Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH:2]([CH:4]([OH:28])[C@H:5]([NH:8]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:6][CH3:7])[CH3:3].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][C@H:5]([CH2:6][CH3:7])[CH:4]([OH:28])[CH:2]([CH3:3])[CH3:1]
Reactant: CC[C@@H](NC(c1ccccc1)(c1ccccc1)c1ccccc1)C(O)C(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC[C@@H](N)C(O)C(C)C
Reaction time: 1 h

Procedure:
To a stirred solution of (3RS,4R)-2-methyl-4-(trityl-amino)-hexan-3-ol (0.53 g, 1 eq, 1.41 mmol) in DCM (20 mL) under an argon atmosphere at room temperature, was added CF3COOH (5 mL) dropwise, and the solution was stirred at this temperature for 1 h. The solvent was evaporated in vacuo, the residue was precipitated from Et2O (10 mL) with hexane (90 mL) with stirring to give a yellow oil. The solvent was decanted from the oil, and the oil was washed with hexane (20 mL) and dried in vacuo to afford the title compound as a light yellow oil. Yield: 0.18 g (100%). (50% de 3S,4R: 50% de 3R,4R). 1H-NMR (d6-DMSO, 250 MHz): δ 0.85-0.99 (m, 9H, NH2CH(CH2CH3)CH(CH(CH3)2)OH), 1.42-1.79 (m, 2H, NH2CH(CH2CH3)CH(CH(CH3)2)OH), 2.95 (m, 1H, NH2CH(CH2CH3)CH(CH(CH3)2)OH), 3.18 (m, 1H, NH2CH(CH2CH3)CH(CH(CH3)2)OH), 3.37 (m, 1H, NH2CH(CH2CH3)CH(CH(CH3)2)OH), 7.58 (bs, 2H, NH2CH(CH2CH3)CH(CH(CH3)2)OH).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:32])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:19]3[C:14](=[CH:15][C:16]([C:20]([O:22]CC4C=CC=CC=4)=[O:21])=[CH:17][CH:18]=3)[C:13]([C:30]#[N:31])=[CH:12]2)=[CH:7][CH:6]=1)[CH3:2].CO>[C].[Pd].O1CCCC1>[CH2:1]([O:3][C:4](=[O:32])[C:5]1[CH:6]=[CH:7][C:8]([N:11]2[C:19]3[C:14](=[CH:15][C:16]([C:20]([OH:22])=[O:21])=[CH:17][CH:18]=3)[C:13]([C:30]#[N:31])=[CH:12]2)=[CH:9][CH:10]=1)[CH3:2]
Reactant: CCOC(=O)c1ccc(-n2cc(C#N)c3cc(C(=O)OCc4ccccc4)ccc32)cc1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: CCOC(=O)c1ccc(-n2cc(C#N)c3cc(C(=O)O)ccc32)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 45.2 %

Procedure:
To a solution of 4-(3-cyano-5-benzyloxycarbonylindol-1-yl)benzoic acid ethyl ester (0.16 g) in a mixed solvent of methanol (5 mL) and tetrahydrofuran (5 mL) was added palladium-carbon powder (0.03 g) at 0° C. under an argon atmosphere, and this mixture was stirred at room temperature under a hydrogen atmosphere for 3 hours. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure to give the title compound (0.057 g).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:34])[C:4]1[C:9]([CH3:10])=[C:8]([O:11][CH3:12])[CH:7]=[C:6]([O:13][Si](C)(C)C(C)(C)C(C)C)[C:5]=1[CH2:23][S:24][CH2:25][C@H:26]([NH2:33])[C:27]1[O:31][N:30]=[C:29]([CH3:32])[N:28]=1.[ClH:35].F[C:37]1[NH:38][CH:39]=[CH:40][N:41]=1>CN(C)C=O>[ClH:35].[CH3:1][O:2][C:3](=[O:34])[C:4]1[C:9]([CH3:10])=[C:8]([O:11][CH3:12])[CH:7]=[C:6]([OH:13])[C:5]=1[CH2:23][S:24][CH2:25][C@H:26]([NH:33][C:37]1[NH:38][CH:39]=[CH:40][N:41]=1)[C:27]1[O:31][N:30]=[C:29]([CH3:32])[N:28]=1
Reactant: COC(=O)c1c(C)c(OC)cc(O[Si](C)(C)C(C)(C)C(C)C)c1CSC[C@H](N)c1nc(C)no1
Reactant: Fc1ncc[nH]1
Agent: Cl
Solvent: CN(C)C=O
Product: COC(=O)c1c(C)c(OC)cc(O)c1CSC[C@H](Nc1ncc[nH]1)c1nc(C)no1
Reaction time: 6 h
Yield: 34.1 %

Procedure:
A solution of 985 mg of (R)-2-[2-amino-2-(3-methyl-1,2,4-oxadiazol-5-yl)-ethylsulfanyl-methyl]-3-[dimethyl-(1,1,2-trimethylpropyl)-silanyloxy]-5-methoxy-6-methyl-benzoic acid methyl ester and 237 mg of 2-fluoroimidazole hydrochloride in 5 ml of N,N-dimethylformamide were stirred under argon at 50° C. for 3 h. A second portion of 117 mg of 2-fluoroimidazole hydrochloride was added and stirring was continued for 6 h. The reaction mixture was cooled and the solvent evaporated in vacuo. The residue was purified by silica gel chromatography using methanol/dichloromethane (1:20, v/v) as eluent to yield 310 mg of (R)-3-hydroxy-2-[2-(imidazol-2-ylamino)-2-(3-methyl-1,2,4-oxadiazol-5-yl)-ethylsulfanylmethyl]-5methoxy-6-methyl-benzoic acid methyl ester hydrochloride as yellow solid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH:17]([C:18]([OH:20])=O)[CH2:16][C:15]2[CH:14]=[C:13]3[O:21][CH2:22][C@H:23]([C:25]4[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]5[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([Cl:40])[CH:34]=5)=[CH:27][CH:26]=4)[O:24][C:12]3=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:74][O:75][C:76](=[O:94])[C@@H:77]([NH2:93])[CH2:78][C:79]1[CH:84]=[CH:83][C:82]([C:85]2[CH:90]=[CH:89][C:88]([C:91]#[N:92])=[CH:87][CH:86]=2)=[CH:81][CH:80]=1.Cl>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH:17]([C:18](=[O:20])[NH:93][C@H:77]([C:76]([O:75][CH3:74])=[O:94])[CH2:78][C:79]2[CH:80]=[CH:81][C:82]([C:85]3[CH:90]=[CH:89][C:88]([C:91]#[N:92])=[CH:87][CH:86]=3)=[CH:83][CH:84]=2)[CH2:16][C:15]2[CH:14]=[C:13]3[O:21][CH2:22][C@H:23]([C:25]4[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]5[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([Cl:40])[CH:34]=5)=[CH:27][CH:26]=4)[O:24][C:12]3=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)N1Cc2cc3c(cc2CC1C(=O)O)OC[C@H](c1ccc(OCc2ccc(Cl)c(Cl)c2)cc1)O3
Reactant: COC(=O)[C@@H](N)Cc1ccc(-c2ccc(C#N)cc2)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)[C@H](Cc1ccc(-c2ccc(C#N)cc2)cc1)NC(=O)C1Cc2cc3c(cc2CN1C(=O)OC(C)(C)C)O[C@@H](c1ccc(OCc2ccc(Cl)c(Cl)c2)cc1)CO3
Temperature: 25 °C
Reaction time: 16 h

Procedure:
(S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7,8-dicarboxylic acid 7-tert-butyl ester, HBTU and DIEA were dissolved in DMF (20 mL). (S)-2-Amino-3-(4′-cyano-biphenyl-4-yl)-propionic acid methyl ester was added and the mixture stirred at r.t. for 16 h. The reaction mixture was poured into 1 N HCl and extracted with ethyl acetate. The organic extracts were combined and washed with 1 N HCl and 10% sodium carbonate, concentrated and purified by column chromatography on silica gel (hexanes-ethyl acetate) to afford the product (4.9 g). LCMS (m/z) 851.
Reaction SMILES: [CH3:1][C:2]([OH:6])([C:4]#[CH:5])[CH3:3]>C(O)(C)C>[CH3:1][C:2]([OH:6])([CH:5]=[CH:4][C:2]([CH3:3])([OH:6])[CH3:1])[CH3:3]
Reactant: C#CC(C)(C)O
Solvent: CC(C)O
Product: CC(C)(O)C=CC(C)(C)O

Procedure:
2,5-Dimethyl-3-hexene-2,5-diol was prepared by free-radical addition of isopropanol to 2-methyl-3-butyne-2-ol by the method of U.S. Pat. No. 3,352,929.
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[C:14]2[C:5]([NH:6][C:7]3[CH2:8][CH:9]([C:18]4[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=4[Cl:25])[CH2:10][C:11](=O)[C:12]=3[C:13]2=[O:16])=[CH:4][CH:3]=1.[CH3:26][N:27]([CH3:32])[CH2:28][CH2:29][CH2:30][NH2:31]>C(O)C>[Cl:1][C:2]1[CH:15]=[C:14]2[C:5]([NH:6][C:7]3[CH2:8][CH:9]([C:18]4[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=4[Cl:25])[CH2:10][C:11](=[N:31][CH2:30][CH2:29][CH2:28][N:27]([CH3:32])[CH3:26])[C:12]=3[C:13]2=[O:16])=[CH:4][CH:3]=1
Reactant: O=C1CC(c2ccc(Cl)cc2Cl)Cc2[nH]c3ccc(Cl)cc3c(=O)c21
Reactant: CN(C)CCCN
Solvent: CCO
Product: CN(C)CCCN=C1CC(c2ccc(Cl)cc2Cl)Cc2[nH]c3ccc(Cl)cc3c(=O)c21
Temperature: 0 °C

Procedure:
A mixture of 3.10 g of 7-chloro-3-(2,4-dichlorophenyl)-3,4-dihydro-1,9(2H,10H)-acridinedione and 1.6 g of N,N-dimethyl-1,3-propanediamine in 125 ml of ethanol is heated under reflux for 1.5 hrs. Approximately 65 ml of solvent is removed by distillation and the resulting turbid solution is filtered. The filtrate is diluted with 50 ml of ether and chilled to 0° C. The solid is collected and recrystallized from a mixture of dichloromethane/ethyl acetate. Dry in vacuo at 80° C. for 4 hrs gives 7-chloro-3-(2,4-dichlorophenyl)-1-[[3-(dimethylamino)propyl]imino]-1,3,4,10-tetrahydro-9(2H)acridinone; mp 168°-170° C.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]([C:12]#[C:13][C:14](=[O:29])[C:15]2[CH:24]=[CH:23][C:22]3[C:21]([CH3:26])([CH3:25])[CH2:20][CH2:19][C:18]([CH3:28])([CH3:27])[C:17]=3[CH:16]=2)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].CO.C1COCC1.[BH4-].[Na+]>O>[OH:1][C:2]1[CH:11]=[C:10]([C:12]#[C:13][CH:14]([OH:29])[C:15]2[CH:24]=[CH:23][C:22]3[C:21]([CH3:25])([CH3:26])[CH2:20][CH2:19][C:18]([CH3:28])([CH3:27])[C:17]=3[CH:16]=2)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)c1ccc(C#CC(=O)c2ccc3c(c2)C(C)(C)CCC3(C)C)cc1O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)c1ccc(C#CC(O)c2ccc3c(c2)C(C)(C)CCC3(C)C)cc1O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
2.9 g (7.4 mmol) of methyl 2-hydroxy-4-[3-oxo-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]benzoate and 100 ml of a methanol/THF (50/50) mixture were introduced into a round-bottomed flask and 140 mg (3.7 mmol) of sodium borohydride were added in small amounts. The reaction mixture was stirred at room temperature for 2 hours, poured into water and extracted with ethyl ether. The organic phase was separated by settling, dried over magnesium sulfate and evaporated. The residue obtained was purified by chromatography on a silica column eluted with a mixture of dichloromethane and hexane (50/50). After evaporation of the solvents, 1.6 g (55%) of the expected compound, with a melting point of 92°-93° C., was recovered.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=1.I[C:12]1[C:13]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][N:29]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:28]2)=[N:14][C:15]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)=[N:16][C:17]=1[O:18][CH3:19].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.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.[Cu]I>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([C:12]3[C:13]([NH:26][C@@H:27]4[CH2:32][CH2:31][CH2:30][N:29]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:28]4)=[N:14][C:15]([N:20]4[CH2:21][CH2:22][O:23][CH2:24][CH2:25]4)=[N:16][C:17]=3[O:18][CH3:19])=[N:7][C:6]=2[CH:10]=1
Reactant: Brc1ccc2scnc2c1
Reactant: COc1nc(N2CCOCC2)nc(N[C@@H]2CCCN(C(=O)OC(C)(C)C)C2)c1I
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Product: COc1nc(N2CCOCC2)nc(N[C@@H]2CCCN(C(=O)OC(C)(C)C)C2)c1-c1nc2cc(Br)ccc2s1

Procedure:
Following the same procedure as in step 3 of Example 337 using 5-bromo-1,3-benzothiazole (74.9 mg, 0.35 mmol, 1.80 equiv), tert-butyl (3R)-3-[[5-iodo-6-methoxy-2-(morpholin-4-yl)pyrimidin-4-yl]amino]piperidine-1-carboxylate (100.0 mg, 0.19 mmol, 1.00 equiv), cesium carbonate (370 mg, 1.14 mmol, 6.00 equiv), Pd(PPh3)4 (40.4 mg, 0.035 mmol, 0.18 equiv), copper (I) iodide (6.7 mg, 0.035 mmol, 0.18 equiv) in DMF (5.0 mL). The crude product was purified by flash chromatography on silica gel, eluting with petroleum ether/ethyl acetate (10:1-5:1) to provide the title compound as a light yellow solid. MS m/z [M+H]+ (ESI): 605
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:25][C:26]2[CH:34]=[CH:33][C:29]([C:30]([OH:32])=O)=[CH:28][CH:27]=2)[C:9]2[S:10][CH:11]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)[N:13]=2)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[CH3:58][O:59][C:60](=[O:64])[CH2:61][CH2:62][NH2:63]>CN(C=O)C.C(OCC)(=O)C>[CH3:58][O:59][C:60](=[O:64])[CH2:61][CH2:62][NH:63][C:30](=[O:32])[C:29]1[CH:33]=[CH:34][C:26]([CH2:25][N:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[C:9]2[S:10][CH:11]=[C:12]([C:14]3[CH:15]=[CH:16][C:17]([O:20][C:21]([F:22])([F:24])[F:23])=[CH:18][CH:19]=3)[N:13]=2)=[CH:27][CH:28]=1
Reactant: COC(=O)CCN
Reactant: O=C(O)c1ccc(CN(c2ccc(Cl)cc2)c2nc(-c3ccc(OC(F)(F)F)cc3)cs2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)CCNC(=O)c1ccc(CN(c2ccc(Cl)cc2)c2nc(-c3ccc(OC(F)(F)F)cc3)cs2)cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 109.3 %

Procedure:
4-({(4-Chlorophenyl)-[4-(4-trifluoromethoxyphenyl)thiazol-2-yl]amino}methyl)benzoic acid (47 g, 93 mmol) was dissolved in DMF (500 mL) and 1-hydoxybenzotriazole (18.9 g, 140 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (26.7 g, 140 mmol) were added and the mixture was stirred at room temperature for 1.5 hours. Di PEA (i 9.1 mL, 111 mmol) and 3-aminopropionic acid methyl ester hydrochloride (15.5 g, 111 mmol) were added to the mixture and the resulting mixture was stirred at room temperature for 16 hours. Ethyl acetate (500 mL) was added and the mixture was washed with water (500 mL). The aqueous phase was extracted with ethyl acetate (500 mL). The combined organic phases were washed with water (2×500 mL) and saturated aqueous ammonium chloride (2×300 mL), dried (Na2SO4) and concentrated in vacuo to afford 60 g (quant.) of crude 3-[4-({(4-chlorophenyl)-[4-(4-trifluoromethoxyphenyl)thiazol-2-yl]amino}methyl)benzoylamino]propionic acid methyl ester as a solid. Recrystallisation from ethanol afforded 31.2 g (55%) pure product.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8](I)=[CH:9][N:10]=2)[CH:7]=1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[C:15]([F:22])[CH:14]=1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:16]3[CH:17]=[CH:18][C:13]([Cl:12])=[CH:14][C:15]=3[F:22])=[CH:9][N:10]=2)[CH:7]=1
Reactant: Brc1ccc2ncc(I)n2c1
Reactant: OB(O)c1ccc(Cl)cc1F
Product: Fc1cc(Cl)ccc1-c1cnc2ccc(Br)cn12

Procedure:
The title compound, light brown solid (0.54 g, 76%), MS (ISP) m/z=327.3 [(M+H)+], mp 159° C., was prepared in accordance with the general method of intermediate E from commercially available 6-bromo-3-iodoimidazo[1,2-a]pyridine (0.7 g, 2.17 mmol) and commercially available 4-chloro-2-fluoro-phenylboronic acid (0.42 g, 2.38 mmol).
Reaction SMILES: [F:1][C:2]1[C:7]([O:8][C:9]2[C:23]([O:24][C:25]3[CH:26]=[N:27][C:28]([S:31]([CH2:34][CH3:35])(=[O:33])=[O:32])=[CH:29][CH:30]=3)=[CH:22][C:12]3[NH:13][C:14]([C:16]4[CH:21]=[CH:20]C=C[N:17]=4)=[N:15][C:11]=3[CH:10]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:36]1C=CC(C=O)=N1>>[F:1][C:2]1[C:7]([O:8][C:9]2[C:23]([O:24][C:25]3[CH:26]=[N:27][C:28]([S:31]([CH2:34][CH3:35])(=[O:32])=[O:33])=[CH:29][CH:30]=3)=[CH:22][C:12]3[NH:13][C:14]([C:16]4[CH:21]=[CH:20][NH:36][N:17]=4)=[N:15][C:11]=3[CH:10]=2)=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: O=Cc1cc[nH]n1
Reactant: CCS(=O)(=O)c1ccc(Oc2cc3[nH]c(-c4ccccn4)nc3cc2Oc2cccnc2F)cn1
Product: CCS(=O)(=O)c1ccc(Oc2cc3[nH]c(-c4cc[nH]n4)nc3cc2Oc2cccnc2F)cn1

Procedure:
The entitled compound was obtained as a colorless solid in the same method as in Example 202 or in accordance with the method or by combining it with an ordinary method but using 4-(2-fluoropyridin-3-yloxy)-5-(6-ethanesulfonyl-pyridin-3-yloxy)-benzene-1,2-diamine obtained in Example 239, and 1H-pyrazole-3-carboxaldehyde.
Reaction SMILES: FC1C=[C:4](C=C(F)C=1)[CH2:5][N:6]1C=CN=C1S.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH:27]=[CH:26][N:25]=[C:24]2[SH:28])=[CH:19][CH:18]=1>>[NH2:6][CH2:5][CH2:4][S:28][C:24]1[N:23]([C:20]2[CH:19]=[CH:18][C:17]([Cl:16])=[CH:22][CH:21]=2)[CH:27]=[CH:26][N:25]=1
Reactant: Sc1nccn1-c1ccc(Cl)cc1
Reactant: Fc1cc(F)cc(Cn2ccnc2S)c1
Product: NCCSc1nccn1-c1ccc(Cl)cc1

Procedure:
The procedure of Example 1 wherein 1-(3,5-difluorobenzyl)-2-mercaptoimidazole is replaced by 1-(4-chlorophenyl)-2-mercaptoimidazole yields 2-(2-aminoethylthio)-1-(4-chlorophenyl)imidazole.
Reaction SMILES: C1(=O)NC(=O)CC1.[C:8]([OH:27])(=O)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]/[CH:16]=[CH:17]\[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].[NH2:28][CH2:29][CH:30]([OH:33])[CH2:31][OH:32]>C(#N)C.O>[OH:33][CH:30]([CH2:31][OH:32])[CH2:29][NH:28][C:8](=[O:27])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]/[CH:16]=[CH:17]\[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Reactant: NCC(O)CO
Agent: O=C1CCC(=O)N1
Solvent: CC#N
Solvent: O
Product: CCCCCCCC/C=C\CCCCCCCC(=O)NCC(O)CO
Yield: 87 %

Procedure:
To a solution of cis-9-octadecenoic acid succinimide (18.3 g, 48.2 mmol) in 50 ml of acetonitrile is added 1-amino-2,3-propanediol (4.4 g, 48.2 mmol) in 50 ml of H2O. After stirring for 12 hours at room temperature the acetonitrile is distilled off and the residue is extracted with ethyl acetate. The combined organic phases are extracted with saturated NaCl solution. The organic phase is dried with MgSO4, filtrated and concentrated. The residue is crystallized from isohexane. Yield: 87% of a colorless powder.
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:13]([NH:14][C:15](=[O:23])OC2C=CC=CC=2)=[N:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=1)[CH3:2].[CH3:24][O:25][C:26]1[CH:27]=[C:28]([N:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)[CH:29]=[C:30]([O:32][CH3:33])[CH:31]=1>>[CH2:1]([O:3][C:4]1[C:13]([NH:14][C:15]([N:37]2[CH2:36][CH2:35][N:34]([C:28]3[CH:27]=[C:26]([O:25][CH3:24])[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=3)[CH2:39][CH2:38]2)=[O:23])=[N:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=1)[CH3:2]
Reactant: COc1cc(OC)cc(N2CCNCC2)c1
Reactant: CCOc1nc2ccccc2nc1NC(=O)Oc1ccccc1
Product: CCOc1nc2ccccc2nc1NC(=O)N1CCN(c2cc(OC)cc(OC)c2)CC1
Yield: 74.7 %

Procedure:
Phenyl N-(2-ethoxyquinoxalin-3-yl)carbamate and 1-(3,5-dimethoxyphenyl)piperazine were reacted by the same way with the example 36 to obtain the titled compound.
Reaction SMILES: Cl[C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[CH2:11]1[C@@H:15]2[CH2:16][NH:17][CH2:18][C@@H:14]2[CH2:13][N:12]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20]>>[CH3:7][N:6]1[C:2]([N:17]2[CH2:16][C@@H:15]3[CH2:11][N:12]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:13][C@@H:14]3[CH2:18]2)=[C:3]([N+:8]([O-:10])=[O:9])[CH:4]=[N:5]1
Reactant: CC(C)(C)OC(=O)N1C[C@H]2CNC[C@H]2C1
Reactant: Cn1ncc([N+](=O)[O-])c1Cl
Product: Cn1ncc([N+](=O)[O-])c1N1C[C@H]2CN(C(=O)OC(C)(C)C)C[C@H]2C1
Yield: 86 %

Procedure:
Reaction of 5-chloro-1-methyl-4-nitro-1H-pyrazole and (3aR,6aS)-tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate gave (3aR,6aS)-tert-butyl 5-(1-methyl-4-nitro-1H-pyrazol-5-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate as a yellow oil (0.36 g, 86%). 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 3.75 (s, 3H), 3.73-3.55 (m, 4H), 3.42-3.33 (m, 2H), 3.17-3.04 (m, 4H), 1.48 (s, 9H)
Reaction SMILES: [C:1]([O:9][CH:10]1[CH2:15][C:14]([CH3:17])([CH3:16])[NH:13][C:12]([CH3:19])([CH3:18])[CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:20]1[CH2:44][CH:21]1[CH2:22][O:23][CH:24]1[CH2:29][CH2:28][CH:27]([C:30]([CH:33]2[CH2:38][CH2:37]C(OCC3OC3)CC2)([CH3:32])[CH3:31])[CH2:26][CH2:25]1>>[OH:20][CH:21]([CH2:44][N:13]1[C:12]([CH3:19])([CH3:18])[CH2:11][CH:10]([O:9][C:1](=[O:8])[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:15][C:14]1([CH3:17])[CH3:16])[CH2:22][O:23][CH:24]1[CH2:25][CH2:26][CH:27]([C:30]([CH:33]2[CH2:26][CH2:25][CH:24]([O:23][CH2:22][CH:21]([OH:20])[CH2:44][N:13]3[C:14]([CH3:17])([CH3:16])[CH2:15][CH:10]([O:9][C:1](=[O:8])[C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH2:11][C:12]3([CH3:19])[CH3:18])[CH2:37][CH2:38]2)([CH3:32])[CH3:31])[CH2:28][CH2:29]1
Reactant: CC(C)(C1CCC(OCC2CO2)CC1)C1CCC(OCC2CO2)CC1
Reactant: CC1(C)CC(OC(=O)c2ccccc2)CC(C)(C)N1
Product: CC(C)(C1CCC(OCC(O)CN2C(C)(C)CC(OC(=O)c3ccccc3)CC2(C)C)CC1)C1CCC(OCC(O)CN2C(C)(C)CC(OC(=O)c3ccccc3)CC2(C)C)CC1

Procedure:
A mixture of 30.0 g of 4-benzoyloxy-2,2,6,6-tetramethylpiperidine and 15.0 g of 2,2-bis[4-(2,3-epoxypropoxy)cyclohexyl]propane was reacted folowing the procedure described in Example 5, giving the desired Compound No. 78 in the form of a colourless, viscous liquid. The Compound had an Rf value of 0.70 on thin-layer chromatography on silica gel developed with a 15:5:1 by volume mixture of n-hexane, triethylamine and ethanol.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:13][C:14]([N:16]2[CH2:25][CH2:24][C:23]3[CH:22]=[N:21][C:20]([NH:26][CH:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[N:19][C:18]=3[CH2:17]2)=[O:15])[C:9]([O:11]C)=[O:10])=[CH:4][C:3]=1[F:33].C1COCC1.[OH-].[Na+].Cl>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:13][C:14]([N:16]2[CH2:25][CH2:24][C:23]3[CH:22]=[N:21][C:20]([NH:26][CH:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[N:19][C:18]=3[CH2:17]2)=[O:15])[C:9]([OH:11])=[O:10])=[CH:4][C:3]=1[F:33]
Reactant: COC(=O)C(NC(=O)N1CCc2cnc(NC3CCOCC3)nc2C1)c1ccc(Cl)c(F)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)C(NC(=O)N1CCc2cnc(NC3CCOCC3)nc2C1)c1ccc(Cl)c(F)c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 45.5 %

Procedure:
To a solution of 44 (610 mg, 1.28 mmol) and THF (5 mL) was added MeOH (1 mL) followed by the dropwise addition of 1M NaOH (5105 μL, 5.11 mmol). The reaction was stirred for 1 h, cooled to 0° C. and acidified to pH 3 with 1N HCl. The mixture was extracted twice with 10% MeOH in DCM (25 mL). The organic layers were combined and concentrated to afford 270 mg (45.6%) of 2-(4-chloro-3-fluorophenyl)-2-(2-(tetrahydro-2H-pyran-4-ylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine-7-carboxamido)acetic acid (46) which was used without further purification.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[O:13])[O:11][C:9](=[O:10])[C:8]2=[CH:14][CH:15]=1)([CH3:4])([CH3:3])[CH3:2].[C:16]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)([CH3:19])([CH3:18])[CH3:17].[Cl-].[Al+3].[Cl-].[Cl-].Cl>ClC(Cl)C>[C:1]([C:5]1[CH:15]=[CH:14][C:8]([C:9]([OH:11])=[O:10])=[C:7]([C:12](=[O:13])[C:23]2[CH:24]=[CH:25][C:20]([C:16]([CH3:19])([CH3:18])[CH3:17])=[CH:21][CH:22]=2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1ccccc1
Reactant: CC(C)(C)c1ccc2c(c1)C(=O)OC2=O
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: CC(Cl)Cl
Product: CC(C)(C)c1ccc(C(=O)c2cc(C(C)(C)C)ccc2C(=O)O)cc1
Temperature: 0 °C
Reaction time: 8 h
Yield: 64 %

Procedure:
Added into a 500 ml three-necked flask under the environment of argon were 4-t-butylphthalic anhydride 36 g (176 mmole), t-butylbenzene 27 g (200 mmole) and dichloroethane 100 ml. The mixture was cooled to 0° C. Aluminum chloride 56 g (420 mmole) was added gradually to them. After the addition, they were stirred at room temperature overnight. After the reaction, ice was added gradually followed by the addition of concentrated hydrochloric acid. After the precipitates were filtered, they were thoroughly washed to give the benzoic acid substance 32 g (yield 64%, white powder).