Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]2[C:8]3([CH2:23][O:24][C:4]=2[CH:3]=1)[C:16]1[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=1)[N:10]([CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[C:9]3=[O:22].[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH:25]([C:2]1[CH:7]=[CH:6][C:5]2[C:8]3([CH2:23][O:24][C:4]=2[CH:3]=1)[C:16]1[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=1)[N:10]([CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[C:9]3=[O:22])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: Nc1ccccc1
Reactant: CCCCCN1C(=O)C2(COc3cc(Br)ccc32)c2ccccc21
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: Cc1ccccc1
Product: CCCCCN1C(=O)C2(COc3cc(Nc4ccccc4)ccc32)c2ccccc21
Temperature: 25 °C
Yield: 66 %

Procedure:
To a solution of 6-bromo-1′-pentylspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one (0.08 g, 0.19 mmol) in anhydrous toluene (4.00 mL) was added aniline (0.03 g, 0.29 mmol), xanthphos (0.02 g, 0.03 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.02 g, 0.02 mmol). The reaction mixture was refluxed for 16 h, cooled down to ambient temperature and concentrated in vacuo to dryness. The black residue was subjected to column chromatography (ethyl acetate/hexane, 1/7) to give the title compound (0.05 g, 62%) as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.40-7.25 (m, 6H), 7.18 (d, 1H), 7.12-7.05 (m, 3H), 6.98-6.90 (m, 2H), 6.71 (d, 1H), 6.57 (d, 1H), 6.48 (dd, 1H), 4.93 (d, 1H), 4.67 (d, 1H), 3.88-3.64 (m, 2H), 1.80-1.65 (m, 2H), 1.45-1.30 (m, 4H), 0.92 (t, 3H); MS (ES+) m/z 399.5 (M+1).
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[OH:10])[CH:2]=[CH2:3].F[C:12]1[CH:25]=[CH:24][C:15]([C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:17])=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+].CN1CCCC1=O>C1(C)C=CC=CC=1>[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][C:21]1[CH:22]=[CH:23][C:18]([C:16]([C:15]2[CH:24]=[CH:25][CH:12]=[CH:13][CH:14]=2)=[O:17])=[CH:19][CH:20]=1)=[CH:2][CH3:3]
Reactant: O=C(c1ccccc1)c1ccc(F)cc1
Reactant: C=CCc1ccccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Solvent: Cc1ccccc1
Product: CC=Cc1ccccc1Oc1ccc(C(=O)c2ccccc2)cc1
Temperature: 100 °C
Reaction time: 3 h

Procedure:
o-Allylphenol (33.5 g), 4-fluorobenzophenone (50.05 g), potassium carbonate (24.20 g), dry N-methylpyrrolidone (160 ml) and toluene (60 ml) are placed in a 3-necked 500 ml flask fitted with a stirrer, reflex condensor and thermometer and the mixture is heated under nitrogen to a temperature between 155°-160° C. and stirred for 3 hours. Water and toluene are separated via a Dean Stark trap and finally after 3 hours the reaction mixture reaches a temperature of 160° C. The mixture is cooled to 100° C. and a 1:1 mixture of toluene/water (400 ml) is added while stirring. After phase separation the aqueous layer is washed with toluene (50 ml) and the combined toluene layers are washed 4 times with water (150 ml). The toluene phase is dried over sodium sulphate and toluene distilled off by use of a rotary evaporator finally in vacuum leaving 4-[o-(1-propenyl)phenoxy]-benzophenone as a light yellow melt. The yield is 73 g.
Reaction SMILES: S([CH2:5][CH2:6][C:7]#[C:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(C)(=O)=O.Cl.[F:16][C:17]([F:32])([F:31])[C:18]1[CH:19]=[C:20]([CH:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH:25]2[OH:30])[CH:21]=[CH:22][CH:23]=1.C([O-])([O-])=O.[K+].[K+]>CC#N>[F:32][C:17]([F:16])([F:31])[C:18]1[CH:19]=[C:20]([CH:24]2[CH2:29][CH2:28][N:27]([CH2:5][CH2:6][C:7]#[C:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH2:26][CH:25]2[OH:30])[CH:21]=[CH:22][CH:23]=1
Reactant: OC1CNCCC1c1cccc(C(F)(F)F)c1
Reactant: CS(=O)(=O)CCC#Cc1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: OC1CN(CCC#Cc2ccccc2)CCC1c1cccc(C(F)(F)F)c1
Yield: 20.5 %

Procedure:
A mixture of 1-mesyl-4-phenylbut-3-yne (352 mg, 1.57 mmol), 4-(3-(trifluoromethyl)phenyl)piperidin-3-ol hydrochloride (530 mg, 1.88 mmol) and K2CO3 (542 mg, 3.93 mmol) in 20 mL of CH3CN is refluxed for 12 hr. The mixture is filtered and washed with EtOAc (3×20 mL). The filtrate is evaporated in vacuo and is purified by flash chromatography to give the product as an off white solid (120 mg, 21%): mp 77-79° C.; 1H NMR (CDCl3) 1.71 (m, 2 H), 2.15 (m, 3 H), 2.40 (bs, 1 H), 2.62 (m, 4 H), 2.72 (m, 1 H), 2.83 (m, 2 H), 7.27-7.81 (m, 9 H).
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:14][O:15][S:16]([C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=2)(=[O:18])=[O:17])[CH2:9]1)C1C=CC=CC=1.[C:26]1([O:32][C:33](Cl)=[O:34])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>ClCCl>[O:32]([C:33]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:14][O:15][S:16]([C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=2)(=[O:17])=[O:18])[CH2:9]1)=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: Cc1ccc(S(=O)(=O)OCC2CN(Cc3ccccc3)CCO2)cc1
Reactant: O=C(Cl)Oc1ccccc1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)OCC2CN(C(=O)Oc3ccccc3)CCO2)cc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of 4-benzyl-2-toluene-p-sulphonyloxymethylmorpholine (5 g.) in dichloromethane (50 ml.), phenylchloroformate (2 ml.) is added and the mixture is stirred at ambient temperature (ca 20°C) for 24 hours. The solvent is evaporated and the residual oil is recrystallised from ethanol to give 4-phenoxycarbonyl-2-toluene-p-sulphonyloxymethylmorpholine, m.p. 101°-103°C.
Reaction SMILES: [CH3:1][CH2:2][O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:15]([OH:17])=O)=[CH:10][CH:9]=2)=[O:5].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH3:40][N:41]([CH3:47])[CH:42]1[CH2:46][CH2:45][NH:44][CH2:43]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH2:2]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:15]([N:44]1[CH2:45][CH2:46][CH:42]([N:41]([CH3:47])[CH3:40])[CH2:43]1)=[O:17])=[CH:10][CH:9]=2)=[O:5])[CH3:1]
Reactant: CCOC(=O)c1cc2cc(C(=O)O)ccc2[nH]1
Reactant: CN(C)C1CCNC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCOC(=O)c1cc2cc(C(=O)N3CCC(N(C)C)C3)ccc2[nH]1
Yield: 68 %

Procedure:
The title compound was synthesized in analogy to example 1, intermediate a), from 1H-indole-2,5-dicarboxylic acid 2-ethyl ester, O-(benzotriazol-1-yl)-N,N,N′, N′-tetramethyluronium tetrafluoroborate (commercially available), 3-(dimethylamino)pyrrolidine (commercially available) and N,N-diisopropylethylamine in N,N-dimethylformamide, to give the desired product as a light brown solid (68%).
Reaction SMILES: Cl[C:2]1[C:3]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)=[CH:4][C:5]([F:8])=[N:6][CH:7]=1.[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1B(O)O.ClC1C=CC=CC=1C1C(C2C=CC(Cl)=CC=2)=CC2N(C(=O)N(CC3C=NC(C(F)(F)F)=CC=3)N=2)C=1C>>[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:2]1[C:3]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)=[CH:4][C:5]([F:8])=[N:6][CH:7]=1
Reactant: OB(O)c1ccccc1Cl
Reactant: Fc1cc(-c2ccc(Cl)cc2)c(Cl)cn1
Agent: Cc1c(-c2ccccc2Cl)c(-c2ccc(Cl)cc2)cc2nn(Cc3ccc(C(F)(F)F)nc3)c(=O)n12
Product: Fc1cc(-c2ccc(Cl)cc2)c(-c2ccccc2Cl)cn1
Yield: 35.4 %

Procedure:
The title compound (0.33 g, 35% yield) as a white foam was prepared from 5-chloro-4-(4-chlorophenyl)-2-fluoropyridine (0.71 g, 2.93 mmol) and 2-chlorophenylboronic acid (0.55 g, 3.52 mmol) in a manner analogous to that in which 6-(2-chlorophenyl)-7-(4-chlorophenyl)-5-methyl-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one was prepared. HPLC/MS: retention time=4.03 min, [M+H]+=318.1.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[C:4](Cl)[N:3]=1.[H][H]>C(O)(=O)C.O.[Pd]>[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=3)[CH2:11][CH2:10]2)=[CH:4][N:3]=1
Reactant: COc1ccc(N2CCC(c3c(N)nc(N)nc3Cl)CC2)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: O
Solvent: CC(=O)O
Product: COc1ccc(N2CCC(c3cnc(N)nc3N)CC2)cc1
Yield: 45.1 %

Procedure:
21.5 g of 2,4-diamino-6-chloro-5-[1-(4-methoxyphenyl)-4-piperidinyl]pyrimidine were dissolved in 350 ml of a mixture of acetic acid and water (1:1) and hydrogenated in the presence of 7 g of 10% palladium/carbon catalyst until the hydrogen uptake ceased or the reaction was complete in accordance with thin-layer chromatography. The catalyst was filtered off over a filter aid and the filtrate was evaporated to dryness. The residue was suspended in water and the pH was adjusted to 9 by addition of aqueous ammonium hydroxide. Filtration yielded a crude product which was chromatographed on silica gel with chloroform/methanol (19:1). There were obtained 8.7 g of 2,4-diamino-5-[1-(4-methoxyphenyl)-4-piperidinyl]pyrimidine of melting point 224°-225° C.
Reaction SMILES: [CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][O:24][CH2:25][C:26]([OH:28])=[O:27])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH3:29][C:30](=[CH2:32])[CH3:31].OS(O)(=O)=O>ClCCl>[C:30]([O:27][C:26](=[O:28])[CH2:25][O:24][CH2:23][CH2:22][O:21][CH2:20][CH2:19][NH:18][C:16]([O:15][CH2:14][CH:12]1[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:5]2[C:13]1=[CH:1][CH:2]=[CH:3][CH:4]=2)=[O:17])([CH3:32])([CH3:31])[CH3:29]
Reactant: O=C(O)COCCOCCNC(=O)OCC1c2ccccc2-c2ccccc21
Reactant: C=C(C)C
Agent: O=S(=O)(O)O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)COCCOCCNC(=O)OCC1c2ccccc2-c2ccccc21
Yield: 84.4 %

Procedure:
A solution of 150 mg (0.389 mmol) of 8-(9-Fluorenylmethoxycarbonylamino)-3,6-dioxaoctanoic acid, 546 mg (9.73 mmol) isobutylene, and 4.3 μL of 95-98% H2SO4 was stirred at r.t. for 3 days. For workup the reaction solution was diluted with dichloromethane and washed with sat. bicarbonate solution. After drying over sodium sulfate the solvent was removed and the residue obtained purified by chromatography on silica gel with a cHex/EtOAc gradient providing 145 mg (84.4%) of the title compound. ESI MS: 464.12 [M+Na]+.
Reaction SMILES: Cl[CH2:2][CH:3]=[CH:4][C:5]1[NH:6][C:7]2[CH:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH3:21])=[C:15]([C:22]([F:25])([F:24])[F:23])[CH:14]=3)[N:10]=[C:9]([C:26]#[N:27])[C:8]=2[N:28]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1>CS(C)=O>[CH2:20]([O:19][C:16]1[CH:17]=[CH:18][C:13]([C:11]2[N:10]=[C:9]([C:26]#[N:27])[C:8]3[N:28]=[C:5]([CH:4]=[CH:3][CH2:2][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)[NH:6][C:7]=3[CH:12]=2)=[CH:14][C:15]=1[C:22]([F:25])([F:24])[F:23])[CH3:21]
Reactant: CCOc1ccc(-c2cc3[nH]c(C=CCCl)nc3c(C#N)n2)cc1C(F)(F)F
Reactant: C1COCCN1
Solvent: CS(C)=O
Product: CCOc1ccc(-c2cc3[nH]c(C=CCN4CCOCC4)nc3c(C#N)n2)cc1C(F)(F)F

Procedure:
A solution of 2-(3-chloro-propenyl)-6-(4-ethoxy-3-trifluoromethyl-phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile (23 mg, 0.05 mmol), morpholine (16.1 mg, 0.15 mmol) in DMSO (500 uL) was heated to 120° C. for 5 minutes. The mixture was purified using ion exchange chromatography to afford the title compound.
Reaction SMILES: [CH2:1]([S:3]([C:6]1[N:10]=[CH:9][NH:8][N:7]=1)(=[O:5])=[O:4])[CH3:2].[CH2:11]([N:14]([CH2:18][CH2:19][CH3:20])[C:15](Cl)=[O:16])[CH2:12][CH3:13]>>[CH2:11]([N:14]([CH2:18][CH2:19][CH3:20])[C:15]([N:8]1[CH:9]=[N:10][C:6]([S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])=[N:7]1)=[O:16])[CH2:12][CH3:13]
Reactant: CCCN(CCC)C(=O)Cl
Reactant: CCS(=O)(=O)c1nc[nH]n1
Product: CCCN(CCC)C(=O)n1cnc(S(=O)(=O)CC)n1

Procedure:
In an analogous manner to that described in Example 20, 3-ethylsulphonyl-1,2,4-triazole was reacted with dipropylcarbamoyl chloride to give 1-dipropylcarbamoyl-3-ethylsulphonyl-1,2,4-triazole, m.p. 44° - 45°C. Elemental analysis satisfactory.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:18][CH2:19][C:20]([CH3:27])([CH3:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH2:18][CH2:19][C:20]([CH3:27])([CH3:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22]
Reactant: Brc1cccc2[nH]ncc12
Reactant: CCOC(=O)C(C)(C)CCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)C(C)(C)CCn1ncc2c(Br)cccc21
Temperature: 80 °C
Reaction time: 24 h
Yield: 40 %

Procedure:
To a solution of 4-bromo-1H-indazole (commercially available from Insight Chemical Solutions Ltd., 826 mg, 4.19 mmol) in DMF (10 ml) at room temperature were added Cs2CO3 (1.37 g, 4.19 mmol) and ethyl 4-bromo-2,2-dimethylbutanoate (D99) (1.40 g, 6.29 mmol) and the resulting mixture was stirred at 80° C. for 24 h then cooled to room temperature and diluted with AcOEt. The organic phase was washed with water, dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel [15-25% EtOAc/cyclohexane] gave the title compound (600 mg, 40%) as orange oil. MS (ES) C15H1981BrN2O2 requires 340, found 341 [M+H]+
Reaction SMILES: Cl[Si:2]([CH2:7][CH3:8])([CH2:5][CH3:6])[CH2:3][CH3:4].C(=O)=O.Br[C:13]([F:16])([F:15])[F:14].C(N(CC)P(N(CC)CC)N(CC)CC)C>CC(C)=O.ClCCl>[CH2:3]([Si:2]([CH2:7][CH3:8])([CH2:5][CH3:6])[C:13]([F:16])([F:15])[F:14])[CH3:4]
Reactant: CC[Si](Cl)(CC)CC
Reactant: FC(F)(F)Br
Agent: CCN(CC)P(N(CC)CC)N(CC)CC
Agent: O=C=O
Solvent: CC(C)=O
Solvent: ClCCl
Product: CC[Si](CC)(CC)C(F)(F)F
Temperature: -78 °C
Reaction time: 2 h
Yield: 69 %

Procedure:
A flask equipped with a dry ice condenser was flame dried under a nitrogen stream, and charged with 25 g (0.17 mol) of chlorotriethylsilane and 40 mL of dichloromethane. After cooling the resulting solution to -78° C. and charging the condenser with dry ice and acetone, 40 mL (0.43 mol) of bromotrifluoromethane (Freon 13B1) that had been condensed into a graduated tube was warmed to room temperature and allowed to distill into the flask. The cold solution was treated dropwise with 66mL (0.24 mol) of hexaethylphosphorous triamide, allowed to stir at -78° C. for two hours, and allowed to stir at room temperature overnight. Low boiling components were then short path distilled into a cold (-78° C.) receiving flask at >1 torr with the pot temperature kept at <50° C. The distillate was further fractionated by removal of the dichloromethane (40°-45° C. at atmospheric pressure) and short path distillation to give 22.0 g of 98% pure (69% yield) triethyltrifluoromethylsilane: bp 52°-54° C. at 10 torr; 1H NMR (CDCl3) δ 0.59-1.16 (m); 19F NMR (CDCl3, relative to CFCl3) - 61.3 ppm (s); IR (neat) 2960, 2915, 2882, 1458, 1413, 1206, 1055, 1020, 734, 693 cm-1 ; mass spectrum (70 eV) m/z (relative intensity) 115 (66, M-CF3), 105 (46), 87 (85), 77 (100), 59 (56), 49 (41), 47 (37), 41 (38). Anal. Calcd. for C7H15F3Si: C, 45.62; H, 8.20. Found: C, 47.53; H, 8.56.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][N:11]=[C:10]([CH:13]([OH:15])[CH3:14])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:16](OC=C)(=[O:18])[CH3:17]>C1(C)C=CC=CC=1>[C:16]([O:15][C@@H:13]([C:10]1[N:9]=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[O:12][N:11]=1)[CH3:14])(=[O:18])[CH3:17]
Reactant: C=COC(C)=O
Reactant: CC(O)c1noc(-c2cccc(Cl)c2)n1
Solvent: Cc1ccccc1
Product: CC(=O)O[C@H](C)c1noc(-c2cccc(Cl)c2)n1
Yield: 49.4 %

Procedure:
12.1 g (53.9 mmol) 1-[5-(3-chlorophenyl)-[1,2,4]oxadiazol-3-yl]ethanol an 1.60 g Novozyme 435® are taken up under Ar in toluene (750 mL). After addition of 5.0 mL (54.2 mmol) vinyl acetate the reaction was run at r.t. o.n., followed by filtration over celite and washing with DCM. The filtrate was purified over silica using DCM neat, followed by EA/Hep=1/1, yielding 7.1 g (49%) of the title compound. 1H NMR: 8.13 (t, 1 H), 8.01 (d, 1 H), 7.55 (d, 1 H), 7.47 (t, 1 H), 6.07 (q, 1 H), 2.15 (s, 3 H), 1.69 (d, 3 H)
Reaction SMILES: C1(C(C2C=CC=CC=2)CCO[C:11](=[S:15])[CH:12]([F:14])[F:13])C=CC=CC=1.[NH2:22][CH2:23][CH:24]1[O:28][C:27](=[O:29])[N:26]([C:30]2[CH:35]=[CH:34][C:33]([N:36]3[CH:41]=[CH:40][C:39](=[O:42])[CH2:38][CH2:37]3)=[C:32]([F:43])[CH:31]=2)[CH2:25]1>CC#N.CN(C=O)C>[F:13][CH:12]([F:14])[C:11]([NH:22][CH2:23][CH:24]1[O:28][C:27](=[O:29])[N:26]([C:30]2[CH:35]=[CH:34][C:33]([N:36]3[CH:37]=[CH:38][C:39](=[O:42])[CH2:40][CH2:41]3)=[C:32]([F:43])[CH:31]=2)[CH2:25]1)=[S:15]
Reactant: NCC1CN(c2ccc(N3C=CC(=O)CC3)c(F)c2)C(=O)O1
Reactant: FC(F)C(=S)OCCC(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: CC#N
Product: O=C1C=CN(c2ccc(N3CC(CNC(=S)C(F)F)OC3=O)cc2F)CC1
Reaction time: 36 h

Procedure:
Difluoro-thioacetic acid-O-(3,3-diphenyl-propyl)ester (84 mg, 0.25 mmol) is added to a solution of 1-[4-(5-aminomethyl-2-oxo-oxazolidin-3-yl)-2-fluoro-phenyl]-2,3-dihydro-1H-pyridin-4-one in MeCN (1.2 mL) and DMF (0.2 mL). This solution is stirred for 36 h at which time the reaction is concentrated under reduced pressure and the title compound is purified by silica gel column chromatography (eluent: 1% MeOH in EtOAc). Yield 45 mg (41%). MS (m/z) 400 [M+1]+. 1H NMR (300 MHz, DMSO-d6) δ 11.32 (s, 1H), 7.83–7.51 (m, 4H), 6.69 (t, J=55.2 Hz, 1H), 5.25–5.17 (m, 2H), 4.39 (t, J=9.1 Hz,1H), 4.22–4.03 (m, 6H), 3.55–3.49 (m, 2H).
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[O:17][C:16](=[O:18])[NH:15][N:14]=2)=[CH:9][CH:8]=1.[CH3:21][O:22][CH2:23][CH2:24]Cl.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[F:20][C:2]([F:1])([F:19])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[O:17][C:16](=[O:18])[N:15]([CH2:24][CH2:23][O:22][CH3:21])[N:14]=2)=[CH:9][CH:8]=1
Reactant: COCCCl
Reactant: O=c1[nH]nc(-c2ccc(OCCCC(F)(F)F)cc2)o1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COCCn1nc(-c2ccc(OCCCC(F)(F)F)cc2)oc1=O
Temperature: 100 °C
Yield: 83.2 %

Procedure:
1.8 g of 5-[4-(4,4,4-trifluorobutoxy)phenyl]-1,3,4-oxadiazol-2(3H)-one, 0.77 g of 2-chloroethyl methyl ether and a solution of 2.15 g of potassium carbonate in 20 ml of dimethylformamide are introduced into a 25 ml three-necked flask. The mixture is heated to 100° C. for 1 h 45 min and is then cooled and poured into 100 ml of water. The precipitate formed is drained, washed with 3 times 50 ml of water and then dissolved in ethyl acetate. The solution is dried over sodium sulphate and filtered, and the solvent is evaporated off. 1.8 g of product are obtained, which product is recrystallized in 10 ml of 96 % ethanol. 1.5 g of product are finally obtained.
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:26]=[CH:25][C:9]2[N:10]=[C:11]([NH:14][CH:15]3[C:19]4[CH:20]=[CH:21][C:22]([F:24])=[CH:23][C:18]=4[O:17][CH2:16]3)[O:12][CH2:13][C:8]=2[CH:7]=1)=[O:4].[CH3:27][O:28][CH2:29][CH2:30][NH2:31]>>[F:24][C:22]1[CH:21]=[CH:20][C:19]2[CH:15]([NH:14][C:11]3[O:12][CH2:13][C:8]4[CH:7]=[C:6]([NH:5][C:3](=[O:4])[CH2:2][NH:31][CH2:30][CH2:29][O:28][CH3:27])[CH:26]=[CH:25][C:9]=4[N:10]=3)[CH2:16][O:17][C:18]=2[CH:23]=1
Reactant: O=C(CCl)Nc1ccc2c(c1)COC(NC1COc3cc(F)ccc31)=N2
Reactant: COCCN
Product: COCCNCC(=O)Nc1ccc2c(c1)COC(NC1COc3cc(F)ccc31)=N2
Yield: 68.9 %

Procedure:
Prepared from the above described rac-2-chloro-N- [2-(6-fluoro-2,3-dihydro-benzofuran-3-ylamino)-4H-benzo[d][1,3]oxazin-6-yl]-acetamide (50 mg, 0.133 mmol, HPLC 1.056 min) and 2-methoxyethylamine (230 ul, 2.66 mmol) according to the procedure described for Example 3 step B. Obtained the title compound as a white solid (38 mg, 70%, HPLC 0.466 min 100%), MS (ISP) m/e=415.3 [(M+H)+].
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]2[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=2[CH3:26])=[O:17])[C:5]2[C:6]([CH3:15])=[CH:7][N:8]([C@H:11]([CH2:13][CH3:14])[CH3:12])[C:9]=2[CH:10]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:35][N:36]([CH:38]=O)[CH3:37].O>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>[CH3:35][N:36]([CH2:38][C:2]1[CH:10]=[C:9]([C:2]2[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]3[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=3[CH3:26])=[O:17])[C:5]3[C:6]([CH3:15])=[CH:7][N:8]([C@@H:11]([CH3:12])[CH2:13][CH3:14])[C:9]=3[CH:10]=2)[CH:5]=[CH:4][CH:3]=1)[CH3:37]
Reactant: CC[C@H](C)n1cc(C)c2c(C(=O)NCc3c(C)cc(C)[nH]c3=O)cc(Br)cc21
Reactant: CN(C)C=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Product: CC[C@H](C)n1cc(C)c2c(C(=O)NCc3c(C)cc(C)[nH]c3=O)cc(-c3cccc(CN(C)C)c3)cc21

Procedure:
(S)-6-bromo-1-(sec-butyl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-methyl-1H-indole-4-carboxamide (100 mg, 0.23 mmol), N,N-dimethyl-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanamine, HCl (100 mg, 0.34 mmol) and Palladium Tetrakis (26 mg, 0.023 mmol) in DMF/water (3 ml:1 ml) were stirred for 10 min under nitrogen. Cesium carbonate (220 mg, 0.68 mmol) was added and the insoluble mixture was irradiated (microwave) at 150° C. for 15 min. The contents were evaporated, dissolved in DCM/MeOH (1:1), and pre-absorbed on silica gel and purified using silica gel chromatography (eluent: DCM/MeOH/NH4OH, gradient 0 to 80:20:2 in DCM). The isolated product was first treated with EtOAc along with some hexanes. The product was then dissolved in MeOH and purified by reverse-phase HPLC (30×100 Varian Polaris C18 column, eluent: 10-80% gradient of MeCN in water with 0.1% TFA). The product fractions were combined, most of the solvent was evaporated, and a sat. solution of NaHCO3 was added. Solids that crashed out were filtered, air-dried for 15 min, and dried in vacuum-oven overnight. The solid product was collected as 87 mg (75%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.38 (br. s., 1 H), 8.23 (t, J=4.67 Hz, 1 H), 7.77 (d, J=1.01 Hz, 1 H), 7.60-7.64 (m, 2 H), 7.40 (t, J=7.58 Hz, 1 H), 7.30 (s, 1 H), 7.20-7.26 (m, 2 H), 5.87 (s, 1 H), 4.59-4.68 (m, 1 H), 4.36 (s, 1 H), 4.35 (s, 1 H), 3.46 (s, 2 H), 2.24 (s, 3 H), 2.18 (s, 9 H), 2.11 (s, 3 H), 1.76-1.88 (m, 2 H), 1.41 (d, J=6.57 Hz, 3 H), 0.74 (t, J=7.33 Hz, 3 H); LCMS: 499.4 (MH+).
Reaction SMILES: [Cl:1][C:2]([F:8])(I)[C:3]([F:6])([F:5])[Cl:4].FC(F)=C(F)F.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.ClC(F)(C(F)(F)Cl)C(F)(F)C(F)(F)[C:37]([F:43])([F:42])[C:38]([F:41])([F:40])[I:39]>>[Cl:1][C:2]([F:8])([C:3]([F:6])([F:5])[Cl:4])[C:37]([F:43])([F:42])[C:38]([F:41])([F:40])[I:39]
Reactant: FC(F)(Cl)C(F)(Cl)I
Reactant: FC(F)(Cl)C(F)(Cl)C(F)(F)C(F)(F)C(F)(F)C(F)(F)I
Agent: FC(F)=C(F)F
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Product: FC(F)(Cl)C(F)(Cl)C(F)(F)C(F)(F)I
Temperature: 130 °C
Yield: 51 %

Procedure:
A mixture of 400 g of 1,2-dichloro-1-iodotrifluoroethane, 140 g of tetrafluoroethene and 4 g of benzoyl peroxide was heated in 1 L autoclave at 130° C. for 4.5 hours. GC analysis of the reaction mixture (458 g) indicated 37% of starting material, 51% of desired product and 7% of 5,6-dichloro-1-iodoperfluorohexane. The reaction mixture was distilled on a 91 cm spinning band column to give 18.6 g of lower boiler, bp 80°-99° C. (mainly starting material), 138.6 g of starting material, bp 100°-102° C., 50.1 g of mixture of starting material and desired product, bp 103°-140° C. and 211 g of pure desired product, bp 140°-142° C.
Reaction SMILES: [OH:1]O.[CH3:3][S:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[S:11]([NH2:14])(=[O:13])=[O:12]>O.C(O)(=O)C>[CH3:3][S:4]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[S:11]([NH2:14])(=[O:13])=[O:12])=[O:1]
Reactant: CSc1ccccc1S(N)(=O)=O
Reactant: OO
Solvent: CC(=O)O
Solvent: O
Product: CS(=O)c1ccccc1S(N)(=O)=O
Reaction time: 0.75 h

Procedure:
14.8 g of hydrogen peroxide (0.13 mol), 30% strength in H2O, were added dropwise at from 25° to 30° C. to a suspension of 26.5 g 6f 2-(methylthio)benzenesulfonamide (0.13 mol) and 2.1 g of Na2WO4 ·2H2O in 88 ml of glacial acetic acid. Stirring was carried out for 45 minutes at 25° C., the reaction mixture was poured onto 400 ml of water and the precipitate was filtered off with suction. It was washed with water and dried under reduced pressure from a water pump at 40° C. 24.3 g (85% of theory) of the title compound were thus obtained.