Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O=O.[H-].[Na+].[C:5]([O:10]CC)(=O)[CH2:6][CH2:7][CH3:8].[CH3:13][C:14](=[O:17])[CH2:15][CH3:16]>N#N.O1CCCC1.O>[CH3:16][CH2:15][C:14](=[O:17])[CH2:13][C:5](=[O:10])[CH2:6][CH2:7][CH3:8]
Reactant: CCC(C)=O
Reactant: CCCC(=O)OCC
Agent: N#N
Agent: O=O
Agent: [H-]
Solvent: O
Solvent: C1CCOC1
Product: CCCC(=O)CC(=O)CC
Yield: 56.3 %

Procedure:
In N2 atmosphere free of water and oxygen, to a 3-neck flask placed in an ice-bath and equipped with addition funnel and reflux condenser were successively added 0.07 mol sodium hydride and 100 ml tetrahydrofuran. To the mixture was added dropwise a solution of 0.06 mol ethyl butyrate and 0.03 mol butanone with stirring. Upon completing the addition, the mixture was heated refluxing for 4 hours. The solvent and composition with a boiling point below 110° C. were removed by distillation. To the residue was added an appropriate amount of saturated saline until the solid composition was just dissolved. The mixture was extracted with ethyl ether for three times. The organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed by distillation to give 2.4 g product.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1Cl)[CH2:5][C:6]1([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8][CH2:7]1.[CH:20]1(B(O)O)[CH2:22][CH2:21]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>O1CCOCC1.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].C1CCCCC1.C(OCC)(=O)C>[NH2:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[CH:20]1[CH2:22][CH2:21]1)[CH2:5][C:6]1([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8][CH2:7]1
Reactant: OB(O)C1CC1
Reactant: CC(C)(C)OC(=O)C1(Cc2ccc(Cl)c(N)c2)CC1
Agent: [Pd]
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CCOC(C)=O
Solvent: C1CCCCC1
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)C1(Cc2ccc(C3CC3)c(N)c2)CC1
Temperature: 150 °C
Reaction time: 1 h

Procedure:
200 mg (0.71 mmol) of tert-butyl 1-(3-amino-4-chlorobenzyl)cyclopropanecarboxylate were dissolved in 6 ml of dioxane, the mixture was inertized with argon and 122 mg (1.42 mmol) of cyclopropylboronic acid, 256 mg (1.21 mmol) of potassium phosphate, 5 mg (0.02 mmol) of tricyclohexylphosphine and 6.5 mg (0.007 mmol) of tris(dibenzylideneacetone)dipalladium were added. The reaction mixture was then stirred in a microwave apparatus (Biotage) at a target temperature of 150° C. for 1 h. The reaction was checked by TLC (mobile phase cyclohexane/ethyl acetate 4:1), after which a further 10 mg of tricyclohexylphosphine and 13 mg of tris(dibenzylideneacetone)dipalladium were metered in, and the reaction mixture was stirred at 150° C. for another 2 h. The mixture was then filtered through kieselguhr, the residue was washed with dioxane and the combined filtrate was concentrated to dryness. The residue obtained was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 4:1). This gave 120 mg (59% of theory) of the target compound.
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.FC(F)(F)C(O)=O.[CH:32]([C:35]1[S:36][CH:37]=[C:38]([C:40]([N:42]2[CH2:66][C:46]3([CH2:49][N:48]([CH2:50][CH2:51][C:52]4[CH:53]=[C:54]([CH:63]=[CH:64][CH:65]=4)[CH2:55][CH2:56][O:57][CH2:58][CH2:59][C:60](O)=[O:61])[CH2:47]3)[O:45][CH2:44][CH2:43]2)=[O:41])[N:39]=1)([CH3:34])[CH3:33].[CH3:67][O:68][CH:69]([O:78][CH3:79])[CH2:70][NH:71][CH:72]1[CH2:77][CH2:76][CH2:75][CH2:74][CH2:73]1.C(N(CC)CC)C>CN(C=O)C>[CH:72]1([N:71]([CH2:70][CH:69]([O:78][CH3:79])[O:68][CH3:67])[C:60](=[O:61])[CH2:59][CH2:58][O:57][CH2:56][CH2:55][C:54]2[CH:63]=[CH:64][CH:65]=[C:52]([CH2:51][CH2:50][N:48]3[CH2:47][C:46]4([CH2:66][N:42]([C:40]([C:38]5[N:39]=[C:35]([CH:32]([CH3:33])[CH3:34])[S:36][CH:37]=5)=[O:41])[CH2:43][CH2:44][O:45]4)[CH2:49]3)[CH:53]=2)[CH2:77][CH2:76][CH2:75][CH2:74][CH2:73]1
Reactant: COC(CNC1CCCCC1)OC
Reactant: CC(C)c1nc(C(=O)N2CCOC3(CN(CCc4cccc(CCOCCC(=O)O)c4)C3)C2)cs1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COC(CN(C(=O)CCOCCc1cccc(CCN2CC3(C2)CN(C(=O)c2csc(C(C)C)n2)CCO3)c1)C1CCCCC1)OC
Temperature: 20 °C
Reaction time: 3 h

Procedure:
HATU (0.201 g) was added in one portion to a stirred solution at 0° C. of 3-(3-(2-(8-(2-isopropylthiazole-4-carbonyl)-5-oxa-2,8-diazaspiro[3.5]nonan-2-yl)ethyl)phenethoxy)propanoic acid trifluoroacetate salt (0.25 g) (example 176 step h), N-(2,2-dimethoxy ethyl)cyclohexanamine (0.076 g) (WO2008075025) and triethylamine (0.283 ml) in DMF (4 mL) at 0° C. The mixture was stirred at 20° C. for 3 hours and then partitioned between ethyl acetate and brine, the organic layer was washed with brine (×2), dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure to afford the subtitled compound. Yield 0.270 g.
Reaction SMILES: [N:1]1([NH:7][C:8](=[O:34])[C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]([C:19]3[CH:28]=[CH:27][C:26]4[C:25]([CH3:30])([CH3:29])[CH2:24][CH2:23][C:22]([CH3:32])([CH3:31])[C:21]=4[CH:20]=3)=[O:18])=[CH:11][C:10]=2[OH:33])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(C)C.C1COCC1.[BH4-].[Na+]>CC(C)=O>[N:1]1([NH:7][C:8](=[O:34])[C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH:17]([OH:18])[C:19]3[CH:28]=[CH:27][C:26]4[C:25]([CH3:29])([CH3:30])[CH2:24][CH2:23][C:22]([CH3:31])([CH3:32])[C:21]=4[CH:20]=3)=[CH:11][C:10]=2[OH:33])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CC1(C)CCC(C)(C)c2cc(C(=O)COc3ccc(C(=O)NN4CCCCC4)c(O)c3)ccc21
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: CC(C)O
Solvent: C1CCOC1
Product: CC1(C)CCC(C)(C)c2cc(C(O)COc3ccc(C(=O)NN4CCCCC4)c(O)c3)ccc21
Temperature: 0 °C
Reaction time: 1 h

Procedure:
3.43 g (7.6 mmol) of N-piperidinyl-2-hydroxy-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthoylmethoxy)benzamide, 100 ml of isopropanol and 50 ml of THF are introduced into a flask. The mixture is cooled to 0° C. and 144 mg (3.81 mmol) of NaBH4 are added. The mixture is stirred at 0° C. for 1 hour. Acetone is added, the solvents are evaporated, the residue is taken up in water and the mixture is adjusted to pH 6-7 with hydrochloric acid (1N). The mixture is extracted with ethyl acetate, washed with water and dried over sodium sulphate, and the solvents are evaporated. The residue obtained is purified by chromatography on a silica column eluted with a mixture of ethyl acetate and hexane (35:65). After evaporation of the solvents, the oil obtained is crystallised in hexane, filtered and dried, and 4.25 g (86%) of the expected product of melting point 124° C. are collected.
Reaction SMILES: [NH:1]1[C:9]2[CH:8]=[C:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[N:6]=[CH:5][C:4]=2[CH:3]=[CH:2]1.[H-].[Na+].F[C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=1>CN(C=O)C>[N+:26]([C:23]1[CH:24]=[CH:25][C:20]([N:1]2[C:5]3[N:6]=[C:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH:8]=[CH:9][C:4]=3[CH:3]=[CH:2]2)=[CH:21][CH:22]=1)([O-:28])=[O:27]
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: CC(C)(C)OC(=O)c1cc2[nH]ccc2cn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)c1ccc2ccn(-c3ccc([N+](=O)[O-])cc3)c2n1
Reaction time: 0.17 h
Yield: 73.4 %

Procedure:
To a solution of tert-butyl 1H-pyrrolo[3,2-c]pyridine-6-carboxylate (120 mg, 0.55 mmol) in DMF (3 mL) at rt, was added NaH (60% in mineral oil, 26.4 mg, 0.66 mmol). The mixture was stirred for 10 min and 4-fluoronitrobenzene (155 mg, 1.1 mmol) was added to the reaction. The resulting mixture was stirred at rt for 1 h. The reaction was quenched with sat. aq. sodium citrate solution, extracted with EtOAc and dried over MgSO4. The product was purified by flash column chromatography (SiO2, 25% EtOAc/CH2Cl2) to give a yellow solid (137 mg, 73%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2.[CH3:13]C(C)([O-])C.[K+].CI.Cl>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:13])[C:7](=[O:12])[CH2:6][CH2:5]2
Reactant: O=C1CCc2cc(Br)ccc2N1
Reactant: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CI
Product: CN1C(=O)CCc2cc(Br)ccc21
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 79.7 %

Procedure:
To a solution of 6-bromo-3,4-dihydroquinolin-2(1H)-one (5 g, 22.1 mmol) in DMF (100 mL) cooled to 0° C. was added potassium tert-butoxide (4.96 g, 44.2 mmol) portionwise and the reaction mixture was stirred at 0° C. for 15 min. Then, methyl iodide (4.08 g, 28.8 mmol) was added and the reaction mixture allowed to warm up to room temperature and stirring was continued over night. More MeI (1.25 g, 8.86 mmol) was added and the reaction mixture was heated to 40° C. until completion of the reaction. The mixture was diluted with EtOAc, poured into 100 mL of 1M HCl and the aqueous phase was extracted with EtOAc (2×200 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 30% EtOAc-heptane gradient to give the title compound (4.23 g, 80%) as an off white solid. MS: 240.0, 242.1 (M+H+).
Reaction SMILES: [C:1]1([CH:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=O)[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl-].[OH:18][NH3+:19]>N1C=CC=CC=1>[C:1]1([CH:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[N:19][OH:18])[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C1CC(c2ccccc2)c2ccccc21
Reactant: [NH3+]O
Agent: [Cl-]
Solvent: c1ccncc1
Product: ON=C1CC(c2ccccc2)c2ccccc21
Yield: 62.7 %

Procedure:
A mixture of 3-phenyl-1-indanone (4.2 g, 20 mmol, J. Chem. Soc. 1949, 2957), hydroxylammonium chloride (2.8 g, 40 mmol) and pyridine (30 ml) was heated at reflux overnight. The reaction mixture was allowed to cool and the solvent was evaporated in vacuo. The residue was dissolved in ethyl acetate and washed with excess 10% citric acid solution. The organic phase was dried (MgSO4) and the solvent evaporated in vacuo to give a solid which was triturated with a mixture of cyclohexane and ethyl acetate. The solid was isolated by filtration and dried in air to give 2.8 g of 3-phenyl-1-indanone oxime as a solid. M.p. 123°-125° C.
Reaction SMILES: C=[C:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:13]=[C:12]([N:14]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[N:11]3[N:31]=[CH:32][CH:33]=[C:10]3[N:9]=2)[CH2:4][CH2:3]1.N1C(C)=CC=CC=1C.O.[O-:43]S([O-])(=S)=O.[Na+].[Na+]>O1CCOCC1.O=[Os](=O)(=O)=O>[CH3:30][Si:27]([CH3:29])([CH3:28])[CH2:26][CH2:25][O:24][CH2:23][N:14]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:20])([CH3:21])[CH3:22])[C:12]1[N:11]2[N:31]=[CH:32][CH:33]=[C:10]2[N:9]=[C:8]([CH:5]2[CH2:4][CH2:3][C:2](=[O:43])[CH2:7][CH2:6]2)[CH:13]=1
Reactant: C=C1CCC(c2cc(N(COCC[Si](C)(C)C)COCC[Si](C)(C)C)n3nccc3n2)CC1
Reactant: O=S([O-])([O-])=S
Agent: O=[Os](=O)(=O)=O
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Solvent: Cc1cccc(C)n1
Product: C[Si](C)(C)CCOCN(COCC[Si](C)(C)C)c1cc(C2CCC(=O)CC2)nc2ccnn12
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
To 5-(4-methylenecyclohexyl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (4.60 g, 9.41 mmol) in dioxane (50 mL) was added OsO4 (2.5 w % in tBuOH, 5 mol %), 2,6-Lutidine (4.37 mL, 37.6 mmol) and H2O (10 mL). The resulting mixture was stirred at rt for 20 min, then NaIO4 (8.05 g, 37.6 mmol) was added and the reaction mixture was stirred at rt overnight. LCMS showed very good conversion to the desired product (491). Na2S2O3 (sat.) was added and the mixture was stirred for 10 min. Dioxane was removed and the residue was extracted with EtOAc, washed with H2O and brine, dried over Na2SO4, and concentrated. The crude product was purified by a SiO2 column (0-40% EtOAc/Hexanes, Rf=0.15 in 20% EtOAc) to afford 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanone as a colorless oil (3.37 g). HPLC-MS TR=2.84 min (UV 254 nm, 5 min method); mass calculated for formula C24H42N4O3Si2 490.3, observed LCMS m/z 491.2 (M+H).
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:32]=[CH:31][C:9]2[N:10]=[C:11]([C:13]3[C:14](=[O:30])[NH:15][CH:16]=[CH:17][C:18]=3[NH:19][CH2:20][CH:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=3)[OH:22])[NH:12][C:8]=2[CH:7]=1)=O)C.[BH4-].[Na+].[CH3:35]O>C(O)(=O)C>[Cl:29][C:25]1[CH:24]=[C:23]([CH:21]([OH:22])[CH2:20][NH:19][C:18]2[CH:17]=[CH:16][NH:15][C:14](=[O:30])[C:13]=2[C:11]2[NH:12][C:8]3[CH:7]=[C:6]([CH2:4][OH:3])[CH:32]=[C:31]([CH3:35])[C:9]=3[N:10]=2)[CH:28]=[CH:27][CH:26]=1
Reactant: CCOC(=O)c1ccc2nc(-c3c(NCC(O)c4cccc(Cl)c4)cc[nH]c3=O)[nH]c2c1
Reactant: CO
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(=O)O
Product: Cc1cc(CO)cc2[nH]c(-c3c(NCC(O)c4cccc(Cl)c4)cc[nH]c3=O)nc12
Temperature: -20 °C
Reaction time: 0.5 h
Yield: 62 %

Procedure:
To a solution of (±)-2-{4-[2-(3-Chloro-phenyl)-2-hydroxy-ethylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}- -3H-benzimidazole-5-carboxylic acid ethyl ester (25 mg, 0,054 mmol) in methanol (2 mL) and acetic acid (1 mL) was added NaBH4 (10 mg, 0.27 mmol) at −20° C. The reaction mixture was stirred at −20° C. for 30 min. and quenched with isopropanol (5 drops). After removal of most solvent, the residue was extracted with EtOAc, washed with water and brine, dried over Na2SO4. After concentration, the crude product was purified by prep. HPLC to yield the title compound (18 mg, 62%). 1H NMR (300 MHz, CD3OD) δ 7.50 (1H, s), 7.48 (1H, s), 7.25–7.38 (4H, m), 7.22 (1H, s), 6.25 (1H, d, J=7.6 Hz), 4.89–4.94 (1H, m), 4.76 (2H, s), 3.51–3.62 (2H, m), 2.62 (3H, s). LCMS (M+H)+ m/z 425 (t=1.64 min.).
Reaction SMILES: [OH-].[Na+].[CH:3]1([C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[S:18][C:17]([NH:19]C(=O)C)=[N:16][C:15]=3[CH3:23])=[CH:10][CH:9]=2)=[O:7])[CH2:5][CH2:4]1>C(O)C>[NH2:19][C:17]1[S:18][C:14]([C:11]2[CH:12]=[CH:13][C:8]([C:6]([CH:3]3[CH2:5][CH2:4]3)=[O:7])=[CH:9][CH:10]=2)=[C:15]([CH3:23])[N:16]=1
Reactant: CC(=O)Nc1nc(C)c(-c2ccc(C(=O)C3CC3)cc2)s1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Cc1nc(N)sc1-c1ccc(C(=O)C2CC2)cc1
Temperature: 85 °C
Reaction time: 1.5 h

Procedure:
Ethanol (34 ml) and 6M NaOH (18.6 ml, 113.2 mmol) were added to N-[5-(4-Cyclopropanecarbonyl-phenyl)-4-methyl-thiazol-2-yl]-acetamide (3.4 g, 11.32 mmol). The reaction mixture was heated to 85° C. for 5.5 hours, after which further NaOH (3.72 ml, 22.64 mmol) was added and heating continues for 1.5 hours. The resulting precipitate was isolated by vacuum filtration. (M+H) 301.26.
Reaction SMILES: C([O-])(=[S:3])C.[K+].[CH2:6]([CH:8]1[CH:12]([CH2:13][C:14]2[N:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[CH2:11]N[C:9]1=[O:20])[CH3:7]>CN(C)C=O>[CH2:6]([CH:8]1[CH:12]([CH2:13][C:14]2[N:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[CH2:11][S:3][C:9]1=[O:20])[CH3:7]
Reactant: CC([O-])=S
Reactant: CCC1C(=O)NCC1Cc1cccnn1
Agent: [K+]
Solvent: CN(C)C=O
Product: CCC1C(=O)SCC1Cc1cccnn1

Procedure:
Potassium thioacetate (3.3 g, 0.029 mol) and 3.0 g (0.0145 mol) of 3-ethyl-4-(3-pyridazinylmethyl)-2-pyrrolidinone (Example 1) are stirred for 6 hours at 150° C. in 50 mL of dimethylformamide. After cooling and evaporating the solvent, the residue is dissolved in 95% methylene chloride/methanol, washed twice with saturated sodium bicarbonate solution and once with water. After drying the organic phase with sodium sulphate, the mixture is filtered and concentrated by evaporation. The product is purified by chromatography in silica gel to give the title compound.
Reaction SMILES: [C:1]([CH2:9][CH2:10][C:11](O)=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].O>C1COCC1>[C:2]1([CH:1]([OH:8])[CH2:9][CH2:10][CH2:11][OH:12])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)CCC(=O)c1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: OCCCC(O)c1ccccc1
Yield: 80 %

Procedure:
3-Benzoylpropionic acid 11a dissolved in THF was reacted with LiAlH4 according to the general procedure. The following workup procedure was used: H2O was added and THF was evaporated. Diethylether and HCl (2M) was added. The aqueous layer was extracted with diethylether and the combined organic layers were washed with H2O, aqueous NaHCO3 (saturated) and H2O. Drying (MgSO4), filtration and evaporation gave 80% yield of 6a. 1H-NMR: 7.35-7.22 (m, 5H, Ar--H); 4.70 (t, 1H, CH--OH); 3.64 (t, 2H, CH2OH); 3.10 (brs, 1H, CH--OH); 2.60 (brs, 1H, CH2 --OH); 1.84 (q, 2H, CH2 --CHOH); 1.72-1.61 (m, 2H, CH2CH2OH).
Reaction SMILES: [C:1]([CH2:6][CH2:7][C:8]1[C:12]([CH3:13])=[C:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[NH:10][CH:9]=1)([O:3][CH2:4][CH3:5])=[O:2].I.[PH2](O)=O.[CH:23](=O)[CH2:24][CH3:25].N>Cl.O.C(O)(=O)C>[CH2:23]([C:9]1[NH:10][C:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:12]([CH3:13])[C:8]=1[CH2:7][CH2:6][C:1]([O:3][CH2:4][CH3:5])=[O:2])[CH2:24][CH3:25]
Reactant: CCC=O
Reactant: CCOC(=O)CCc1c[nH]c(C(=O)OCC)c1C
Agent: Cl
Agent: I
Agent: N
Solvent: CC(=O)O
Solvent: O
Product: CCCc1[nH]c(C(=O)OCC)c(C)c1CCC(=O)OCC

Procedure:
3-(2-Carbethoxy-ethyl)-4-methyl-5-carbethoxypyrrole (0.4 g (35)), 5ml of hydriodic acid, 5 ml of acetic acid, 1 ml of hypophosphorous acid and 0.23 ml of propionaldehyde were reacted as above. The solution was poured into 60 ml of water which was then brought to pH 5 with ammonia. The precipitate (of the partially hydrolyzed product) was esterified in 5 ml of 5% ethanolic HCl. The solvent was evaporated and the residue was distilled then recrystallized from pentane (0.1 g), m.p. 61.5°-63.5° C (lit. 63° - 64° C.).
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:13]([CH2:14][O:15]C(=O)C)[O:12][C@H:11]2[C@H:7]([N:8]=[C:9]([N:19]3[CH2:22][CH2:21][CH2:20]3)[S:10]2)[C@H:6]1[O:23]C(=O)C)(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO>[N:19]1([C:9]2[S:10][C@H:11]3[O:12][C@H:13]([CH2:14][OH:15])[C@@H:5]([OH:4])[C@H:6]([OH:23])[C@H:7]3[N:8]=2)[CH2:22][CH2:21][CH2:20]1
Reactant: CC(=O)OC[C@H]1O[C@@H]2SC(N3CCC3)=N[C@@H]2[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: OC[C@H]1O[C@@H]2SC(N3CCC3)=N[C@@H]2[C@@H](O)[C@@H]1O
Reaction time: 0.08 h
Yield: 41.3 %

Procedure:
A solution of (3aR,5R,6S,7R,7aR)-5-(acetoxymethyl)-2-(azetidin-1-yl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diyl diacetate (360 mg, 0.93 mmol) in methanol (5 mL) was treated with potassium carbonate (13 mg, 0.09 mmol) overnight at 40° C. The reaction mixture was concentrated under vacuum to give a residue, which was purified by Prep-HPLC with the following conditions [(Agilent 1200 prep HPLC): Column, X-Bridge C18, 19*50 mm 3.5 um; mobile phase, Water with 0.05% NH4OH and CH3CN (3% CH3CN up to 9% in 5 min; Detector, UV 220 nm)] to give compound 3 as a white solid (100 mg, 40%). (ES, m/z) [M+H]+ 261.0; 1H NMR (300 MHz, DMSO+D2O) δ 6.25-6.27 (d, J=6.3 Hz, 1H), 3.92-3.96 (t, J=5.7 Hz, 1H), 3.83-3.88 (m, 4H), 3.68-3.71 (t, J=4.8 Hz, 1H), 3.55-3.58 (m, 1H), 3.25-3.42 (m, 3H), 2.21-2.26 (m, 2H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][N:17]=3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[CH3:24].[O:25]1[CH2:29][CH2:28][NH:27][C:26]1=[O:30]>>[CH3:22][C:21]1[C:16]([N:13]2[CH2:14][CH2:15][N:10]([C:8]([C:5]3[CH:6]=[CH:7][C:2]([N:27]4[CH2:28][CH2:29][O:25][C:26]4=[O:30])=[C:3]([CH3:24])[CH:4]=3)=[O:9])[CH2:11][CH2:12]2)=[N:17][CH:18]=[C:19]([CH3:23])[CH:20]=1
Reactant: Cc1cnc(N2CCN(C(=O)c3ccc(Br)c(C)c3)CC2)c(C)c1
Reactant: O=C1NCCO1
Product: Cc1cnc(N2CCN(C(=O)c3ccc(N4CCOC4=O)c(C)c3)CC2)c(C)c1
Yield: 13.4 %

Procedure:
By reaction and treatment in the same manner as in Example 111 and using (4-bromo-3-methylphenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone (388 mg) described in Preparation Example 68 and oxazolidin-2-one (87 mg), the title compound (52.7 mg) was obtained.
Reaction SMILES: [CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([N+:13]([O-])=O)[N:10]=[CH:9]2)=[C:5]([CH3:16])[O:4][N:3]=1.[H][H]>[Pd].CO>[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([NH2:13])[N:10]=[CH:9]2)=[C:5]([CH3:16])[O:4][N:3]=1
Reactant: Cc1noc(C)c1Cn1cnc([N+](=O)[O-])c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: Cc1noc(C)c1Cn1cnc(N)c1
Yield: 92.5 %

Procedure:
3,5-dimethyl-4-((4-nitro-1H-imidazol-1-yl)methyl)isoxazole (example 10-40b) (1.0 g, 4.5 mmol) and 10% palladium on charcoal (200 mg) in methanol (40 mL) was shaken on a Parr shaker under a pressure of 2.5 bar hydrogen for 2 hours. Filtration through a plug of celite followed by rotary evaporation afforded 1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-imidazol-4-amine as a yellowish-red solid (800 mg, 93% yield). MS M+H calculated 193, found 193.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[C:11](=[C:13]([C:17]([NH2:19])=[O:18])[CH:14]=[CH:15][CH:16]=3)[N:12]=2)=[CH:4][CH:3]=1.N1C=CC=CC=1.[C:26](Cl)(=[O:28])[CH3:27]>ClCCl>[C:26]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]3[C:11](=[C:13]([C:17]([NH2:19])=[O:18])[CH:14]=[CH:15][CH:16]=3)[N:12]=2)=[CH:6][CH:7]=1)(=[O:28])[CH3:27]
Reactant: NC(=O)c1cccc2oc(-c3ccc(N)cc3)nc12
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(=O)Nc1ccc(-c2nc3c(C(N)=O)cccc3o2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 89 %

Procedure:
To a solution of 2-(4-aminophenyl)benzo[d]oxazole-4-carboxamide (150 mg, 0.59 mmol) in dichloromethane (5 mL) was added pyridine (51 mg, 0.65 mmol) and acetyl chloride (49 mg, 0.62 mmol) at 0° C., and the mixture was stirred at room temperature for 4 hr, then the solvent was evaporated under reduced pressure and the residue was re-crystallized in methanol to obtain 2-(4-acetamidophenyl)benzo[d]oxazole-4-carboxamide as a white solid (155 mg, yield 89%). 1H-NMR (400 MHz, DMSO-d6) δ 2.10 (s, 3H), 7.49-7.53 (t, J=8 Hz, 1H), 7.83-7.85 (d, J=8 Hz, 2H), 7.95-7.99 (m, 3H), 8.23-8.26 (d, J=8 Hz, 2H), 8.48 (s, 1H), 10.36 (s, 1H); LC-MS (ESI) m/z 296 [M+1]+.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][N:5]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH:7][C:6]1=[O:16].[C:17](OC(=O)C)(=[O:19])[CH3:18]>>[CH3:1][O:2][CH2:3][CH2:4][N:5]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:7]([C:17](=[O:19])[CH3:18])[C:6]1=[O:16]
Reactant: COCCn1cc(-c2ccccc2)[nH]c1=O
Reactant: CC(=O)OC(C)=O
Product: COCCn1cc(-c2ccccc2)n(C(C)=O)c1=O

Procedure:
Approximately 21.8 g of 1-(2-methoxyethyl)-4-phenyl-4-imidazolin-2-one and 120 ml. of acetic anhydride is refluxed together for four hours. The acetic anhydride is distilled out at reduced pressure. The residual semisolid is recrystallized from ether to yield the title compound as a white solid; m.p. 73°-75° C.