Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH:4]([C:6]2[CH:7]=[C:8]([CH:13]=[CH:14][CH:15]=2)[C:9](OC)=[O:10])[CH3:5])[CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[CH:1]1([CH:4]([C:6]2[CH:7]=[C:8]([CH2:9][OH:10])[CH:13]=[CH:14][CH:15]=2)[CH3:5])[CH2:3][CH2:2]1
Reactant: COC(=O)c1cccc(C(C)C2CC2)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(c1cccc(CO)c1)C1CC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of methyl 3-(1-cyclopropylethyl)benzoate (0.917 g, 4.48 mmol) in THF (50 mL) was added lithium aluminum hydride (1.0 M in THF, 13.5 mL, 13.5 mmol). After stirring at rt for 15 min the reaction was cooled and quenched with water, extracted into ethyl acetate (three times) and concentrated under vacuum. Purification by silica gel chromatography (30% EtOAc/hexanes) afforded the desired product.
Reaction SMILES: [C:1]([O:4][C:5]1[CH:10]=[C:9]([Br:11])[CH:8]=[CH:7][C:6]=1[C@@H:12]1[C@@H:15]([CH2:16][CH2:17][C@H:18]([O:26][Si](C(C)(C)C)(C)C)[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[C:14](=[O:34])[N:13]1[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)(=[O:3])[CH3:2].F.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(#N)C>[C:1]([O:4][C:5]1[CH:10]=[C:9]([Br:11])[CH:8]=[CH:7][C:6]=1[C@@H:12]1[C@@H:15]([CH2:16][CH2:17][C@@H:18]([C:19]2[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=2)[OH:26])[C:14](=[O:34])[N:13]1[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Oc1cc(Br)ccc1[C@@H]1[C@@H](CC[C@H](O[Si](C)(C)C(C)(C)C)c2ccc(F)cc2)C(=O)N1c1ccccc1
Agent: *CC(*)C
Agent: F
Agent: O=P([O-])([O-])[O-]
Solvent: CC#N
Product: CC(=O)Oc1cc(Br)ccc1[C@@H]1[C@@H](CC[C@H](O)c2ccc(F)cc2)C(=O)N1c1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 100.2 %

Procedure:
5-Bromo-2-{(2S,3R)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-4-oxo-1-phenylazetidin-2-yl}phenyl acetate (140.0 mg, 0.223 mmol) was dissolved in acetonitrile (8.0 mL) and 48% hydrofluoric acid (0.8 mL) into a polypropylene Falcon® tube. The reaction was stirred for 4 h at room temperature and then poured into 0.5 M potassium phosphate (50 mL), extracted with 1:1 ethyl acetate-hexane (50 mL), washed with saturated sodium bicarbonate solution (50 mL) and brine (50 mL), dried over sodium sulfate, filtered, concentrated and purified by chromatography (12 g silica gel, 15% to 90% ethyl acetate-hexane) to afford 5-bromo-2-{(2S,3R)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxo-1-phenylazetidin-2-yl}phenyl acetate (114.5 mg, 100% yield) as a clear foam; Rf 0.11 (1:4 ethyl acetate-hexane).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][CH2:8][CH:9]2[CH2:12]OS(C)(=O)=O)=[CH:5][CH:4]=1.[C-:18]#[N:19].[Na+]>CS(C)=O>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][CH2:8][CH:9]2[CH2:12][C:18]#[N:19])=[CH:5][CH:4]=1
Reactant: [C-]#N
Reactant: COc1ccc2c(c1)C(COS(C)(=O)=O)CC2
Agent: [Na+]
Solvent: CS(C)=O
Product: COc1ccc2c(c1)C(CC#N)CC2
Temperature: 0 °C

Procedure:
12.8 g (50 mmol) of methanesulphonic acid (6-methoxyindan-1-ylmethyl) ester and 3.7 g (75 mmol) of sodium cyanide are dissolved in 70 ml of dimethyl sulphoxide and heated at 80° for 6 hours. The reaction mixture is poured onto 200 ml of ice-water and extracted three times by shaking with 100 ml of toluene each time. The organic phases are combined, subsequently washed with saturated sodium chloride solution and dried over magnesium sulphate. After removing the solvent in vacuo, crude 2-(6-methoxyindan-1-yl)acetonitrile is obtained.
Reaction SMILES: Br[CH2:2][C:3]1[NH:8][C:7]([C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=[N:6][CH:5]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[Cl:21])[C:4]=1[C:22]([O:24][CH2:25][CH3:26])=[O:23].Cl.[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH:29]1[CH2:34][C:35]([OH:37])=[O:36]>>[Cl:21][C:15]1[CH:16]=[C:17]([Cl:20])[CH:18]=[CH:19][C:14]=1[CH:5]1[N:6]=[C:7]([C:9]2[S:10][CH:11]=[CH:12][N:13]=2)[NH:8][C:3]([CH2:2][N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH:29]2[CH2:34][C:35]([OH:37])=[O:36])=[C:4]1[C:22]([O:24][CH2:25][CH3:26])=[O:23]
Reactant: CCOC(=O)C1=C(CBr)NC(c2nccs2)=NC1c1ccc(Cl)cc1Cl
Reactant: O=C(O)CC1COCCN1
Agent: Cl
Product: CCOC(=O)C1=C(CN2CCOCC2CC(=O)O)NC(c2nccs2)=NC1c1ccc(Cl)cc1Cl
Yield: 60.8 %

Procedure:
Ethyl 6-(bromomethyl)-4-(2,4-dichlorophenyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate (0.29 g, 0.61 mmol) was reacted with 2-(morpholin-3-yl)acetic acid hydrochloride (0.11 g, 0.61 mmol) according to the procedure as described in Example 1, Step C to give the title compound as a light yellow solid (0.2 g, 60%). The compound was characterized by the following spectroscopic data:
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[N:4]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)[N:3]=1.[CH3:19][O:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[CH:25][CH:26]=1.ClCCl.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:19][O:20][C:21]1[CH:26]=[C:25]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=3)[N:4]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][O:14]3)[N:3]=2)[CH:24]=[CH:23][CH:22]=1
Reactant: COc1cccc(B(O)O)c1
Reactant: N#Cc1ccc2c(c1)c(Br)nn2C1CCCCO1
Agent: [Fe+2]
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: COCCOC
Solvent: ClCCl
Product: COc1cccc(-c2nn(C3CCCCO3)c3ccc(C#N)cc23)c1
Yield: 87 %

Procedure:
The title compound was prepared as described in Example 161, using 3-bromo-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carbonitrile (0.350 g, 1.14 mmol), in ethylene glycol dimethyl ether (10 mL), 3-methoxy phenyl boronic acid (0.260 g, 1.71 mmol), [1,1′-bis(diphenylphosphino)-ferrocene] complex with dichloromethane (1:1) (0.131 g, 0.114 mmol), and potassium phosphate (1.20 g, 5.7 mmol): (0.333 g, 87% yield): ES-MS (m/z) 334 [M+1]+.
Reaction SMILES: [N:1]1([C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-])=O)[CH:10]=2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(O)C.[H][H]>[Pd]>[NH2:15][C:11]1[CH:10]=[C:9]([C:7]([N:1]2[CH2:2][CH2:3][O:4][CH2:5][CH2:6]2)=[O:8])[CH:14]=[CH:13][CH:12]=1
Reactant: O=C(c1cccc([N+](=O)[O-])c1)N1CCOCC1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: Nc1cccc(C(=O)N2CCOCC2)c1

Procedure:
Morpholin-4-yl-(3-nitro-phenyl)-methanone (2.74 g, 11.6 mmol) was dissolved in Ethanol (30.0 mL, 514 mmol) and the solution was carefully added to a Parr vessel containing 10% Palladium on Carbon (0.750 g, 56.2 mmol) under nitrogen. The mixture was then placed on a Parr hydrogenation apparatus and was allowed to shake at 55 psi until uptake of hydrogen ceased. The catalyst was then filtered to afford (3-Amino-phenyl)-morpholin-4-yl-methanone without further purification. (M+H)=207.6.
Reaction SMILES: [N:1]([CH:4]([CH3:6])[CH3:5])=[C:2]=[O:3].[C:7]([O:11][C:12]([NH:14][C@@H:15]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1)[C:16]([O:18][CH3:19])=[O:17])=[O:13])([CH3:10])([CH3:9])[CH3:8].C(N(CC)CC)C>C(Cl)Cl>[C:7]([O:11][C:12]([NH:14][C@@H:15]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][C:2](=[O:3])[NH:1][CH:4]([CH3:6])[CH3:5])=[CH:23][CH:22]=1)[C:16]([O:18][CH3:19])=[O:17])=[O:13])([CH3:10])([CH3:8])[CH3:9]
Reactant: CC(C)N=C=O
Reactant: COC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)OC(C)(C)C
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)[C@H](Cc1ccc(OC(=O)NC(C)C)cc1)NC(=O)OC(C)(C)C
Reaction time: 1 h
Yield: 65.7 %

Procedure:
2-Isocyanatopropane (Aldrich, Cat. #141070) (22 mg, 0.25 mmol) was added to a solution of methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-hydroxyphenyl)propanoate (50 mg, 0.2 mmol) and triethylamine (26 mg, 0.25 mmol) in methylene chloride (2 mL). The reaction was stirred for 1 h. The reaction was partitioned between water and ethyl acetate. The organic phase was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give crude product, (S)-methyl 2-(tert-butoxycarbonylamino)-3-(4-(isopropylcarbamoyloxy)phenyl)propanoate (50 mg, 80%) as a white solid. Analytical LCMS (M+H-Boc)+: m/z=281.0.
Reaction SMILES: 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.Cl[C:44]1[C:53]([CH3:54])=[C:52]([Cl:55])[C:51]2[C:46](=[CH:47][C:48]([F:57])=[CH:49][C:50]=2[F:56])[N:45]=1.[CH3:58][C:59]1([CH3:66])[CH2:64][NH:63][C:62](=[O:65])[CH2:61][CH2:60]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CCOC(C)=O.C(Cl)Cl.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]>[Cl:55][C:52]1[C:51]2[C:46](=[CH:47][C:48]([F:57])=[CH:49][C:50]=2[F:56])[N:45]=[C:44]([N:63]2[CH2:64][C:59]([CH3:66])([CH3:58])[CH2:60][CH2:61][C:62]2=[O:65])[C:53]=1[CH3:54]
Reactant: CC1(C)CCC(=O)NC1
Reactant: Cc1c(Cl)nc2cc(F)cc(F)c2c1Cl
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Solvent: ClCCl
Product: Cc1c(N2CC(C)(C)CCC2=O)nc2cc(F)cc(F)c2c1Cl
Temperature: 100 °C

Procedure:
XantPhos (273 mg, 0.472 mmol), 2,4-dichloro-5,7-difluoro-3-methylquinoline (780 mg, 3.20 mmol), 5,5-dimethylpiperidin-2-one (400 mg, 3.20 mmol), cesium carbonate (1.40 g, 4.40 mmol) and Pd2(dba)3 (140 mg, 0.160 mmol) was slurried in 1,4-dioxane (8.5 mL) and heated in a microwave reactor at 100° C. for 3 h. The reaction was cooled to rt and then diluted with EtOAc and DCM. The slurry was then filtered and concentrated. The residue was purified by column chromatography (silica gel, 0 to 50% EtOAc:DCM) to give 1-(4-chloro-5,7-difluoro-3-methylquinolin-2-yl)-5,5-dimethylpiperidin-2-one. Mass Spectrum (ESI) m/e=339.1 (M+1).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].[CH:15]([N:18]1[CH2:23][CH2:22][CH:21]([NH2:24])[CH2:20][CH2:19]1)([CH3:17])[CH3:16]>O1CCOCC1>[CH:15]([N:18]1[CH2:23][CH2:22][CH:21]([NH:24][C:2]2[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][C:3]=2[N+:12]([O-:14])=[O:13])[CH2:20][CH2:19]1)([CH3:17])[CH3:16]
Reactant: NS(=O)(=O)c1ccc(Cl)c([N+](=O)[O-])c1
Reactant: CC(C)N1CCC(N)CC1
Solvent: C1COCCO1
Product: CC(C)N1CCC(Nc2ccc(S(N)(=O)=O)cc2[N+](=O)[O-])CC1
Temperature: 90 °C
Reaction time: 16 h

Procedure:
A suspension of 4-chloro-3-nitrobenzenesulfonamide (1.664 g) triethylamine (2 mL) and 1-isopropylpiperidin-4-amine (1 g) in dioxane (10 mL) was stirred for 16 hours at 90° C. The reaction mixture was cooled to room temperature and the solid material was filtered off. The solid material was washed with 20% methanol/dichloromethane, and the mixture was dried under vacuum, to provide the product.
Reaction SMILES: [F:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][NH:10][CH2:9][C:8]2=[O:13])=[CH:4][CH:3]=1.C([O:18][CH:19]=[C:20]([C:26](OCC)=O)[C:21]([O:23][CH2:24][CH3:25])=[O:22])C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]3[CH:26]=[C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:19]([OH:18])=[C:9]3[C:8]2=[O:13])=[CH:4][CH:3]=1
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Reactant: O=C1CNCCN1Cc1ccc(F)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CCOC(=O)c1cn2c(c1O)C(=O)N(Cc1ccc(F)cc1)CC2
Temperature: 80 °C
Reaction time: 8 h

Procedure:
A mixture of 1-(4-fluorobenzyl)piperazin-2-one (10.0 g, 48.0 mmol) and diethyl ethoxymethylenemalonate (10.9 g, 50.4 mmol) in toluene (250 mL) was heated in a sealed tube at 80° C. for 4 hours. The resultant mixture was concentrated under vacuum. The residue was dissolved in anhydrous DMF (350 mL), cooled to 0° C. under an atmosphere of nitrogen, and treated with a solution of lithium bis(trimethylsilyl)amide in THF (1 M, 57.4 mL, 57.4 mmol). The reaction mixture was stirred at room temperature overnight and concentrated under vacuum. The residue was partitioned between ethyl acetate and dilute aqueous HCl. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was triturated with diethyl ether, and the solid precipitated was filtered to provide the titled compound.
Reaction SMILES: COC[N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[N:13]([CH3:26])S(C2C=CC([N+]([O-])=O)=CC=2)(=O)=O)[CH:6]=[C:5]1[C:27]([O:29][CH2:30][CH3:31])=[O:28].Cl>C(O)C>[CH3:26][NH:13][C:11]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:12]=1[NH:4][C:5]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:6]2
Reactant: CCOC(=O)c1cc2cccc(N(C)S(=O)(=O)c3ccc([N+](=O)[O-])cc3)c2n1COC
Agent: Cl
Solvent: CCO
Product: CCOC(=O)c1cc2cccc(NC)c2[nH]1
Temperature: 70 °C
Reaction time: 12 h
Yield: 26 %

Procedure:
To a solution of ethyl 1-(methoxymethyl)-7-{methyl[(4-nitrophenyl)sulfonyl]amino}-1H-indole-2-carboxylate (1.42 g) in ethanol (10 mL) was added 6N hydrochloric acid (10 mL), and the mixture was stirred at 70° C. for 12 hr. The reaction mixture was concentrated, water was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained residue was dissolved in N,N-dimethylformamide (8 mL), lithium hydroxide (520 mg) and mercaptoacetic acid (430 μL) were added, and the mixture was stirred at room temperature for 12 hr. To the reaction mixture was added methyl iodide (100 μL), and the mixture was stirred at room temperature for 1 hr. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained residue was subjected to silica gel column chromatography (ethyl acetate:hexane=1:1) to give a yellow amorphous (182 mg, yield 26%). M+1=219.
Reaction SMILES: C(OC(N1C[CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C@@H:21]3[O:30][C:25]4=[N:26][CH:27]=[CH:28][CH:29]=[C:24]4[O:23][CH2:22]3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.N1CC[CH:34]([O:37][CH2:38][C:39]([NH2:41])=[O:40])[CH2:33]C1>>[O:23]1[C:24]2[C:25](=[N:26][CH:27]=[CH:28][CH:29]=2)[O:30][C@@H:21]([C:18]2[CH:17]=[CH:16][C:15]([CH2:14][N:11]3[CH2:12][CH2:33][CH:34]([O:37][CH2:38][C:39]([NH2:41])=[O:40])[CH2:9][CH2:10]3)=[CH:20][CH:19]=2)[CH2:22]1
Reactant: CC(C)(C)OC(=O)N1CCN(Cc2ccc([C@H]3COc4cccnc4O3)cc2)CC1
Reactant: NC(=O)COC1CCNCC1
Product: NC(=O)COC1CCN(Cc2ccc([C@H]3COc4cccnc4O3)cc2)CC1

Procedure:
Compound 274 is synthesized from Intermediate C and 2-(piperidin-4-yloxy)acetamide according to General Method K. (LC/MS method 16: ES+ m/z 384.3 [M+H]+, Rt=0.32 min)
Reaction SMILES: [CH3:1][Sn:2]([CH3:11])([CH3:10])[C:3]1[S:7][C:6]([CH2:8][OH:9])=[CH:5][CH:4]=1.[I-].[Na+].Cl[CH2:15][C:16]([N:18]1[CH2:23][CH2:22][S:21][CH2:20][CH2:19]1)=[O:17]>>[N:18]1([C:16](=[O:17])[CH2:15][O:9][CH2:8][C:6]2[S:7][C:3]([Sn:2]([CH3:11])([CH3:10])[CH3:1])=[CH:4][CH:5]=2)[CH2:23][CH2:22][S:21][CH2:20][CH2:19]1
Reactant: C[Sn](C)(C)c1ccc(CO)s1
Reactant: O=C(CCl)N1CCSCC1
Agent: [I-]
Agent: [Na+]
Product: C[Sn](C)(C)c1ccc(COCC(=O)N2CCSCC2)s1

Procedure:
The 1-thiomorpholin-4-yl-2-(5-trimethylstannanyl-thiophen-2-ylmethoxy)-ethanone employed is prepared analogously to example (3a) (stage b)) starting from (5-trimethylstannanyl-thiophen-2-yl)-methanol (7.66 g; 27.67 mmol; described, in example (3a), stage a)), sodium iodide (4.07 g; 27.34 mmol) and 2-chloro-1-thiomorpholiri-4-yl-ethanone (5.92 g; 32.94 mmol)
Reaction SMILES: [CH3:1][CH:2]([OH:13])[CH2:3][C:4]([CH3:12])([O:6][O:7][C:8]([CH3:11])([CH3:10])[CH3:9])[CH3:5].N1C2C(=CC=CC=2)C=CC=1.Cl[C:25]([O:27][CH:28]([CH3:30])[CH3:29])=[O:26].Cl.N1C2C(=CC=CC=2)C=CC=1>CCCCC>[C:25](=[O:26])([O:27][CH:28]([CH3:30])[CH3:29])[O:13][CH:2]([CH3:1])[CH2:3][C:4]([CH3:12])([O:6][O:7][C:8]([CH3:11])([CH3:10])[CH3:9])[CH3:5]
Reactant: CC(C)OC(=O)Cl
Reactant: CC(O)CC(C)(C)OOC(C)(C)C
Agent: Cl
Solvent: c1ccc2ncccc2c1
Solvent: CCCCC
Product: CC(C)OC(=O)OC(C)CC(C)(C)OOC(C)(C)C
Reaction time: 72 h

Procedure:
A four-necked 500 ml. round-bottomed flask was equipped with a mechanical stirrer, reflux condenser surmounted by calcium chloride drying tube, addition funnel and thermometer. A solution of 19 g. (0.1 mole) 1,3-dimethyl-3-(t-butylperoxy)butyl alcohol and 13.3 g (slightly over 0.1 mole) quinoline in 250 ml. pentane was placed in the flask which was placed in a water bath at 221/2 ° C. Then 12.3 g (0.1 mole) isopropyl chloroformate was added dropwise over 5 minutes; the temperature did not rise over 23° C. Reaction was not complete after 3 days. Another 3 g. of quinoline was added, and the reaction was completed after another 3 days as indicated by the fact that no further precipitate of quinoline hydrochloride formed when an aliquot of clean pentane solution was withdrawn from the reaction mixture and allowed to stand for 15 minutes. The quinoline hydrochloride was filtered off and washed with 25 ml pentane which was added to the pentane solution. This solution was then successively washed with 25 ml. of 7% hydrochloric acid, two 50 ml. portions of water, and finally dried over sodium sulfate. After removal of drying agent and pentane, a yield of 23.8 g. (86.4%) of material found to be 1,3-dimethyl-3-(t-butylperoxy)butyl isopropyl carbonate by infrared analysis, was obtained.
Reaction SMILES: [H-].[Na+].[CH:3]1([OH:9])[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4]1.[Si:10](Cl)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]>C1COCC1.C(OC(=O)C)C>[Si:10]([O:8][CH:5]1[CH2:6][CH2:7][CH:3]([OH:9])[CH2:4]1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]
Reactant: OC1CCC(O)C1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)OC1CCC(O)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 34.9 %

Procedure:
Sodium Hydride (3.77 g, 0.094 mol, 60% in mineral oil) was added to a solution of 1,3-cyclopentanediol (9.62 g, 0.094 mol) in 100 mL of THF. A slight generation of gas was observed. After stirring at room temperature for 1 h, tert-butyldimethylsilyl chloride (14.2 g, 0.094 mol) was added and the mixture was stirred at room temperature over night. The reaction mixture was diluted with 500 mL of ethylacetate and washed with 125 mL of 10% K2CO3, brine, and dried over Na2SO4. The solution was concentrated and dried in vacuo to give 20.3 g of crude product as a colorless oil. Further purification over SiO2 using a gradient elution 5% EtOAc/hexanes to 10% EtOAc/hexanes provided the desired compound as a colorless oil (7.1 g, 35% yield).
Reaction SMILES: [Br:1][C:2]1[CH:6]=[C:5](/[CH:7]=[N:8]/[S:9]([C:11]([CH3:14])([CH3:13])[CH3:12])=[O:10])[O:4][N:3]=1.CC(C[AlH]CC(C)C)C>C1COCC1>[Br:1][C:2]1[CH:6]=[C:5]([CH2:7][NH:8][S:9]([C:11]([CH3:14])([CH3:13])[CH3:12])=[O:10])[O:4][N:3]=1
Reactant: CC(C)(C)S(=O)/N=C/c1cc(Br)no1
Agent: CC(C)C[AlH]CC(C)C
Solvent: C1CCOC1
Product: CC(C)(C)S(=O)NCc1cc(Br)no1
Reaction time: 1.5 h

Procedure:
To a chilled (−78° C.) yellow solution of 2-methyl-propane-2-sulfinic acid 1-(3-bromo-isoxazol-5-yl)-meth-(E)-ylideneamide (129 mg, 0.462 mmol) in THF (7 mL) was added a 1 M solution of DIBAH (1.2 mL, 1.2 mmol) in hexanes dropwise. After 1.5 hours, the reaction was quenched with MeOH (4 mL) and the cold bath was removed. The mixture was concentrated in vacuo and the residue was treated with 1 N aqueous NaOH (10 mL) and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to afford 2-methyl-propane-2-sulfinic acid (3-bromo-isoxazol-5-ylmethyl)-amide which was used without further purification. MS m/z 281.35 (M), 283.32 (M+2).
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl.O1CCCC1.O.CN(C)C=O>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: Nc1ccccn1
Reactant: O=C(O)C(CC1CCCC1)c1ccc(Cl)c(Cl)c1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: O
Product: O=C(Nc1ccccn1)C(CC1CCCC1)c1ccc(Cl)c(Cl)c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 40.9 %

Procedure:
A solution of 3-cyclopentyl-2-(3,4-dichlorophenyl)-propionic acid (114 mg, 0.39 mmol) in methylene chloride (10 mL) was treated with I drop of N,N-dimethylformamide and then cooled to 0° C. The reaction mixture was then treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.22 mL, 0.44 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution of 2-aminopyridine (78 mg, 0.83 mmol) and N,N-diisopropylethylamine (0.16 mL, 0.95 mmol) in tetrahydrofuran (2 mL). The resulting reaction mixture was stirred at 25° C. for 14 h. The reaction mixture was then diluted with water (10 mL) and extracted with methylene chloride (2×15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, hexanes then 19/1 to 4/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3,4-dichloro-phenyl)-N-pyridin-2-yl-propionamide (58 mg, 50%) as a white foam: EI-HRMS m/e calcd for C19H20Cl2N2O (M+) 362.0953, found 362.0955.
Reaction SMILES: [CH3:1][N:2]1[CH2:9][CH2:8][N:7](CC2C=CC=CC=2)[CH2:6][C:3]21[CH2:5][CH2:4]2.[ClH:17]>CO>[ClH:17].[ClH:17].[CH3:1][N:2]1[CH2:9][CH2:8][NH2+:7][CH2:6][C:3]21[CH2:5][CH2:4]2
Reactant: CN1CCN(Cc2ccccc2)CC12CC2
Agent: Cl
Solvent: CO
Product: CN1CC[NH2+]CC12CC2
Reaction time: 4 h
Yield: 60.3 %

Procedure:
4-Methyl-7-(phenylmethyl)-4,7-diazaspiro[2.5]octane (1.43 g, 6.624 mmol) was dissolved in 10 mL of MeOH, degassed and placed under argon. Pd(OH)2 (140 mg) was added, and the contents were hydrogenated for 4 h under 50 psi. The contents were then filtered to remove the catalyst, 1N HCl (14.57 mL, 14.57 mmol) was added to the filtrate, and the filtrate was concentrated in vacuo to provide pure 4-methyl-4-aza-7-azoniaspiro[2.5]octane, dihydrochloride (0.8 g, 60%). LCMS: (M+H)+: 127.2.
Reaction SMILES: O=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11]O)O)O)O)O.[CH3:13][O:14][C@H:15]1[O:20][CH:19]([CH2:21][OH:22])[C@H:18]([OH:23])[C@@H:17]([OH:24])[C@@H:16]1[OH:25]>>[CH3:2][CH2:3][CH2:5][CH2:7][CH2:9][CH2:11][CH2:2][CH2:3][CH2:5][CH2:7][CH2:9][CH2:13][O:14][C@@H:15]1[O:20][C@H:19]([CH2:21][OH:22])[C@@H:18]([OH:23])[C@H:17]([OH:24])[C@H:16]1[OH:25]
Reactant: CO[C@H]1OC(CO)[C@H](O)[C@@H](O)[C@@H]1O
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Product: CCCCCCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Temperature: 120 °C

Procedure:
The insoluble material was filtered, washed with Skellysolve B® solvent, a hydrocarbon solvent boiling in the range of 60° to 70° C., and then dried by heating at 120° C. at a pressure of about 4 mm. mercury. The dry material, which had a mass of 20.15 g., was analyzed by liquid chromatography and was found to contain approximately 88 weight percent methyl polyglucoside. This corresponds to approximately 0.11 moles of glucose units using the following conversion: ##EQU1## Therefore, of the 0.14 moles of methyl glucoside initially present, approximately 0.11 moles (or 79 percent) formed methyl polyglucoside rather than the desired dodecyl glucoside.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N+:26]([O-])=O)=[C:7]([CH:25]=1)[CH2:8][N:9]([CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:10](=[O:18])[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1.[H][H]>C(OCC)(=O)C.C(O)C.[Pd]>[NH2:26][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:25][C:7]=1[CH2:8][N:9]([CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:10](=[O:18])[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1
Reactant: CCOC(=O)CN(Cc1cc(OC)ccc1[N+](=O)[O-])C(=O)c1ccc(Cl)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Solvent: CCOC(C)=O
Product: CCOC(=O)CN(Cc1cc(OC)ccc1N)C(=O)c1ccc(Cl)cc1

Procedure:
1.0 g (2.5 mmol) of ethyl [(5-methoxy-2-nitrobenzyl)-(4-chlorobenzoyl)amino]acetate was dissolved in a mixture of 10 ml of ethyl acetate and 10 ml of ethanol. 360 mg of 10% palladium/carbon was added to the obtained solution, and they were stirred in the presence of hydrogen at room temperature for 4 hours. The reaction mixture was filtered through Celite and the solvent was evaporated. The obtained crude product was purified by the silica gel column chromatography to obtain the title compound.