Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[NH:5][C:4](=[O:13])[C:3]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[H-].[Na+].C([CH:24]([C:28](Cl)=[O:29])[C:25](Cl)=[O:26])C.[O:31]1CCCC1>>[C:28]([CH2:24][C:25]([NH:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[NH:5][C:4](=[O:13])[C:3]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:26])([OH:29])=[O:31]
Reactant: Nc1c(-c2ccccc2)c(=O)[nH]c2cc(Cl)ccc12
Reactant: CCC(C(=O)Cl)C(=O)Cl
Reactant: C1CCOC1
Agent: [H-]
Agent: [Na+]
Product: O=C(O)CC(=O)Nc1c(-c2ccccc2)c(=O)[nH]c2cc(Cl)ccc12
Temperature: 60 °C

Procedure:
A solution of 4-amino-7-chloro-3-phenyl-2(1H)-quinolone (Example 2) (0.5 g) in 50 ml tetrahydrofuran was stirred under an atmosphere of nitrogen and treated with sodium hydride (0.3 g, 80% disp. in mineral oil). This was followed by the addition after 1 h of ethyl malonyl chloride (1.8 ml). The reaction mixture was heated at 60° C. for 14 h, cooled and partitioned between ethyl acetate and water. The organic phase was washed with water (2×) before the solvent was removed in vacuo. The residue was saponified using 4N sodium hydroxide lo (100 ml) and ultrasound. The solution was adjusted to pill using conc. HCl then extracted into ethyl acetate, dried (MgSO4) and the solvent was removed in vacuo. The residue was purified by preparative HPLC followed by recrystallisation from DMF-water to give the title compound (50 mg); mp 260° C. decomposed; δ (360 MHz, DMSO) 3.22 (2H, s, CH2CO2H), 7.22-7.76 (7H, m, aromatics), 7.87 (1H, d, 5-H, J=8.4 Hz), 9.97 (1H, s, NHCOCH2CO2H), 12.13 (1H, s, NH). Found: C, 60.29; H, 3.83; N, 7.69. C18H13N2O4Cl requires C, 60.60; H, 3.67; N, 7.85%.
Reaction SMILES: C[O:2][C:3](=[O:41])[CH2:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]([C@H:13]2[C@H:17]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[C:19]=3[F:25])[C@:16]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=3[F:35])([C:26]#[N:27])[C@H:15]([CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])[NH:14]2)=[O:12])[CH2:7][CH2:6]1.O[Li].O>CO.O>[ClH:24].[Cl:24][C:20]1[C:19]([F:25])=[C:18]([C@@H:17]2[C@:16]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=3[F:35])([C:26]#[N:27])[C@H:15]([CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])[NH:14][C@H:13]2[C:11]([N:8]2[CH2:7][CH2:6][CH:5]([CH2:4][C:3]([OH:41])=[O:2])[CH2:10][CH2:9]2)=[O:12])[CH:23]=[CH:22][CH:21]=1
Reactant: COC(=O)CC1CCN(C(=O)[C@@H]2N[C@@H](CC(C)(C)C)[C@](C#N)(c3ccc(Cl)cc3F)[C@H]2c2cccc(Cl)c2F)CC1
Agent: [Li]O
Solvent: O
Solvent: CO
Product: CC(C)(C)C[C@@H]1N[C@@H](C(=O)N2CCC(CC(=O)O)CC2)[C@H](c2cccc(Cl)c2F)[C@@]1(C#N)c1ccc(Cl)cc1F
Product: Cl
Temperature: 60 °C
Reaction time: 8 h

Procedure:
To a stirred solution of rac {1-[(2R,3S,4R,5S)-3-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-piperidin-4-yl}-acetic acid methyl ester (556 mg, 0.92 mmol) in methanol (8 mL), LiOH.H2O (Aldrich, 80 mg) in 1 mL of water was added. The mixture was stirred at 60° C. overnight. The reaction was quenched with addition of water. The mixture was filtered and the filtrate was concentrated to removed methanol. The aqueous layer was washed with EtOAc (2×5 mL) and acidified with 3N HCl. The mixture was then extracted with EtOAc (3×6 mL). The extracts were combined and dried over sodium sulfate and concentrated to give a white solid. 649 mg.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH3:13])[C:11]([C:14]#[N:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH:16]1([C:22](Cl)=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1>>[C:14]([C:11]1[N:12]([CH3:13])[C:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:1][C:22]([CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:23])=[CH:3][CH:4]=2)=[CH:9][CH:10]=1)#[N:15]
Reactant: O=C(Cl)C1CCCCC1
Reactant: Cn1c(C#N)ccc1-c1ccc(N)cc1
Product: Cn1c(C#N)ccc1-c1ccc(NC(=O)C2CCCCC2)cc1

Procedure:
The title compound was prepared according to the general procedure for acylation of 5-(4-aminophenyl)-1-methyl-1H-pyrrole-2-carbonitrile using cyclohexanecarbonyl chloride (67 μL, 0.55 mmol) to provide N-[4-(5-cyano-1-methyl-1H-pyrrol-2-yl)phenyl]cyclohexanecarboxamide (0.039 g).
Reaction SMILES: [C:1]([O:10]CC)(=O)[C:2]#[C:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].Cl.[CH3:14][N:15](C)[NH2:16].[OH-].[Na+].CCOC(C)=O>CCO.O>[OH:10][C:1]1[CH:2]=[C:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[N:15]([CH3:14])[N:16]=1
Reactant: CN(C)N
Reactant: CCOC(=O)C#CC(=O)OCC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Solvent: CCOC(C)=O
Product: CCOC(=O)c1cc(O)nn1C
Temperature: 20 °C
Reaction time: 1 h
Yield: 17 %

Procedure:
To a solution of diethyl but-2-ynedioate (100 g, 0.588 mol) in a mixture of EtOH (600 mL) and water (600 mL) was added a solution of 1,1-dimethylhydrazine hydrochloride (68 g, 0.705 mol) and NaOH (28.2 g, 0.705 mol) in water (150 mL) dropwise at 0° C. over a period of 20 min. The mixture was stirred at 0° C. for 30 min and 20° C. for 60 min. To the reaction mixture was added EtOAc (800 mL) and stirred. The mixture was separated and the aqueous layer was concentrated. The residue was dissolved in 1N HCl (1 L) and stirred at rt for 90 min. CH2Cl2 (500 mL) was added and the mixture stirred, separated and the aqueous layer was concentrated. The residue was purified by chromatography (petroleum ether/EtOAc 10:1-3:1) to give the title compound (17 g, 17% yield) as a white solid.
Reaction SMILES: [CH2:1]([CH:3]([CH2:34][CH2:35][CH2:36][CH3:37])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH:26]([CH2:31][CH3:32])[CH2:27][CH2:28][CH2:29][CH3:30])=[CH:20][CH:19]=3)[N:15]=[C:14](O)[N:13]=2)=[CH:8][CH:7]=1)[CH3:2].S(Cl)(Cl)=O.[C:42]1([CH:49]=[CH:48][CH:47]=[C:45]([OH:46])[CH:44]=1)[OH:43].Cl>C1(C)C(C)=CC=CC=1.CN(C)C=O>[CH2:1]([CH:3]([CH2:34][CH2:35][CH2:36][CH3:37])[CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[N:17]=[C:16]([C:18]3[CH:19]=[CH:20][C:21]([O:24][CH2:25][CH:26]([CH2:31][CH3:32])[CH2:27][CH2:28][CH2:29][CH3:30])=[CH:22][CH:23]=3)[N:15]=[C:14]([C:47]3[CH:48]=[CH:49][C:42]([OH:43])=[CH:44][C:45]=3[OH:46])[N:13]=2)=[CH:10][CH:11]=1)[CH3:2]
Reactant: CCCCC(CC)COc1ccc(-c2nc(O)nc(-c3ccc(OCC(CC)CCCC)cc3)n2)cc1
Reactant: Oc1cccc(O)c1
Agent: Cl
Solvent: O=S(Cl)Cl
Solvent: Cc1ccccc1C
Solvent: CN(C)C=O
Product: CCCCC(CC)COc1ccc(-c2nc(-c3ccc(OCC(CC)CCCC)cc3)nc(-c3ccc(O)cc3O)n2)cc1
Reaction time: 0.25 h
Yield: 51.1 %

Procedure:
55.6 g (0.11 mol) of 4,6-bis[4-(2-ethylhexyloxy)phenyl]-s-triazin-2-ol in 300 ml of xylene, to which 1 ml of dimethylformamide has been added, are placed in a 1.5 l sulfonating flask fitted with stirrer, cooler, internal thermometer, dropping funnel and gas outlet. 17.0 g (0.14 mol) of thionyl chloride are added dropwise at an internal temperature of 75-80 C. with vigorous stirring over the course of 15 minutes. After the evolution of gas has subsided, the temperature is raised to 100 C. The reaction is complete after 2 hours (checking by thin-layer chromatography). Excess thionyl chloride is distilled off from the reaction vessel under a slight vacuum, and the intermediate 2-chloro-4,6-bis[4-(2-ethylhexyloxy)phenyl]-s-triazine is reacted further directly. 16.2 g (0.12 mol) of dry, sublimed aluminium chloride are introduced at 50 C. (about 1 minute), whereby the temperature rises to 65 C. The initially clear, yellow solution becomes a red, then olive suspension. 13.3 g (0.12 mol) of resorcinol are added in portions at 50-55 C. (about 10 minutes) and the mixture is then heated to 85 C. After 3 hours the thin-layer chromatogram shows no further starting material. The mixture is cooled to 70 C. and the aluminium complex is hydrolysed by slow dropwise addition of 300 ml of 5% hydrochloric acid, during which the temperature should not exceed 80 C. The solvent (xylene) is removed by steam distillation, and the oily residue is stirred with 500 ml of hot toluene and filtered over silica gel. The filtrate is digested with active charcoal and filtered again. The filtrate is dried over sodium sulfate and the solvent is distilled off. For further purification, the viscous brown residue (69 g) is dissolved in 150 ml of toluene/ethyl acetate (95/5) and subjected to column chromatography (6 cm×60 cm silica gel 60), to give 33.6 g (51% of theory) of 4-{4,6-bis[4-(2-ethylhexyloxy)phenyl]-s-triazin-2-yl}-1,3-dihydroxybenzene as a viscous yellow oil.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:18]=[C:17]([C:19]([OH:21])=[O:20])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)=[CH:5][CH:4]=1.[C:22](OC(=O)C)(=[O:24])[CH3:23]>O1CCCC1>[C:22]([NH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:18]=[C:17]([C:19]([OH:21])=[O:20])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)=[CH:5][CH:4]=1)(=[O:24])[CH3:23]
Reactant: CC(=O)OC(C)=O
Reactant: NCc1ccc(-c2nc(C(=O)O)c3ccccc3n2)cc1
Solvent: C1CCOC1
Product: CC(=O)NCc1ccc(-c2nc(C(=O)O)c3ccccc3n2)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Into a 500-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 2-[4-(aminomethyl)phenyl]quinazoline-4-carboxylic acid (2.6 g, 9.31 mmol, 1.00 equiv), oxolane (200 mL) and acetyl acetate (20 mL). The resulting solution was stirred for 3 h at 25° C. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (20:1-5:1). This resulted in 500 mg (17%) of 2-[4-(acetamidomethyl)phenyl]quinazoline-4-carboxylic acid as a light yellow solid. MS (ESI) m/z 322 ([M+H]+).
Reaction SMILES: Cl[C:2]1[S:3][C:4]2[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:5]=2[N:6]=1.[CH2:12]1[CH2:17][CH2:16][CH:15]([CH2:18][C@H:19]([NH2:23])[C:20]([OH:22])=O)[CH2:14][CH2:13]1.Cl.Cl.[F:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33][CH2:34][CH2:35][NH2:36])=[CH:29][CH:28]=1>>[Cl:11][C:9]1[CH:8]=[CH:7][C:5]2[N:6]=[C:2]([NH:23][C@@H:19]([CH2:18][CH:15]3[CH2:14][CH2:13][CH2:12][CH2:17][CH2:16]3)[C:20]([NH:36][CH2:35][CH2:34][NH:33][C:30]3[CH:31]=[CH:32][C:27]([F:26])=[CH:28][CH:29]=3)=[O:22])[S:3][C:4]=2[CH:10]=1
Reactant: Clc1ccc2nc(Cl)sc2c1
Reactant: N[C@@H](CC1CCCCC1)C(=O)O
Reactant: NCCNc1ccc(F)cc1
Agent: Cl
Product: O=C(NCCNc1ccc(F)cc1)[C@H](CC1CCCCC1)Nc1nc2ccc(Cl)cc2s1

Procedure:
The title compound was prepared from 2,6-dichlorobenzothiazole, L-cyclohexylalanine and N1-(4-fluoro-phenyl)-ethane-1,2-diamine-2HCl using the procedure analogous to that described in example 2. 1H NMR (DMSO-d6, 400 MHz) δ 8.30 (d, 1H, J=8.0 Hz), 8.17 (t, 1H, J=5.6 Hz), 7.72 (d, 1H, J=2.4 Hz), 7.23 (d, 1H, J=8.4 Hz), 7.15 (dd, 1H, J=8.4 Hz, J=2.4 Hz), 6.84(m, 2H), 6.50(m, 2H), 4.40(m, 1H), 3.16(m, 2H), 2.97(m, 2H), 1.55(m, 7H), 1.30(m, 1H), 1.05(m, 3H), 0.83(m, 2H). HPLC-MS calcd. for C24H28ClFN4OS (M+H+)475.17, found 475.3.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH:5]=1)([O-:3])=[O:2].Br[CH2:14][C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][C:16]=1[O:25][CH3:26].O>ClCCl>[CH3:26][O:25][C:16]1[CH:17]=[C:18]([CH:23]=[CH:24][C:15]=1[CH2:14][C:10]1[C:6]2[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=[CH:11][C:7]=2[S:8][CH:9]=1)[C:19]([O:21][CH3:22])=[O:20]
Reactant: COC(=O)c1ccc(CBr)c(OC)c1
Reactant: O=[N+]([O-])c1ccc2sccc2c1
Solvent: O
Solvent: ClCCl
Product: COC(=O)c1ccc(Cc2csc3ccc([N+](=O)[O-])cc23)c(OC)c1

Procedure:
Stannic chloride (0.41 g.) was added to a stirred solution of 5-nitrobenzo[b]thiophene (0.28 g.) and methyl 4-bromomethyl-3-methoxybenzoate (B) (0.61 g.) in dichloromethane (5 ml.). The mixture was heated under reflux for 18 hours. The cooled mixture was poured into water (10 ml.) and extracted with dichloromethane (2×20 ml.). The combined extracts were dried (MgSO4) and evaporated. The oil was purified by flash chromatography on silica gel (100 ml.) eluting with 1:9 v/v ethyl acetate:hexane. The solid obtained was crystallized from hexane to give methyl 3-methoxy-4-(5-nitrobenzo[b]thien-3-ylmethyl)benzoate (I) as a solid (0.16 g., 30%); NMR: (250 MHz, CDCl3): 3.92(s, 3H, OCH3), 3.98(s,3H, OCH3), 4.28(s,2H, CH2 --Ar), 7.15 (d,1H), 7.22(s,1H), 7.56(m,2H), 7.93(d,1H), 8.19(dd, 1H); 8.73(d,1H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][CH:24]=1)[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([NH:15][C:16](=[O:21])[CH2:17][CH:18]3[CH2:20][CH2:19]3)[N:14]=2)[N:11]=1.[CH3:25][N:26]1[C:30]([C:31](Cl)=[O:32])=[CH:29][C:28]([CH3:34])=[N:27]1.[CH3:35]N(C)C(=O)C>>[CH:18]1([CH2:17][C:16]([NH:15][C:13]2[N:14]=[C:9]3[CH:8]=[CH:7][C:6]([O:5][C:4]4[CH:22]=[CH:23][C:24]([CH3:35])=[C:2]([NH:1][C:31]([C:30]5[N:26]([CH3:25])[N:27]=[C:28]([CH3:34])[CH:29]=5)=[O:32])[CH:3]=4)=[N:11][N:10]3[CH:12]=2)=[O:21])[CH2:19][CH2:20]1
Reactant: Nc1cccc(Oc2ccc3nc(NC(=O)CC4CC4)cn3n2)c1
Reactant: CC(=O)N(C)C
Reactant: Cc1cc(C(=O)Cl)n(C)n1
Product: Cc1cc(C(=O)Nc2cc(Oc3ccc4nc(NC(=O)CC5CC5)cn4n3)ccc2C)n(C)n1
Yield: 61 %

Procedure:
Using N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]-2-cyclopropylacetamide (120 mg, 0.356 mmol), 1,3-dimethyl-1H-pyrazole-5-carbonyl chloride (59 mg, 0.374 mmol) and N,N-dimethylacetamide (4.0 mL), and by a reaction in the same manner as in Example 148, the title compound (99 mg, 61%) was obtained as a pale-yellow powder.
Reaction SMILES: I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:12])[N:10]=2)[CH:7]=1.C[Si]([C:24]#[CH:25])(C)C.N1CCCCC1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cl-].[NH4+]>[C:24]([C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:12])[N:10]=2)[CH:7]=1)#[CH:25]
Reactant: C#C[Si](C)(C)C
Reactant: O=C(Nc1ccccc1)c1cn2cc(I)ccc2n1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCNCC1
Product: C#Cc1ccc2nc(C(=O)Nc3ccccc3)cn2c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
0.2 g of 6-iodo-N-phenylimidazo[1,2-a]pyridine-2-carboxamide, 156 μl of trimethylsilylacetylene, 20 mg of dichlorobis(triphenylphosphine)palladium and 2 ml of piperidine are charged to a 20 ml microwave tube. The mixture is heated for 15 minutes in the microwave device adjusted to 130° C. After cooling, the mixture is poured into 50 ml of a saturated aqueous ammonium chloride solution. Extraction is carried out twice with 70 ml of ethyl ether. The combined organic phases are separated by settling, dried and concentrated to dryness under reduced pressure. The residue is taken up in 4 ml of a 1M solution of tetrabutylammonium fluoride in THF and stirred at 25° C. for 16 hours. After evaporating the reaction medium to dryness, the residue is chromatographed on silica, elution being carried out with a mixture of cyclohexane and ethyl acetate (gradient from 0 to 35%), to give 30 mg of 6-ethynyl-N-phenylimidazo[1,2-a]pyridine-2-carboxamide in the form of a beige solid.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([O:22][CH2:23][O:24][CH3:25])([C:18]([F:21])([F:20])[F:19])[C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=1[CH2:26][CH2:27][CH3:28].[CH3:29][N:30]1[C:34]([CH3:36])([CH3:35])[C:33](=[O:37])[NH:32][C:31]1=[O:38].C(=O)([O-])[O-].[K+].[K+]>>[F:15][C:14]([F:17])([F:16])[C:13]([C:10]1[CH:11]=[CH:12][C:7]([O:6][CH2:5][CH2:4][CH2:3][CH2:2][N:32]2[C:33](=[O:37])[C:34]([CH3:36])([CH3:35])[N:30]([CH3:29])[C:31]2=[O:38])=[C:8]([CH2:26][CH2:27][CH3:28])[CH:9]=1)([O:22][CH2:23][O:24][CH3:25])[C:18]([F:21])([F:20])[F:19]
Reactant: CN1C(=O)NC(=O)C1(C)C
Reactant: CCCc1cc(C(OCOC)(C(F)(F)F)C(F)(F)F)ccc1OCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CCCc1cc(C(OCOC)(C(F)(F)F)C(F)(F)F)ccc1OCCCCN1C(=O)N(C)C(C)(C)C1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 96.8 %

Procedure:
4-[1,1,1,3,3,3-Hexafluoro-2-(methoxymethyl)oxypropan-2-yl]-2-propylphenyl 4-bromobutyl ether (70 mg, 0.15 mmol), 1,5,5-trimethylimidazolidine-2,4-dione (24.8 mg, 0.17 mmol) and potassium carbonate (31.1 mg, 0.23 mmol) were added, followed by stirring overnight at room temperature. The reaction solution was extracted with ethyl acetate-water, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel preparative thin-layer chromatography (hexane:ethyl acetate=3:1) to obtain 78.8 mg of the title compound (yield: 100%) as a colorless oil.
Reaction SMILES: [CH3:1][CH:2]([CH3:7])[CH2:3][N+:4]([O-:6])=[O:5].C(=O)([O-])[O-].[K+].[K+].[CH:14](O)([OH:19])[C:15]([F:18])([F:17])[F:16].O>C(OC)(C)(C)C>[CH3:1][CH:2]([CH3:7])[CH:3]([N+:4]([O-:6])=[O:5])[CH:14]([OH:19])[C:15]([F:18])([F:17])[F:16]
Reactant: OC(O)C(F)(F)F
Reactant: CC(C)C[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: COC(C)(C)C
Solvent: O
Product: CC(C)C(C(O)C(F)(F)F)[N+](=O)[O-]
Temperature: 15 °C
Reaction time: 0.08 h
Yield: 84 %

Procedure:
3A Molecular sieves (27.04 g) were heated at 120° C. under vacuum for 20 hours and added to a solution of 2-methyl-1-nitropropane (13.0 g) in methyl tert-butyl ether (420 ml). The mixture was stirred for 5 minutes, potassium carbonate (64.5 g) added and the mixture stirred a further 30 minutes. The mixture was cooled to 15° C. and fluoral hydrate (22.0 g) was added over 30 minutes. The reaction mixture was stirred at ambient temperature for 16 hours, then cooled to 15° C. and water (270 ml) added. After stirring for 5 minutes at ambient temperature, the organic phase was separated and washed with 10% aqueous potassium carbonate, 2M hydrochloric acid solution and water. Solvent was then removed by evaporation under reduced pressure at a temperature below 40° C. and the oil azeotroped dry with isopropyl alcohol at a temperature below 50° C. to give 4-methyl-3-nitro-1,1,1-trifluoro-2-pentanol (21.3 g) as an oil, which was used without further purification.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[C:17]([CH2:21][CH:22]([CH3:24])[CH3:23])=[CH:16][N:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:25])[C:4]=1[OH:26])[CH3:2].Br[CH2:28][CH2:29][OH:30]>C(O)(C)C.[OH-].[Na+].CC(=O)OCC>[CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[C:17]([CH2:21][CH:22]([CH3:23])[CH3:24])=[CH:16][N:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:25])[C:4]=1[O:26][CH2:28][CH2:29][OH:30])[CH3:2]
Reactant: OCCBr
Reactant: CCc1cc(-c2noc(-c3cc(C)c(CC(C)C)cn3)n2)cc(C)c1O
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CC(C)O
Product: CCc1cc(-c2noc(-c3cc(C)c(CC(C)C)cn3)n2)cc(C)c1OCCO
Reaction time: 6 h
Yield: 79.8 %

Procedure:
To a solution of the compound of Example 32 (1.00 g, 2.85 mmol) in isopropanol (10 mL) and 3 M aq. NaOH (3 mL), 2-bromo-ethanol (1.42 g, 11.4 mmol) is added. The mixture is stirred at 60° C. for 24 h before another portion of 2-bromo-ethanol (176 mg, 1.41 mmol) is added. Stirring is continued at 60° C. for 6 h. The mixture is diluted with EA and washed with water. The org. extract is dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 4:1 to 3:1 to give the title compound (900 mg) as a colourless oil; LC-MS: tR=1.10 min, [M+H]+=396.09.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([N:24]2[CH:29]=[CH:28][C:27](=[O:30])[NH:26][C:25]2=[O:31])[CH:8]=[C:9]([C:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[C:18]([OH:23])[CH:19]=3)[CH:14]=2)[C:10]=1[O:11][CH3:12])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[F:38][C:39]([F:51])([F:50])[C:40]([F:49])([S:45](F)(=[O:47])=[O:46])[C:41]([F:44])([F:43])[F:42]>CN(C)C=O>[F:44][C:41]([F:42])([F:43])[C:40]([F:49])([S:45]([O:23][C:18]1[CH:17]=[CH:16][C:15]2[C:20](=[CH:21][CH:22]=[C:13]([C:9]3[CH:8]=[C:7]([N:24]4[CH:29]=[CH:28][C:27](=[O:30])[NH:26][C:25]4=[O:31])[CH:6]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[C:10]=3[O:11][CH3:12])[CH:14]=2)[CH:19]=1)(=[O:47])=[O:46])[C:39]([F:51])([F:50])[F:38]
Reactant: O=S(=O)(F)C(F)(C(F)(F)F)C(F)(F)F
Reactant: COc1c(-c2ccc3cc(O)ccc3c2)cc(-n2ccc(=O)[nH]c2=O)cc1C(C)(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1c(-c2ccc3cc(OS(=O)(=O)C(F)(C(F)(F)F)C(F)(F)F)ccc3c2)cc(-n2ccc(=O)[nH]c2=O)cc1C(C)(C)C
Temperature: 50 °C
Reaction time: 2 h

Procedure:
To a stirred solution of 6.0 g of 1-(3-tert-butyl-5-(6-hydroxynaphthalen-2-yl)-4-methoxyphenyl)pyrimidine-2,4(1H,3H)-dione (14.4 mmol, 1.0 equivalent) in 60 mL of N,N-dimethylformamide was added 4.0 g of 325-mesh potassium carbonate (29 mmol, 2.0 equivalents). 1,1,1,2,3,3,3-heptafluoropropane-2-sulfonyl fluoride (3.6 g, 14.3 mmol, 1.0 equivalents) was added over 30 minutes, and the mixture was stirred for 2 hours. An additional portion of 1,1,1,2,3,3,3-heptafluoropropane-2-sulfonyl fluoride (0.21 g, 0.83 mmol, 0.06 equivalents) was added, and the mixture was stirred for 1.5 hours. The inorganic solids were separated by filtration, and the flask and filter cake were rinsed with 75 mL of ethyl acetate. The solution was diluted with an additional 75 mL of ethyl acetate and the resultant solution was washed four times with 50 mL portions of 10 wt % aqueous sodium chloride, followed by 50 mL of saturated aqueous sodium chloride solution. The organic solution was dried over sodium sulfate, the drying agent was filtered off and the organic solution was concentrated in vacuo. The resultant oil was dissolved in 7 mL of ethyl acetate, which resulted in crystallization after stirring for a few minutes. Heptanes (90 mL) were added slowly to the stirred mixture. The product was isolated by filtration, washed with 20 mL of heptanes and dried in vacuo with heating at 50° C. The title compound was isolated as a white solid (8.30 g, 89% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.05 (s, 1H), 7.95 (d, J=9.6 Hz, 1H), 7.93 (d, J=9.6 Hz, 1H), 7.83 (dd, J=8.5, 1.7 Hz, 1H), 7.78 (d, J=2.4 Hz, 1H), 7.40 (dd, J=8.9, 2.4 Hz, 1H), 7.36 (d, J=7.9 Hz, 1H), 7.27-7.23 (m, 2H), 5.81 (d, J=7.9 Hz, 1H), 3.29 (s, 3H), 1.46 (s, 9H) (NH not observed in this spectrum). 13C NMR (101 MHz, CDCl3) δ ppm 162.7 (C), 157.5 (C), 149.8 (C), 146.9 (C), 145.0 (C), 144.5 (CH), 137.2 (C), 135.1 (C), 133.0 (C), 132.2 (C), 132.2 (C), 130.5 (CH), 128.5 (CH), 128.1 (CH), 127.4 (CH), 127.2 (CH), 124.4 (CH), 119.9 (CH), 118.9 (CH), 102.4 (CH), 60.9 (CH3), 35.8 (C), 30.8 (CH3). 19F NMR (564 MHz, DMSO) δ ppm −71.08 (6F), −167.87 (1F). LC-MS m/z 649.1 [M+H]+.
Reaction SMILES: [F:1][C:2]([F:21])([C:5]([F:20])([F:19])[C:6]([F:18])([F:17])[C:7]([F:16])([F:15])[C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10])[CH:3]=[CH2:4].[CH:22]1[CH2:26][CH:25]=[CH:24][CH:23]=1.C([O:31]O)CCC>C1(C)C=CC=CC=1>[O:31]1[CH:22]2[CH:23]1[CH:24]1[CH2:25][CH:26]2[CH:3]([C:2]([F:21])([F:1])[C:5]([F:19])([F:20])[C:6]([F:17])([F:18])[C:7]([F:15])([F:16])[C:8]([F:13])([F:14])[C:9]([F:12])([F:11])[F:10])[CH2:4]1
Reactant: C=CC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Reactant: C1=CCC=C1
Reactant: CCCCOO
Solvent: Cc1ccccc1
Product: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C1CC2CC1C1OC21
Reaction time: 24 h

Procedure:
103 g (250 mmol) of the Diels-Alder reaction product of 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octene (perfluorohexylethene) and cyclopentadiene are mixed in 10 ml of dry toluene with 815 mg (2.5 mmol) of molybdenum acetylacetonate, and 104 ml of a 3.6 molar solution oft-butyl hydroperoxide in toluene (375 mmol) are added dropwise at 25° C. within 50 minutes. During this time, the temperature rises to 45° C. The solution is then held at 60° C. for 24 hours, after which the solvent, t-butanol and any remaining t-butyl hydroperoxideis distilled off in a rotary evaporator under reduced pressure. The residueis filtered over silica gel, followed by washing with two 10 ml portions oftoluene. In the course of the distillation over a packed column 15 cm long which is packed with 4 mm glass rings, the product distils at a pressure of 350 mbar and a boiling point of 54° to 56° C.