Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[C:7]([N:21]2[N:30]=[CH:29][C:28]3[C:23](=[C:24]([F:35])[CH:25]=[C:26]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH:27]=3)[C:22]2=[O:36])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16](Br)[C:15](=[O:19])[N:14]([CH3:20])[CH:13]=1)(=[O:3])[CH3:2].[N:37]1[N:38]2[CH2:45][CH2:44][CH2:43][C:39]2=[CH:40][C:41]=1[NH2:42].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[C:1]([O:4][CH2:5][C:6]1[C:7]([N:21]2[N:30]=[CH:29][C:28]3[C:23](=[C:24]([F:35])[CH:25]=[C:26]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH:27]=3)[C:22]2=[O:36])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:42][C:41]2[CH:40]=[C:39]3[CH2:43][CH2:44][CH2:45][N:38]3[N:37]=2)[C:15](=[O:19])[N:14]([CH3:20])[CH:13]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)OCc1c(-c2cc(Br)c(=O)n(C)c2)ccnc1-n1ncc2cc(C(C)(C)C)cc(F)c2c1=O
Reactant: Nc1cc2n(n1)CCC2
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: CC(=O)OCc1c(-c2cc(Nc3cc4n(n3)CCC4)c(=O)n(C)c2)ccnc1-n1ncc2cc(C(C)(C)C)cc(F)c2c1=O
Temperature: 25 °C
Yield: 41.8 %

Procedure:
A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with (4-(5-bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)pyridin-3-yl)methyl acetate 142c (166.2 mg, 0.30 mmol), 162c (24.6 mg, 0.20 mmol), cesium carbonate (130 mg, 0.40 mmol), and 1,4-dioxane (4.0 mL). After bubbling nitrogen through the suspension for 10 minutes, Xantphos (23 mg, 0.040 mmol) and tris(dibenzylideneacetone)dipalladium(0) (14 mg, 0.020 mmol) were added. The system was subjected to three cycles of vacuum/nitrogen flush and heated at reflux for 2.5 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (3×10 mL). The combined organic layer was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (100:1 to 50:1 to afford 162d (50 mg, 42%) as a yellow solid. MS-ESI: [M+H]+ 598.3
Reaction SMILES: [C:1]([CH:4]1[C:9](=O)[CH2:8][C:7]([CH3:12])([CH3:11])[CH2:6][C:5]1=[O:13])(=O)[CH3:2].[NH:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1)[NH2:15]>C(O)C>[N:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[N:14]1[C:9]2[CH2:8][C:7]([CH3:12])([CH3:11])[CH2:6][C:5](=[O:13])[C:4]=2[C:1]([CH3:2])=[N:15]1
Reactant: NNc1ccccn1
Reactant: CC(=O)C1C(=O)CC(C)(C)CC1=O
Solvent: CCO
Product: Cc1nn(-c2ccccn2)c2c1C(=O)CC(C)(C)C2
Temperature: 80 °C
Reaction time: 4 h

Procedure:
A mixture of 2-acetyl-5,5-dimethyl-cyclohexane-1,3-dione (0.5 g, 2.75 mmol), prepared as described in example 2, and 2-hydrazino-pyridine (0.3 g, 2.75 mmol) in ethanol (15 ml) was stirred at 80° C. for 4 hours. After evaporation of the solvent, the residue was chromatographed on silica gel (cyclohexane:ethyl acetate=10:20). The title compound was obtained as a colourless solid (0.5 g, 73%): m.p. 122-123° C.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7](OCC)(=[O:15])[CH2:8][CH2:9]/[CH:10]=[CH:11]/[CH2:12][CH:13]=[CH2:14].C=CC(O)CC=C>>[CH2:7]([OH:15])[CH2:8][CH2:9]/[CH:10]=[CH:11]/[CH2:12][CH:13]=[CH2:14]
Reactant: C=CC/C=C/CCC(=O)OCC
Agent: C=CCC(O)C=C
Agent: [Al+3]
Agent: [H-]
Product: C=CC/C=C/CCCO
Yield: 92 %

Procedure:
trans-4,7-Octadienol (bp 100°-102° C./20 mm) was prepared in 92% yield by lithium aluminum hydride reduction of ethyl trans-4,7-octadienoate, which was prepared in 87% yield via the Claisen orthoester rearrangement of 1,5-hexadien-3-ol by the method of Johnson et al., J. Am. Chem. Soc., 92, 741 (1970).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2[CH2:12][N:13]1[C:21]([C:22]2[N:23]([CH3:35])[CH:24]=[C:25]([NH:27]C(=O)OC(C)(C)C)[N:26]=2)=[C:20]2[C:15]([N:16]([CH2:39][CH:40]3[CH2:42][CH2:41]3)[C:17](=[O:38])[N:18]([CH3:37])[C:19]2=[O:36])=[N:14]1.C(O)(C(F)(F)F)=O>ClCCl>[NH2:27][C:25]1[N:26]=[C:22]([C:21]2[N:13]([CH2:12][C:5]3[C:4]4[C:9](=[CH:10][CH:11]=[C:2]([Cl:1])[CH:3]=4)[N:8]=[CH:7][CH:6]=3)[N:14]=[C:15]3[C:20]=2[C:19](=[O:36])[N:18]([CH3:37])[C:17](=[O:38])[N:16]3[CH2:39][CH:40]2[CH2:41][CH2:42]2)[N:23]([CH3:35])[CH:24]=1
Reactant: Cn1cc(NC(=O)OC(C)(C)C)nc1-c1c2c(=O)n(C)c(=O)n(CC3CC3)c2nn1Cc1ccnc2ccc(Cl)cc12
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cn1cc(N)nc1-c1c2c(=O)n(C)c(=O)n(CC3CC3)c2nn1Cc1ccnc2ccc(Cl)cc12

Procedure:
This compound was synthesized by treating tert-butyl 2-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-5-methyl-4,6-dioxo-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-d]pyrimidin-3-yl]-1-methyl-1H-imidazol-4-ylcarbamate with 10% TFA in dichloromethane at room temperature for 5 hours. Mass: 491.26 (M+H).
Reaction SMILES: [NH2:1][C:2]1[C:7]2[NH:8][CH:9]([CH2:12][OH:13])[CH2:10][O:11][C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:14](O)(=O)[CH3:15]>>[CH3:14][C:15]1[N:8]2[C:7]3[C:6]([O:11][CH2:10][CH:9]2[CH2:12][OH:13])=[CH:5][CH:4]=[CH:3][C:2]=3[N:1]=1
Reactant: Nc1cccc2c1NC(CO)CO2
Reactant: CC(=O)O
Product: Cc1nc2cccc3c2n1C(CO)CO3
Temperature: 95 °C
Reaction time: 8 h

Procedure:
(5-Amino-3,4-dihydro-2H-benzo[1,4]oxazin-3-yl)-methanol (11.8 g, 21.0 mmole) was dissolved in acetic acid (400 mL) and the resulting mixture was stirred at 95° C. overnight. After completion, the reaction was cooled to room temperature and solvent was removed under vacuum and replaced with methanol. Potassium carbonate (2 g) was added and the mixture stirred at room temperature for 1 hour. The solvent was removed and the residue partitioned between 400 mL each of methylene chloride and saturated aqueous sodium bicarbonate. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuum. The crude residue was column chromatographed on silica gel using first methylene chloride to remove impurities and then 5% methanol/methylene chloride to elute 2.34 g of the title compound. 1H NMR (DMSO-d6): δ 7.10 (d, 1H); 7.00 (t, 1H); 6.60 (d, 1H); 5.30 (t, 1H); 4.60 (d, 2H); 4.10 (dd, 1H); 3.60 (m, 2H); 2.50 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2.[CH3:13][N:14]([CH3:18])[C:15](Cl)=[O:16].C(N(CC)CC)C>C1C=CC=CC=1>[CH3:13][N:14]([CH3:18])[C:15](=[O:16])[NH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2
Reactant: Nc1ccc2c(c1)CCC(=O)N2
Reactant: CN(C)C(=O)Cl
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: CN(C)C(=O)Nc1ccc2c(c1)CCC(=O)N2

Procedure:
6-Amino-3,4-dihydrocarbostyril (1 g) is suspended in benzene (20 ml), and thereto is added dropwise a solution of N,N-dimethylcarbamoyl chloride (0.86 ml) in benzene (10 ml) at room temperature. The mixture is reacted at 50° C. for 3 hours, and thereto is added triethylamine (0.86 ml), and the mixture is further reacted at 50° to 60° C. for 5 hours. After the reaction, benzene is distilled off under reduced pressure, and water is added to the residue. The resulting precipitate is separated by filtration and washed with water. The crystal thus obtained is purified by silica gel column chromatography (solvent; chloroform:methanol=100:1) and then recrystallized from methanol-diethyl ether to give 6-(3,3-dimethylureido)-3,4-dihydrocarbostyril (0.6 g), as colorless prisms, m.p. 181°-183° C.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[C:7](I)[CH:6]=[CH:5][C:3]=1[NH2:4].[NH:10]1[CH:14]=[N:13][CH:12]=[N:11]1>CN(C=O)C.C(OCC)(=O)C.[Cu](I)I>[Cl:1][C:2]1[CH:8]=[C:7]([N:10]2[CH:14]=[N:13][CH:12]=[N:11]2)[CH:6]=[CH:5][C:3]=1[NH2:4]
Reactant: Nc1ccc(I)cc1Cl
Reactant: c1nc[nH]n1
Agent: I[Cu]I
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Nc1ccc(-n2cncn2)cc1Cl
Temperature: 25 °C
Reaction time: 72 h
Yield: 78 %

Procedure:
2-Chloro-4-iodoaniline (2 g, 7.9 mmol), 1,2,4-triazole (0.62 g, 9 mmol) and copper iodide (0.15 g, 0.79 mmol) in DMF (10 ml) were heated to 140° C. and stirred under dry nitrogen for 72 hours. The reaction was cooled to room temperature and diluted with ethyl acetate (50 ml). The organic layer was washed with water, brine, dried over sodium sulfate and filtered. The solvent was removed under vacuum and the residue purified by silica gel column chromatography eluting with 20% ethyl acetate in dichloromethane to give the title compound as a white powder (1.2 g, 78%). 1H-NMR (500 MHz, CDCl3): δ 4.43 (s, 2H), 6.76 (d, J=8.7 Hz, 1H), 7.23 (dd, J=2.5 Hz, 8.6 Hz, 1H), 7.48 (d, J=2.4 Hz, 1H), 7.94 (s, 1H), 8.36 (s, 1H).
Reaction SMILES: [I-].[CH3:2][N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2[S:13][CH:14]=[C:15]([C:17]3[CH:18]=[N+:19]([CH3:23])[CH:20]=[CH:21][CH:22]=3)[N:16]=2)=[CH:4]1.[BH4-].[Na+].[H][H].[ClH:28]>C(O)C.O>[ClH:28].[CH3:2][N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2[S:13][CH:14]=[C:15]([C:17]3[CH2:18][NH+:19]([CH3:23])[CH2:20][CH2:21][CH:22]=3)[N:16]=2)=[CH:4]1
Reactant: Cn1cc(-c2nc(-c3ccc[n+](C)c3)cs2)c2ccccc21
Reactant: [H][H]
Agent: Cl
Agent: [BH4-]
Agent: [I-]
Solvent: CCO
Solvent: O
Product: Cn1cc(-c2nc(C3=CCC[NH+](C)C3)cs2)c2ccccc21
Reaction time: 0.5 h

Procedure:
3-[2-(1-Methylindol-3-yl)-1,3-thiazol-4-yl]-1-methylpyridinium iodide (0.8 g) was suspended in ethanol (20 ml) and Water (1 ml). Sodium borohydride (0.1g) was added in portions with much evolution of hydrogen. After 30 minutes the intense yellow coloration was replaced by a light brown hue. 5M Hydrochloric acid was added dropwise to quench excess sodium borohydride. The contents of the flask were poured onto a saturated solution of sodium bicarbonate which was extracted with dichloromethane (4×150 ml). This was washed with brine, dried (MgSO4) and evaporated under reduced pressure. The residue was purified by column chromatography on silica using 10% methanol in dichloromethane as eluant yielding 0.4 g. This was further purified by dissolving in methanol; addition of methanolic HCl (20 ml) precipitated the hydrochloride as a yellow powder. This was recrystallised from aqueous ethanol, m.p. 235° C. (dec). δH 2.6-2.8 (2 H, m, β-pyr), 3.08 (3 H, s, NMe pyr), 3.16-3.28 (1 H, m, α-pyr), 3.65 (1 H, mc, γ-pyr), 3.74 (1 H, d, J=15.6 Hz, H-1 α-pyr), 4.14 (1 H, d, J=15.6 Hz, H-1 α-pyr), 6.53 (1 H, mc, H-4 γ-pyr), 7.09 (1 H, s, SCH), 7.23 and 7.30 (2 H, 2×t, J=7.9 Hz, H-5 and H-6), 7.37 (1 H, d, J=7.9 Hz), 7.53 (1 H, d, J=7.8 Hz), 7.75 (1 H, s, H-2); m/z 309 (M+ free base, 100%), 265 (40 ), 168 (40), 96 (35).
Reaction SMILES: [C:1]1([CH2:7][O:8][C:9](=[O:29])[NH:10][CH2:11][CH2:12][C:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[NH:15][C:14]=2[C:22]([CH3:28])([CH3:27])[CH:23]([OH:26])CO)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)=O.C(Cl)Cl.[O-]S([O-])(=O)=O.[Na+].[Na+]>O>[C:1]1([CH2:7][O:8][C:9](=[O:29])[NH:10][CH2:11][CH2:12][C:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[NH:15][C:14]=2[C:22]([CH3:27])([CH3:28])[CH:23]=[O:26])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)(c1[nH]c2ccccc2c1CCNC(=O)OCc1ccccc1)C(O)CO
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: ClCCl
Solvent: O
Product: CC(C)(C=O)c1[nH]c2ccccc2c1CCNC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of (±)-N-[2-[2-(2,3-dihydroxy-1,1-dimethylpropyl)-1H-indol-3-yl]ethyl]-carbamic acid phenylmethyl ester (0.323 g, 0.81 mol) in 1:1 acetone/CH2Cl2 (19.5 mL) was added NaIO4 (0.350 g, 1.64 mmol) in H2O (2.2 mL). The reaction mixture was stirred for 3 h at rt. Solid Na2SO4 was added. The mixture was filtered. The filtrate was extracted with CH2Cl2. The CH2Cl2 extracts were dried, filtered, and concentrated to an oil. This oil was purified by silica chromatography to give the title compound: TLC Rf=0.31 (1:1 heptane/EtOAc); MS (ESI+) m/z 365.2; 1H NMR (300 MHz, CDCl3) δ 9.56 (1H), 8.11 (1H), 7.64 (1H), 7.37 (5H), 7.21 (1H), 7.13 (1H), 5.14 (2H), 4.92 (1H), 3.45 (2H), 2.95 (2H), 1.60 (6H).
Reaction SMILES: [N+:1]([C:4]1[N:5]=[C:6]2[N:11]([CH:12]=1)[CH2:10][CH2:9][CH:8]([CH2:13][O:14][Si](C(C)C)(C(C)C)C(C)C)[O:7]2)([O-:3])=[O:2].Cl.C(=O)=O.CC(C)=O.N>CCO.CO>[N+:1]([C:4]1[N:5]=[C:6]2[N:11]([CH:12]=1)[CH2:10][CH2:9][CH:8]([CH2:13][OH:14])[O:7]2)([O-:3])=[O:2]
Reactant: CC(C)[Si](OCC1CCn2cc([N+](=O)[O-])nc2O1)(C(C)C)C(C)C
Agent: Cl
Agent: N
Agent: O=C=O
Solvent: CCO
Solvent: CC(C)=O
Solvent: CO
Product: O=[N+]([O-])c1cn2c(n1)OC(CO)CC2
Temperature: 25 °C
Reaction time: 35 h
Yield: 96.1 %

Procedure:
A suspension of silyl ether 133 (1.627 g, 4.58 mmol) in a solution of 1% HCl in 95% EtOH (desilylation conditions described by Cunico et al., 1980) (58 mL) was stirred at room temperature for 35 h. The resulting solution was cooled (CO2/acetone), neutralised by dropwise addition of 7 M NH3 in MeOH (7 mL) with stirring, and then concentrated to dryness and the residue was chromatographed on silica gel. Elution with 0-2% MeOH/CH2Cl2 firstly gave foreruns, and then further elution with 2% MeOH/CH2Cl2 gave (2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-7-yl)methanol (134) (877 mg, 96%) as a pale yellow solid: mp (THF/MeOH/CH2Cl2/hexane) 179-181° C.; 1H NMR [(CD3)2SO] δ 8.04 (s, 1H), 5.12 (t, J=5.8 Hz, 1H), 4.48 (dtd, J=10.2, 4.7, 2.5 Hz, 1H), 4.13 (ddd, J=12.5, 5.8, 3.0 Hz, 1H), 4.04 (ddd, J=12.4, 11.0, 5.1 Hz, 1H), 3.64 (m, 2H), 2.18 (dtd, J=14.4, 5.0, 2.8 Hz, 1H), 2.03 (dtd, J=14.4, 10.6, 5.7 Hz, 1H). Anal. (C7H9N3O4) C, H, N.
Reaction SMILES: Cl.[F:2][C:3]([F:30])([F:29])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]1[CH:28]=[CH:27][C:23]([C:24](Cl)=[O:25])=[CH:22][CH:21]=1.C(Cl)Cl.[OH:34][CH:35]([CH2:40][CH3:41])[C:36]([O:38][CH3:39])=[O:37].CN(C)C>CCOCC>[F:2][C:3]([F:30])([F:29])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]1[CH:28]=[CH:27][C:23]([C:24]([O:34][CH:35]([C:36]([O:38][CH3:39])=[O:37])[CH2:40][CH3:41])=[O:25])=[CH:22][CH:21]=1
Reactant: O=C(Cl)c1ccc(NCCCCCCCCCCCCCCCC(F)(F)F)cc1
Reactant: CCC(O)C(=O)OC
Agent: CN(C)C
Agent: Cl
Solvent: CCOCC
Solvent: ClCCl
Product: CCC(OC(=O)c1ccc(NCCCCCCCCCCCCCCCC(F)(F)F)cc1)C(=O)OC
Temperature: 25 °C
Reaction time: 17 h

Procedure:
To a solution of 10.0 g. 4-[15-(trifluoromethyl)-pentadecylamino]benzoyl chloride hydrochloride in 200 ml. methylene chloride is added dropwise a solution of 3 g. methyl α-hydroxybutyrate and 5 g. trimethylamine in 100 ml. ether. After 17 hours stirring at room temperature, the precipitate is collected and washed with several portions of ether. The ether solution is washed with water, dried and evaporated to yield the product as a white solid.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4](=[S:6])[NH2:5].Cl[CH:13]([C:19]([CH3:21])=O)[C:14]([O:16][CH2:17][CH3:18])=[O:15]>C(O)C>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4]1[S:6][C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:19]([CH3:21])[N:5]=1
Reactant: CCOC(=O)C(Cl)C(C)=O
Reactant: NC(=S)c1c(F)cccc1F
Solvent: CCO
Product: CCOC(=O)c1sc(-c2c(F)cccc2F)nc1C
Reaction time: 0.5 h

Procedure:
To a solution of the compound prepared in Example 344 (50 g) in ethanol (250 mL) was added ethyl 2-chloroacetoacetate (42 mL) at room temperature. The mixture was heated to reflux for 12 hours, cooled and concentrated. The residue was stirred with hexane (250 mL) for 30 minutes, filtered and then washed with hexane (50 mL). The solid was dried to obtain the title compound (48.6 g) having the following physical data.
Reaction SMILES: C([O:3][C:4](=O)[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]([F:21])([F:20])[F:19])=[CH:13][CH:12]=2)=[N:7][C:6]=1[C:22]([F:25])([F:24])[F:23])C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[F:21][C:18]([F:19])([F:20])[O:17][C:14]1[CH:15]=[CH:16][C:11]([C:8]2[N:7]=[C:6]([C:22]([F:23])([F:24])[F:25])[C:5]([CH2:4][OH:3])=[CH:10][CH:9]=2)=[CH:12][CH:13]=1
Reactant: CCOC(=O)c1ccc(-c2ccc(OC(F)(F)F)cc2)nc1C(F)(F)F
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: OCc1ccc(-c2ccc(OC(F)(F)F)cc2)nc1C(F)(F)F

Procedure:
In analogy to the procedure described in example 43D], 6-(4-trifluoromethoxy-phenyl)-2-trifluoromethyl-nicotinic acid ethyl ester was treated with lithium aluminium hydride to give the title compound as colorless crystals.
Reaction SMILES: B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.Br[C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][CH:21]=1.CC([O-])=O.[K+].Br[C:36]1[CH:41]=[CH:40][C:39]([NH:42][C:43]2[S:44][C:45]3[CH:51]=[C:50]([F:52])[CH:49]=[CH:48][C:46]=3[N:47]=2)=[CH:38][CH:37]=1.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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>[F:52][C:50]1[CH:49]=[CH:48][C:46]2[N:47]=[C:43]([NH:42][C:39]3[CH:40]=[CH:41][C:36]([C:20]4[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][CH:21]=4)=[CH:37][CH:38]=3)[S:44][C:45]=2[CH:51]=1
Reactant: Fc1ccc2nc(Nc3ccc(Br)cc3)sc2c1
Reactant: COC(=O)c1ccc(Br)cc1
Agent: [Pd+2]
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CC(=O)[O-]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(-c2ccc(Nc3nc4ccc(F)cc4s3)cc2)cc1
Temperature: 80 °C
Yield: 17.7 %

Procedure:
A mixture of bis(pinacolato)diboron (0.35 g, 1.4 mmol), methyl 4-bromobenzoate (0.30 g, 1.4 mmol), palladium(II) acetate (0.01 g, 0.04 mmol), and KOAc (0.41 g, 4.2 mmol) in DMF (7.5 mL) was degassed with argon for 30 min at rt. The mixture was then heated at 80° C. for 4 h. After the mixture was cooled to rt, N-(4-bromophenyl)-6-fluoro-1,3-benzothiazol-2-amine (0.45 g, 1.4 mmol), tetrakis(triphenylphosphine)palladium(0) (0.05 g, 0.04 mmol), and saturated aqueous NaHCO3 (5 mL) were added. The mixture was heated at 85° C. overnight. Upon cooling to rt, the mixture was diluted with EtOAc. The combined organic phases were separated, dried over Na2SO4, and concentrated in vacuo. Purification by column chromatography (25% EtOAc in hexanes) yielded 0.094 g (18%) of the title compound. LC/MS m/z 379.3 (MH+); retention time 3.87 min. 1H NMR (400 MHz, CD3OD) δ 3.93 (s, 3H), 7.05 (t, 1H), 7.39-7.81 (m, 8H), 8.03 (d, 2H).
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@@H:9]([O:15]C(=O)C)[C@@H:8]([CH2:19][O:20]C(=O)C)[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34](/[CH:37]=[CH:38]/[CH2:39][C:40](O)=[O:41])=[CH:33][CH:32]=2)=[C:28]([CH:43]([CH3:45])[CH3:44])[NH:27][N:26]=1)(=O)C.[NH2:46][C:47]([CH3:52])([CH3:51])[C:48]([NH2:50])=[O:49].Cl.NCC(N)=O>>[C:48]([C:47]([NH:46][C:40]([CH2:39][CH2:38][CH2:37][C:34]1[CH:33]=[CH:32][C:31]([CH2:30][C:29]2[C:25]([O:24][C@@H:6]3[O:7][C@H:8]([CH2:19][OH:20])[C@H:9]([OH:15])[C@H:10]([OH:11])[C@H:5]3[OH:4])=[N:26][NH:27][C:28]=2[CH:43]([CH3:45])[CH3:44])=[CH:36][CH:35]=1)=[O:41])([CH3:52])[CH3:51])(=[O:49])[NH2:50]
Reactant: CC(C)(N)C(N)=O
Reactant: CC(=O)OC[C@H]1O[C@@H](Oc2n[nH]c(C(C)C)c2Cc2ccc(/C=C/CC(=O)O)cc2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@H]1OC(C)=O
Agent: Cl
Agent: NCC(N)=O
Product: CC(C)c1[nH]nc(O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)c1Cc1ccc(CCCC(=O)NC(C)(C)C(N)=O)cc1

Procedure:
The title compound was prepared in a similar manner to that described in Example 1 using 3-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyloxy)-4-({4-[(1E)-3-carboxyprop-1-enyl]-phenyl}methyl)-5-isopropyl-1H-pyrazole and 2-amino-2-methylpropionamide instead of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-({4-[(1E)-3-carboxyprop-1-enyl]-phenyl}methyl)-5-isopropyl-1H-pyrazole and glycinamide hydrochloride, respectively.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C@@H:7]([CH2:13][NH2:14])[CH2:6]2.C(=O)([O-])[O-].[K+].[K+].[CH2:21](Br)[CH:22]=[CH2:23]>CC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C@@H:7]([CH2:13][NH:14][CH2:23][CH:22]=[CH2:21])[CH2:6]2
Reactant: C=CCBr
Reactant: COc1cc2c(cc1OC)[C@@H](CN)C2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: C=CCNC[C@H]1Cc2cc(OC)c(OC)cc21
Reaction time: 60 h

Procedure:
To 3.9 g (20 mmol) of {[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}amine in 40 mL of acetone, at ambient temperature, there are added, all at once, 4.1 g (30 mmol/1.5 eq.) of potassium carbonate, and then there are quickly added dropwise 1.9 mL (22 mmol/1.1 eq.) of allyl bromide. Stirring is carried out at ambient temperature for 60 hours; the salts are then filtered off and the filtrate is concentrated. The residue (4.8 g) is chromatographed over 300 g of silica (eluant: dichloromethane/ethanol/ammonia: 98/2/0.2) to yield the desired product.
Reaction SMILES: [Si:1]([O:8][CH:9]1[CH2:13][C:12]([CH3:15])([OH:14])[C:11]([CH2:16][CH:17]=[CH2:18])=[CH:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.[CH3:28][O:29][CH2:30]Cl.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)(Cl)Cl>[Si:1]([O:8][CH:9]1[CH2:13][C:12]([CH3:15])([O:14][CH2:28][O:29][CH3:30])[C:11]([CH2:16][CH:17]=[CH2:18])=[CH:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]
Reactant: COCCl
Reactant: C=CCC1=CC(O[Si](C)(C)C(C)(C)C)CC1(C)O
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClC(Cl)Cl
Product: C=CCC1=CC(O[Si](C)(C)C(C)(C)C)CC1(C)OCOC
Yield: 82 %

Procedure:
To a solution mixture of 4.7 g of (1RS,4RS)-3-allyl-4-methyl-4-hydroxy-2-cyclopenten-1-yl (t-butyldimethylsilyl) ether, 6.8 g of N,N-diisopropylethylamine and 50 ml of chloroform was added 2.66 ml of chloromethyl methyl ether under ice-cooling and the resulting mixture was allowed to react at room temperature for 8 hours. Then the reaction liquid was poured into ice-cooled 5% aqueous solution of citric acid and extracted two times with diethyl ether. The combined ether layer was washed successively with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue thus obtained was subjected to silica gel column chromatography to obtain 4.5 g of (1RS,4RS)-3-allyl-4-methyl-4-methoxymethoxy-2-cyclopenten-1-yl (t-butyldimethylsilyl) ether. Yield 82%
Reaction SMILES: C(ONC(N)=N)CC.C(OC([N:16]([O:27][CH2:28][CH2:29][CH2:30][O:31][C:32]1[CH:37]=[C:36]([CH3:38])[CH:35]=[C:34]([O:39][S:40]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[S:49]([N:52]([CH2:59][CH2:60][C:61]#[N:62])[CH2:53][C:54]2[O:55][CH:56]=[CH:57][CH:58]=2)(=[O:51])=[O:50])(=[O:42])=[O:41])[CH:33]=1)[C:17]([NH:19]C(OC(C)(C)C)=O)=[NH:18])=O)(C)(C)C.Cl.CO.C(C(=CC1C=CC(O)=CC=1)C(O)=O)#N>>[CH3:38][C:36]1[CH:35]=[C:34]([O:39][S:40]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[S:49]([N:52]([CH2:59][CH2:60][C:61]#[N:62])[CH2:53][C:54]2[O:55][CH:56]=[CH:57][CH:58]=2)(=[O:50])=[O:51])(=[O:41])=[O:42])[CH:33]=[C:32]([CH:37]=1)[O:31][CH2:30][CH2:29][CH2:28][O:27][NH:16][C:17]([NH2:19])=[NH:18]
Reactant: Cc1cc(OCCCON(C(=N)NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)cc(OS(=O)(=O)c2ccccc2S(=O)(=O)N(CCC#N)Cc2ccco2)c1
Agent: CCCONC(=N)N
Agent: Cl
Agent: N#CC(=Cc1ccc(O)cc1)C(=O)O
Solvent: CO
Product: Cc1cc(OCCCONC(=N)N)cc(OS(=O)(=O)c2ccccc2S(=O)(=O)N(CCC#N)Cc2ccco2)c1
Yield: 42 %

Procedure:
3-5-methyl-3-(2-(N-(2-cyanoethyl)-N-(2-furanylmethyl)aminosulfonyl)phenylsulfonyloxy)phenoxy]propoxyguanidine: The title compound was prepared in 42% yield from N,N′-bis-(tert-butoxycarbony)-3-[5-methyl-3-(2-(N-(2-cyanoethyl)-N-(2-furanylmethyl)aminosulfonyl)phenylsulfonyloxy)phenoxy]propoxyguanidine, as prepared in the previous step, in a manner analogous to step i of Example 20 (without HCl-methanol acidification). 1H NMR (300 MHz, CDCl3) δ 8.23 (dd, 1H, J=7.9, 1.3 Hz), 8.14 (dd, 1H, J=7.9, 1.4 Hz), 7.76 (td, 1H, J=7.7, 1.4 Hz), 7.67 (td, 1H, J=7.7, 1.3 Hz), 7.29 (t, 1H, J=1.3 Hz), 6.56 (m, 2H), 6.51 (m, 1H), 6.28 (m, 2H), 4.61 (s, 2H), 3.91 (m, 4H), 3.62 (t, 2H, J=7.1 Hz), 2.53 (t, 2H, J=7.1 Hz), 2.20 (s, 3H), 2.00 (pentet, 2H, J=6.1 Hz). Mass spectrum (MALDI-TOF, α-cyano-4-hydroxycinnamic acid matrix) calcd. for C25H29N5O8S2: 592.2 (M+H), 614.1 (M+Na). Found: 592.2, 614.4.