Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=1.[O:20]1[C:24]2[CH:25]=[CH:26][C:27](B(O)O)=[CH:28][C:23]=2[O:22][CH2:21]1>>[F:9][C:5]1[C:6]([F:8])=[CH:7][C:2]([C:27]2[CH:26]=[CH:25][C:24]3[O:20][CH2:21][O:22][C:23]=3[CH:28]=2)=[C:3]([C:10]2[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=2)[CH:4]=1
Reactant: OB(O)c1ccc2c(c1)OCO2
Reactant: CS(=O)(=O)c1ccc(-c2cc(F)c(F)cc2Br)cc1
Product: CS(=O)(=O)c1ccc(-c2cc(F)c(F)cc2-c2ccc3c(c2)OCO3)cc1
Yield: 98.6 %

Procedure:
Following the general procedure outlined in Synthetic Scheme I, 2.24 g (6.45 mmol) of 1-bromo-4,5-difluoro-2-[4-(methylsulfonyl)phenyl]benzene (Example 18, Step 2) was reacted with 1.39 g (8.38 mmol) of (1,3-benzodioxol-5-yl)boronic acid (Step 1). Purification by silica gel chromatography (MPLC) with ethyl acetate/hexane (1:4) gave 2.47 g (99%) of 5-[4,5-difluoro-2-[4-(methylsulfonyl)phenyl]phenyl]-1,3-benzodioxole as a colorless solid: mp 110.0-111.0° C.; NMR (CDCl3) δ 3.05 (s, 3H), 5.95 (s, 2H), 6.47-6.52 (m, 2H), 6.67 (d, J=8.5 Hz, 1H),-7.16-7.24 (m, 2H), 7.32 (d, J=8.5 Hz, 2H), 7.82 (d, J=8.5 Hz, 2H). MS (FAB): m/e 395 (M+Li). Anal. Calc'd for C20H14F2O4S: C, 61.85; H, 3.63. Found: C, 61.92; H, 3.66.
Reaction SMILES: [Br:1][C:2]1[C:3]([F:21])=[CH:4][C:5]2[CH:11]3[CH2:12][CH:9]([CH2:10]3)[N:8]3[CH:13]=[C:14]([C:16]([O:18][CH3:19])=[O:17])[N:15]=[C:7]3[C:6]=2[CH:20]=1.[F:22][C:23]1[CH:24]=[C:25]([CH:31]=[O:32])[C:26]([O:29][CH3:30])=[N:27][CH:28]=1>>[Br:1][C:2]1[C:3]([F:21])=[CH:4][C:5]2[CH:11]3[CH2:10][CH:9]([CH2:12]3)[N:8]3[C:13]([CH:31]([C:25]4[C:26]([O:29][CH3:30])=[N:27][CH:28]=[C:23]([F:22])[CH:24]=4)[OH:32])=[C:14]([C:16]([O:18][CH3:19])=[O:17])[N:15]=[C:7]3[C:6]=2[CH:20]=1
Reactant: COC(=O)c1cn2c(n1)-c1cc(Br)c(F)cc1C1CC2C1
Reactant: COc1ncc(F)cc1C=O
Product: COC(=O)c1nc2n(c1C(O)c1cc(F)cnc1OC)C1CC(C1)c1cc(F)c(Br)cc1-2
Yield: 68 %

Procedure:
Methyl 10-bromo-9-fluoro-3-((5-fluoro-2-methoxypyridin-3-yl)(hydroxy)methyl)-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxylate was prepared similarly according to the procedure in Example 9. Methyl 10-bromo-9-fluoro-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxylate was reacted with 5-fluoro-2-methoxy-pyridine-3-carbaldehyde to afford 196 mg (68% yield) of the title compound.
Reaction SMILES: [CH2:1]([C:3]1[NH:7][N:6]=[C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=[C:11]([C:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[O:20])[N:10]=2)[CH:4]=1)[CH3:2].[BH4-].[Na+].Cl>CO.C1COCC1>[CH2:1]([C:3]1[NH:7][N:6]=[C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=[C:11]([CH:19]([C:21]3[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=3)[OH:20])[N:10]=2)[CH:4]=1)[CH3:2]
Reactant: CCc1cc(Nc2nc(C(=O)c3ccc(F)cc3)nc3ccccc23)n[nH]1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: CCc1cc(Nc2nc(C(O)c3ccc(F)cc3)nc3ccccc23)n[nH]1
Reaction time: 0.5 h
Yield: 6.9 %

Procedure:
To crude (4-(5-ethyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)(4-fluorophenyl)methanone (104 mg, 0.28 mmol) in 1:1 MeOH/THF (4 mL) at rt was added sodium borohydride (22 mg, 0.57 mmol), and the solution was stirred for 30 min, after which 4N HCl (0.1 mL) was added. The mixture was concentrated to dryness, and the residue was purified by preparative HPLC (Varian diphenyl reverse phase column, eluting with a gradient of solvent B=0.05% HOAc/ACN and solvent A=0.05% HOAc/H2O) to afford (4-(5-ethyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)(4-fluorophenyl)methanol (7 mg). 1H NMR (300 MHz, DMSO-d6) δ 1.24 (t, 3H) 2.62 (q, 2H) 5.67 (m, 1H) 5.83 (s, 1H) 6.45 (s, 1H) 7.13 (t, 2H) 7.53-7.57 (m, 3H) 7.81 (s, 2H) 8.59 (d, 1H) 10.42 (bs, 1H) 12.15 (bs, 1H); LC-MS (ESI) m/z 364 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:10]2[C:15]([F:16])=[CH:14][C:13]([C:17]([OH:20])([CH3:19])[CH3:18])=[CH:12][C:11]=2[F:21])=[CH:5][C:6]=1[C:7]([NH2:9])=[O:8].Cl[C:23]1[N:28]=[C:27]([CH3:29])[C:26]([C:30]2[N:31]=[N:32][NH:33][CH:34]=2)=[CH:25][CH:24]=1>>[F:16][C:15]1[CH:14]=[C:13]([C:17]([OH:20])([CH3:18])[CH3:19])[CH:12]=[C:11]([F:21])[C:10]=1[C:4]1[S:3][C:2]([NH:1][C:23]2[CH:24]=[CH:25][C:26]([C:30]3[N:31]=[N:32][NH:33][CH:34]=3)=[C:27]([CH3:29])[N:28]=2)=[C:6]([C:7]([NH2:9])=[O:8])[CH:5]=1
Reactant: Cc1nc(Cl)ccc1-c1c[nH]nn1
Reactant: CC(C)(O)c1cc(F)c(-c2cc(C(N)=O)c(N)s2)c(F)c1
Product: Cc1nc(Nc2sc(-c3c(F)cc(C(C)(C)O)cc3F)cc2C(N)=O)ccc1-c1c[nH]nn1

Procedure:
The title compound was prepared as described in Example 1 using 2-amino-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide (60 mg, 0.19 mmol) and 6-chloro-2-methyl-3-(1H-1,2,3-triazol-4-yl)pyridine (Example 433, Step 3) (59 mg, 0.19 mmol) as starting materials.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][OH:16])=[CH:11][CH:10]=2)[CH:5]=[C:4]([C:17]2[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=2[O:24][CH2:25][CH3:26])[N:3]=1.[C:27]1(=[O:33])[O:32][C:30](=[O:31])[CH2:29][CH2:28]1>C(Cl)(Cl)Cl>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][O:16][C:27](=[O:33])[CH2:28][CH2:29][C:30]([OH:32])=[O:31])=[CH:11][CH:10]=2)[CH:5]=[C:4]([C:17]2[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=2[O:24][CH2:25][CH3:26])[N:3]=1
Reactant: CCOc1ccc(Cl)cc1-c1cc(Nc2ccc(CO)cc2)nc(N)n1
Reactant: O=C1CCC(=O)O1
Solvent: ClC(Cl)Cl
Product: CCOc1ccc(Cl)cc1-c1cc(Nc2ccc(COC(=O)CCC(=O)O)cc2)nc(N)n1
Reaction time: 16 h
Yield: 100 %

Procedure:
To a stirred suspension of the title compound of Example 44 (0.300 g, 0.809 mmol) and succinic anhydride (0.097 g, 0.971 mmol) in chloroform (10 ml) was added 4-dimethyl-amino-pyridine (0.138 g, 1.13 mmol). After stirring for 16 hours, the mixture was concentrated under reduced pressure. Water (10 ml) was added and the mixture was adjusted to pH 2 by addition of aqueous potassium hydrogen sulfate solution (0.5 M). The solid was filtered and dried under reduced pressure to provide the title compound (0.381 g, 81% yield). 1H NMR (DMSO-d6) δ1.38 (t, 3H, J=6.9 Hz, CH3), 2.48-2.50 (m, 2H, CH2), 2.50-2.52 (m, 2H, CH2), 4.13 (q, 2H, J=6.9 Hz, CH2), 5.05 (s, 2H, CH2), 6.28 (s, 2H, NH2), 6.79 (s, 1H, Ar), 7.14 (d, 1H, J=8.9 Hz, Ar), 7.29 (d, 2H, J=8.9 Hz, Ar), 7.41 (dd, 1H, J=8.9 Hz, 2.9 Hz, Ar), 7.71 (d, 2H, J=8.5 Hz, Ar), 7.93 (s, 1H, Ar), 9.22 (s, 1H, NH), 12.05 (s, 1H, COOH).
Reaction SMILES: [S-:1][C:2]#[N:3].[C:4]([O:7][C:8](=O)[CH3:9])(=[O:6])[CH3:5]>N1C=CC=CC=1.ClCCl>[C:4]([O:7][CH2:8][CH2:9][S:1][C:2]#[N:3])(=[O:6])[CH3:5]
Reactant: N#C[S-]
Reactant: CC(=O)OC(C)=O
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(=O)OCCSC#N
Temperature: 25 °C
Reaction time: 6 h

Procedure:
A mixture of 2-bromoethanol (7.0 g) and potassium thiocyanate (5.4 g) in methanol (40 ml) was refluxed for 7 hours. After precipitate was filtered off, the filtrate was evaporated under reduced pressure. The residue was suspended in chloroform/methanol (5/1). The precipitate was filtered off. The filtrate was evaporated under reduced pressure to give the thiocyanate (4.4 g). To a mixture of the thiocyanate in pyridine (4.8 ml)/dichloromethane (20 ml) was added acetic anhydride (5.3 ml) in dichloromethane (5 ml) at 5° C. The mixture was stirred at room temperature for 6 hours. The precipitate was filtered off. The filtrate was washed with water, dried over sodium sulfate and evaporated under reduced pressure to give 2-thiocyanatoethyl acetate (5.6 g).
Reaction SMILES: [CH3:1][CH2:2][C@@H:3]([C@@H:5]1[NH:29][C:27](=[O:28])[C@@H:26]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:37][CH2:38][CH3:39])=[CH:35][CH:36]=2)[NH:25][C:23](=[O:24])[CH2:22][CH2:21][S:20][S:19][CH2:18][C@@H:17]([C:40]([N:42]2[C@H:46]([C:47]([NH:49][C@H:50]([C:55]([NH:57][CH2:58][C:59]([NH2:61])=[O:60])=[O:56])[CH2:51][CH2:52][CH2:53][NH2:54])=[O:48])[CH2:45][CH2:44][CH2:43]2)=[O:41])[NH:16][C:14](=[O:15])[C@H:13]([CH2:62][C:63]([NH2:65])=[O:64])[NH:12][C:10](=[O:11])[C@H:9]([C@H:66]([OH:68])[CH3:67])[NH:8][C:6]1=[O:7])[CH3:4].O.N.OO>C(#N)C>[CH3:1][CH2:2][C@@H:3]([C@@H:5]1[NH:29][C:27](=[O:28])[C@@H:26]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:37][CH2:38][CH3:39])=[CH:35][CH:36]=2)[NH:25][C:23](=[O:24])[CH2:22][CH2:21][S:20][S:19][CH2:18][C@@H:17]([C:40]([N:42]2[C@H:46]([C:47]([NH:49][C@H:50]([C:55]([NH:57][CH2:58][C:59]([NH2:61])=[O:60])=[O:56])[CH2:51][CH2:52][CH2:53][NH2:54])=[O:48])[CH2:45][CH2:44][CH2:43]2)=[O:41])[NH:16][C:14](=[O:15])[C@H:13]([CH2:62][C:63]([NH2:65])=[O:64])[NH:12][C:10](=[O:11])[CH:9]([C@H:66]([OH:68])[CH3:67])[NH:8][C:6]1=[O:7])[CH3:4]
Reactant: CCOc1ccc(C[C@H]2NC(=O)CCSSC[C@@H](C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCN)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)CC)NC2=O)cc1
Agent: N
Agent: OO
Solvent: CC#N
Solvent: O
Product: CCOc1ccc(C[C@H]2NC(=O)CCSSC[C@@H](C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCN)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)C([C@@H](C)O)NC(=O)[C@H]([C@@H](C)CC)NC2=O)cc1

Procedure:
dissolving the linear atosiban in an acetonitrile aqueous solution, adjusting the pH value with ammonia water, adding H2O2 for oxidizing, filtering, purifying, and transferring to acetate salt and obtain the atosiban acetate.
Reaction SMILES: C([O:3][C:4](=[O:32])[CH2:5][S:6][C:7]1[S:11][C:10]([NH:12][C:13]([N:15]([CH2:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)[C:16]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]([F:23])[C:17]=2[F:24])=[O:14])=[N:9][CH:8]=1)C.C1(CN(C2C=CC(S(C)(=O)=O)=CC=2)C(=O)NC2SC=C(CC(O)=O)N=2)CCCC1.CN(CC1CCCCC1)C1C=CC(F)=C(F)C=1F.C(OC(=O)CSC1SC(N)=NC=1)C>>[CH:26]1([CH2:25][N:15]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]([F:23])[C:17]=2[F:24])[C:13](=[O:14])[NH:12][C:10]2[S:11][C:7]([S:6][CH2:5][C:4]([OH:32])=[O:3])=[CH:8][N:9]=2)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1
Reactant: CCOC(=O)CSc1cnc(NC(=O)N(CC2CCCCC2)c2ccc(F)c(F)c2F)s1
Agent: CCOC(=O)CSc1cnc(N)s1
Agent: CN(CC1CCCCC1)c1ccc(F)c(F)c1F
Agent: CS(=O)(=O)c1ccc(N(CC2CCCC2)C(=O)Nc2nc(CC(=O)O)cs2)cc1
Product: O=C(O)CSc1cnc(NC(=O)N(CC2CCCCC2)c2ccc(F)c(F)c2F)s1

Procedure:
The title compound was prepared via {2-[3-(cyclohexylmethyl)-3-(2,3,4-trifluoro-phenyl)ureido]-thiazol-5-ylsulfanyl}-acetic acid ethyl ester in a similar manner as described for the synthesis of {2-[3-cyclopentylmethyl-3-(4-methanesulfonyl-phenyl)-ureido]-thiazol-4-yl}-acetic acid, using (methyl-cyclohexylmethyl-(2,3,4-trifluorophenyl)-amine and (2-amino-thiazol-5-ylsulfanyl)acetic acid ethyl ester.
Reaction SMILES: [CH2:1]([O:8][C@H:9]([CH3:19])[C:10]([N-]N1CCOCC1)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:20]([Li])([CH3:22])[CH3:21].[Cl-].[NH4+]>C1COCC1.CCCCC>[CH2:1]([O:8][C@@H:9]([C:10](=[O:11])[CH:20]([CH3:22])[CH3:21])[CH3:19])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: [Li]C(C)C
Reactant: C[C@@H](OCc1ccccc1)C(=O)[N-]N1CCOCC1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCCCC
Product: CC(C)C(=O)[C@@H](C)OCc1ccccc1
Reaction time: 3 h
Yield: 94 %

Procedure:
To a stirred solution of (R)-2-benzyloxypropionyl N-morpholinyl amide (10 mmol) in THF (20 mL) under nitrogen atmosphere at −78° C. was added dropwise isopropyl lithium (15 mmol) in pentane. The reaction mixture was stirred at −78 C for 3 h (monitored by tlc). The reaction mixture was poured into saturated ammonium chloride solution and then extracted with ethyl acetate (3×25 mL). The combined extract was washed with water (2×25 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by passing through a short silica gel column using a 0-25% gradient of ether and n-pentane as eluents to give pure 20a as a colorless liquid in 94% yield. 1H NMR (400 MHz, CDCl3): δ 1.08 (3H, d); 1.10 (3H, d); 1.36 (3H, d); 3.02 (1H, m); 4.06 (1H, q); 4.46 (2H, dd); 7.33-7.34 (5H, m). MS (ESI) m/z 207.13 (M+H+).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([CH:20]([CH3:22])[CH3:21])[NH:11][C:12]=2[C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.[CH:23](=[O:26])[C:24]#[CH:25]>C1COCC1.CC(C)=O>[F:19][C:16]1[CH:17]=[CH:18][C:13]([C:12]2[N:11]=[C:10]([CH:20]([CH3:22])[CH3:21])[N:9](/[CH:25]=[CH:24]/[CH:23]=[O:26])[C:8]=2[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[CH:14][CH:15]=1
Reactant: C#CC=O
Reactant: CC(C)c1nc(-c2ccc(F)cc2)c(-c2ccc(F)cc2)[nH]1
Solvent: CC(C)=O
Solvent: C1CCOC1
Product: CC(C)c1nc(-c2ccc(F)cc2)c(-c2ccc(F)cc2)n1/C=C/C=O

Procedure:
A solution of 4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazole (200 mg) and propiolaldehyde (75% solution in toluene, 0.15 ml) in dry THF (15 ml) were heated under reflux, under nitrogen for 24 h. The residue was dissolved in acetone and absorbed onto silica gel before purifying by CC eluting with petroleum ether (b.p. 40°-60°)/ethyl acetate (2:1) to give the title compound (84 mg) as a pale yellow solid, δ(CDCl3), 1.49 (d,J=7 Hz, Me2CH), 3.25 (septet, J=7 Hz, Me2CH), 5.67 (dd,J=15 Hz, 7 Hz,CH=CH.CHO), 6.95 and 7.10-7.60 (t,J=9 Hz and m, CH=CH.CHO and aromatic protons), 9.40 (d, J=7 Hz, CH=CH.CHO).
Reaction SMILES: [O:1]=[C:2]1[C:10]2([C:14]3=[CH:15][C:16]4[O:20][CH2:19][O:18][C:17]=4[CH:21]=[C:13]3[O:12][CH2:11]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:22][CH2:23][CH:24]=O.[NH2:26][CH2:27][CH:28]1[CH2:30][CH2:29]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C1(OC2C=CC(C=O)=CC=2)C=CC=CC=1>C1COCC1.CCOCC>[CH:28]1([CH2:27][NH:26][CH2:24][CH2:23][CH2:22][N:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[C:10]3([C:14]4=[CH:15][C:16]5[O:20][CH2:19][O:18][C:17]=5[CH:21]=[C:13]4[O:12][CH2:11]3)[C:2]2=[O:1])[CH2:30][CH2:29]1
Reactant: NCC1CC1
Reactant: O=CCCN1C(=O)C2(COc3cc4c(cc32)OCO4)c2ccccc21
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=Cc1ccc(Oc2ccccc2)cc1
Solvent: CCOCC
Solvent: C1CCOC1
Product: O=C1N(CCCNCC2CC2)c2ccccc2C12COc1cc3c(cc12)OCO3
Reaction time: 8 h
Yield: 63.7 %

Procedure:
To a solution of 3-(2′-oxospiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-1′(2′H)-yl)propanal (0.07 g, 0.20 mmol) in THF (5.00 mL) was added (aminomethyl)cyclopropane (0.30 mmol) and MP-triacetoxyborohydride (0.26 g, 0.60 mmol). After overnight shaking, the polymer-bound 4-phenyloxybenzaldehyde (0.25 g, 0.18 mmol) was added. After another overnight shaking, the mixture was diluted with ether (10.0 mL) and filtered. The filtrate was concentrated in vacuo to dryness. The residue was recrystallized to give the title compound (0.05 g) in 62% yield as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.32-6.92 (m, 4H), 6.49 (s, 1H), 6.12 (s, 1H), 5.83 (m, 2H), 4.86 (m, 1H), 4.64 (m, 1H), 3.97-3.77 (m, 2H), 2.87-2.80 (m, 2H), 2.66-2.56 (m, 2H), 1.02-0.94 (m, 1H), 0.56-0.47 (m, 2H), 0.25-0.18 (m, 2H); MS (ES+) m/z 393.3 (M+1).
Reaction SMILES: [CH2:1](O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]C.[C:9]([O:13][CH3:14])(=[O:12])[CH:10]=[CH2:11].C(OOC(C)(C)C)(C)(C)C>[Br-].[Zn+2].[Br-]>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH:14]1[O:13][C:9](=[O:12])[CH2:10][CH2:11]1
Reactant: C=CC(=O)OC
Reactant: CCCCCCCO
Agent: CC(C)(C)OOC(C)(C)C
Agent: [Br-]
Agent: [Zn+2]
Product: CCCCCCC1CCC(=O)O1
Temperature: 165 °C

Procedure:
To an autoclave (a volume of 1 L) was charged 349 g (3.0 mol) of n-heptanol and 0.06 g (0.27 mmol) of zinc bromide. The mixture was heated and stirred at 165° C. Into the mixture in this state was injected a mixed liquor of 57 g (0.66 mol) of methyl acrylate and 9.9 g (0.068 mol) of di-t-butylperoxide over 6 hours. The resulting mixture was stirred at the temperature for further 1 hour. Subsequently, unreacted n-heptanol was distilled off followed by vacuum distillation, yielding γ-decalactone. Gas chromatographic analysis showed that the yield of γ-decalactone was 69%. The resulting γ-decalactone was plastic-like in odor and acidulous, which indicated an inferior aroma.
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1)#[N:2].[S-:12][C:13]#[N:14].[NH4+]>CC(C)=O>[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([N:14]=[C:13]=[S:12])=[O:8])=[CH:5][CH:4]=1)#[N:2]
Reactant: N#C[S-]
Reactant: N#Cc1ccc(C(=O)Cl)cc1
Agent: [NH4+]
Solvent: CC(C)=O
Product: N#Cc1ccc(C(=O)N=C=S)cc1
Yield: 98.5 %

Procedure:
4-Cyanobenzoyl chloride (10 g) was added in portions to a solution of ammonium thiocyanate (4.6 g) in acetone (100 ml) at room temperature, followed by heating under reflux for 10 minutes. The reaction mixture was ice-cooled, and after removal of the insoluble substance by filtration, the filtrate was evaporated under reduced pressure to give 4-cyanobenzoyl isothiocyanate (11.2 g).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[NH:21][S:22]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)(=[O:24])=[O:23].[S:31](Cl)([C:34]1[C:46]2[CH:45]=[CH:44][CH:43]=[C:39]([N:40]([CH3:42])[CH3:41])[C:38]=2[CH:37]=[CH:36][CH:35]=1)(=[O:33])=[O:32]>>[CH3:41][N:40]([CH3:42])[C:39]1[CH:43]=[CH:44][CH:45]=[C:46]2[C:38]=1[CH:37]=[CH:36][CH:35]=[C:34]2[S:31]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]2)=[CH:4][C:3]=1[NH:21][S:22]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)(=[O:23])=[O:24])(=[O:33])=[O:32]
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(N)c(NS(=O)(=O)c3ccccc3)c2)CC1
Reactant: CN(C)c1cccc2c(S(=O)(=O)Cl)cccc12
Product: CN(C)c1cccc2c(S(=O)(=O)Nc3ccc(N4CCNCC4)cc3NS(=O)(=O)c3ccccc3)cccc12

Procedure:
5-(Dimethylamino)-N-{4-(1-piperazinyl)-2-[(phenylsulfonyl)amino]phenyl}-1-naphthalenesulfonamide was synthesized from N-{2-amino-5-(4-t-butyloxycarbonyl-piperazinyl)-phenyl}benzenesulfonamide and dansylchloride (64 mg, 0.239 mmol) according to general method 3 to give 60 mg of a purple solid. MS (posES-FIA) m/z=Found: 566.3. Calcd: 566.18. 1H NMR δ 8.84 (d, 1H), 8.60 (d, 1H), 8.08 (d, 2H), 7.84-7.47 (m, 7H), 6.70 (d, 1H), 6.56-6.53 (m, 1H), 6.41-6.37 (m, 1H), 3.46 (s, 6H), 3.25-3.12 (m, 8H).
Reaction SMILES: [OH-].[K+].[CH3:3][C:4]1[C:5](=[O:11])[NH:6][C:7](=[S:10])[NH:8][CH:9]=1.[CH3:12]I>CCO>[CH3:3][C:4]1[C:5](=[O:11])[NH:6][C:7]([S:10][CH3:12])=[N:8][CH:9]=1
Reactant: CI
Reactant: Cc1c[nH]c(=S)[nH]c1=O
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CSc1ncc(C)c(=O)[nH]1
Yield: 86.6 %

Procedure:
A solution of 85% KOH (3.3 g, 50.7 mmol) and 5-methyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (7.2 g, 50.7 mmol) in absolute EtOH (100 ml) was stirred for 1 hour and then MeI (7.2 g, 50.7 mmol) was added dropwise. After refluxing the mixture for 2 hours, the solvent was removed under vacuum. The residue was triturated with water and the solid was filtered and dried in an oven to give 6.86 g of the title compound as a white powder (87% yield).
Reaction SMILES: [C-:1]1([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]Br)[CH:5]=[CH:4][CH:3]=[CH:2]1.[CH-:23]1[CH:27]=[CH:26][CH:25]=[CH:24]1.[Fe+2:28].[C:29]([O-:32])(=[S:31])[CH3:30].[K+]>>[C:29]([S:31][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][C-:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1)(=[O:32])[CH3:30].[CH-:23]1[CH:27]=[CH:26][CH:25]=[CH:24]1.[Fe+2:28]
Reactant: CC([O-])=S
Reactant: BrCCCCCCCCCCCCCCCC[c-]1cccc1
Agent: [Fe+2]
Agent: [K+]
Agent: c1cc[cH-]c1
Product: CC(=O)SCCCCCCCCCCCCCCCC[c-]1cccc1
Yield: 89.7 %

Procedure:
16-Ferrocenylhexadecyl bromide 26 (1.1 g, 2.3 mmol) was treated with potassium thioacetate (0.4 g, 3.5 mmol) for 20 h following the same procedure described for 27 to afford yellow crystals (1.0 g, 93%): mp 55–57° C.; 1H NMR δ 1.25 (s, 22H), 1.51 (m, 2H), 2.30 (m, 2H), 2.32 (s, 3H), 2.86 (m, 2H), 4.04 (s, 2H), 4.05 (s, 2H), 4.09 (s, 5H); 13C NMR δ 29.5, 29.8, 30.2, 30.3, 30.3, 31.8, 67.7, 68.8, 69.2, 90.0, 197.5; FAB-MS obsd 484.2518, calcd exact mass 484.2514; Anal. Calcd for C28H44FeOS: C, 69.40; H, 9.15; Found: C, 69.45; H, 9.07.
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[CH:14]=[N:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]=1)=[O:4].C(NC(=O)[C@H](C)C[C@H](O)[C@@H](NC(OC(C)(C)C)=O)CC(C)(C)CC(N1C2C(=CC=CC=2)CCC1C(OC)=O)=O)CCC>C(O)C.[Pd]>[CH3:1][NH:2][C:3]([CH:5]1[CH2:14][NH:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6]1)=[O:4]
Reactant: CNC(=O)c1cnc2ccccc2n1
Agent: [Pd]
Agent: CCCCNC(=O)[C@H](C)C[C@H](O)[C@H](CC(C)(C)CC(=O)N1c2ccccc2CCC1C(=O)OC)NC(=O)OC(C)(C)C
Solvent: CCO
Product: CNC(=O)C1CNc2ccccc2N1

Procedure:
0.33 g of 2-(methylaminocarbonyl)quinoxaline in 15 ml of ethanol is hydrogenated in the presence of 0.07 g of palladium-on-charcoal (10% of Pd) at room temperature for 6 h: Rf (P)=0.45.
Reaction SMILES: [C:1]1([C:7](=[O:22])[C:8]([S:20][CH3:21])=[CH:9][CH:10]=[C:11]([N:17]([CH3:19])[CH3:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:23][B-](F)(F)F.CN(C)C(C(OCC)=O)=CC=[N+](C)C.CC[O-].[Na+]>C(O)C>[CH3:19][N:17]([CH3:18])[C:11](=[CH:10][CH:9]=[C:8]([S:20][CH3:21])[C:7]([C:1]1[CH:2]=[CH:3][C:4]([F:23])=[CH:5][CH:6]=1)=[O:22])[C:12]([O:14][CH2:15][CH3:16])=[O:13]
Reactant: CCOC(=O)C(=CC=C(SC)C(=O)c1ccccc1)N(C)C
Reactant: F[B-](F)(F)F
Agent: CCOC(=O)C(=CC=[N+](C)C)N(C)C
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)C(=CC=C(SC)C(=O)c1ccc(F)cc1)N(C)C

Procedure:
The procedure is as in Example 4 for the preparation of ethyl 6-phenyl-6-oxo-5-methylthio-2-dimethylamino-2,4-hexadienoate, starting with N-(3-dimethylamino-3-ethoxycarbonylpropenylidene)-N-methylmethanaminium tetrafluoroborate (10 g), a 2M ethanolic solution of sodium ethylate (21 cc) and α-methylthio-4-fluoroacetophenone (6.5 g) in ethanol (100 cc). After purification by chromatography on a silica column with a mixture of cyclohexane and ethyl acetate (50:50 by volume) as eluent, ethyl 2-dimethylamino-6-(4-fluorophenyl)-5-methylthio-6-oxo-2,4-hexadienoate (9 g) is obtained in the form of an orange-coloured oil, and is used in the crude state in the subsequent syntheses.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])C)=[O:15])[CH:11]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:10]=1.FC(F)(F)C(O)=O.ClC(OC1C=[CH:42][C:41]([N+:44]([O-:46])=[O:45])=[CH:40]C=1)=O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14]([O:16][C:17]2[CH:20]=[CH:42][C:41]([N+:44]([O-:46])=[O:45])=[CH:40][CH:19]=2)=[O:15])[CH:11]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:10]=1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: CC(C)(C)OC(=O)N1CC(c2cc(F)ccc2F)=CC1c1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(Oc1ccc([N+](=O)[O-])cc1)N1CC(c2cc(F)ccc2F)=CC1c1ccccc1

Procedure:
To a flame-dried flask equipped with stir bar under nitrogen was charged 2-3 (0.71 g, 1.98 mmol) and anhydrous CH2Cl2 (50 mL). The resulting solution was treated with trifluoroacetic acid (10 mL) and stirred 1 hour at 25° C. Upon completion, the reaction was concentrated, taken up in CH2Cl2 (50 mL) and washed with 5% NaHCO3 (50 mL). The organic layer was dried (MgSO4), filtered and concentrated under reduced pressure. The resulting free-amine was dissolved in anhydrous CH2Cl2 (50 mL) and treated with p-nitrophenyl chloroformate (0.44 g, 2.17 mmol). The resulting solution was stirred 4 hours at 25° C. until completion. The reaction was concentrated to give 19-1 as a yellow oil: 1H NMR (300 MD, CDCl3) δ 8.22 (d, J=9.4 Hz, 1H), (d, J=9.1 Hz, 1H), 7.38 (m, 5H), 7.02 (m, 5H), 6.43 (m, 1H), 5.85 (m, 1H), 4.90 (m, 2H); LRMS m/z (M+H) 422.9 found, 423.1 required.