Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][N:3]=1.[Br:9][C:10]1[CH:15]=[CH:14][C:13]([SH:16])=[CH:12][CH:11]=1.C(=O)([O-])[O-].[K+].[K+].C(O)CO>[Cu](I)I.CC(O)C>[Br:9][C:10]1[CH:15]=[CH:14][C:13]([S:16][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[N:3][CH:4]=2)=[CH:12][CH:11]=1
Reactant: Clc1ccc(I)cn1
Reactant: Sc1ccc(Br)cc1
Agent: I[Cu]I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: OCCO
Solvent: CC(C)O
Product: Clc1ccc(Sc2ccc(Br)cc2)cn1
Temperature: 80 °C
Yield: 83.9 %

Procedure:
2-Chloro-5-iodopyridine (1.11 g, 4.64 mmol, Sigma-Aldrich, St. Louis, Mo.), 4-bromothiophenol (0.88 g, 4.64 mmol, Sigma-Aldrich, St. Louis, Mo.), copper iodide (44 mg, 0.23 mmol, Strem Chemical Inc, Newburyport, Mass.), potassium carbonate (1.28 g, 9.29 mmol), ethylene glycol (0.52 mL, 9.29 mmol), and iPrOH (10 mL) were added to a reaction vial. The vial was closed, purged with nitrogen for several minutes, and heated at 80° C. for 16 h. After cooling to room temperature, the reaction mixture was diluted with water (10 mL) and extracted with CH2Cl2 (20 mL) and then EtOAc (20 mL). The combined organic extracts were combined and the solvents were removed under reduced pressure. The residue was absorbed onto a plug of silica gel and purified by column chromatography (24 g of silica gel, 0 to 10% EtOAc in hexanes), to provide 5-((4-bromophenyl)sulfanyl)-2-chloropyridine (1.17 g) as white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.41 (d, J=2.54 Hz, 1H), 7.81 (dd, J=2.54, 8.41 Hz, 1H), 7.57-7.61 (m, 2H), 7.54 (d, J=8.41 Hz, 1H), 7.30-7.35 (m, 2H); m/z (ESI, +ve ion) 300.0 (M+H)+.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[S:8])[CH:6]=[C:5]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[N:4]=[C:3]1[CH2:15][C:16]([O-:18])=O.[Na+].Cl.CN(C)CCCN=C=NCC.[CH3:32][C@@H:33]1[CH2:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[NH:34]1>CN(C=O)C.N1C=CC=CC=1>[CH3:32][C@@H:33]1[CH2:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[N:34]1[C:16](=[O:18])[CH2:15][C:3]1[N:2]([CH3:1])[C:7](=[S:8])[CH:6]=[C:5]([N:9]2[CH2:10][CH2:11][O:12][CH2:13][CH2:14]2)[N:4]=1
Reactant: C[C@@H]1Cc2ccccc2N1
Reactant: Cn1c(CC(=O)[O-])nc(N2CCOCC2)cc1=S
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: [Na+]
Solvent: c1ccncc1
Solvent: CN(C)C=O
Product: C[C@@H]1Cc2ccccc2N1C(=O)Cc1nc(N2CCOCC2)cc(=S)n1C

Procedure:
The product is prepared by following the procedure described in example 4e (step 4e) using 250 mg of sodium (1-methyl-4-morpholin-4-yl-6-thioxo-1,6-dihydropyrimidin-2-yl)acetate in 6 ml of DMF and 6 ml of pyridine are added 512 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride and 126 mg of (R)-2-methyl-2,3-dihydro-1H-indole (which can be prepared according to Krasnov, V. P. et al. (Mendeleev Commun. 2002, 12(1), 27-28)).
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C@H:6]1[CH2:11][CH2:10][C@H:9]([NH:12][C:13]2[CH:18]=[C:17]([C:19]3[C:27]4[C:22](=[N:23][CH:24]=[C:25]([O:28][CH3:29])[CH:26]=4)[NH:21][CH:20]=3)[CH:16]=[C:15]([Cl:30])[N:14]=2)[CH2:8][CH2:7]1)=[O:4].[CH:31]1([NH2:37])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1.C(N(CC)CC)C>CN(C=O)C>[Cl:30][C:15]1[N:14]=[C:13]([NH:12][C@H:9]2[CH2:10][CH2:11][C@H:6]([NH:5][C:3](=[O:4])[CH2:2][NH:37][CH:31]3[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]3)[CH2:7][CH2:8]2)[CH:18]=[C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([O:28][CH3:29])[CH:26]=3)[NH:21][CH:20]=2)[CH:16]=1
Reactant: COc1cnc2[nH]cc(-c3cc(Cl)nc(N[C@H]4CC[C@H](NC(=O)CCl)CC4)c3)c2c1
Reactant: NC1CCCCC1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COc1cnc2[nH]cc(-c3cc(Cl)nc(N[C@H]4CC[C@H](NC(=O)CNC5CCCCC5)CC4)c3)c2c1

Procedure:
A mixture of Example 251a (50.0 mg, 0.112 mmol), cyclohexanamine (0.038 mL, 0.335 mmol) and triethylamine (0.054 mL, 0.39 mmol) in DMF (1.0 mL) was stirred at 60° C. for 2.5 hours. The reaction mixture was concentrated and purified by reverse-phase HPLC as described in Example 56 to give the title compound (44.6 mg) as trifluoroacetic acid salts. 1H NMR (400 MHz, CD3OD) ppm 1.20-1.53 (m, 9H), 1.72 (m, 1H), 1.83-1.95 (m, 2H), 1.98-2.25 (m, 6H), 3.07 (m, 1H), 3.67-3.84 (m, 4H), 3.96 (s, 3H), 6.80 (d, J=1.53 Hz, 1H), 6.89 (d, J=1.22 Hz, 1H), 7.87-7.94 (m, 2H), 8.08 (d, J=2.44 Hz, 1H). MS (DCI+) m/z 511.3 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[Br:14][C:15]1[CH:16]=[C:17]([O:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:18]([NH:21][C:22]2[S:23][CH:24]=[C:25]([CH2:27]Cl)[N:26]=2)=[N:19][CH:20]=1>CN1C(=O)CCC1>[Br:14][C:15]1[CH:16]=[C:17]([O:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:18]([NH:21][C:22]2[S:23][CH:24]=[C:25]([CH2:27][NH:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[N:26]=2)=[N:19][CH:20]=1
Reactant: ClCc1csc(Nc2ncc(Br)cc2Oc2ccccc2)n1
Reactant: Nc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN1CCCC1=O
Product: Brc1cnc(Nc2nc(CNc3ccccc3)cs2)c(Oc2ccccc2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 29.2 %

Procedure:
Aniline (0.0352 g, 0.378 mmol) was dissolved in 2 mL NMP at ambient temperature. Cs2CO3 (0.0246 g, 0.0756 mmol) and solid 5-bromo-N-(4-(chloromethyl)thiazol-2-yl)-3-phenoxypyridin-2-amine (0.030 g, 0.0756 mmol) were added to the reaction and the mixture was stirred at ambient temperature overnight. The reaction was concentrated to dryness, dissolved in CH2Cl2, washed with water, dried over Na2SO4, and concentrated to dryness. The residue was purified by preparative HPLC to give the title compound (0.010 g, 29.2% yield) as tan solids. 1H NMR (CDCl3) δ 4.34 (br s, 3H), 6.67-6.74 (m, 4H), 7.07 (d, J=8.0 Hz, 2H), 7.13 (d, J=1.8 Hz, 1H), 7.18 (t, J=7.7 Hz, 2H), 7.24-7.27 (m, 1H), 7.43 (t, J=7.9 Hz, 2H), 8.13 (d, J=1.6 Hz, 1H), 8.74 (br s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:22][CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH3:21])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.N1C(C)=CC=CC=1C.[CH3:42][O:43][C:44]([CH:46]1[CH2:51][CH2:50][CH:49](CN2C=CC(N)=N2)[CH2:48][CH2:47]1)=[O:45]>C(Cl)Cl>[CH3:42][O:43][C:44]([CH:46]1[CH2:51][CH2:50][CH:49]([CH2:21][N:18]2[CH:19]=[CH:20][C:16]([NH:15][C:13](=[O:14])[C@@H:12]([C:4]3[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[C:2]([Cl:1])[CH:3]=3)[CH2:22][CH:23]3[CH2:24][CH2:25][CH2:26][CH2:27]3)=[N:17]2)[CH2:48][CH2:47]1)=[O:45]
Reactant: COC(=O)C1CCC(Cn2ccc(N)n2)CC1
Reactant: Cn1ccc(NC(=O)[C@H](CC2CCCC2)c2ccc(S(C)(=O)=O)c(Cl)c2)n1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: Cc1cccc(C)n1
Product: COC(=O)C1CCC(Cn2ccc(NC(=O)[C@H](CC3CCCC3)c3ccc(S(C)(=O)=O)c(Cl)c3)n2)CC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 38.3 %

Procedure:
2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 125 mg, 0.38 mmol) was dissolved in methylene chloride (2 mL) and a 2.0 M solution of oxalyl chloride in methylene chloride (190 μL, 0.38 mmol) was added and the reaction stirred at 25° C. for 15 min. The solution was chilled to 0° C. and 2,6-lutidine (89 μL, 0.76 mmol) was added dropwise. The reaction continued to stir at 0° C. for 15 min. The 4-(3-amino-pyrazol-1-ylmethyl)-cyclohexanecarboxylic acid methyl ester (90 mg, 0.38 mmol) was added as a pre-dissolved reaction in methylene chloride (2 mL), the ice bath was removed and the reaction continued to stir at 25° C. for 25 min. The reaction was diluted with methylene chloride (100 mL), washed with water (2×30 mL), saturated aqueous brine solution (1×20 mL), dried over magnesium sulfate and concentrated in vacuo to a beige foam. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 0% ethyl acetate/methylene chloride to 15% ethyl acetate/methylene chloride) afforded 4-{3-[2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-cyclohexanecarboxylic acid methyl ester (80 mg, 38%) as a white foam: ESI-LRMS m/e calcd for C27H36ClN3O5S [M+] 549.21, found 550.36 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 0.91-1.07 (m, 2H, CH2), 1.06-1.21 (m, 2H, CH2), 1.32-1.47 (m, 2H, CH2), 1.46-1.56 (m, 2H, CH2), 1.56-1.93 (m, 9H, CH and 4×CH2), 1.93-2.04 (m, 2H, CH2), 2.11-2.32 (m, 2H, 2×CH), 3.26 (s, 3H, SO2CH3), 3.54 (t, J=7.5 Hz, 1H, CH), 3.66 (s, 3H, CO2CH3), 3.80 (d, J=7.0 Hz, 2H, NCH2), 6.64 (d, Jo=2.2 Hz, 1H, Ar), 7.21 (d, Jo=2.2 Hz, 1H, Ar), 7.46 (dd, Jo=8.1, Jm=1.7 Hz. 1H, Ar), 7.59 (d, Jm=1.7 Hz, 1H, Ar), 7.58 (s, 1H, NH), 8.09 (d, Jo=8.1 Hz, 1H, Ar).
Reaction SMILES: [Cl:1][C:2]1[NH:7][C:6]2=[N:8][CH:9]=[C:10]([I:11])[C:5]2=[C:4]([Cl:12])[N:3]=1.[S:13](Cl)([C:16]1[CH:22]=[CH:21][C:19]([CH3:20])=[CH:18][CH:17]=1)(=[O:15])=[O:14].C(N(C(C)C)CC)(C)C>ClCCl>[Cl:1][C:2]1[N:3]=[C:4]([Cl:12])[C:5]2[C:10]([I:11])=[CH:9][N:8]([S:13]([C:16]3[CH:22]=[CH:21][C:19]([CH3:20])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[C:6]=2[N:7]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: Clc1nc(Cl)c2c(I)cnc-2[nH]1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(S(=O)(=O)n2cc(I)c3c(Cl)nc(Cl)nc32)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 92.2 %

Procedure:
2,4-dichloro-5-iodo-1H-pyrrolo[2,3-d]pyrimidine (660 mg, 2.103 mmol) and tosyl-chloride (441 mg, 2.31 mmol) were combined in dry dichloromethane (20 ml). Diisopropylethylamine (0.734 mL, 4.21 mmol) was added and the reaction mixture was let stir at rt for 18 h. The reaction was then diluted with dichloromethane and the organic layer was washed with a saturated solution of sodium bicarbonate, water and a saturated solution of brine, then dried over sodium sulfate. Solvents were removed under reduced pressure and the residue purified by chromatography on SiO2 to afford 2,4-dichloro-5-iodo-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidine (901 mg, 1.94 mmol) as a yellow solid. ESIMS (M+H)+=469.
Reaction SMILES: S(Cl)([Cl:4])(=O)=O.[OH:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]([CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH2:14][C:15]([O:17][CH3:18])=[O:16])=[C:9]([O:24][CH3:25])[CH:8]=1>C1C=CC=CC=1.C(OCC)(=O)C>[Cl:4][C:12]1[C:7]([OH:6])=[CH:8][C:9]([O:24][CH3:25])=[C:10]([CH:13]([CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH2:14][C:15]([O:17][CH3:18])=[O:16])[CH:11]=1
Reactant: CCCCCC(CC(=O)OC)c1ccc(O)cc1OC
Reactant: O=S(=O)(Cl)Cl
Solvent: c1ccccc1
Solvent: CCOC(C)=O
Product: CCCCCC(CC(=O)OC)c1cc(Cl)c(O)cc1OC
Temperature: 70 °C
Reaction time: 3.5 h
Yield: 88 %

Procedure:
604 mg (4.48 mmol) of sulfuryl chloride were added to a solution of 1.26 g (4.48 mmol) of methyl 3-(4-hydroxy-2-methoxyphenyl)octanoate (prepared as described in Preparation 44) in 10 ml of benzene, and the resulting mixture was stirred at 70° C. for 3.5 hours. At the end of this time, the reaction mixture was diluted with ethyl acetate, and the diluted solution was washed with an aqueous solution of sodium carbonate, with water and with a saturated aqueous solution of sodium chloride, after which it was dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through 100 g of silica gel, using a 1:2 by volume mixture of ethyl acetate and hexane as the eluent, to give the title compound as an oily substance in a 88% yield.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]1[CH2:12][CH2:13][N:14]([CH3:17])[CH2:15][CH:16]=1.[C:18]1([S:28](Cl)(=[O:30])=[O:29])[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[CH:20][CH:19]=1>>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([S:28]([C:18]1[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH:21]=[CH:20][CH:19]=1)(=[O:30])=[O:29])[CH:6]=[C:5]2[C:11]1[CH2:12][CH2:13][N:14]([CH3:17])[CH2:15][CH:16]=1
Reactant: CN1CC=C(c2c[nH]c3ccc(F)cc23)CC1
Reactant: O=S(=O)(Cl)c1cccc2ccccc12
Product: CN1CC=C(c2cn(S(=O)(=O)c3cccc4ccccc34)c3ccc(F)cc23)CC1

Procedure:
(28.2 mg, 52%), from 5-fluoro-3-(1-methyl-1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (Example 4b, 29.4 mg, 0.128 mmol) and 1-naphthylsulfonyl chloride (58 mg, 0.26 mmol); HRMS-FAB+ for C24H22N2O2SF calculated MH+ : 421.13861; found: 421.14099.
Reaction SMILES: [OH:1][C:2]1[CH2:7][C:6]([CH:16]([CH3:18])[CH3:17])([CH2:8][CH2:9][C:10]2[S:14][CH:13]=[N:12][C:11]=2[CH3:15])[O:5][C:4](=[O:19])[CH:3]=1.[C:20]([C:24]1[CH:29]=[C:28]([CH2:30][OH:31])[C:27]([CH3:32])=[CH:26][C:25]=1[S:33]S(C1C=CC(C)=CC=1)(=O)=O)([CH3:23])([CH3:22])[CH3:21].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:20]([C:24]1[CH:29]=[C:28]([CH2:30][OH:31])[C:27]([CH3:32])=[CH:26][C:25]=1[S:33][C:3]1[C:4](=[O:19])[O:5][C:6]([CH:16]([CH3:17])[CH3:18])([CH2:8][CH2:9][C:10]2[S:14][CH:13]=[N:12][C:11]=2[CH3:15])[CH2:7][C:2]=1[OH:1])([CH3:23])([CH3:22])[CH3:21]
Reactant: Cc1ccc(S(=O)(=O)Sc2cc(C)c(CO)cc2C(C)(C)C)cc1
Reactant: Cc1ncsc1CCC1(C(C)C)CC(O)=CC(=O)O1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc(SC2=C(O)CC(CCc3scnc3C)(C(C)C)OC2=O)c(C(C)(C)C)cc1CO

Procedure:
The title compound was prepared according to General Method 16a using 4-hydroxy-6-isopropyl-6-[2-(4-methyl-thiazol-5-yl)-ethyl]-5,6-dihydro-pyran-2-one (Example E-1; 0.22 g, 0.78 mmol), toluene-4-thiosulfonic acid S-(2-tert-butyl-4-hydroxymethyl-5-methyl-phenyl)ester (Example BB-2; 0.33 g, 0.90 mmol), potassium carbonate (1.0 g, 7.2 mmol), and DMF (4 mL). The product was chromatographed on silica gel, eluting with 10% MeOH in CH2Cl2, to give the title compound, mp 138-141° C.
Reaction SMILES: [CH2:1]([O:9][C:10]1[C:11](=[O:22])[O:12][C:13]2[C:20]([OH:21])=[CH:19][CH:18]=[CH:17][C:14]=2[C:15]=1[OH:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[C:23]([O:26][CH2:27][CH2:28][CH2:29]Br)(=[O:25])[CH3:24]>>[CH2:1]([O:9][C:10]1[C:11](=[O:22])[O:12][C:13]2[C:20]([O:21][CH2:29][CH2:28][CH2:27][O:26][C:23](=[O:25])[CH3:24])=[CH:19][CH:18]=[CH:17][C:14]=2[C:15]=1[OH:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCCOc1c(O)c2cccc(O)c2oc1=O
Reactant: CC(=O)OCCCBr
Product: CCCCCCCCOc1c(O)c2cccc(OCCCOC(C)=O)c2oc1=O

Procedure:
In the same manner as in Reference Example 1, except that an equimolar amount of 3-octyloxy-4,8-dihydroxy-2H-1-benzopyran-2-one was used in place of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, and 3-bromopropyl acetate was used in place of 2-bromoethyl acetate in Reference Example 1, 3-octyloxy-4-hydroxy-8-(3-acetoxypropyloxy)-2H-1-benzopyran-2-one was obtained.
Reaction SMILES: ClC1C=CC(OC)=C(NC([C:11]2[C:20](O)=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=2)=O)C=1.[OH2:24]>[OH-].[Na+]>[CH:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[OH:24])[CH:12]=1
Reactant: COc1ccc(Cl)cc1NC(=O)c1cc2ccccc2cc1O
Reactant: O
Agent: [Na+]
Agent: [OH-]
Product: Oc1cccc2ccccc12
Temperature: 90 °C

Procedure:
By reference to manufacturing example 1 according to an embodiment described in Japanese Patent Laid-Open Publication No. Hei 11-272014, a naphthol pigment (a pigment red 238) is prepared. More specifically, 50 parts by mass (0.21 parts by mol) of 3-Amino-4-Methoxybenzanilide is dispersed into 1000 parts of mass of water, into which ice is added to set a temperature to 0° C. to 5° C. The resultant solution is agitated for 20 minutes after the addition of 60 parts by mass (0.58 parts by mol) of 35% HCl water solution, and then agitated for 60 minutes after the addition of 50 parts by mass (0.22 parts by mol) of 30% nitrite soda water solution. Subsequently, 2 parts by mass (0.02 parts by mol) of sulfamic acid are added to the solution to remove nitrite, and 50 parts by mass (0.37 parts by mol) of acetic acid soda and 75 parts by mass (1.12 parts by mol) of 90% acetic acid are further added to the solution, to thereby obtain a diazonium salt solution. Separately from this preparation, 68 parts by mass (0.21 parts by mol) of N-(5-chloro-2-methoxyphenyl)-3-hydroxy-2-naphthalenecarboxylic amide is dissolved in 1000 parts by mass of water in conjunction with 25 parts by mass (0.63 parts by mol) of caustic soda at a temperature of 80° C. or lower, to which 3 parts by mass (corresponding to 2.49 weight percent relative to the pigment) of minerite 100 is further added to obtain a coupler solution. The coupler solution is added to the above-described diazonium salt solution at a temperature of 10° C. or lower in order to induce a coupling reaction, and then treated by heat at 90° C. Subsequently, the resultant solution is filtered and rinsed, and then dried at a temperature of 100° C. Further, the resultant product having been dried is pulverized. As a result, 117 parts by mass (0.20 parts by mol) of a naphthol pigment is obtained. The obtained naphthol pigment has a volume average particle size D50 of 70 nm. This pigment is hereinafter referred to as “naphthol pigment A.”
Reaction SMILES: [CH2:1]([NH:8][CH2:9][CH2:10][NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:12](Cl)(Cl)=[S:13].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O>[CH2:1]([N:8]1[CH2:9][CH2:10][N:11]=[C:12]1[SH:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: S=C(Cl)Cl
Reactant: NCCNCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: SC1=NCCN1Cc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 17.5 %

Procedure:
Solutions of 10.9 g (0.067 mol) N-benzylethylenediamine (Example 2) and 7.65 g (0.067 mol) thiophosgene, each dissolved in 50 ml toluene, were added dropwise and concurrently to a stirred mixture of 14.1 g (0.133 mol) sodium carbonate dissolved in 100 ml water and 100 ml toluene which had been chilled to 0° C. After the 20-30 minute addition period the reaction mixture was allowed to warm to ambient temperature and stirring was continued at this temperature for one hour. The reaction mixture was filtered and the insoluble solid, 7.2 g, was recrystallized twice from methanol-ethyl acetate to give 2.25 g (18% yield) of desired product, m.p. 177°-182° C.
Reaction SMILES: [Sn](CC)(CC)(CC)[CH2:2][CH3:3].N#N.[Si:12]([O:19][CH2:20][CH:21]1[CH2:35][C:34]2[C:23](=[CH:24][C:25]3[N+:30]([O-:31])=[N:29][C:28](I)=[N:27][C:26]=3[CH:33]=2)[CH2:22]1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]>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>[Si:12]([O:19][CH2:20][CH:21]1[CH2:35][C:34]2[C:23](=[CH:24][C:25]3[N+:30]([O-:31])=[N:29][C:28]([CH2:2][CH3:3])=[N:27][C:26]=3[CH:33]=2)[CH2:22]1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]
Reactant: CC(C)(C)[Si](C)(C)OCC1Cc2cc3nc(I)n[n+]([O-])c3cc2C1
Reactant: CC[Sn](CC)(CC)CC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: N#N
Solvent: C1COCCO1
Product: CCc1nc2cc3c(cc2[n+]([O-])n1)CC(CO[Si](C)(C)C(C)(C)C)C3
Yield: 87.9 %

Procedure:
Et4Sn (1.47 mL, 7.5 mmol) and Pd(PPh3)4 (154 mg, 0.99 mmol) were added to a N2-purged, stirred solution of iodide 133 (2.27 g, 4.97 mmol) in dry dioxane (30 mL) at 20° C. and the reaction mixture was stirred at reflux temperature under N2. After 5 h more Et4Sn (1.5 mL, 7.5 mmol) and Pd(PPh3)4 (150 mg, 0.98 mmol) were added and the mixture stirred at reflux temperature for 5 h. The mixture was cooled and partitioned between EtOAc and water. The organic layer was separated, dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-5%) of EtOAc/pet. ether, to give 1-oxide 135 (1.57 g, 88%) as a yellow solid: mp (EtOAc/pet. ether) 63-65° C.; 1H NMR δ 8.23 (s, 1H, H-9), 7.72 (s, 1H, H-5), 3.59-3.66 (m, 2H, CH2O), 3.14-3.24 (m, 2H, CH2), 2.92-3.06 (m, 4H, H-6, H-8), 2.72-2.83 (m, 1H, H-7), 1.43 (t, J=7.5 Hz, 3H, CH3), 0.87 [s, 9H, SiC(CH3)3], 0.04 [s, 6H, Si(CH3)2]. Anal. calcd for C19H29N3O2Si: C, 63.5; H, 8.1; N, 11.7. Found: C, 63.3; H, 8.2; N, 11.4%.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[C@H:15]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][NH:13][C:12]1=[O:23])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:24](=O)([O-])[O-].[K+].[K+].CI>CC(C)=O>[CH3:24][N:13]1[CH2:14][C@@H:15]([C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[C:12]1=[O:23]
Reactant: O=C([O-])[O-]
Reactant: CC(C)(C)OC(=O)[C@@H]1CNC(=O)N1C(=O)OCc1ccccc1
Agent: [K+]
Solvent: CC(C)=O
Solvent: CI
Product: CN1C[C@@H](C(=O)OC(C)(C)C)N(C(=O)OCc2ccccc2)C1=O
Temperature: 25 °C
Reaction time: 144 h
Yield: 89.8 %

Procedure:
9.6 g of tert.-butyl (4S)-3-benzyloxycarbonyl-2-oxo-imidazolidine-4-carboxylate are dissolved in 200 ml of acetone, and 8.3 g of anhydrous potassium carbonate and 14.2 g of methyl iodide are added thereto. The mixture is stirred at room temperature for 6 days. The reaction mixture is treated in the same manner as described in Preparation 1-(2), whereby 9.0 g of tert.-butyl (4S)-1-methyl-3-benzyloxycarbonyl-2-oxo-imidazolidine-4-carboxylate are obtained as colorless crystals. Yield: 89.8% The physico-chemical properties of this product are identical with those of the sample obtained in Preparation 1-(2).
Reaction SMILES: [CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:17]([F:18])=[CH:16][C:13]([C:14]#[N:15])=[C:12]([NH:19][C@H:20]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[CH3:21])[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.NC(C1C=CC(F)=C([NH:38][S:39]([CH3:42])(=[O:41])=[O:40])C=1)C.CCN(C(C)C)C(C)C>C(O)CCC>[C:14]([C:13]1[C:12]([NH:19][C@@H:20]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[C:24]([NH:38][S:39]([CH3:42])(=[O:41])=[O:40])[CH:23]=2)[CH3:21])=[N:11][C:10]([NH:9][C:6]2[CH:5]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[NH:8][N:7]=2)=[C:17]([F:18])[CH:16]=1)#[N:15]
Reactant: CC(N)c1ccc(F)c(NS(C)(=O)=O)c1
Reactant: C[C@H](Nc1nc(Nc2cc(C3CC3)[nH]n2)c(F)cc1C#N)c1ccc(F)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCCCO
Product: C[C@@H](Nc1nc(Nc2cc(C3CC3)[nH]n2)c(F)cc1C#N)c1ccc(F)c(NS(C)(=O)=O)c1
Temperature: 150 °C
Yield: 20.2 %

Procedure:
To a 10-ml microwave vessel was added, 2-chloro-6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-5-fluoronicotinonitrile (Method 1, 600 mg, 2.3 mmol), N-[5-(1-aminoethyl)-2-fluorophenyl]methanesulfonamide (Method 61, 500 mg, 2.3 mmol), DIEA (0.5 ml, 2.76 mmol), and n-butanol (5 ml). The vessel was sealed and subjected to microwave heating at 150° C. for 5 hours (CEM Discover System). The resulting mixture was then purified by silica gel chromatography using 5% MeOH/DCM. The racemic product obtained was then chirally purified by HPLC on Chiralcel OJ column (500×50 mm, 20 microns) using 50:25:25:0.1% of hexane/MeOH/EtOH/diethylamine at 118 ml/min. The chiral purification gave 220 mg of N-{5-[(1R)-1-({3-cyano-6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-5-fluoropyridin-2-yl}amino)ethyl]-2-fluorophenyl}methanesulfonamide 1H NMR: δ 11.77-12.26 (br s, 1H), 9.51 (s, 1H), 9.34-9.48 (br s, 1H), 7.62 (d, J=10.55 Hz, 1H), 7.39 (d, J=8.29 Hz, 1H), 7.02-7.23 (m, 3H), 6.00 (s, 1H), 5.07-5.24 (m, 1H), 2.95 (s, 3H), 1.81-1.95 (m, 1H), 1.49 (d, J=7.54 Hz, 3H), 0.88-0.97 (m, 2H), 0.57-0.68 (m, 2H). MS: Calcd.: 473. Found: [M+H]+ 474 and 223 mg of N-{5-[(1S)-1-({3-cyano-6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-5-fluoropyridin-2-yl}amino)ethyl]-2-fluorophenyl}methanesulfonamidel; 1H NMR: 11.73-12.38 (br s, 1H), 9.42 (s, 1H), 8.41-9.12 (br s, 1H), 7.61 (d, J=11.30 Hz, 1H), 7.37 (d, J=7.54 Hz, 1H), 6.96-7.24 (m, 3H), 6.02 (s, 1H), 5.05-5.26 (m, 1H), 2.90 (s, 3H), 1.79-1.96 (m, 1H), 1.49 (d, J=6.78 Hz, 3H), 0.89-0.98 (m, 2H), 0.59-0.67 (m, 2H). MS: Calcd.: 473. Found: [M+H]+ 474.