Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C@@H:2]([CH2:10][O:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH2:3][CH2:4][O:5][S:6]([CH3:9])(=[O:8])=[O:7].N1C=CN=C1.[C:21]([Si:25](Cl)([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)([CH3:24])([CH3:23])[CH3:22].O>CN(C)C=O>[Si:25]([O:1][C@@H:2]([CH2:10][O:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH2:3][CH2:4][O:5][S:6]([CH3:9])(=[O:8])=[O:7])([C:21]([CH3:24])([CH3:23])[CH3:22])([C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: CS(=O)(=O)OCC[C@@H](O)COS(C)(=O)=O
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)[Si](O[C@H](CCOS(C)(=O)=O)COS(C)(=O)=O)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of methanesulfonic acid (R)-3-hydroxy-4-methanesulfonyloxy-butyl ester (7.5 g) obtained in Step 1 in N,N-dimethylformamide (30 mL) were added imidazole (2.9 g) and tert-butylchlorodiphenylsilane (10.3 mL) under ice-cooling, followed by stirring the reaction mixture at room temperature for 12 hours. To the reaction mixture was added water under ice-cooling, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate:hexane (volume ratio)=1:2 to 1:1) to give methanesulfonic acid (R)-3-(tert-butyldiphenylsilanyloxy)-4-methanesulfonyloxy-butyl ester (11.4 g).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:36])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:26]=[CH:25][C:24]([B:27]3[O:31][C:30]([CH3:33])([CH3:32])[C:29]([CH3:35])([CH3:34])[O:28]3)=[CH:23][CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].[C:37](OC(N1C(C(O)=O)C2CC1CC2)=O)(C)(C)[CH3:38]>>[CH3:1][O:2][C:3](=[O:36])[NH:4][CH:5]([C:9]([N:11]1[CH:12]([C:16]2[NH:17][C:18]([C:21]3[CH:22]=[CH:23][C:24]([B:27]4[O:28][C:29]([CH3:34])([CH3:35])[C:30]([CH3:33])([CH3:32])[O:31]4)=[CH:25][CH:26]=3)=[CH:19][N:20]=2)[CH:13]2[CH2:14][CH:15]1[CH2:37][CH2:38]2)=[O:10])[CH:6]([CH3:8])[CH3:7]
Reactant: COC(=O)NC(C(=O)N1CCCC1c1ncc(-c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)[nH]1)C(C)C
Reactant: CC(C)(C)OC(=O)N1C2CCC(C2)C1C(=O)O
Product: COC(=O)NC(C(=O)N1C2CCC(C2)C1c1ncc(-c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)[nH]1)C(C)C

Procedure:
This compound was synthesized using the procedure used to make [2-Methyl-1-(2-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester using 2-Aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-tert-butyl ester. LCMS-ESI+: calc'd for C28H39BN4O5: 522.30 (M+); Found: 523.31 (M+H+).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([N:10]=[C:11]=[O:12])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].Cl.[CH3:14][O:15][C:16](=[O:19])[CH2:17][NH2:18].C(N(CC)CC)C>ClCCl>[CH3:14][O:15][C:16](=[O:19])[CH2:17][NH:18][C:11]([NH:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1)=[O:12]
Reactant: O=C=Nc1cccc([N+](=O)[O-])c1
Reactant: COC(=O)CN
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)CNC(=O)Nc1cccc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 97.1 %

Procedure:
To a suspension of 3-nitrophenyl isocyanate (10 g, 61 mmol) and glycine methyl ester hydrochloride (8.4 g, 67 mmol, 1.1 equiv.) in dichloromethane (250 mL) was added triethylamine (10 mL, 72 mmol, 1.2 equiv.) at 0° C. The resulting solution was stirred at room temperature overnight. The resulting dark brown solution was concentrated and triturated in water to give a light yellow suspension. The suspension was filtered and the filter cake was washed with water and air-dried to give [[[(3-nitrophenyl)amino]carbonyl]aminoacetic acid methyl ester (15 g) in quantitative yield.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[C:9]([F:11])[C:8]([N+:12]([O-])=O)=[CH:7][C:6]=1[OH:15])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+]>CCO.[Pd]>[C:1]([C:5]1[CH:10]=[C:9]([F:11])[C:8]([NH2:12])=[CH:7][C:6]=1[OH:15])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1cc(F)c([N+](=O)[O-])cc1O
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCO
Product: CC(C)(C)c1cc(F)c(N)cc1O
Yield: 159.7 %

Procedure:
To a refluxing solution of 2-tert-butyl-4-fluoro-5-nitrophenol (400 mg, 1.88 mmol) and ammonium formate (400 mg, 6.1 mmol) in EtOH (20 mL) was added 5% Pd—C (260 mg). The mixture was refluxed for additional 1 h, cooled and filtered through Celite. The solvent was removed by evaporation to give 2-tert-butyl-5-amino-4-fluorophenol (C-7) (550 mg, 83%). 1H NMR (400 MHz, DMSO-d6) δ 8.83 (br s, 1H), 6.66 (d, J=13.7 Hz, 1H), 6.22 (d, J=8.5 Hz, 1H), 4.74 (br s, 2H), 1.26 (s, 9H); HPLC ret. time 2.58 min, 10-99% CH3CN, 5 min run; ESI-MS 184.0 m/z (MH+).
Reaction SMILES: C(N(C(C)C)CC)(C)C.[Cl:10][C:11]1[N:16]=[C:15](Cl)[C:14]([C:18]([F:21])([F:20])[F:19])=[CH:13][N:12]=1.Cl.[CH3:23][S:24]([C:27]1[CH:28]=[C:29]([CH2:33][NH2:34])[CH:30]=[CH:31][CH:32]=1)(=[O:26])=[O:25].ClC1C(C(F)(F)F)=CN=C(NCC2C=CC=C(S(C)(=O)=O)C=2)N=1>C1COCC1.C(Cl)Cl>[Cl:10][C:11]1[N:16]=[C:15]([NH:34][CH2:33][C:29]2[CH:30]=[CH:31][CH:32]=[C:27]([S:24]([CH3:23])(=[O:26])=[O:25])[CH:28]=2)[C:14]([C:18]([F:21])([F:20])[F:19])=[CH:13][N:12]=1
Reactant: CS(=O)(=O)c1cccc(CN)c1
Reactant: FC(F)(F)c1cnc(Cl)nc1Cl
Agent: CS(=O)(=O)c1cccc(CNc2ncc(C(F)(F)F)c(Cl)n2)c1
Agent: Cl
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CS(=O)(=O)c1cccc(CNc2nc(Cl)ncc2C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 38.7 %

Procedure:
Diisopropylethylamine (31.5 mL, 180 mmol) was added to a suspension of 2,4-dichloro-5-trifluoromethylpyrimidine (XL, 15.0 g, 69.4 mmol) and 1-[3-(methylsulfonyl)phenyl]methanamine hydrochloride (13.3 g, 60 mmol) in THF (300 mL) at 0° C., and the resulting mixture stirred at room temperature overnight. The mixture was then evaporated to dryness, the residue taken up in methylene chloride (100 mL) and the resulting solution washed with water (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue obtained was taken up in hot methylene chloride (35 mL) then left to stir overnight at room temperature. The separated solid was isolated by filtration (9.4 g) and determined to be a pure sample of the more polar component of the product mixture (4-chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-2-amine XLIVb). The mother liquors were adsorbed onto silica gel and chromatographed over silica gel eluting with hexane:ethyl acetate 50:50 to afford 8.5 g of pure non-polar material (2-chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-4-amine XLIVa) and a further 0.7 g of the polar component.
Reaction SMILES: [CH3:1][C:2]1([CH3:9])[CH2:7][CH2:6][C:5](=[O:8])[CH:4]=[CH:3]1.C(O[CH2:15][N:16]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:17][Si](C)(C)C)CCC.C(=O)([O-])[O-].[K+].[K+]>ClCCl.FC(F)(F)C(O)=O>[CH2:22]([N:16]1[CH2:17][CH:6]2[CH:7]([C:2]([CH3:9])([CH3:1])[CH2:3][CH2:4][C:5]2=[O:8])[CH2:15]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: CCCCOCN(Cc1ccccc1)C[Si](C)(C)C
Reactant: CC1(C)C=CC(=O)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC1(C)CCC(=O)C2CN(Cc3ccccc3)CC21
Reaction time: 3 h

Procedure:
To a solution of 5 g of 4,4-dimethylcyclohex-2-enone and 12.4 cm3 of N-butoxymethyl-N-trimethylsilylmethylbenzylamine in 100 cm3 of dichloromethane are added, at a temperature of 10° C., 5 drops of trifluoroacetic acid. The reaction mixture is stirred at this temperature for 3 hours, then potassium carbonate is added and the solution is filtered through a sinter funnel and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (particle size 0.04-0.06 mm, diameter 5.2 cm, height 25 cm), eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (85/15 by volume) and collecting 100 cm3 fractions. Fractions 39 to 63 are combined and concentrated to dryness under reduced pressure (2.7 kPa). 3.64 g of (3aRS,7aRS)-2-benzyl-7,7-dimethyl-4-perhydroisoindolone are obtained in the form of a yellow oil.
Reaction SMILES: Br[C:2]1[C:14]2N[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]=2[CH:5]=[CH:4]C=1.[C:15]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])(=[O:18])[CH:16]=[CH2:17].[CH2:24]([N:26]([CH2:29][CH3:30])[CH2:27][CH3:28])[CH3:25]>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[C:20]([O:19][C:15](=[O:18])[CH:16]=[CH:17][C:10]1[CH:11]=[CH:25][C:24]2[N:26]([CH2:29][C:30]3[CH:4]=[CH:5][C:6]([C:7]4[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=4)=[CH:14][CH:2]=3)[C:27]3[C:7]([C:8]=2[CH:9]=1)=[CH:6][CH:5]=[CH:4][CH:28]=3)([CH3:23])([CH3:22])[CH3:21]
Reactant: C=CC(=O)OC(C)(C)C
Reactant: CCN(CC)CC
Reactant: Brc1cccc2c1[nH]c1ccccc12
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)C=Cc1ccc2c(c1)c1ccccc1n2Cc1ccc(-c2ccccc2)cc1
Temperature: 100 °C
Yield: 60 %

Procedure:
A mixture of the above bromo-carbazole (7.15 g, 18 mmol), tert-butyl acrylate (3.01 g, 23.3 mmol), palladium acetate (40 mg, 0.2 mmol), tri-o-tolylphosphine (220 mg, 0.7 mmol) and triethylamine (10 ml) in an screw cap ampoule was heated at 100° C. for 20 h. The cooled reaction mixture was diluted with ethyl acetate (75 ml), washed with water (3×20 ml), dried (MgSO4), filtered and evaporated in vacuo. The residue (9.6 g) was purified by column chromatography on silicagel (600 ml) using toluene as eluent which afforded 4.92 g (60%) of 3-(9-(biphenyl-4-ylmethyl)-9H-carbazol-3-yl)acrylic acid tert-butyl ester as a solid.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][N:3]=[C:2]1/[CH:6]=[N:7]/[S:8]([C:10]([CH3:13])([CH3:12])[CH3:11])=[O:9].[CH3:14][Mg]Br>ClCCl>[O:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH:6]([NH:7][S:8]([C:10]([CH3:13])([CH3:12])[CH3:11])=[O:9])[CH3:14]
Reactant: CC(C)(C)S(=O)/N=C/c1ncco1
Reactant: C[Mg]Br
Solvent: ClCCl
Product: CC(NS(=O)C(C)(C)C)c1ncco1
Temperature: 0 °C
Reaction time: 1 h
Yield: 101.2 %

Procedure:
In a round-bottomed flask, 2-methyl-propane-2-sulfinic acid 1-oxazol-2-yl-meth-(E)-ylideneamide (414 mg, 2.07 mmol) was dissolved in dichloromethane (7 ml). The reaction mixture was cooled to 0° C. and methylmagnesium bromide (3.0 M in diethyl ether, 0.76 ml, 2.28 mmol) was added dropwise. The reaction mixture was stirred at 0° C. for 1 h then quenched with saturated aqueous NH4Cl and extracted with ethyl acetate (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated to afford 453 mg (96%) of 2-methyl-propane-2-sulfinic acid (1-oxazol-2-yl-ethyl)-amide as a yellow oil.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:34]2[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=2)([OH:33])[CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][C:18]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([CH3:32])([CH3:31])[C:27]([O:29][CH3:30])=[O:28])=[CH:22][CH:21]=3)=[O:19])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[BH4-].[Na+]>CO>[CH3:40][C:37]1[CH:36]=[CH:35][C:34]([C:8]([C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=2)([OH:33])[CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH:18]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([CH3:32])([CH3:31])[C:27]([O:29][CH3:30])=[O:28])=[CH:22][CH:21]=3)[OH:19])[CH2:11][CH2:10]2)=[CH:39][CH:38]=1
Reactant: COC(=O)C(C)(C)c1ccc(C(=O)CCCN2CCC(C(O)(c3ccc(C)cc3)c3ccc(C)cc3)CC2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COC(=O)C(C)(C)c1ccc(C(O)CCCN2CCC(C(O)(c3ccc(C)cc3)c3ccc(C)cc3)CC2)cc1
Reaction time: 2 h

Procedure:
To a −10° C. solution of 6.8 g (0.013 mol) of methyl 4-[4-[4-(bis(4-methylphenyl)hydroxymethyl)-1-piperidinyl]-1-oxobutyl]-α,α-dimethylphenylacetate, prepared in accordance with Example 9, in 150 mL of methanol in a 500 mL round bottom flask equipped with a mechanical stirrer is slowly added 0.86 g (0.023 mol) of sodium borohydride, and the reaction is stirred for 2 hr. The methanol is removed in vacuo, and the residue is partitioned between ethyl acetate and aqueous sodium bicarbonate solution. The aqueous layer is extracted with ethyl acetate, the combined organic layers are dried with sodium sulfate, and the ethyl acetate is removed in vacuo to provide crude product. The resultant material is purified by column chromatography (Davisil grade 633 silica gel, packed in methylene chloride, material applied in chloroform, and eluted with a gradient of 2% methanol to methylene chloride to 5% methanol to methylene chloride) to afford methyl 4-[4-[4-(bis(4-methylphenyl)hydroxymethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylphenylacetate.
Reaction SMILES: [CH3:1][CH2:2][C@@H:3]([C:22]([C@H:24]([C@@H:26]([OH:42])[C@@H:27]([CH2:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[C:33]([OH:38])[C:32]=1[C:39]([OH:41])=[O:40])[CH3:28])[CH3:25])=O)[C@H:4]1[O:8][C@@:7]([C@@H:11]2[O:16][C@@H:15]([CH3:17])[C@@:14]([OH:20])([CH2:18][CH3:19])[CH2:13][CH2:12]2)([CH2:9][CH3:10])[CH2:6][C@@H:5]1[CH3:21].Cl.[NH2:44][OH:45]>C(O)C>[OH:45][NH3+:44].[CH3:37][C:34]1[CH:35]=[CH:36][C:31]([CH2:30][CH2:29][CH:27]([CH3:28])[CH:26]([OH:42])[CH:24]([CH3:25])[C:22](=[N:44][OH:45])[CH:3]([CH2:2][CH3:1])[CH:4]2[CH:5]([CH3:21])[CH2:6][C:7]([CH2:9][CH3:10])([CH:11]3[CH2:12][CH2:13][C:14]([CH2:18][CH3:19])([OH:20])[CH:15]([CH3:17])[O:16]3)[O:8]2)=[C:32]([C:39]([O-:41])=[O:40])[C:33]=1[OH:38]
Reactant: CC[C@@H](C(=O)[C@@H](C)[C@@H](O)[C@H](C)CCc1ccc(C)c(O)c1C(=O)O)[C@H]1O[C@](CC)([C@H]2CC[C@](O)(CC)[C@H](C)O2)C[C@@H]1C
Reactant: NO
Agent: Cl
Solvent: CCO
Product: CCC(C(=NO)C(C)C(O)C(C)CCc1ccc(C)c(O)c1C(=O)[O-])C1OC(CC)(C2CCC(O)(CC)C(C)O2)CC1C
Product: [NH3+]O

Procedure:
A mixture of 10 g of crystalline antibiotic X-537A and 5 g of hydroxylamine hydrochloride in 50 ml ethanol containing 5 ml pyridine was heated under reflux for 60 hours. The solution was evaporated to dryness and 5 ml water added. The solid product was triturated and filtered, then recrystallized from aqueous ethanol to give (-)-3-methyl-6-{7-ethyl-4-hydroxy-6-hydroxyimino-3,5-dimethyl-7-[5-ethyl-3-methyl-5-(5-ethyl-5-hydroxy-6-methyl-2-tetrahydro-pyranyl)-2-tetrahydrofuryl]heptyl} salicylic acid, hydroxylammonium salt; m.p. 168°-170°, [α]D25 -12.34° (1%, DMSO).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([O:11][CH3:12])=[O:10].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.N1([C:28](=[O:30])[CH3:29])C=CN=C1.CN(C=O)C>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([C:28](=[O:30])[CH3:29])[C:9]([O:11][CH3:12])=[O:10]
Reactant: CC(=O)n1ccnc1
Reactant: COC(=O)Cc1ccccc1Br
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: COC(=O)C(C(C)=O)c1ccccc1Br
Reaction time: 1 h
Yield: 93.6 %

Procedure:
A round bottomed flask was charged with a magnetic stir bar and methyl 2-(2-bromophenyl)acetate (25 g, 109 mmol) and THF (50 mL). This solution was cooled to −78° C. before drop wise addition of a 1M solution of LiHMDS in THF (218 ml, 218 mmol). The reaction was stirred for 30 min at −78° C. before addition of 1-(1H-imidazol-1-yl)ethanone (14.42 g, 131 mmol) dissolved in a mixture of THF:DMF (112 mL THF, 24 mL DMF). The solution was stirred for 1 h before quenching with sat'd aqueous NH4Cl (˜250 mL) and diluting with EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc (˜2×250 mL). The combined organic extract was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified via silica gel chromatography using an eluent of ethyl acetate/hexanes (10:1) to afford methyl 2-(2-bromophenyl)-3-oxobutanoate (32.5 g, 102 mmol, 93% yield).
Reaction SMILES: [CH2:1]([C:5]1[N:9]([CH:10]2[C:18]3[C:13](=[CH:14][C:15]([C:19]4[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=4[C:21]#[N:22])=[CH:16][CH:17]=3)[CH2:12][CH2:11]2)[C:8](=[O:27])[C:7]2([CH2:31][CH2:30][CH2:29][CH2:28]2)[N:6]=1)[CH2:2][CH2:3][CH3:4].C[Sn]([N:36]=[N+:37]=[N-:38])(C)C>C1(C)C(C)=CC=CC=1>[CH2:1]([C:5]1[N:9]([CH:10]2[C:18]3[C:13](=[CH:14][C:15]([C:19]4[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=4[C:21]4[NH:38][N:37]=[N:36][N:22]=4)=[CH:16][CH:17]=3)[CH2:12][CH2:11]2)[C:8](=[O:27])[C:7]2([CH2:28][CH2:29][CH2:30][CH2:31]2)[N:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCC1=NC2(CCCC2)C(=O)N1C1CCc2cc(-c3ccccc3C#N)ccc21
Reactant: C[Sn](C)(C)N=[N+]=[N-]
Solvent: Cc1ccccc1C
Product: CCCCC1=NC2(CCCC2)C(=O)N1C1CCc2cc(-c3ccccc3-c3nnn[nH]3)ccc21
Temperature: 25 °C
Yield: 31.2 %

Procedure:
A mixture of 2-[1-(2-butyl-4-oxo-1,3-diaza-spiro[4.4]non-1-en-3-yl)-indan -5yl]-benzonitrile (150 mg, 0.36 mmol) and trimethyltin azide (196 mg, 0.91 mmol) was heated under reflux in xylene (5.0 mL) for 25 hours. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was chromatographed on SiO2 -gel using a gradient of 2.5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2 to give 51 mg of a colorless oil. The oil was dissolved in EtOAc and hexanes were added to precipitate the product. The white solid was filtered and dried. 1H NMR (250 MHz, d4 -MeOH): d 7.58 (m, 2 H), 7.47 (m, 2 H), 7.00 (s, 1 H), 6.85 (s, 2 H), 5.50 (t, 1 H), 2.95 (m, 2 H), 2.35 (m, 4 H), 1.90-1.41 (m), 1.22 (m, 2 H), 0.80 (t, 3 H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][SH:10])=[CH:4][CH:3]=1.Br[C:12]1[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][S:10][C:12]2[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=2)=[CH:4][CH:3]=1
Reactant: SCCc1ccc(Cl)cc1
Reactant: O=Cc1ccc(Br)cc1
Product: O=Cc1ccc(SCCc2ccc(Cl)cc2)cc1

Procedure:
Title product was prepared from 2-(4-chlorophenyl)ethyl mercaptan and 4-bromobenzaldehyde according to the method of Preparation 7.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[CH3:7].[CH3:8][C:9]1[CH:13]=[CH:12][S:11][C:10]=1[CH:14]=O.C(OC(=O)C)(=O)C>C(O)(C)C>[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[CH:7]=[CH:14][C:10]1[S:11][CH:12]=[CH:13][C:9]=1[CH3:8]
Reactant: Cc1nccn1C
Reactant: Cc1ccsc1C=O
Solvent: CC(C)O
Solvent: CC(=O)OC(C)=O
Product: Cc1ccsc1C=Cc1nccn1C
Yield: 41.2 %

Procedure:
A mixture was prepared by admixing together in a 1.0 liter-3-necked round bottomed flask 144.0 grams (1.5 moles) of 1,2-dimethylimidazole, 189.3 grams (1.5 moles) of 3-methyl-2-thiophenecarboxaldehyde and 450 cubic centimeters (cc) of acetic anhydride. The flask was equipped with a stirrer, thermometer and a 12 foot distillation column. The mixture was stirred and heated at ~150° C. for ~2 hours. The temperature increased to ~160° C. At this time 250 cc of the distillate (mostly acetic acid by-product and acetic anhydride) had been collected. An additional 250 cc of acetic anhydride was added to the reaction flash and the heating continued until the temperature again rose to ~160° C. At this time about 320 cc of the distillate had been collected. The reaction mixture in the flask was thereafter concentrated under vacuum giving a residue of 427.0 grams. This residue was mixed with 500 cc of isopropyl alcohol and the resulting dark colored solution concentrated under vacuum giving a residue of 410 grams. This residue was distilled under reduced pressure. The first fraction (124 grams, boiling at 72°-76° C/0.2-0.4 millimeters of mercury (mm)) consisted mainly of starting material. The main fraction, which was the free base of the desired compound was collected in a yield of 155 grams and boiled at 172°-174° C/0.6 mm. The thick tarry pot residue weighed 115 grams. The main fraction was mixed with 150 cc of ethanol and 150 cc of concentrated hydrochloric acid. The insoluble yellow crystals which formed were filtered, washed with ~1.0 liter of ethanol and dried to give 126.3 grams of 1-methyl-2-(2-(3-methyl-2-thienyl)ethenyl)1H-imidazole:monohydrochloride, (Compound I) melting at 287°-288° C. The product was recovered in a yield of 34.9 percent of theoretical.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:6]([C:7]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=O)=[CH:5][CH:4]=1.[CH3:17][N:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[NH2:19].O>C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:6]([C:7](=[N:19][N:18]([CH3:17])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:5][CH:4]=1
Reactant: CN(N)c1ccccc1
Reactant: CCOC(=O)CC(=O)c1ccc(OC)cc1
Solvent: O
Solvent: CC(=O)O
Product: CCOC(=O)CC(=NN(C)c1ccccc1)c1ccc(OC)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 99 %

Procedure:
In 60 ml of acetic acid were dissolved 15 g of ethyl p-methoxybenzoylacetate and 8.25 g of 1-methyl-1-phenylhydrazine and the resulting solution was stirred at room temperature for 12 hours. The reaction mixture was poured into iced water and extracted with ethyl acetate. The extract was washed with aqueous solution of sodium hydrogen carbonate and water in that order, dried over anhydrous magnesium sulfate and concentrated to provide 21.8 g of the desired compound as a yellow oil.
Reaction SMILES: [O:1]1[CH2:5][CH:2]1[CH:3]=[CH2:4].[C:6]([O:9]C(=O)C)(=[O:8])[CH3:7].C(N(CC)CC)C.C[O:21][CH2:22][CH2:23]OCCOC>>[C:6]([O:9][CH:2]([CH2:5][O:1][C:22](=[O:21])[CH3:23])[CH:3]=[CH2:4])(=[O:8])[CH3:7]
Reactant: C=CC1CO1
Reactant: CC(=O)OC(C)=O
Reactant: COCCOCCOC
Solvent: CCN(CC)CC
Product: C=CC(COC(C)=O)OC(C)=O
Temperature: 125 °C
Reaction time: 0.25 h
Yield: 92 %

Procedure:
A 300-mL autoclave was charged with 40 mL (0.50 mol) of 3,4-epoxy-1-butene, 63.2 g (0.62 mol) acetic anhydride, 4.06 g (0.041 mol) of triethylamine and 4.2 mL of diglyme. The autoclave was purged with nitrogen twice, then the vessel was pressurized to 8 bars (100 psig) with nitrogen. The agitator was started and an initial sample was taken. The mixture was heated to 125° C. During the course of 2.5 hrs, samples were taken every 15 min for analysis by GC. GC analysis of the crude mixture after 2.5 hrs revealed a 92% yield of 3,4-diacetoxy-1-butene with a 92% selectivity and 0.36% 3,4-epoxy-1-butene. The reaction was observed to be first order in 3,4-epoxy-1-butene with a first order rate constant of 0.037 min-1 (Table A). This example demonstrates the catalytic effect of the tertiary amine alone.
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:5]([O:23][CH3:24])=[CH:6][C:7]2[O:12][C:11](=[O:13])[C:10]([CH2:14][CH2:15]OS(C)(=O)=O)=[C:9]([CH3:21])[C:8]=2[CH:22]=1)[CH3:2].[CH3:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1>C(O)C.C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4]1[C:5]([O:23][CH3:24])=[CH:6][C:7]2[O:12][C:11](=[O:13])[C:10]([CH2:14][CH2:15][N:36]3[CH2:35][CH2:34][N:33]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=4[O:26][CH3:25])[CH2:38][CH2:37]3)=[C:9]([CH3:21])[C:8]=2[CH:22]=1)[CH3:2]
Reactant: CCOc1cc2c(C)c(CCOS(C)(=O)=O)c(=O)oc2cc1OC
Reactant: COc1ccccc1N1CCNCC1
Solvent: CCO
Solvent: ClC(Cl)Cl
Product: CCOc1cc2c(C)c(CCN3CCN(c4ccccc4OC)CC3)c(=O)oc2cc1OC
Yield: 54 %

Procedure:
Process A; starting materials: 6-ethoxy-3-[2-(methanesulphonyloxy)ethyl]-7-methoxy-4-methyl-2H-1-benzopyran-2-one (Example 29) and 1-(2-methoxyphenyl)piperazine; yield 54%; m.p. 143°-145° C. (from ethanol/chloroform).