O:2].[CH:17]([CH:20]1[O:25][CH2:24][CH:23]([C:26](Cl)=[O:27])[CH2:22][O:21]1)([CH3:19])[CH3:18].C(N(CC)CC)C>CC(N(C)C)=O>[N+:1]([C:4]1[CH:5]=[C:6]([CH:13]=[C:14]([NH:16][C:26]([CH:23]2[CH2:22][O:21][CH:20]([CH:17]([CH3:19])[CH3:18])[O:25][CH2:24]2)=[O:27])[CH:15]=1)[C:7]([NH:9][CH2:10][CH2:11][OH:12])=[O:8])([O-:3])=[O:2]
Reactant: Nc1cc(C(=O)NCCO)cc([N+](=O)[O-])c1
Reactant: CC(C)C1OCC(C(=O)Cl)CO1
Solvent: CC(=O)N(C)C
Solvent: CCN(CC)CC
Product: CC(C)C1OCC(C(=O)Nc2cc(C(=O)NCCO)cc([N+](=O)[O-])c2)CO1

Procedure:
40 g (0.177 mole) of 3-nitro-5-amino-N-(2-hydroxyethyl)benzamide are dissolved in 400 cm3 of DMAC. The addition of 74.9 g (0.389 mole) of 2-isopropyl-1,3-dioxane-5-carboxylic acid chloride in the presence of triethylamine (54.6 cm3) gives rise to an exothermic reaction.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[C:14]([OH:21])[CH:15]=[CH:16][CH:17]=3)[N:12]=2)=[CH:6][CH:5]=1)([O-])=O.C1(N)C(F)=C(F)C(F)=C(N)C=1F.[ClH:34].Cl>[Zn].[Cl-].[NH4+].O.C(O)C>[ClH:34].[ClH:34].[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[C:14]([OH:21])[CH:15]=[CH:16][CH:17]=3)[N:12]=2)=[CH:8][CH:9]=1
Reactant: O=[N+]([O-])c1ccc(Nc2ccc3cccc(O)c3n2)cc1
Agent: Cl
Agent: Nc1c(F)c(N)c(F)c(F)c1F
Agent: [Cl-]
Solvent: O
Solvent: CCO
Product: Nc1ccc(Nc2ccc3cccc(O)c3n2)cc1

Procedure:
The 2-[(4-nitrophenyl)amino]quinol-8-ol (11) obtained above was reduced with a boiling zinc/ammonium chloride/water/ethanol mixture. The corresponding amine was isolated in dihydrochloride form.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][C:11]3([CH2:15]OS(C)(=O)=O)[CH2:14][CH2:13][CH2:12]3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[NH3:21]>CO>[NH2:21][CH2:15][C:11]1([NH:10][C:6]2[CH:5]=[C:4]3[C:9](=[CH:8][CH:7]=2)[NH:1][N:2]=[CH:3]3)[CH2:14][CH2:13][CH2:12]1
Reactant: N
Reactant: CS(=O)(=O)OCC1(Nc2ccc3[nH]ncc3c2)CCC1
Solvent: CO
Product: NCC1(Nc2ccc3[nH]ncc3c2)CCC1
Temperature: 25 °C
Yield: 39 %

Procedure:
A solution of methanesulfonic acid 1-(1H-indazol-5-ylamino)-cyclobutylmethyl ester (1.31 g, ca. 3.18 mmol) in 7N NH3 in methanol (40 mL) was heated at 75° C. in a sealed tube. After 14 hours the reaction mixture was cooled to ambient temperature, concentrated in vacuo to a gum, then purified by chromatography (silica, 0 to 20% of a 9:1 MeOH:NH4OH solution in DCM) to furnish (1-aminomethyl-cyclobutyl)-(1H-indazol-5-yl)-amine (0.266 g, 1.23 mmol, 39%) as a foam.
Reaction SMILES: [OH:1][CH2:2][CH2:3][O:4][C:5]1[C:10]([CH3:11])=[CH:9][C:8]([CH2:12][CH2:13][C:14]([C:16]2[S:17][C:18]([CH3:27])=[C:19]3[CH2:24][C:23]([CH3:26])([CH3:25])[CH2:22][CH2:21][C:20]=23)=[O:15])=[CH:7][C:6]=1[CH3:28].CCN(C(C)C)C(C)C.[CH3:38][S:39](Cl)(=[O:41])=[O:40]>C(Cl)Cl>[CH3:11][C:10]1[CH:9]=[C:8]([CH2:12][CH2:13][C:14](=[O:15])[C:16]2[S:17][C:18]([CH3:27])=[C:19]3[CH2:24][C:23]([CH3:25])([CH3:26])[CH2:22][CH2:21][C:20]=23)[CH:7]=[C:6]([CH3:28])[C:5]=1[O:4][CH2:3][CH2:2][O:1][S:39]([CH3:38])(=[O:41])=[O:40]
Reactant: Cc1cc(CCC(=O)c2sc(C)c3c2CCC(C)(C)C3)cc(C)c1OCCO
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(CCC(=O)c2sc(C)c3c2CCC(C)(C)C3)cc(C)c1OCCOS(C)(=O)=O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 106.1 %

Procedure:
To a solution of 3-[4-(2-hydroxy-ethoxy)-3,5-dimethyl-phenyl]-1-(3,5,5-trimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-propan-1-one (130 mg, 0.325 mmol) in DCM (10 mL) and DIPEA (0.09 mL, 0.52 mmol) is added methane sulfonylchloride (0.03 mL, 0.39 mmol) at 0° C. The reaction mixture is stirred at 0° C. for 30 min. The reaction mixture is diluted with DCM, washed with 0.1 N aq. NaOH followed by 10% aq. citric acid solution, dried over MgSO4 and evaporated to give methanesulfonic acid 2-{2,6-dimethyl-4-[3-oxo-3-(3,5,5-trimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-propyl]-phenoxy}-ethyl ester (165 mg) as a yellow oil; LC-MS: tR=1.17 min, [M+1]+=479.26.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[CH:4][N:3]=1.[C:13](OC(=O)C)(=[O:15])[CH3:14]>>[C:13]([NH:1][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[CH:4][N:3]=1)(=[O:15])[CH3:14]
Reactant: CCOC(=O)c1cncnc1N
Reactant: CC(=O)OC(C)=O
Product: CCOC(=O)c1cncnc1NC(C)=O
Yield: 59 %

Procedure:
Compound 21 (0.72 g, 4.3 mmol) was mixed with 8 mL of acetic anhydride and the reaction mixture was stirred under reflux for 2 h until no starting material was observed by TLC (4:1 EtOAc/hexanes). The reaction mixture was concentrated in vacuo and the product was purified by flash chromatography (CH2Cl2/EtOAc) to yield 0.53 g of compound 22 in 59% yield.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([N:8]2[C:13](=[O:14])[N:12]([CH3:15])[C:11](=[O:16])[CH2:10][NH:9]2)[CH:5]=[C:4]([Cl:17])[C:3]=1[CH:18]([C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=1)[C:19]#[N:20].[C:28](Cl)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>N1C=CC=CC=1>[C:28]([N:9]1[CH2:10][C:11](=[O:16])[N:12]([CH3:15])[C:13](=[O:14])[N:8]1[C:6]1[CH:5]=[C:4]([Cl:17])[C:3]([CH:18]([C:21]2[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][CH:26]=2)[C:19]#[N:20])=[C:2]([Cl:1])[CH:7]=1)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: CN1C(=O)CNN(c2cc(Cl)c(C(C#N)c3ccc(Cl)cc3)c(Cl)c2)C1=O
Solvent: c1ccncc1
Product: CN1C(=O)CN(C(=O)c2ccccc2)N(c2cc(Cl)c(C(C#N)c3ccc(Cl)cc3)c(Cl)c2)C1=O
Reaction time: 8 h
Yield: 20.2 %

Procedure:
To a stirred mixture of 3 parts of 2,6-dichloro-α-(4-chlorophenyl)-4-(3,4,5,6-tetrahydro-4-methyl-3,5-dioxo-1,2,4-triazin-2(1H)-yl)benzeneacetonitrile and 20 parts of pyridine were added dropwise 1.7 parts of benzoyl chloride during a period of 5 minutes at room temperature and under nitrogen atmosphere. Upon complete addition, stirring was continued overnight at room temperature. The reaction mixture was evaporated 1n vacuo and the residue was stirred in water. The product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was purified twice by column chromatography over silica gel using trichloromethane as eluent. The pure fractions were collected and the eluent was evaporated in vacuo. The residue was crystallized from 8 parts of acetonitrile. The product was filtered off, washed with 2,2'-oxybispropane and dried, yielding 0.8 parts (20.2%) of 1-benzoyl-2-[3,5-dichloro-4-[(4-chlorophenyl)cyanomethy]phenyl]-1,6-dihydro-4-methyl-1,2,4-triazine-3,5(2H,4H)-dione; mp. 148.4° C. (compound 79).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6](B(O)O)[CH:5]=[CH:4][N:3]=1.Br[C:12]1[CH:13]=[C:14]([NH:19][C:20](=[O:37])[C@@H:21]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:15]=[C:16]([Cl:18])[CH:17]=1.[F-].[Cs+].COCCOC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:18][C:16]1[CH:15]=[C:14]([NH:19][C:20](=[O:37])[C@@H:21]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:13]=[C:12]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([CH3:1])[CH:7]=2)[CH:17]=1
Reactant: Cc1cc(B(O)O)ccn1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C(=O)Nc1cc(Cl)cc(Br)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cs+]
Agent: [F-]
Solvent: COCCOC
Product: Cc1cc(-c2cc(Cl)cc(NC(=O)[C@H](Cc3ccccc3)NC(=O)OC(C)(C)C)c2)ccn1
Temperature: 85 °C
Yield: 66.2 %

Procedure:
2-methylpyridin-4-ylboronic acid (327 mg, 2.39 mmol), (S)-tert-butyl 1-(3-bromo-5-chlorophenylamino)-1-oxo-3-phenylpropan-2-ylcarbamate (542 mg, 1.19 mmol), tetrakis(triphenylphosphine)palladium (345 mg, 0.30 mmol), cesium fluoride (544 mg, 3.58 mmol) were added to a vial then DME (4778 μl, 1194 μmol) was added and the mixture was heated to 85° C. for 8 h. The reaction was loaded and purified on Phenomenex Geminni C18 HPLC 50 mm×250 mm running ACN/Water/0.1% TFA in a linear gradient. The fractions containing the desired product were combined and concentrated to afford tert-butyl (S)-1-(3-chloro-5-(2-methylpyridin-4-yl)phenylamino)-1-oxo-3-phenylpropan-2-ylcarbamate (367 mg, 66% yield). tert-butyl (S)-1-(3-chloro-5-(2-methylpyridin-4-yl)phenylamino)-1-oxo-3-phenylpropan-2-ylcarbamate (367 mg, 0.78 mmol) was dissolved in DCM (3 mL) and TFA (1 mL) add stirred for 3 h. The solution was concentrated to afford (2S)-2-amino-N-(3-chloro-5-(2-methylpyridin-4-yl)phenyl)-3-phenylpropanamide (280 mg, 99%).
Reaction SMILES: [CH2:1]([OH:5])[CH2:2][CH2:3][OH:4].[Na].[Cl:7][C:8]1[CH:15]=[C:14](F)[CH:13]=[CH:12][C:9]=1[C:10]#[N:11]>O>[Cl:7][C:8]1[CH:15]=[C:14]([O:4][CH2:3][CH2:2][CH2:1][OH:5])[CH:13]=[CH:12][C:9]=1[C:10]#[N:11]
Reactant: OCCCO
Reactant: N#Cc1ccc(F)cc1Cl
Agent: [Na]
Solvent: O
Product: N#Cc1ccc(OCCCO)cc1Cl
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 50.6 %

Procedure:
To 1,3-propanediol (320 mg, 4.2 mmol) was added sodium (21 mg, 0.92 mmol). The mixture is stirred at room temperature for 10 minutes and 2-chloro-4-fluoro-benzonitrile (156 mg, 1.0 mmol) was added. The reaction was heated to 105° C. for 24 hours. The reaction was cooled to room temperature, was diluted with water and was extracted with Et2O (3×). The organic solution was dried (MgSO4), filtered and concentrated. The residue was purified by reverse phase high pressure chromatography eluting with a solvent gradient (15% of 0.1% formic acid/CH3CN in 0.1% formic acid/water to 100% of 0.1% formic acid/water) to provide 107 mg of 2-chloro-4-(3-hydroxy-propoxy)-benzonitrile. 1H NMR (CDCl3) δ 7.54 (d, 1H), 7.00 (m, 1H), 6.85 (dd, 1H), 4.15 (t, 2H), 3.83 (t, 2H), 2.04 (m, 2H).
Reaction SMILES: C([O:8][C:9]1[CH:30]=[C:29]([Cl:31])[C:12]([CH2:13][CH:14]2[CH2:18][CH2:17][N:16]([CH:19]3[CH2:27][CH2:26][C:22]4[NH:23][CH:24]=[N:25][C:21]=4[CH2:20]3)[C:15]2=[O:28])=[C:11]([Cl:32])[CH:10]=1)C1C=CC=CC=1>C(OCC)(=O)C.CO.[OH-].[Pd+2].[OH-]>[Cl:31][C:29]1[CH:30]=[C:9]([OH:8])[CH:10]=[C:11]([Cl:32])[C:12]=1[CH2:13][CH:14]1[CH2:18][CH2:17][N:16]([CH:19]2[CH2:27][CH2:26][C:22]3[NH:23][CH:24]=[N:25][C:21]=3[CH2:20]2)[C:15]1=[O:28]
Reactant: O=C1C(Cc2c(Cl)cc(OCc3ccccc3)cc2Cl)CCN1C1CCc2[nH]cnc2C1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CO
Product: O=C1C(Cc2c(Cl)cc(O)cc2Cl)CCN1C1CCc2[nH]cnc2C1
Reaction time: 16 h

Procedure:
Add palladium hydroxide to a nitrogen purged solution of 3-(4-Benzyloxy-2,6-dichloro-benzyl)-1-(4,5,6,7-tetrahydro-1H-benzoimidazol-5-yl)-pyrrolidin-2-one (4.3 g, 9.2 mmol) (Preparation 12) in 50 ml of ethyl acetate and 15 ml of methanol. Add about 22 psi of pressurized nitrogen and stir for 16 h. Filter this mixture and concentrate to afford 3-(2,6-Dichloro-4-hydroxy-benzyl)-1-(4,5,6,7-tetrahydro-1H-benzoimidazol-5-yl)-pyrrolidin-2-one as solid product (2 g). MS: m/z (M+1)=380.
Reaction SMILES: [CH:1]1[C:10]2[C:11]3[CH:20]=[CH:19][C:18]4C(NC(=O)[C:16]5[C:17]=4[C:12]=3[C:13](=[CH:14][CH:15]=5)[C:8]3[C:9]=2[C:4]2[C:5](C(NC(=O)[C:3]=2[CH:2]=1)=O)=[CH:6][CH:7]=3)=O.S(C(CC(OCCCCCCCC)=O)C(OCCCCCCCC)=O)(O)(=O)=O.[Na]>>[CH:14]1[C:13]2=[C:12]3[C:11]([C:10]4[C:9]5[C:4](=[CH:5][CH:6]=[CH:7][C:8]2=5)[CH:3]=[CH:2][CH:1]=4)=[CH:20][CH:19]=[CH:18][C:17]3=[CH:16][CH:15]=1
Reactant: O=C1NC(=O)c2ccc3c4ccc5c6c(ccc(c7ccc1c2c73)c64)C(=O)NC5=O
Agent: CCCCCCCCOC(=O)CC(C(=O)OCCCCCCCC)S(=O)(=O)O
Agent: [Na]
Product: c1cc2cccc3c4cccc5cccc(c(c1)c23)c54

Procedure:
Example 12 describes the conditioning of crude perylenediimide presscake (Pigment Violet 29) according to the invention. Comparison Example 13 was carried out by the same method as used for Example 12 except for omitting the N-lauryl-β-iminodipropionic acid sodium salt. Comparison Example 14 was carried out by the same method as used for Example 12 except for omitting the N-lauryl-β-iminodipropionic acid sodium salt and the mixture of sodium dioctyl sulfosuccinate and aliphatic naphtha during conditioning.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][CH2:14][O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:11][O:10][C:9]1([CH3:23])[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)C.O=[Al]O[Al]=O.[Rh]>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][CH2:14][O:15][CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)[CH2:11][O:10][C:9]1([CH3:23])[CH3:22])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1[C@@H](CCOc2ccccc2)COC1(C)C
Agent: [Rh]
Agent: O=[Al]O[Al]=O
Solvent: CCO
Product: CC(C)(C)OC(=O)N1[C@@H](CCOC2CCCCC2)COC1(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 94.9 %

Procedure:
To a solution of (S)-2,2-dimethyl-4-(2-phenoxy-ethyl)-oxazolidine-3-carboxylic acid tert-butyl ester (150 mg) in ethanol (3 ml) at room temperature was added rhodium on activated alumina (15 mg). The mixture was stirred under an atmosphere of hydrogen (1 atm) at room temperature for 16 h. The catalyst was removed by filtration and the filtrate was concentrated in vacuo to yield (S)-4-(2-cyclohexyloxy-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester as a black oil (145 mg, 95%); MS (ISP): 328.4 ([M+H]+).
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][CH2:9][CH2:8][NH:7]1)=[O:5])[CH3:2].C(N(CC)CC)C.[C:19](Cl)([Cl:21])=[S:20]>C1C=CC=CC=1>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][CH2:9][CH2:8][N:7]1[C:19]([Cl:21])=[S:20])=[O:5])[CH3:2]
Reactant: S=C(Cl)Cl
Reactant: CCOC(=O)N1CCCCN1
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: CCOC(=O)N1CCCCN1C(=S)Cl
Temperature: 25 °C
Reaction time: 4 h

Procedure:
With the temperature maintained at 30° or below, a mixture of N-ethoxycarbonylhexahydropyridazine (1.5 g, 9.49 mmol) and triethylamine (1.0 g, 9.49 mmol) in 8 ml of benzene is added dropwise to a stirring solution of thiophosgene (1.1 g, 9.49 mmol) in 10 ml of benzene. The reaction is stirred at RT for 4 hours, and is then diluted with benzene to 50 ml, quickly washed with water and with brine, dried and stripped to give N-ethoxycarbonyl-N'-chlorothiocarbonylhexahydropyridazine.
Reaction SMILES: [NH2:1][C:2]1[C:11]([CH3:12])=[CH:10][C:9](Br)=[CH:8][C:3]=1[C:4]([NH:6][CH3:7])=[O:5].ClC1C=CC=CC=1.[C-]#N.[Na+].[CH3:24][NH:25]CCNC>[Cu]I.O>[NH2:1][C:2]1[C:11]([CH3:12])=[CH:10][C:9]([C:24]#[N:25])=[CH:8][C:3]=1[C:4]([NH:6][CH3:7])=[O:5]
Reactant: CNCCNC
Reactant: CNC(=O)c1cc(Br)cc(C)c1N
Agent: [Cu]I
Agent: [C-]#N
Agent: [Na+]
Solvent: Clc1ccccc1
Solvent: O
Product: CNC(=O)c1cc(C#N)cc(C)c1N
Temperature: 25 °C

Procedure:
A 100-mL three-necked flask equipped with a mechanical stirrer, thermometer and condenser was charged with 2-amino-5-bromo-N,3-dimethylbenzamide (prepared by the method of Example 1) (99.1% purity, 5.0 g, 0.02 mol) and chlorobenzene (20 g) while maintaining a flow of nitrogen through a gas inlet line connected to the condenser. The reaction mixture was stirred at room temperature, and powdered sodium cyanide (powdered just prior to use) (1.25 g, 0.024 mol, assuming 95% purity), copper(I) iodide (0.57 g, 0.003 mol) and N,N′-dimethylethylenediamine (1.51 g, 0.017 mol) were added. The mixture was heated at reflux (about 130° C.) for 4.5 h and then cooled to 25° C., and water (20 mL) was added over 5 minutes, and the resulting mixture was stirred for 30 minutes. The mixture was filtered, and the solid collected was washed with water (2×10 mL) and chlorobenzene (10 mL), and then dried to a constant weight in a vacuum-oven at 50° C. to give the title compound (3.6 g) as an off-white solid melting at 202-203° C.