Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:6](Cl)=[O:7].C1(C2[NH:24][CH2:23][CH:22]([CH2:25][Cl:26])[O:21]2)C=CC=CC=1.Cl>C(Cl)(Cl)Cl.N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:6]([NH:24][CH2:23][CH:22]([OH:21])[CH2:25][Cl:26])=[O:7]
Reactant: ClCC1CNC(c2ccccc2)O1
Reactant: COc1ccc(C(=O)Cl)cc1OC
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: COc1ccc(C(=O)NCC(O)CCl)cc1OC
Temperature: 25 °C
Yield: 72.3 %

Procedure:
A solution of 15.2 g of 3,4-dimethoxybenzoyl chloride in 40 ml of chloroform is added dropwise to a solution of 15.0 g 2-phenyl-5-chloromethyloxazolidine in a mixture of 200 ml of chloroform and 6 ml of pyridine at a temperture of -40° C. under agitation. This solution is then heated to room temperature. After a reaction period of 14 hours, 20 ml of concentrated hydrochloric acid are added, the phases are thoroughly mixed for a period of 10 minutes and then are separated. The separated aqueous phase is diluted with water to twice its volume and then is saturated with sodium chloride and extracted with chloroform. After drying the chloroform-extract and evaporating the solvent, 15.0 g of N-(3,4-dimethoxybenzoyl)-3-chloro-1-aminopropan-2-ol is obtained as an oil which can be further reacted without any purification. After crystallization from ethanol/toluene the compound exhibits a melting point of 104°-106° C.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9]2[CH:14]=[C:13]([C:15]3[C:20]([Cl:21])=[CH:19][CH:18]=[C:17]([NH:22][CH2:23][CH:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)[N:16]=3)[C:12]([Cl:30])=[CH:11][N:10]=2)[CH2:4][CH2:3]1.[S:31]1(=[O:39])(=[O:38])[CH2:36][CH2:35][C:34](=O)[CH2:33][CH2:32]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[Cl:21][C:20]1[C:15]([C:13]2[C:12]([Cl:30])=[CH:11][N:10]=[C:9]([NH:8][C@H:5]3[CH2:6][CH2:7][C@H:2]([NH:1][CH:34]4[CH2:35][CH2:36][S:31](=[O:39])(=[O:38])[CH2:32][CH2:33]4)[CH2:3][CH2:4]3)[CH:14]=2)=[N:16][C:17]([NH:22][CH2:23][CH:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[CH:18][CH:19]=1
Reactant: O=C1CCS(=O)(=O)CC1
Reactant: NC1CCC(Nc2cc(-c3nc(NCC4CCOCC4)ccc3Cl)c(Cl)cn2)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=S1(=O)CCC(N[C@H]2CC[C@H](Nc3cc(-c4nc(NCC5CCOCC5)ccc4Cl)c(Cl)cn3)CC2)CC1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Compound N2′-(4-aminocyclohexyl)-3,5′-dichloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine (0.100 g, 0.222 mmol) (synthesized in the same manner as in Example 1b), 2,3,5,6-tetrahydro-4H-thiopyran-4-one 1,1-dioxide (0.036 g, 0.244 mmol), and triethylamine (0.251 ml, 0.182 g, 1.798 mmol) were dissolved in anhydrous CH2Cl2 (1.0 ml) and placed under argon. This solution was then treated with sodium triacetoxyborohydride (0.094 g, 0.444 mmol). The reaction was then stirred at room temperature for 18 hours. At this time a LC-MS was run. The reaction was about 25% complete. Additional 2,3,5,6-tetrahydro-4H-thiopyran-4-one 1,1-dioxide (˜4 equivalents) and sodium triacetoxy borohydride (˜8 equivalents) were added and the reaction continued for additional 27 hours. The reaction was about 60% complete as indicated by LC/MS. The reaction was quenched with sat NaHCO3 (15 ml). This was extracted with EtOAc (3×15 ml). The combined extracts were washed with brine (1×15 ml), dried (Na2SO4), filtered and the solvent removed in vacuo. The material was purified using the HPLC and lyophilized to give 19.7 mg off-white powder of the title compound as its TFA salt. LCMS (m/z): 582/584 (MH+), retention time=0.58 min.
Reaction SMILES: [C:1]1([CH3:12])[CH:6]=[C:5]([CH3:7])[CH:4]=[C:3]([CH3:8])[C:2]=1[CH2:9][CH:10]=[O:11].C[Mg+].[Br-].[CH3:16]COCC>C1COCC1>[C:3]1([CH3:8])[CH:4]=[C:5]([CH3:7])[CH:6]=[C:1]([CH3:12])[C:2]=1[CH2:9][CH:10]([OH:11])[CH3:16]
Reactant: Cc1cc(C)c(CC=O)c(C)c1
Reactant: CCOCC
Agent: C[Mg+]
Agent: [Br-]
Solvent: C1CCOC1
Product: Cc1cc(C)c(CC(C)O)c(C)c1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 68.3 %

Procedure:
Mesitylacetaldehyde (0.68 g, 4.19 mmol) was dissolved in THF (5.0 mL, dry) and MeMgBr in Et2O (3.0M, 0.75 g, 6.29 mmol)) was added slowly at 0° C. The cooling bath was removed and the reaction mixture was stirred at rt for 4.5 h. The mixture was cooled to 0° C. and excess Grignard reagent was hydrolyzed with HCl (1N). The mixture was diluted with water and extracted with Et2O. The organic layer was dried over Na2SO4, evaporated and the residue was purified by column chromatography on silica gel using MTBE, heptane and DCM as eluant giving the title compound (0.51 g, 61%). 1H NMR (CDCl3, 500 MHz) δ 6.88-6.85 (m, 2H), 4.08-3.99 (m, 1H), 2.87-2.72 (m, 2H), 2.32 (s, 6H), 2.26 (s, 3H), 1.29 (d, 3H).
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH:9]=[N:10][CH2:11][C:12]2[C:13]([NH2:19])=[N:14][C:15]([CH3:18])=[N:16][CH:17]=2)=[CH:4][N:3]=1.CC1N=C(N)C(CO)=CN=1>>[CH3:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH2:9][NH:10][CH2:11][C:12]2[C:13]([NH2:19])=[N:14][C:15]([CH3:18])=[N:16][CH:17]=2)=[CH:4][N:3]=1
Reactant: Cc1ncc(C=NCc2cnc(C)nc2N)c(N)n1
Agent: Cc1ncc(CO)c(N)n1
Product: Cc1ncc(CNCc2cnc(C)nc2N)c(N)n1

Procedure:
And, neither 2-methyl-4-amino-5-pyrimidylmethylidene-(2-methyl-4-amino-5-pyrimidylmethyl)amine nor 2-methyl-4-amino-5-hydroxymethylpyrimidine was detected.
Reaction SMILES: C1(COC([NH:11][C@@H:12]([C:23]([NH:25][C@H:26]([C:39]([N:41]2[CH2:46][CH2:45][N:44]([C:47]3[CH:52]=[CH:51][N:50]=[CH:49][CH:48]=3)[CH2:43][CH2:42]2)=[O:40])[CH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[O:24])[CH2:13][C:14]2[CH:19]=[C:18]([Cl:20])[C:17]([OH:21])=[C:16]([Cl:22])[CH:15]=2)=O)C=CC=CC=1.S([O-])(O)(=O)=O.[K+].[H][H]>CO.[Pd]>[Cl:20][C:18]1[CH:19]=[C:14]([CH:15]=[C:16]([Cl:22])[C:17]=1[OH:21])[CH2:13][C@H:12]([C:23]([NH:25][C@H:26]([C:39]([N:41]1[CH2:42][CH2:43][N:44]([C:47]2[CH:52]=[CH:51][N:50]=[CH:49][CH:48]=2)[CH2:45][CH2:46]1)=[O:40])[CH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:36])[CH3:37])=[O:33])=[O:24])[NH2:11]
Reactant: CC(C)(C)OC(=O)NCCCC[C@H](NC(=O)[C@@H](Cc1cc(Cl)c(O)c(Cl)c1)NC(=O)OCc1ccccc1)C(=O)N1CCN(c2ccncc2)CC1
Reactant: [H][H]
Agent: [Pd]
Agent: O=S(=O)([O-])O
Agent: [K+]
Solvent: CO
Product: CC(C)(C)OC(=O)NCCCC[C@H](NC(=O)[C@H](N)Cc1cc(Cl)c(O)c(Cl)c1)C(=O)N1CCN(c2ccncc2)CC1

Procedure:
A solution of 6 g (7.9 mmol) of 1-[N2—[N-[(phenylmethoxy)carbonyl]-3,5-dichloro-D-tyrosyl]-N6-[(1,1-dimethylethoxy)carbonyl]-L-lysyl]-4-(4-pyridinyl)-piperazine in a mixture of 200 ml of methanol and 20 ml of aqueous 1 M potassium hydrogen sulphate solution was hydrogenated in the presence of 0.5 g palladium black as catalyst at room temperature under 3 bar of hydrogen pressure for 40 minutes. The catalyst was filtered off, the reaction mixture was evaporated to dryness in vacuo and the residue adjusted to a pH of about 10 by the addition of 2 ml of concentrated aqueous ammonia solution. The product was extracted several times with isopropanol, the combined isopropanol extracts were evaporated down in vacuo and the residue was purified by column chromatography (LiChroprep, Si60 particle size: 20-40 μm, Messrs. Merck (Darmstadt); eluant: methylene chloride/methanol/ammonia=350/75/75/10 (v/v/v/v)). 2.5 g (51% of theory) of a colourless amorphous solid substance were obtained.
Reaction SMILES: [CH2:1]1[C:3]([NH2:7])([C:4]([OH:6])=[O:5])[CH2:2]1.[CH3:8][CH:9]([CH3:25])[C:10]([O:12][CH2:13][O:14][C:15](ON1C(=O)CCC1=O)=[O:16])=[O:11]>>[C:10]([O:12][CH2:13][O:14][C:15]([NH:7][C:3]1([C:4]([OH:6])=[O:5])[CH2:2][CH2:1]1)=[O:16])(=[O:11])[CH:9]([CH3:25])[CH3:8]
Reactant: NC1(C(=O)O)CC1
Reactant: CC(C)C(=O)OCOC(=O)ON1C(=O)CCC1=O
Product: CC(C)C(=O)OCOC(=O)NC1(C(=O)O)CC1
Yield: 43.6 %

Procedure:
Following the general procedure for the synthesis of acyloxyalkyl carbamates, ACPC (121 mg, 1.2 mmol) and (2,5-dioxoazolidinyloxycarbonyloxy)methyl 2-methylpropanoate (259 mg, 1.0 mmol) were reacted to provide 107 mg (44% yield) of the title compound (9) as a white powder after work-up and mass-guided preparative HPLC purification. 1H NMR (CDCl3, 400 MHz): δ=5.99 (br s, 0.2H), 5.78 (br s, 0.4H), 5.73 (s, 1.6H), 5.59 (s, 0.8H), 2.59 (m, 1H), 1.62 (m, 2H), 1.31 (m, 2H), 1.19 (d, 6H). MS (ESI) m/z 246.10 (M+H)+; 263.11 (M+NH4)+; 268.09 (M+Na)+; 244.11 (M−H)−.
Reaction SMILES: Cl.[Cl:2][C:3]1[C:7]([Cl:8])=[C:6]([CH3:9])[NH:5][C:4]=1[C:10]([NH:12][CH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)=[O:11].Br[C:20]1[S:21][C:22]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][N:24]=1>CN1C(=O)CCC1>[Cl:2][C:3]1[C:7]([Cl:8])=[C:6]([CH3:9])[NH:5][C:4]=1[C:10]([NH:12][CH:13]1[CH2:18][CH2:17][N:16]([C:20]2[S:21][C:22]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][N:24]=2)[CH2:15][CH2:14]1)=[O:11]
Reactant: COC(=O)c1cnc(Br)s1
Reactant: Cc1[nH]c(C(=O)NC2CCNCC2)c(Cl)c1Cl
Agent: Cl
Solvent: CN1CCCC1=O
Product: COC(=O)c1cnc(N2CCC(NC(=O)c3[nH]c(C)c(Cl)c3Cl)CC2)s1

Procedure:
3,4-Dichloro-5-methyl-N-piperidin-4-yl-1H-pyrrole-2-carboxamide hydrochloride (Intermediate 1, 0.300 g, 0.961 mmol) was dissolved in NMP (3 ml). TEA (267 μl, 1.922 mmol) was added followed by the addition of methyl 2-bromo-1,3-thiazole-5-carboxylate (0.213 g, 0.961 mmol) at room temperature. Using a Smith Microwave Synthesizer, the mixture was subjected to single-mode microwave at 150° C. for 20 minutes and was partitioned between water and EtOAc. The organic layer was washed with water and combined organic phase was dried over magnesium sulfate and concentrated to give the desired product. (432 mg).
Reaction SMILES: [C:1]1([CH3:20])[CH:6]=[CH:5][C:4]([S:7]([N:10]2[CH:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[C:17]([OH:19])=O)=[CH:11]2)(=[O:9])=[O:8])=[CH:3][CH:2]=1.C(N(CC)CC)C.Cl.[C:29]([NH:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[NH2:43])([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30]>C(Cl)CCl.CN(C=O)C>[C:32]([O:31][C:29](=[O:30])[NH:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[NH:43][C:17](=[O:19])/[CH:16]=[CH:15]/[C:12]1[CH:13]=[CH:14][N:10]([S:7]([C:4]2[CH:3]=[CH:2][C:1]([CH3:20])=[CH:6][CH:5]=2)(=[O:8])=[O:9])[CH:11]=1)([CH3:35])([CH3:33])[CH3:34]
Reactant: CC(C)(C)OC(=O)Nc1ccccc1N
Reactant: Cc1ccc(S(=O)(=O)n2ccc(/C=C/C(=O)O)c2)cc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: ClCCCl
Product: Cc1ccc(S(=O)(=O)n2ccc(/C=C/C(=O)Nc3ccccc3NC(=O)OC(C)(C)C)c2)cc1

Procedure:
Starting materials: (E)-3-[1-(toluene-4-sulfonyl)-1H-pyrrol-3yl]-acrylic acid (compound A1) (0.400 g), HOBtH2O (0.285 g), triethylamine (652 μl), DMF (25 ml), EDC?HCl (0.698 g), N—BOC-1,2-phenylenediamine (0.286 g). Reaction conditions: room temperature, 1 hour; room temperature, 2 hours.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[OH-].[Na+].[CH2:13](Br)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]>O>[OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH3:13])=[O:7])=[CH:4][CH:3]=1
Reactant: CCCCCCCCCCCCCCBr
Reactant: O=C(O)c1ccc(O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCCCCCCCCCCCCOC(=O)c1ccc(O)cc1

Procedure:
To a solution of 2.76 g (20 mmol) of 4-hydroxybenzoic acid and 800 mg (200 mmol) of sodium hydroxide in 12 ml of water was added 250 mg of methyl tricaprylammonium chloride and 4.67 g (17 mmol) of n-tetradecylbromide. The mixture was heated at reflux for 4 h and then diluted with 30 ml of water. The mixture was extracted with 2×30 ml ether. The ether extracts were combined and washed with water and saturated NaCl solution. The solvent was removed in-vacuo and the residue purified by flash chromatography (silica; 10% ethyl acetate in hexanes) to give the title compound as a white solid.
Reaction SMILES: CS([O:5][CH:6]1[CH2:9][N:8]([C:10]([C:12]2[O:13][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:15][N:16]=2)=[O:11])[CH2:7]1)(=O)=O.O[C:24]1[CH:31]=[CH:30][C:27]([CH:28]=[O:29])=[CH:26][CH:25]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>CC(N(C)C)=O>[C:17]1([C:14]2[O:13][C:12]([C:10]([N:8]3[CH2:9][CH:6]([O:5][C:24]4[CH:31]=[CH:30][C:27]([CH:28]=[O:29])=[CH:26][CH:25]=4)[CH2:7]3)=[O:11])=[N:16][N:15]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=Cc1ccc(O)cc1
Reactant: CS(=O)(=O)OC1CN(C(=O)c2nnc(-c3ccccc3)o2)C1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: O=Cc1ccc(OC2CN(C(=O)c3nnc(-c4ccccc4)o3)C2)cc1
Temperature: 110 °C
Reaction time: 5 h
Yield: 66.1 %

Procedure:
Intermediate 53B (5.0 g, 15.5 mmol) was dissolved in DMA (40 mL) and 4-hydroxybenzaldehyde (2.17 g, 17.8 mmol) was added followed by Cs2CO3 (5.8 g, 17.8 mmol). The mixture was stirred at 110° C. for 5 h. Water was added and the mixture was extracted trice with DCM. The solution was filtered through a phase separator and the solvent was removed by evaporation. Ether was added to the residue and the formed solid was filtered and washed with ether. The product was dried in vacuo to give 3.58 g (66%) of 71A as a beige solid. 1H NMR (500 MHz, CDCl3): δ 4.37 (m, 1H), 4.70 (m, 1H), 4.79 (m, 1H), 5.18 (m, 2H), 6.91 (d, 2H), 7.53 (t, 2H), 7.60 (t, 1H), 7.87 (d, 2H), 8.16 (d, 2H), 9.92 (s, 1H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:14]2[CH2:18][C@H:17]([CH2:19][OH:20])[O:16][C:15]2=[O:21])[CH:5]=[CH:6][C:7]=1[N:8]1[CH:12]=[C:11]([CH3:13])[N:10]=[CH:9]1.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>N1C=CC=CC=1.C(N(CC)CC)C>[F:1][C:2]1[CH:3]=[C:4]([N:14]2[CH2:18][C@H:17]([CH2:19][O:20][S:23]([CH3:22])(=[O:25])=[O:24])[O:16][C:15]2=[O:21])[CH:5]=[CH:6][C:7]=1[N:8]1[CH:12]=[C:11]([CH3:13])[N:10]=[CH:9]1
Reactant: CS(=O)(=O)Cl
Reactant: Cc1cn(-c2ccc(N3C[C@H](CO)OC3=O)cc2F)cn1
Solvent: CCN(CC)CC
Solvent: c1ccncc1
Product: Cc1cn(-c2ccc(N3C[C@H](COS(C)(=O)=O)OC3=O)cc2F)cn1
Reaction time: 2 h
Yield: 78.2 %

Procedure:
(5R)-3-(3-Fluoro-4-(4-methylimidazol-1-yl)phenyl)-5-hydroxymethyloxazolidin-2-one (11.8 g, 40.5 mM) was stirred in a mixture of pyridine (200 ml) and triethylamine (4.86 g, 48.2 mM) under nitrogen in an ice-bath. Methanesulfonyl chloride (5.16 g, 45 mM) was added dropwise, and the mixture stirred for 2 hours, allowing the temperature to rise to ambient. Solvent was evaporated, and the residue stirred vigorously with a mixture of aqueous sodium bicarbonate (5%, 200 ml) and isohexane (200 ml). The precipitate was filtered, washed with water then isohexane, and dried. The residue was recrystallised from hot acetone (200 ml) by dilution with isohexane (300 ml) to give the title product (11.7 g), mp 151–153°.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:27]([CH3:29])[CH3:28])[C:6]2[O:10][C:9]([C:11]3[CH:25]=[CH:24][C:14]([C:15]([NH:17][CH2:18][CH:19]4[CH2:23][CH2:22][NH:21][CH2:20]4)=[O:16])=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:26]=1)#[N:2].C(N(CC)CC)C.[Br:37][C:38]1[CH:43]=[CH:42][C:41]([CH2:44]Br)=[CH:40][CH:39]=1>CO>[Br:37][C:38]1[CH:43]=[CH:42][C:41]([CH2:44][N:21]2[CH2:22][CH2:23][CH:19]([CH2:18][NH:17][C:15](=[O:16])[C:14]3[CH:13]=[CH:12][C:11]([C:9]4[O:10][C:6]5[C:5]([CH:27]([CH3:29])[CH3:28])=[CH:4][C:3]([C:1]#[N:2])=[CH:26][C:7]=5[N:8]=4)=[CH:25][CH:24]=3)[CH2:20]2)=[CH:40][CH:39]=1
Reactant: CC(C)c1cc(C#N)cc2nc(-c3ccc(C(=O)NCC4CCNC4)cc3)oc12
Reactant: BrCc1ccc(Br)cc1
Solvent: CO
Solvent: CCN(CC)CC
Product: CC(C)c1cc(C#N)cc2nc(-c3ccc(C(=O)NCC4CCN(Cc5ccc(Br)cc5)C4)cc3)oc12
Temperature: 150 °C
Yield: 67.2 %

Procedure:
To a solution of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-(pyrrolidin-3-ylmethyl)benzamide (78 mg) in 2 ml of methanol was added 558 μl of triethylamine and 50 mg of 1-bromo-4-(bromomethyl)benzene. The solution was heated to 150° C. via microwave for 30 min, cooled, and purified via column chromatography on a Biotage Horizon 40M column eluting with 1 column volume of 100% hexanes, followed by a gradient of 0 to 100% ethyl acetate in hexanes over 10 column volumes, followed by 6 column volumes at 100% ethyl acetate to provide the title compound (75 mg, 68%). Mass spectrum (ESI) 559.0 (M+2). 1H NMR (500 MHz, CDCl3): δ 8.32 (d, J=8.5 Hz, 2H), 7.96 (s, 1H), 7.91 (d, J=8.2 Hz, 2H), 7.52 (s, 1H), 7.42 (d, J=8.2 Hz, 2H), 7.16 (d, J=8.2 Hz, 2H), 3.52 (m, 3H), 2.98 (td, J=9.1, 2.9, 1H), 2.76 (d, J=9.6 Hz, 1H), 2.58 (m, 2H), 2.32 (m, 1H), 2.14 (m, 1H), 1.68 (m, 1H), 1.48 (d, J=6.8 Hz, 6H).
Reaction SMILES: [C:1]([Si:5]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[O:6][CH:7]1[CH2:12][CH2:11][CH:10]([CH:13]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[C:24]([Cl:25])=[CH:23][C:22](OS(C(F)(F)F)(=O)=O)=[CH:21][C:20]=3[Cl:34])[C:14]2=[O:35])[CH2:9][CH2:8]1)([CH3:4])([CH3:3])[CH3:2].[CH3:48][O:49][C:50]([C:52]1[CH:57]=[CH:56][C:55](B(O)O)=[CH:54][CH:53]=1)=[O:51].C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.O.C(OCC)(=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>[CH3:48][O:49][C:50]([C:52]1[CH:57]=[CH:56][C:55]([C:22]2[CH:21]=[C:20]([Cl:34])[C:19]([CH2:18][N:15]3[CH2:16][CH2:17][CH:13]([CH:10]4[CH2:9][CH2:8][CH:7]([O:6][Si:5]([C:1]([CH3:3])([CH3:4])[CH3:2])([C:36]5[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=5)[C:42]5[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=5)[CH2:12][CH2:11]4)[C:14]3=[O:35])=[C:24]([Cl:25])[CH:23]=2)=[CH:54][CH:53]=1)=[O:51]
Reactant: COC(=O)c1ccc(B(O)O)cc1
Reactant: CC(C)(C)[Si](OC1CCC(C2CCN(Cc3c(Cl)cc(OS(=O)(=O)C(F)(F)F)cc3Cl)C2=O)CC1)(c1ccccc1)c1ccccc1
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: [Na+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)c1ccc(-c2cc(Cl)c(CN3CCC(C4CCC(O[Si](c5ccccc5)(c5ccccc5)C(C)(C)C)CC4)C3=O)c(Cl)c2)cc1
Temperature: 80 °C
Reaction time: 1 h
Yield: 93.3 %

Procedure:
Bring a mixture of trifluoro-methanesulfonic acid 4-{3-[4-(tert-butyl-diphenyl-silanyloxy)-cyclohexyl]-2-oxo-pyrrolidin-1-ylmethyl}-3,5-dichloro-phenyl ester (0.61 g, 0.84 mmol), 4-methoxycarbonylphenylboronic acid (0.18 g, 1 mmol), sodium carbonate (0.267 g, 2.52 mmol) in THF (15 mL) and water (5 mL) to 60° C. To the mixture at 60° C., add Pd(PPh3)4 (0.048 g, 0.04 mmol). Raise the reaction temperature to 80° C. and stir for 1 hour. Cool the reaction, dilute with ethyl acetate, and wash with water and brine. Dry the organic layer (Na2SO4), remove the solvent in vacuo to afford crude product, and purify on silica gel column with 25% ethyl acetate in hexanes to afford 0.56 g (93%) of the titled product. MS (m/z): 714 (M+).
Reaction SMILES: [CH3:1][C:2]1OC([Si](C)(C)C)=[CH:4][C:3]=1C=O.CI.[CH2:15]([Si:17]([CH2:27][CH3:28])([CH2:25][CH3:26])[C:18]1[O:19][CH:20]=[C:21]([CH:23]=[O:24])[CH:22]=1)[CH3:16].ICCCC>>[CH2:1]([C:20]1[O:19][C:18]([Si:17]([CH2:25][CH3:26])([CH2:15][CH3:16])[CH2:27][CH3:28])=[CH:22][C:21]=1[CH:23]=[O:24])[CH2:2][CH2:3][CH3:4]
Reactant: Cc1oc([Si](C)(C)C)cc1C=O
Reactant: CC[Si](CC)(CC)c1cc(C=O)co1
Solvent: CI
Solvent: CCCCI
Product: CCCCc1oc([Si](CC)(CC)CC)cc1C=O

Procedure:
Using the same procedure as for 5-methyl-2-trimethylsilyl-4-furaldehyde but substituting 2-trimethylsilyl-4-furaldehyde and methyl iodide with 2-triethylsilyl-4-furaldehyde and 1-iodobutane, respectively, gives 5-butyl-2-triethylsilyl-4-furaldehyde. IR (neat) 1690 cm-1; 'HNMR (CDCl3) 0.73 (q, 6H, J=8.4 Hz), 0.95 (m, 12H), 1.36 (p, 2H, J=7.5 Hz), 1.69 (p, 2H, J=7.5 Hz), 2.94 (t, 2H, J=7.5 Hz), 6.89 (s, 1H) and 9.91 (s, 1H) 13CNMR (CDCl3): 3.03, 7.17, 13.6, 22.2, 26.8, 30.4, 118.6, 122.5 158.4, 170.2 and 184.8. LRMS m/e (% abundance) 266 (M+, 20) 238 (20) 237 (100), 87 (10) and 75 (20); HRMS exact mass calculated for C15H26O2Si 266.1702, found 266.1690.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:19][CH2:20][CH:21]([CH2:39][OH:40])[O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[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][CH3:18].[C:41]([C:43]1[CH:44]=[C:45]([CH:48]=[CH:49][CH:50]=1)[CH2:46]Br)#[N:42].O>O1CCCC1>[CH2:3]([O:19][CH2:20][CH:21]([CH2:39][O:40][CH2:46][C:45]1[CH:48]=[CH:49][CH:50]=[C:43]([C:41]#[N:42])[CH:44]=1)[O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[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][CH3:18]
Reactant: N#Cc1cccc(CBr)c1
Reactant: CCCCCCCCCCCCCCCCOCC(CO)OCCCCCCCCCCCCCCCC
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCCCCCCCCCCCCCCCOCC(COCc1cccc(C#N)c1)OCCCCCCCCCCCCCCCC
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 68 %

Procedure:
Sodium hydride (1.056 g. of 50 wt. % mineral oil dispersion, 22 mmoles) was added to a solution of 1,2-di-O-(n-hexadecyl)-glycerol (9.73 g., 18 mmoles) in tetrahydrofuran (150 ml.) and the resulting solution stirred for 20 minutes at room temperature under nitrogen. m-Cyanobenzyl bromide (4.0 g., 20 mmoles) was added and the reaction mixture stirred overnight at room temperature under nitrogen. Water (200 ml.) was then added cautiously and the resulting mixture extracted with ethyl acetate (3×150 ml.). The combined ethyl acetate extract was dried (MgSO4), filtered and evaporated in vacuo to an oil (12 g.), which was purified by silica gel chromatography (elution with benzene:hexane) [8.0 g., 68% yield, oil, ir (CHCl3) 2230 cm-1 ].
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[CH:3][C:2]=1[N:11]1[CH2:22][CH2:21][C:14]2([C:19](=[O:20])[NH:18][CH2:17][CH2:16][CH2:15]2)[CH2:13][CH2:12]1.C1COCC1.Br[CH2:29][C:30]1[CH:38]=[CH:37][CH:36]=[C:35]2[C:31]=1[CH:32]=[CH:33][N:34]2S(C1C=CC(C)=CC=1)(=O)=O>[NH4+].[Cl-]>[NH:34]1[C:35]2[C:31](=[C:30]([CH2:29][N:18]3[CH2:17][CH2:16][CH2:15][C:14]4([CH2:21][CH2:22][N:11]([C:2]5[CH:3]=[N:4][C:5]6[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=6)[N:1]=5)[CH2:12][CH2:13]4)[C:19]3=[O:20])[CH:38]=[CH:37][CH:36]=2)[CH:32]=[CH:33]1
Reactant: O=C1NCCCC12CCN(c1cnc3ccccc3n1)CC2
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c(CBr)cccc32)cc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: O=C1N(Cc2cccc3[nH]ccc23)CCCC12CCN(c1cnc3ccccc3n1)CC2
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 55.3 %

Procedure:
To a solution of 9-quinoxalin-2-yl-2,9-diaza-spiro[5.5]undecan-1-one (100 mg, 0.34 mmol) in THF (5 ml) sodium hydride 95% (18 mg, 0.74 mmol) was added and the mixture was stirred for 10 min at rt. Then 4-bromomethyl-1-(toluene-4-sulfonyl)-1H-indole (147 mg, 0.4 mmol) was added and the reaction mixture was heated at 50° C. over 18 h. Saturated aqueous NH4Cl solution (50 ml) was added and the reaction mixture was extracted with methylene chloride. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting crude product was purified by flash chromatography (EtOAc/hexane 4:6) to yield 80 mg (55%) of the title compound. [1H NMR (DMSO, 600 MHz) δ 11.14 (br.s, 1H), 8.84 (s, 1H), 7.81 (d, 1H, J=8.28 Hz), 7.63-7.52 (m, 2H), 7.44-7.34 (m, 2H), 7.34-7.25 (m, 2H), 7.03 (t, 1H), 6.82 (d, 1H, J=7.06 Hz), 6.43 (br.s., 1H), 4.76 (s, 2H), 4.35-4.25 (m, 2H), 3.48-3.38 (2H, m), 3.13 (t, 2H), 2.21-2.04 (m, 2H), 1.91-1.80 (m, 2H), 1.77-1.65 (m, 2H), 1.62-1.52 (m, 2H), LCMS RtE=2.70 min, [M+H]+=426.4].