Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([Si:5](Cl)([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].[OH:9][CH2:10][CH:11]([CH3:21])[O:12][C:13]1[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=1[CH:15]=[O:16].CCN(C(C)C)C(C)C.N1C=CN=C1>O1CCOCC1>[C:1]([Si:5]([CH3:7])([CH3:6])[O:9][CH2:10][CH:11]([CH3:21])[O:12][C:13]1[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=1[CH:15]=[O:16])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CC(CO)Oc1ccccc1C=O
Agent: c1c[nH]cn1
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: CC(CO[Si](C)(C)C(C)(C)C)Oc1ccccc1C=O
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 59.9 %

Procedure:
Tert-butyl-chloro-dimethyl-silane (649 mg; 4.3 mmol; 1.1 eq.) was added to a solution of 2-(2-hydroxy-1-methyl-ethoxy)-benzaldehyde (705 mg; 3.91 mmol; 1 eq.), DIEA (867 μL; 4.69 mmol; 1.2 eq.) and 1H-imidazole (27 mg; 0.39 mmol; 0.1 eq.) in 1,4-dioxane (20 mL) and the resulting mixture was stirred at room temperature for 10 minutes. After dilution with EA, the solution was washed with sat. aq. NH4Cl (3×), dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (20% to 50% EA in cyclohexane) to afford the title compound (690 mg, 60%) as a colourless oil. 1H NMR (300 MHz, DMSO-d6) δ 10.47-10.33 (m, 1H), 7.72-7.55 (m, 2H), 7.30 (d, J=8.5 Hz, 1H), 7.05 (t, J=7.5 Hz, 1H), 4.71 (d, J=4.2 Hz, 1H), 3.77 (dd, J=4.8, 2.1 Hz, 2H), 1.28 (d, J=6.2 Hz, 3H), 0.84-0.75 (m, 9H), 0.04-0.07 (m, 6H).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([CH:36]=[C:37]([C:39]([O:41]C)=[O:40])[CH:38]=1)[CH2:8][CH:9]([CH2:13][CH2:14][CH2:15][S:16]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:10]([OH:12])=[O:11])([CH3:4])([CH3:3])[CH3:2].C([SiH](C(C)C)C(C)C)(C)C.FC(F)(F)C(O)=O>ClCCl>[C:39]([C:37]1[CH:36]=[C:7]([CH2:8][CH:9]([CH2:13][CH2:14][CH2:15][SH:16])[C:10]([OH:12])=[O:11])[CH:6]=[C:5]([C:1]([CH3:3])([CH3:4])[CH3:2])[CH:38]=1)([OH:41])=[O:40]
Reactant: COC(=O)c1cc(CC(CCCSC(c2ccccc2)(c2ccccc2)c2ccccc2)C(=O)O)cc(C(C)(C)C)c1
Agent: CC(C)[SiH](C(C)C)C(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)(C)c1cc(CC(CCCS)C(=O)O)cc(C(=O)O)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 54.6 %

Procedure:
To a solution of 2-(3-tert-butyl-5-methoxycarbonyl-benzyl)-5-[(triphenylmethyl)thio]pentanoic acid XII (5.5 g, 9.7 mmol) in dichloromethane (30 mL) were added triisopropylsilane (2.4 mL, 11.6 mmol) and trifluoroacetic acid (10 mL), and the mixture was stirred at room temperature for 10 minutes. The solvent was removed under reduced pressure and the crude material was purified by silica gel chromatography (1% AcOH in Hexanes/EtOAc, 4:1) to afford 3-carboxy-5-(1,1-dimethylethyl)-alpha-(3-mercaptopropyl)-benzenepropanoic acid 49 (1.7 g, 5.3 mmol, 55%) as a white solid: 1H NMR (CD3OD) δ 1.3 (s, 9H), 1.5–1.8 (m, 4H), 2.4 (m, 2H), 2.6–2.7 (m, 1H), 2.8–2.9 (m, 1H), 2.9–3.0 (m, 1H), 7.5 (s, 1H), 7.7 (s, 1H), 7.8 (s, 1H); 13C NMR (CD3OD) δ 24.8, 31.7 (3C), 31.9, 32.9, 35.6, 39.5, 48.6, 125.7, 128.5, 131.6, 132.0, 140.9, 152.8, 170.3, 179.0. Anal. Calcd for C17H24O4S: C, 62.93; H, 7.46; S, 9.88. Found: C, 63.02; H, 7.36; S, 9.82.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[C:6]([NH2:11])[CH:5]=1)([O-:3])=[O:2].[C:12](O)(=O)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[K+].[Br-]>C(Cl)(Cl)Cl.CO>[C:13]1([C:12]2[NH:11][C:6]3[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:9]=[CH:8][C:7]=3[N:10]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Nc1ccc([N+](=O)[O-])cc1N
Reactant: O=C(O)c1ccccc1
Agent: [Br-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Solvent: CO
Product: O=[N+]([O-])c1ccc2nc(-c3ccccc3)[nH]c2c1
Yield: 70 %

Procedure:
Prepared from 4-nitrophenylenediamine and benzoic acid in a manner similar to that of Example 9b. Yield: 70%; Rf (9/1 chloroform/methanol): 0.45; IR (KBr): 3290, 1500, 1330, 1290 cm−1.
Reaction SMILES: [C:1]([N:11]1[CH2:13][C:12]1([CH3:15])[CH3:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[C:16]([CH:20]([C:22]([CH3:25])([CH3:24])[CH3:23])[OH:21])([CH3:19])([CH3:18])[CH3:17].B(F)(F)F.CCOCC.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:1]([NH:11][C:12]([CH3:14])([CH3:15])[CH2:13][O:21][CH:20]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:16]([CH3:19])([CH3:18])[CH3:17])([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]
Reactant: CC(C)(C)C(O)C(C)(C)C
Reactant: CC1(C)CN1C(=O)OCc1ccccc1
Agent: FB(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOCC
Product: CC(C)(COC(C(C)(C)C)C(C)(C)C)NC(=O)OCc1ccccc1
Reaction time: 8 h

Procedure:
N-Cbz-2,2-Dimethyl aziridine and di-t-butylmethanol are dissolved in CH2Cl2 at 0° C. under argon. Boron trifluoride etherate is added and the flask is stirred overnight. The contents are poured into saturated NaHCO3 and extracted with ethyl acetate. The organic layer is dried over MgSO4 and evaporated to yield N-Cbz-2-amino-2-methyl-1-[di-(t-butyl)-methoxy]propane.
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]1[CH:9]=[C:8]([F:10])[C:7]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[C:6]([C:16]#[CH:17])[CH:5]=1.[C:18]([C:22]1[N:27]=[CH:26][C:25]([CH:28]=[CH:29][C:30](O)=[O:31])=[C:24]([C:33]([F:36])([F:35])[F:34])[CH:23]=1)([CH3:21])([CH3:20])[CH3:19].CN1C(=O)CCC1>C1COCC1>[C:18]([C:22]1[N:27]=[CH:26][C:25]([CH:28]=[CH:29][C:30]([NH:2][CH2:3][C:4]2[CH:9]=[C:8]([F:10])[C:7]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[C:6]([C:16]#[CH:17])[CH:5]=2)=[O:31])=[C:24]([C:33]([F:36])([F:34])[F:35])[CH:23]=1)([CH3:21])([CH3:19])[CH3:20]
Reactant: C#Cc1cc(CN)cc(F)c1NS(C)(=O)=O
Reactant: CC(C)(C)c1cc(C(F)(F)F)c(C=CC(=O)O)cn1
Agent: Cl
Solvent: C1CCOC1
Solvent: CN1CCCC1=O
Product: C#Cc1cc(CNC(=O)C=Cc2cnc(C(C)(C)C)cc2C(F)(F)F)cc(F)c1NS(C)(=O)=O
Yield: 30.2 %

Procedure:
N-(4-Aminomethyl-2-ethynyl-6-fluoro-phenyl)-methanesulfonamide HCl salt (11.2 mg, 0.04 mmol) was reacted with 3-(6-tert-butyl-4-trifluoromethyl-pyridin-3-yl)-acrylic acid (1.0 eq, 11.0 mg) DMTMM (1.0 eq, 11.1 mg) and NMP (1.2 eq, 6 μl) in THF to give the title compound (6 mg, 30.2%) after purification by column chromatography (Hex/EtOAc=3/2).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:4][C:3]=1[OH:13].C(=O)([O-])[O-].[K+].[K+].I[CH2:21][CH3:22].O>CN(C)C=O.C(OCC)(=O)C>[CH2:21]([O:13][C:3]1[CH:4]=[CH:5][C:6]([O:8][C:9]([F:11])([F:12])[F:10])=[CH:7][C:2]=1[Br:1])[CH3:22]
Reactant: CCI
Reactant: Oc1ccc(OC(F)(F)F)cc1Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOc1ccc(OC(F)(F)F)cc1Br
Temperature: 25 °C

Procedure:
2-Bromo-4-trifluoromethoxyphenol (Description 11, 1 g) was dissolved in N,N dimethylformamide (12 ml) and potassium carbonate (1.07 g) was added. Iodoethane (0.78 ml) was added and the mixture was stirred at room temperature. Water (150 ml) and ethyl acetate were added and the layers were separated. The organic layer was washed with brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with hexane/EtOAc (100:0 increasing to 95:5) to give the title compound as a colourless oil (1.02 g). 1H NMR (250 MHz, CDCl3) δ1.47 (3 H, t, J 7.0 Hz), 4.09 (2 H, q, J 7.0 Hz), 6.85 (1 H, d, J 9.0 Hz), 7.11 (1 H, m), and 7.43 (1 H, m).
Reaction SMILES: [F:1][C:2]([F:42])([F:41])[C:3]1[CH:4]=[C:5]([CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21](O)=[O:22])=[CH:17][CH:16]=2)[CH2:10][C@H:9]1[CH2:24][C:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[NH:27][CH:26]=1)=[O:7].Cl.[CH2:44]([NH:46][CH2:47][CH3:48])[CH3:45].CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(=O)(O)[O-].[Na+]>ClCCl>[F:42][C:2]([F:41])([F:1])[C:3]1[CH:4]=[C:5]([CH:34]=[C:35]([C:37]([F:38])([F:40])[F:39])[CH:36]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]([N:46]([CH2:47][CH3:48])[CH2:44][CH3:45])=[O:22])=[CH:17][CH:16]=2)[CH2:10][C@H:9]1[CH2:24][C:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[NH:27][CH:26]=1)=[O:7]
Reactant: CCNCC
Reactant: O=C(O)c1ccc(CN2CCN(C(=O)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)[C@H](Cc3c[nH]c4ccccc34)C2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])O
Solvent: ClCCl
Product: CCN(CC)C(=O)c1ccc(CN2CCN(C(=O)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)[C@H](Cc3c[nH]c4ccccc34)C2)cc1
Reaction time: 5 h
Yield: 65.2 %

Procedure:
To a stirred mixture of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-(4-carboxybenzyl)-2-(1H-indol-3-ylmethyl)piperazine (150 mg) and diethylamine hydrochloride (28 mg) in dry dichloromethane (5 ml) were added a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (40 mg) in dichloromethane (1ml) and 1-hydroxybenzotriazole (34 mg) at room temperature. After 5 hours, the reaction mixture was poured into aqueous sodium bicarbonate solution (20 ml). The organic layer was separated and washed with brine and dried over magnesium sulfate. The crude product obtained was purified by column chromatography on silica gel using ethyl acetate-n-hexane (4:1) to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-(N,N-diethylaminocarbonyl)benzyl]-2-(1H-indol-3-ylmethyl)piperazine (107 mg) as a powder.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@:12]([CH2:14][O:15]C(=O)CCCCC)([CH3:13])[CH2:11][O:10][C:9]1([CH3:24])[CH3:23])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>ClCCl>[C:1]([O:5][C:6]([N:8]1[C@:12]([CH2:14][OH:15])([CH3:13])[CH2:11][O:10][C:9]1([CH3:24])[CH3:23])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCCCCC(=O)OC[C@@]1(C)COC(C)(C)N1C(=O)OC(C)(C)C
Agent: CC(C)C[Al+]CC(C)C
Agent: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: [H-]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1C(C)(C)OC[C@]1(C)CO
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 100 %

Procedure:
3-t-Butoxycarbonyl-2,2-dimethyl-(4R)-n-hexanoyloxymethyl-4-methyloxazolidine (13.7 g, 39.9 mmol) obtained in Reference example 2(a) was dissolved in dichloromethane (200 ml), and the hexane solution of 1.0M diisobutylaluminium hydride (99 ml, 99.7 mmol) was added dropwise thereto at −78° C. After, the reaction mixture was stirred for 30 minutes at −78° C., cooled down to room temperature, and 10 wt % aqueous potassium sodium tartrate solution (200 ml) was added thereto followed by stirring vigorously for 30 minutes. The reaction solution was extracted with diethyl ether, and after the ether layer was dried over anhydrous sodium sulfate, the solvent was evaporated in vacuo. The residue was purified by flash chromatography on a silica gel column (elution solvent; n-hexane:ethyl acetate=5:2) to afford the title compound (10.5 g, 100% yield) as a white crystalline solid.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:14](=[O:15])[CH:13]=[CH:12]O[C:10]=1[CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:17][CH2:18][CH2:19][NH2:20].[OH-].[Na+].Cl>O.C(O)C>[CH2:1]([O:8][C:9]1[C:14](=[O:15])[CH:13]=[CH:12][N:20]([CH2:19][CH2:18][OH:17])[C:10]=1[CH3:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1occc(=O)c1OCc1ccccc1
Reactant: NCCO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Cc1c(OCc2ccccc2)c(=O)ccn1CCO
Temperature: 25 °C
Reaction time: 144 h

Procedure:
3-Benzyloxy-2-methyl-4-pyrone (4.8 g), prepared as described under Example 10, and 2-hydroxyethylamine (1.22 g) are dissolved in water (220 ml) and ethanol (100 ml) containing sodium hydroxide (2 g) is added. The mixture is stirred at room temperature for 6 days and is then acidified with concentrated hydrochloric acid to pH 2, and evaporated to dryness. The resulting colourless solid is washed with water and extracted into chloroform (2×50 ml). The chloroform extracts are combined, dried over magnesium sulphate, and evaporated to yield 3-benzyloxy-1-(2'-hydroxyethyl)-2-methylpyrid-4-one, as a white solid (3.4 g), m.p. 198°-199° C.
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH2:12][NH2:13])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[F:14][C:15]([F:26])([F:25])[C:16]1[CH:24]=[CH:23][CH:22]=[CH:21][C:17]=1[C:18](Cl)=[O:19].C(N(CC)CC)C.O>CCOCC.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([CH2:12][NH:13][C:18]([C:17]2[C:16]([C:15]([F:14])([F:25])[F:26])=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:19])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:7]=1
Reactant: NCc1ncc(C(F)(F)F)cc1Cl
Reactant: O=C(Cl)c1ccccc1C(F)(F)F
Solvent: CCN(CC)CC
Solvent: O
Solvent: CCOCC
Product: O=C(NCc1ncc(C(F)(F)F)cc1Cl)c1ccccc1C(F)(F)F
Reaction time: 8 h

Procedure:
A solution of (3-chloro-5-trifluoromethyl-2-pyridyl)methylamine (0.35 g) in dry ether (2 ml) was added to a solution of 2-trifluoromethylbenzoyl chloride (0.39 g) and triethylamine (0.27 ml) in dry ether (5 ml) and the mixture stirred overnight. Water (20 ml) and ethyl acetate (10 ml) were added and the organic phase was separated and washed with aqueous sodium hydrogen carbonate, dried and evaporated under reduced pressure. The residue was purified by silica gel chromatography to give the title product, m.p. 127-30° C.
Reaction SMILES: [OH:1][CH2:2][C:3]1[N:4]=[CH:5][N:6]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][N:20]([C:28]4[CH:32]=[CH:31][O:30][N:29]=4)C(OC(C)(C)C)=O)[O:16][C:15]3=[O:33])=[CH:10][C:9]=2[F:34])[CH:7]=1.FC(F)(F)C(O)=O>ClCCl>[O:30]1[CH:31]=[CH:32][C:28]([NH:20][CH2:19][C@@H:17]2[O:16][C:15](=[O:33])[N:14]([C:11]3[CH:12]=[CH:13][C:8]([N:6]4[CH:7]=[C:3]([CH2:2][OH:1])[N:4]=[CH:5]4)=[C:9]([F:34])[CH:10]=3)[CH2:18]2)=[N:29]1
Reactant: CC(C)(C)OC(=O)N(C[C@H]1CN(c2ccc(-n3cnc(CO)c3)c(F)c2)C(=O)O1)c1ccon1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1O[C@@H](CNc2ccon2)CN1c1ccc(-n2cnc(CO)c2)c(F)c1
Reaction time: 0.5 h
Yield: 66.9 %

Procedure:
3-(4-(4-Hydroxymethylimidazol-1-yl)-3-fluorophenyl)-5(R)-(N-(t-butoxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one (360 mg, 0.76 mM) was dissolved in dichloromethane (10 ml) and treated with trifluoroacetic acid (10 ml). After stirring for 30 minutes solvent was evaporated, the residue repeatedly evaporated to dryness with dichloromethane (3×10 ml), and the resulting gum dissolved in water (10 ml). The solution was made basic with concentrated aqueous ammonia, and the resulting precipitate filtered, washed with water and dried to give title product (190 mg).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][CH:18]=2)[O:12][CH2:13][C:14]#[N:15])[C:5]([Cl:19])=[CH:4][N:3]=1.[NH2:20][C:21]1[C:22]([O:34][CH3:35])=[CH:23][C:24]2[N:30]([CH3:31])[C:29](=[O:32])[O:28][CH2:27][CH2:26][C:25]=2[CH:33]=1>>[Cl:19][C:5]1[C:6]([NH:8][C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][CH:18]=2)[O:12][CH2:13][C:14]#[N:15])=[N:7][C:2]([NH:20][C:21]2[C:22]([O:34][CH3:35])=[CH:23][C:24]3[N:30]([CH3:31])[C:29](=[O:32])[O:28][CH2:27][CH2:26][C:25]=3[CH:33]=2)=[N:3][CH:4]=1
Reactant: N#CCOc1cccc(Nc2nc(Cl)ncc2Cl)c1
Reactant: COc1cc2c(cc1N)CCOC(=O)N2C
Product: COc1cc2c(cc1Nc1ncc(Cl)c(Nc3cccc(OCC#N)c3)n1)CCOC(=O)N2C
Yield: 50 %

Procedure:
In an analogous manner to Example 1503, the product was prepared from [3-(2,5-Dichloro-pyrimidin-4-ylamino)-phenoxy]-acetonitrile and 2-Amino-3-methoxy-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-one. Product isolated as a white solid (45 mg, 50%). mp: 227-229° C., MS (ESI+): 481 (M+H), 1H-NMR (CDCl3, 400 MHz) δ 8.91 (s, 1H), 8.15 (s, 1H), 7.96 (s, 1H), 7.73 (s, 1H), 7.37 (s, 1H), 7.35 (s, 1H), 7.30 (t, 1H), 6.99 (s, 1H), 6.82 (d, J=8 Hz, 1H), 5.11 (s, 2H), 4.28 (t, 2H), 3.83 (s, 3H), 3.28 (s, 3H), 2.71 (t, 2H).
Reaction SMILES: [Si:1]([O:18][CH2:19][C:20]1[C:25]([CH3:26])=[CH:24][CH:23]=[C:22](/[C:27](/[CH3:50])=[CH:28]\[CH2:29][O:30]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[C:21]=1[CH3:51])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)(=O)C>[Si:1]([O:18][CH2:19][C:20]1[C:25]([CH3:26])=[CH:24][CH:23]=[C:22](/[C:27](/[CH3:50])=[CH:28]\[CH2:29][OH:30])[C:21]=1[CH3:51])([C:14]([CH3:16])([CH3:17])[CH3:15])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C/C(=C/COC(c1ccccc1)(c1ccccc1)c1ccccc1)c1ccc(C)c(CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c1C
Solvent: CC(=O)O
Product: C/C(=C/CO)c1ccc(C)c(CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c1C
Yield: 28.4 %

Procedure:
A solution of 1-tert-butyldiphenylsilyloxymethyl-2,6-dimethyl-3-((Z)-1-methyl-3-trityloxy-1-propenyl)benzene (500 mg) in acetic acid (5 ml) was heated at 60° C. for 10 hours. The cooled reaction mixture was concentrated in vacuo and ethyl acetate was added thereto. The mixture was washed with aqueous sodium bicarbonate solution, water and brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by flash silica gel chromatography eluted with n-hexane-ethyl acetate to give 1-tert-butyldiphenylsilyloxymethyl-2,6-dimethyl-3-((Z)-3-hydroxy-1-methyl-1-propenyl)benzene (92 mg) as colorless oil.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH2:13])(=[O:12])=[O:11])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH3:14][O:15][C:16]1[CH:23]=[C:22]([O:24][CH3:25])[C:21]([C:26]2[N:27]([CH3:35])[C:28]3[C:33]([CH:34]=2)=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:20][C:17]=1[CH:18]=O>>[CH3:14][O:15][C:16]1[CH:23]=[C:22]([O:24][CH3:25])[C:21]([C:26]2[N:27]([CH3:35])[C:28]3[C:33]([CH:34]=2)=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:20][C:17]=1/[CH:18]=[CH:2]/[C:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([NH2:13])(=[O:11])=[O:12])=[CH:8][CH:9]=1)=[O:3]
Reactant: COc1cc(OC)c(-c2cc3ccccc3n2C)cc1C=O
Reactant: CC(=O)c1ccc(S(N)(=O)=O)cc1
Product: COc1cc(OC)c(-c2cc3ccccc3n2C)cc1/C=C/C(=O)c1ccc(S(N)(=O)=O)cc1
Yield: 90 %

Procedure:
The title compound was prepared by condensing 4-acetyl-benzenesulfonamide (Ex-26A) and 2,4-dimethoxy-5-(1-methyl-1H-indol-2-yl)-benzaldehyde (Ex-116A) in a similar manner as described in Ex-3. Yellow solid, 90% yield, mp 148–150° C. 1H-NMR (CDCl3) δ 8.17 (d, J=16 Hz, 1H), 8.09 (d, J=9 Hz, 2H), 8.01 (d, J=9 Hz, 2H), 7.68 (s, 1H), 7.64 (d, J=8 Hz, 1H), 7.47 (d, J=16 Hz, 1H), 7.35 (d, J=8 Hz, 1H), 7.22–7.26 (m, 1H), 7.11–7.16 (m, 1H), 6.58 (s, 1H), 6.50 (s, 1H), 4.92 (br, 2H), 4.02 (s, 3H), 3.90 (s, 3H), 3.58 (s, 3H). MS m/z=477 ([M+H]+, 100%). HRMS (ES+) Calcd. for C26H24NO5S: 477.1484. Found: 477.1487.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][C:5]#[C:6][C:7]1[N:8]([CH2:23][C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=[CH:26][CH:25]=2)[CH:9]=[C:10]2[C:15]=1[C:14](=O)[N:13]([CH3:17])[C:12](=O)[N:11]2[CH2:19][CH:20]([CH3:22])[CH3:21].[H][H]>C(O)C.[Pd]>[OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]1[N:8]([CH2:23][C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=[CH:26][CH:25]=2)[CH:9]=[C:10]2[C:15]=1[CH2:14][N:13]([CH3:17])[CH2:12][N:11]2[CH2:19][CH:20]([CH3:22])[CH3:21]
Reactant: [H][H]
Reactant: CC(C)Cn1c(=O)n(C)c(=O)c2c(C#CCCCO)n(Cc3cccc4ccccc34)cc21
Agent: [Pd]
Solvent: CCO
Product: CC(C)CN1CN(C)Cc2c1cn(Cc1cccc3ccccc13)c2CCCCCO

Procedure:
The compound of Example 13, 5-(5-hydroxypent-1-ynyl)-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-1 H-pyrrolo[3,4-d]pyrimidine-2,4(3 H,6 H)-dione (75 mg) was suspended in ethanol (50 ml). A suspension of 10% palladium on carbon (7 mg) in ethanol (3 ml) was added and the mixture was hydrogenated. When hydrogen uptake ceased, the reaction mixture was filtered and the solvent was removed by rotary evaporation. The crude product was purified by chromatography on silica eluting with ethyl acetate:isohexane(3:1) to give the title compound (29 mg) as an oil.
Reaction SMILES: C(O)(=O)C.[N+:5]([C:8]1[C:9]([SH:18])=[N:10][CH:11]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=1)([O-])=O.C(OCC)(=O)C>[Fe].O>[NH2:5][C:8]1[C:9]([SH:18])=[N:10][CH:11]=[C:12]([C:14]([F:16])([F:15])[F:17])[CH:13]=1
Reactant: O=[N+]([O-])c1cc(C(F)(F)F)cnc1S
Agent: [Fe]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CC(=O)O
Product: Nc1cc(C(F)(F)F)cnc1S
Temperature: 25 °C
Yield: 93.2 %

Procedure:
To a mixture of 2.87 g of iron, 10 ml of acetic acid and 10 ml of water was added a mixture of 3.84 g of 3-nitro-5-(trifluoromethyl)pyridine-2-thiol and 10 ml of ethyl acetate at 70° C. over a period of 10 minutes. The reaction mixture was cooled down to room temperature, then, to the reaction mixture was added water, and the resultant mixture was extracted with ethyl acetate twice. The combined organic layers were washed with water and saturated saline, dried over magnesium sulfate, then, concentrated under reduced pressure to obtain 3.1 g of 3-amino-5-(trifluoromethyl)pyridine-2-thiol.
Reaction SMILES: [C:1]([O:10]C)(=O)[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[SH:4].[C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[N:15]=1)#[N:13].C(N(CC)CC)C>C1(C)C=CC=CC=1>[CH3:20][C:16]1[N:15]=[C:14]([C:12]2[S:4][C:3]3[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=3[C:1](=[O:10])[N:13]=2)[CH:19]=[CH:18][CH:17]=1
Reactant: Cc1cccc(C#N)n1
Reactant: COC(=O)c1ccccc1S
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: Cc1cccc(-c2nc(=O)c3ccccc3s2)n1
Yield: 54.7 %

Procedure:
A mixture of methyl thiosalicylate (0.85 g, 5.1 mmol), 2-cyano-6-methylpyridine (0.60 g, 5.1 mmol), triethylamine (1.10 ml, 7.9 mmol) and toluene (1.1 ml) was refluxed for 9 hrs. After cooling, the precipitated crystals were collected by filtration and recrystallized from ethanol to give the titled compound (0.71 g, 55%).
Reaction SMILES: [H-].[Na+].[CH2:3]([O:7][C:8]1[N:13]=[CH:12][N:11]=[C:10]([CH:14]([OH:21])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:9]=1)[C:4]#[C:5][CH3:6].[CH3:22][O:23][CH2:24]Cl.[Cl-].[NH4+]>O1CCCC1>[CH2:3]([O:7][C:8]1[N:13]=[CH:12][N:11]=[C:10]([CH:14]([O:21][CH2:22][O:23][CH3:24])[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:9]=1)[C:4]#[C:5][CH3:6]
Reactant: CC#CCOc1cc(C(O)c2ccccc2)ncn1
Reactant: COCCl
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC#CCOc1cc(C(OCOC)c2ccccc2)ncn1
Reaction time: 0.25 h
Yield: 106.5 %

Procedure:
In 1.5 ml of tetrahydrofuran was suspended 0.05 g of sodium hydride (60% in oil), to which 0.2 g of 6-(2-butynyloxy)-4-(α-hydroxybenzyl)pyrimidine was added under ice cooling, followed by stirring for 15 minutes. Then, 0.2 ml of a tetrahydrofuran solution containing 0.08 g of chloromethyl methyl ether was slowly added dropwise, followed by further stirring at the same temperature for 2 hours. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution and extracted three times with chloroform. The chloroform layers were combined, washed with water, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography to give 0.25 g of 6-(2-butynyloxy)-4-(α-methoxymethoxybenzyl)pyrimidine (the present compound (137)).
Reaction SMILES: [N:1]1[C:2]([C:15]2[N:19]([CH:20]([CH3:22])[CH3:21])[N:18]=[C:17]([CH:23]=O)[N:16]=2)=[CH:3][N:4]2[C:10]=1[C:9]1[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=1[O:7][CH2:6][CH2:5]2.Cl.[CH3:26][NH:27][CH3:28].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.C1COCC1.C(Cl)Cl>[N:1]1[C:2]([C:15]2[N:19]([CH:20]([CH3:21])[CH3:22])[N:18]=[C:17]([CH2:23][N:27]([CH3:28])[CH3:26])[N:16]=2)=[CH:3][N:4]2[C:10]=1[C:9]1[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=1[O:7][CH2:6][CH2:5]2
Reactant: CC(C)n1nc(C=O)nc1-c1cn2c(n1)-c1ccccc1OCC2
Reactant: CNC
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CC(C)n1nc(CN(C)C)nc1-c1cn2c(n1)-c1ccccc1OCC2
Temperature: 25 °C
Reaction time: 18 h
Yield: 14.2 %

Procedure:
A mixture of 5-(4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-2-yl)-1-isopropyl-1H-[1,2,4]triazole-3-carbaldehyde (85 mg, 0.26 mmol), acetic acid (catalytic, 2 drops), 4 Å molecular sieves and dimethylamine hydrochloride (24 mg, 0.29 mmol) in THF (5 mL) was stirred at RT for 10 min before the addition of sodium triacetoxyborohydride (66 mg, 0.31 mmol). After stirring at RT for a further 18 h the reaction mixture was diluted with DCM, the organic layer washed with saturated aqueous sodium bicarbonate followed by water and then brine, then dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to RPHPLC (C18 column, gradient 5 to 98% methanol in water+0.1% HCO2H) to give 318 as a white solid (13 mg, 14%). LCMS: RT=3.18 min, [M+H]+353. 1H NMR 400 MHz (DMSO-d6) δ: 8.45 (1H, dd, J=8.02, 1.76 Hz), 7.97 (1H, s), 7.39-7.32 (1H, m), 7.19-7.19 (1H, m), 7.09 (1H, dd, J=8.15, 1.25 Hz), 5.89 (1H, m), 4.54 (4H, d, J=2.46 Hz), 3.47 (2H, s), 2.24 (6H, s), 1.51 (6H, d, J=6.59 Hz)