Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:7](=[CH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:8]Cl)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Si]([N:21]([Si](C)(C)C)[C:22]1[CH:27]=[CH:26][NH:25][C:24](=[O:28])[N:23]=1)(C)C>C1C=CC=CC=1>[C:1]1([C:7](=[CH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:8][N:25]2[CH:26]=[CH:27][C:22]([NH2:21])=[N:23][C:24]2=[O:28])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: ClCC(=Cc1ccccc1)c1ccccc1
Reactant: C[Si](C)(C)N(c1cc[nH]c(=O)n1)[Si](C)(C)C
Solvent: c1ccccc1
Product: Nc1ccn(CC(=Cc2ccccc2)c2ccccc2)c(=O)n1

Procedure:
A solution of 10 parts of 2,3-diphenylallyl chloride in 43.9 parts of benzene is treated with 20 parts of bis-trimethylsilylcytosine under a nitrogen atmosphere and then the reaction container is sealed and maintained at a temperature of 65° for 120 hours. The solid which forms is collected by filtration, washed with benzene and recrystallized from a 1:1 acetic acid-water mixture to yield 1-(2,3 -diphenylallyl)-4-amino-2-oxo-1,2-dihydro-pyrimidine. That product displays nuclear magnetic resonance maxima at about 293, 405, 425, 437, 453 and 461 Hertz and is represented structurally by the following formula ##STR8##
Reaction SMILES: O.[OH-].[Li+].C[O:5][C:6](=[O:40])[CH2:7][C:8]1[C:17]([CH3:18])=[C:16]([C:19]2[CH:24]=[CH:23][C:22]([S:25]([C:28]3[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=3)(=[O:27])=[O:26])=[CH:21][CH:20]=2)[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:39])[CH:14]=2)[CH:9]=1>C1COCC1.O>[F:39][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH2:7][C:6]([OH:40])=[O:5])[C:17]([CH3:18])=[C:16]2[C:19]1[CH:20]=[CH:21][C:22]([S:25]([C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]([F:37])([F:36])[F:38])=[CH:30][CH:29]=2)(=[O:27])=[O:26])=[CH:23][CH:24]=1
Reactant: COC(=O)Cc1cc2ccc(F)cc2c(-c2ccc(S(=O)(=O)c3ccc(OC(F)(F)F)cc3)cc2)c1C
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Cc1c(CC(=O)O)cc2ccc(F)cc2c1-c1ccc(S(=O)(=O)c2ccc(OC(F)(F)F)cc2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 86.8 %

Procedure:
Lithium hydroxide monohydrate (0.011 g, 0.26 mmol) was added to a stirred solution of {6-fluoro-3-methyl-4-[4-(4-trifluoromethoxy-benzenesulfonyl)-phenyl]-naphthalen-2-yl}-acetic acid methyl ester (0.032 g, 0.06 mmol) in a 3:1 THF—H2O mixture (4 mL). The reaction mixture was stirred for 16 hours at room temperature. The THF was distilled off under reduced pressure, and the crude residue was diluted with water, acidified [pH˜2] via the drop-wise addition of an aqueous solution of hydrochloric acid (6.0 N). The mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. Trituration with hexanes afforded {6-fluoro-3-methyl-4-[4-(4-trifluoromethoxy-benzenesulfonyl)-phenyl]-naphthalen-2-yl}-acetic acid (0.027 g, 87%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.48 (br. s, 1 H) 8.23 (d, J=8.90 Hz, 2 H) 8.16 (d, J=8.30 Hz, 2 H) 7.97-8.05 (m, 1 H) 7.90 (s, 1 H) 7.68 (d, J=8.70 Hz, 2 H) 7.54 (d, J=8.80 Hz, 2H) 7.34-7.43 (m, 1H) 6.63 (d, J=10.90 Hz, 1 H) 3.83 (s, 2 H) 2.03 (s, 3 H) MS calcd. for C26H17F4O5S [(M−H)−] 517, obsd. 517.3.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([N:10]3[C:14]4=[N:15][CH:16]=[CH:17][CH:18]=[C:13]4[N:12]([CH2:19][CH3:20])[C:11]3=[O:21])=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.Cl[C:23]1[N:27](COCC[Si](C)(C)C)[C:26]2[CH:36]=[CH:37][CH:38]=[CH:39][C:25]=2[N:24]=1>CN1C(=O)CCC1>[NH:24]1[C:25]2[CH:39]=[CH:38][CH:37]=[CH:36][C:26]=2[N:27]=[C:23]1[N:1]1[C:9]2[C:4](=[CH:5][C:6]([N:10]3[C:14]4=[N:15][CH:16]=[CH:17][CH:18]=[C:13]4[N:12]([CH2:19][CH3:20])[C:11]3=[O:21])=[CH:7][CH:8]=2)[CH2:3][CH2:2]1
Reactant: CCn1c(=O)n(-c2ccc3c(c2)CCN3)c2ncccc21
Reactant: C[Si](C)(C)CCOCn1c(Cl)nc2ccccc21
Solvent: CN1CCCC1=O
Product: CCn1c(=O)n(-c2ccc3c(c2)CCN3c2nc3ccccc3[nH]2)c2ncccc21
Temperature: 120 °C
Reaction time: 12 h

Procedure:
A mixture of 3-(2,3-dihydro-1H-indol-5-yl)-1-ethyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one obtained from example 13e) and 2-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole (108 mg) in NMP (2.0 ml) was stirred at 120° C. for 12 h, treated with sat.NaHCO3aq. and extracted with AcOEt. The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was purified by preparative HPLC and crystallized from AcOEt/Hexane to give 3-[1-(1H-benzimidazol-2-yl)-2,3-dihydro-1H-indol-5-yl]-1-ethyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (12 mg).
Reaction SMILES: [N:1]([O-])=O.[Na+].[CH3:5][O:6][C:7]1[CH:13]=[CH:12][C:10]([NH2:11])=[C:9]([CH3:14])[CH:8]=1>O.C(O)(=O)C>[CH3:5][O:6][C:7]1[CH:8]=[C:9]2[C:10](=[CH:12][CH:13]=1)[NH:11][N:1]=[CH:14]2
Reactant: COc1ccc(N)c(C)c1
Reactant: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: COc1ccc2[nH]ncc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 18 %

Procedure:
A solution of sodium nitrite (3.38 g, 49.0 mmol) in water (8.1 ml) was added to a solution of 4-methoxy-2-methylaniline (6.69 g, 48.8 mmol) in acetic acid (350 ml) in an ice-water bath while maintaining the temperature at 25° C. or lower, and stirred overnight at room temperature. Then, the reaction solution was poured into water and extracted with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and then distilled under reduced pressure to remove the solvent, and the resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol=9/1) to obtain 5-methoxy-1H-indazole (1.30 g, 18%).
Reaction SMILES: [N+:1]([C:4]1[CH:26]=[CH:25][CH:24]=[CH:23][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[N+:20]([O-])=O)[CH:8]=1)([O-])=O.C(O)CCC.[H][H]>[Pd].C(N(CC)CC)C>[NH2:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[O:13][C:9]1[CH:10]=[CH:11][CH:12]=[C:7]([O:6][C:5]2[CH:23]=[CH:24][CH:25]=[CH:26][C:4]=2[NH2:1])[CH:8]=1
Reactant: [H][H]
Reactant: O=[N+]([O-])c1ccccc1Oc1cccc(Oc2ccccc2[N+](=O)[O-])c1
Agent: [Pd]
Solvent: CCN(CC)CC
Solvent: CCCCO
Product: Nc1ccccc1Oc1cccc(Oc2ccccc2N)c1
Temperature: 25 °C

Procedure:
A mixture of 145.3 g of 1,3-bis(2-nitrophenoxy)benzene, 340 mL of butanol, 9 mL of triethylamine, and 1.7 g of 5% palladium on carbon was heated to 70° C. in a 1.0 liter stainless steel stirred autoclave and pressurized with hydrogen to 4.1 MPa. This pressure was maintained for 1 hour after the hydrogen uptake had ceased. The autoclave was cooled to room temperature and discharged. The product slurry redissolved on reheating; the solution was filtered through diatomaceous earth to remove the catalyst, cooled to room temperature, and the product precipitated with hexane. The precipitated product was recovered by filtration and vacuum dried at 70° C. The yield of 1,3-bis(2-aminophenoxy)benzene was 95.2 g (79%).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl.[CH3:19][O:20][NH:21][CH3:22]>ClCCl>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:21]([O:20][CH3:19])[CH3:22])=[O:7])=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccc(Br)cc1
Reactant: CNOC
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CON(C)C(=O)c1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 83.6 %

Procedure:
To a stirred solution of 4-bromobenzoyl chloride (20.0 g, 91.1 mmol) in dichloromethane (300 mL) at −78° C. was added triethylamine (28.0 mL, 200.0 mmol), and O,N-dimethylhydroxylamine hydrochloride (9.33 g, 95.6 mmol). The resulting solution was allowed to warm to room temperature, stirred for 1.5 hours, and then concentrated. The residue was triturated in acetone and the resulting solid was dissolved in ethyl acetate washed with water and brine. The organic layer was dried over magnesium sulfate, filtered, and concentrated to give 4-bromo-N-methoxy-N-methylbenzamide (18.6 g, 84%). To a solution of 4-bromo-N-methoxy-N-methylbenzamide (3.0 g, 12.29 mmol) in THF (30 mL) at 0° C. under nitrogen was added 2-thienyllithium (1.0 M in THF, 15 mL, 15 mmol) slowly over 10 minutes. The solution was stirred at 0° C. for 1 hour, poured into a saturated aqueous ammonium chloride solution (150 mL), and extracted several times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated. The residue was triturated with ether to give (4-bromophenyl)(thien-2-yl)methanone as a brown solid (1.1 g, 34%). MS (ES) m/z 266.9.
Reaction SMILES: O.O.O.O.O.O.O.O.O=[C:10]1[C:15](=O)[C:14](=O)[C:13](=O)[C:12](=O)[C:11]1=O.[C:21]1([NH2:28])[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[NH2:27]>C(O)(=O)C.C(O)C.C(Cl)(Cl)Cl>[CH:10]1[C:15]2[C:14](=[N:27][C:22]3[C:23]4[C:24]([C:25]5[C:26]([C:21]=3[N:28]=2)=[N:28][C:21]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:27]=5)=[N:28][C:21]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:27]=4)[CH:13]=[CH:12][CH:11]=1
Reactant: O=C1C(=O)C(=O)C(=O)C(=O)C1=O
Reactant: Nc1ccccc1N
Solvent: CCO
Solvent: O
Solvent: ClC(Cl)Cl
Product: c1ccc2nc3c(nc2c1)c1nc2ccccc2nc1c1nc2ccccc2nc31
Temperature: 140 °C
Yield: 40 %

Procedure:
The title compound was synthesized according to a modified literature procedure.30 Hexaketocyclohexane octahydrate (10.0 g, 32.0 mmol) and 1,2-phenylenediamine SM17 (10.4 g, 96.0 mmol) were refluxed in 500 ml of glacial acetic acid:ethanol (1:1) at 140° C. for 24 hours. The reaction mixture was then filtered and washed with ca. 200 ml of hot glacial acid. The solid was then refluxed with 200 ml of 30% nitric acid for 3 hours at 140° C. The yellow solid (12.6 g) was filtered and dried under vacuum. An amount 2.0 g was sublimed at high vacuum (3.2×10−6 torr and t=350° C.) to yield 0.77 g (estimated extrapolated yield=40%) of yellow solid. The yield could be increased with prolonged sublimation time. This compound is slightly soluble in CHCl3. 1H NMR (CDCl3, 300 MHz) δ 8.73-8.69 (dd, J=6.6 Hz; J2=3.6 Hz, 6H), 8.08-8.043 (m, 6H). 13C NMR (CDCl3, 75 MHz), 143.57, 132.30, 130.65, 119.05, 98.58. Anal. Calcd. for C24H12N6: C, 74.99; H, 3.15; N, 21.86. Found: C, 74.76; H, 3.11; N, 21.66.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[Cl:11].[OH-].[K+].[F:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]([CH3:24])[C:22]#[N:23])=[CH:17][CH:16]=1>N1C=CC=CC=1>[Cl:11][C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[C:21]([CH3:24])([C:18]1[CH:19]=[CH:20][C:15]([F:14])=[CH:16][CH:17]=1)[C:22]#[N:23]
Reactant: O=[N+]([O-])c1ccc(Cl)c(Cl)c1
Reactant: CC(C#N)c1ccc(F)cc1
Agent: [K+]
Agent: [OH-]
Solvent: c1ccncc1
Product: CC(C#N)(c1ccc(F)cc1)c1ccc([N+](=O)[O-])cc1Cl
Temperature: 5 °C
Reaction time: 10 h

Procedure:
To a stirred solution of 20 parts of 1,2-dichloro-4-nitrobenzene in 160 parts of pyridine was added a paste of 28 parts of solid potassium hydroxide and 40 parts of pyridine. After cooling to 5° C., there was added dropwise 15.6 parts of 4-fluoro-α-methylbenzeneacetonitrile. Upon completion, the whole was further stirred for 10 hours at -5° C. The cooling bath was removed and the reaction mixture was diluted with 80 parts of benzene. The whole was filtered and the filtrate was evaporated. The residue was poured into water and the product was extracted with methylbenzene. The latter was dried, filtered and evaporated. The solid residue was crystallized from a mixture of 1,1'-oxybisethane and benzene, yielding 15 parts of α-(2-chloro-4-nitrophenyl)-4-fluoro-α-methylbenzeneacetonitrile; mp. 133.1° C. (intermediate 2).
Reaction SMILES: [CH:1]1([N:4]([CH2:18][C:19]2[O:20][CH:21]=[C:22]([C:24](O)=[O:25])[N:23]=2)[S:5]([C:8]2[C:13]([CH3:14])=[CH:12][C:11]([O:15][CH3:16])=[CH:10][C:9]=2[CH3:17])(=[O:7])=[O:6])[CH2:3][CH2:2]1.Cl.[NH:28]1[CH2:32][CH2:31][N:30]=[C:29]1[C:33]1[CH:38]=[CH:37][C:36]([CH2:39][CH2:40][NH:41][CH3:42])=[CH:35][CH:34]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:1]1([N:4]([CH2:18][C:19]2[O:20][CH:21]=[C:22]([C:24]([N:41]([CH2:40][CH2:39][C:36]3[CH:35]=[CH:34][C:33]([C:29]4[NH:30][CH2:31][CH2:32][N:28]=4)=[CH:38][CH:37]=3)[CH3:42])=[O:25])[N:23]=2)[S:5]([C:8]2[C:9]([CH3:17])=[CH:10][C:11]([O:15][CH3:16])=[CH:12][C:13]=2[CH3:14])(=[O:7])=[O:6])[CH2:3][CH2:2]1
Reactant: COc1cc(C)c(S(=O)(=O)N(Cc2nc(C(=O)O)co2)C2CC2)c(C)c1
Reactant: CNCCc1ccc(C2=NCCN2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(C)c(S(=O)(=O)N(Cc2nc(C(=O)N(C)CCc3ccc(C4=NCCN4)cc3)co2)C2CC2)c(C)c1

Procedure:
The title compound was prepared according to general procedure AH using 2-({cyclopropyl[(4-methoxy-2,6-dimethylphenyl)sulfonyl]amino}methyl)-1,3-oxazole-4-carboxylic acid (100 mg, 0.26 mmol), the bis HCl salt of 2-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-N-methylethanamine (65 mg, 0.23 mmol), EDCI (60 mg, 0.31 mmol), HOBt (42 mg, 0.31 mmol) and DIPEA (0.2 mL, 1.04 mmol) in DMF (8 mL).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([C:19]([N:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:20])[CH:18]=1)[C:5]([NH:7][CH2:8][C:9]1[CH:10]=[N:11][C:12]([CH3:15])=[N:13][CH:14]=1)=[O:6].[CH3:26][C:27]1[CH:28]=[CH:29][C:30]([Sn](CCCC)(CCCC)CCCC)=[N:31][CH:32]=1.C1(C)C=CC=CC=1>O.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>[CH3:26][C:27]1[CH:28]=[CH:29][C:30]([C:2]2[CH:3]=[C:4]([CH:16]=[C:17]([C:19]([N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[O:20])[CH:18]=2)[C:5]([NH:7][CH2:8][C:9]2[CH:10]=[N:11][C:12]([CH3:15])=[N:13][CH:14]=2)=[O:6])=[N:31][CH:32]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(C)cn1
Reactant: Cc1ncc(CNC(=O)c2cc(Br)cc(C(=O)N3CCCC3)c2)cn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: Cc1ccc(-c2cc(C(=O)NCc3cnc(C)nc3)cc(C(=O)N3CCCC3)c2)nc1

Procedure:
A mixture of 3-bromo-N-((2-methylpyrimidin-5-yl)methyl)-5-(pyrrolidine-1-carbonyl)benzamide (25 mg, 0.059 mmol), 5-methyl-2-(tributylstannyl)pyridine (40 mg, 0.10 mmol), tetrakis(triphenylphosphine)palladium(0) (5 mg, 0.0043 mmol), and toluene (1 mL) under nitrogen was subjected to microwave irradiation at 120° C. for 1 hour. After cooling, the mixture was diluted with water and extracted with EtOAc. The combined organic layers were dried over Na2SO4, and concentrated. The residue was purified by flash chromatography to afford the title compound as a white solid.
Reaction SMILES: N[C@H](C(NC(C([O-])=O)C([O-])=O)=O)CO.CCOC(/N=N/C(OCC)=O)=O.[CH2:27]([O:29][C:30]([CH:32]([NH-:38])[C:33]([O:35][CH2:36][CH3:37])=[O:34])=[O:31])[CH3:28].[C:39]([N:49]1[CH2:51][CH:50]1[C:52](O)=[O:53])([O:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=[O:40]>C1COCC1>[CH2:27]([O:29][C:30]([CH:32]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[N:38]1[CH2:51][CH:50]([NH:49][C:39]([O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:40])[C:52]1=[O:53])=[O:31])[CH3:28]
Reactant: O=C(O)C1CN1C(=O)OCc1ccccc1
Reactant: CCOC(=O)C([NH-])C(=O)OCC
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: N[C@@H](CO)C(=O)NC(C(=O)[O-])C(=O)[O-]
Solvent: C1CCOC1
Product: CCOC(=O)C(C(=O)OCC)N1CC(NC(=O)OCc2ccccc2)C1=O

Procedure:
The Cbz protected serylaminomalonate (0.5 g, 1.2 mmoles) and 0.33 g (1.2 mmoles) of TPP in 30 mL of THF were treated with 0.2 mL (1.29 mmoles) of DEAD for 1 hour at R.T. The mixture was chromatographed as above, yielding 0.29 g (63% mass recovery) of the mixture of the title compound and 1-Cbz-2-carboxyaziridine diethoxycarbonylmethylamide. 105 mg of the mixture was prep TLC'd (silica, 2 mm, ether/hexanes, 4 times). The title compound eluted first, and after evaporation, 64.1 mg (0.18 mmoles, 15%) was isolated as an oil. IR (neat) 1770, 1750, 1715. NMR 1.13-1.33 (6H, m), 3.56-3.7 (2H, m), 4.0-4.4 (4H, m), 4.6-4.8 (1H, m), 5.1 (3H, 2 overlapping singlets), 5.8-6 (1H, m), 7.4 (5H, s). The aziridine side product: 39.5 mg (0.1 mmoles, 8.7%) IR (neat) 1760, 1730. NMR 1.16-1.33 (6H, t), 2.4-2.6 (2H, dd), 3.06-3.16 (1H, dd), 4.1-4.4 (4H, dq), 4.5-4.8 (1H, b), 5.06-5.1 (1H, d), 5.13 (2H, s), 7.4 (5H, s).
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.[H-].[Na+].Br[CH2:10][CH2:11][CH2:12][CH:13]1[CH2:18][CH2:17][N:16]([CH:19]=[O:20])[CH2:15][CH2:14]1>CN(C)C=O>[CH3:1][C:2]1[N:3]([CH2:10][CH2:11][CH2:12][CH:13]2[CH2:14][CH2:15][N:16]([CH:19]=[O:20])[CH2:17][CH2:18]2)[CH:4]=[CH:5][N:6]=1
Reactant: Cc1ncc[nH]1
Reactant: O=CN1CCC(CCCBr)CC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1nccn1CCCC1CCN(C=O)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 83.5 %

Procedure:
A mixture of 2-methylimidazole (2 g, 0.025M) and sodium hydride (1.2 g, 50% in mineral oil, 0.025M) in dimethylformamide (20 ml) was stirred at room temperature for 1/2 hr. The reaction mixture was then heated at 50° C. and the solution of 4(3-bromopropyl)piperidine carboxaldehyde (4.6 g, 0.02M) in dimethylformamide (20 ml) was added slowly. After completing the addition, the reaction was heated at 50° C. for 4 hrs and then solvent was removed in vacuo. Water (80 ml) was added to the residue and the mixture was extracted with methylene chloride. The combined extracts, dried over sodium sulfate, were stripped to dryness to yield an oil. The oil was purified on silica gel column, eluted with methanol chloroform (1:9 v/v) to give 4-[3-(2-methyl-1H-imidazol-1-yl)-propyl]-1-piperidinecarboxaldehyde (3.86 g, 88% yield).
Reaction SMILES: [NH2:1][CH2:2][CH:3]([C:5]1[CH:13]=[C:9]([C:10]([NH2:12])=[O:11])[C:8]([OH:14])=[CH:7][CH:6]=1)[OH:4].[CH3:15][N:16]([CH2:23][CH2:24][C:25](=O)[CH3:26])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[BH3-]C#N.[Na+]>C(O)C>[CH3:15][N:16]([CH2:23][CH2:24][CH:25]([NH:1][CH2:2][CH:3]([C:5]1[CH:13]=[C:9]([C:10]([NH2:12])=[O:11])[C:8]([OH:14])=[CH:7][CH:6]=1)[OH:4])[CH3:26])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: CC(=O)CCN(C)c1ccccc1
Reactant: NCC(O)c1ccc(O)c(C(N)=O)c1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCO
Product: CC(CCN(C)c1ccccc1)NCC(O)c1ccc(O)c(C(N)=O)c1
Reaction time: 16 h

Procedure:
To a solution of 20 mmol 5-(2-amino-1-hydroxyethyl)salicylamide and 3.54 g (20 mmol) 4-(N-methylanilino)-2-butanone [procedure of Craig, et al, J. Org. Chem., 29, 410 (1964)] in 100 ml ethanol add 1.26 g (20 mmol) NaCNBH3. Stir 16 hrs., concentrate, and partition between EtOAc and 1.0 N NaHCO3 solution. Dry and concentrate the organic layer. Recrystallize the residue from methanol to give a white solid, mp 150°-2°.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N:10]1[CH:14]=[CH:13][CH:12]=[N:11]1)[CH:5]=O.N1(C2C=C[C:23]([CH:24]=[O:25])=CC=2)C=CC=N1>>[F:1][C:2]1[CH:3]=[C:4](/[CH:5]=[CH:23]/[CH:24]=[O:25])[CH:7]=[CH:8][C:9]=1[N:10]1[CH:14]=[CH:13][CH:12]=[N:11]1
Reactant: O=Cc1ccc(-n2cccn2)cc1
Reactant: O=Cc1ccc(-n2cccn2)c(F)c1
Product: O=C/C=C/c1ccc(-n2cccn2)c(F)c1

Procedure:
The title compound was prepared by a procedure analogous to Reference Example 30 by substituting 3-fluoro-4-(1H-pyrazol-1-yl)benzaldehyde (prepared as described in Reference Example 6) for the 4-(1H-pyrazol-1-yl)-benzaldehyde of Reference Example 30. MS 217 (M+H)+.
Reaction SMILES: C([O:3][C:4](=[O:36])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[CH2:22][N:23]2[C@@H:27]([CH3:28])[C@@H:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[O:25][C:24]2=[O:35])[CH:7]=1)C.[OH-].[Na+]>>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([O:14][C:8]2[CH:7]=[C:6]([CH2:5][C:4]([OH:36])=[O:3])[CH:11]=[CH:10][C:9]=2[O:12][CH3:13])=[C:16]([CH2:22][N:23]2[C@@H:27]([CH3:28])[C@@H:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[O:25][C:24]2=[O:35])[CH:17]=1
Reactant: CCOC(=O)Cc1ccc(OC)c(Oc2ccc(Cl)cc2CN2C(=O)O[C@H](c3ccccc3)[C@@H]2C)c1
Agent: [Na+]
Agent: [OH-]
Product: COc1ccc(CC(=O)O)cc1Oc1ccc(Cl)cc1CN1C(=O)O[C@H](c2ccccc2)[C@@H]1C

Procedure:
Prepared according to the procedure described in Example 24, Step 8, using the following starting materials: {3-[4-chloro-2((4S,5R)-4-methyl-2-oxo-5-phenyl-oxazolidin-3-ylmethyl)-phenoxy]-4-methoxy-phenyl}-acetic acid ethyl ester and sodium hydroxide.
Reaction SMILES: B(Br)(Br)Br.[CH:5]1([CH2:10][CH:11]([C:20]2[CH:25]=[CH:24][C:23]([O:26]C)=[C:22]([O:28]C)[CH:21]=2)[C:12]([NH:14][C:15]2[S:16][CH:17]=[CH:18][N:19]=2)=[O:13])[CH2:9][CH2:8][CH2:7][CH2:6]1.[OH-].[NH4+].O>C(Cl)Cl>[CH:5]1([CH2:10][CH:11]([C:20]2[CH:25]=[CH:24][C:23]([OH:26])=[C:22]([OH:28])[CH:21]=2)[C:12]([NH:14][C:15]2[S:16][CH:17]=[CH:18][N:19]=2)=[O:13])[CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: COc1ccc(C(CC2CCCC2)C(=O)Nc2nccs2)cc1OC
Agent: BrB(Br)Br
Agent: [NH4+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: O=C(Nc1nccs1)C(CC1CCCC1)c1ccc(O)c(O)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 15.8 %

Procedure:
A 1.0M solution of boron tribromide in methylene chloride (7.43 mL, 7.43 mmol) at 25° C. was treated with a solution of 3-cyclopentyl-2-(3,4-dimethoxy-phenyl)-N-thiazol-2-yl-propionamide (prepared as in Example 113, 0.27 g, 0.74 mmol) in methylene chloride (7.43 mL). This solution was stirred at 25° C. for 1 h. At this time, the reaction was cooled to 0° C. and treated with a dilute aqueous ammonium hydroxide solution. This mixture was stirred at 0° C. for 20 min. At this time, the reaction was poured into water and was extracted with chloroform (3×50 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 70/30 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3,4-dihydroxy-phenyl)-N-thiazol-2-yl-propionamide (38.8 mg, 15.7%) as a white solid: mp 170-173° C.; EI-HRMS m/e calcd for C17H20N2O3S (M+) 332.1194 found 332.1192.
Reaction SMILES: [CH3:1][N:2]1[N:6]=[N:5][C:4]([C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=2)=[N:3]1.[Br:14]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:14][CH2:13][C:10]1[CH:11]=[CH:12][C:7]([C:4]2[N:5]=[N:6][N:2]([CH3:1])[N:3]=2)=[CH:8][CH:9]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccc(-c2nnn(C)n2)cc1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: Cn1nnc(-c2ccc(CBr)cc2)n1

Procedure:
A stirred solution of 45 grams (0.258 mole) of 2-methyl-5-(4-methylphenyl)-1,2,3,4-tetrazole (known compound), 46 grams (1 equivalent) of N-bromosuccinimide, and a catalytic amount of benzoyl peroxide in 200 mL of carbon tetrachloride was irradiated with light during a 3.5 hour period. The mixture was then cooled in an ice bath and filtered to collect 35.1 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10](N)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1.N([O-])=O.[Na+].C1C=CN=CC=1.[FH:25]>>[Cl:1][C:2]1[CH:11]=[C:10]([F:25])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1
Reactant: COc1ccc2nc(Cl)cc(N)c2c1
Reactant: F
Agent: O=N[O-]
Agent: [Na+]
Solvent: c1ccncc1
Product: COc1ccc2nc(Cl)cc(F)c2c1
Temperature: 30 °C
Reaction time: 1 h
Yield: 40 %

Procedure:
A solution of 2-chloro-6-methoxyquinolin-4-amine (4.50 g, 21.6 mmol) in HF-pyridine (45 mL) was cooled to −10-0° C. Then NaNO2 (1.80 g, 26.1 mmol) was added portionwise and the mixture was stirred at 0° C. for 1 hour and at 30° C. for 1 hour. Then the mixture was heated to 65° C. for 1.5 hours. The mixture was quenched with ice-water (100 mL); the aqueous layer was neutralized with 2 M NaOH to pH 7. The mixture was filtered off and the filtrate was extracted with EtOAc (50 mL×3), the organic layer was washed with brine (100 mL), dried over Na2SO4 and concentrated in vacuo. Purification by column chromatography on silica gel (PE/EtOAc=15/1) gave Intermediate 7 (3.60 g, yield: 40%). 1H NMR (CDCl3 400 MHz): δ 7.92 (dd, J=9.2, 1.6 Hz, 1H), 7.40 (dd, J=9.2, 2.8 Hz, 1H), 7.25 (s, 1H), 7.10 (d, J=9.2 Hz, 1H), 3.97 (s, 3H).