Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:3]1[CH:7]=[CH:6][N:5]=[CH:4]1)[CH3:2].[Cl:8][CH2:9][CH2:10][S:11]([Cl:14])(=[O:13])=[O:12]>CN(C=O)C>[Cl-:8].[CH2:1]([N+:3]1[CH:7]=[CH:6][N:5]([CH2:9][CH2:10][S:11]([Cl:14])(=[O:13])=[O:12])[CH:4]=1)[CH3:2]
Reactant: CCn1ccnc1
Reactant: O=S(=O)(Cl)CCCl
Solvent: CN(C)C=O
Product: CC[n+]1ccn(CCS(=O)(=O)Cl)c1
Product: [Cl-]
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To DMF were added 2.1 g of 1-ethylimidazole and 5.0 g of 2-chloroethanesulfonyl chloride. This mixture was stirred at room temperature for 12 hours. The resultant reaction mixture was concentrated under a reduced pressure and then added dropwise to ether to obtain 1-ethyl-3-chlorosulfonylethylimidazolium chloride as a reddish-brown substance. To this reaction product was added 20 g of a 10% aqueous poly(allylamine) solution, followed by 200 ml of water. The mixture was reacted at 100° C. for 2 days in the presence of NaOH in an amount equivalent to the amino groups. To the resultant reaction mixture was added 100 ml of ethanol. After this mixture was allowed to stand at 0° C., the yellow powder precipitated was recovered by centrifuging to obtain a poly[allylsulfonamide-ethyl(1-ethyl)imidazolium]. To the thus-obtained molten salt polymer was added LiTFSI. Thus, a polyelectrolyte represented by the following formula was obtained. ##STR12##
Reaction SMILES: [NH2:1][C:2]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][C:11]2([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=3)[CH2:16][CH2:15][CH2:14][N:13]([C:17](=[O:24])[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:12]2)[CH2:4][CH2:3]1.C(N(CC)CC)C.[C:46]1([C:51](Cl)=[O:52])[S:50][CH:49]=[CH:48][CH:47]=1.Cl>C(Cl)Cl>[OH2:24].[ClH:31].[C:17]([N:13]1[CH2:14][CH2:15][CH2:16][C:11]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=2)([CH2:10][CH2:9][CH2:8][N:5]2[CH2:4][CH2:3][C:2]([NH:1][C:51](=[O:52])[C:46]3[S:50][CH:49]=[CH:48][CH:47]=3)([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:7][CH2:6]2)[CH2:12]1)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=C(Cl)c1cccs1
Reactant: NC1(c2ccccc2)CCN(CCCC2(c3ccc(Cl)c(Cl)c3)CCCN(C(=O)c3ccccc3)C2)CC1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O
Product: O=C(NC1(c2ccccc2)CCN(CCCC2(c3ccc(Cl)c(Cl)c3)CCCN(C(=O)c3ccccc3)C2)CC1)c1cccs1
Yield: 101.6 %

Procedure:
This compound is prepared by the procedure described in step B of EXAMPLE 19, starting from 1.5 g of the compound obtained in step A of EXAMPLE 19, 0.55 g of triethylamine and 0.4 g of 2-thenoyl chloride in 10 ml of DCM. The residue is chromatographed on silica H using DCM and then a DCM/MeOH mixture (95/5; v/v) as the eluent. The product obtained is taken up with DCM and acidified to pH 1 by the addition of ethereal hydrogen chloride and the precipitate obtained is filtered off to give 0.99 g of the expected product, m.p.=198-200° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([CH3:18])[CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:4][CH:3]=1.Br[C:20]1[C:21]2[C:22]3[CH:36]=[CH:35][S:34][C:23]=3[C:24](=[O:33])[NH:25][C:26]=2[C:27]([CH3:32])=[CH:28][C:29]=1[O:30][CH3:31]>>[CH3:31][O:30][C:29]1[CH:28]=[C:27]([CH3:32])[C:26]2[NH:25][C:24](=[O:33])[C:23]3[S:34][CH:35]=[CH:36][C:22]=3[C:21]=2[C:20]=1[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([CH3:18])[CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:4][CH:3]=1
Reactant: C[C@@H](CNC(=O)OC(C)(C)C)c1ccc(Br)cc1
Reactant: COc1cc(C)c2[nH]c(=O)c3sccc3c2c1Br
Product: COc1cc(C)c2[nH]c(=O)c3sccc3c2c1-c1ccc([C@@H](C)CNC(=O)OC(C)(C)C)cc1
Yield: 54.3 %

Procedure:
Following General Procedure E, (R)-tert-butyl 2-(4-bromophenyl)propylcarbamate (60 mg, 0.20 mmol) was reacted with 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (60 mg, 0.20 mmol) to afford the desired product (52 mg, 62%) as a brown solid: ESI MS m/z 479 [C27H30N2O4S]+
Reaction SMILES: [C:1]([C:3]1[CH:25]=[CH:24][C:6]2[NH:7][C:8]3[N:9]=[CH:10][CH:11]=[CH:12][C:13]=3[C:14]([C:20]([F:23])([F:22])[F:21])([CH2:15][O:16][CH:17]([CH3:19])[CH3:18])[C:5]=2[CH:4]=1)#[N:2].C1C(=O)N([Br:33])C(=O)C1.CCOC(C)=O.CCCCCC>C(#N)C>[Br:33][C:11]1[CH:10]=[N:9][C:8]2[NH:7][C:6]3[CH:24]=[CH:25][C:3]([C:1]#[N:2])=[CH:4][C:5]=3[C:14]([C:20]([F:21])([F:22])[F:23])([CH2:15][O:16][CH:17]([CH3:19])[CH3:18])[C:13]=2[CH:12]=1
Reactant: CC(C)OCC1(C(F)(F)F)c2cc(C#N)ccc2Nc2ncccc21
Reactant: O=C1CCC(=O)N1Br
Solvent: CCOC(C)=O
Solvent: CC#N
Solvent: CCCCCC
Product: CC(C)OCC1(C(F)(F)F)c2cc(C#N)ccc2Nc2ncc(Br)cc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 97.3 %

Procedure:
To a stirred solution of 7-cyano-5-trifluoromethyl-5-isopropoxymethyl-5,10-dihydrobenzo[b][1,8]naphthyridine (14)(61 mg, 0.176 mmol) in anhydrous acetonitrile (2 mL) at room temperature was added NBS (38 mg, 0.211 mmol). The reaction mixture was stirred at room temperature for 1 h 30 min. The reaction was quenched with 1:1 saturated aqueous NaHCO3/water (20 mL), and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. Flash chromatography (20%-30% EtOAc-Hexane) furnished 15 (73 mg, 97% yield) as an off-white solid: m.p. 76-77° C.; low resolution mass spectrum (ESI) m/z 426.2 [(M+H)+ calcd for C18H16BrF3N3O: 426.05].
Reaction SMILES: C[O:2][C:3]([C:5]1[N:6]([CH3:25])[N:7]=[C:8](/[CH:10]=[CH:11]\[C:12]2[C:13]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)=[N:14][O:15][C:16]=2[CH3:17])[CH:9]=1)=[O:4].O.[OH-].[Li+]>C1COCC1.O>[F:24][C:21]1[CH:20]=[CH:19][C:18]([C:13]2[C:12](/[CH:11]=[CH:10]\[C:8]3[CH:9]=[C:5]([C:3]([OH:4])=[O:2])[N:6]([CH3:25])[N:7]=3)=[C:16]([CH3:17])[O:15][N:14]=2)=[CH:23][CH:22]=1
Reactant: COC(=O)c1cc(/C=C\c2c(-c3ccc(F)cc3)noc2C)nn1C
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Cc1onc(-c2ccc(F)cc2)c1/C=C\c1cc(C(=O)O)n(C)n1
Reaction time: 12 h
Yield: 85 %

Procedure:
To a solution of 5-{(Z)-2-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-vinyl}-2-methyl-2H-pyrazole-3-carboxylic acid methyl ester (6.29 mmol) in THF (14 mL) was added lithium hydroxide monohydrate (37.79 mmol) in water (18 mL) and the resulting mixture stirred for 12 h. After evaporation the mixture was diluted with water (10 mL) and citric acid (10%) and extracted with ethyl acetate (2×80 mL). The combined extracts were then dried with sodium sulfate, filtered and evaporated to afford 5-{(Z)-2-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-vinyl}-2-methyl-2H-pyrazole-3-carboxylic acid (mg, 85%) as a white solid. MS: m/e=328.2 [M+H]+.
Reaction SMILES: [C:1]12([CH2:11][CH2:12][C:13]3[NH:17][C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[CH3:24])=[N:15][C:14]=3[C:25](O)=[O:26])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH3:28][O:29][C:30](=[O:40])[C:31]1[C:36]([CH3:37])=[CH:35][CH:34]=[C:33]([NH2:38])[C:32]=1[CH3:39]>>[CH3:28][O:29][C:30](=[O:40])[C:31]1[C:36]([CH3:37])=[CH:35][CH:34]=[C:33]([NH:38][C:25]([C:14]2[N:15]=[C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[CH3:24])[NH:17][C:13]=2[CH2:12][CH2:11][C:1]23[CH2:10][CH:5]4[CH2:4][CH:3]([CH2:9][CH:7]([CH2:6]4)[CH2:8]2)[CH2:2]3)=[O:26])[C:32]=1[CH3:39]
Reactant: Cc1ccccc1-c1nc(C(=O)O)c(CCC23CC4CC(CC(C4)C2)C3)[nH]1
Reactant: COC(=O)c1c(C)ccc(N)c1C
Product: COC(=O)c1c(C)ccc(NC(=O)c2nc(-c3ccccc3C)[nH]c2CCC23CC4CC(CC(C4)C2)C3)c1C
Yield: 65.4 %

Procedure:
5-(2-Adamantan-1-yl-ethyl)-2-o-tolyl-1H-imidazole4-carboxylic acid (Example 93) (374 mg, 1.00 mmol) was reacted with 3-amino-2,6-dimethyl-benzoic acid methyl ester (prepared from 2,6-dimethyl-benzoic acid by nitration, esterification and reduction) (179 mg, 1.00 mmol) according to the procedure of Example 20, step d. The crude product was purified by flash chromatography (silica, hexane/ethyl acetate 2:1) to afford colourless foam (344 mg, 64%). 1H NMR (300 MHz, CDCl3) 9.32 (1H, br s), 9.22 (1H, br s), 8.12 (1H, d), 7.55 (1H, d), 7.29 (3H, m), 7.08 (1H, d), 3.92 (3H, s), 3.12 (2H, m) 2.63 (3H, s), 2.28 (6H, s), 1.97 (3H, s), 1.74-1.44 (14H, m).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[O:10][C:11]([O:17][CH2:18][CH3:19])=[C:12]([C:14]([OH:16])=O)[N:13]=1.O.O[C:22]1[C:30]2N=N[NH:27][C:26]=2[CH:25]=[CH:24][CH:23]=1.N=C=N.NC1C=CC=CC=1>C(Cl)Cl>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[O:10][C:11]([O:17][CH2:18][CH3:19])=[C:12]([C:14]([NH:27][C:26]2[CH:30]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:16])[N:13]=1
Reactant: Oc1cccc2[nH]nnc12
Reactant: CCOc1oc(-c2c(F)cccc2F)nc1C(=O)O
Agent: N=C=N
Solvent: Nc1ccccc1
Solvent: O
Solvent: ClCCl
Product: CCOc1oc(-c2c(F)cccc2F)nc1C(=O)Nc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 102 %

Procedure:
To a solution of 2-(2,6-difluorophenyl)-5-ethoxyoxazole-4-carboxylic acid (0.10 g, 0.37 mmol) and hydroxybenzotriazole monohydrate (0.06 g, 0.39 mmol) in DCM (4 mL) was added PS-carbodiimide resin (0.36 g, 0.45 mmol, 1.25 mmol/g) followed by aniline (39 uL, 0.43 mmol). The resulting mixture was stirred at room temperature for 4 hours when a further portion of aniline (7 uL, 0.08 mmol) was added and the reaction stirred at room temperature overnight. The mixture was filtered through a silica-carbonate cartridge, followed by a MP-TsOH resin cartridge which was rinsed with DCM and MeOH to afford 2-(2,6-difluorophenyl)-5-ethoxy-N-phenyloxazole-4-carboxamide (0.13 g) which was used without further purification. LCMS (1) Rt: 2.30; m/z (ES+) 345.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][Br:12].[C:13]1([Li])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C1COCC1>[Br:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: BrCCCCCCCCCCBr
Reactant: [Li]c1ccccc1
Solvent: C1CCOC1
Product: BrCCCCCCCCCCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 61.7 %

Procedure:
To a 250 mL flask in ice-water bath was added 1,10-dibromodecane (46.0 g, 153 mmol) and anhydrous THF (100 ml) under nitrogen. Phenyl lithium (1.8 M in dibutyl ether, 28.5 mL, 51 mmol) was added dropwise. After addition was completed, the reaction mixture was stirred for 1 hour and warmed to room temperature. After 48 hours, it was quenched with H2O (200 mL), extracted with CH2Cl2 (200 mL×2) and dried. After concentration, the residue was distilled to give a colorless oil (9.35 g, yield 61.7%) at 130° C./0.07 mmHg. 1H NMR (CDCl3, 500 MHz) δ=7.27-7.32 (m, 2H), 7.20 (d, J=6.5 Hz, 3H), 3.43 (t, J=7.0 Hz, 2H), 2.62 (t, J=8.0 Hz, 2H), 1.84-1.96 (m, 2H), 1.60-1.68 (m, 2H), 1.41-1.52 (m, 2H), 1.24-1.41 (m, 10H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[H-].[Na+].[CH3:18]I>CN(C=O)C>[CH3:18][NH:1][C:2]1[CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:5]=[C:4]([CH:3]=1)[C:12]([O:14][CH3:15])=[O:13]
Reactant: CI
Reactant: COC(=O)c1cc(N)cc(C(=O)OC)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CNc1cc(C(=O)OC)cc(C(=O)OC)c1
Temperature: 0 °C
Reaction time: 8 h
Yield: 53.8 %

Procedure:
A solution of dimethyl 5-aminoisophthalate (0.250 g, 1.17 mmol, 1 eq) dissolved in 3 mL anhydrous DMF was added dropwise to a stirred suspension of NaH (60% dispersion in mineral oil, 0.14 g, 3.5 mmol, 3 eq) in 2 mL anhydrous DMF at 0° C. under Ar. MeI (0.23 mL, 0.53 g, 3.7 mmol, 3.2 eq) was added dropwise to the resulting mixture. The reaction was stirred at 0° C. to room temperature overnight. The reaction was poured into ice water to quench. The aqueous mixture was extracted with EtOAc (×2), and the combined organic extracts were washed with water (×3), brine (×1), and dried over Na2SO4. The inorganics were filtered off, and the solvent was removed in vacuo. Purification via flash chromatography on silica gel yielded 0.14 g (0.63 mmol, 54% yield) of dimethyl 5-(methylamino)isophthalate.
Reaction SMILES: C([O:4][CH2:5][CH2:6][O:7][C:8]1[CH:21]=[CH:20][C:11]([C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:13])=[CH:10][CH:9]=1)(=O)C.[OH-].[Na+].Cl>C(O)C>[OH:4][CH2:5][CH2:6][O:7][C:8]1[CH:21]=[CH:20][C:11]([C:12]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[O:13])=[CH:10][CH:9]=1
Reactant: CC(=O)OCCOc1ccc(C(=O)c2ccccc2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(c1ccccc1)c1ccc(OCCO)cc1
Reaction time: 0.33 h

Procedure:
43 g (0.15 mole) of 4-(2-acetoxyethoxy)-benzophenone are dissolved in 60 ml of ethanol and boiled with 17 ml of 32% strength sodium hydroxide solution under reflux, with stirring, for 20 minutes. After cooling, the reaction mixture is neutralized with hydrochloric acid, whereupon the end product is precipitated as a white solid. The reaction mixture is poured into 500 ml of water, and the solid is filtered off with suction, washed and dried in vacuo at 50° C. for 5 hours. This gives 35 g (95%) of 4-(2-hydroxyethoxy)-benzophenone, melting point 82° C.
Reaction SMILES: [Cl-].[Ce+3].[Cl-].[Cl-].[CH2:5]([Li])[CH2:6][CH2:7][CH3:8].[CH3:10][C:11]1[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[C:13]([CH3:19])[C:12]=1[C:20]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([CH:30]([CH3:32])[CH3:31])[CH:23]=1)=[O:21].[NH4+].[Cl-]>O1CCCC1>[CH3:10][C:11]1[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[C:13]([CH3:19])[C:12]=1[C:20]([C:22]1[C:27]([CH2:5][CH2:6][CH2:7][CH3:8])=[CH:26][C:25]([O:28][CH3:29])=[C:24]([CH:30]([CH3:32])[CH3:31])[CH:23]=1)=[O:21]
Reactant: COc1cc(C)c(C(=O)c2ccc(OC)c(C(C)C)c2)c(C)c1
Reactant: [Li]CCCC
Agent: [Ce+3]
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCCCc1cc(OC)c(C(C)C)cc1C(=O)c1c(C)cc(OC)cc1C
Reaction time: 2 h
Yield: 43 %

Procedure:
To anhydrous cerium chloride (3.16 g, 12.8 mmol) dry tetrahydrofuran (50 mL) was added with stirring under argon and stirring was continued for 2 hours at room temperature. The resultant suspension was then cooled to -78° C., and 6.4 mL of n-butyllithium (2.0M in pentane) was added with stirring, whereupon the color of the suspension turned from white to yellow. After maintaining the same temperature for 30 minutes, (2,6-dimethyl-4-methoxyphenyl)-(3-isopropyl-4-methoxyphenyl) methanone (10) (1 g, 3.20 mmol) in tetrahydrofuran (5 mL) was added and the mixture was stirred for 3 hours at -78° C. and for 2 hours at 0° C. The reaction mixture was treated with sat. NH4Cl solution, filtered through Celite, and extracted with ethyl acetate. The combined extracts were dried (Na2SO4), evaporated, and the residue was purified by flash column chromatography (silica gel, 95:5 hexane/ethylacetate) to give (2,6-dimethyl-4-methoxyphenyl)-(6-n-butyl-3-isopropyl-4-methoxyphenyl) methanone (15) (500 mg, 43%); 1HNMR (CDCl3) δ 0.98 (t, 3H), 1.03 (d, 6H), 1.41 (m, 2H), 1.59 (m, 2H), 2.09 (s, 6H), 3.05 (t, 2H), 3.14 (heptet, 1H),3.86 (d, 6H), 6.52 (d, 2H), 6.73 (s, 2H), 7.22 (s, 1H).
Reaction SMILES: [CH2:1]([C:3]1[N:8]=[C:7]([NH2:9])[CH:6]=[CH:5][CH:4]=1)[CH3:2].C(N(CC)CC)C.[C:17](Cl)(=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19]>ClCCl>[CH2:1]([C:3]1[N:8]=[C:7]([NH:9][C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])[CH:6]=[CH:5][CH:4]=1)[CH3:2]
Reactant: CCc1cccc(N)n1
Reactant: CC(C)(C)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCc1cccc(NC(=O)C(C)(C)C)n1
Reaction time: 2 h
Yield: 54.1 %

Procedure:
A solution of 6-ethyl-pyridin-2-ylamine (20 g, 0.164 mol) and triethylamine (29.6 mL, 0.213 mol) in dichloromethane (200 mL, 0.8 M) is cooled to 0° C. and carefully treated with pivaloyl chloride (26.2 mL, 0.213 mol). After stirring for 2 h, the solution is quenched with aq NaHCO3, extracted with dichloromethane and concentrated. The resulting oil is filtered through a plug of silica gel using ethyl acetate. The filtrate is concentrated and triterated with heptane to give N-(6-ethyl-pyridin-2-yl)-2,2-dimethyl-propionamide (18.3 g, 54%) as a white crystalline solid. mp 59-62° C.; Rf 0.31 (25% ethyl acetate in hexanes); 1H NMR (DMSO-d6, 300 MHz) δ 9.56 (s, 1 H), 7.85 (d, J=8.4 Hz, 1 H), 7.63 (t, J=7.8 Hz, 1 H), 6.93 (d, J=7.5 Hz, 1 H), 2.65 (q, J=7.8 Hz, 2 H), 1.20 (s, 9 H), 1.18 (t, 7.8 Hz, 3 H); LRMS calcd for C12H18N2O: 206.2; found 206.0 (M)+. Anal. Calcd for C12H18N2O: C, 69.87; H, 8.80; N, 13.58. Found C, 69.60; H, 8.67; N, 13.42.
Reaction SMILES: [CH:1](=[O:6])[CH2:2][CH:3]([CH3:5])[CH3:4].[CH2:7]([Mg]Cl)[CH2:8][CH2:9][CH3:10]>C1COCC1>[CH3:4][CH:3]([CH2:2][CH:1]([OH:6])[CH2:7][CH2:8][CH2:9][CH3:10])[CH3:5]
Reactant: CCCC[Mg]Cl
Reactant: CC(C)CC=O
Solvent: C1CCOC1
Product: CCCCC(O)CC(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 76.5 %

Procedure:
A solution of isovaleraldehyde (5.o g, 58 mmol) in dry THF (15 ml) was added to a stirred 2M THF solution of n-butylmagnesium chloride (30 ml, 60 mmol) at 0° C. under argon. The mixture was allowed to warm up to room temperature and was stirred overnight. The reaction was quenched by the addition of aqueous ammonium chloride (50 ml) and extracted with diethyl ether (200 ml). The organic extracts were dried over anhydrous potassium carbonate, filtered and concentrated to give 2-methyloctan-4-ol (6.4 g, 77%) as a clear oil.
Reaction SMILES: [Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.[OH:12][CH:13]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:14][CH2:15][CH2:16][O:17][C:18](=[O:26])[NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(Cl)Cl>[O:12]=[C:13]([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[CH2:14][CH2:15][CH2:16][O:17][C:18](=[O:26])[NH:19][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: O=C(Nc1ccccc1)OCCCC(O)c1ccccc1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: O=C(Nc1ccccc1)OCCCC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 819.3 %

Procedure:
Pyridinium chlorochromate (15.28 g, 70.9 mmol) was added to a solution of phenyl-carbamic acid 4-hydroxy-4-phenyl-butyl ester (13.48 g, 4.73 mmol), prepared in the previous step, in 300 ml of methylene chloride and the mixture stirred at room temperature for 2.5 hours. The reaction was poured onto 700 g of a silica gel (230-400 mesh) column made with methylene chloride. Eluting with 0.5%-1.5% ethyl acetate-methylene chloride gave phenyl-carbamic acid 4-oxo-4-phenyl-butyl ester (10.98 g, 82%) as a white solid, mp 121-123° C.
Reaction SMILES: [CH2:1]([C:3]1([CH3:6])[CH2:5][O:4]1)[CH3:2].[N-:7]=[N+:8]=[N-:9].[Na+]>>[CH2:1]([C@@:3]1([CH3:6])[CH2:5][O:4]1)[CH3:2].[N:7]([CH2:5][C@:3]([CH3:6])([OH:4])[CH2:1][CH3:2])=[N+:8]=[N-:9]
Reactant: CCC1(C)CO1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Product: CC[C@@](C)(O)CN=[N+]=[N-]
Product: CC[C@@]1(C)CO1
Temperature: 24 °C
Reaction time: 1 h
Yield: 41 %
Yield: 43 %

Procedure:
500 mg (5.8 mmol) of racemic 2-ethyl-2-methyloxirane was dissolved in 100 mL Tris-SO4 buffer (200 mM, pH 7.5), followed by addition of purified enzyme (15 mg of halohydrin dehalogenase HheC in 450 μL buffer) and 189 mg (2.9 mmol) NaN3. The reaction mixture was stirred at room temperature (24° C.) and monitored by gas chromatography (GC). The reaction was stopped after 1 h and extracted three times by adding 50 mL ethylacetate. The combined organic phases were dried over Na2SO4 and evaporated. The crude product was chromatographed on a silica gel 60 H using pentane/CH2Cl2 (4:6) as eluent. This yielded pure (S)-2-ethyl-2-methyloxirane (205 mg, 41% yield, e.e.>99%) and (R)-azido-2-methylbutan-2-ol (320 mg, 43% yield, e.e.>99%). Optical purities were determined by GC using a Chiraldex G-TA column (30 m×0.25 mm×0.25 μm). The NMR data were identical with those of synthesized racemic reference compounds.
Reaction SMILES: [CH2:1]([CH2:3][NH2:4])[OH:2].[CH2:5]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH:6]1[O:8][CH2:7]1>>[OH:8][CH:6]([CH2:5][O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH2:7][NH:4][CH2:3][CH2:1][OH:2]
Reactant: NCCO
Reactant: CCCCCCCCCCCCCCCCOCC1CO1
Product: CCCCCCCCCCCCCCCCOCC(O)CNCCO
Reaction time: 0.75 h
Yield: 62.4 %

Procedure:
61.1 g (1.0 mol) of ethanolamine was introduced into a 200-ml four-necked flask equipped with a stirrer, a dropping funnel, a thermometer and a reflux condenser and heated to 60° to 70° C. under stirring. 24.3 g (0.082 mol) of hexadecyl glycidyl ether was added dropwise thereto over a period of 45 minutes. After the addition was completed, the resulting mixture was heated and stirred under the same conditions as those described above for additional two hours. Then unreacted ethanolamine was distilled off under reduced pressure (79 to 81° C./20 Torr). The residue was purified by silica gel flash column chromatography to thereby give 18.4 g of the compound (IIIa) at a yield of 63%. The data of the 1H-NMR of the obtained compound are as follows:
Reaction SMILES: C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[NH:8][CH2:9][CH2:10][S:11][C:12](OC2C=CC([N+]([O-])=O)=CC=2)=[O:13])C=CC=CC=1.[OH:36][CH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1>>[OH:36][CH:37]1[CH2:42][CH2:41][N:40]([C:12]([S:11][CH2:10][CH2:9][NH2:8])=[O:13])[CH2:39][CH2:38]1
Reactant: OC1CCNCC1
Reactant: O=C(Oc1ccc([N+](=O)[O-])cc1)SCCNC(c1ccccc1)(c1ccccc1)c1ccccc1
Product: NCCSC(=O)N1CCC(O)CC1
Yield: 146.3 %

Procedure:
N-triphenylmethyl-2-paranitrophenoxycarbonylthioethylamine (300 mg) and 4-hydroxypiperidine (219 mg) were subjected to similar reactions to those described in References 2 and 4 to give 2-(4-hydroxypiperidino)carbonylthioethylamine (crude formate: 185 mg) which was then dissolved in anhydrous methanol (3 ml). To the reaction solution were added triethylamine (515 μl) and mitomycin A (207 mg: 0.8 molar equivalent). The reaction solution was treated in a similar manner to that described in Example 1 to obtain Compound 43 (325 mg) in the form of grayish blue powders with a yield of 84%.
Reaction SMILES: O=C1[C:6]2([CH2:11][CH2:10][C:9](=[O:12])[CH2:8][CH2:7]2)C(=O)CC1.C(C(C)CC1CC(CC2C=C[C:28]([O:31]C)=[CH:27]C=2)CCC1=O)#N.[Br-].COC1C=CC(C[P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(C1OC1)Cl>C1(C)C=CC=CC=1>[O:12]1[C:9]2([CH2:8][CH2:7][CH2:6][CH2:11][CH2:10]2)[O:31][CH2:28][CH2:27]1
Reactant: O=C1CCC2(CC1)C(=O)CCC2=O
Reactant: COc1ccc(CC2CCC(=O)C(CC(C)C#N)C2)cc1
Agent: COc1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Br-]
Solvent: ClCC1CO1
Solvent: Cc1ccccc1
Product: C1CCC2(CC1)OCCO2
Yield: 136.4 %

Procedure:
2-(2-Cyanopropyl)-4-(4-methoxybenzyl)cyclohexanone 1,4-Dioxospiro[4,5]decan-8-one (45.6 g) was added to a mixture of 4-methoxybenzyl triphenylphosphonium bromide (127.3 g) and epichlorohydrin (100 ml) in toluene (1500 ml) and heated at reflux under a nitrogen atmosphere for 36 hours. The solvent was evaporated under reduced pressure and the residue was extracted into hexane. The hexane solution was evaporated under reduced pressure and the residue distilled at 24° C./1 mmHg to give 8-(4-methoxybenzylidine)- 1,4-dioxaspiro[4,5]-decane, (19 g).
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][CH3:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC1[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][CH:20]=[CH:19][N:18]=1.BrC1C(OCC)=[CH:31][CH:30]=[CH:29]N=1>>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH2:29][CH2:30][CH3:31])[C:15]2[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOc1cccnc1Br
Reactant: O=[N+]([O-])c1cccnc1Cl
Reactant: CNC1CCN(Cc2ccccc2)CC1
Product: CCCN(c1ncccc1[N+](=O)[O-])C1CCN(Cc2ccccc2)CC1

Procedure:
Following the general procedure of EXAMPLE 70, and making non-critical variations but substituting 1-benzyl-4-(propylamino)piperidine (EXAMPLE 112) for 1-benzyl-4-(methylamino)piperidine and 2-chloro-3-nitropyridine for 2-bromo-3-ethoxypyridine and using a reaction time of 10 min, the title compound is obtained, C,H,N: Anal. Calcd for C20H26N4O2 : C=67.77, H=7.39, N=15.81-found: C=67.44, H=7.42, N=15.60.