Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[NH2:2][C@@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10](=[O:26])[C:11]2[CH:16]=[CH:15][CH:14]=[N:13][C:12]=2[O:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([S:24][CH3:25])[CH:19]=2)[CH2:5][CH2:4]1.C(N(CC)CC)C.[CH:34]1([CH2:37][C:38](O)=[O:39])[CH2:36][CH2:35]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[CH:34]1([CH2:37][C:38]([NH:2][C@@H:3]2[CH2:8][CH2:7][C@H:6]([NH:9][C:10](=[O:26])[C:11]3[CH:16]=[CH:15][CH:14]=[N:13][C:12]=3[O:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([S:24][CH3:25])[CH:19]=3)[CH2:5][CH2:4]2)=[O:39])[CH2:36][CH2:35]1
Reactant: O=C(O)CC1CC1
Reactant: CSc1cccc(Oc2ncccc2C(=O)N[C@H]2CC[C@@H](N)CC2)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CSc1cccc(Oc2ncccc2C(=O)N[C@H]2CC[C@@H](NC(=O)CC3CC3)CC2)c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
N-(cis-4-Aminocyclohexyl)-2-[3-(methylsulfanyl)phenoxy]nicotinamide hydrochloride (100 mg, 0.25 mmol) was dissolved in dimethylformamide (1.7 ml) and triethylamine (106 μl, 0.76 mmol) was added followed by cyclopropylacetic acid (28 mg, 0.25 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (97 mg, 0.51 mmol) and 1-hydroxybenzotriazole (38 mg, 0.28 mmol). The reaction was stirred under nitrogen at room temperature for 18 h and the solvent was removed under reduced pressure. The residue was suspended in saturated aqueous sodium bicarbonate solution (5 ml) and extracted with ethyl acetate (3×10 ml). The organic phase was washed with brine (5 ml), dried over MgSO4 and the solvent was removed under reduced pressure. The residue was triturated with diethyl ether to give N-{cis-4-[(cyclopropylacetyl)amino]cyclohexyl}-2-[3-(methylsulfanyl)phenoxy]nicotinamide (99 mg) as a white solid.
Reaction SMILES: C[Li].[CH3:3]COCC.[OH:8][CH:9]([C:19]1[C:24]([CH3:25])=[C:23]([O:26][CH3:27])[C:22]([O:28][CH3:29])=[C:21]([O:30][CH3:31])[C:20]=1[O:32][CH3:33])[C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=[O:15])=[CH:12][CH:11]=1.COC1C(OC)=C(OC)C(OC)=C(C)C=1C=O.[Cl-].[NH4+]>O1CCCC1.[Cl-].[Zn+2].[Cl-]>[CH3:3][O:15][C:14](=[O:16])[C:13]1[CH:12]=[CH:11][C:10]([CH:9]([OH:8])[C:19]2[C:24]([CH3:25])=[C:23]([O:26][CH3:27])[C:22]([O:28][CH3:29])=[C:21]([O:30][CH3:31])[C:20]=2[O:32][CH3:33])=[CH:18][CH:17]=1
Reactant: CCOCC
Reactant: COc1c(C)c(C(O)c2ccc(C(=O)O)cc2)c(OC)c(OC)c1OC
Agent: COc1c(C)c(C=O)c(OC)c(OC)c1OC
Agent: [Cl-]
Agent: [Li]C
Solvent: C1CCOC1
Product: COC(=O)c1ccc(C(O)c2c(C)c(OC)c(OC)c(OC)c2OC)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 33 %

Procedure:
To a solution of zinc chloride (1.91 mmol) in dry tetrahydrofuran (9.6 ml) was added under ice-cooling a 1.4 M methyllithium/ether solution (4.1 ml, 5.73 mmol), and the mixture was stirred at 0° C. for 30 minutes. The reaction mixture was cooled to −78° C., to which was added a solution of the compound (500 mg, 1.91 mmol) obtained in Step 1 in dry tetrahydrofuran (2.0 ml) and the mixture was further stirred at −78° C. for 4 hours. Subsequently, a solution of 2,3,4,5-tetramethoxy-6-methylbenzaldehyde (1.38 g, 5.73 mmol) in dry tetrahydrofuran (2 ml) was added and the mixture was stirred overnight at room temperature. To the reaction mixture an aqueous solution of saturated ammonium chloride (2.5 ml) was added at 0° C. After concentrating under reduced pressure, the concentrate was diluted with water and extracted three times with chloroform. After the organic layer was dried, the solvent was distilled off. After purification by a silica gel column chromatography (ethyl acetate : hexane=1:2), the title compound (237 mg, 0.63 mmol, yield 33%) was obtained.
Reaction SMILES: [CH3:1]I.[F:3][C:4]1[CH:5]=[C:6]([C:11]2[N:12]([CH3:17])[C:13](=[S:16])[NH:14][N:15]=2)[CH:7]=[C:8]([F:10])[CH:9]=1.[OH-].[Na+]>CC(C)=O.O>[F:10][C:8]1[CH:7]=[C:6]([C:11]2[N:12]([CH3:17])[C:13]([S:16][CH3:1])=[N:14][N:15]=2)[CH:5]=[C:4]([F:3])[CH:9]=1
Reactant: CI
Reactant: Cn1c(-c2cc(F)cc(F)c2)n[nH]c1=S
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)=O
Product: CSc1nnc(-c2cc(F)cc(F)c2)n1C
Temperature: 25 °C
Reaction time: 3 h
Yield: 92.7 %

Procedure:
MeI (1.4 mL, 22.4 mmol) was added to a mixture of 5-(3,5-difluorophenyl)-4-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (5 g, 22 mmol) in acetone (80 mL). NaOH (0.9 g, 22 mmol) in H2O (20 mL) was added and the reaction was stirred for 3 h at r.t. The formed precipitate was filtered off and the solution is evaporated to half volume and the formed precipitate was filtered off and combined with the first filtrate to give 4.92 g (93%) of the title compound.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][C:7]=1[N+:14]([O-])=O.[H][H]>CCO.[Pd]>[NH2:14][C:7]1[CH:8]=[C:9]([CH:12]=[CH:13][C:6]=1[NH:5][CH2:4][CH2:3][CH2:2][OH:1])[C:10]#[N:11]
Reactant: N#Cc1ccc(NCCCO)c([N+](=O)[O-])c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: N#Cc1ccc(NCCCO)c(N)c1

Procedure:
A mixture of 1.12 g (5.06 mmol) of 4-[(3-hydroxypropyl)amino]-3-nitrobenzonitrile (Intermediate 11) and 26.94 mg of 10% Pd on charcoal in 39 ml of EtOH is shaken in an hydrogen atmosphere (14 psi) for 20 hr at rt. After filtration and evaporation 1.012 g of the pure title compound are obtained.
Reaction SMILES: [CH2:1]([CH2:5][C:6](=O)[CH3:7])[C:2]([CH3:4])=O.[NH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[C:12]([Cl:17])[CH:11]=1>>[Cl:17][C:12]1[CH:11]=[C:10]([N:9]2[C:6]([CH3:7])=[CH:5][CH:1]=[C:2]2[CH3:4])[CH:15]=[CH:14][C:13]=1[OH:16]
Reactant: CC(=O)CCC(C)=O
Reactant: Nc1ccc(O)c(Cl)c1
Product: Cc1ccc(C)n1-c1ccc(O)c(Cl)c1

Procedure:
Utilizing the general procedure outlined in EXAMPLE 1, acetonyl acetone (0.83 mL, 7.0 mmol) and 4-amino-2-chlorophenol (1.0 g, 7.0 mmol) reacted to give 1-(3-chloro-4-hydroxyphenyl)-2,5-dimethylpyrrole as a brown solid: 1H NMR (CDCl3, 500 MHz) δ 7.22 (d, 1H), 7.10 (d, 1H), 7.05 (dd, 1H), 5.88 (s, 2H), 5.66 (br s, 1H), 2.03 (s, 6H); MS (ESI) 222 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]([CH3:15])[CH2:10][C:11](=[O:14])[NH:12][N:13]=2)=[CH:4][CH:3]=1.[Cl:16][CH:17]([CH3:21])[C:18](Cl)=[O:19]>C1(C)C=CC=CC=1>[Cl:16][CH:17]([CH3:21])[C:18]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]([CH3:15])[CH2:10][C:11](=[O:14])[NH:12][N:13]=2)=[CH:4][CH:3]=1)=[O:19]
Reactant: CC(Cl)C(=O)Cl
Reactant: CC1CC(=O)NN=C1c1ccc(N)cc1
Solvent: Cc1ccccc1
Product: CC(Cl)C(=O)Nc1ccc(C2=NNC(=O)CC2C)cc1
Yield: 90.9 %

Procedure:
6.0 g (29.6 millimoles) of 6-(p-aminophenyl)-5-methyl-4,5-dihydropyridaz-3-one and 4.1 g (32.3 millimoles) of 2-chloropropionyl chloride in 100 ml of absolute toluene are kept at 80° C. for 4 hours. The product is filtered off at 10° C., washed with water and dried under reduced pressure at 50° C. 7.9 g (91% of theory) of 6-[p-(2-chloropropionylamino)-phenyl]-5-methyl-4,5-dihydropyridaz-3-one are isolated as beige crystals which, after recrystallization from methanol, melt at 215°-217° C.
Reaction SMILES: [CH2:1](OCC)C.C(N(CC)CC)C.Cl[Si](C)(C)C.[CH:18]([C:21]1[C@H:26]2[C@H:27]3[C@H:36]([CH2:37][CH2:38][C@:24]2([CH3:25])[C:23](=[O:41])[CH:22]=1)[C:35]1[CH:34]=[CH:33][C:32]([O:39][CH3:40])=[CH:31][C:30]=1[CH2:29][CH2:28]3)([CH3:20])[CH3:19].[Cl-].[NH4+].Cl>O1CCCC1>[CH:18]([C@:21]1([CH3:1])[C@H:26]2[C@H:27]3[C@H:36]([CH2:37][CH2:38][C@:24]2([CH3:25])[C:23](=[O:41])[CH2:22]1)[C:35]1[CH:34]=[CH:33][C:32]([O:39][CH3:40])=[CH:31][C:30]=1[CH2:29][CH2:28]3)([CH3:20])[CH3:19]
Reactant: COc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)C=C(C(C)C)[C@@H]12
Reactant: CCOCC
Agent: C[Si](C)(C)Cl
Agent: Cl
Agent: [Cl-]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)C[C@](C)(C(C)C)[C@@H]12
Temperature: -78 °C
Yield: 87.2 %

Procedure:
A solution of lithium dimethyl cuprate (0.61 mmol) in dry diethyl ether (1.5 ml) [prepared at 0° C. from copper(I) iodide (118 mg; 0.61 mmol) and methyl lithium (0.8 ml; 1.6M; 1.28 mmol)] was cooled to -78° C. Triethylamine (0.1 ml; 0.72 mmol) and chlorotrimethylsilane (0.1 ml; 0.79 mmol) were sequentially added. Stirring at -78° C. was maintained for 5 min., before a solution of the isopropyl eneone (10) (100 mg; 0.31 mmol) in dry tetrahydrofuran (3 ml) was added dropwise. The reaction was stirred for a further 30 min. at 0° C. Saturated aqueous ammonium chloride and dilute HCl were added. To allow complete hydrolysis of the enol silyl ether, the mixture was stirred at 20° C. for 15 min. The residue upon work-up (ethyl acetate) (97 mg) was chromatographed on silica gel (10 g), and eluting with ethyl acetate-toluene (1:49) gives 15β-isopropyl-3-methoxy-15β-methylestra-1,3,5(10)-trien-17-one (11) (92 mg; 86%), m.p. 113°-115° C. (from diisopropyl ether); [α]D +87° (c 0.9); υmax 1724 cm-1 (CO); δH (C6D6), 0.68 (6H, d, J 6.0 Hz, 15α-CHMe2), 0.87 (3H, s, 15β-Me), 0.98 (3H, s, 13β-Me), 1.62 obsc (1H, q, J 6.0 Hz, 15α-CHMe2), 1.95 and 2.15 (each 1H, d, J 19.1 Hz, 16α- and 16β-H), 2.68 (2H, m, 6-H2), 3.44 (3H, s, 3-OMe), 6.70 (1H, d, J 2.6 Hz, 4-H), 6.79 (1H, dd, J 8.8 and 2.6 Hz, 2-H), and 7.09 (1H, d, J 8.8 Hz, 1-H); δH (CDCl3) 0.87 and 0.89 (each 3H, d, J 6.7 Hz, 15α-CHMe2), 1.13 (3H, s, 13β-Me), 1.32 (3H, s, 15β-Me), 2.23 obsc. (2H, d, J 18.7 Hz, 16α- and 16β-H), 2.87 (3H, m, 6-H2), 3.77 (3H, s, 3-OMe), 6.68 (1H, d, J 2.8 Hz, 4-H), 6.75 (1H, dd, J 8.8 and 2.8 Hz, 2-H), and 7.20 (1H, d, J 8.8 Hz, 1-H); δC 17.8 (C-18), 18.4 and 18.8 (15α-CHMe2), 23.0 (C-11), 26.1 (C-7), 27.8 (15β-Me), 30.0 (C-8), 34.5 (C-12), 36.9 (15α-CHMe2), 37.7 (C-6), 41.5 (C-15), 44.6 (C-9), 45.0 (C-16), 49.9 (C-13), 51.6 (C-14), 55.2 (3-OMe), 111.6 (C-2), 113.6 (C-4), 126.5 (C-1), 132.2 (C-10), 137.4 (C-5), 157.6 (C-3), and 220.3 (C-17) (Found: C, 81.2; H, 9.6%; M+, 340. C23H32O2 requires C, 81.1; H, 9.5%; M, 340).
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[CH3:6][N:7]1[CH2:13][CH2:12][C:11]2[CH:14]=[CH:15][S:16][C:10]=2[CH:9]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:8]1.CN(C)[CH:25]=[O:26]>>[CH3:6][N:7]1[CH2:13][CH2:12][C:11]2[CH:14]=[C:15]([CH:25]=[O:26])[S:16][C:10]=2[CH:9]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:8]1
Reactant: CN(C)C=O
Reactant: CN1CCc2ccsc2C(c2ccccc2)C1
Solvent: O=P(Cl)(Cl)Cl
Product: CN1CCc2cc(C=O)sc2C(c2ccccc2)C1

Procedure:
Phosphorous oxychloride (4.6 ml) was added dropwise to a stirred solution of 6-methyl-8-phenyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]azepine (3.98 g) in dimethylformamide (17 ml) cooled in an ice bath. The mixture was heated to 60° for 18 hours and then evaporated. The residue was dissolved in iced water (50 ml), basified with 2M sodium hydroxide to pH~12 and extracted with dichloromethane (2×100 ml). The extracts were dried, filtered and evaporated to a brown oil. Crystallisation from hexane gave the title product as yellow crystals (m.p. 88°).
Reaction SMILES: [SH-:1].[Na+].Cl[C:4]1[N:9]2[N:10]=[CH:11][C:12]([C:13]([O:15]CC)=[O:14])=[C:8]2[N:7]=[C:6]([CH3:18])[CH:5]=1.Cl.[OH-].[K+]>O>[C:13]([C:12]1[CH:11]=[N:10][N:9]2[C:4]([SH:1])=[CH:5][C:6]([CH3:18])=[N:7][C:8]=12)([OH:15])=[O:14]
Reactant: [SH-]
Reactant: CCOC(=O)c1cnn2c(Cl)cc(C)nc12
Agent: Cl
Agent: [K+]
Agent: [Na+]
Solvent: O
Product: Cc1cc(S)n2ncc(C(=O)O)c2n1
Temperature: 60 °C
Reaction time: 1 h
Yield: 95.6 %

Procedure:
To a solution of 19 g of sodium hydrosulfide dissolved in 2 liter of water. 19 g (79 mmole) of 7-chloro-3-ethoxycarbonyl-5-methylpyrazolo[1,5-a]pyrimidine was added and stirred at 60° C. for 1 hour. 1he pH of the mixture was adjusted to about 2 with 2N hydrochloric acid under ice-cooling and stirring and the crystals precipitated were collected by filtration and washed with water. The crystals obtained were added to a solution containing 20 g of potassium hydroxide and 150 ml of water and stirred at 60° C. for 2 hours. Then, the pH thereof was adjusted to about 2 with 6N hydrochloric acid under ice-cooling and stirring and the crystals precipitated were collected by filtration. The crystals obtained were washed with water and then dried to obtain 15.8 g of the title compound (Yield: 95.6%).
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:12])=[C:4]([N+:9]([O-:11])=[O:10])[C:5](=[O:8])[NH:6][CH:7]=1.[H-].[Na+].[CH3:15][O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21]Cl)=[CH:19][CH:18]=1.C(OCC)(=O)C>CN(C=O)C>[CH3:15][O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][N:6]2[CH:7]=[C:2]([Br:1])[C:3]([CH3:12])=[C:4]([N+:9]([O-:11])=[O:10])[C:5]2=[O:8])=[CH:19][CH:18]=1
Reactant: COc1ccc(CCl)cc1
Reactant: Cc1c(Br)c[nH]c(=O)c1[N+](=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COc1ccc(Cn2cc(Br)c(C)c([N+](=O)[O-])c2=O)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 68 %

Procedure:
To a stirred solution of 5-bromo-4-methyl-3-nitro-2-pyridone (0.60 g, 2.5 mmol) in DMF (15 mL) was added sodium hydride (60% suspension in oil, 0.103 g). After 30 minutes, 4-methoxybenzyl chloride (0.35 mL) was added, and the mixture was stirred overnight at rt. Ethyl acetate was added and the organic phase was washed with water, dried (Na2SO4), filtered and evaporated. Chromatography of the residue over silica gel (ethyl acetate/hexane 1/1) gave 1-(4-methoxybenzyl)-5-bromo-4-methyl-3-nitro-2-pyridone (0.60 g, 1.7 mmol, 68%).
Reaction SMILES: C(OC([NH:8][C@@H:9]([CH3:12])[CH2:10][OH:11])=O)(C)(C)C.[Cl:13][C:14]1[CH:15]=[C:16]([CH:21]=[CH:22][C:23]=1O)[C:17]([O:19][CH3:20])=[O:18].N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[Cl:13][C:14]1[CH:15]=[C:16]([CH:21]=[CH:22][C:23]=1[O:11][CH2:10][C@@H:9]([NH2:8])[CH3:12])[C:17]([O:19][CH3:20])=[O:18]
Reactant: C[C@@H](CO)NC(=O)OC(C)(C)C
Reactant: COC(=O)c1ccc(O)c(Cl)c1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Solvent: C1CCOC1
Product: COC(=O)c1ccc(OC[C@H](C)N)c(Cl)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 45.2 %

Procedure:
To a cooled (0° C.) solution of (S)-2-(N-tert-butoxycarbonylamino)-1-propanol (1.05 g, 5.99 mmol), methyl 3-chloro-4-hydroxybenzoate (1.12 g, 6.00 mmol), and PhP (2.36 g, 9.00 mmol) in THF (20 mL) was added diisopropyl azodicarboxylate (DIAD) (1.77 mL, 8.99 mmol), and the resulting mixture was heated under reflux for 2 days. The solution was evaporated off and the residue was dissolved in CH2Cl2 (20 mL) and TFA (10 mL). The resulting mixture was stirred at room temp for 1.5 hr. The solution was concentrated in vacuo, and the residue was dissolved in CHCl3. The mixture was extracted with H2O, and the aqueous layer was made basic by the addition of sat. NaHCO3. This basic aqueous layer was extracted with CHCl3. The extract was washed with brine, dried over Na2SO4 and evaporated to give 660 mg (2 steps, 32%) methyl (S)-3-chloro-4-(2-amino-1-propoxy)benzoate as a colorless oil. 1H-NMR (CDCl3) δ1.21 (d, 3 H, J=6.4 Hz), 3.41-3.48 (m, 1 H), 3.77-3.81 (m, 1 H), 3.89 (s, 3 H), 3.98-4.01 (m, 1 H), 6.91-6.94 (m, 1 H), 7.90-7.93 (m, 1 H), 8.05-8.06 (m, 1 H).
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[NH:11]1[C:19]2[C:14](=[CH:15][C:16]([CH2:20][N:21]3[CH2:26][CH2:25][CH:24]([C:27]4[CH:28]=[C:29]([NH:33][C:34](=[O:38])[CH:35]([CH3:37])[CH3:36])[CH:30]=[CH:31][CH:32]=4)[CH2:23][CH2:22]3)=[CH:17][CH:18]=2)[CH:13]=[CH:12]1>>[CH3:36][CH:35]([CH3:37])[C:34]([NH:33][C:29]1[CH:30]=[CH:31][CH:32]=[C:27]([CH:24]2[CH2:23][CH2:22][N:21]([CH2:20][C:16]3[CH:15]=[C:14]4[C:19](=[CH:18][CH:17]=3)[N:11]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=3[N+:8]([O-:10])=[O:9])[CH:12]=[CH:13]4)[CH2:26][CH2:25]2)[CH:28]=1)=[O:38]
Reactant: O=[N+]([O-])c1ccccc1I
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(Cc3ccc4[nH]ccc4c3)CC2)c1
Product: CC(C)C(=O)Nc1cccc(C2CCN(Cc3ccc4c(ccn4-c4ccccc4[N+](=O)[O-])c3)CC2)c1

Procedure:
Prepared by Procedure C and Scheme Q1, with CuBr in place of Cu, using 1-iodo-2-nitrobenzene and N-{3-[1-(1H-indol-5-ylmethyl)-4-piperidinyl]phenyl}-2-methylpropanamide: ESMS m/e: 497.2 (M+H)+.
Reaction SMILES: F[C:2](F)(F)[CH:3]([C:8]([F:15])([F:14])[C:9]([F:13])([F:12])[CH2:10][CH3:11])C(F)(F)F.CCC(=O)C(=O)CC>>[F:12][C:9]([F:13])([C:8]([F:15])([F:14])[CH2:3][CH3:2])[CH2:10][CH3:11]
Reactant: CCC(F)(F)C(F)(F)C(C(F)(F)F)C(F)(F)F
Agent: CCC(=O)C(=O)CC
Product: CCC(F)(F)C(F)(F)CC

Procedure:
As another example, 2-trifluoromethyl-1,1,1,3,3,4,4-heptafluorohexane may be prepared by fluorinating commercially available 3,4-hexanedione to form 3,3,4,4-tetrafluorohexane which may then be dehydrogenated to form 3,3,4,4-tetrafluoro-1-hexene. CF3 may then be added to the 3,3,4,4-tetrafluoro-1-hexene to form 2-trifluoromethyl-1,3,3,4,4-pentafluorohexane which may then be dehydrogenated to form 2-trifluoromethyl-1,3,3,4,4-pentafluoro-1-hexene. The 2-trifluoromethyl-1,3,3,4,4-pentafluoro-1-hexene may then be reacted with hydrogen fluoride to form 2-trifluoromethyl-1,1,3,3,4,4-hexafluorohexane which may then be dehydrogenated to form 2-trifluoromethyl-1,1,3,3,4,4-hexafluoro-1-hexene which may then be reacted with hydrogen fluoride to form 2-trifluoromethyl-1,1,1,3,3,4,4-heptafluorohexane.
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([N+:13]([O-])=O)[CH:8]=1)=[O:5].Cl.[OH-].[NH4+]>C(O)C>[NH2:13][C:9]1[CH:8]=[C:7]([NH:6][C:4](=[O:5])[C:3]2[CH:16]=[CH:17][C:18]([F:20])=[CH:19][C:2]=2[Cl:1])[CH:12]=[CH:11][CH:10]=1
Reactant: O=C(Nc1cccc([N+](=O)[O-])c1)c1ccc(F)cc1Cl
Agent: Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: CCO
Product: Nc1cccc(NC(=O)c2ccc(F)cc2Cl)c1
Yield: 68.8 %

Procedure:
Combine 3-nitroaniline (3.0 g, 21.7 mmol), dichloromethane (100 mL), pyridine (2.11 mL, 26.0 mmol) and 2-chloro-4-fluorobenzoyl chloride (3.07 mL, 23.9 mmol). Stir at room temperature overnight. Filter the white precipitate, rinse with ether (2×10 mL), and dry under vacuum to provide 2-chloro-4-fluoro-N-(3-nitrophenyl)benzamide (4.92 g, 77%). Combine the 2-chloro-4-fluoro-N-(3-nitrophenyl)benzamide (4.92 g, 16.7 mmol) with ethanol (150 mL), SnCl2-2H2O (18.9 g, 83.6 mmol) and concentrated hydrochloric acid (8.24 mL, 83.6 mmol). Stir at reflux under a nitrogen atmosphere for 2 hr. Neutralize with ammonium hydroxide (15 mL). Filter through Celite®, wash with dichloromethane (2×15 mL), separate the filtrate, extract with dichloromethane (2×80 mL), and dry the combined organic layers over magnesium sulfate. Filter and concentrate to dryness to provide the title intermediate as an off-white solid (3.04 g, 69%): mass spectrum (ion spray): m/z=265.0 (M+1); 1H NMR (DMSO-d6): 10.16 (bs, N—H), 7.60 (dd, J=6.2 Hz, 8.6 Hz, 1H), 7.54 (dd, J=2.5 Hz, 9.0 Hz, 1H), 7.30 (td, J=2.5 Hz, 8.5 Hz, 1H), 7.04 (t, J=2.0 Hz, 1H), 6.93 (t, J=8.0 Hz, 1H), 6.74 (bd, J=7.9 Hz, 1H), 6.29 (dd, J=2.2 Hz, 7.9 Hz, 1H), 5.10 (bs, 2H).
Reaction SMILES: [I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[O:9]=[C:10]([CH3:26])[CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1.O>CS(C)=O>[CH3:26][C:10]1([CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH2:2][O:9]1
Reactant: CC(=O)CCN1CCN(C(=O)OC(C)(C)C)CC1
Reactant: C[S+](C)(C)=O
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CC(C)(C)OC(=O)N1CCN(CCC2(C)CO2)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 87 %

Procedure:
Trimethylsulfoxonium iodide (7.8 g, 35 mmol) was gradually added to a suspension of sodium hydride (1.2 g, 35 mmol) in DMSO (120 ml), under a nitrogen atmosphere, and the mixture was stirred at room temperature for 2 hours. To which a solution of tert-butyl 4-(3-oxobutyl)piperazine-1-carboxylate (6.1 g, 23.8 mmol) in DMSO (10 ml) was gradually added dropwise, and the mixture was stirred at room temperature for 1.5 hours, and then at 50 to 60° C. for 1.5 hours. The reaction solution was allowed to return to room temperature, poured into iced water, and extracted with ethyl acetate three times. The extracts were combined, washed with water three times and then washed with a saturated saline solution, and dried over sodium sulfate. After filtration, the filtrate was concentrated under a reduced pressure to afford tert-butyl 4-[2-(2-methyl-2-oxiranyl)ethyl]piperazine-1-carboxylate (5.6 g, 87%) as a light yellow oil.
Reaction SMILES: F[C:2]1[CH:3]=[C:4]([N:8]2[CH:12]=[C:11]([C:13]#[C:14][C:15]3[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=3)[C:18]#[N:19])[N:10]=[C:9]2[CH3:23])[CH:5]=[N:6][CH:7]=1.Cl.[CH3:25][NH:26][CH3:27]>>[CH3:25][N:26]([CH3:27])[C:2]1[CH:3]=[C:4]([N:8]2[CH:12]=[C:11]([C:13]#[C:14][C:15]3[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=3)[C:18]#[N:19])[N:10]=[C:9]2[CH3:23])[CH:5]=[N:6][CH:7]=1
Reactant: Cc1nc(C#Cc2cccc(C#N)c2)cn1-c1cncc(F)c1
Reactant: CNC
Agent: Cl
Product: Cc1nc(C#Cc2cccc(C#N)c2)cn1-c1cncc(N(C)C)c1

Procedure:
The title compound, MS: m/e=328.4 (M+), was prepared in accordance with the general method of example 27 from 3-[1-(5-fluoro-pyridin-3-yl)-2-methyl-1H-imidazol-4-ylethynyl]-benzonitrile and dimethylamine hydrochloride.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:43]=[C:44]([CH3:46])[CH:45]=1)[C:6]([C:8]1[N:13]([CH2:14][C:15]2[CH:16]=[C:17]([N:22](CC3C=CC(OC)=CC=3)[C:23](=[O:28])[C:24]([F:27])([F:26])[F:25])[CH:18]=[C:19]([F:21])[CH:20]=2)[C:12](=[O:38])[NH:11][C:10](=[O:39])[C:9]=1[CH:40]([CH3:42])[CH3:41])=[O:7])#[N:2].O>C(#N)C.C(OCC)(=O)C>[C:1]([C:3]1[CH:4]=[C:5]([CH:43]=[C:44]([CH3:46])[CH:45]=1)[C:6]([C:8]1[N:13]([CH2:14][C:15]2[CH:16]=[C:17]([NH:22][C:23](=[O:28])[C:24]([F:27])([F:26])[F:25])[CH:18]=[C:19]([F:21])[CH:20]=2)[C:12](=[O:38])[NH:11][C:10](=[O:39])[C:9]=1[CH:40]([CH3:41])[CH3:42])=[O:7])#[N:2]
Reactant: COc1ccc(CN(C(=O)C(F)(F)F)c2cc(F)cc(Cn3c(C(=O)c4cc(C)cc(C#N)c4)c(C(C)C)c(=O)[nH]c3=O)c2)cc1
Solvent: CC#N
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1cc(C#N)cc(C(=O)c2c(C(C)C)c(=O)[nH]c(=O)n2Cc2cc(F)cc(NC(=O)C(F)(F)F)c2)c1
Reaction time: 24 h
Yield: 76.2 %

Procedure:
N-{3-[6-(3-Cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2 H-pyrimidin-1-ylmethyl]-5-fluoro-phenyl}-2,2,2-trifluoro-N-(4-methoxy-benzyl)-acetamide (389 mg, 0.61 mmol) was dissolved in acetonitrile (6 ml). With stirring, ceric ammonium nitrate (669 mg, 1.2 mmol) and distilled water (3 ml) were added in this order. After 24 hr., the mixture was diluted with ethyl acetate, washed with water, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography (eluent, EA:hexane (1:2)) to afford 240 mg (76%) of a white solid. 1H NMR (200 MHz, DMSO-d6) δ 1.03 (3H, d, J=6.8 Hz), 1.18 (3H, d, J=6.8 Hz), 2.09 (1H, m), 2.32 (3H, s), 4.42 (1H, d, J=16.8 Hz), 4.97 (1H, d, J=16.8 Hz), 6.80 (1H, m), 7.08 (1H, s), 7.31 (1H, m), 7.91 (1H, s), 7.96 (1H, s), 8.16 (1H, s), 11.28 (1H, s), 11.69 (1H, s).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([N+:10]([O-:12])=[O:11])[C:6]([CH3:9])=[N:7][CH:8]=1)#[CH:2].Cl.[CH3:14][NH:15][CH3:16].C([BH3-])#N.[Na+]>CCO>[CH3:14][N:15]([CH3:16])[CH2:2][CH2:1][C:3]1[CH:8]=[N:7][C:6]([CH3:9])=[C:5]([N+:10]([O-:12])=[O:11])[CH:4]=1
Reactant: C#Cc1cnc(C)c([N+](=O)[O-])c1
Reactant: CNC
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCO
Product: Cc1ncc(CCN(C)C)cc1[N+](=O)[O-]
Yield: 40.7 %

Procedure:
To a solution of 5-ethynyl-2-methyl-3-nitropyridine (930 mg, 5.74 mmol) in EtOH (7 mL) were added dimethylamine hydrochloride (2.34 g, 28.7 mmol) and sodium cyanoborohydride (0.721 g, 11.5 mmol). The reaction mixture was allowed to stir at reflux for 24 h, concentrated, and treated with 4N NaOH (10 mL). The solution was extracted with DCM (2×200 mL). The organic solutions were combined, washed with brine (200 mL), dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography to give N,N-dimethyl-2-(6-methyl-5-nitropyridin-3-yl)ethanamine (489 mg, 41%). LCMS (AA): Rt=1.35 min, m/z=210 (M+H).