Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[S:6][C:7]([C:13]([O:15]C)=[O:14])=[C:8]([C:9]([F:12])([F:11])[F:10])[C:4]=2[CH:3]=1.[Li+].[OH-].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.CO.O>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[S:6][C:7]([C:13]([OH:15])=[O:14])=[C:8]([C:9]([F:12])([F:11])[F:10])[C:4]=2[CH:3]=1
Reactant: COC(=O)c1sc2ccc(Cl)cc2c1C(F)(F)F
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: O=C(O)c1sc2ccc(Cl)cc2c1C(F)(F)F
Reaction time: 4 h

Procedure:
A mixture of compound 18e (574 mg, 1.95 mmol) and LiOH (187 mg, 7.80 mmol) in THF/MeOH/H2O (4/4/4 mL) was stirred for 4 h. A 15% citric acid solution (20 mL) was added, and the mixture was then extracted with EtOAc (3×). The combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue, compound 18f, was dried under reduced pressure for 18 h and was used without purification.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]=[O:9])=[N:6][CH:7]=1.[CH2:10]([Mg]Br)[CH3:11].C(OCC)C>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([OH:9])[CH2:10][CH3:11])=[N:6][CH:7]=1
Reactant: CC[Mg]Br
Reactant: O=Cc1ccc(Br)cn1
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCC(O)c1ccc(Br)cn1
Temperature: 25 °C
Reaction time: 6 h
Yield: 45 %

Procedure:
To a solution of 5-bromopicolinaldehyde (2.0 g, 10.8 mmol) in THF (20 mL) was added 3.0 M solution of ethyl magnesium bromide in diethyl ether (7.1 ml, 21.5 mmol) at 0° C. The reaction mixture was allowed to warm to room temperature and was stirred for 6 h. The reaction mixture was quenched with saturated ammonium chloride solution (20 mL) and water (15 mL), extracted with ethyl acetate (200 mL), dried over sodium sulphate and concentrated under reduced pressure to obtain crude product. The crude product was purified by a Biotage Isolera® One column (using 10% ethyl acetate and hexane (0.72 g, (45% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.57 (d, 1H), 8.01-7.98 (dd, 1H), 7.445 (d, 1H), 5.36 (d, 1H), 4.49-4.45 (dd, 1H), 1.65-1.61 (m, 2H), 0.815 (t, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1Cl)[N:8]([CH2:13][CH3:14])[CH:7]=[C:6]([C:15]([OH:17])=[O:16])[C:5]2=[O:18].[CH2:19]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)[CH:20]=[CH2:21].ClCl>N1C=CC=CC=1>[CH2:19]([N:22]1[CH2:27][CH2:26][N:25]([C:11]2[CH:10]=[C:9]3[C:4]([C:5](=[O:18])[C:6]([C:15]([OH:17])=[O:16])=[CH:7][N:8]3[CH2:13][CH3:14])=[CH:3][C:2]=2[Cl:1])[CH2:24][CH2:23]1)[CH:20]=[CH2:21]
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(Cl)c(Cl)cc21
Reactant: C=CCN1CCNCC1
Agent: ClCl
Solvent: c1ccncc1
Product: C=CCN1CCN(c2cc3c(cc2Cl)c(=O)c(C(=O)O)cn3CC)CC1
Reaction time: 2 h
Yield: 78 %

Procedure:
2 g of 6,7-dichloro-1-ethyl-4-oxo-1,4-dihydro quinoline-3-carboxylic acid, 3.8 g of 1-allylpiperazine and 20 cm3 of pyridine were heated under reflux. After 2 hours, dissolution of the acid was complete; after 11 hours, determination of the ionised chlorine (93% of theory) showed that the reaction was substantially complete. The solution was concentrated to dryness in vacuo, the residue was taken up in water (20 cm3) and the suspension was brought to pH 7.5 by the addition of acetic acid, whilst stirring. The precipitate was filtered off, washed with water and recrystallised from methyl cellosolve. 2.05 g of 7-(4-allylpiperazinyl)-6-chloro-1-ethyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid, m.p. 212° C., were obtained.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[C:7]([C@@H:11]1[NH:16][C:15](=O)[CH2:14][O:13][CH2:12]1)([CH3:10])([CH3:9])[CH3:8]>C1COCC1>[C:7]([C@H:11]1[CH2:12][O:13][CH2:14][CH2:15][NH:16]1)([CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)(C)[C@H]1COCC(=O)N1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(C)[C@H]1COCCN1
Temperature: 0 °C
Yield: 91.3 %

Procedure:
To an ice cold, stirred suspension of NaH (60% in oil, 1.6 g, 39.0 mmol) in toluene (53 mL) was added dropwise a solution of (S)-2-amino-4,5-dimethylpentan-1-ol (2.0 g, 17.0 mmol) in toluene (37 mL). After the addition was completed, the reaction mixture was warmed to room temperature and a solution of ethyl chloroacetate (2.3 g, 19.0 mmol) in toluene (10 mL) was added in a dropwise manner. The resulting mixture was then stirred at reflux for 20 h, cooled to room temperature, and solid ammonium chloride (2.1 g, 39.0 mmol) was added to the reaction. The mixture was stirred for 20 min and then concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 98:2 CH2Cl2/CH3OH to 95:5 CH2Cl2/CH3OH) to give (S)-5-tert-butylmorpholin-3-one (2.0 g, 74%) as a light yellow solid. To ice-cold THF (9 mL) was added LiAlH4 (1.0 M solution in THF, 26.0 mL, 26.0 mmol). Once the addition was complete, a solution of (S)-5-tert-butylmorpholin-3-one (2.0 g, 13.0 mmol) in THF (8.0 mL) was added dropwise over 20 min. Once the addition was completed, the ice bath was removed and the reaction mixture stirred at reflux for 20 h. The reaction was cooled in an ice-bath and to his was slowly added H2O (1.2 mL), then 15% aqueous solution of sodium hydroxide (1.2 mL), and then H2O (1.2 mL). The resulting mixture was stirred at room temperature for 1.5 h and then filtered washing the solids with EtOAc (50 mL). The filtrate was concentrated at room temperature under reduced pressure to provide (S)-3-tert-butylmorpholine (1.7 g, 97%) as a light yellow oil. 1H NMR and MS consistent.
Reaction SMILES: [CH2:1]([S:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[N:24]([CH3:25])[C:13]2=[N:14][CH:15]=[C:16]([CH:18](O)[C:19]([F:22])([F:21])[F:20])[CH:17]=[C:12]2[N:11]=1)[CH3:2].C1(C)C=CC=CC=1.S(Cl)([Cl:35])=O.C(=O)([O-])O.[Na+]>N1C=CC=CC=1>[Cl:35][CH:18]([C:16]1[CH:17]=[C:12]2[N:11]=[C:10]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[S:3][CH2:1][CH3:2])[N:24]([CH3:25])[C:13]2=[N:14][CH:15]=1)[C:19]([F:22])([F:21])[F:20]
Reactant: O=S(Cl)Cl
Reactant: CCSc1ccccc1-c1nc2cc(C(O)C(F)(F)F)cnc2n1C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CCSc1ccccc1-c1nc2cc(C(Cl)C(F)(F)F)cnc2n1C
Temperature: 50 °C

Procedure:
To a mixture of 1-[2-(2-ethylsulfanyl-phenyl)-3-methyl-3H-imidazo[4,5-b]pyridin-6-yl]-2,2,2-trifluoro-ethanol (98 mg), toluene (10 ml), and pyridine (50 μl), thionyl chloride (1 ml) was added. The mixture was stirred with heating at 50° C. for 5 hours, and then saturated aqueous sodium hydrogen carbonate solution was poured, and extracted with ethyl acetate. The combined organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 66 mg of 6-(1-chloro-2,2,2-trifluoro-ethyl)-2-(2-ethylsulfanyl-phenyl)-3-methyl-3H-imidazo[4,5-b]pyridine (hereinafter referred to as Present Compound 266).
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[OH:11])[CH:6]=[O:7])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3].CCOCC>C1COCC1>[CH2:1]([C:3]1[CH:4]=[C:5]([CH2:6][OH:7])[CH:8]=[CH:9][C:10]=1[OH:11])[CH3:2]
Reactant: CCc1cc(C=O)ccc1O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCc1cc(CO)ccc1O
Temperature: 0 °C
Reaction time: 2 h
Yield: 92.7 %

Procedure:
To a solution of 3-ethyl-4-hydroxybenzaldehyde (4.7 g, 26 mmol) in anhydrous THF (150 mL) at 0° C. under N2 was added dropwise 1 M LiAlH4 in Et2O (52 mL, 52.2 mmol). The resulting mixture was stirred at 0° C. for 2 h and then quenched by cautious addition of water and stirred for 15 minutes. The reaction mixture was then absorbed onto silica and loaded onto a silica pad which was washed with EtOAc. The EtOAc washings were collected and concentrated in vacuo to afford the title compound as a colourless oil (3.67 g).
Reaction SMILES: [CH2:1]([S:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][CH3:17])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[CH3:23][S:24](Cl)(=[O:26])=[O:25].Cl>O.CCCCCC.O1CCCC1>[CH2:1]([S:8][C:9]1[N:10]=[C:11]([N:15]([CH2:16][CH3:17])[S:24]([CH3:23])(=[O:26])=[O:25])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCNc1cccc(SCc2ccccc2)n1
Reactant: CS(=O)(=O)Cl
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: O
Product: CCN(c1cccc(SCc2ccccc2)n1)S(C)(=O)=O
Reaction time: 0.5 h
Yield: 42.9 %

Procedure:
To a mixture of 6 g of 2-benzylthio-6-ethylaminopyridine and 60 ml of tetrahydrofuran was added dropwise 17.3 ml of a 1.65 mol/l hexane solution of n-butyl lithium at -10° to 0° C. in a nitrogen stream. To the reaction mixture was added 3.4 g of methysulfonyl chloride at 0° to 15° C., followed by reacting for 0.5 hour. After completion of the reaction, the reaction mixture was poured into water, made weakly acidic with hydrochloric acid, and extracted with methylene chloride. The extract was dried over anhydrous sodium sulfate, followed by concentration under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent; ethyl acetate/hexane=1/19 by volume) to obtain 3.4 g of N-(6-benzylthiopyridine-2-yl)-N-ethylmethylsulfonamide as an orange crystal.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[CH3:10][C@H:11](OS(C1C=CC(C)=CC=1)(=O)=O)[CH2:12][CH2:13][CH3:14].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH3:10][CH:11]([O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1)[CH2:12][CH2:13][CH3:14]
Reactant: CCC[C@H](C)OS(=O)(=O)c1ccc(C)cc1
Reactant: O=Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCC(C)Oc1ccc(C=O)cc1

Procedure:
40 g of 4-hydroxybenzaldehyde, 80 of (S)-1-methylbutyl-p-toluene sulfonate and 46 g of potassium carbonate were refluxed in acetone for 12 hours, insoluble matters were removed from the reaction solution while the reaction solution was hot, and the solvent used was distilled out. The residue was purified by column chromatography to obtain 4-(1-methylbutyloxy)benzaldehyde (30).
Reaction SMILES: Cl[CH2:2][C:3]1[N:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.C([O-])([O-])=O.[K+].[K+].[OH:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH2:23][OH:24]>CN(C=O)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:11]=[N:12][C:3]=1[CH2:2][O:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH2:23][OH:24]
Reactant: OCc1cccc(O)c1
Reactant: ClCc1ncc2ccccc2n1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [Br-]
Solvent: CN(C)C=O
Product: OCc1cccc(OCc2ncc3ccccc3n2)c1
Temperature: 25 °C
Reaction time: 120 h
Yield: 85.8 %

Procedure:
To a solution of 5.00 g (28 mmol) of 2-chloromethylquinazoline in 50 ml of DMF, 4.26 g (31 mmol) of K2CO3 and 903 mg (2.8 mmol) of tetra-n-butylammonium bromide were added. 3-Hydroxybenzyl alcohol (3.48 g, 28 mmol) was added further, followed by stirring at room temperature for 5 days. The reaction mixture was concentrated under reduced pressure, followed by the addition of CHCl3 and water to extract the reaction product into the organic layer. The extract was dried over Na2SO4 and then concentrated under reduced pressure. The residue was recrystallized from a CHCl3 -n-hexane mixed solvent, whereby 6.4 g of the title compound was obtained as pale yellow powder (yield: 93.1%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:39]=[CH:40][CH:41]=1)[CH2:5][NH:6][C:7]([O:9][CH2:10][C@@H:11]1[C@@H:15]([O:16][CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)[CH2:14][C@@H:13]([O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)[C@H:12]1[CH2:30]/[CH:31]=[CH:32]\[CH2:33][CH2:34][CH2:35][C:36](O)=[O:37])=[S:8].C(N(CC)CC)C.C(OC(Cl)=O)C.[CH2:55]([CH2:57][NH2:58])[OH:56]>C(Cl)Cl.CCOC(C)=O>[OH:56][CH2:55][CH2:57][NH:58][C:36]([CH2:35][CH2:34][CH2:33]/[CH:32]=[CH:31]\[CH2:30][C@H:12]1[C@@H:13]([O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)[CH2:14][C@@H:15]([O:16][CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)[C@@H:11]1[CH2:10][O:9][C:7](=[S:8])[NH:6][CH2:5][C:4]1[CH:39]=[CH:40][CH:41]=[C:2]([Cl:1])[CH:3]=1)=[O:37]
Reactant: NCCO
Reactant: O=C(O)CCC/C=C\C[C@H]1[C@H](COC(=S)NCc2cccc(Cl)c2)[C@@H](OC2CCCCO2)C[C@H]1OC1CCCCO1
Agent: CCOC(=O)Cl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: O=C(CCC/C=C\C[C@@H]1[C@@H](COC(=S)NCc2cccc(Cl)c2)[C@H](OC2CCCCO2)C[C@@H]1OC1CCCCO1)NCCO
Temperature: 25 °C
Yield: 61.2 %

Procedure:
A solution of acid 7 (60 mg, 0.10 mmol) and triethylamine (30 mg, 0.30 mmol) in CH2Cl2 (2 mL) was cooled to 0° C. and ethylchloroformate (11 μL, 0.12 mmol) was added. After 0.5 h ethanolamine (7.2 μL, 0.12 mmol) was added and the reaction was allowed to warm to room temperature for 12 h. The reaction was diluted with EtOAc and washed with 1N HCl, saturated aqueous NaHCO3 and brine. The organic portion was dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography (silica gel, 100% EtOAc followed by 19:1 EtOAc/MeOH) provided 40 mg of the above titled compound.
Reaction SMILES: Cl[C:2]1[C:7]([Cl:8])=[N:6][CH:5]=[CH:4][N:3]=1.[NH2:9][CH2:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[O:18])[CH2:13][CH2:12]1>C(OCC)(=O)C>[F:27][C:24]1[CH:25]=[CH:26][C:21]([CH2:20][O:19][C:17]([N:14]2[CH2:15][CH2:16][CH:11]([CH2:10][NH:9][C:2]3[C:7]([Cl:8])=[N:6][CH:5]=[CH:4][N:3]=3)[CH2:12][CH2:13]2)=[O:18])=[CH:22][CH:23]=1
Reactant: NCC1CCN(C(=O)OCc2ccc(F)cc2)CC1
Reactant: Clc1nccnc1Cl
Solvent: CCOC(C)=O
Product: O=C(OCc1ccc(F)cc1)N1CCC(CNc2nccnc2Cl)CC1
Temperature: 110 °C

Procedure:
To 2,3-dichloropyrazine (0.160 gm, 0.00107 mol) was added 4-fluorobenzyl 4-(aminomethyl)piperidine-1-carboxylate (INTERMEDIATE 2C) (0.86 gm, 0.00322 mol) and the resulting mixture heated under nitrogen at 110° C. for 30 min. The reaction was cooled, diluted with ethyl acetate (5 mL), and washed with 10% aqueous sodium/citric acid pH=5.2 (3×30 mL), and 10% aqueous sodium bicarbonate (30 mL). The ethyl acetate extract was dried over sodium sulfate, filtered through a pad of silica and concentrated to an oil. Crystallization from ether/hexane gave 4-[(3-chloro-pyrazin-2-ylamino)-methyl]-piperidine-1-carboxylic acid 4-fluoro-benzyl ester.
Reaction SMILES: Cl.[NH2:2][C@H:3]([C:5]([NH2:7])=[O:6])[CH3:4].[C:8]([C:10]1[CH:38]=[CH:37][C:13]([CH2:14][C@@:15]2([CH3:36])[N:19]3[C:20]([S:23](Cl)(=[O:25])=[O:24])=[CH:21][N:22]=[C:18]3[N:17]([C:27]3[CH:32]=[C:31]([Cl:33])[CH:30]=[C:29]([Cl:34])[CH:28]=3)[C:16]2=[O:35])=[CH:12][CH:11]=1)#[N:9]>CN(C=O)C.CN(C1C=CN=CC=1)C.CCOC(C)=O>[C:8]([C:10]1[CH:11]=[CH:12][C:13]([CH2:14][C@@:15]2([CH3:36])[N:19]3[C:20]([S:23]([NH:2][C@@H:3]([CH3:4])[C:5]([NH2:7])=[O:6])(=[O:25])=[O:24])=[CH:21][N:22]=[C:18]3[N:17]([C:27]3[CH:28]=[C:29]([Cl:34])[CH:30]=[C:31]([Cl:33])[CH:32]=3)[C:16]2=[O:35])=[CH:37][CH:38]=1)#[N:9]
Reactant: C[C@@]1(Cc2ccc(C#N)cc2)C(=O)N(c2cc(Cl)cc(Cl)c2)c2ncc(S(=O)(=O)Cl)n21
Reactant: C[C@H](N)C(N)=O
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C[C@H](NS(=O)(=O)c1cnc2n1[C@](C)(Cc1ccc(C#N)cc1)C(=O)N2c1cc(Cl)cc(Cl)c1)C(N)=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 79.6 %

Procedure:
L-Alaninamide hydrochloride (0.151 g, 1.209 mmol) was dissolved in anhydrous DMF and DMAP (0.197 g, 1.612 mmol) was added to the solution. The reaction mixture was stirred at room temperature for 1 h. Then, (R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl chloride (0.24 g, 0.484 mmol) in anhydrous DMF was added to the reaction mixture and stirred for additional 10 min. The reaction solution was diluted with EtOAc and washed with water, 1 N HCl and then water. The organic phase was dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to afford 0.211 g of the title compound as a white scaly solid (M+1, 547.2).
Reaction SMILES: [CH3:1]/[C:2](/[CH:8]=[N:9]/[N:10]=[C:11]([NH2:13])[NH2:12])=[N:3]\[N:4]=[C:5]([NH2:7])[NH2:6].Cl.C(O)(C)C>O>[CH3:1][C:2](=[N:3][NH:4][C:5](=[NH:6])[NH2:7])[CH:8]=[N:9][NH:10][C:11](=[NH:12])[NH2:13]
Reactant: CC(/C=N/N=C(N)N)=N\N=C(N)N
Agent: Cl
Solvent: CC(C)O
Solvent: O
Product: CC(C=NNC(=N)N)=NNC(=N)N
Temperature: 30 °C
Reaction time: 1 h

Procedure:
A suspension of etude MGBG (460 g) in 920 g DI water was warmed to 40°-50° C. to give a clear pale yellow solution. The mixture was cooled to 30° C. and 920 mg conc. HCl was added. A pH of 0-1 was measured with litmus paper. Isopropanol (350 g, 446 mL) was added rapidly and the mixture stirred for 1 hour at 28°-32° C. The solutions were filtered to remove insoluble material. The filtrate was added to the reaction flask and acidified further with 0.5 g of conc. HCl The isopropanol (1.84 kg) was added over 10-15 minutes to the vigorously stirred solution. The mixture was cooled to 8°-12° C. and stirred for an additional hour. The solids were collected and the cake was rinsed with 2×200 mL isopropanol. After drying in a vacuum oven at 30°-40° C. for 24 hours, the recovery was about 90%. HPLC (ETI)=0.65%, nmr (dmsod6); IR (Kbr).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8](O)=[CH:7][CH:6]=1.[H-].[Na+].S([O-])(=O)(=O)C.C1(OCCO)C2C(=CC=CC=2)C=CC=1>CN(C)C=O>[CH3:1][O:2][C:3](=[O:13])[C:4](=[O:12])[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1
Reactant: COC(=O)C(=O)c1ccc(O)cc1
Agent: CS(=O)(=O)[O-]
Agent: OCCOc1cccc2ccccc12
Agent: [H-]
Solvent: CN(C)C=O
Product: COC(=O)C(=O)c1ccccc1
Temperature: 60 °C
Reaction time: 0.25 h

Procedure:
A stirred mixture of 4-hydroxy-alpha-oxobenzeneacetic acid methyl ester (0.724 g) in dimethylformamide (10 mL) under argon was treated with 55% sodium hydride (0.175 g), stirred for 15 minutes and treated with the mesylate of 2-(1-naphthyloxy)ethanol (1.37 g). The mixture was heated at 60° C. overnight and worked up as in Example 20. The material was purified by HPLC (dichloromethane-hexane; 4:1 ) and crystallized from diethyl etherhexane to provide 0.8 g of 4-[2-(1-naphthalenyloxy)ethyl]oxy]-alpha-oxobenzeneacetic acid methyl ester, mp 87°-91° C.
Reaction SMILES: Br.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:4]=1[C:12]1[N:13]=[C:14]([NH2:17])[S:15][CH:16]=1.[C:18]1([C:24]2[CH:29]=[CH:28][C:27]([S:30](Cl)(=[O:32])=[O:31])=[CH:26][CH:25]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:4]=1[C:12]1[N:13]=[C:14]([NH:17][S:30]([C:27]2[CH:26]=[CH:25][C:24]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:29][CH:28]=2)(=[O:32])=[O:31])[S:15][CH:16]=1
Reactant: O=S(=O)(Cl)c1ccc(-c2ccccc2)cc1
Reactant: Nc1nc(-c2cc([N+](=O)[O-])ccc2Cl)cs1
Agent: Br
Product: O=[N+]([O-])c1ccc(Cl)c(-c2csc(NS(=O)(=O)c3ccc(-c4ccccc4)cc3)n2)c1

Procedure:
The title compound was prepared from 4-(2-chloro-5-nitrophenyl)-1,3-thiazol-2-amine hydrobromide and 4-phenylbenzenesulfonyl chloride as described in the synthetic METHOD B to give a white solid (11.9 mg) with purity >90%. MS (pos) m/z 472.1.
Reaction SMILES: C([C:4]1[CH:5]=[CH:6][C:7]2[N:8](C[Si](C)(C)C)[C:9]3[C:14]([C:15]=2[CH:16]=1)=[CH:13][CH:12]=[CH:11][CH:10]=3)C=C.C1C2NC3C(=CC=CC=3)C=2C=CC=1.[Br:35]Br.[H-].[Na+].ClC[Si](C)(C)C.C([Li])CCC>N1C=CC=CC=1.O1CCCC1.CC(C)=O>[Br:35][C:4]1[CH:5]=[CH:6][C:7]2[NH:8][C:9]3[C:14]([C:15]=2[CH:16]=1)=[CH:13][CH:12]=[CH:11][CH:10]=3
Reactant: C=CCc1ccc2c(c1)c1ccccc1n2C[Si](C)(C)C
Reactant: BrBr
Agent: C[Si](C)(C)CCl
Agent: [H-]
Agent: [Li]CCCC
Solvent: c1ccncc1
Solvent: C1CCOC1
Solvent: CC(C)=O
Product: Brc1ccc2[nH]c3ccccc3c2c1

Procedure:
A preferred example is the use of 3-(2-propenyl)-N-trimethylsilylmethylcarbazole as the polymerizable monomer in a photoresist. 3-Bromocarbazole is prepared by treating carbazole in pyridine with a solution of bromine in pyridine. The purified product is converted to the N-trimethylsilylmethyl derivative by sequential treatment in tetrahydrofuran with sodium hydride and chloromethyltrimethylsilane, followed by refluxing. The purified product is treated with n-butyllithium, acetone, and worked up to give an intermediate alcohol, which is converted to 3(2-propenyl)-N-trimethylsilylmethylcarbazole by treatment with thionyl chloride in pyridine at 50° C. The product is purified by column chromatography to give a very viscous liquid.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([S:12]([N:15]3[CH2:20][CH2:19][CH:18]([OH:21])[CH2:17][CH2:16]3)(=[O:14])=[O:13])[C:6]=2[CH:5]=[CH:4][N:3]=1.[C:22]1([CH3:32])[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1>N1C=CC=CC=1>[Cl:1][C:2]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([S:12]([N:15]3[CH2:16][CH2:17][CH:18]([O:21][S:28]([C:25]4[CH:26]=[CH:27][C:22]([CH3:32])=[CH:23][CH:24]=4)(=[O:30])=[O:29])[CH2:19][CH2:20]3)(=[O:14])=[O:13])[C:6]=2[CH:5]=[CH:4][N:3]=1
Reactant: O=S(=O)(c1cccc2c(Cl)nccc12)N1CCC(O)CC1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OC2CCN(S(=O)(=O)c3cccc4c(Cl)nccc34)CC2)cc1
Temperature: 0 °C
Reaction time: 24 h

Procedure:
To 40 ml of pyridine were added 3.11 g of the thus obtained 1-(1-chloro-5-isoquinolinesulfonyl)-4-hydroxypiperidine and 3.81 g of p-toluenesulfonyl chloride. The resulting mixture was stirred at a temperature of 15° C. to 20° C. for 24 hours. To the reaction mixture was added 100 g of ice water, followed by extraction twice with 100 ml each of dichloromethane. The dichloromethane layer was dried with anhydrous magnesium sulfate and the dichloromethane was removed under reduced pressure to obtain 4.46 g of 1-(1-chloro-5-isoquinolinesulfonyl)-4-p-toluenesulfonyloxypiperidine.
Reaction SMILES: [O:1]=[C:2]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:6]2[S:14][C:15]([C:23](O)=[O:24])=[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:5]=2[CH:4]=[CH:3]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:40][N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1>C(Cl)Cl>[CH3:40][N:41]1[CH2:46][CH2:45][N:44]([C:23]([C:15]2[S:14][C:6]3[N:7]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[C:2](=[O:1])[CH:3]=[CH:4][C:5]=3[C:16]=2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:24])[CH2:43][CH2:42]1
Reactant: CN1CCNCC1
Reactant: O=C(O)c1sc2c(ccc(=O)n2-c2ccccc2)c1-c1ccccc1
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: ClCCCl
Product: CN1CCN(C(=O)c2sc3c(ccc(=O)n3-c3ccccc3)c2-c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 65.8 %

Procedure:
To a suspension of the compound of Example 59 (100 mg, 0.29 mmol) in DCM (2 mL) was added EDC (67 mg, 0.348 mmol) and HOBT (43 mg, 0.32 mmol) and the mixture stirred at r.t. for 15 minutes. A solution N-methyl piperazine (28 mg, 0.32 mmol) in DCM (0.5 mL) was added and the reaction stirred at r.t. for 18 h. The reaction mixture was diluted with DCM (10 mL), washed with water (2×5 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified by chromatography on silica (0–20% THF in DCM) to give the title compound as an off-white solid (82 mg). δH (DMSO-d6) 7.67 (1H, dd, J 10, 1 Hz), 7.62–7.52 (3H, m), 7.51–7.40 (5H, m), 7.35–7.31 (2H, m), 6.51 (1H, dd, J 10, 1 Hz), 2.44 (8H, m), 1.88 (3H, s). LCMS (ES+) RT 2.18 minutes, 430 (M+H)+.