Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:7]([C:8](=[O:10])[CH3:9])=[CH:6][N:5]=[C:4]2[N:11]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[CH:12]=[CH:13][C:3]=12.[CH2:22]([N:29]1[CH2:34][CH2:33][CH:32]([NH2:35])[CH2:31][CH2:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)C(C)C)(C)C>>[CH2:22]([N:29]1[CH2:34][CH2:33][CH:32]([NH:35][C:2]2[C:7]([C:8](=[O:10])[CH3:9])=[CH:6][N:5]=[C:4]3[N:11]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[CH:12]=[CH:13][C:3]=23)[CH2:31][CH2:30]1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: NC1CCN(Cc2ccccc2)CC1
Reactant: CC(=O)c1cnc2c(ccn2COCC[Si](C)(C)C)c1Cl
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)c1cnc2c(ccn2COCC[Si](C)(C)C)c1NC1CCN(Cc2ccccc2)CC1
Yield: 58.3 %

Procedure:
1-(4-Chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-5-yl)ethanone (400 mg, 1.23 mmol) and 1-benzylpiperidin-4-amine (1.70 mL, 8.93 mmol) was stirred with N,N-diisopropylethylamine (251 μL. 1.47 mmol) at 140° C. for one day. The reaction mixture was purified by silica gel column chromatography (hexane/ethyl acetate=1/1 (v/v)) to give the title compound (343 mg, yield 58%).
Reaction SMILES: [F:1][C:2]([F:15])([C:11]([F:14])([F:13])[F:12])[C:3]([F:10])([F:9])[C:4](=[CH2:8])[C:5](O)=[O:6].[NH2:16][C:17]([NH2:19])=[O:18].C(OC(=O)C)(=O)C>C(O)C>[F:1][C:2]([F:15])([C:11]([F:14])([F:13])[F:12])[C:3]([F:10])([F:9])[CH:4]1[CH2:8][NH:19][C:17](=[O:18])[NH:16][C:5]1=[O:6]
Reactant: NC(N)=O
Reactant: C=C(C(=O)O)C(F)(F)C(F)(F)C(F)(F)F
Solvent: CC(=O)OC(C)=O
Solvent: CCO
Product: O=C1NCC(C(F)(F)C(F)(F)C(F)(F)F)C(=O)N1
Temperature: 100 °C
Reaction time: 0.67 h
Yield: 63.8 %

Procedure:
A mixture of α-heptafluoropropylacrylic acid (240 mg; 1.0 mmole), urea (64 mg; 1.1 mmoles) and acetic anhydride (0.6 ml) was heated at 100° C. with stirring for 40 minutes. Then, ethanol (3 ml) was added to the reaction mixture to give 180 mg (yield: 64%) of 5-heptafluoropropyldihydrouracil as colorless crystals. m.p.: 223°-224 (decomp.).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH:9](Br)[CH3:10].[CH3:12][C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[NH2:21])=[O:14]>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH:9]([NH:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[C:13](=[O:14])[CH3:12])[CH3:10]
Reactant: CC(=O)c1ccccc1N
Reactant: CC(Br)c1c(Cl)cccc1Cl
Product: CC(=O)c1ccccc1NC(C)c1c(Cl)cccc1Cl
Temperature: 100 °C
Reaction time: 8 h
Yield: 15.9 %

Procedure:
A mixture of 5.5 g of 1,3-dichloro-2-(1-bromoethyl)benzene and 2.9 g of 2-(methylcarbonyl)benzeneamine was stirred for 8 hours at 100° C. After cooling, the reaction mixture was purified by column chromatography (silica gel; CH2Cl2 /hexane 50:50). The eluent of the desired fraction was evaporated and the residue was triturated in hexane. The product was filtered off and dried in vacuo at 60° C., yielding 1.05 g (16.2%) of (±)-1-[2-[[1-(2,6-dichlorophenyl)ethyl]amino]phenyl]ethanone; mp. 122.8° C. (comp. 10).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][N:12]2[N:21]=[C:20]([S:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]2=[O:29])=[O:10])=[CH:4][CH:3]=1.ClC1C=C(C=CC=1)C(OO)=[O:35]>C(Cl)Cl.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][N:12]2[N:21]=[C:20]([S:22]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[O:35])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]2=[O:29])=[O:10])=[CH:4][CH:3]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=C(Cc1ccc(Cl)cc1)Nn1nc(Sc2ccccc2)c2ccccc2c1=O
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: O=C(Cc1ccc(Cl)cc1)Nn1nc(S(=O)c2ccccc2)c2ccccc2c1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 21.9 %

Procedure:
A mixture of the product from Example 58 (0.0200 g, 0.047 mmol) and 3-chlorobenzoperoxoic acid (0.0125 g, 0.051 mmol) in DCM (0.5 mL) was stirred at room temperature for 1 hour, diluted with EtOAc, washed with sat NaHCO3 and brine, dried (Na2SO4), filtered, and chromatographed (8-10% EtOAc/DCM) to give 4.5 mg of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 11.90 (s, 1H), 8.44-8.48 (m, 1H), 8.30-8.34 (m, 1H), 7.86-7.96 (m, 2H), 7.70-7.76 (m, 2H), 7.50-7.61 (m, 3H), 7.38-7.46 (m, 4H), 3.76 (s, 2H); MS (ESI−) M/Z 436 (M−H)−.
Reaction SMILES: [CH2:1]([N:3]([CH2:6][CH2:7][O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=O)=[CH:11][CH:10]=1)[CH2:4][CH3:5])[CH3:2].[NH3:17]>C(O)C.[Ni]>[CH2:1]([N:3]([CH2:6][CH2:7][O:8][C:9]1[CH:16]=[CH:15][C:12]([CH2:13][NH2:17])=[CH:11][CH:10]=1)[CH2:4][CH3:5])[CH3:2]
Reactant: N
Reactant: CCN(CC)CCOc1ccc(C=O)cc1
Agent: [Ni]
Solvent: CCO
Product: CCN(CC)CCOc1ccc(CN)cc1
Temperature: 80 °C
Reaction time: 12 h
Yield: 65 %

Procedure:
To the solution of 4-diethylaminoethoxybenzaldehyde X in 180 ml 10% solution of ammonia in anhydrous ethanol, 4.5 g RaNi was added and the mixture was heated to 80° C. at the pressure 68 atm in the autoclave under hydrogen input to the reaction mixture under stirring for 12 hours. The mixture was cooled, the catalyst was filtered off, washed with ethanol. The solvent was distilled off from the solution and the distillation residue was purified by distillation under the reduced pressure. Afforded 13 g (65%) of 4-diethylaminoethoxybenzylamine XI. Colourless fluid 138-140° C./0.5 torr, n20D=1.520. Lit. [6.7] reports 130° C./0.3 torr, n20D=1.5220.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][S:9]([CH3:12])(=[O:11])=[O:10])=[N:6][CH:7]=1.Br[CH2:14][CH2:15]Br>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([S:9]([CH3:12])(=[O:11])=[O:10])[CH2:15][CH2:14]2)=[N:6][CH:7]=1
Reactant: BrCCBr
Reactant: CS(=O)(=O)Cc1ccc(Br)cn1
Product: CS(=O)(=O)C1(c2ccc(Br)cn2)CC1
Yield: 19 %

Procedure:
The title compound was prepared from 5-bromo-2-methanesulfonylmethyl-pyridine and 1,2-dibromoethane following a procedure analogous to that described in Step 3 for Intermediate 4. Yield: 19% of theory; LC (method 3): tR=2.52 min; Mass spectrum (ESI+): m/z=276/278 (Br) [M+H]+.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]([OH:9])=O.S(Cl)([Cl:12])=O>CCCCCC>[CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]([Cl:12])=[O:9]
Reactant: Cn1cccc1C(=O)O
Reactant: O=S(Cl)Cl
Solvent: CCCCCC
Product: Cn1cccc1C(=O)Cl
Yield: 93.9 %

Procedure:
A mixture of 0.13 g of 1-methyl-1H-pyrrole-2-carboxylic acid, 0.15 g of thionyl chloride and 5 ml of hexane was heated under reflux for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain 0.14 g of 1-methyl-1H-pyrrole-2-carbonyl chloride. To a mixture of 0.22 g of N-(2-aminobenzoyl)-N′-ethoxycarbonylhydrazine and 10 ml of pyridine was added 0.14 g of the resulting 1-methyl-1H-pyrrole-2-carbonyl chloride, and the mixture was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.11 g of the present compound (2) of the formula:
Reaction SMILES: [CH3:1][O:2][C:3]([CH3:8])([CH3:7])[CH2:4][CH2:5][OH:6].[F:9][C:10]([F:22])([F:21])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[S:17](Cl)(=[O:19])=[O:18].C([O-])(O)=O.[Na+].C(OCC)(=O)C>C(Cl)Cl>[F:22][C:10]([F:9])([F:21])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[S:17]([O:6][CH2:5][CH2:4][C:3]([O:2][CH3:1])([CH3:8])[CH3:7])(=[O:18])=[O:19]
Reactant: COC(C)(C)CCO
Reactant: O=S(=O)(Cl)c1ccccc1C(F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: COC(C)(C)CCOS(=O)(=O)c1ccccc1C(F)(F)F
Temperature: 25 °C
Reaction time: 4 h
Yield: 80.4 %

Procedure:
To a solution of 3-methoxy-3-methylbutane-1-ol (2.8 g, 24 mmol) and TEA (1.6 g, 16 mmol) in CH2Cl2 (15 mL) was added o-(trifluoromethyl)benzenesulfonyl chloride (1.9 g, 8 mmol) dissolved in CH2Cl2 (20 mL). The solution was stirred at rt for 4 h. Saturated aqueous NaHCO3 (15 mL) was added to the solution and mixture was stirred at rt for 30 min. The organics were extracted with CH2Cl2 (75 mL) and washed with 1 M HCl (2×25 mL), saturated aqueous NaHCO3 (1×25 mL) and saturated aqueous NaCl (1×25 mL). The organics were dried over Na2SO4 and concentrated to give a crude mixture. Silica gel chromatography with ethyl acetate in hexanes yielded the desired product (2.1 g, 81%). 1H NMR (400 MHz CDCl3) δ 8.23 (m, 1H), 7.91 (m, 1H), 7.74 (m, 2H), 4.25 (t, 2H, J=7.5 Hz), 3.10 (s, 1H), 1.92 (t, 2H, J=7.5 Hz) 1.13 (s, 6H). Anal. Calcd. For C13H17F3O4S: C, 47.85; H, 5.25. Found: C, 47.95; H, 5.11.
Reaction SMILES: [O:1]=[C:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][N:8]=2)[N:3]1[CH2:12][C:13]([OH:15])=O.[Br:16][C:17]1[C:18]([C:23]2[NH:27][N:26]=[CH:25][N:24]=2)=[C:19]([NH2:22])[S:20][CH:21]=1>>[Br:16][C:17]1[C:18]([C:23]2[NH:27][N:26]=[CH:25][N:24]=2)=[C:19]([NH:22][C:13](=[O:15])[CH2:12][N:3]2[C:4]3[C:9](=[N:8][CH:7]=[CH:6][CH:5]=3)[CH2:10][CH2:11][C:2]2=[O:1])[S:20][CH:21]=1
Reactant: Nc1scc(Br)c1-c1ncn[nH]1
Reactant: O=C(O)CN1C(=O)CCc2ncccc21
Product: O=C(CN1C(=O)CCc2ncccc21)Nc1scc(Br)c1-c1ncn[nH]1

Procedure:
N-(4-Bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide was prepared from 2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetic acid (42 mg, 0.203 mmol) and 4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-amine (25 mg, 0.102 mmol) according to protocol A. Retention time (min)=1.274, method [7], MS (ESI) 433.0 (M+H); 1H NMR (300 MHz, CD3OD) δ 8.35 (s, 1H), 8.23 (d, J=4.5 Hz, 1H), 7.65 (d, J=9.2 Hz, 1H), 7.45 (dd, J=9.2, 4.5 Hz, 1H), 7.12 (s, 1H), 4.91 (s, 2H) 3.34-3.33 (m, 2H), 2.98-2.93 (m, 2H).
Reaction SMILES: [NH2:1][C:2]1[C:3]([S:12]CC2C=CC=CC=2)=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].C(O)(=O)C.Cl.[N:25]([O-])=O.[Na+]>O>[S:12]1[C:3]2[C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:9][CH:10]=[CH:11][C:2]=2[N:1]=[N:25]1
Reactant: COC(=O)c1cccc(N)c1SCc1ccccc1
Reactant: O=N[O-]
Agent: Cl
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: COC(=O)c1cccc2nnsc12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 65.4 %

Procedure:
A mixture of methyl 3-amino-2-(benzylthio)benzoate (26.9 g, 98.4 mmol), acetic acid (1.00 L, 1.75 mol), water (200 mL) and concentrated hydrochloric acid (172 mL, 2.06 mol) was stirred at room temperature for 30 min. To the reaction mixture was added a solution of sodium nitrite (7.59 g, 110 mmol) in water (200 mL) at 0° C. and the mixture was stirred at 0-5° C. for 2 hr. The precipitate was collected by filtration, washed with water, and dried under reduced pressure to give the title compound (12.5 g, yield 65%).
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5](/[CH:6]=[N:7]\[OH:8])=[CH:4][CH:3]=1.[Cl:11]N1C(=O)CCC1=O>CN(C=O)C>[OH:8]/[N:7]=[C:6](\[Cl:11])/[C:5]1[CH:9]=[CH:10][C:2]([F:1])=[CH:3][CH:4]=1
Reactant: O/N=C\c1ccc(F)cc1
Reactant: O=C1CCC(=O)N1Cl
Solvent: CN(C)C=O
Product: O/N=C(\Cl)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 100.2 %

Procedure:
To a solution of (E)- and/or (Z)-4-fluoro-benzaldehyde oxime (100 g, 719 mmol) in DMF (500 mL) was added N-chlorosuccinimide (110 g, 791 mmol) portionwise keeping the temperature below 70° C. The reaction mixture was stirred at room temperature for 2.5 h and then extracted with tert-butyl methyl ether to afford the title compound (125 g, 100%) which was obtained as a yellow oil. MS: m/e=173.1 [M]+.
Reaction SMILES: C([O:3][C:4](=O)[C@@H:5]([NH2:18])[C@@H:6]([C:8]1[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=1)[OH:7])C.[BH4-].[K+].Cl.O>CO>[NH2:18][C@H:5]([CH2:4][OH:3])[C@@H:6]([C:8]1[CH:9]=[CH:10][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:12][CH:13]=1)[OH:7]
Reactant: CCOC(=O)[C@@H](N)[C@H](O)c1ccc(S(C)(=O)=O)cc1
Agent: Cl
Agent: [BH4-]
Agent: [K+]
Solvent: O
Solvent: CO
Product: CS(=O)(=O)c1ccc([C@@H](O)[C@H](N)CO)cc1
Temperature: 25 °C

Procedure:
(2S,3R)-Ethyl-2-amino-3-[4-(methylsulfonyl)phenyl]-3-hydroxy-propanoate (Compound VIc) (10 g, 0.0348 moles) in methanol (about 100 mL) is reacted in a reaction vessel with potassium borohydride (about 2.8 g, 0.0522 moles) over about 6 hours while maintaining the temperature below about 60° C. The reaction is cooled to ambient room temperature and about 1N HCl and water (about 75 mL) are added. Thereafter, the solution is heated to evaporate the methanol. Next, sodium hydroxide is added (about 25%), the resulting solids are filtered and washed with water, then dried to yield (1R,2R)-2-amino-1-[4-(methylsulfonyl)phenyl]-1,3-propanediol (Compound V wherein R1 is methylsulfonyl).
Reaction SMILES: [H-].[K+].[CH3:3][C:4]1([CH3:22])[O:8][CH:7]2[CH2:9][C:10]([CH3:21])([CH3:20])[C:11]([CH2:15][Si](C)(C)C)(O)[C:12]([CH3:13])=[C:6]2[O:5]1.O>O1CCCC1>[CH3:3][C:4]1([CH3:22])[O:8][CH:7]2[CH2:9][C:10]([CH3:21])([CH3:20])[C:11](=[CH2:15])[C:12]([CH3:13])=[C:6]2[O:5]1
Reactant: CC1=C2OC(C)(C)OC2CC(C)(C)C1(O)C[Si](C)(C)C
Agent: [H-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: C=C1C(C)=C2OC(C)(C)OC2CC1(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 171.8 %

Procedure:
23 ml of a 20% suspension of potassium hydride in oil (containing about 3.7 g/92 mmol KH) were pipetted into a 500 ml round flask provided with a magnetic stirrer and dropping funnel having a fitted argon bubble counter and washed three times with 10 ml of hexane each time. Then, 120 ml of tetrahydrofuran were added thereto and a solution of 25.0 g (83 mmol) of 2,2,4,6,6-pentamethyl-5,6,7,7a-tetrahydro-5-trimethylsilylmethyl-1,3-benzodioxol-5-ol in 220 ml of tetrahydrofuran was added dropwise thereto at room temperature and the mixture was stirred at room temperature for 30 minutes (GC control: educt no longer present). Then, the mixture was cooled to 0° C. and 50 ml of water were slowly added dropwise. An analogous working up to that in (i) gave 29.7 g of crude 2,2,4,6,6-pentamethyl-5,6,7,7a-tetrahydro-5-methylidene-1,3-benzodioxol as a yellowish oil. A distillation on a very short Vigreux column gave at a boiling temperature of 50° C./0.02 mbar (2 Pa) 15.6 g (90% yield) of pure product as a colorless oil. 1H-NMR (CDCl3, 250 MHz): inter alia 1.12 and 1.23 (2s, in each case 3H, C(6)—(CH3)2), 1.50 and 1.53 (2s, in each case 3H, C(2)(CH3)2), 1.73 (s, 3H, C(4)—CH3), 4.55 (m, 1H, CH—O—), 4.79 (d, J=6 Hz, ═CH2); IR (film): 1693, 1112 cm−1; mass spectrum: 208 (M+, 40), 107(100);
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([NH:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.[O:12]=[C:13]([N:18]1[CH2:23][CH2:22][N:21]([C:24](=[O:35])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]([F:34])([F:33])[F:32])[CH2:20][CH2:19]1)[CH2:14][C:15](O)=[O:16].CC(C)N=C=NC(C)C>C1COCC1>[CH3:9][NH:8][C:6](=[O:7])[C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:15](=[O:16])[CH2:14][C:13](=[O:12])[N:18]2[CH2:19][CH2:20][N:21]([C:24](=[O:35])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:31]([F:32])([F:34])[F:33])[CH2:22][CH2:23]2)=[CH:11][CH:10]=1
Reactant: CNC(=O)c1ccc(N)cc1
Reactant: O=C(O)CC(=O)N1CCN(C(=O)c2ccccc2C(F)(F)F)CC1
Agent: CC(C)N=C=NC(C)C
Solvent: C1CCOC1
Product: CNC(=O)c1ccc(NC(=O)CC(=O)N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)cc1
Reaction time: 8 h
Yield: 39.2 %

Procedure:
4-Amino-N-methyl-benzamide (40 g, 0.3 mol) was added to a stirred solution of 3-oxo-3-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-propionic acid (100 mg, 0.3 mmol) and DIC (50 mg, 0.4 mmol) in THF (2 mL) and the mixture was stirred overnight. The resulting precipitate was filtered and extracted with ethyl acetate. The organic layer was washed with brine solution, dried over Na2SO4 and concentrated. The residue was purified by column chromatography using basic alumina (methanol in chloroform) to afford 56 mg (40%) of N-methyl-4-{3-oxo-3-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-propionylamino}-benzamide. LCMS: 477.17 (M+1)+, 94.5%, 1H NMR: (DMSO-d6): δ 7.8 (m, 2H), 7.6 (m, 4H), 7.4 (m, 1H), 4.0 (m, 2H), 3.8 (m, 4H), 3.6 (m, 3H), 3.2 (m, 2H), 3.0 (d, 3H).
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:15][N:14]=[C:13]([C:16]3[CH:17]=[CH:18][C:19](C=O)=[N:20][CH:21]=3)[N:12]=2)=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3].C(C1C=CC(C2ON=C(C3N=CC([CH2:45][NH:46][CH:47]4[CH2:50][CH:49]([C:51]([OH:53])=[O:52])[CH2:48]4)=NC=3)N=2)=CC=1)C(C)C>>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[O:15][N:14]=[C:13]([C:16]3[CH:17]=[CH:18][C:19]([CH2:45][NH:46][C@@H:47]4[CH2:50][C@H:49]([C:51]([OH:53])=[O:52])[CH2:48]4)=[N:20][CH:21]=3)[N:12]=2)=[CH:9][CH:10]=1)[CH:2]([CH3:4])[CH3:3]
Reactant: CC(C)Cc1ccc(-c2nc(-c3ccc(C=O)nc3)no2)cc1
Reactant: CC(C)Cc1ccc(-c2nc(-c3cnc(CNC4CC(C(=O)O)C4)cn3)no2)cc1
Product: CC(C)Cc1ccc(-c2nc(-c3ccc(CN[C@H]4C[C@@H](C(=O)O)C4)nc3)no2)cc1

Procedure:
The title compound was prepared from 5-[5-(4-isobutylphenyl)-1,2,4-oxadiazol-3-yl]pyridine-2-carbaldehyde by procedures analogous to those described in Examples (1A-1B) for the preparation of 3-({5-[5-(4-isobutyl-phenyl)-[1,2,4]oxadiazol-3-yl]-pyrazin-2-ylmethyl}-amino)-cyclobutanecarboxylic acid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:22][O:23][C:24]1[CH:25]=[C:26]([C:34]2[CH:35]=[C:36]([CH:39]=[CH:40][CH:41]=2)[CH2:37]Cl)[CH:27]=[C:28]([O:32][CH3:33])[C:29]=1[O:30][CH3:31]>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH2:37][C:36]2[CH:39]=[CH:40][CH:41]=[C:34]([C:26]3[CH:27]=[C:28]([O:32][CH3:33])[C:29]([O:30][CH3:31])=[C:24]([O:23][CH3:22])[CH:25]=3)[CH:35]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COc1cc(-c2cccc(CCl)c2)cc(OC)c1OC
Reactant: CC(C)(C)OC(=O)N1CCC(Nc2ccc(F)cc2)CC1
Product: COc1cc(-c2cccc(CN(c3ccc(F)cc3)C3CCN(C(=O)OC(C)(C)C)CC3)c2)cc(OC)c1OC

Procedure:
1-(tert-Butoxycarbonyl)-4-[(4-fluorophenyl)amino]piperidine (589 mg) and 3-(3,4,5-trimethoxyphenyl)benzyl chloride (586 mg) was treated in the same manner as described in Example 9 to give light yellow amorphous of the title compound.
Reaction SMILES: [C:1](Cl)(=O)[C:2]([Cl:4])=[O:3].[CH3:7][O:8][C:9](=[O:20])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]CC(O)=O>C(Cl)(Cl)Cl>[CH3:7][O:8][C:9]([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:1][C:2]([Cl:4])=[O:3])=[O:20]
Reactant: O=C(Cl)C(=O)Cl
Reactant: COC(=O)CCCCCCCC(=O)O
Solvent: ClC(Cl)Cl
Product: COC(=O)CCCCCCCC(=O)Cl
Temperature: 50 °C

Procedure:
In a separate process, 23.9 g of azelaic monomethylester was dissolved in 30 ml chloroform. Oxalylchloride (15 ml) was added, all at once, and the mixture refluxed 2 hours at 50° C. The mixture was cooled; excess solvent and oxalylchloride were evaporated. After distillation, 25.8 g of CH3OCO(CH2)7COCl was obtained.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:26]2[N:30]=[CH:29][NH:28][N:27]=2)=[C:4]([NH:7][C:8](=[O:25])[CH2:9][N:10]2[C:19]3[C:14](=[CH:15][C:16]([C:20]([F:23])([F:22])[F:21])=[CH:17][CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:24])[S:5][CH:6]=1.[N:31]1([CH2:36][CH2:37][CH2:38]O)[CH2:35][CH2:34][CH2:33][CH2:32]1>>[Cl:1][C:2]1[C:3]([C:26]2[N:30]=[CH:29][N:28]([CH2:38][CH2:37][CH2:36][N:31]3[CH2:35][CH2:34][CH2:33][CH2:32]3)[N:27]=2)=[C:4]([NH:7][C:8](=[O:25])[CH2:9][N:10]2[C:19]3[C:14](=[CH:15][C:16]([C:20]([F:23])([F:22])[F:21])=[CH:17][CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:24])[S:5][CH:6]=1
Reactant: O=C(Cn1c(=O)ccc2cc(C(F)(F)F)ccc21)Nc1scc(Cl)c1-c1nc[nH]n1
Reactant: OCCCN1CCCC1
Product: O=C(Cn1c(=O)ccc2cc(C(F)(F)F)ccc21)Nc1scc(Cl)c1-c1ncn(CCCN2CCCC2)n1

Procedure:
The title compound was prepared from N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide (110 mg, 242 umol) and 3-(pyrrolidin-1-yl)propan-1-ol (325 mg, 2.52 mmol) using the procedures described in Example 1.76. HPLC purification gave N-(4-chloro-3-(1-(3-(pyrrolidin-1-yl)propyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide. Method [7] Retention time 4.65 min by HPLC (M+=565 and 567). 1H NMR (300 MHz, DMSO-d6) δ 12.10 (s, 1H), 8.50 (s, 1H), 8.28 (s, 1H), 8.21 (d, J=9.3 Hz, 1H), 7.91 (d, J=9.3 Hz, 1H), 7.70 (d, J=9.3 Hz, 1H), 7.17 (s, 1H), 6.86 (d, J=9.3 Hz, 1H), 5.31 (s, 2H), 4.31 (t, J=6.6 Hz, 2H), 3.20 (broad m, 6H), 2.18 (m, 2H), 1.99 (m, 2H), 1.83 (m, 2H).
Reaction SMILES: [Cl:1][C:2]([Cl:10])([Cl:9])[CH:3]([OH:8])[CH:4]=[C:5]([CH3:7])[CH3:6].[C:11](OC(=O)C)(=[O:13])[CH3:12].N1C=CC=CC=1>CCCCCC>[Cl:1][C:2]([Cl:10])([Cl:9])[CH:3]([O:8][C:11](=[O:13])[CH3:12])[CH:4]=[C:5]([CH3:7])[CH3:6]
Reactant: CC(C)=CC(O)C(Cl)(Cl)Cl
Reactant: CC(=O)OC(C)=O
Solvent: CCCCCC
Solvent: c1ccncc1
Product: CC(=O)OC(C=C(C)C)C(Cl)(Cl)Cl
Yield: 81.3 %

Procedure:
A mixture of 53 g of 1,1,1-trichloro-2-hydroxy-4-methyl-3-pentene, 28 g of acetic anhydride, and 1.23 ml of pyridine was heated at 95°-100° for one hour. The reaction mixture was then dissolved in 500 ml of hexane. This solution was washed thrice with 150 ml portions of water and dried over anhydrous magnesium sulfate. After stripping the hexane, the residue was distilled under reduced pressure, yielding 52 g of 1,1,1-trichloro-2-acetoxy-4-methyl-3-pentene; bp 85°-90°/4-4.3 mm. An nmr spectrum of this product was consistent with the assigned structure.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[N+:6]([O-])[CH:7]=1.FC(F)(F)C(OC(=O)C(F)(F)F)=[O:17]>CN(C)C=O>[Br:1][C:2]1[C:3](=[O:17])[NH:4][C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[N:6][CH:7]=1
Reactant: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Reactant: CCOC(=O)c1ncc(Br)c[n+]1[O-]
Solvent: CN(C)C=O
Product: CCOC(=O)c1ncc(Br)c(=O)[nH]1
Temperature: 50 °C

Procedure:
To a 0° C. cooled solution of 5-bromo-2-(ethoxycarbonyl)pyrimidine 1-oxide (3, 0.62 g, 2.5 mmol) in dimethylformamide (6 mL), trifluoroacetic anhydride (3.1 g, 15 mmol) was added dropwise. The reaction mixture was heated at 50° C. for 18 h. TLC showed consumption of starting material and solvent was removed under reduced pressure. The residue was triturated with methanol (2 mL) and filtered. The solid was washed with diethyl ether and dried under reduced pressure to afford ethyl 5-bromo-6-oxo-1,6-dihydropyrimidine-2-carboxylate (4) as off white solid. Yield: 0.21 g, 34%; MS (ESI) m/z 245.09 [M−1]−.
Reaction SMILES: C[O:2][C:3]1[C:8]2[C:9]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([NH2:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)=[N:10][N:11]([CH:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[C:7]=2[CH:6]=[CH:5][N:4]=1.[I-].[Na+].Cl[Si](C)(C)C.O>C(#N)C>[O:2]=[C:3]1[C:8]2[C:9]([C:18]3[CH:19]=[CH:20][C:21]([S:24]([NH2:27])(=[O:26])=[O:25])=[CH:22][CH:23]=3)=[N:10][N:11]([CH:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[C:7]=2[CH:6]=[CH:5][NH:4]1
Reactant: COc1nccc2c1c(-c1ccc(S(N)(=O)=O)cc1)nn2C1CCOCC1
Agent: C[Si](C)(C)Cl
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: NS(=O)(=O)c1ccc(-c2nn(C3CCOCC3)c3cc[nH]c(=O)c23)cc1
Temperature: 60 °C
Reaction time: 0.5 h
Yield: 96.9 %

Procedure:
To a solution of 4-(4-methoxy-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]pyridin-3-yl)benzenesulfonamide (106 mg) in acetonitrile (10 mL) were added sodium iodide (82.0 mg) and chloro(trimethyl)silane (0.276 mL), and the mixture was stirred at 60° C. for 30 min. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and the obtained solid was washed with ethyl acetate/diisopropyl ether to give the title compound (99.0 mg).