Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N#N.C[O:4][C:5]1[CH:6]=[C:7]([C:15]2[C:16]([C:21]([NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]3[S:34][C:33]([CH2:35][C:36]([OH:38])=[O:37])=[CH:32][CH:31]=3)=[O:22])=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:8]=[C:9]([O:13]C)[C:10]=1[O:11]C.B(Br)(Br)Br.O>C(Cl)Cl>[OH:4][C:5]1[CH:6]=[C:7]([C:15]2[C:16]([C:21]([NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]3[S:34][C:33]([CH2:35][C:36]([OH:38])=[O:37])=[CH:32][CH:31]=3)=[O:22])=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:8]=[C:9]([OH:13])[C:10]=1[OH:11]
Reactant: COc1cc(-c2ccccc2C(=O)Nc2ccccc2-c2ccc(CC(=O)O)s2)cc(OC)c1OC
Agent: BrB(Br)Br
Agent: N#N
Solvent: O
Solvent: ClCCl
Product: O=C(O)Cc1ccc(-c2ccccc2NC(=O)c2ccccc2-c2cc(O)c(O)c(O)c2)s1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 19.7 %

Procedure:
(The following reaction is done in an anhydrous N2 atmosphere.) Dissolve (5-{2-[(3′,4′,5′-Trimethoxy-biphenyl-2-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid (86) (55 mg, 0.11 mmol) in anhydrous DCM (3.2 mL) at −78° C., add dropwise a 1M solution of BBr3 in DCM (730 μL, 0.73 mmol) and stir for additional 30 min at −78° C. After slowly warming up stir the reaction solution for additional 4 h at rt. Cool reaction mixture to 0° C., add dropwise water. Extract the mixture with EtOAc (3×), wash combined organic layer with brine and dry it with Na2SO4. Purify the crude product by preparative RP HPLC (gradient, water/CH3CN 95:5 to 5:95) to obtain (5-{2-[(3′,4′,5′-Trihydroxy-biphenyl-2-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid (87) (10 mg, 18%) as a yellow solid. 1H NMR (400 MHz, CD3OD): 3.88 (s, 2H); 6.50 (s, 2H); 6.66 (d, 1H, J=3.5 Hz); 6.93 (d, 1H, J=3.5 Hz); 7.23 (t; 1H, J=7.3 Hz); 7.35 (t, 1H, J=7.6 Hz); 7.38-7.46 (m, 3H); 7.50 (t, 1H, J=7.3 Hz); 7.62 (d, 1H, J=8.0 Hz); 7.84 (d, 1H, J=8.0 Hz).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2([CH3:23])[C:19](=[O:20])[C:18]3[C:13](=[CH:14][C:15](Cl)=[CH:16][CH:17]=3)[NH:12][C:11]2=[O:22])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:24][N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>>[CH3:23][C:10]1([C:7]2[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[C:19](=[O:20])[C:18]2[C:13](=[CH:14][C:15]([N:28]3[CH2:29][CH2:30][N:25]([CH3:24])[CH2:26][CH2:27]3)=[CH:16][CH:17]=2)[NH:12][C:11]1=[O:22]
Reactant: CN1CCNCC1
Reactant: CC1(c2ccc([N+](=O)[O-])cc2)C(=O)Nc2cc(Cl)ccc2C1=O
Product: CN1CCN(c2ccc3c(c2)NC(=O)C(C)(c2ccc([N+](=O)[O-])cc2)C3=O)CC1
Yield: 31 %

Procedure:
A mixture of 3-(4-nitro-phenyl)-7-chloro-3-methyl-1H-quinoline-2,4-dione (0.3 g, 0.90 mmol) and 1-methylpiperazine (3.0 mL) was heated at reflux temperature overnight. Excessive 1-methylpiperazine was removed by evaporation in vacuo. The residue was diluted with water (50 mL), and the resulting suspension was extracted with ethyl acetate (50 mL×3). The organic layer was washed with brine (50 ml×2), dried over anhydrous MgSO4, and concentrated under reduced pressure. The pure objective compound (0.11 g, 31%) was obtained as yellow solid by a flash column chromatography (CH2Cl2: MeOH=20:1): 1H NMR (200 MHz, CDCl3) δ 1.90 (s, 3H, CH3), 2.35 (s, 3H, NCH3), 2.50-2.55 (m, 4H, NCH2), 3.35-3.44 (m, 4H, NCH2), 6.13 (d, J=2.4 Hz, 1H, ArH), 6.64 (dd, J=9.2, 2.4 Hz, 1H, ArH), 7.52 (d, J=9.0 Hz, 2H, ArH), 7.82 (d, J=8.8 Hz, 1H, ArH), 8.15 (d, J=9.2 Hz, 2H, ArH); m.p. 150-151° C.; MS(EI) m/e 394 [M+].
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:15]2[O:14][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:12][C:11](=O)[C:10]=2[CH:9]=[CH:8][CH:7]=1)=[O:5])[CH3:2].COC1C=CC(P2SP(C3C=CC(OC)=CC=3)[S:32]2)=CC=1>C1(C)C=CC=CC=1>[C:16]1([C:13]2[O:14][C:15]3[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:7][CH:8]=[CH:9][C:10]=3[C:11](=[S:32])[CH:12]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CCOC(=O)c1cccc2c(=O)cc(-c3ccccc3)oc12
Reactant: COc1ccc(P2SP(c3ccc(OC)cc3)S2)cc1
Solvent: Cc1ccccc1
Product: CCOC(=O)c1cccc2c(=S)cc(-c3ccccc3)oc12
Temperature: 25 °C
Yield: 123.2 %

Procedure:
A solution of 4.0g of 8-ethoxycarbonyl-2-phenyl-4-oxo-4H-1-benzopyran (prepared as described in Da Re et al., Ber. 1962, 99 (1966)) and 3.55 g of 2,4-bis-(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane (Lawesson's reagent) in 68 ml of toluene was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature and evaporated to dryness in vacuo. The crude residue was rinsed with petroleum ether and filtered to give a solid. The material was purified by flash chromatography on silica gel, eluting with a petroleum ether - ethyl acetate gradient (9:1 to 7:3). Evaporation in vacuo of the collected fractions yielded 3.99 g of pure title compound, melting at 161°-163° C. after recrystallization from cyclohexane.
Reaction SMILES: [CH3:1][O:2][CH:3]1[C:8]([O:11][CH3:12])([O:9][CH3:10])[CH2:7][CH2:6][N:5](C(OCC)=O)[CH2:4]1.[OH-].[K+]>CC(O)C>[CH3:1][O:2][CH:3]1[C:8]([O:11][CH3:12])([O:9][CH3:10])[CH2:7][CH2:6][NH:5][CH2:4]1
Reactant: CCOC(=O)N1CCC(OC)(OC)C(OC)C1
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)O
Product: COC1CNCCC1(OC)OC
Temperature: 10 °C
Yield: 75.4 %

Procedure:
A mixture of 117.7 parts of ethyl 3,4,4-trimethoxy-1-piperidinecarboxylate, 267.3 parts of potassium hydroxide and 720 parts of 2-propanol was stirred and refluxed for 4 hours. The reaction mixture was evaporated. 900 Parts of water were added to the residue and the whole was stirred in a boiling water-bath. The last traces of 2-propanol were removed by evaporation on a Rotavapor. After cooling to 10° C., the product was extracted twice with 280 parts of 1,1'-oxybisethane. The extracts were dried, filtered and evaporated, yielding 62.9 parts (75.4%) of 3,4,4-trimethoxypiperidine as a residue (intermediate 65).
Reaction SMILES: [Si]([O:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([CH2:15][OH:16])[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.[Cl:17][C:18]1[CH:19]=[C:20]([S:25]([NH2:28])(=[O:27])=[O:26])[CH:21]=[CH:22][C:23]=1F.[H-].[Na+]>O1CCCC1>[Cl:17][C:18]1[CH:19]=[C:20]([S:25]([NH2:28])(=[O:26])=[O:27])[CH:21]=[CH:22][C:23]=1[O:16][CH2:15][C@H:12]1[CH2:11][CH2:10][C@H:9]([OH:8])[CH2:14][CH2:13]1
Reactant: NS(=O)(=O)c1ccc(F)c(Cl)c1
Reactant: CC(C)(C)[Si](C)(C)O[C@H]1CC[C@H](CO)CC1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: NS(=O)(=O)c1ccc(OC[C@H]2CC[C@H](O)CC2)c(Cl)c1
Reaction time: 1 h

Procedure:
(Trans-4-(tert-butyldimethylsilyloxy)cyclohexyl)methanol (275 mg, prepared according to a procedures in WO 2008/124878) and 3-chloro-4-fluorobenzenesulfonamide (259 mg) in tetrahydrofuran (15 mL) were treated with sodium hydride (180 mg, 60%) overnight. The reaction was quenched with water (1 mL) and trifluoroacetic acid (4 mL) was added. The resulting mixture was stirred for 1 hour and concentrated. The residue was triturated with water and methanol to provide the title compound.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[N:10]([CH2:11][CH2:12][N:13]([CH3:23])[C:14](=[O:22])[O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:9][CH2:8][S:7][C:6]=2[CH:24]=1.I.[S:26]1[CH:30]=[CH:29][CH:28]=[C:27]1[C:31](SC)=[NH:32]>C(O)C.O.C(=O)([O-])[O-].[Na+].[Na+]>[CH3:23][N:13]([CH2:12][CH2:11][N:10]1[CH2:9][CH2:8][S:7][C:6]2[CH:24]=[C:2]([NH:1][C:31]([C:27]3[S:26][CH:30]=[CH:29][CH:28]=3)=[NH:32])[CH:3]=[CH:4][C:5]1=2)[C:14](=[O:22])[O:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: CN(CCN1CCSc2cc(N)ccc21)C(=O)Oc1ccccc1
Reactant: CSC(=N)c1cccs1
Agent: I
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CN(CCN1CCSc2cc(NC(=N)c3cccs3)ccc21)C(=O)Oc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 68.3 %

Procedure:
To a stirred solution of phenyl 2-(7-amino-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethyl(methyl)carbamate (80 mg, 0.233 mmol) in ethanol (5 mL) under argon was added methyl thiophene-2-carbimidothioate hydroiodide (133 mg, 0.466 mmol). The mixture was then stirred overnight at room temperature. The mixture was then diluted with water and sodium carbonate and then extracted with dichloromethane (2×). The combined organics were dried, filtered, concentrated, and then chromatographed in ethyl acetate, yielding the desired product (72 mg, 68%). 1H NMR (DMSO-d6) δ 7.74-7.69 (m, 1H), 7.58-7.56 (m, 1H), 7.42-7.34 (m, 2H), 7.25-7.17 (m, 1H), 7.14-7.05 (m, 3H), 6.83-6.80 (m, 1H), 6.53-6.44 (m, 2H), 6.36 (brs, 2H), 3.63-3.55 (m, 4H), 3.49-3.45 (m, 2H), 3.11, 2.98 (2s, 3H), 3.06-3.01 (m, 2H); MS-EI: (m/z, %) 452 (M+, 97), 288 (100).
Reaction SMILES: C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[F:15][C:16]([F:31])([F:30])[C:17]1[O:21][N:20]=[C:19]([C:22]2[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=2)[CH:25]=O)[N:18]=1.[C:32]1([C:38]2[N:39]=[C:40]([C:43]3([CH2:49][NH2:50])[CH2:48][CH2:47][O:46][CH2:45][CH2:44]3)[S:41][CH:42]=2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>ClC(Cl)C>[C:32]1([C:38]2[N:39]=[C:40]([C:43]3([CH2:49][NH:50][CH2:25][C:24]4[CH:27]=[CH:28][CH:29]=[C:22]([C:19]5[N:18]=[C:17]([C:16]([F:31])([F:30])[F:15])[O:21][N:20]=5)[CH:23]=4)[CH2:44][CH2:45][O:46][CH2:47][CH2:48]3)[S:41][CH:42]=2)[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1
Reactant: NCC1(c2nc(-c3ccccc3)cs2)CCOCC1
Reactant: O=Cc1cccc(-c2noc(C(F)(F)F)n2)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(Cl)Cl
Product: FC(F)(F)c1nc(-c2cccc(CNCC3(c4nc(-c5ccccc5)cs4)CCOCC3)c2)no1
Temperature: 25 °C
Reaction time: 8 h
Yield: 21.6 %

Procedure:
Sodium triacetoxy borohydride (200 mg, 0.9 mmol) was added to a solution of 3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzaldehyde (140 mg, 0.6 mmol) and (4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)methanamine (170 mg, 0.6 mmol) in dry dichloroethane (20 mL) at 0° C. under nitrogen atmosphere and stirred at room temperature for 8 h. The reaction mixture was carefully quenched with 10% NaHCO3 solution and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluent 20-25% EtOAc in petroleum ether) to get 1-(4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)-N-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)methanamine (65 mg, yield 22%): 1H NMR (400 MHz, CDCl3) δ 7.98 (m, 2H), 7.89 (d, J=7.6 Hz, 2H), 7.48 (s, 1H), 7.46-7.27 (m, 5H), 3.86-3.81 (m, 4H), 3.69-3.64 (m, 2H), 2.91 (s, 2H), 2.36 (m, 2H), 2.03-1.97 (ddd, J=13.7 Hz, 9.7 Hz, 4 Hz, 2H). MS (ESI) m/z: Calculated for C25H23F3N4O2S: 500.15. found: 501.0 (M−H)−.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([CH2:12][N:13]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[N:17]([C:24](=[O:47])[C:25]3[CH:30]=[CH:29][C:28]([NH:31][C:32](=[O:46])[C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=4[C:39]4[CH:44]=[CH:43][C:42]([CH3:45])=[CH:41][CH:40]=4)=[CH:27][CH:26]=3)[CH2:16][CH2:15][C:14]2=[O:48])=[O:11])[CH2:6][CH2:5]1.C(N(CC)CC)C.[C:56](OC(=O)C)(=[O:58])[CH3:57]>ClCCl.CN(C)C1C=CN=CC=1>[C:56]([O:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([CH2:12][N:13]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[N:17]([C:24](=[O:47])[C:25]3[CH:30]=[CH:29][C:28]([NH:31][C:32](=[O:46])[C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=4[C:39]4[CH:44]=[CH:43][C:42]([CH3:45])=[CH:41][CH:40]=4)=[CH:27][CH:26]=3)[CH2:16][CH2:15][C:14]2=[O:48])=[O:11])[CH2:6][CH2:5]1)(=[O:58])[CH3:57]
Reactant: CC(=O)OC(C)=O
Reactant: Cc1ccc(-c2ccccc2C(=O)Nc2ccc(C(=O)N3CCC(=O)N(CC(=O)N4CCN(CCO)CC4)c4ccccc43)cc2)cc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)OCCN1CCN(C(=O)CN2C(=O)CCN(C(=O)c3ccc(NC(=O)c4ccccc4-c4ccc(C)cc4)cc3)c3ccccc32)CC1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 108.1 %

Procedure:
To a solution of 1-[[4-(2-hydroxyethyl)-1-piperazinyl]carbonylmethyl}-5-{4-[2-(4-methylphenyl)benzoylamino]benzoyl}-1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one (178 mg) and triethylamine (31 mg) in dichloromethane (4 ml) was added acetic anhydride (31 mg) and the mixture was stirred at ambient temperature for 1.5 hours. To the mixture was added 4-dimethylaminopyridine (10 mg) and acetic anhydride (10 mg), and then the mixture was stirred at ambient temperature for 15 minutes. The resulting mixture was diluted with dichloromethane and the organic layer was washed successively with saturated aqueous sodium bicarbonate solution and brine. Drying, filtering and the removal of solvents afforded a crude product. The crude product was triturated with a mixture of diethyl ether and n-hexane (1:1) to give 1-{[4-(2-acetoxyethyl)-1-piperazinyl]-carbonylmethyl)-5-{4-[2-(4-methylphenyl)benzoylamino]-benzoyl}-1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one (205 mg) as a slightly-yellow powder.
Reaction SMILES: N[C:2]1[C:3]2[C:27]3([CH2:31][CH2:30]OC3)[C:26](=[O:32])[NH:25][C:4]=2[N:5]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])[N:9]=2)[N:7]=1.N1CCCC[CH2:34]1>CC(C)=O.C(OCC)(=O)C>[F:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[CH2:17][N:10]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:16]2[C:8]([C:6]2[N:7]=[CH:2][C:3]3[C:27](=[C:31]([CH3:34])[CH3:30])[C:26](=[O:32])[NH:25][C:4]=3[N:5]=2)=[N:9]1
Reactant: Nc1nc(-c2nn(Cc3ccccc3F)c3ncccc23)nc2c1C1(CCOC1)C(=O)N2
Reactant: C1CCNCC1
Solvent: CCOC(C)=O
Solvent: CC(C)=O
Product: CC(C)=C1C(=O)Nc2nc(-c3nn(Cc4ccccc4F)c4ncccc34)ncc21

Procedure:
500 mg (1.388 mmol) of Example 4 were initially charged in acetone (50 ml), 0.274 ml (2.775 mmol) of piperidine was added and the mixture was heated under reflux for 1 h. After cooling, a precipitate was filtered off and washed with acetone, and the filtrate was concentrated under reduced pressure. This residue was then purified by chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate gradient). The material obtained in this manner was once more slurried in ethyl acetate, filtered off, washed with ethyl acetate and dried under high vacuum. This gave 101 mg of the title compound as a solid (18% of theory).
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:10][CH:9]=2)=[N:6][CH:7]=1.[CH2:23]([O:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[CH2:23]([O:30][C:31]1[CH:36]=[C:35]([C:2]2[CH:3]=[N:4][C:5]([C:8]3[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:10][CH:9]=3)=[N:6][CH:7]=2)[CH:34]=[CH:33][CH:32]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: OB(O)c1cccc(OCc2ccccc2)c1
Reactant: CCCCCCCCOc1ccc(-c2ncc(Br)cn2)cc1
Product: CCCCCCCCOc1ccc(-c2ncc(-c3cccc(OCc4ccccc4)c3)cn2)cc1

Procedure:
5-Bromo-2-(4-octyloxyphenyl)pyrimidine and 3-benzyloxybenzeneboronic acid are reacted analogously to Example 1 to give 5-(3-benzyloxyphenyl)-2-(4-octyloxyphenyl)pyrimidine. ##STR35## Removal of the benzyl protecting group from 5-(3-benzyloxyphenyl)-2-(4-octyloxyphenyl) pyrimidine by hydrogenation analogously to Example i gives 5-(3-hydroxyphenyl)-2-(4-octyloxyphenyl) pyrimidine. ##STR36##
Reaction SMILES: [Cl:1][C:2]1[CH:23]=[C:22]([CH3:24])[C:5]([O:6][C:7]2[C:12]([CH2:13]Cl)=[C:11]([NH:15][CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[CH:10]=[C:9]([CH3:21])[N:8]=2)=[C:4]([CH3:25])[CH:3]=1>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH3:25])[C:5]([O:6][C:7]2[C:12]([CH3:13])=[C:11]([NH:15][CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[CH:10]=[C:9]([CH3:21])[N:8]=2)=[C:22]([CH3:24])[CH:23]=1
Reactant: CCC(CC)Nc1cc(C)nc(Oc2c(C)cc(Cl)cc2C)c1CCl
Solvent: C1CCOC1
Product: CCC(CC)Nc1cc(C)nc(Oc2c(C)cc(Cl)cc2C)c1C
Reaction time: 0.08 h

Procedure:
To a solution of (2-(4-Chloro-2,6-dimethyl-phenoxy)-3-chloromethyl-6-methyl-pyridin-4-yl]-(1-ethyl-propyl)-amine (75 mg, 0.196 mmol) in dry THF was added 1.0M BH3 in THF (0.59 ml, 0.59 mmol) and stirred for 2 hr. The mixture was quenched with dilute HCl and stirred for 5 min. The reaction mixture was neutralized with 2N NaOH, water and extracted with ethyl acetate. The organic layer was separated, dried and concentrated to dryness. The residue was purified through silica gel column chromatography to give the title compound as a colorless oil.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][N:8]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[C:5]2=[N:6][CH:7]=1.C([Li])(C)(C)C.[CH3:26][C:27]([CH3:29])=[O:28].O>O1CCCC1>[CH:12]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[N:8]1[C:5]2=[N:6][CH:7]=[C:2]([C:27]([OH:28])([CH3:29])[CH3:26])[CH:3]=[C:4]2[CH:10]=[CH:9]1)([CH3:14])[CH3:13]
Reactant: CC(C)[Si](C(C)C)(C(C)C)n1ccc2cc(Br)cnc21
Reactant: CC(C)=O
Agent: [Li]C(C)(C)C
Solvent: O
Solvent: C1CCOC1
Product: CC(C)[Si](C(C)C)(C(C)C)n1ccc2cc(C(C)(C)O)cnc21
Temperature: -78 °C
Reaction time: 0.33 h

Procedure:
To 5-bromo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (2, 2.0 g, 5.66 mmol, prepared as described in Example 4) in tetrahydrofuran (20.0 mL), cooled in a −78° C. acetone/dry ice bath, under an atmosphere of nitrogen, was added tert-butyllithium (1.7 M in tetrahydrofuran, 7.3 mL, 12 mmol) dropwise. After 20 minutes, acetone (0.830 mL, 11 mmol) was added dropwise to the reaction. The reaction was stirred for 30 minutes at −78° C. and then allowed to reach room temperature. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 10% ethyl acetate in hexane to give the compound (9, 1.30 g, 69%). MS (ESI) [M+H+]+=333.
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.[SH:11][C:12]1[O:13][C:14]2[C:20]([C:21](OC)=[O:22])=[CH:19][CH:18]=[CH:17][C:15]=2[N:16]=1.Cl>C1(C)C=CC=CC=1.C1COCC1>[OH:22][CH2:21][C:20]1[C:14]2[O:13][C:12]([SH:11])=[N:16][C:15]=2[CH:17]=[CH:18][CH:19]=1
Reactant: COC(=O)c1cccc2nc(S)oc12
Agent: CC(C)C[Al+]CC(C)C
Agent: Cl
Agent: [H-]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: OCc1cccc2nc(S)oc12
Reaction time: 0.5 h
Yield: 93.6 %

Procedure:
A 1.0M solution of diisobutyl aluminum hydride in toluene (10 ml) was slowly dropped, under argon atmosphere at −78° C., into a solution of 2-mercapto-7-methoxycarbonylbenzoxazole (1.1 g, 5.0 mmol) in THF (20 ml) followed by stirring for 30 minutes. At that temperature, a 1.0M solution of diisobutyl aluminum hydride in toluene (5 ml) was slowly dropped thereinto followed by stirring for 30 minutes. After cooling, diluted hydrochloric acid was added to the reaction mixture to decompose the excessive diisobutyl aluminum hydride, after then extracted with ethyl acetate. The organic layer was washed with diluted hydrochloric acid solution and a saturated sodium chloride solution, dried over sodium sulfate and the solvent was evaporated therefrom. The resulting crude product was recrystallized from hexane-acetone-methanol to provide 848 mg (yield 94%) of 7-hydroxymethyl-2-mercaptobenzooxazole as colorless needles.
Reaction SMILES: [CH3:1][CH:2]([CH3:6])[C:3](=[O:5])[CH3:4].[C:7](#[N:10])[CH:8]=[CH2:9].Cl>>[CH3:1][C:2]([CH3:6])([C:3](=[O:5])[CH3:4])[CH2:9][CH2:8][C:7]#[N:10]
Reactant: C=CC#N
Reactant: CC(=O)C(C)C
Agent: Cl
Product: CC(=O)C(C)(C)CCC#N
Temperature: 35 °C
Reaction time: 18 h

Procedure:
A mixture of 40 g of 3-methyl-2-butanone and 2 g of Triton B was heated to 35° C., and 20 g of acrylonitrile was added to the mixture over a period of 1 hour. Then, the mixture was stirred for 18 hours, and hydrochloric acid was added to the mixture to make the mixture acidic and the mixture was extracted with ether.
Reaction SMILES: Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[O:4][C:3]=1[CH2:13][OH:14].[C:15]1([CH3:24])[CH:20]=[CH:19][CH:18]=[C:17](B(O)O)[CH:16]=1.C([O-])([O-])=O.[Cs+].[Cs+]>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>[OH:14][CH2:13][C:3]1[O:4][C:5](=[O:12])[C:6]2[C:11]([C:2]=1[C:17]1[CH:16]=[C:15]([CH3:24])[CH:20]=[CH:19][CH:18]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2
Reactant: O=c1oc(CO)c(Br)c2ccccc12
Reactant: Cc1cccc(B(O)O)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: Cc1cccc(-c2c(CO)oc(=O)c3ccccc23)c1
Yield: 40.2 %

Procedure:
The title compound was made in a similar way as that of the intermediate B2 using 4-bromo-3-(hydroxymethyl)-1H-isochromen-1-one (Intermediate A1, 0.5 g, 1.96 mmol), m-tolylboronic acid (0.400 g, 2.94 mmol), Pd(PPh3)4 (0.113 g, 0.098 mmol) and Cs2CO3 (0.64 g, 1.96 mmol) to afford the title compound (0.21 g, 40%).
Reaction SMILES: [C:1]([Si:5]([CH3:32])([CH3:31])[O:6][CH:7]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:8][CH2:9][CH2:10][C:11]([N:13]1[CH:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:16][O:15][C:14]1=[O:24])=[O:12])([CH3:4])([CH3:3])[CH3:2].[CH3:33][O:34][C:35]1[CH:51]=[CH:50][C:38]([CH:39]=[N:40][C:41]2[CH:46]=[CH:45][C:44]([N+:47]([O-:49])=[O:48])=[CH:43][CH:42]=2)=[CH:37][CH:36]=1.C(N(C(C)C)CC)(C)C.C[Si](Cl)(C)C.S([O-])(O)=O.[Na+]>C(O)(=O)C>[C:1]([Si:5]([CH3:32])([CH3:31])[O:6][CH:7]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:8][CH2:9][CH:10]([CH:39]([C:38]1[CH:50]=[CH:51][C:35]([O:34][CH3:33])=[CH:36][CH:37]=1)[NH:40][C:41]1[CH:42]=[CH:43][C:44]([N+:47]([O-:49])=[O:48])=[CH:45][CH:46]=1)[C:11]([N:13]1[CH:17]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:16][O:15][C:14]1=[O:24])=[O:12])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OC(CCCC(=O)N1C(=O)OCC1c1ccccc1)c1ccccc1
Reactant: COc1ccc(C=Nc2ccc([N+](=O)[O-])cc2)cc1
Agent: C[Si](C)(C)Cl
Agent: O=S([O-])O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(=O)O
Product: COc1ccc(C(Nc2ccc([N+](=O)[O-])cc2)C(CCC(O[Si](C)(C)C(C)(C)C)c2ccccc2)C(=O)N2C(=O)OCC2c2ccccc2)cc1
Temperature: -30 °C
Reaction time: 12 h
Yield: 74 %

Procedure:
To 5.4 g (12.0 mmol) of product 1 and 6.2 g (24 mmol) of product 2 in 135 ml of methylenehloride 8 ml of diisopropylethylamine is added at 10° C. and 4.8 ml of trimethylsilylchloride is added dropwise. After 1 h 14 ml of a 1 molar solution of titantetrachloride in methylenehloride is added dropwise at −10° C. It is stirred for 3 h at −10° C. and further 12 h at −30° C. stored without stirring. Afterwards 8 ml of acetic acid and 140 ml of a 7% aqueous solution of tartratic acid is added and it is stirred for further 2 h at room temperature. After addition of 50 ml of a 20% aqueous solution of sodiumhydrogensulfit it is stirred for another 1 h and extracted with methylenehloride. The organic phase is dried by magnesium sulfate, evaporated and purified by chromatography on silica gel/Ethylacetate/heptane=1/3->1/1. 6.3 g (74%) of product 3 is obtained in form of a light yellow solid compound: C40H47N3O7Si (709.92) MS (ESI+) 710 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]([F:15])([F:14])[C:10]([F:13])([F:12])[F:11])[C:5]([Cl:16])=[CH:4][C:3]=1[N+:17]([O-])=O>O1CCCC1.[Ni]>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]([F:14])([F:15])[C:10]([F:12])([F:13])[F:11])[C:5]([Cl:16])=[CH:4][C:3]=1[NH2:17]
Reactant: O=[N+]([O-])c1cc(Cl)c(OC(F)(F)C(F)(F)F)cc1Cl
Agent: [Ni]
Solvent: C1CCOC1
Product: Nc1cc(Cl)c(OC(F)(F)C(F)(F)F)cc1Cl

Procedure:
41 g of 2,5-dichloro-4-pentafluoroethoxynitrobenzene are dissolved in 410 ml of tetrahydrofuran and hydrogenated at room temperature for 32 hours in the presence of Raney nickel (H2 absorption: 7.62 l). The reaction mixture is filtered and concentrated and the residue is distilled. The title compound of formula ##STR13## is obtained in the form of a colourless liquid; b.p. 56°-61° C./0.04 torr.
Reaction SMILES: Br[C:2]1[CH:6]=[CH:5][O:4][CH:3]=1.[C:7]([C:10]1[N:11]=[C:12]([CH3:16])[O:13][C:14]=1[CH3:15])(=[O:9])[CH3:8]>>[CH3:16][C:12]1[O:13][C:14]([CH3:15])=[C:10]([C:7]([C:2]2[CH:6]=[CH:5][O:4][CH:3]=2)([OH:9])[CH3:8])[N:11]=1
Reactant: Brc1ccoc1
Reactant: CC(=O)c1nc(C)oc1C
Product: Cc1nc(C(C)(O)c2ccoc2)c(C)o1

Procedure:
Starting with 3-bromofuran and 4-acetyl-2,5dimethyloxazole and following the general method of Example 4 the title compound was prepared.