Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH2:7].[CH3:9][O:10][N:11]=[C:12]([C:18](OCC)=[O:19])[C:13](OCC)=[O:14].Cl>C[O-].[Na+]>[CH3:9][O:10][N:11]=[C:12]1[C:18](=[O:19])[NH:8][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=2[NH:7][C:13]1=[O:14]
Reactant: CCOC(=O)C(=NOC)C(=O)OCC
Reactant: Nc1ccccc1N
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Product: CON=c1c(=O)[nH]c2ccccc2[nH]c1=O

Procedure:
A mixture of iN sodium methylate (162 ml), o-phenylenediamine (17.5 g, 162 mmol) and diethyl 2-(methoxyimino)malonate (32.91 g, 162 mmol) is heated to reflux for 5 hr. After cooling, the mixture is acidified with 2N HCl (162 ml) and pale yellowish crystals (14.3 g, 41%) are filtered off.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH:5]=O.[NH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>CC(O)=O.C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH2:5][N:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: O=Cc1ccc([N+](=O)[O-])c(F)c1
Reactant: C1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: ClCCl
Product: O=[N+]([O-])c1ccc(CN2CCCCC2)cc1F
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 58.2 %

Procedure:
To a mixture of 3-fluoro-4-nitrobenzaldehyde (4.85 g, 28.7 mmol), piperidine (3.12 mL, 31.5 mmol) and 20 drops of AcOH in DCM was added sodium triacetoxyborohydride (6.69 g, 31.5 mmol), and the resulting suspension was stirred at RT for 30 minutes. The reaction was made basic with 2N aqueous NaOH, and extracted with DCM. The organic layer was washed with brine and was dried over sodium sulfate, filtered and concentrated in vacuo to yield a red oil. The residual oil was purified via MPLC, eluting with a gradient of 0-100% EtOAc in hexane to yield 1-(3-fluoro-4-nitrobenzyl)piperidine (3.98 g, 16.70 mmol, 58.2% yield) as an orange oil.
Reaction SMILES: C([O:5][C:6](=[O:20])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](=[O:19])[CH2:13][CH2:14][S:15][C:16](=[O:18])[CH3:17])(C)(C)C>C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>[C:16]([S:15][CH2:14][CH2:13][C:12]([N:8]1[CH2:9][CH2:10][CH2:11][C@H:7]1[C:6]([OH:20])=[O:5])=[O:19])(=[O:18])[CH3:17]
Reactant: CC(=O)SCCC(=O)N1CCC[C@H]1C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: COc1ccccc1
Product: CC(=O)SCCC(=O)N1CCC[C@H]1C(=O)O
Reaction time: 1 h

Procedure:
1-(3-Acetylthiopropanoyl)-L-proline-t-butyl ester (4.7 g.) is dissolved in a mixture of anisole (34 ml.) and trifluoroacetic acid (68 ml.) and the mixture is kept at room temperature for 1 hour. The solvents are removed in vacuo and the residue is precipitated from ether-hexane several times. The residue (3.5 g.) is dissolved in acetonitrile (25 ml.) and dicyclohexylamine (2.8 ml.) is added. The crystalline salt is filtered and recrystallized from isopropanol. Yield 3.8 g.. m.p. 176°-177°. The salt is reconverted to 1-(3-acetylthiopropanoyl)-L-proline as in Example 1, yield 1.25 g., m.p. 89°-90° (ethyl acetate-hexane).
Reaction SMILES: [Br:1]Br.[Cl:3][C:4]1[CH:12]=[CH:11][C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH:5]=1>C(O)(=O)C>[Br:1][C:10]1[C:6]2[CH:5]=[C:4]([Cl:3])[CH:12]=[CH:11][C:7]=2[S:8][CH:9]=1
Reactant: Clc1ccc2sccc2c1
Reactant: BrBr
Solvent: CC(=O)O
Product: Clc1ccc2scc(Br)c2c1
Temperature: 50 °C
Yield: 76.5 %

Procedure:
A solution of bromine (0.31 g, 1.95 mmol) in 1.0 ml glacial acetic acid was added to a stirred solution of 5-chlorobenzo[b]thiophene (0.300 g, 1.77 mmol)in glacial acetic acid (1.0 ml) under nitrogen atmosphere. The reaction was heated to 50° C. for 4 hours, the volatiles removed under reduced pressure, the residue diluted in methylene chloride, washed with aq. sodium bicarbonate and with brine and dried over sodium sulfate. Evaporation gave 0.335 g (76%) of a tan solid. mp 85°-86 C., FDMS m/e=249 (M+2).
Reaction SMILES: [C:1]1([N:7]2[C:11]([CH2:12][CH2:13][CH:14]=O)=[CH:10][C:9]([CH2:16][CH2:17][CH3:18])=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:19][CH:20]1[CH2:25][NH:24][CH2:23][CH2:22][N:21]1[C:26]1[CH:27]=[C:28]([CH3:32])[CH:29]=[CH:30][CH:31]=1.CCN(C(C)C)C(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[CH3:19][CH:20]1[CH2:25][N:24]([CH2:14][CH2:13][CH2:12][C:11]2[N:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[N:8]=[C:9]([CH2:16][CH2:17][CH3:18])[CH:10]=2)[CH2:23][CH2:22][N:21]1[C:26]1[CH:27]=[C:28]([CH3:32])[CH:29]=[CH:30][CH:31]=1
Reactant: CCCc1cc(CCC=O)n(-c2ccccc2)n1
Reactant: Cc1cccc(N2CCNCC2C)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Product: CCCc1cc(CCCN2CCN(c3cccc(C)c3)C(C)C2)n(-c2ccccc2)n1

Procedure:
132 mg (94%) of target compound was obtained by using a method same as in Example 1 by using 3-(1-phenyl-3-propyl-1H-pyrazol-5-yl)propanal (75 mg, 0.310 mmol), 2-methyl-1-m-tolylpiperazine (59 mg, 0.310 mmol), DIPEA (0.081 mL, 0.465 mmol) and NaBH(OAc)3 (197 mg, 0.930 mmol).
Reaction SMILES: [CH:1]1([NH:7][C:8]2[C:13]([C:14](O)=[O:15])=[CH:12][N:11]=[C:10]3[N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[CH:18]=[CH:19][C:9]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.C[N:30](C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.N.CO.[Cl-].[NH4+]>ClCCl>[CH:1]1([NH:7][C:8]2[C:13]([C:14]([NH2:30])=[O:15])=[CH:12][N:11]=[C:10]3[N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:25])[CH3:26])[CH:18]=[CH:19][C:9]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: C[Si](C)(C)CCOCn1ccc2c(NC3CCCCC3)c(C(=O)O)cnc21
Reactant: CCN=C=NCCCN(C)C
Agent: Cl
Agent: N
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CO
Product: C[Si](C)(C)CCOCn1ccc2c(NC3CCCCC3)c(C(N)=O)cnc21
Yield: 71 %

Procedure:
4-(Cyclohexylamino)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid (100 mg, 0.257 mmol) in dichloromethane (2 mL) was stirred with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (10 mg, 0.052 mmol), N-hydroxybenzotriazole (50 mg, 0.37 mmol) and 7 M ammonia-methanol solution (0.2 mL, 1.4 mmol) at room temperature for one day. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1→0/1 (v/v)) to give the title compound as a pale yellow amorphous (71.1 mg, yield 71%).
Reaction SMILES: [NH2:1][CH2:2][C@@H:3]1[C@H:8]([CH3:9])[CH2:7][CH2:6][CH2:5][N:4]1[C:10]([C:12]1[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:13]=1[C:19]1[N:24]=[CH:23][CH:22]=[CH:21][N:20]=1)=[O:11].Cl[C:26]1[O:27][C:28]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:29]=2[N:30]=1>>[F:35][C:32]1[CH:33]=[CH:34][C:28]2[O:27][C:26]([NH:1][CH2:2][C@@H:3]3[C@H:8]([CH3:9])[CH2:7][CH2:6][CH2:5][N:4]3[C:10]([C:12]3[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:13]=3[C:19]3[N:20]=[CH:21][CH:22]=[CH:23][N:24]=3)=[O:11])=[N:30][C:29]=2[CH:31]=1
Reactant: Fc1ccc2oc(Cl)nc2c1
Reactant: Cc1ccc(-c2ncccn2)c(C(=O)N2CCC[C@@H](C)[C@H]2CN)c1
Product: Cc1ccc(-c2ncccn2)c(C(=O)N2CCC[C@@H](C)[C@H]2CNc2nc3cc(F)ccc3o2)c1

Procedure:
The title compound was prepared following the same general protocol as described for Example A2 using ((2S,3R)-2-(aminomethyl)-3-methylpiperidin-1-yl)(5-methyl-2-(pyrimidin-2-yl)phenyl)methanone and 2-chloro-5-fluorobenzo[d]oxazole. MS (ESI) 460 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH:9]([NH:13][CH2:14][CH2:15][CH3:16])[CH2:10]2)=[CH:5][CH:4]=1.[C:17]([O:21][C:22]([N:24]1[CH2:30][CH2:29][C:28](=[O:31])[N:27]([CH2:32][CH2:33][CH2:34][CH:35]=O)[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[C:17]([O:21][C:22]([N:24]1[CH2:30][CH2:29][C:28](=[O:31])[N:27]([CH2:32][CH2:33][CH2:34][CH2:35][N:13]([CH:9]2[CH2:8][CH2:7][C:6]3[C:11](=[CH:12][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[CH2:10]2)[CH2:14][CH2:15][CH3:16])[CH2:26][CH2:25]1)=[O:23])([CH3:18])([CH3:19])[CH3:20]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)N(CCCC=O)CC1
Reactant: CCCNC1CCc2ccc(OC)cc2C1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: CCCN(CCCCN1CCN(C(=O)OC(C)(C)C)CCC1=O)C1CCc2ccc(OC)cc2C1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a solution of (7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-propyl-amine prepared as described in Example 1 (800 mg, 3.3 mmol, 1 eq) in 1,2-dichlororethane (40 mL) under inert atmosphere was added 5-oxo-4-(4-oxo-butyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester (1.0 g, 3.6 mmol, 1.1 eq.) in a single portion followed by the sodium triacetoxyborohydride (1.7 g, 8.25 mmol, 2.5 eq.). The reaction was stirred at room temperature for 20 hr, concentrated in-vacuo and then partitioned between 10% KOH (50 mL) and ethyl acetate (100 mL). The organic layer was washed with brine, dried (MgSO4) and concentrated. Purification by silica gel chromatography gave 1.1 g of 4-{4-[(7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-propyl-amino]-butyl}-5 -oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester.
Reaction SMILES: C[CH:2]([O:21][CH2:22]C1NC=CN=1)[C:3]1[CH:4]=[C:5]([N:9]2[C:13]3[CH:14]=[CH:15][C:16]([CH:18]=[N:19][OH:20])=[CH:17][C:12]=3[N:11]=[CH:10]2)[CH:6]=[CH:7][CH:8]=1.CC(OCC1NC=CN=1)C1C=C([N:36]2[C:40]3[CH:41]=[CH:42][C:43]([CH:45]=O)=CC=3N=C2)C=CC=1.CN1C(COCC2C=C(N3C4C=CC(C=NO)=CC=4N=C3)C=CC=2)=NC=N1.CON.CN1C(COCC2C=C(N3C4C=CC(C=NO)=CC=4N=C3)C=CC=2)=CC=N1.S1C=CN=C1COCC1C=C(N2C3C=CC(C=NO)=CC=3N=C2)C=CC=1.S1C=CN=C1COCC1C=C(N2C3C=CC(C=O)=CC=3N=C2)C=CC=1>>[N:36]1[CH:40]=[CH:41][CH:42]=[C:43]([CH2:22][O:21][CH2:2][C:3]2[CH:4]=[C:5]([N:9]3[C:13]4[CH:14]=[CH:15][C:16]([CH:18]=[N:19][OH:20])=[CH:17][C:12]=4[N:11]=[CH:10]3)[CH:6]=[CH:7][CH:8]=2)[CH:45]=1
Reactant: CC(OCc1ncc[nH]1)c1cccc(-n2cnc3cc(C=O)ccc32)c1
Reactant: CC(OCc1ncc[nH]1)c1cccc(-n2cnc3cc(C=NO)ccc32)c1
Agent: CON
Agent: Cn1nccc1COCc1cccc(-n2cnc3cc(C=NO)ccc32)c1
Agent: Cn1ncnc1COCc1cccc(-n2cnc3cc(C=NO)ccc32)c1
Product: ON=Cc1ccc2c(c1)ncn2-c1cccc(COCc2cccnc2)c1

Procedure:
To a solution of compound 12a (220 mg, 0.64 mmol) and pyridine (0.08 mL, 1.5 equiv) in ethanol (2 mL) was added hydroxylamine hydrochloride (500 mg) and the reaction mixture was stirred at RT for 3 hours. The reaction mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (100 mL), washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel using a mixture of ethyl acetate and pet-ether as the eluent to afford compound 14a (180 mg, 78%) as a solid. Mp 154-154.8° C. In analogy herewith, the following compounds were prepared: 1-[3-(1-Methyl-1H-imidazol-2-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14b) from 12b. Mp 209.8-211.7° C. and 1-[3-(2-Methyl-2H-[1,2,4]triazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14c) from 12c. Mp 145.8-147.7° C. O-Methyl 1-[3-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14h) from 12c and O-methyl hydroxylamine. LC-ESI-HRMS of [M+H]+ shows 377.1724 Da. Calc. 377.172525 Da, dev. −0.3 ppm 1-[3-(2-Methyl-2H-pyrazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14e) from 12e. LC-ESI-HRMS of [M+H]+ shows 362.1603 Da. Calc. 362.161625 Da, dev. −3.7 ppm O-Methyl 1-[3-(2-methyl-2H-pyrazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14i) from 12e and O-methyl hydroxyl amine. LC-ESI-HRMS of [M+H]+ shows 376.1755 Da. Calc. 376.177325 Da, dev. −4:9 ppm 1-[3-(1,3-Thiazol-2-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14j) from 12g. LC-ESI-HRMS of [M+H]+ shows 365.1074 Da. Calc. 365.107225 Da, dev. 0.5 ppm O-Methyl 1-[3-(1,3-thiazol-2-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14g) from 12g and O-methyl hydroxylamine. LC-ESI-HRMS of [M+H]+ shows 379.1238 Da. Calc. 379.122825 Da, dev. 2.6 ppm and 1-[3-(Pyridin-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14d) 1-[3-(Pyrimidin-4-ylmethoxymethyl)-phenyl]-1H-benzoimidazole-5-carbaldehyde oxime (14f) are prepared likewise.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:17][N:18]1[CH2:23][CH2:22][C:21](=[C:24]2[C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=3[CH:28]=[CH:27][C:26]3[CH:35]=[CH:36][CH:37]=[CH:38][C:25]2=3)[CH2:20][CH2:19]1)[C:13]([O:15]C)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>C(O)C>[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:17][N:18]1[CH2:23][CH2:22][C:21](=[C:24]2[C:25]3[CH:38]=[CH:37][CH:36]=[CH:35][C:26]=3[CH:27]=[CH:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]2=3)[CH2:20][CH2:19]1)[C:13]([OH:15])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)[C@H](CN1CCC(=C2c3ccccc3C=Cc3ccccc32)CC1)NC(=O)OCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(N[C@@H](CN1CCC(=C2c3ccccc3C=Cc3ccccc32)CC1)C(=O)O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of methyl (S)-2-benzyloxycarbonylamino-3-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidin-1-yl]propionate(2 g, 3.9 mmol) in 30 ml ethanol was added 10 ml of 1N NaOH aqueous solution. The mixture was then stirred at room temperature for 3 hours. After removing most ethanol under reduced pressure, the remaining mixture was diluted with ice-water and neutralized with acetic acid. The mixture was then extracted with chloroform (2×30 ml). The combined chloroform extract was washed with saline and dried over Na2SO4. After evaporating to dryness, the solid residue was recrystallized from ethanol to afford the title compound as a white crystalline. Yield:1.77 g (91%)
Reaction SMILES: [C:1]([O:5][C:6](=[O:17])[C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[C:9](F)[CH:8]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[CH2:19]([O:21][C:22](=[O:26])[CH2:23][CH2:24][NH2:25])[CH3:20].CCN(C(C)C)C(C)C>CN(C=O)C.O>[C:1]([O:5][C:6](=[O:17])[C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[C:9]([NH:25][CH2:24][CH2:23][C:22]([O:21][CH2:19][CH3:20])=[O:26])[CH:8]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)c1ccc([N+](=O)[O-])c(F)c1
Reactant: CCOC(=O)CCN
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)CCNc1cc(C(=O)OC(C)(C)C)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 85.7 %

Procedure:
3-fluoro-4-nitro-benzoic acid tert-butyl ester (1 g, 4.14 mmol) and Beta-Alanine ethyl ester hydrochloride 1.037 g, 6.75 mmol) were dissolved in DMF (10 ml). To the solution DIEA 0.872 g, 6.75 mmol) was added and the mixture stirred at room temperature overnight. The reaction mixture was diluted with water (100 ml), extracted with Ethyl acetate 3×, dried over MgSO4, filtered and evaporated to dryness to afford 1.2 g of solid was obtained (86%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]([O:10]CC)=O.Cl.[C:14](OCC)(=O)[CH:15]=C.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>CCO.O=[Pt]=O>[CH2:7]1[CH:2]2[N:1]([CH2:6][CH2:5][CH2:4][CH2:3]2)[CH2:15][CH2:14][C:8]1=[O:10]
Reactant: CCOC(=O)Cc1ccccn1
Reactant: C=CC(=O)OCC
Agent: O=[Pt]=O
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: Cl
Solvent: CCO
Product: O=C1CCN2CCCCC2C1
Temperature: 25 °C

Procedure:
To a solution of ethyl 2-pyridylacetate (9.2 mL, 60.5 mmol) in EtOH (100 mL) were added 6 N HCl (16 mL) and PtO2 (1 g). The reaction was stirred at room temperature under H2 until complete. The solvent was removed under reduced pressure, and the residue was diluted with 2 M NH4OH solution until slightly basic. The mixture was extracted with ether (3×50 mL). The combined organics were dried over Na2SO4, filtered and concentrated. The resulting yellow oil was diluted with EtOH (100 mL), and ethyl acrylate (14.5 mL, 133 mmol) and TEA (36 mL, 256 mmol) were added. The mixture was stirred at room temperature under argon for three days. The mixture was concentrated, and the resulting colorless oil was dried under vacuum. The oil was dissolved in THF (25 mL) and cooled to −78° C. LiHMDS (84 mL, 84 mmol) was added dropwise, and the mixture was stirred at −78° C. for 2 h. The reaction was quenched with H2O, diluted with ether, washed with sat. NaHCO3 solution and dried over Na2SO4. The organic solution was filtered and concentrated. The resulting oil was diluted with 6 M HCl (70 mL) and heated to reflux overnight. The mixture was cooled, neutralized with solid KHCO3 and extracted with ether. The combined organics were dried over Na2SO4. filtered and concentrated to give hexahydro-1H-quinolizin-2(6H)-one, which was carried forward without purification. The crude oil was dissolved in EtOH (15 mL), and 1-(3-bromophenyl)-1-methylhydrazine hydrochloride (2.1 g, 8.81 mmol) was added followed by concentrated HCl (15 mL). The reaction mixture was heated to reflux overnight. The mixture was concentrated, and the residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) to give the title compound (1.02 g, 36%) as an off-white solid: 1H NMR (500 MHz, CDCl3) δ 7.49 (d, J=2.0 Hz, 1H), 7.27 (d, J=8.5 Hz, 1H), 7.10 (dd, J=8.5, 1.5 Hz, 1H), 4.56 (s, 2H), 4.03 (d, J=14.0 Hz, 1H), 3.62 (s, 3H), 3.41-3.35 (m, 1H), 3.20-3.16 (m, 1H), 2.92 (dd, J=16.0, 2.5 Hz, 1H), 2.64-2.53 (m, 2H), 2.40-2.37 (m, 1H), 2.03-2.00 (m, 1H), 1.85-1.67 (m, 2H), 1.52-1.45 (m, 1H); ESI MS m/z 319 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[C:5]([CH:7]1[CH2:12][CH2:11][N:10]([CH3:13])[CH2:9][CH2:8]1)=[O:6].[CH3:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=1)[C:21](Cl)=[O:22]>>[CH3:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=1)[C:21]([NH:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[C:5]([CH:7]1[CH2:8][CH2:9][N:10]([CH3:13])[CH2:11][CH2:12]1)=[O:6])=[O:22]
Reactant: CN1CCC(C(=O)c2cccc(N)c2)CC1
Reactant: Cc1cccc(C(=O)Cl)c1
Product: Cc1cccc(C(=O)Nc2cccc(C(=O)C3CCN(C)CC3)c2)c1
Yield: 96.1 %

Procedure:
Beginning with 4-[3-aminobenzoyl]-1-methylpiperidine (50 mg, 0.229 mmol) and 3-methylbenzoyl chloride (91 μl, 0.687 mmol), 74.0 mg (96%) of the title compound were recovered.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:10](Cl)=[CH:9][C:5]=1[C:6]([OH:8])=[O:7])([O-:3])=[O:2].[CH3:14][CH:15]1[O:20][CH:19]([CH3:21])[CH2:18][NH:17][CH2:16]1>C(OCC)(=O)C>[N+:1]([C:4]1[CH:12]=[CH:11][C:10]([N:17]2[CH2:16][CH:15]([CH3:14])[O:20][CH:19]([CH3:21])[CH2:18]2)=[CH:9][C:5]=1[C:6]([OH:8])=[O:7])([O-:3])=[O:2]
Reactant: O=C(O)c1cc(Cl)ccc1[N+](=O)[O-]
Reactant: CC1CNCC(C)O1
Solvent: CCOC(C)=O
Product: CC1CN(c2ccc([N+](=O)[O-])c(C(=O)O)c2)CC(C)O1
Temperature: 120 °C
Reaction time: 6 h

Procedure:
The mixture of 5 g 2-nitro-5-chlorobenzoic acid and 15 ml 2,6-dimethylmorpholine is stirred at 120° C. for 6 hours. To the reaction mixture 150 ml of ethyl acetate is added. The precipitated yellow crystalline material is filtered off, dissolved in 15 ml water. The pH of the mixture is set to 6 with acetic acid. The precipitated material is filtered off, washed with water and dried, to obtain 4.2 g of the title compound (MH+:281).
Reaction SMILES: [C:1]([NH:5][C:6](=[O:11])[CH2:7][C:8](=O)[CH3:9])([CH3:4])([CH3:3])[CH3:2].[NH3:12]>>[C:1]([NH:5][C:6](=[O:11])/[CH:7]=[C:8](\[NH2:12])/[CH3:9])([CH3:4])([CH3:3])[CH3:2]
Reactant: N
Reactant: CC(=O)CC(=O)NC(C)(C)C
Product: C/C(N)=C/C(=O)NC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
N-t-butyl-3-ketobutanamide (0.29 g) was dissolved in saturated ethanolic ammonia (15 ml) and stirred overnight at room temperature. The solution was evaporated to yield N-t-butyl-3-aminocrotonamide which was used directly. The crude residue was dissolved in ethanol (8 ml), 2-chlorobenzaldehyde (0.28 g) and ethyl 4-[2-(2-methylbenzimidazol-1-yl)ethoxy]-3-ketobutanoate (0.61 g) were added. The mixture was heated at reflux overnight, cooled and the solvent removed under reduced pressure. The residue was chromatographed on silica eluting with 4% diethylamine in ethyl acetate. The fractions containing the product were combined and evaporated. The residue was re-chromatographed on silica eluting with 5% methanol in ethyl acetate. The fractions containing the product were combined and evaporated to yield the title compound (0.17 g, 15%). m.p. 157°-161° C. Found: C, 65.66; H, 6.68; N, 9.74. C31H37C1N4O4 requires C, 65.89; H, 6.60; N, 9.91%.
Reaction SMILES: [Cl:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:15]#[C:16][Si](C)(C)C.C(=O)([O-])[O-].[K+].[K+]>CO.C1COCC1>[Cl:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:13][CH2:14]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:15]#[CH:16]
Reactant: C[Si](C)(C)C#Cc1ccc2c(nnn2CC2CC2)c1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: C1CCOC1
Product: C#Cc1ccc2c(nnn2CC2CC2)c1Cl
Reaction time: 18 h

Procedure:
A solution of 4-chloro-1-(cyclopropylmethyl)-5-[(trimethylsilyl)ethynyl]-1H-benzotriazole (0.72 g, 2.4 mmol) in MeOH (21 mL) and THF (2.1 mL) was treated with potassium carbonate (0.33 g, 2.4 mmol) and stirred for 18 hours. The mixture was concentrated in vacuo and the residue was dissolved in dichloromethane and washed with brine. The organic extracts were dried with magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (0-35% EtOAc in hexanes), providing the titled compound as a faint yellow oil: 1H-NMR (400 MHz, CDCl3) δ 7.60 (d, J=8.6 Hz, 1H), 7.43 (d, J=8.6 Hz, 1H), 4.52 (d, J=7.1 Hz, 2H), 3.44 (s, 1H), 1.36-1.43 (m, 1H), 0.66-0.71 (m, 2H), 0.48-0.52 (m, 2H) ppm; LRMS m/z (M+H) 234.1 [calculated for C12H11ClN3: 234.1].
Reaction SMILES: [Si]([O:8][CH2:9][C@H:10]1[O:14][C@@H:13]([N:15]2[CH:22]=[CH:21][C:19](=[O:20])[NH:18][C:16]2=[O:17])[C@H:12]([S:23][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:11]1[O:32][C:33]([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)([C:42]1[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=1)[C:34]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[C:24]([S:23][C@@H:12]1[C@H:11]([O:32][C:33]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)([C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)[C:42]2[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=2)[C@@H:10]([CH2:9][OH:8])[O:14][C@H:13]1[N:15]1[CH:22]=[CH:21][C:19](=[O:20])[NH:18][C:16]1=[O:17])(=[O:31])[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: COc1ccc(C(O[C@H]2[C@@H](SC(=O)c3ccccc3)[C@H](n3ccc(=O)[nH]c3=O)O[C@@H]2CO[Si](C)(C)C(C)(C)C)(c2ccccc2)c2ccc(OC)cc2)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: COc1ccc(C(O[C@H]2[C@@H](SC(=O)c3ccccc3)[C@H](n3ccc(=O)[nH]c3=O)O[C@@H]2CO)(c2ccccc2)c2ccc(OC)cc2)cc1

Procedure:
5'-O-(tert-Butyldimethylsilyl)-3'-O-(4,4'-dimethoxytrityl)-2'-deoxy-2'-(benzoylthio)-uridine (1.4 mmole) was treated with 20 ml of 1.0M tetrabutylammonium fluoride in THF at room temperature for 16 hr. The solvent was removed and the residue was purified on silica gel column chromatography to provide 2'-(benzoylthio)-3'-O-(4,4'-dimethoxytrityl)-2'-deoxyuridine.