Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:23][CH2:22][C:21]([C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([S:38][CH2:39][CH2:40][C:41]5[N:45]([CH2:46][CH2:47][CH3:48])[CH:44]=[N:43][N:42]=5)=[CH:34][CH:33]=4)=[O:30])=[CH:20][C:19]=3[CH:49]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].ClC1C=CC=C(C(OO)=[O:58])C=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>ClCCl>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]([CH3:27])[CH3:28])[CH2:23][CH2:22][C:21]([C:29]([NH:31][C:32]4[CH:33]=[CH:34][C:35]([S:38]([CH2:39][CH2:40][C:41]5[N:45]([CH2:46][CH2:47][CH3:48])[CH:44]=[N:43][N:42]=5)=[O:58])=[CH:36][CH:37]=4)=[O:30])=[CH:20][C:19]=3[CH:49]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(SCCc4nncn4CCC)cc2)CCN3CC(C)C)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(S(=O)CCc4nncn4CCC)cc2)CCN3CC(C)C)cc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 83.5 %

Procedure:
7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[2-(4-propyl-4H-1,2,4-triazol-3-yl)ethylthio]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (1.1 g) was dissolved in dichloromethane (40 ml), and the mixture was cooled to −78° C. A solution of 3-chloroperbenzoic acid (0.6 g) in dichloromethane (10 ml) was added dropwise to the mixture. The mixture was stirred for 1 hour at −78° C., and then, sodium thiosulfate solution was added to the mixture, and the mixture was concentrated, and extracted with ethyl acetate. The organic layer was washed with sodium bicarbonate solution, water and saturated brine, and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off. The residue was purified by silica gel column chromatography (elution solvent: triethylamine/methanol/ethyl acetate), to give 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[2-(4-propyl-4H-1,2,4-triazol-3-yl)ethylsulfinyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 50) (0.94 g) as yellow amorphous.
Reaction SMILES: [I-:1].[Na+].Cl[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][S:9]([N:12]([CH2:14][C:15]([F:24])([F:23])[C:16]([F:22])([F:21])[C:17]([F:20])([F:19])[F:18])[CH3:13])(=[O:11])=[O:10]>C(C(C)=O)C>[F:23][C:15]([F:24])([C:16]([F:22])([F:21])[C:17]([F:20])([F:19])[F:18])[CH2:14][N:12]([CH3:13])[S:9]([CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][I:1])(=[O:11])=[O:10]
Reactant: [I-]
Reactant: CN(CC(F)(F)C(F)(F)C(F)(F)F)S(=O)(=O)CCCCCCl
Agent: [Na+]
Solvent: CCC(C)=O
Product: CN(CC(F)(F)C(F)(F)C(F)(F)F)S(=O)(=O)CCCCCI
Yield: 96.6 %

Procedure:
300 mg of sodium iodide were added to a solution of 355 mg of the product of Step A in 3 ml of methyl ethyl ketone and the mixture was refluxed for 4 hours. After evaporation of the solvent, the residue was taken up in water and extracted with ethyl acetate. The extracts were washed with an aqueous solution of sodium thiosulfate, then of sodium chloride, and evaporated to dryness under reduced pressure to obtain 425 mg of the expected product in the form of a colourless oil which slowly crystallized.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19]CC1C=CC=CC=1)[N:15]=[CH:14][N:13]=[C:12]2[N:27]1[CH2:32][CH2:31][CH:30]([N:33]2[C:42](=[O:43])[C:41]3[C:36](=[CH:37][CH:38]=[C:39]([CH3:44])[CH:40]=3)[N:35]([CH3:45])[C:34]2=[O:46])[CH2:29][CH2:28]1)C1C=CC=CC=1.CN(C=O)C>C(O)C>[OH:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[OH:19])[N:15]=[CH:14][N:13]=[C:12]2[N:27]1[CH2:32][CH2:31][CH:30]([N:33]2[C:42](=[O:43])[C:41]3[C:36](=[CH:37][CH:38]=[C:39]([CH3:44])[CH:40]=3)[N:35]([CH3:45])[C:34]2=[O:46])[CH2:29][CH2:28]1
Reactant: Cc1ccc2c(c1)c(=O)n(C1CCN(c3ncnc4cc(OCc5ccccc5)c(OCc5ccccc5)cc34)CC1)c(=O)n2C
Solvent: CN(C)C=O
Solvent: CCO
Product: Cc1ccc2c(c1)c(=O)n(C1CCN(c3ncnc4cc(O)c(O)cc34)CC1)c(=O)n2C
Yield: 68.9 %

Procedure:
The procedure similar to that described in Example 79 was repeated, except that 200.0 mg (0.33 mmol) of Compound 88 obtained in Example 67 was used in place of Compound 87 and DMF was used as a reaction solvent in place of ethanol. As a result, 98.5 mg (yield: 70%) of Compound 97 was obtained as white crystals.
Reaction SMILES: [CH:1]1([C:4]2[C:5]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[CH:6][C:7]([C:10]([OH:12])=O)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[C:19]([O:23][C:24](=[O:31])[CH:25]([NH2:30])[C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:22])([CH3:21])[CH3:20]>>[CH:1]1([C:4]2[C:5]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[CH:6][C:7]([C:10]([NH:30][CH:25]([C:26]([CH3:29])([CH3:28])[CH3:27])[C:24]([O:23][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:31])=[O:12])=[N:8][CH:9]=2)[CH2:2][CH2:3]1
Reactant: CC(C)(C)OC(=O)C(N)C(C)(C)C
Reactant: O=C(O)c1cc(OCC(F)(F)F)c(C2CC2)cn1
Product: CC(C)(C)OC(=O)C(NC(=O)c1cc(OCC(F)(F)F)c(C2CC2)cn1)C(C)(C)C

Procedure:
The title compound was synthesized in analogy to Example 112e, using 5-Cyclopropyl-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (Example 48c) and 2-Amino-3,3-dimethyl-butyric acid tert-butyl ester (CAN 99285-38-8) as starting materials and isolated (490 mg, 92%); MS (ESI, m/z): 431.6 (M+H+).
Reaction SMILES: C[O:2][C:3]([C:5]1[NH:6][C:7]2[C:12]([CH:13]=1)=[C:11]([O:14][CH:15]([CH3:17])[CH3:16])[CH:10]=[CH:9][CH:8]=2)=[O:4].[Li+].[OH-].O>C1COCC1>[CH:15]([O:14][C:11]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:12]=1[CH:13]=[C:5]([C:3]([OH:4])=[O:2])[NH:6]2)([CH3:17])[CH3:16]
Reactant: COC(=O)c1cc2c(OC(C)C)cccc2[nH]1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)Oc1cccc2[nH]c(C(=O)O)cc12
Reaction time: 48 h

Procedure:
4-Isopropoxy-1H-indole-2-carboxylic acid methyl ester 76 (114 mg, 0.49 mmol) is dissolved in 5 ml of THF. A 2M-solution of LiOH in water (2.5 ml, 5 mmol) is added and the mixture is stirred for 48 hours. The solvent is then evaporated and the residue is partitioned between water and EtOAc. The water layer is acidified with HCl and extracted twice with EtOAc. The combined organic layers are washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated to give a yellow powder.
Reaction SMILES: [CH:1]1([NH:4]C)[CH2:3][CH2:2]1.CO[C:8](=[O:19])[C:9]1[C:14]([I:15])=[CH:13][C:12]([Cl:16])=[CH:11][C:10]=1[CH2:17]Br.[C:20]([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1>[CH:1]1([N:4]2[CH:17]([CH3:20])[C:10]3[C:9](=[C:14]([I:15])[CH:13]=[C:12]([Cl:16])[CH:11]=3)[C:8]2=[O:19])[CH2:3][CH2:2]1
Reactant: COC(=O)c1c(I)cc(Cl)cc1CBr
Reactant: CNC1CC1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: CC1c2cc(Cl)cc(I)c2C(=O)N1C1CC1
Temperature: 100 °C
Reaction time: 2 h
Yield: 35.4 %

Procedure:
A mixture of cyclopropyl-methylamine (1.3 mmol, 0.111 mL), 2-bromomethyl-4-chloro-6-iodo-benzoic acid methyl ester (0.389 g, 1.0 mmol), and K2CO3 (0.277 g, 2 mmol) in toluene (4 mL) was heated with stirring at 100° C. for 2 h. The resulting mixture was filtered and concentrated. Silica gel column chromatography using 30% ethyl acetate in hexane afforded 2-Cyclopropyl methyl-5-chloro-7-iodo-2,3-dihydro-isoindol-1-one (0.123 g, 35%). 1H NMR (300 MHz, CDCl3): δ (ppm) 0.32 (m, 2H), 0.60 (m, 2H), 1.04 (m, 1H), 3.46 (d, 2H), 4.36 (s, 2H), 7.43 (s, 1H), 7.90 (s, 1H). GC-MS: m/z 347 (M)+0.332 (M−15)+
Reaction SMILES: [O:1]=[C:2]1[C:11]2[CH:10]=[CH:9][N:8]=[C:7]3[NH:12][CH:13]=[C:5]([C:6]=23)[CH2:4][N:3]1[CH2:14][CH:15]1[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16]1.Cl>O1CCOCC1>[NH:17]1[CH2:18][CH2:19][CH:15]([CH2:14][N:3]2[CH2:4][C:5]3=[CH:13][NH:12][C:7]4[C:6]3=[C:11]([CH:10]=[CH:9][N:8]=4)[C:2]2=[O:1])[CH2:16]1
Reactant: CC(C)(C)OC(=O)N1CCC(CN2Cc3c[nH]c4nccc(c34)C2=O)C1
Agent: Cl
Solvent: C1COCCO1
Product: O=C1c2ccnc3[nH]cc(c23)CN1CC1CCNC1
Reaction time: 1 h
Yield: 104 %

Procedure:
To a solution of tert-butyl 3-((5-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)methyl)pyrrolidine-1-carboxylate (10 mg, 0.03 mmol) in dioxane at 0° C. was added 4N HCl in dioxane (0.019 mL, 0.075 mmol) and the reaction mixture was stirred for 1 h to give a solid. The solid was filtered and dried to afford the title compound (8.0 mg) as its HCl salt. 1H NMR (400 MHz, CD3OD) δ 1.90 (br. s., 1 H) 2.24 (br. s., 1 H) 2.96 (br. s., 1 H) 3.17 (br. s., 2 H) 3.59 (d, J=5.05 Hz, 1 H) 3.71-3.83 (m, 2 H) 3.87 (br. s., 1 H) 5.18 (br. s., 2 H) 7.64 (br. s., 1 H) 7.80 (br. s., 1 H) 8.55 (br. s., 1 H). [M+H] found 257.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:21]=[CH:20][CH:19]=[CH:18][C:4]=1[CH:5]([O:13][CH:14]1[CH2:17][NH:16][CH2:15]1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[Cl:12].[N-]=C=O.ClC1C=CC=CC=1C(O[CH:37]1[CH2:40][N:39]([C:41](NC(C)(C)C)=[O:42])[CH2:38]1)C1C=CC=CC=1Cl>>[Cl:12][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[CH:5]([O:13][CH:14]1[CH2:17][N:16]([C:41]([NH:39][CH2:38][CH2:37][CH3:40])=[O:42])[CH2:15]1)[C:4]1[CH:18]=[CH:19][CH:20]=[CH:21][C:3]=1[Cl:2]
Reactant: CC(C)(C)NC(=O)N1CC(OC(c2ccccc2Cl)c2ccccc2Cl)C1
Reactant: Clc1ccccc1C(OC1CNC1)c1ccccc1Cl
Agent: Cl
Agent: [N-]=C=O
Product: CCCNC(=O)N1CC(OC(c2ccccc2Cl)c2ccccc2Cl)C1

Procedure:
This material was prepared from 3-(2,2′-dichlorobenzhydryloxy)azetidine hydrochloride (68) and the corresponding commercially available isocyanate using the procedure described for compound (69).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][OH:5].[F:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]=[C:15]2[NH:23][CH:24]2[CH2:29][CH2:28][N:27]([CH2:30][CH2:31][N:32]=[C:33]=[S:34])[CH2:26][CH2:25]2)=[CH:9][CH:8]=1>O1CCCC1>[OH2:5].[F:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]=[C:15]2[NH:23][CH:24]2[CH2:25][CH2:26][N:27]([CH2:30][CH2:31][NH:32][C:33]([NH:1][CH2:2][CH2:3][CH2:4][OH:5])=[S:34])[CH2:28][CH2:29]2)=[CH:9][CH:8]=1
Reactant: Fc1ccc(Cn2c(NC3CCN(CCN=C=S)CC3)nc3ccccc32)cc1
Reactant: NCCCO
Solvent: C1CCOC1
Product: O
Product: OCCCNC(=S)NCCN1CCC(Nc2nc3ccccc3n2Cc2ccc(F)cc2)CC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 64 %

Procedure:
A mixture of 3.75 parts of 3-amino-1-propanol, 20.5 parts of 1-(4-fluorophenylmethyl)-N-[1-(2-isothiocyanatoethyl)-4-piperidinyl]-1H-benzimidazol-2-amine and 450 parts of tetrahydrofuran was stirred for 3 hours at room temperature. The reaction mixture was evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (96:4 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile, yielding 16 parts (64%) of N-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-N'(3-hydroxypropyl)thiourea monohydrate; mp. 124.6° C. (compound 30).
Reaction SMILES: [CH2:1]([O:4][C:5]1([CH3:55])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[CH:17]=[C:18]([C:20]4[CH:21]=[C:22]([C:26]5[CH:31]=[C:30]([O:32][C:33]([F:36])([F:35])[F:34])[CH:29]=[CH:28][C:27]=5[O:37][C@H:38]([CH2:40][CH:41]=C)[CH3:39])[CH:23]=[CH:24][CH:25]=4)[N:19]=[C:15]3[C:14]([CH3:43])=[C:13]([CH3:44])[C:12]=2[C@H:45]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])[C:46]([O:48][CH3:49])=[O:47])[CH2:7][CH2:6]1)[CH:2]=C.O.[BH4-].C([N+](CCCC)(CCCC)CCCC)CCC>ClCCCl.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3OC(C)C)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1.C(Cl)Cl>[C:51]([O:50][C@@H:45]([C:12]1[C:13]([CH3:44])=[C:14]([CH3:43])[C:15]2=[N:19][C:18]3=[CH:17][N:16]2[C:11]=1[N:8]1[CH2:9][CH2:10][C:5]([CH3:55])([O:4][CH2:1][CH2:2][CH2:41][CH2:40][C@H:38]([CH3:39])[O:37][C:27]2[CH:28]=[CH:29][C:30]([O:32][C:33]([F:34])([F:35])[F:36])=[CH:31][C:26]=2[C:22]2[CH:21]=[C:20]3[CH:25]=[CH:24][CH:23]=2)[CH2:6][CH2:7]1)[C:46]([O:48][CH3:49])=[O:47])([CH3:52])([CH3:53])[CH3:54]
Reactant: C=CCOC1(C)CCN(c2c([C@H](OC(C)(C)C)C(=O)OC)c(C)c(C)c3nc(-c4cccc(-c5cc(OC(F)(F)F)ccc5O[C@@H](C)CC=C)c4)cn23)CC1
Agent: Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)=Cc2ccccc2OC(C)C)c(C)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [BH4-]
Solvent: ClCCCl
Solvent: ClCCl
Solvent: O
Product: COC(=O)[C@@H](OC(C)(C)C)c1c(C)c(C)c2nc3cn2c1N1CCC(C)(CC1)OCCCC[C@H](C)Oc1ccc(OC(F)(F)F)cc1-c1cccc-3c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 38.3 %

Procedure:
A solution of (S)-methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-7,8-dimethyl-2-(2′-((S)-pent-4-en-2-yloxy)-5′-(trifluoromethoxy)-[1,1′-biphenyl]-3-yl)imidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate (0.20 g, 0.262 mmol, 1 equiv) and TsOH monohydrate (50 mg, 0.262 mmol, 1 equiv) in DCE (100 mL) was heated to 80° C. The Hoveyda Grubbs 2nd generation catalyst (16 mg, 0.026 mmol, 0.1 equiv) was added. The pale green brown solution was stirred for 3 h. Upon cooling to ambient temperature, the reaction was washed with saturated aqueous NaHCO3, dried (Na2SO4), and concentrated in vacuo. The crude product was taken up in 20:1 DCE:water (2.8 mL) and tetrabutylammonium borohydride (135 mg, 0.524 mmol, 2 equiv) was added. After 1 h, the reaction mixture was diluted with DCM, washed with water, dried (Na2SO4), and concentrated in vacuo. The crude product was purified by silica gel flash column chromatography (0-100% EtOAc [2% TEA]/hexane) to provide the product (74 mg, 38%) as a tan foam. LCMS (ESI, M+1): 738.80.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:22])[C:4]1[C:9](Cl)=[CH:8][C:7]([CH3:11])=[N:6][C:5]=1[O:12][C:13]1[C:18]([CH3:19])=[CH:17][C:16]([CH3:20])=[CH:15][C:14]=1[CH3:21].[CH2:23]([CH:25]([NH2:28])[CH2:26][CH3:27])[CH3:24]>CS(C)=O>[CH3:1][O:2][C:3](=[O:22])[C:4]1[C:9]([NH:28][CH:25]([CH2:26][CH3:27])[C:23]#[CH:24])=[CH:8][C:7]([CH3:11])=[N:6][C:5]=1[O:12][C:13]1[C:18]([CH3:19])=[CH:17][C:16]([CH3:20])=[CH:15][C:14]=1[CH3:21]
Reactant: COC(=O)c1c(Cl)cc(C)nc1Oc1c(C)cc(C)cc1C
Reactant: CCC(N)CC
Solvent: CS(C)=O
Product: C#CC(CC)Nc1cc(C)nc(Oc2c(C)cc(C)cc2C)c1C(=O)OC
Temperature: 130 °C

Procedure:
A mixture of 4-chloro-6-methyl-2-(2,4,6-trimethyl-phenoxy)-nicotinic acid methyl ester and 1-ethyl-propyl-amine in DMSO was heated at 130° C. overnight. The mixture was quenched with water, brine and extracted with ethyl acetate. The organic layer was dried and concentrated to dryness. The residue was purified through silica gel column chromatography to give the title compound. 1H NMR(CDCl3) d 8.26(d,1H), 6.87(s,2H), 6.26(s,1H), 4.11 (m,1H), 3.87(s,3H), 2.324(m,1H), 2.30(s,3H), 2.17s,3H), 2.08(s,6H), 1.92(q,2H), 1.16(t,3H) ppm.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:19]=[CH:18][C:12]2[CH:13]=[CH:14][C:15](=[O:17])[O:16][C:11]=2[CH:10]=1.C(N(CC)CC)C.C(C1[C:36]([OH:37])=[C:35]([C:38](C)(C)C)[CH:34]=C(C)C=1)(C)(C)C.C(Cl)(=O)C(C)=C>O1CCCC1.CN(C)C1C=CN=CC=1>[CH3:38][C:35](=[CH2:34])[C:36]([O:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:19]=[CH:18][C:12]2[CH:13]=[CH:14][C:15](=[O:17])[O:16][C:11]=2[CH:10]=1)=[O:37]
Reactant: O=c1ccc2ccc(OCCCCCCO)cc2o1
Reactant: Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Agent: C=C(C)C(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: C=C(C)C(=O)OCCCCCCOc1ccc2ccc(=O)oc2c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
4.2 g (16 mmol) of 7-(6-hydroxy-hexyloxy)-2H-1 -benzopyran-2-one were dissolved in 40 ml of absolute tetrahydrofuran with the exclusion of moisture, treated with 1.82 g (18 mmol) of triethylamine, 0.004 g (0.3 mmol) of 4-dimethylaminopyridine and a spatula tip of 2,6-di-tert.-butyl-p-cresol and cooled to 0° C. 1.7 ml of methacryloyl chloride were added dropwise to this solution within 10 min. The mixture was stirred at 0° C. for one hour and at room temperature for a further hour. Subsequently, the white precipitate which separated was filtered off and rinsed with tetrahydrofuran. The filtrate was evaporated to dryness and the residue was chromatographed on silica gel with acetone/cyclohexane (1:4). In this manner there were obtained 4 g of 6-(2-oxo-2H-1-benzopyran-7-yloxy)-hexyl 2-methyl-acrylate as a colourless liquid. λmax. (in CH2Cl2)=322.7 nm (ε=15110 l/mol cm).
Reaction SMILES: C([Si](C)(C)[O:6][C:7]([C:16]1[CH:21]=[CH:20][C:19]([CH:22]([S:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)(=[O:26])=[O:25])[CH3:23])=[CH:18][CH:17]=1)([C:12]([F:15])([F:14])[F:13])[C:8]([F:11])([F:10])[F:9])(C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C1C[O:56]CC1>>[C:7]([OH:6])([C:12]([F:15])([F:14])[F:13])=[O:56].[F:11][C:8]([F:9])([F:10])[C:7]([C:16]1[CH:17]=[CH:18][C:19]([CH:22]([S:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)(=[O:25])=[O:26])[CH3:23])=[CH:20][CH:21]=1)([OH:6])[C:12]([F:15])([F:14])[F:13]
Reactant: C1CCOC1
Reactant: CC(c1ccc(C(O[Si](C)(C)C(C)(C)C)(C(F)(F)F)C(F)(F)F)cc1)S(=O)(=O)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Product: CC(c1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1)S(=O)(=O)c1ccccc1
Product: O=C(O)C(F)(F)F
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 86 %

Procedure:
The product from step 2 (120 mg, 0.23 mmol) was dissolved in anhydrous THF (2 mL) under argon and cooled to 0° C. 1 M tetrabutylammonium fluoride solution in THF (0.5 mL, 0.5 mmol) was added and the reaction stirred for 30 min. The reaction was quenched at 0° C. with saturated NH4Cl and diluted with ethyl acetate. The layers were separated and the organic phase was washed with brine, dried (MgSO4), and concentrated in vacuo. Purification by reverse phase HPLC using a gradient elution of 60:40H2O/TFA:CH3CN to 0:100H2O/TFA:CH3CN at 254 nm afforded the title compound as a white solid (81 mg, 86%): mp=136° C. 1H NMR (CDCl3) δ 7.48-7.41 (m, 3H), 7.37 (d, 2H), 7.24 (m, 2H), 7.08 (d, 2H), 1H), 3.40 (br s, 1H), 1.67 (d, 3H). MS (ES+) m/z 430 (M+NH4+). Anal. Calc. for C17H14SO3F6: C, 49.52; H, 3.42. Found: C, 49.55; H, 3.28.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]([NH:5][CH:6]1[CH2:10][CH2:9][NH:8][CH2:7]1)=[O:4].C(O)C.Cl[C:17]1[N:26]=[C:25]2[C:20]([C:21](=[O:34])[C:22]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:23][N:24]2[CH:27]=[CH2:28])=[CH:19][C:18]=1[F:35]>C(N(CC)CC)C>[F:35][C:18]1[CH:19]=[C:20]2[C:25](=[N:26][C:17]=1[N:8]1[CH2:9][CH2:10][CH:6]([NH:5][C:3](=[O:4])[C:2]([F:1])([F:11])[F:12])[CH2:7]1)[N:24]([CH:27]=[CH2:28])[CH:23]=[C:22]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[C:21]2=[O:34]
Reactant: C=Cn1cc(C(=O)OCC)c(=O)c2cc(F)c(Cl)nc21
Reactant: O=C(NC1CCNC1)C(F)(F)F
Solvent: CCO
Solvent: CCN(CC)CC
Product: C=Cn1cc(C(=O)OCC)c(=O)c2cc(F)c(N3CCC(NC(=O)C(F)(F)F)C3)nc21
Yield: 84.8 %

Procedure:
A mixture of 3-trifluoroacetylaminopyrrolidine (5.46 g), ethanol (60 ml) and triethylamine (3 g) was added to ethyl 7-chloro-6-fluoro-1,4-dihydro-4-oxo-1-vinyl-1,8-naphthyridine-3-carboxylate (5.93 g) obtained according to Reference Example 1. The mixture was heated under reflux for one hour. After ice-cooling, the resulting crystals were collected by filtration and washed with ethanol. Recrystallization of the crude crystals from ethanol-chloroform gave 7.5 g of ethyl 6-fluoro-7-(3-trifluoroacetylamino-1-pyrrolidinyl)-1,4-dihydro-4-oxo-1-vinyl-1,8-naphthyridine-3-carboxylate, m.p. 280°-282° C. A solution of the compound (4.4 g) thus obtained in 1 N sodium hydroxide (80 ml) was stirred for 2 hours at 60° C. At the same temperature the mixture was adjusted to pH 7-8 by addition of acetic acid. After ice-cooling, the resulting crystals were collected by filtration, washed with water, and dissolved in hot 10% acetic acid, followed by treating with charcoal.
Reaction SMILES: [F:1][S:2]([O:5][CH3:6])(=[O:4])=[O:3].[CH2:7]([N:9]1[CH2:13][C@@H:12]([S:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[CH2:11][C@H:10]1[C:24](=[O:27])[NH:25][CH3:26])[CH3:8]>C(Cl)Cl>[F:1][S:2]([O-:5])(=[O:4])=[O:3].[CH2:7]([N+:9]1([CH3:6])[CH2:13][C@@H:12]([S:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[CH2:11][C@H:10]1[C:24](=[O:27])[NH:25][CH3:26])[CH3:8]
Reactant: COS(=O)(=O)F
Reactant: CCN1C[C@@H](SCc2ccc(OC)cc2)C[C@H]1C(=O)NC
Solvent: ClCCl
Product: CC[N+]1(C)C[C@@H](SCc2ccc(OC)cc2)C[C@H]1C(=O)NC
Product: O=S(=O)([O-])F
Temperature: 25 °C
Reaction time: 4 h

Procedure:
187 μl of methyl fluorosulfonate were added, whilst ice-cooling, to a solution of 700 mg of (2S, 4S)-1-ethyl-4-(4-methoxybenzylthio)-2-methylcarbamoylpyrrolidine dissolved in 30 ml of dry methylene chloride, and the mixture was stirred at room temperature for 4 hours. At the end of this time, the solvent was removed by distillation under reduced pressure, and the residue was washed repeatedly by decantation with diethyl ether and dried under reduced pressure to afford 950 mg of the title compound as a colorless oil.
Reaction SMILES: O.[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[OH:9].CO[CH:12]1[CH2:16][CH2:15][CH:14](OC)O1>C(O)(=O)C>[N:2]1([C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[OH:9])[CH:12]=[CH:16][CH:15]=[CH:14]1
Reactant: Nc1ccccc1O
Reactant: COC1CCC(OC)O1
Solvent: CC(=O)O
Solvent: O
Product: Oc1ccccc1-n1cccc1
Temperature: 100 °C
Yield: 74.1 %

Procedure:
A 5 L 3-neck round bottom flask was fitted with a mechanical stirrer, a heating mantle, a water cooled reflux condenser, a temperature probe/controller and a nitrogen inlet/outlet. The vessel was charged with (50 g, 0.46 mol) of 2-aminophenol and acetic acid (750 mL) which provided a very dark solution. Stirring was commenced and the vessel was charged with 2,5-dimethoxytetrahydrofuran (59.4 mL, 0.458 mol) dropwise over 2 minutes. The dark mixture was then heated at 100° C. for 15 min. The mixture was allowed to cool to room temperature and was filtered through a pad of Celite to remove residual solids. The filtrate was concentrated under reduced pressure azeotroping with toluene. The residual oil was dissolved in ethyl acetate (1000 mL) and was partitioned with water (500 mL). The organic layer was separated and was washed with water (500 mL), dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to provide 2-(1H-pyrrol-1-yl)phenol (54 g, 74%) as a dark oil. ESI-MS m/z calc. 159.1. found 160.2 (M+1)+. Retention time: 2.67 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.37-7.23 (m, 2H), 7.13-6.97 (m, 2H), 6.91 (t, J=1.9 Hz, 2H), 6.43 (t, J=1.9 Hz, 2H), 5.35 (s, 1H). 3-(1H-Pyrrol-1-yl)pyridin-2-ol was also synthesized using the procedure described above.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11](I)=[CH:10][CH:9]=1.C[Si]([C:19]#[CH:20])(C)C.N1C=CC=CC=1>C(N(CC)CC)C>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:19]#[CH:20])=[CH:10][CH:9]=1
Reactant: C#C[Si](C)(C)C
Reactant: Ic1ccc(OCC2OCCO2)cc1
Solvent: CCN(CC)CC
Solvent: c1ccncc1
Product: C#Cc1ccc(OCC2OCCO2)cc1
Yield: 83 %

Procedure:
1-[(1,3-Dioxolan-2-yl)methyloxy]-4-iodobenzene (36.3 g) and trimethylsilylacetylene (50.0 g) were reacted in the presence of bistriphenylphosphinepalladium dichloride (2.50 g) and cuprous iodide (1.25 g), in triethylamine (140 ml) and pyridine (70 ml) at 60° C. for 2 hr. The reaction solution was partitioned between ethyl acetate and water. The resulting organic layer was washed with water, dried and concentrated. The resulting residue was dissolved in methanol and treated with 2N sodium hydroxide, to give 20.1 g of the title compound.
Reaction SMILES: [C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)O)[OH:2].[NH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][NH2:22].[O:23]=O>ClCC(Cl)CCl.ClC=C(Cl)Cl>[C:16]1([C:5]2[C:6](=[O:23])[CH:7]=[CH:8][C:1](=[O:2])[CH:3]=2)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1.[NH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][NH2:22]
Reactant: Oc1ccccc1O
Reactant: O=O
Agent: NCCCCCCCCCCCCN
Solvent: ClC=C(Cl)Cl
Solvent: ClCC(Cl)CCl
Product: O=C1C=CC(=O)C(c2ccccc2)=C1

Procedure:
About 14.54 g (0.0782 mol) 2-phenyl-hydrooquinone, about 0.2 g (0.0018 mol) catechol (chemical name 1,2-dihydroxybenzene) and about 16 g (0.08 mol) 1,12diaminododecane were dissolved in a solvent mixture comprising of about 30 mL of 1,2,3trichloropropane and 60 mL of trichloroethylene. Oxygen was then passed at a flow rate of about 50 cc/min through the solution for about one hour. About 0.2 g of cupric sulfate was then added to the reaction mixture. Oxygen flow was reinstated for about an additional two hours. At the end of the polymerization reaction most of the trichloroethylene was removed under high vacuum, without raising the temperature above 35° C. This solution of poly-(2-phenyl-benzoquinone-1,12-diaminododecane) polymer can be used directly for coating purposes.