Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:5]1[N:10]2[N:11]=[CH:12][CH:13]=[C:9]2[N:8]([C@H:14]2[CH2:19][CH2:18][C@H:17]([O:20][CH2:21]C(OCC)=O)[CH2:16][CH2:15]2)[C:7](=[O:27])[C:6]=1[CH2:28][C:29]1[CH:30]=[N:31][C:32]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[C:41]#[N:42])=[CH:33][CH:34]=1)[CH2:2][CH2:3][CH3:4].[CH3:43][Mg]Br.C([O:49][CH2:50][CH3:51])(=O)C>O1CCCC1>[CH2:1]([C:5]1[N:10]2[N:11]=[CH:12][CH:13]=[C:9]2[N:8]([C@H:14]2[CH2:19][CH2:18][C@H:17]([O:20][CH2:21][C:50]([OH:49])([CH3:51])[CH3:43])[CH2:16][CH2:15]2)[C:7](=[O:27])[C:6]=1[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[C:41]#[N:42])=[N:31][CH:30]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCOC(C)=O
Reactant: C[Mg]Br
Reactant: CCCCc1c(Cc2ccc(-c3ccccc3C#N)nc2)c(=O)n([C@H]2CC[C@H](OCC(=O)OCC)CC2)c2ccnn12
Solvent: C1CCOC1
Product: CCCCc1c(Cc2ccc(-c3ccccc3C#N)nc2)c(=O)n([C@H]2CC[C@H](OCC(C)(C)O)CC2)c2ccnn12
Reaction time: 3 h

Procedure:
To a solution of ethyl ({trans-4-[7-butyl-6-{[6-(2-cyanophenyl)pyridin-3-yl]methyl}-5-oxopyrazolo[1,5-a]pyrimidin-4(5H)-yl]cyclohexyl}oxy)acetate (0.26 g) in tetrahydrofuran (3 mL) was added dropwise methylmagnesium bromide (1 M tetrahydrofuran solution, 1.4 mL) at 0° C., and the mixture was stirred for 3 hr. To the reaction mixture were added ethyl acetate and then saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (0.16 g, 63%).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3](OS(C2C=CC(C)=CC=2)(=O)=O)[CH:2]=1.[C:22]([C:24]1[CH:29]=[CH:28][C:27]([NH2:30])=[CH:26][CH:25]=1)#[CH:23]>CCCCCCC.CCOC(C)=O>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:23]#[C:22][C:24]2[CH:29]=[CH:28][C:27]([NH2:30])=[CH:26][CH:25]=2)[CH:2]=1
Reactant: C#Cc1ccc(N)cc1
Reactant: Cc1ccc(S(=O)(=O)Oc2cnc3ccccc3c2)cc1
Solvent: CCOC(C)=O
Solvent: CCCCCCC
Product: Nc1ccc(C#Cc2cnc3ccccc3c2)cc1

Procedure:
This product was prepared from toluene-4-sulfonic acid quinolin-3-yl ester and 4-ethynyl-phenylamine following the general procedure for the Sonogashira cross-coupling reaction described above. Chromatography eluent: heptane/EtOAc 6:4; yield (120 mg, 98%); 1H NMR δ (CDCl3): 8.98 (s, 1H), 8.34 (s, 1H), 8.21 (d, J=8.60 Hz, 1H), 7.87-7.71 (d m, 2H), 7.68-7.57 (m, 1H), 7.40 (d, J=8.36 Hz, 2H), 6.67 (d, J=8.38 Hz, 2H), 4.46 (br s, 2H); LCMS m/z: 244.
Reaction SMILES: [C:1]1([CH2:7][S:8](Cl)(=[O:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:12][CH2:13][CH:14]1[CH2:19][CH2:18][CH:17]([C:20]([O:22]C)=[O:21])[CH2:16][CH2:15]1.Br[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1>>[F:32][C:29]1[CH:30]=[CH:31][C:26]([CH2:25][N:12]([CH2:13][CH:14]2[CH2:19][CH2:18][CH:17]([C:20]([OH:22])=[O:21])[CH2:16][CH2:15]2)[S:8]([CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:10])=[O:9])=[CH:27][CH:28]=1
Reactant: O=S(=O)(Cl)Cc1ccccc1
Reactant: COC(=O)C1CCC(CN)CC1
Reactant: Fc1ccc(CBr)cc1
Product: O=C(O)C1CCC(CN(Cc2ccc(F)cc2)S(=O)(=O)Cc2ccccc2)CC1

Procedure:
Prepared as in example 5-10 from phenylmethanesulfonyl chloride and methyl 4-(aminomethyl)cyclohexanecarboxylate and 1-(bromomethyl)-4-fluorobenzene. MS (M−H, 418); 1NMR (400 MHz, DMSO-d6): δ, ppm: 0.639 (m, 2H), 0.897 (m, 2H), 1.034 (m, 1H), 1.467 (d, broad, 2H, J=11.2 Hz), 1.709 (d, broad, 2H, J=11.2 Hz), 1.961 (m, 1H), 2.828 (d, 2H, J=7.6 Hz), 4.207 (s, 2H), 4.449 (s, 2H), 7.155 (t, 2H, J=9.2 Hz), 7.377 (m, 7H), 12 (s, broad, 1H)
Reaction SMILES: [NH2:1][CH2:2][C:3]1[C:12]([NH2:13])=[C:11]2[C:6]([CH:7]=[CH:8][CH:9]=[N:10]2)=[CH:5][CH:4]=1.N1([S:19](N2C=C[N+](C)=C2)(=[O:21])=[O:20])C=CN=C1.FC(F)(F)S([O-])(=O)=O>CC#N>[CH2:2]1[C:3]2[CH:4]=[CH:5][C:6]3[C:11](=[N:10][CH:9]=[CH:8][CH:7]=3)[C:12]=2[NH:13][S:19](=[O:21])(=[O:20])[NH:1]1
Reactant: C[n+]1ccn(S(=O)(=O)n2ccnc2)c1
Reactant: NCc1ccc2cccnc2c1N
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: CC#N
Product: O=S1(=O)NCc2ccc3cccnc3c2N1
Yield: 6 %

Procedure:
7-Aminomethyl-quinolin-8-amine (Intermediate 211) (50 mg, 0.29 mmol) and 1-(1H-imidazole-1-sulfonyl)-3-methyl-1H-imidazol-3-ium; trifluoromethanesulfonate (157 mg, 0.43 mmol) in MeCN (5 ml) was stirred at room temperature for 18 h. The reaction mixture was concentrated in vacuo. The crude residue was purified by preparative HPLC (basic conditions) to give the title compound (4.5 mg, 6%).
Reaction SMILES: [CH2:1]([C:8]1[O:12][CH:11]=[N:10][C:9]=1[C:13](O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(C1OC=NC=1CO)C1C=CC=CC=1.S(Cl)([Cl:32])=O>>[CH2:1]([C:8]1[O:12][CH:11]=[N:10][C:9]=1[CH2:13][Cl:32])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1ncoc1Cc1ccccc1
Agent: OCc1ncoc1Cc1ccccc1
Product: ClCc1ncoc1Cc1ccccc1

Procedure:
5-Benzyl-4-oxazolecarboxylic acid is converted to 5-benzyl-4-hydroxymethyloxazole by the procedure of Example 135. Treating this hydroxymethyl compound with thionyl chloride gives 5-benzyl-4-chloromethyloxazole.
Reaction SMILES: Br[C:2]1[C:6]2[CH:7]=[N:8][C:9]([NH2:23])=[C:10]([O:11][C@@H:12]([C:14]3[C:19]([Cl:20])=[CH:18][CH:17]=[C:16]([F:21])[C:15]=3[Cl:22])[CH3:13])[C:5]=2[O:4][CH:3]=1.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C(=O)([O-])[O-].[K+].[K+].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.O>[C:24]([O:28][C:29]([N:31]1[CH2:32][CH:33]=[C:34]([C:2]2[C:6]3[CH:7]=[N:8][C:9]([NH2:23])=[C:10]([O:11][C@@H:12]([C:14]4[C:19]([Cl:20])=[CH:18][CH:17]=[C:16]([F:21])[C:15]=4[Cl:22])[CH3:13])[C:5]=3[O:4][CH:3]=2)[CH2:35][CH2:36]1)=[O:30])([CH3:27])([CH3:25])[CH3:26]
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Reactant: C[C@@H](Oc1c(N)ncc2c(Br)coc12)c1c(Cl)ccc(F)c1Cl
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: [K+]
Solvent: C1COCCO1
Solvent: O
Product: C[C@@H](Oc1c(N)ncc2c(C3=CCN(C(=O)OC(C)(C)C)CC3)coc12)c1c(Cl)ccc(F)c1Cl

Procedure:
A mixture of 3-bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)-ethoxy]-furo[3,2-c]pyridin-6-ylamine (100.0 mg, 0.2381 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (88.3 mg, 0.286 mmol), Pd(PPh3)4 (10 mg, 0.01 mmol), potassium carbonate (98.7 mg, 0.714 mmol) and 4:1 dioxane:water (4 mL) was microwaved at 100° C. for 2 h. The solution was concentrated in vacuo, and dry-loaded onto silica gel for column chromatography, eluted with 2-5% MeOH in DCM. Fractions containing the product were concentrated in vacuo to afford the title compound as an off-white solid. 1H NMR (CD3OD, 400 MHz): δ=1.49 (s, 9H), 1.88 (d, J=6.8 Hz, 3H), 2.48 (d, J=1.5 Hz, 2H), 3.59-3.69 (m, 2H), 4.11 (br, s, 2H), 6.26 (br, s, 1H), 6.50 (q, J=6.9 Hz, 1H), 7.19-7.25 (m, 1H), 7.40 (dd, J=9.0, 4.9 Hz, 1H), 7.64 (s, 1H), 8.20 (s, 1H). MS (ES+): m/z 522.14 [MH+]. HPLC: tR=3.51 min (ZQ3, polar—5 min).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][C:12]([C:18]4[CH:19]=[CH:20][C:21]([C:24](O)=[O:25])=[N:22][CH:23]=4)=[CH:13][CH:14]=3)[CH2:9]2)[CH:5]=[C:4]([N:27]2[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]2)[N:3]=1.[NH2:34][C@H:35]1[CH2:40][CH2:39][C@H:38]([OH:41])[CH2:37][CH2:36]1>>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][C:12]([C:18]4[CH:19]=[CH:20][C:21]([C:24]([NH:34][C@H:35]5[CH2:40][CH2:39][C@H:38]([OH:41])[CH2:37][CH2:36]5)=[O:25])=[N:22][CH:23]=4)=[CH:13][CH:14]=3)[CH2:9]2)[CH:5]=[C:4]([N:27]2[CH2:28][CH2:29][N:30]([CH3:33])[CH2:31][CH2:32]2)[N:3]=1
Reactant: N[C@H]1CC[C@H](O)CC1
Reactant: CN1CCN(c2cc(N3CCc4ccc(-c5ccc(C(=O)O)nc5)cc4C3)nc(N)n2)CC1
Product: CN1CCN(c2cc(N3CCc4ccc(-c5ccc(C(=O)N[C@H]6CC[C@H](O)CC6)nc5)cc4C3)nc(N)n2)CC1

Procedure:
This compound was prepared by using procedures analogous to those described for the synthesis of Example 18 starting from 5-{2-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-1,2,3,4-tetrahydroisoquinolin-7-yl}pyridine-2-carboxylic acid and trans-4-aminocyclohexanol (Acros Organics, Cat. 34668). LCMS (M+H)+: m/z=543.4.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([O:22][CH3:23])=[C:6]([CH:21]=1)[CH2:7][N:8]1[C:16]2[C:11](=[N:12][CH:13]=[CH:14][C:15]=2[CH3:17])[C:10]([C:18](O)=[O:19])=[CH:9]1.F[CH2:25][CH2:26][NH2:27].[CH2:28](N(CC)CC)[CH3:29].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>ClCCl.O>[CH:25]1([CH2:26][NH:27][C:18]([C:10]2[C:11]3=[N:12][CH:13]=[CH:14][C:15]([CH3:17])=[C:16]3[N:8]([CH2:7][C:6]3[CH:21]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[O:22][CH3:23])[CH:9]=2)=[O:19])[CH2:29][CH2:28]1
Reactant: NCCF
Reactant: CCN(CC)CC
Reactant: COc1ccc(F)cc1Cn1cc(C(=O)O)c2nccc(C)c21
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Solvent: ClCCl
Solvent: O
Product: COc1ccc(F)cc1Cn1cc(C(=O)NCC2CC2)c2nccc(C)c21
Temperature: 25 °C
Reaction time: 16 h
Yield: 24 %

Procedure:
See FIG. 16(b). To a stirred solution of 1-(5-fluoro-2-methoxybenzyl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid (0.22 g, 0.000699 moles) in dichloromethane (10 mL) were added 2-fluoroethan-1-amine (0.06 g, 0.000836 moles), triethylamine (0.29 ml, 0.002 moles) and T3P (1.32 ml, 0.002 moles) and the mixture was stirred for 16 h at room temperature. The reaction mixture was poured in to water and extracted with dichloromethane. The combined organic layer was washed with water, brine and the solvent was evaporated under reduced pressure. The crude was purified by flash column chromatography using 50% ethyl acetate in hexane to afford N-(cyclopropylmethyl)-1-(5-fluoro-2-methoxybenzyl)-7-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide as a off-white solid. Yield-24%. ES+MS m/z: 368. 1H NMR (400 MHz, DMSO-d6) δ ppm: 0.22-0.24 (m, 2H ), 0.48-0.50 (m, 2H ), 1.05-1.09 (m, 1H ), 2.44 (s, 3H ), 3.28 (t, 2H , J=6.2 Hz), 3.86 (s, 3H ), 5.63 (s, 2H ), 5.97-6.00 (m, 1H ), 7.03-7.04 (m, 1H ), 7.12-7.14 (m, 2H ), 8.22 (s, 1H ), 8.37 (d, 1H , J=4.8 Hz), 9.01 (t, 1H , J=5.6 Hz).
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[C:10]([N+:12]([O-:14])=[O:13])[CH:9]=[CH:8][C:5]=1[CH:6]=[O:7])([O-:3])=[O:2].[C:15]([O:19][CH3:20])(=[O:18])[CH:16]=[CH2:17].C1N2CCN(CC2)C1>O1CCOCC1.O>[N+:1]([C:4]1[CH:11]=[C:10]([N+:12]([O-:14])=[O:13])[CH:9]=[CH:8][C:5]=1[CH:6]([OH:7])[C:16](=[CH2:17])[C:15]([O:19][CH3:20])=[O:18])([O-:3])=[O:2]
Reactant: O=Cc1ccc([N+](=O)[O-])cc1[N+](=O)[O-]
Reactant: C=CC(=O)OC
Agent: C1CN2CCN1CC2
Solvent: O
Solvent: C1COCCO1
Product: C=C(C(=O)OC)C(O)c1ccc([N+](=O)[O-])cc1[N+](=O)[O-]
Temperature: 25 °C

Procedure:
2,4-Dinitrobenzaldehyde was dissolved in dioxane and water, methyl acrylate and triethylenediamine were added thereto at room temperature, and the whole was stirred to obtain methyl 2-[(2,4-dinitrophenyl)(hydroxy)methyl]acrylate.
Reaction SMILES: C(N(CC)CC)C.[Br:8][C:9]1[CH:10]=[N:11][S:12][C:13]=1[NH:14][C@H:15]([C:20]([OH:22])=O)[CH2:16][CH:17]([CH3:19])[CH3:18].Cl.[NH2:24][CH2:25][C:26]#[N:27].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>CN(C)C=O.O>[Br:8][C:9]1[CH:10]=[N:11][S:12][C:13]=1[NH:14][C@H:15]([C:20]([NH:27][CH2:26][C:25]#[N:24])=[O:22])[CH2:16][CH:17]([CH3:18])[CH3:19]
Reactant: CC(C)C[C@H](Nc1sncc1Br)C(=O)O
Reactant: N#CCN
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)C[C@H](Nc1sncc1Br)C(=O)NCC#N
Temperature: 25 °C
Reaction time: 3 h
Yield: 88.6 %

Procedure:
Triethylamine (0.16 mL, 1.1 mmol) was added dropwise to a solution of N-(4-bromoisothiazol-5-yl)leucine (92 mg, 0.31 mmol), aminoacetonitrile hydrochloride (58 mg, 0.63 mmol) and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (180 mg, 0.35 mmol) in N, N-dimethylformamide (1.0 mL) at 0° C. After stirring at rt for 3 h, the reaction vessel contents were poured into water and extracted with a 1:1 mixture of ether and ethyl acetate (3×). The combined extracts were washed with saturated sodium bicarbonate solution, then with saturated sodium chloride solution, and dried (Na2SO4). Concentration under reduced pressure and flash chromatography of the residue on silica gel eluting with a mixture of ethyl acetate and hexanes (2:3) afforded 91 mg of N2-(4-bromoisothiazol-5-yl)-N1-(cyanomethyl)leucinamide as a colorless foam.
Reaction SMILES: [NH2:1][C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.O.Cl>C(O)(C)C>[CH2:7]1[CH2:6][CH2:5][CH:4]([CH2:3][C@H:2]([NH2:1])[C:10]([OH:12])=[O:11])[CH2:9][CH2:8]1
Reactant: N[C@@H](Cc1ccccc1)C(=O)O
Agent: Cl
Solvent: O
Solvent: CC(C)O
Product: N[C@@H](CC1CCCCC1)C(=O)O
Temperature: 55 °C
Reaction time: 7 h

Procedure:
20 g (121 mmol) L-phenylalanine are dissolved or suspended in 200 ml deionised water, 200 ml isopropanol and 12.2 ml (146 mmol) 37% hydrochloric acid. After addition of 2 g of the Pt/Rh catalyst, 4% Pt+1% Rh on activated carbon (water content approx. 50%, corresponding to approx. 5 wt. % catalyst relative to L-phenylalanine used), the reaction mixture is introduced into a 1 l hydrogenation autoclave. After being rendered inert with nitrogen three times, it is rinsed with hydrogen twice, then a hydrogen overpressure of 8-10 bar is established and the reaction solution heated to 50-60° C. After approximately 6 to 8 hours, hydrogen uptake is completed (theoretical amount of H2 8.1 l). The hydrogenator is depressurised and once again rendered inert with nitrogen three times. The still hot reaction solution is extracted with a nutsch filter and the catalyst is washed with 50 ml deionised water. The filtrate is first concentrated to low volume in vacuo (the isopropanol largely removed), the residue then adjusted to a pH of 5-6 with 50% sodium hydroxide solution. It is cooled to a temperature of 0-10° C., the product is extracted with a nutsch filter, rinsed with 50 ml deionised water and dried in a drying oven in vacuo at 50-70° C.
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[N:13]([CH2:16][C@H:17]1[CH2:22][CH2:21][C@H:20]([CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:19][CH2:18]1)[CH2:14][CH3:15])=O.[CH3:29][S:30][CH2:31][CH2:32][O:33][C:34]1[CH:35]=[N:36][C:37]([NH2:40])=[N:38][CH:39]=1>>[CH3:29][S:30][CH2:31][CH2:32][O:33][C:34]1[CH:39]=[N:38][C:37]([NH:40][CH2:1][C:3]2[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=2[N:13]([CH2:16][C@H:17]2[CH2:18][CH2:19][C@H:20]([CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:21][CH2:22]2)[CH2:14][CH3:15])=[N:36][CH:35]=1
Reactant: CCOC(=O)C[C@H]1CC[C@H](CN(CC)c2ccc(C(F)(F)F)cc2C=O)CC1
Reactant: CSCCOc1cnc(N)nc1
Product: CCOC(=O)C[C@H]1CC[C@H](CN(CC)c2ccc(C(F)(F)F)cc2CNc2ncc(OCCSC)cn2)CC1

Procedure:
By using ethyl trans-[4-({[2-(formyl)-4-(trifluoromethyl)phenyl](ethyl)amino}methyl)cyclohexyl]acetate instead of 2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)benzaldehyde, the reaction with 5-[2-(methylthio)ethoxy]pyrimidin-2-amine and treatments were performed in the same manner as those of Step 4 of Example 1 to obtain ethyl trans-{4-[({2-[({5-[2-(methylthio)ethoxy]pyrimidin-2-yl}amino)methyl]-4-(trifluoromethyl)phenyl}(ethyl)amino)methyl]cyclohexyl}acetate as a pale yellow oil.
Reaction SMILES: C.[S:2]([OH:12])(=[O:11])([C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[CH:6][CH:5]=1)=[O:3].[N:13]([O-])=O.[Na+]>O>[OH-:3].[S:2]([C:4]1[CH:5]=[CH:6][C:7]([N+:10]#[N:13])=[CH:8][CH:9]=1)([OH:12])(=[O:11])=[O:3]
Reactant: O=N[O-]
Reactant: Nc1ccc(S(=O)(=O)O)cc1
Agent: C
Agent: [Na+]
Solvent: O
Product: N#[N+]c1ccc(S(=O)(=O)O)cc1
Product: [OH-]

Procedure:
This example illustrates the preparation of a carbon black product having an attached p-C6H4SO3- group. A fluffy carbon black (200 g) having a CTAB surface area of 350 m2 /g and a DBP of 120 cc/100 g carbon and 42.4 g sulfanilic acid were placed in the batch pin pelletizer. After mixing for 40 seconds by means of the rotor, a solution of 20.7 of sodium nitrite, NaNO2, in 150 g water was added to the pelletizer. 4-Sulfobenzene diazonium hydroxide inner salt is formed in situ which reacts with the carbon black. After mixing for 45 seconds by means of the rotor, the carbon black product was transformed into pellets. These were dried in an oven at 120° C. The pelletized product had handling properties at least comparable to conventionally pelletized carbon blacks and was dispersible. Using the aqueous residue test, it has a 325 mesh residue of 0.6% compared to 97% for the untreated, fluffy black.
Reaction SMILES: NC(N)=[S:3].[ClH:5].Cl.[CH2:7]([N:14]1[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][CH2:22][Cl:23])[CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(N(CC)CC)C.[OH-].[Na+]>O.C(O)C>[ClH:23].[ClH:5].[CH2:7]([N:14]1[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][CH2:22][SH:3])[CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: ClCCCN1CCN(Cc2ccccc2)CC1
Reactant: NC(N)=S
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(CC)CC
Solvent: O
Solvent: CCO
Product: SCCCN1CCN(Cc2ccccc2)CC1
Yield: 72.2 %

Procedure:
15 g of thiourea were added to a solution of 35 g of 1-benzyl-4-(3-chloropropyl)piperazine dihydrochloride, 20 g of triethylamine and 250 ml of reagent ethanol, and the mixture was refluxed for 8 hours. After the addition of a solution of 10 g of sodium hydroxide in 50 ml of water, the resulting mixture was refluxed for 4 additional hours. The ethanol was removed in vacuo, and water added to the residue which was extracted with methylene chloride, dried (sodium sulfate), and the salt was precipitated with ethereal hydrochloric acid to give 25.1 g (78% of theory) of 3-(4-benzylpiperazin-1-yl)propanethiol dihydrochloride as a white crystalline solid, M.p. 270°-273° C. (dec.).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[C:6](=[O:10])[CH2:7][CH2:8][CH2:9][C:2]1=2.[Br:11]Br.[OH-].[Na+]>C(O)(=O)C.O>[Br:11][C:5]1[S:1][C:2]2[CH2:9][CH2:8][CH2:7][C:6](=[O:10])[C:3]=2[CH:4]=1
Reactant: O=C1CCCc2sccc21
Reactant: BrBr
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: O
Product: O=C1CCCc2sc(Br)cc21
Temperature: 0 °C
Reaction time: 18 h
Yield: 92.2 %

Procedure:
6,7-Dihydro-4-Benzo[B]thiophenone (1.5 g, 9.86 mmol) was dissolved in acetic acid (10 mL) and water (10 mL). The mixture was cooled to 0° C. and bromine (0.51 mL, 9.86 mmol) was added drop-wise. After 20 min at 0° C. the reaction was warmed to room temperature and stirred for 18 hr. The reaction mixture was cooled in ice and then treated with 1 M aqueous sodium hydroxide solution until the mixture was basic. A precipitate formed which was collected by filtration, washed with water and dried in a vacuum oven at 50° C. to afford the title compound as a grey solid (2.1 g, 96%).
Reaction SMILES: [N:1]1[C:14]2[C:5](=[CH:6][CH:7]=[C:8]3[C:13]=2[N:12]=[CH:11][CH:10]=[CH:9]3)[C:4](C(Cl)=[O:16])=[CH:3][CH:2]=1.C(N(C)[C:31]([C:33]1[C:46]2[C:37](=[C:38]3[C:43](=[CH:44][CH:45]=2)[CH:42]=[CH:41][CH:40]=[N:39]3)[N:36]=[CH:35][CH:34]=1)=[O:32])CCCCCCCCCCC.[CH3:48][CH2:49][CH2:50][CH2:51][CH:52]([OH:57])[CH2:53][CH2:54][CH2:55][CH3:56]>N1C=CC=CC=1>[N:12]1[C:13]2[C:8](=[CH:7][CH:6]=[C:5]3[C:14]=2[N:1]=[CH:2][CH:3]=[CH:4]3)[CH:9]=[CH:10][C:11]=1[C:31]([O:57][CH:52]([CH2:53][CH2:54][CH2:55][CH3:56])[CH2:51][CH2:50][CH2:49][CH3:48])=[O:32].[CH2:48]([C:45]1[CH:44]=[C:43]2[C:38]([N:39]=[CH:40][CH:41]=[CH:42]2)=[C:37]2[C:46]=1[C:33]([C:31]([O-:32])=[O:16])=[CH:34][CH:35]=[N:36]2)[CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56]
Reactant: CCCCC(O)CCCC
Reactant: O=C(Cl)c1ccnc2c1ccc1cccnc12
Reactant: CCCCCCCCCCCCN(C)C(=O)c1ccnc2c1ccc1cccnc12
Solvent: c1ccncc1
Product: CCCCC(CCCC)OC(=O)c1ccc2ccc3cccnc3c2n1
Product: CCCCCCCCCc1cc2cccnc2c2nccc(C(=O)[O-])c12

Procedure:
5-nonyl 1,10-phenanthroline carboxylate was synthesized as follows: 1 equivalent of 1,10-phenanthroline-4-carbonyl chloride (prepared as described above in the discussion of N-dodecyl-N-methy-1,10-phenanthroline-4-carboxamide) was reacted with 1 equivalent of 5-nonanol in the presence of pyridine to give the desired product, 5-nonyl-1,10-phenanthroline-4-carboxylate.
Reaction SMILES: [C@H:1]12[CH2:8][CH2:7][CH2:6][C@H:5]1[CH2:4][C@@H:3]([C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[NH:2]2.Cl.[CH2:20]([O:27][C:28]([N:30]1[CH2:35][CH2:34][CH:33]([CH2:36][CH2:37][CH2:38][CH2:39][C@H:40]([NH:46][C@H:47]([C:49](O)=[O:50])[CH3:48])[C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:32][CH2:31]1)=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.Cl.C(N(CC)CC)C.P(C#N)(=O)(OCC)OCC>CN(C)C=O.O>[CH2:20]([O:27][C:28]([N:30]1[CH2:35][CH2:34][CH:33]([CH2:36][CH2:37][CH2:38][CH2:39][C@H:40]([NH:46][C@H:47]([C:49]([N:2]2[C@H:3]([C:9]([O:11][CH2:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[O:10])[CH2:4][C@H:5]3[C@@H:1]2[CH2:8][CH2:7][CH2:6]3)=[O:50])[CH3:48])[C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:32][CH2:31]1)=[O:29])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: O=C(OCc1ccccc1)[C@@H]1C[C@@H]2CCC[C@@H]2N1
Reactant: CCOC(=O)[C@H](CCCCC1CCN(C(=O)OCc2ccccc2)CC1)N[C@@H](C)C(=O)O
Agent: CCOP(=O)(C#N)OCC
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: CCOC(=O)[C@H](CCCCC1CCN(C(=O)OCc2ccccc2)CC1)N[C@@H](C)C(=O)N1[C@H](C(=O)OCc2ccccc2)C[C@@H]2CCC[C@@H]21
Yield: 37.3 %

Procedure:
In 10 ml of N,N-dimethylformamide are dissolved 0.56 g of benzyl (S,S,S)-2-azabicyclo[3,3,0]octane-3-carboxylate·hydrochloride and 0.5 g of N-[(S)-5-(1-benzyloxycarbonyl-4-piperidyl)-1-ethoxycarbonylpentyl]-L-alanine·hydrochloride, and 0.3 g of triethylamine is added to the solution under ice-cooling with stirring, followed by addition of 0.5 ml of diethyl phosphorocyanidate. After stirring for 30 minutes, there is added to the mixture 0.1 g of triethylamine, followed by stirring for 30 minutes and at room temperature for 1 hour. The reaction mixture is diluted with 100 ml of water and extracted with 100 ml of ethyl acetate. The extract is washed with 5% aqueous phosphoric acid and water, successively, and dried over anhydrous magnesium sulfate. The solvent is distilled off under reduced pressure, and the residue is purified by silica gel column chromatography (hexane:acetone=3:1) to give 0.26 g of benzyl (S,S,S)-2-[N-[(S)-5-(1-benzyloxycarbonyl-4-piperidyl)-1-ethoxycarbonylpentyl]-L-alanyl]-2-azabicyclo-[3,3,0]octane-3-carboxylate as a colorless oil.
Reaction SMILES: C(O[C:6]([N:8]1[CH2:12][C:11](=[N:13][O:14][CH3:15])[CH2:10][C@H:9]1[C:16]([OH:18])=O)=[O:7])(C)(C)C.[C:19](=[N:22]O)([NH2:21])[CH3:20].[Cl:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31]1[CH:36]=[CH:35][C:34](C(O)=O)=[CH:33][CH:32]=1.CC1C=CC=CC=1C1C=CC(C(O)=O)=CC=1>>[CH3:15][O:14][N:13]=[C:11]1[CH2:10][C@@H:9]([C:16]2[O:18][N:22]=[C:19]([CH3:20])[N:21]=2)[N:8]([C:6]([C:34]2[CH:33]=[CH:32][C:31]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[Cl:24])=[CH:36][CH:35]=2)=[O:7])[CH2:12]1
Reactant: CC(N)=NO
Reactant: O=C(O)c1ccc(-c2ccccc2Cl)cc1
Reactant: CON=C1C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)C1
Agent: Cc1ccccc1-c1ccc(C(=O)O)cc1
Product: CON=C1C[C@@H](c2nc(C)no2)N(C(=O)c2ccc(-c3ccccc3Cl)cc2)C1
Yield: 31 %

Procedure:
Following the general methods as outlined in Example 1 (Method B), starting from (2S,4EZ)-1-(tert-butoxycarbonyl)-4-(methoxyimino)-2-pyrrolidine-carboxylic acid (Intermediate 2), N′-hydroxyethanimidamide (Intermediate 7) and 2′-chloro[1,1′-biphenyl]-4-carboxylic acid (Intermediate 10), the title compound was isolated, after flash-chromatography, as a mixture of E-/Z-isomers as an oil in 31% yield (98.5% purity by HPLC).