Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br.[OH:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([O:13][CH2:14][C:15](O)=O)=[CH:8][CH:9]=[N:10]2)=[CH:5][CH:4]=1.[F:18][C:19]1[C:20]([NH:31][NH2:32])=[N:21][CH:22]=[C:23]([C:25]2[O:29][N:28]=[C:27]([CH3:30])[CH:26]=2)[CH:24]=1>>[F:18][C:19]1[C:20]2[N:21]([C:15]([CH2:14][O:13][C:7]3[C:6]4[C:11](=[CH:12][C:3]([OH:2])=[CH:4][CH:5]=4)[N:10]=[CH:9][CH:8]=3)=[N:32][N:31]=2)[CH:22]=[C:23]([C:25]2[O:29][N:28]=[C:27]([CH3:30])[CH:26]=2)[CH:24]=1
Reactant: Cc1cc(-c2cnc(NN)c(F)c2)on1
Reactant: O=C(O)COc1ccnc2cc(O)ccc12
Agent: Br
Product: Cc1cc(-c2cc(F)c3nnc(COc4ccnc5cc(O)ccc45)n3c2)on1

Procedure:
The material was prepared using general method A (with 2-(7-hydroxyquinolin-4-yloxy)acetic acid hydrobromide and 1-(3-fluoro-5-(3-methylisoxazol-5-yl)pyridin-2-yl)hydrazine
Reaction SMILES: [CH3:1][C:2]1[C:3]([N+:11]([O-:13])=[O:12])=[C:4]([CH:8]=[CH:9][CH:10]=1)C(O)=O.[N-:14]=[N+]=[N-].[Na+].[OH-].[NH4+]>S(=O)(=O)(O)O>[CH3:1][C:2]1[C:3]([N+:11]([O-:13])=[O:12])=[C:4]([CH:8]=[CH:9][CH:10]=1)[NH2:14]
Reactant: Cc1cccc(C(=O)O)c1[N+](=O)[O-]
Reactant: [N-]=[N+]=[N-]
Agent: O=S(=O)(O)O
Agent: [NH4+]
Agent: [Na+]
Product: Cc1cccc(N)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 48 h
Yield: 99.2 %

Procedure:
A stirred solution of 3-methyl-2-nitrobenzoic acid (18.1 g, 0.1 mole) in 150 ml of concentrated sulfuric acid was cooled to -5°. Sodium azide (7.5 g, 0.115 mole) was added portionwise to the reaction mixture. After complete addition the reaction mixture was heated at 55° for three hours, then stirred at room temperature for two days. The reaction mixture was poured into ice water and the resulting solution made alkaline (pH 9) with concentrated ammonium hydroxide. A solid precipitate formed and was collected by filtration to give 3-methyl-2-nitroaniline (15.1 g, mp 105°-108.5°).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[F:6][C:7]1([F:13])[CH2:9][CH:8]1[CH2:10][CH2:11][OH:12].C(N(CC)CC)C.O>C1COCC1>[CH3:1][S:2]([O:12][CH2:11][CH2:10][CH:8]1[CH2:9][C:7]1([F:13])[F:6])(=[O:4])=[O:3]
Reactant: OCCC1CC1(F)F
Reactant: CS(=O)(=O)Cl
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCC1CC1(F)F
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Methanesulfonyl chloride (1.35 mL) was added to a solution of 2-(2,2-difluorocyclopropyl)ethanol (1.42 g) and triethylamine (3.24 mL) in THF (20 mL) dropwise at 0° C. The mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (1.31 g) as a pale yellow oil.
Reaction SMILES: [CH2:1]([C:3]1[C:11]2[N:10]=[CH:9][NH:8][C:7]=2[CH:6]=[CH:5][C:4]=1[C:12]#[N:13])[CH3:2].[O:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C1(C)C=CC=CC=1>[CH2:1]([C:3]1[C:11]2[N:10]=[CH:9][N:8]([CH:15]3[CH2:16][CH2:17][CH2:18][CH2:19][O:14]3)[C:7]=2[CH:6]=[CH:5][C:4]=1[C:12]#[N:13])[CH3:2]
Reactant: CCc1c(C#N)ccc2[nH]cnc12
Reactant: C1CCOCC1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: Cc1ccccc1
Product: CCc1c(C#N)ccc2c1ncn2C1CCCCO1
Yield: 68.5 %

Procedure:
To a solution of 4-ethyl-1H-benzo[d]imidazole-5-carbonitrile (6.8 g, 0.04 mol) in dry toluene (70 mL) was added tetrahydro-2H-pyran (10.53 g, 0.12 mol, 3 equiv.) and pyridinium-p-toluenesulfonate (4 g, 0.02 mol, 0.5 equiv.) and the reaction mixture was heated at reflux for 16 h. The reaction mixture was concentrated, quenched with water and extracted with EtOAc. The combined organic layers were washed with brine and then dried (Na2SO4), filtered, and concentrated. The crude product was purified by SiO2 chromatography eluting with 50% EtOAc/hexane to afford 4-ethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole-5-carbonitrile (7 g, 69% yield) as a yellow oil.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([NH:16][S:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[C:26]([F:29])([F:28])[F:27])(=[O:19])=[O:18])[CH:12]=[C:13]([CH3:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37].C([O-])([O-])=O.[K+].[K+]>CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([N:16]([S:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[C:26]([F:29])([F:28])[F:27])(=[O:19])=[O:18])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH:12]=[C:13]([CH3:15])[CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CCCCCBr
Reactant: Cc1cc(NS(=O)(=O)c2ccccc2C(F)(F)F)cc(OCc2ccccc2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)CCCCCN(c1cc(C)cc(OCc2ccccc2)c1)S(=O)(=O)c1ccccc1C(F)(F)F
Temperature: 60 °C
Reaction time: 12 h
Yield: 100.3 %

Procedure:
3-Benzyloxy-5-methyl-1-(2-trifluoromethylphenylsulfonylamino)benzene (550 mg, 1.3 mmol), as prepared in the preceding step, ethyl 6-bromohexanoate (290 mg, 1.3 mmol), and K2CO3 (1.0 g) were mixed in N,N-dimethylformamide (10 mL). The mixture was heated to 60° C. and stirred for 12 h. The solid was removed by filtration, and the filtrate was evaporated under high vacuum. The residue was dissolved in ethyl acetate (100 mL), washed with saturated aqueous NaHCO3 (2×50 mL) and brine (2×50 mL), and dried over Na2SO4. The solvent was evaporated in vacuo to give the title compound as a pale red oil (735 mg, 100%) which was directly used for the next step. 1H-NMR (300 MHz, CDCl3) δ 7.85 (d, J=7.7 Hz, 1 H), 7.71 (d, J=7.8 Hz, 1 H), 7.60 (t, J=7.7 Hz, 1 H), 7.47 (t, J=7.7 Hz, 1 H), 7.37 (m, 5 H), 6.71 (s, 1 H), 6.53 (s, 1 H), 6.51 (s, 1 H), 4.95 (s,2H), 4.11 (q, J=7.1 Hz, 2 H),3.66(t,J=7.0 Hz, 2 H), 2.25 (t, J=7.4 Hz, 2 H), 2.23 (s, 3 H), 1.33-1.62 (m, 6 H), 1.24 (t, J=7.1 Hz, 3 H).
Reaction SMILES: Br[C:2]1[C:3]([O:17][CH3:18])=[CH:4][C:5]2[S:9][C:8]([NH:10][C:11]([NH:13][CH2:14][CH3:15])=[O:12])=[N:7][C:6]=2[CH:16]=1.[CH3:19][C:20]1([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:25][CH2:24][N:23]([C:26]2[N:31]=[CH:30][C:29](B3OC(C)(C)C(C)(C)O3)=[CH:28][N:27]=2)[CH2:22][CH2:21]1.C(Cl)Cl.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:14]([NH:13][C:11]([NH:10][C:8]1[S:9][C:5]2[CH:4]=[C:3]([O:17][CH3:18])[C:2]([C:29]3[CH:28]=[N:27][C:26]([N:23]4[CH2:24][CH2:25][C:20]([CH3:19])([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:21][CH2:22]4)=[N:31][CH:30]=3)=[CH:16][C:6]=2[N:7]=1)=[O:12])[CH3:15]
Reactant: CCNC(=O)Nc1nc2cc(Br)c(OC)cc2s1
Reactant: CCOC(=O)C1(C)CCN(c2ncc(B3OC(C)(C)C(C)(C)O3)cn2)CC1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: C1COCCO1
Solvent: ClCCl
Product: CCNC(=O)Nc1nc2cc(-c3cnc(N4CCC(C)(C(=O)OCC)CC4)nc3)c(OC)cc2s1
Temperature: 110 °C

Procedure:
1-(5-Bromo-6-methoxy-1,3-benzothiazol-2-yl)-3-ethyl-urea (Intermediate 11) (200 mg, 66 mass %, 0.40 mmol), ethyl 4-methyl-1-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl]piperidine-4-carboxylate (crude, 638 mg, 47 mass %, 0.80 mmol) and Pd(dppf)Cl2.DCM (16 mg, 0.02 mmol) were dissolved in dioxane (7.5 mL) in a microwave vial and a solution of cesium carbonate (391 mg, 1.20 mmol) in water (2.5 mL) was added. The vial was capped, the mixture degassed and heated in the microwave at 110° C. for 30 minutes. The mixture was poured into water, extracted into EtOAc (4×20 mL) and the organic layers washed with brine, dried over Na2SO4 and concentrated to dryness in vacuo. A yellow solid was obtained and the mixture purified by chromatography, Biotage SP4, 12 g Si cartridge, 0-5% MeOH in DCM. The relevant fractions were combined to give a brown solid which was further purified by chromatography, Biotage SP4, 12 g Si cartridge, 50% EtOAc in hexane (isocratic) then the column flushed with EtOAc. The relevant fractions were combined to give Compound 191 as a white solid, 110 mg (55%). 1H NMR (MeCN-d3): δ 1.19 (3H, t, J=7.2 Hz), 1.26 (3H, s), 1.29 (3H, t, J=7.1 Hz), 1.49 (2H, ddd, J=14.0, 10.5 and 4.1 Hz), 2.14 (2H, m), 3.32 (4H, m), 3.87 (3H, s), 4.20 (2H, q, J=7.1 Hz), 4.37 (2H, dt, J=14.0 and 4.1 Hz), 6.16 (1H, br s), 7.51 (1H, s), 7.61 (1H, s), 8.55 (2H, s), 8.77 (1H, br s). MS: 499.12 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[N:3]=[C:4]([CH2:21][CH3:22])[C:5]([NH:10][C@@H:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][C@@H:12]2[OH:20])=[N:6][C:7]=1[CH2:8][CH3:9].[CH:23]1(C2N=C(N[C@@H]3C4C(=CC=CC=4)C[C@@H]3O)C(CC)=NC=2)CC1>>[Br:1][C:2]1[N:3]=[C:4]([CH2:21][CH3:22])[C:5]([NH:10][C@@H:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][C@@H:12]2[OH:20])=[N:6][C:7]=1[CH:8]1[CH2:23][CH2:9]1
Reactant: CCc1nc(N[C@@H]2c3ccccc3C[C@@H]2O)c(CC)nc1Br
Reactant: CCc1ncc(C2CC2)nc1N[C@@H]1c2ccccc2C[C@@H]1O
Product: CCc1nc(Br)c(C2CC2)nc1N[C@@H]1c2ccccc2C[C@@H]1O

Procedure:
Following the procedure for the preparation of (1R,2S)-1-[(5-bromo-3,6-diethylpyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol but substituting (1R,2S)-1-[(6-cyclopropyl-3-ethylpyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol and making non-critical variations provided the title compound as a solid: 1H NMR (CDCl3) δ 0.93-1.09, 1.28-1.39, 2.35-2.43, 2.60-2.67, 2.99-3.05, 3.22-3.29, 4.70, 5.04, 5.44-5.49, 7.23-7.32; MS (ESI+) for C18H20BrN3O m/z 374 (M+H)+.
Reaction SMILES: Cl.[OH:2][CH2:3][C:4]1[N:5]=[CH:6][NH:7][CH:8]=1.C(N(CC)CC)C.[C:16]([Si:20]([CH3:23])([CH3:22])Cl)([CH3:19])([CH3:18])[CH3:17]>ClCCl.CN(C=O)C>[Si:20]([O:2][CH2:3][C:4]1[N:5]=[CH:6][NH:7][CH:8]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:23])[CH3:22]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OCc1c[nH]cn1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OCc1c[nH]cn1

Procedure:
4-Hydroxymethylimidazole hydrochloride (5.03 g) was dissolved in a mixed solvent of dichloromethane (90 mL) and DMF (20 mL), and to the solution triethylamine (8.25 g) was added at 0° C. tert-Butyldimethylchlorosilane (6.14 g) was then added to the mixture, and the resultant mixture was stirred at room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was then purified by column chromatography on silica gel (chloroform:methanol=20:1) to obtain the title compound.
Reaction SMILES: [Mg].[CH3:2][C:3]1[O:9][C:6]([CH:7]=[O:8])=[CH:5][CH:4]=1.[CH2:10](Cl)[C:11]#[CH:12].C(Br)C#C>[Cl-].[Zn+2].[Cl-].C(Cl)C#C.C1(C)C=CC=CC=1.O1CCCC1>[OH:8][CH:7]([C:6]1[O:9][C:3]([CH3:2])=[CH:4][CH:5]=1)[CH2:12][C:11]#[CH:10]
Reactant: Cc1ccc(C=O)o1
Reactant: C#CCCl
Agent: C#CCBr
Agent: [Cl-]
Agent: [Mg]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: C#CCC(O)c1ccc(C)o1
Temperature: 10 °C
Yield: 85.8 %

Procedure:
In the same flask as in Example 1, there were charged granular magnesium (18.2 g), dry zinc chloride (20.4 g) and dry tetrahydrofuran (220 g). Propargyl chloride (0.55 g) was added thereto at 10° C. while stirring. The resultant mixture was kept in an adiabatic condition, whereupon the reaction proceeded. When the heat generation stopped, a mixture of 5-methylfurfural (55.06 g), propargyl chloride (38.6 g), propargyl bromide (11.9 g) and toluene (55 g) was dropwise added to the reaction mixture at 30° C. in 6 hours while stirring under cooling. The resultant mixture was kept at room temperature for 30 minutes while stirring. After completion of the reaction, the reaction mixture was treated in the same manner as in Example 1 to give 2-(1-hydroxy-3-butynyl)-5-methylfuran (64.4 g) in a yield of 86% (based on the starting 5-methylfurfural).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([OH:13])=[C:6]2[C:10]3([CH2:12][CH2:11]3)[CH2:9][O:8][C:7]=12.CN(C=O)C.Cl[C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][N:21]=1>>[CH3:1][C:2]1[C:7]2[O:8][CH2:9][C:10]3([CH2:12][CH2:11]3)[C:6]=2[C:5]([O:13][C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][N:21]=2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(O)c2c1OCC21CC1
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Solvent: CN(C)C=O
Product: Cc1ccc(Oc2ccc([N+](=O)[O-])cn2)c2c1OCC21CC1
Temperature: 80 °C
Reaction time: 2 h
Yield: 90.5 %

Procedure:
To a solution of 7-methylspiro[2H-benzofuran-3,1′-cyclopropane]-4-ol (Intermediate 13, 176 mg, 1 mmol) in dry DMF (4 ml) potassium carbonate (207 mg, 1.5 mmol) and then 2-chloro-5-nitropyridine (158 mg, 1 mmol) were added and the reaction mixture was stirred for 2 hours at 80° C. After cooling the reaction mixture was quenched with water (2 ml), diluted with brine (10 ml) and extracted with ethyl acetate (2×20 ml). The organic layer was dried over sodium sulfate, filtered and evaporated affording the title compound (270 mg) as an orange solid that was used in the next step as crude material without further purification.
Reaction SMILES: Br[C:2]1[N:3]=[C:4]([C:23]2[O:24][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[N:26][N:27]=2)[C:5]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:42]2[CH2:43][CH2:44][N:45]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:46][CH:47]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:11]([O:10][C:9]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:5]1[N:6]=[CH:7][C:2]([C:42]2[CH2:47][CH2:46][N:45]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:44][CH:43]=2)=[N:3][C:4]=1[C:23]1[O:24][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[N:26][N:27]=1)=[O:15])([CH3:14])([CH3:13])[CH3:12]
Reactant: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)c1ncc(Br)nc1-c1nnc(-c2ccccc2)o1
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CC=C(c2cnc(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)c(-c3nnc(-c4ccccc4)o3)n2)CC1
Temperature: 100 °C
Yield: 81.4 %

Procedure:
Tert-butyl N-[5-bromo-3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl]-N-tert-butoxycarbonyl-carbamate (2.4633 g, 4.752 mmol) was dissolved in DMF (19.24 mL) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (2.204 g, 7.128 mmol) and Pd(PPh3)2Cl2 (196.6 mg, 0.4752 mmol) were added followed by Na2CO3 (7.130 mL of 2 M, 14.26 mmol) and the reaction heated at 100° C. under nitrogen for 15 minutes. The reaction mixture was allowed to cool to RT and the solvent removed in vacuo. The mixture was diluted with EtOAc/water and the organic layer washed with water (×4) followed by brine (×3). After drying over MgSO4, the reaction was filtered and evaporated to dryness to give a dark brown oil which was purified on silica gel by flash column chromatography (0-40% EtOAc/Petrol) to afford the title compound (2.40 g, 81% Yield).
Reaction SMILES: [C:1]([C:6]1[NH:7][C:8]([CH2:15][CH2:16][CH3:17])=[C:9]([CH3:14])[C:10]=1[CH2:11][CH2:12][CH3:13])(OCC)=O.[CH3:18]C1OC(C)OC(C)O1>>[CH2:1]([C:6]1[NH:7][C:8]([CH2:15][CH2:16][CH3:17])=[C:9]([CH3:14])[C:10]=1[CH2:11][CH2:12][CH3:13])[CH3:18]
Reactant: CCCc1[nH]c(C(=O)OCC)c(CCC)c1C
Reactant: CC1OC(C)OC(C)O1
Product: CCCc1[nH]c(CC)c(CCC)c1C

Procedure:
2-Carbethoxy-3,5-di(n-propyl)-4-methyl-pyrrole was reductively alkylated with paraldehyde to yield 2-ethyl-3,5-di(n-propyl)-4-methyl-pyrrole. ##STR105##
Reaction SMILES: [CH3:1][N:2]1[C:9]([NH:10][OH:11])=[CH:8][C:6](=[O:7])[N:5]([CH3:12])[C:3]1=[O:4].[C:13](OC(=O)C)(=O)[CH3:14]>>[CH3:13][C:14]1[O:11][N:10]=[C:9]2[C:8]=1[C:6](=[O:7])[N:5]([CH3:12])[C:3](=[O:4])[N:2]2[CH3:1]
Reactant: CC(=O)OC(C)=O
Reactant: Cn1c(NO)cc(=O)n(C)c1=O
Product: Cc1onc2c1c(=O)n(C)c(=O)n2C

Procedure:
One gram of 1,3-dimethyl-6-hydroxyaminouracil is boiled with 10 ml of acetic anhydride at 140° C. for 1 hour and, when hot, the insolubles are filtered off. The filtrate is concentrated to dryness to recover 0.7 g of the captioned compound as colorless needles. As recrystallized from ethanol, the compound melts at 200°-202° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:13])[CH2:5][C:6]1[CH:7]=[N+:8]([O-])[CH:9]=[CH:10][CH:11]=1)[CH3:2].P(Cl)(Cl)([Cl:16])=O>>[CH2:1]([O:3][C:4](=[O:13])[CH2:5][C:6]1[C:7]([Cl:16])=[N:8][CH:9]=[CH:10][CH:11]=1)[CH3:2]
Reactant: O=P(Cl)(Cl)Cl
Reactant: CCOC(=O)Cc1ccc[n+]([O-])c1
Product: CCOC(=O)Cc1cccnc1Cl
Yield: 50 %

Procedure:
A mixture of 1.56 g (8.6 mol) of 3-pyridineacetic acid ethyl ester 1-oxide (for preparation, see A. R. Katritzky, J. Chem. Soc., 1956, 2404) and 15 ml of phosphorous oxychloride was heated to 80° C. for 3 hours. After cooling, the solvent was evaporated and the residue was poured onto ice water and solid sodium bicarbonate was added until the pH was basic. The organic layer was extracted with ethyl acetate and the combined extracts were dried over sodium sulfate and evaporated to an oil which was purified by flash chromatography with an ethyl acetate-hexane (1:4-1:1) eluant. The fractions containing the less polar isomer (Rf 0.3, ethyl acetate-hexane (3:7)) were combined and evaporated to yield 584 mg (50%) of the title compound of this preparation as an oil. 1H NMR (CDCl3): δ 1.22 (3H, t, J=7), 3.76 (2H, s), 4.15 (2H, q, J=7), 7.11-7.21 (2H, m), 8.25-8.31 (1H, m).
Reaction SMILES: C([Li])CCC.CCCCCC.[O:12]([C:30]1[CH:35]=[C:34]([O:36][CH3:37])[CH:33]=[C:32]([O:38][CH3:39])[CH:31]=1)[Si:13]([C:26]([CH3:29])([CH3:28])[CH3:27])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CN(C)[CH:42]=[O:43].[Cl-].[NH4+]>C(OCC)C>[O:12]([C:30]1[CH:35]=[C:34]([O:36][CH3:37])[C:33]([CH:42]=[O:43])=[C:32]([O:38][CH3:39])[CH:31]=1)[Si:13]([C:26]([CH3:28])([CH3:29])[CH3:27])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CN(C)C=O
Reactant: COc1cc(OC)cc(O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: CCOCC
Product: COc1cc(O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)cc(OC)c1C=O
Temperature: 0 °C
Yield: 41.3 %

Procedure:
Under nitrogen, a 1.60 M solution of n-butyl lithium in hexane (31 mL, 49 mmol) was added to a solution of 1-t-butyldiphenylsiloxy-3,5-dimethoxybenzene (14.68 g, 39.0 mmol) in anhydrous diethyl ether (200 mL) stirred in an ice bath. The reaction mixture was stirred at 35° C. for 3 hours and cooled in the ice bath, followed by the addition of dimethylformamide (9.21 mL, 119.4 mmol). After stirring at room temperature for 1 hour, saturated aqueous ammonium chloride was added, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to yield 4-t-butyldiphenylsiloxy-2,6-dimethoxybenzaldehyde as a colorless crystalline powder (melting point: 177.5–120.0° C.) (6.77 g, yield: 41%).
Reaction SMILES: [Si:1]([O:8][CH2:9][CH:10]([OH:23])[CH2:11][N:12]1[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[N:14]=[C:13]1[N+]([O-])=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+]>CN(C=O)C>[Si:1]([O:8][CH2:9][CH:10]1[O:23][C:13]2=[N:14][C:15]([N+:17]([O-:19])=[O:18])=[CH:16][N:12]2[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OCC(O)Cn1cc([N+](=O)[O-])nc1[N+](=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCC1Cn2cc([N+](=O)[O-])nc2O1
Temperature: -15 °C
Reaction time: 0.83 h
Yield: 64.1 %

Procedure:
A solution of alcohol 88 (2.04 g, 5.89 mmol) in anhydrous DMF (20 mL) under N2 at −20° C. was treated with 60% NaH (0.34 g, 8.50 mmol). After stirring at −20 to −10° C. for 50 min, the reaction was quenched with EtOAc and water (150 mL), and extracted with EtOAc (500 mL). The extract was washed with water (2×100 mL) and brine (100 mL), backextracting with EtOAc (100 mL), and then the solvent was removed. Chromatography of the residue on silica gel, eluting with 40-67% EtOAc/petroleum ether, gave 2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole (89) (1.13 g, 64%) as a pale yellow solid: mp (EtOAc/petroleum ether) 142-144° C.; 1H NMR (CDCl3) δ 7.52 (s, 1H), 5.33 (m, 1H), 4.29 (d, J=7.2 Hz, 2H), 4.05 (dd, J=11.9, 3.5 Hz, 1H), 3.86 (dd, J=11.9, 2.8 Hz, 1H), 0.81 (s, 9H), 0.08, 0.03 (2 s, 2×3H). Anal. (C12H21N3O4Si) C, H, N.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([NH:7][NH2:8])=[O:6].[CH2:12](OC(OCC)(OCC)C)[CH3:13]>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([C:5]2[O:6][C:12]([CH3:13])=[N:8][N:7]=2)[CH:9]=[CH:10][CH:11]=1
Reactant: NNC(=O)c1cccc(Br)c1
Reactant: CCOC(C)(OCC)OCC
Solvent: CC(=O)O
Product: Cc1nnc(-c2cccc(Br)c2)o1
Temperature: 150 °C
Reaction time: 3 h
Yield: 33.5 %

Procedure:
In a pressure vessel was suspended 3-bromobenzohydrazide (1.8 g, 8.37 mmol) in 14 ml acetic acid. 1,1,1-Triethoxyethane (4.6 ml, 25 mmol) was added and the reaction was stirred at 150° C. for 3 h. The solvent was concentrated under reduced pressure and the crude was washed with sodium bicarbonate and brine. The organic layer was dried over sodium sulphate, filtered and evaporated under reduced pressure. The residue was re-dissolved in dichloromethane, concentrated under reduced pressure and a solid was precipitated. This solid was washed with diethylether, filtered and dried in the vacuum oven at 40° C. to obtain 670 mg (35% yield) of the title compound. Purity 100%.
Reaction SMILES: [CH3:1][NH2:2].[CH3:3][O:4][C:5]1[CH:21]=[CH:20][C:8]2[S:9](=[O:19])[C:10]([C:16]([NH2:18])=[O:17])=[C:11](OC(C)C)[C:7]=2[CH:6]=1>C(#N)C>[CH3:3][O:4][C:5]1[CH:21]=[CH:20][C:8]2[S:9](=[O:19])[C:10]([C:16]([NH2:18])=[O:17])=[C:11]([NH:2][CH3:1])[C:7]=2[CH:6]=1
Reactant: CN
Reactant: COc1ccc2c(c1)C(OC(C)C)=C(C(N)=O)S2=O
Solvent: CC#N
Product: CNC1=C(C(N)=O)S(=O)c2ccc(OC)cc21
Reaction time: 0.5 h
Yield: 86 %

Procedure:
Monomethylamine gas is passed into a room temperature solution of 5-methoxy-3-(1-methylethoxy)benzo[b]thiophene-2-carboxamide-1-oxide (250 mg, 0.89 mmol) [Boschelli, et al., U.S. Pat. No. 5,208,253 (1993)] in acetonitrile. A precipitate forms almost immediately and stirring is continued for 30 minutes. The solid is collected and dried to provide 5-methoxy-3-(methylamino)benzo[b]thiophene-2-carboxamide-1-oxide in 86% yield; mp=244°-244.5° C. dec.
Reaction SMILES: [CH2:1]([CH:3]([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:4][N:5]1[C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH3:2].[C:22](Cl)(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[Cl-].[Al+3].[Cl-].[Cl-]>ClCCl>[CH2:1]([CH:3]([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:4][N:5]1[C:6]2[CH:7]=[CH:8][C:9]([C:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:29])=[CH:10][C:11]=2[C:12]2[C:17]1=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH3:2]
Reactant: O=C(Cl)c1ccccc1
Reactant: CCCCC(CC)Cn1c2ccccc2c2ccccc21
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CCCCC(CC)Cn1c2ccccc2c2cc(C(=O)c3ccccc3)ccc21
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 15.6 %

Procedure:
To a solution of 9-(2-ethyl-hexyl)-9H-carbazole (7.0 g, 0.025 mol) in dichloromethane (30 ml), benzoyl chloride (4.5 g, 0.0525 mol) was added and stirred for 15 minutes at room temperature. Aluminium chloride (7.3 g, 0.055 mol) was added in portions while the temperature was maintained below 30° C. The reaction mixture was allowed to stir at room temperature for 15 hours. The reaction mixture was poured into ice (150 g) and distilled water (100 ml) and diluted with dichloromethane (200 ml). The organic layer was separated and washed with a saturated solution of sodium bicarbonate (250 ml) and a saturated solution of sodium chloride (250 ml). The organic layer was dried over MgSO4, filtered and the solvent was removed under reduced pressure. The residual solid was purified on a Prochrom LC80 Column using ethyl acetate/n-hexane (20/80) as eluent. TLC shows a yellow fluorescent product with Rf-value of 0.48 in dichloromethane as eluent. Evaporation of the pooled fractions yielded 1.5 g of [9-(2-ethyl-hexyl)-9H-carbazol-3-yl]-phenyl-methanone.