Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.[C:9]([O:13][CH3:14])(=[O:12])[CH:10]=[CH2:11].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C:2]1[N:3]=[CH:4][C:5](/[CH:11]=[CH:10]/[C:9]([O:13][CH3:14])=[O:12])=[CH:6][CH:7]=1
Reactant: C=CC(=O)OC
Reactant: Nc1ccc(Br)cn1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CC#N
Product: COC(=O)/C=C/c1ccc(N)nc1
Temperature: 100 °C
Reaction time: 8 h
Yield: 27.4 %

Procedure:
2-Amino-5-bromopyridine (13.5 g, 78.0 mmol), methyl acrylate (10.1 g, 117 mmol) and tris(2-methylphenyl)phosphine (4.75 g, 15.6 mmol) were dissolved in acetonitrile (200 mL), palladium(II) acetate (1.75 g, 7.8 mmol) was added and the mixture was stirred overnight under an argon atmosphere at 100° C. After cooling the reaction mixture, the insoluble material was removed by filtering through celite and the solvent was evaporated under reduced pressure. The residue was dissolved in saturated aqueous sodium hydrogencarbonate and chloroform, and he mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform, then 0%-5% methanol/ethyl acetate), and recrystallized from ethyl acetate-hexane to give the title compound (3.81 g, yield 27%) as yellow crystals.
Reaction SMILES: [F:1][C:2]1[CH:26]=[CH:25][C:5]([O:6][C:7]2[N:24]=[CH:23][CH:22]=[CH:21][C:8]=2[C:9]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19]C)=[CH:15][CH:14]=2)=[O:10])=[CH:4][CH:3]=1>CCOCC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[N:24]=[CH:23][CH:22]=[CH:21][C:8]=2[C:9]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)=[O:10])=[CH:25][CH:26]=1
Reactant: COc1ccc(CNC(=O)c2cccnc2Oc2ccc(F)cc2)cc1
Solvent: CCOCC
Product: O=C(NCc1ccc(O)cc1)c1cccnc1Oc1ccc(F)cc1

Procedure:
The compound of Example 104 was prepared according to the procedure of Example 103 substituting the corresponding ether for 2-(4-Fluoro-phenoxy)-N-(4-methoxy-benzyl)-nicotinamide. The duration of reaction was between 1 and 24 hours.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[C:4]1[C:5](=[CH:10][C:11]([O:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH:17]=[CH:16]2)=[CH:12][CH:13]=1)[C:6]([O:8][CH3:9])=[O:7]>C1COCC1.[Pd]>[CH3:1][O:2][C:3](=[O:21])[C:4]1[C:5](=[CH:10][C:11]([O:14][CH:15]2[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]2)=[CH:12][CH:13]=1)[C:6]([O:8][CH3:9])=[O:7]
Reactant: COC(=O)c1ccc(OC2C=CCCC2)cc1C(=O)OC
Agent: [Pd]
Solvent: C1CCOC1
Product: COC(=O)c1ccc(OC2CCCCC2)cc1C(=O)OC

Procedure:
4-(Cyclohex-2-enyloxy)-phthalic acid dimethyl ester [Example A37] (67 mg, 0.23 mmol) was hydrogenated under an atmosphere of hydrogen at room temperature and pressure with 10% wet Pd/C (ca. 200 mg) in THF (5 mL) for 24 h. The catalyst was removed by filtration and the solvent was evaporated under vacuum. The crude material was purified by flash chromatography on silica gel eluting with 0–20% MeOH in DCM to yield 4-cyclohexyloxy-phthalic acid dimethyl ester as an oil. m/z (APCI+) 293 (15%, [M+H]+), 179 (100), 261 (65).
Reaction SMILES: [CH2:1]1[C:5]2=[C:6]([CH:13]=O)[C:7]3[CH:8]=[N:9][CH:10]=[CH:11][C:12]=3[N:4]2[CH2:3][CH2:2]1.C([O-])(=O)C.[NH4+].[N+:20]([CH2:23][CH3:24])([O-:22])=[O:21]>>[N+:20]([C:23]([CH3:24])=[CH:13][C:6]1[C:7]2[CH:8]=[N:9][CH:10]=[CH:11][C:12]=2[N:4]2[CH2:3][CH2:2][CH2:1][C:5]=12)([O-:22])=[O:21]
Reactant: O=Cc1c2n(c3ccncc13)CCC2
Reactant: CC[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: [NH4+]
Product: CC(=Cc1c2n(c3ccncc13)CCC2)[N+](=O)[O-]
Temperature: 100 °C
Yield: 77 %

Procedure:
To a solution of 2,3-dihydro-1H-3a,6-diaza-cyclopenta[a]indene-8-carbaldehyde (0.30 g 1.6 mMol) in nitroethane (3.00 ml) was added ammonium acetate (0.30 g 3.9 mMol) and the mixture was heated to 100° C. for 4 h with stirring under argon. The mixture was cooled to room temperature and purified by chromatography on silicagel gel (ca 30 g) eluting first with ethyl acetate (ca 100 ml) then with a mixture of ethyl acetate (9 parts) and methanol (1 part). The product fraction were combined, concentrated and the residue was recrystallised from ethyl acetate to yield the title compound (0.30 g, 77%) as yellow crystals. mp 141-142° C. Found C, 64.05; H, 5.51; N, 17.14%; C13H13N3O2 requires C, 64.19; H, 5.39; N, 17.27%.
Reaction SMILES: Br[CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([Cl:19])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.[CH2:21]([NH2:23])[CH3:22].C(OCC)(=O)C.C([O-])(O)=O.[Na+]>C1COCC1>[Cl:19][C:17]1[CH:16]=[C:13]([CH:12]=[C:11]([O:10][C:5]2[C:6]([Cl:9])=[CH:7][CH:8]=[C:3]([CH2:2][NH:23][CH2:21][CH3:22])[C:4]=2[F:20])[CH:18]=1)[C:14]#[N:15]
Reactant: CCN
Reactant: N#Cc1cc(Cl)cc(Oc2c(Cl)ccc(CBr)c2F)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCNCc1ccc(Cl)c(Oc2cc(Cl)cc(C#N)c2)c1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 106.4 %

Procedure:
A solution of 3-{[3-(bromomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.50 g, 1.33 mmol) in THF (10 mL) was added dropwise to a 2M solution of EtNH2 (6.67 mL, 13.33 mmol) in THF. The flask was sealed and stirred at RT overnight. Ethyl acetate (100 ml) and saturated NaHCO3 solution (100 ml) were added. The organic layer was washed with brine (150 mL), dried over MgSO4, filtered and concentrated to give the title compound (0.48 g, quant.) as a tan solid. 1H NMR shows title compound plus a little residual EtNH2. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.04 (br. s., 1H), 7.83 (s, 1H), 7.62 (s, 2H), 7.45-7.55 (m, 2H), 4.14 (s, 2H), 2.95 (q, 2H), 1.18 (t, 3H). LCMS m/z 340.0 (M+H).
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[CH:6][N:7]=[C:8]([C:11]3[C:16]([CH2:17][CH3:18])=[CH:15][CH:14]=[CH:13][C:12]=3[CH2:19][CH3:20])[CH:9]=2)[N:4]([C:21]2[CH:26]=[CH:25][C:24]([CH:27]([CH3:29])[CH3:28])=[CH:23][CH:22]=2)[CH:3]=1.[CH2:30]([Sn](CCCC)(CCCC)C=C)[CH2:31]CC.[F-].[K+]>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.CN(C=O)C>[CH2:17]([C:16]1[CH:15]=[CH:14][CH:13]=[C:12]([CH2:19][CH3:20])[C:11]=1[C:8]1[CH:9]=[C:10]2[C:2]([CH:30]=[CH2:31])=[CH:3][N:4]([C:21]3[CH:26]=[CH:25][C:24]([CH:27]([CH3:28])[CH3:29])=[CH:23][CH:22]=3)[C:5]2=[CH:6][N:7]=1)[CH3:18]
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Reactant: CCc1cccc(CC)c1-c1cc2c(Br)cn(-c3ccc(C(C)C)cc3)c2cn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [F-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C=Cc1cn(-c2ccc(C(C)C)cc2)c2cnc(-c3c(CC)cccc3CC)cc12
Temperature: 100 °C

Procedure:
A mixture of 3-bromo-5-(2,6-diethyl-phenyl)-1-(4-isopropyl-phenyl)-1H-pyrrolo[2,3-c]pyridine (440 mg, 0.98 mmol), tributyl-vinyl-stannane (620 mg, 1.96 mmol), Pd(PPh3)4 (113 mg, 0.098 mmol), and DMF (5 mL) is heated to 100° C. for 3 h under nitrogen. The mixture is poured to a saturated aqueous KF solution (20 mL), and the resultant mixture is stirred for three hours at room temperature. The product is extracted with EtOAc (70 mL×3). The combined organic extracts are washed with water (100 mL×3) and brine (100 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue is purified by chromatography on silica gel (Hexane/EtOAc, 10:1) to afford 5-(2,6-diethyl-phenyl)-1-(4-isopropyl-phenyl)-3-vinyl-1H-pyrrolo[2,3-c]pyridine as a colorless oil.
Reaction SMILES: [CH2:1]([NH:3][C:4]1[CH:9]=[C:8]([O:10]C)[CH:7]=[CH:6][C:5]=1[CH:12]1[CH2:21][CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:22]C)[CH:18]=2)[CH2:13]1)[CH3:2].Cl.[N:25]1([CH2:32][CH2:33][O:34][C:35]2[CH:43]=[CH:42][C:38]([C:39](Cl)=O)=[CH:37][C:36]=2[F:44])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1>>[N:25]1([CH2:32][CH2:33][O:34][C:35]2[CH:43]=[CH:42][C:38]([CH2:39][CH2:2][CH2:1][NH:3][C:4]3[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:5]=3[CH:12]3[CH2:21][CH2:20][C:19]4[CH:18]=[C:17]([OH:22])[CH:16]=[CH:15][C:14]=4[CH2:13]3)=[CH:37][C:36]=2[F:44])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1
Reactant: O=C(Cl)c1ccc(OCCN2CCCCCC2)c(F)c1
Reactant: CCNc1cc(OC)ccc1C1CCc2cc(OC)ccc2C1
Agent: Cl
Product: Oc1ccc2c(c1)CCC(c1ccc(O)cc1NCCCc1ccc(OCCN3CCCCCC3)c(F)c1)C2
Yield: 49.7 %

Procedure:
Synthesized from ethyl[5-methoxy-2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenyl]amine (400 mg) and 4-(2-azepan-1-ylethoxy)-3-fluorobenzoyl chloride hydrochloride (560 mg) according to an analogous synthetic method to Example 187, the title compound (340 mg) was obtained.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][CH2:14][CH3:15])[N:8]=[C:7]2[C:3]=1[NH:4][C:5](=[O:20])[N:6]2[CH2:16][CH2:17][CH2:18]Cl.[NH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1>CS(C)=O>[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][CH2:14][CH3:15])[N:8]=[C:7]2[C:3]=1[NH:4][C:5](=[O:20])[N:6]2[CH2:16][CH2:17][CH2:18][N:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: CCCCOc1nc(N)c2[nH]c(=O)n(CCCCl)c2n1
Reactant: C1CCNC1
Solvent: CS(C)=O
Product: CCCCOc1nc(N)c2[nH]c(=O)n(CCCN3CCCC3)c2n1
Temperature: 25 °C
Reaction time: 16 h
Yield: 26.3 %

Procedure:
The product from step (vii) (0.15 g) was dissolved in DMSO (2 mL) and pyrrolidine (0.18 g) was added. The reaction mixture was stirred at rt for 16 h. The reaction mixture was filtered through a filter disc and purified via RP-prep-HPLC to give title compound (0.044 g).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[N:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[H-].[Na+].Br[CH:16]([CH3:22])[C:17]([O:19][CH2:20][CH3:21])=[O:18].O>CN(C=O)C>[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[N:9][N:10]2[CH:16]([CH3:22])[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc2cn[nH]c2c1
Reactant: CCOC(=O)C(C)Br
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)n1ncc2ccc([N+](=O)[O-])cc21

Procedure:
6-Nitroindazole (10 g) was dissolved in dry DMF (200cm3) and 50% sodium hydride (2.94 g) added portionwise with stirring. After 20 minutes ethyl 2-bromopropionate (8cm3) was added and the mixture stirred at room temperature for 4 hours, poured into water (1L) and extracted with ethyl acetate four times. The combined organic extracts were washed with water, dried (MgSO4), filtered and the filtrate concentrated under vacuum. The residue was purified by chromatography (SiO2 ; hexane: t-butylmethyl ether, 7:3) to give ethyl 2-(6-nitroindazol-1-yl)propionate (1.3 g) m.p. 99.7°-100.1° C.; M+ =263;
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]1[CH:11]=[CH:12][C:13]([O:17][CH3:18])=[C:14]([NH2:16])[CH:15]=1.[C:19]([C:22]1[CH:27]=[CH:26][C:25]([N:28]=[C:29]=[S:30])=[CH:24][CH:23]=1)([OH:21])=[O:20]>O1CCCC1>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]1[CH:11]=[CH:12][C:13]([O:17][CH3:18])=[C:14]([NH:16][C:29](=[S:30])[NH:28][C:25]2[CH:24]=[CH:23][C:22]([C:19]([OH:21])=[O:20])=[CH:27][CH:26]=2)[CH:15]=1
Reactant: COc1ccc(-c2cc3ccccc3[nH]2)cc1N
Reactant: O=C(O)c1ccc(N=C=S)cc1
Solvent: C1CCOC1
Product: COc1ccc(-c2cc3ccccc3[nH]2)cc1NC(=S)Nc1ccc(C(=O)O)cc1

Procedure:
The product from Example 1, Step B, 5-(1H-indol-2-yl)-2-methoxy-phenylamine (0.286 g, 1.0 mmol) was mixed with 4-carboxyphenyl isothiocyanate (0.185 g, 1.03 mmol) in tetrahydrofuran (40 mL). The solvent was boiled off on the rotary evaporator (no vacuum), and ethyl acetate was added to the residue and the insoluble material was collected by filtration. The collected solid was taken up in tetrahydrofuran, concentrated to dryness, and triturated again with ethyl acetate to give the product as a white solid (0.180 g), mp 201-203° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH:9]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH:10]=[CH:11][C:12]([O:14][CH3:15])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>CO.[Pd]>[C:1]([O:5][C:6]([NH:8][CH:9]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)C=CC(NC(=O)OC(C)(C)C)c1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: COC(=O)CCC(NC(=O)OC(C)(C)C)c1ccccc1
Reaction time: 2 h

Procedure:
To a solution of methyl 4-[(t-butoxycarbonyl)-amino]-4-phenylbut-2-enoate (3.17 g) in methanol (100 mL) was added palladium on carbon (250 mg (10% by wt. Pd)). The mixture was then placed under 50 psig hydrogen gas, and was shaken on a Parr hydrogenator for 2 hours. The mixture was then filtered through celite, concentrated in vacuo and purified by silica gel flash chromatography (3:1 hexanes:ethyl acetate) to afford methyl 4-[(t-butoxycarbonyl)-amino]-4-phenylbutanoate as a pale yellow oil in a yield of 2.61 g (82%). 1H NMR (CDCl3) δ 1.45 (s, 9H), 2.07 (m, 2H), 2.36 (m, 2H), 3.69 (s, 3H), 4.59 (m, 1H), 5.15 (br s, 1H (NH)), 7.21-7.34 (m, 5H).
Reaction SMILES: [NH2:1][C:2]1[C:7]2=[C:8]([C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26]4[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=4[F:36])=[O:24])=[CH:18][CH:17]=3)[C:9]([CH2:13][O:14][CH3:15])=[C:10]([CH:11]=O)[N:6]2[N:5]=[CH:4][N:3]=1.[NH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(Cl)Cl>[NH2:1][C:2]1[C:7]2=[C:8]([C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26]4[CH:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[CH:28][C:27]=4[F:36])=[O:24])=[CH:18][CH:17]=3)[C:9]([CH2:13][O:14][CH3:15])=[C:10]([CH2:11][N:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)[N:6]2[N:5]=[CH:4][N:3]=1
Reactant: COCc1c(-c2ccc(NC(=O)Nc3cc(C(F)(F)F)ccc3F)cc2)c2c(N)ncnn2c1C=O
Reactant: C1COCCN1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(Cl)Cl
Product: COCc1c(-c2ccc(NC(=O)Nc3cc(C(F)(F)F)ccc3F)cc2)c2c(N)ncnn2c1CN1CCOCC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 45.3 %

Procedure:
To a suspension of Intermediate AW (N-{4-[4-amino-7-formyl-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoro-methyl)phenyl]urea (50 mg, 0.1 mmol)) and morpholine (0.01 ml, 0.12 mmol) in dichloroethane (3 ml) was added sodium triacetoxyborohydride (67 mg, 0.31 mmol). The reaction was stirred under N2 at rt for 16 h. The reaction mixture was diluted with CH2Cl2 and subsequently quenched with aqueous saturated NaHCO3. The organic phase was collected, dried (Na2SO4), concentrated and purified via column chromatography (95:5 v/v CH2Cl2-MeOH) to afford 26 mg of the title compound (yield 46%). 1H-NMR (DMSO-d6) 9.32 (s, 1H), 8.96 (d, J=2 Hz, 1H), 8.64 to 8.61 (dd, J=8, 2 Hz, 1H), 7.90 (s, 1H), 7.59 to 7.34 (m, 6H), 4.29 (s, 2H), 3.86 (s, 2H), 3.55 to 3.50 (m, 4H), 3.14 (s, 3H), 2.47-2.41 (m, 4H); MS [M+H]+=573.9; LCMS RT=2.53 min.
Reaction SMILES: [CH2:1]([SnH2:5][CH2:6][CH2:7][CH2:8][CH3:9])[CH2:2][CH2:3][CH3:4].[C:10]([O:13][CH:14]=[CH2:15])(=[O:12])[CH3:11]>C1CCCCC1>[C:10]([O:13][CH2:14][CH2:15][Sn:5]([CH2:15][CH2:14][O:13][C:10](=[O:12])[CH3:11])([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:1][CH2:2][CH2:3][CH3:4])(=[O:12])[CH3:11]
Reactant: CCCC[SnH2]CCCC
Reactant: C=COC(C)=O
Solvent: C1CCCCC1
Product: CCCC[Sn](CCCC)(CCOC(C)=O)CCOC(C)=O

Procedure:
2.349 g (0.01 mole) of dibutyltin dihydride, 1.722 g (0.02 mole) of distilled vinyl acetate and 2 g of anhydrous cyclohexane were introduced into a Pyrex® vessel thermostated at 25° C. The solution was exposed to ultraviolet rays for 3 hours. The cyclohexane was then removed under vacuum at ambient temperature. The expected product was obtained pure in quantitative yield.
Reaction SMILES: [H-].[Li+].[Cl:3][C:4]1[CH:21]=[CH:20][C:7]([NH:8][C:9]2[S:10][C:11]3[N:19]=[CH:18][CH:17]=[CH:16][C:12]=3[C:13](=[O:15])[N:14]=2)=[CH:6][CH:5]=1.Cl[CH2:23][C:24](=[O:26])[CH3:25]>CN(C=O)C>[Cl:3][C:4]1[CH:21]=[CH:20][C:7]([N:8]=[C:9]2[N:14]([CH2:23][C:24](=[O:26])[CH3:25])[C:13](=[O:15])[C:12]3[CH:16]=[CH:17][CH:18]=[N:19][C:11]=3[S:10]2)=[CH:6][CH:5]=1
Reactant: CC(=O)CCl
Reactant: O=c1nc(Nc2ccc(Cl)cc2)sc2ncccc12
Agent: [H-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: CC(=O)Cn1c(=Nc2ccc(Cl)cc2)sc2ncccc2c1=O
Reaction time: 0.05 h
Yield: 50.3 %

Procedure:
In an atmosphere of argon, a mixture of 26 mg (3.3 mmol) of lithium hydride and 5 ml of DMF was put in a 100 ml flask. To the flask was then connected a dropping funnel which contained 800 mg (2.8 mmol) of 2-(4-chloroanilino)-4H-pyrido[3,2-e]-1,3-thiazin-4-one and 10 ml of DMF. The solution of 2-(4-chloroanilino)-4H-pyrido[3,2-e]-1,3-thiazin-4-one was then added dropwise to the aforementioned mixture with stirring in 3 minutes. The mixture was further stirred for 30 minutes. To the mixture was then added a mixture of 332 mg of chloroacetone and 2 ml of DMF. The mixture was then stirred for 8 hours. After the termination of reaction, the mixture was concentrated under reduced pressure. The resulting residue was then extracted with water and ethyl acetate. The resulting organic phase was separated, washed with water and saturated brine, and then dried over sodium sulfate. The drying agent was then removed by filtration. The filtrate was then concentrated under reduced pressure. The resulting residue was then purified through silica gel column chromatography (eluant: 1/1 mixture of ethyl acetate and normal hexane). As a result, 487 mg of 2-[(4-chlorophenyl)imino]-2,3-dihydro-3-(2-oxopropyl)-4H-pyrido[3,2-e]-1,3-thiazin-4-one was obtained as a low polarity substance, and 267 mg of 2-[N-(4-chlorophenyl)-N-(2-oxopropyl)amino]-4H-pyrido[3,2-e]-1,3-thiazin-4-one was obtained as a high polarity substance. 1) 2-[(4-Chlorophenyl)imino]-2,3-dihydro-3-(2-oxopropyl)-4H-pyrido[3,2-e]-1,3-thiazin-4-one
Reaction SMILES: CC(C)([O-])C.[K+].[C:7]([OH:12])(=[O:11])[C:8]([CH3:10])=[CH2:9].[C:13](=[O:20])([O:16][CH:17](Cl)[CH3:18])[O:14][CH3:15]>CN(C=O)C.C1OCCOCCOCCOCCOCCOC1>[C:13](=[O:20])([O:16][CH:17]([O:11][C:7](=[O:12])[C:8]([CH3:10])=[CH2:9])[CH3:18])[O:14][CH3:15]
Reactant: COC(=O)OC(C)Cl
Reactant: C=C(C)C(=O)O
Agent: C1COCCOCCOCCOCCOCCO1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C=C(C)C(=O)OC(C)OC(=O)OC
Temperature: 25 °C
Reaction time: 72 h
Yield: 71.8 %

Procedure:
Potassium tert. butoxide (3.70 g, 0.033 mol ) was added to a solution of methacrylic acid (2.84 g, 0.033 mol) in DMF (100 ml). Methyl 1-chloroethyl carbonate (4.55 g, 0.033 mol) from Example 1u(i) above was added to the resulting suspension. 18-crown-6 (0.61 g, 2.3 mmol) was then added and the reaction mixture was left with stirring at room temperature for 3 days. The reaction mixture was filtered and the solvent was removed under reduced pressure. The residue was dissolved in chloroform (100 ml) and washed with saturated aqueous sodium hydrogen carbonate (50 ml) and water (50 ml). The organic phase was dried (MgSO4) and the solvent removed under reduced pressure. Flash chromatography gave 4.46 g (72%) of the title product.
Reaction SMILES: CS(C)=O.[H-].[Na+].[SH:7][CH2:8][CH2:9][OH:10].Br[CH2:12][CH2:13][C:14]([CH3:22])([CH3:21])[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17]>O>[OH:10][CH2:9][CH2:8][S:7][CH2:12][CH2:13][C:14]([CH3:21])([CH3:22])[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17]
Reactant: OCCS
Reactant: CCOC(=O)CC(C)(C)CCBr
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CCOC(=O)CC(C)(C)CCSCCO
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A mixture of 50 ml. dimethyl sulphoxide and 42.2 mmol sodium hydride is maintained at 80° C. for 45 minutes. It is then cooled to ambient temperature, 3.3 g. (42,2 mmol) 2-mercaptoethanol and then 10.0 g. (42,2 mmol) ethyl 5-bromo-3,3-dimethylpentanoate are added thereto and the reaction mixture is stirred for 3 hours at ambient temperature. It is then poured into water and extracted with diethyl ether. The ethereal phase is dried with anhydrous sodium sulphate and then evaporated. After chromatography of the residue on silica gel with a mixture of equal parts by volume of diethyl ether and cyclohexane, there are obtained 6.8 g. (70% of theory) of the desired product in the form of a colourless oil.
Reaction SMILES: [CH2:1]([NH:8][C:9]1[CH:10]=[C:11]([CH:14]=[C:15]([S:24](=[O:27])(=[O:26])[NH2:25])[C:16]=1[S:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:12][OH:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.OO.C(O)(=[O:32])C>O>[CH2:1]([NH:8][C:9]1[CH:10]=[C:11]([CH:14]=[C:15]([S:24](=[O:27])(=[O:26])[NH2:25])[C:16]=1[S:17]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:32])[CH2:12][OH:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(=O)O
Reactant: NS(=O)(=O)c1cc(CO)cc(NCc2ccccc2)c1Sc1ccccc1
Agent: OO
Solvent: O
Product: NS(=O)(=O)c1cc(CO)cc(NCc2ccccc2)c1S(=O)c1ccccc1
Reaction time: 24 h

Procedure:
A mixture of 3-benzylamino-4-phenylthio-5-sulfamylbenzyl alcohol (8.0 g; prepared as described in Example 24), hydrogen peroxide (10 ml, 30% in water) and acetic acid (80 ml) is stirred at 22°-25° C. for 24 hours. The resulting solution is diluted with water (40 ml) and cooled to precipitate crude 3-benzylamino-4-phenylsulfinyl-5-sulfamylbenzyl alcohol. After recrystallization from a mixture of ethanol and 2-methoxyethanol it is obtained with a melting point of 213°-214° C.
Reaction SMILES: C([O:5][C:6](=[O:41])[CH2:7][C:8]1([C:28]([O:30][CH:31]2[CH:36]([CH:37]([CH3:39])[CH3:38])[CH2:35][CH2:34][CH:33]([CH3:40])[CH2:32]2)=[O:29])[N:13]2[CH:14]=[CH:15][CH:16]=[C:12]2[C:11](=[O:17])[N:10]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][C:20]=2[F:26])[C:9]1=[O:27])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[Br:25][C:22]1[CH:23]=[CH:24][C:19]([CH2:18][N:10]2[C:9](=[O:27])[C:8]([C:28]([O:30][CH:31]3[CH:36]([CH:37]([CH3:39])[CH3:38])[CH2:35][CH2:34][CH:33]([CH3:40])[CH2:32]3)=[O:29])([CH2:7][C:6]([OH:41])=[O:5])[N:13]3[CH:14]=[CH:15][CH:16]=[C:12]3[C:11]2=[O:17])=[C:20]([F:26])[CH:21]=1
Reactant: CC1CCC(C(C)C)C(OC(=O)C2(CC(=O)OC(C)(C)C)C(=O)N(Cc3ccc(Br)cc3F)C(=O)c3cccn32)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC1CCC(C(C)C)C(OC(=O)C2(CC(=O)O)C(=O)N(Cc3ccc(Br)cc3F)C(=O)c3cccn32)C1

Procedure:
A mixture of 2-(4-bromo-2-fluorobenzyl)-4-(-)-menthyloxycarbonyl-1,3-dioxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-4-acetic acid tert-butyl ester (Diastereomer A) (30.0 g) and trifluoroacetic acid (112.5 g, 76.0 ml) in anhydrous dichloromethane (120 ml) was refluxed for 1.5 hours and concentrated under reduced pressure. The residue was dissolved in a mixture of acetonitrile and toluene. The resulting solution was evaporated under reduced pressure to give the title compound (Diastereomer A) (27.3 g, quantitative) as a brown oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:18]2[C:13](=[CH:14][C:15]([F:21])=[C:16](F)[C:17]=2[F:19])[C:12](=[O:22])[C:11]([C:23]([OH:25])=[O:24])=[CH:10]1.[NH2:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[CH2:32][NH:31][CH2:30]2.C1CCN2C(=NCCC2)CC1>CN(C=O)C>[NH2:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[CH2:32][N:31]([C:16]1[C:17]([F:19])=[C:18]3[C:13]([C:12](=[O:22])[C:11]([C:23]([OH:25])=[O:24])=[CH:10][N:9]3[C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])=[CH:14][C:15]=1[F:21])[CH2:30]2
Reactant: O=C(O)c1cn(-c2ccc(F)cc2F)c2c(F)c(F)c(F)cc2c1=O
Reactant: Nc1ccc2c(c1)CNC2
Solvent: C1CCC2=NCCCN2CC1
Solvent: CN(C)C=O
Product: Nc1ccc2c(c1)CN(c1c(F)cc3c(=O)c(C(=O)O)cn(-c4ccc(F)cc4F)c3c1F)C2
Yield: 20 %

Procedure:
178 mg of 1-(2,4-difluorophenyl)-6,7,8-trifluoro-1,4- dihydro-4-oxoquinoline-3-carboxylic acid, 81 mg of 5-aminoisoindoline, 137 mg of DBU, and 1.5 ml of anhydrous DMF were processed in the same manner as in Example 20 to produce 47 mg of the target compound.