Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O-].[Na+].[NH:4]([CH2:11][CH2:12][C:13]#[N:14])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.O[CH:16]([C:22]1[CH:32]=[C:31]([O:33][CH3:34])[C:25]([N:26]([CH3:30])[C:27](=[O:29])[CH3:28])=[C:24]([O:35][CH3:36])[CH:23]=1)CS(C)(=O)=O.CS(C)=O>O>[NH:4]([CH:11]=[C:12]([C:13]#[N:14])[CH2:16][C:22]1[CH:32]=[C:31]([O:33][CH3:34])[C:25]([N:26]([CH3:30])[C:27](=[O:29])[CH3:28])=[C:24]([O:35][CH3:36])[CH:23]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: COc1cc(C(O)CS(C)(=O)=O)cc(OC)c1N(C)C(C)=O
Reactant: N#CCCNc1ccccc1
Agent: C[O-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: COc1cc(CC(C#N)=CNc2ccccc2)cc(OC)c1N(C)C(C)=O

Procedure:
A mixture of 3.24 g. of sodium methylate, 8.75 g. of β-anilino-propionitrile and 14.9 g. of 4'-[1-hydroxy-2-(methylsulfonyl)-ethyl]-2',6'-dimethoxy-N-methylacetanilide in 60 ml. of absolute dimethylsulfoxide was stirred at 50° C. for 4 hours with the exclusion of moisture. The solution was poured into 600 ml. of water. The resulting emulsion was extracted with two 400 ml. portions of ethyl acetate. Thereafter, the ethyl acetate extracts were washed with two 150 ml. portions of water, combined, dried over magnesium sulfate and evaporated under vacuum. Recrystallization of the residue from ethyl acetate gave 4'-(3-anilino-2-cyano-allyl)-2',6'-dimethoxy-N-methyl-acetanilide having a melting point of 202°-204° C.
Reaction SMILES: Br[C:2]([F:17])([F:16])[O:3][C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]=1[O:14][CH3:15].[Sb](F)(F)[F:19]>C(OCC)C.[Sb](Cl)(Cl)(Cl)(Cl)Cl>[CH3:15][O:14][C:5]1[CH:6]=[C:7]([CH:12]=[CH:13][C:4]=1[O:3][C:2]([F:17])([F:19])[F:16])[C:8]([O:10][CH3:11])=[O:9]
Reactant: COC(=O)c1ccc(OC(F)(F)Br)c(OC)c1
Reactant: F[Sb](F)F
Agent: Cl[Sb](Cl)(Cl)(Cl)Cl
Solvent: CCOCC
Product: COC(=O)c1ccc(OC(F)(F)F)c(OC)c1
Temperature: 170 °C
Reaction time: 4 h
Yield: 77.5 %

Procedure:
Antimony (V) Chloride (26.4 mg, 0.088 mmol) was added to a stirred, room temperature mixture of 173A (550 mg, 1.768 mmol) and antimony trifluoride (221 mg, 1.238 mmol) in a sealed tube, and the mixture was stirred at 170° C. for 4 h. The mixture was cooled, diluted with diethyl ether (50 mL), washed with water (50 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel; 24 g prepacked column, eluting with EtOAc/isohexane=10% to give methyl 3-methoxy-4-(trifluoromethoxy)benzoate 173B (240 mg, 0.959 mmol, 54.3% yield) as a white solid.
Reaction SMILES: Cl[C:2]1[C:7]2[CH:8]=[C:9]([S:11]([O-:13])=[O:12])[S:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[Li+].[CH3:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20]Br)=[CH:18][CH:17]=1.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25]>C(#N)C>[CH3:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20][S:11]([C:9]2[S:10][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([N:34]4[CH2:33][CH2:32][N:31]([C:29]([O:28][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:30])[CH2:36][CH2:35]4)[C:7]=3[CH:8]=2)(=[O:13])=[O:12])=[CH:18][CH:17]=1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: O=S([O-])c1cc2c(Cl)nccc2s1
Reactant: Cc1ccc(CBr)cc1
Agent: [Li+]
Solvent: CC#N
Product: Cc1ccc(CS(=O)(=O)c2cc3c(N4CCN(C(=O)OC(C)(C)C)CC4)nccc3s2)cc1

Procedure:
Lithium 4-chlorothieno[3,2-c]pyridine-2-sulfinate (0.44 mmol) was treated with 4-methylbenzylbromide (0.59 mmol) as described in Method P above and then reacted further with tert-butyl-piperazine-1-carboxylate as described in Method Q. Yield 0.005 g (3% over two steps). Beige solid. 1H NMR (300 MHz, CDCl3) δ 8.15 (d, J=6 Hz 1H), 7.40 (s, 1H), 7.00-7.16 (m, 4H), 4.42 (s, 2H), 3.46-3.60 (m, 4H), 3.37-3.46 (m, 4H), 2.34 (s, 3H), 1.49 (s, 9H); MS (ESI+) for C24H29N3O4S2 m/z 488 (M+H)+. HPLC 69%, RT 2.06 min (YMC ODS AQ, 33×3 mm, 10-90% acetonitrile in 3 min).
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][CH:5]([C:8]([NH:10][C:11]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:12]=2[C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][N:17]=2)=[O:14])=[O:9])[CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:35][CH2:36][CH2:37][CH2:38]Br>CN(C)C=O.C(OCC)(=O)C>[ClH:22].[Cl:27][C:24]1[CH:25]=[CH:26][C:11]([NH:10][C:8]([CH:5]2[CH2:6][CH2:7][CH:2]([N:1]3[CH2:38][CH2:37][CH2:36][CH2:35]3)[CH2:3][CH2:4]2)=[O:9])=[C:12]([CH:23]=1)[C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][N:17]=1)=[O:14]
Reactant: NC1CCC(C(=O)Nc2ccc(Cl)cc2C(=O)Nc2ccc(Cl)cn2)CC1
Reactant: BrCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cl
Product: O=C(Nc1ccc(Cl)cn1)c1cc(Cl)ccc1NC(=O)C1CCC(N2CCCC2)CC1
Temperature: 80 °C
Yield: 154.2 %

Procedure:
2-[(4-Aminocyclohexylcarbonyl)amino]-5-chloro-N-(5-chloropyridin-2-yl)benzamide (300 mg, 0.74 mmol) was diluted with dimethylformamide (8 mL). Potassium carbonate (307 mg, 2.22 mmol) and 1,4-dibromobutane (88 mL, 0.74 mmol) were added. The reaction was heated to 80° C. over the weekend. The reaction was cooled to room temperature, diluted with ethyl acetate (50 mL) and washed with water (5×10 mL). The ethyl acetate layer was dried over sodium sulfate, filtered and concentrated. The crude material was purified by HPLC to give 284 mg (77%) of the title compound as a white solid.
Reaction SMILES: Br.[CH3:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[N:5]([CH2:14][CH2:15][NH:16][CH3:17])[N:4]=1.[CH3:18][S:19]([NH:22][C:23]1[CH:32]=[CH:31][C:26]([C:27](=[O:30])[CH2:28]Br)=[CH:25][CH:24]=1)(=[O:21])=[O:20].C(N(CC)CC)C>C(O)C>[OH2:13].[CH3:18][S:19]([NH:22][C:23]1[CH:32]=[CH:31][C:26]([C:27](=[O:30])[CH2:28][N:16]([CH2:15][CH2:14][N:5]2[N:4]=[C:3]([CH3:2])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]2=[O:13])[CH3:17])=[CH:25][CH:24]=1)(=[O:21])=[O:20].[CH3:18][S:19]([NH:22][C:23]1[CH:32]=[CH:31][C:26]([C:27](=[O:30])[CH2:28][N:16]([CH2:15][CH2:14][N:5]2[N:4]=[C:3]([CH3:2])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]2=[O:13])[CH3:17])=[CH:25][CH:24]=1)(=[O:21])=[O:20]
Reactant: CNCCn1nc(C)c2ccccc2c1=O
Reactant: CS(=O)(=O)Nc1ccc(C(=O)CBr)cc1
Agent: Br
Solvent: CCO
Solvent: CCN(CC)CC
Product: Cc1nn(CCN(C)CC(=O)c2ccc(NS(C)(=O)=O)cc2)c(=O)c2ccccc12
Product: O

Procedure:
2-(4-Methyl-2H-phthalazin-1-on-2-yl)-N-methylethylamine hydrobromide (2 g), 4-methanesulphonamidophenacyl bromide (1.8 g) and triethylamine (1.5 g) in ethanol (50 ml) were stirred at room temperature for 2 hours. The solvent was removed, the residue taken up in methylene chloride (100 ml), washed (aqueous sodium bicarbonate), dried (MgSO4) and evaporated. Chromatography on silica [Merck `Kieselgel 60` (Trade Mark)] eluting with methylene chloride containing methanol (0% up to 5%) gave, after collection and evaporation of appropriate fractions, an oil which was triturated with ethanol to give the title compound, yield 1.63 g, m.p. 176°-179°.
Reaction SMILES: CS(O[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH2:16][CH:17]=[CH2:18])(=O)=O.[Cl:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[NH:25][CH:24]=[C:23]2[CH2:29][C:30]([NH2:33])([CH3:32])[CH3:31].N1C2C(=CC=CC=2)C(CC(N)(C)C)=C1>>[ClH:19].[NH:25]1[C:26]2[C:22](=[CH:21][CH:20]=[CH:28][CH:27]=2)[C:23]([CH2:29][C:30]([NH:33][CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][CH2:16][CH:17]=[CH2:18])([CH3:31])[CH3:32])=[CH:24]1
Reactant: CC(C)(N)Cc1c[nH]c2ccc(Cl)cc12
Reactant: C=CCOc1ccccc1OCCOS(C)(=O)=O
Agent: CC(C)(N)Cc1c[nH]c2ccccc12
Product: C=CCOc1ccccc1OCCNC(C)(C)Cc1c[nH]c2ccccc12
Product: Cl

Procedure:
Proceeding as in Example 3, but replacing 2-[2-(cyclopropylmethyloxy)phenoxy]ethyl methanesulfonate with 2-[2-(2-propenyloxy)phenoxy]ethyl methanesulfonate and [2-(5-chloro-1H-indol-3-yl)-1,1-dimethylethyl]amine with [2-(1H-indol-3-yl)-1,1-dimethylethyl]amine, gave [2-(1H-indol-3-yl)-1,1-dimethylethyl]{2-[2-(2-propenyloxy)phenoxy]ethyl}amine hydrochloride, m.p. 55°-156° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([NH2:11])[C:3]=1[NH2:12].[C:13](O)(=O)[CH:14]([CH3:16])[CH3:15].Cl.[OH-].[Na+]>>[Br:1][C:2]1[C:3]2[N:12]=[C:13]([CH:14]([CH3:16])[CH3:15])[NH:11][C:4]=2[CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1
Reactant: Nc1cc([N+](=O)[O-])cc(Br)c1N
Reactant: CC(C)C(=O)O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: CC(C)c1nc2c(Br)cc([N+](=O)[O-])cc2[nH]1
Temperature: 105 °C
Yield: 85.7 %

Procedure:
A mixture of 3-bromo-5-nitrobenzene-1,2-diamine (4 g, 17.24 mmol) and isobutyric acid (7.99 ml, 86 mmol) in 3M HCl (100 ml, 300 mmol) was heated to 105° C. for 5 days. The mixture was allowed to cool to room temperature and was poured into chilled 5M Sodium Hydroxide (60.0 ml, 300 mmol) solution. The resulting mixture was allowed to stand in an ice bath and the brown solid that precipitated was collected by filtration. The solid was washed several times with H2O and then dried in a vacuum oven at 50° C. leaving desired product as a dark solid (4.2 g, 71% yield). MS (ES+) m/e: 283.0, 284.0 [M+H]+
Reaction SMILES: [CH3:1][C:2]1([CH3:13])[O:11][C:10]2[C:5](=[CH:6][N:7]=[CH:8][CH:9]=2)[CH:4]2[O:12][CH:3]12.[Cl:14][C:15]1[CH:16]=[CH:17][C:18]2[O:22][C:21]([NH2:23])=[N:20][C:19]=2[CH:24]=1>>[Cl:14][C:15]1[CH:16]=[CH:17][C:18]2[O:22][C:21]([NH:23][CH:4]3[C:5]4[CH:6]=[N:7][CH:8]=[CH:9][C:10]=4[O:11][C:2]([CH3:13])([CH3:1])[CH:3]3[OH:12])=[N:20][C:19]=2[CH:24]=1
Reactant: Nc1nc2cc(Cl)ccc2o1
Reactant: CC1(C)Oc2ccncc2C2OC21
Product: CC1(C)Oc2ccncc2C(Nc2nc3cc(Cl)ccc3o2)C1O

Procedure:
Following the procedure in Example 1, using (±)-2,2-dimethyl-1a,7b-dihydro-2H-1,3-dioxa-6-aza-cyclopropa[a]naphthalene and 5-chloro-benzooxazol-2-ylamine as starting materials, the title compound was prepared as a pale yellow solid.
Reaction SMILES: [OH:1][CH2:2][C@@:3]12[C@@H:20]3[C@H:11]([C@H:12]4[C@@:16]([CH2:18][CH2:19]3)([CH3:17])[C:15](=[O:21])[CH2:14][CH2:13]4)[CH2:10][CH2:9][C:8]1=[CH:7][C:6](=[O:22])[CH2:5][CH2:4]2.[C:23]1([Si:29]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)Cl)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.N1C=CC=CC=1>C1C=CC=CC=1>[CH3:2][O-:1].[C:37]1([Si:29]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[O:1][CH2:2][C@@:3]23[C@@H:20]4[C@H:11]([C@H:12]5[C@@:16]([CH2:18][CH2:19]4)([CH3:17])[C:15](=[O:21])[CH2:14][CH2:13]5)[CH2:10][CH2:9][C:8]2=[CH:7][C:6](=[O:22])[CH2:5][CH2:4]3)[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1
Reactant: C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@]43CO)[C@@H]1CCC2=O
Reactant: Cl[Si](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: c1ccccc1
Solvent: c1ccncc1
Product: C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@]43CO[Si](c3ccccc3)(c3ccccc3)c3ccccc3)[C@@H]1CCC2=O
Product: C[O-]
Reaction time: 18 h

Procedure:
A solution of 9.0 gm (0.03 mole) of 19-hydroxy-4-androstene-3,17-dione, 11.8 gm (0.04 mole) of triphenylchlorosilane and 9.6 gm (0.12 mole) of pyridine contained in 100 ml of benzene is refluxeed for a period of 18 hours. The resulting suspension is filtered and concentrated in vacuo to a yellow oil. The oil is placed on a silica gel chromatographic column packed in chloroform which is further eluted with chloroform. The chloroform eluant is evaporated to dryness in vacuo and recrystallized from methanol to yield 19-(triphenylsiloxy)-4-androstene-3,17-dione methanolate having a m.p. 100°-2° C., uv max (MeOH) 223 nm (ε30,430), 242 nm (ε17,300).
Reaction SMILES: [NH2:1][C:2]1[C:7]([CH3:8])=[CH:6][N:5]=[C:4]([Cl:9])[CH:3]=1.[OH:10][C:11]1[CH:16]=[C:15]([CH3:17])[O:14][C:13](=O)[CH:12]=1.[Cl-].[Li+].CO>ClCCl>[Cl:9][C:4]1[CH:3]=[C:2]([N:1]2[C:15]([CH3:17])=[CH:16][C:11]([OH:10])=[CH:12][C:13]2=[O:14])[C:7]([CH3:8])=[CH:6][N:5]=1
Reactant: Cc1cc(O)cc(=O)o1
Reactant: Cc1cnc(Cl)cc1N
Agent: [Cl-]
Agent: [Li+]
Solvent: CO
Solvent: ClCCl
Product: Cc1cnc(Cl)cc1-n1c(C)cc(O)cc1=O
Temperature: 160 °C
Yield: 6 %

Procedure:
A well-powdered mixture of 4-amino-5-methyl-2-chloropyridine (0.5 g, 3.5 mmol), 4-hydroxy-6-methyl-pyrone (0.665 g, 5.3 mmol), and lithium chloride (0.025 g, 0.6 mmol) was heated at 160° C. for 20 min in a sealed tube. The resulting melt was cooled and the product was isolated by silica gel flash chromatography using 3% methanol in dichloromethane. Appropriate fractions were combined, concentrated under reduced pressure and the resulting solid was triturated with ethyl acetate, cooled and filtered. The solid was washed with ethyl acetate and dried to give 0.053 g of the title compound as a yellow powder. ES-MS: m/z=251 (M+H).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:14]([C:15]#[N:16])=[C:13]([CH3:17])[N:12]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)[C:11](=[O:28])[NH:10]2)=[C:5]([S:29]([CH2:32][CH3:33])(=[O:31])=[O:30])[CH:4]=1)#[N:2].[CH3:34][Si](C)(C)[N-][Si](C)(C)C.[Li+].IC>C1COCC1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:14]([C:15]#[N:16])=[C:13]([CH3:17])[N:12]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)[C:11](=[O:28])[N:10]2[CH3:34])=[C:5]([S:29]([CH2:32][CH3:33])(=[O:31])=[O:30])[CH:4]=1)#[N:2]
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: CCS(=O)(=O)c1cc(C#N)ccc1[C@H]1NC(=O)N(c2cccc(C(F)(F)F)c2)C(C)=C1C#N
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CI
Product: CCS(=O)(=O)c1cc(C#N)ccc1[C@@H]1C(C#N)=C(C)N(c2cccc(C(F)(F)F)c2)C(=O)N1C
Reaction time: 0.33 h
Yield: 82 %

Procedure:
The reaction was carried out under argon. (4S)-4-[4-Cyano-2-(ethylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (71.2 mg, 0.15 mmol) was initially charged in absolute THF (6 ml), and a 1 M solution of lithium hexamethyldisilazide (LiHMDS) in THF (180 μl; 1.2 eq.) was added at −78° C. After 20 min of stirring, iodomethane (47 μl; 5 eq.) was added, and the mixture was stirred with gradual warming from −78° C. to RT for 60 h. The reaction mixture was then purified directly by preparative HPLC (column: Gromsil, C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→80:20). This gave the title compound as a colorless solid (60 mg, 82% of theory).
Reaction SMILES: Br[C:2]1[C:7]([N:8](COC)[S:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5]([Cl:25])=[CH:4][N:3]=1.[F:26][C:27]1[CH:38]=[CH:37][C:30]([C:31](N(OC)C)=[O:32])=[CH:29][CH:28]=1.Cl.O1CCOCC1>O.CCOC(C)=O>[C:18]([C:15]1[CH:16]=[CH:17][C:12]([S:9]([NH:8][C:7]2[C:2]([C:31](=[O:32])[C:30]3[CH:37]=[CH:38][C:27]([F:26])=[CH:28][CH:29]=3)=[N:3][CH:4]=[C:5]([Cl:25])[CH:6]=2)(=[O:11])=[O:10])=[CH:13][CH:14]=1)([CH3:19])([CH3:21])[CH3:20]
Reactant: CON(C)C(=O)c1ccc(F)cc1
Reactant: COCN(c1cc(Cl)cnc1Br)S(=O)(=O)c1ccc(C(C)(C)C)cc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1COCCO1
Product: CC(C)(C)c1ccc(S(=O)(=O)Nc2cc(Cl)cnc2C(=O)c2ccc(F)cc2)cc1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
N-(2-Bromo-5-chloro-pyridin-3-yl)-4-tert-butyl-N-methoxymethyl-benzenesulfonamide (140 mg, 300 mmol) was placed in a dry 2-neck 10 mL round-bottom flask. The flask was evacuated and purged with nitrogen, followed by the addition of THF (1 mL). The homogeneous mixture was lowered to −5° C. and iPrMgCl (0.33 mL, 2.0 M) was added dropwise. Upon completion of the addition, the reaction was stirred 90 minutes, followed by the slow addition of 4-fluoro-N-methoxy-N-methyl-benzamide (137 mg, 750 mmol). The reaction was stirred overnight, during which the ice-bath warmed to room temperature. The following day, the reaction was quenched with a small quantity of MeOH and the solvents evaporated in vacuo. The residue was subsequently treated with 4.0 M HCl in dioxane (1 mL, 4.0 mmol) and H2O (0.33 mL), and then stirred at 80° C. for two hours. The resultant solution was diluted with EtOAc, washed with water, saturated sodium bicarbonate, and brine; dried with MgSO4, and evaporated employing reduced pressure. The crude residue was subsequently purified via reverse phase HPLC (Column: Varian Dynamax 250×21.4 mm Microsorb100-8 C18, 0.1% TFA/H2O (Eluent A): 0.1% TFA/MeCN (Eluent B)): 1H NMR (400 MHz, CDCl3) δ 10.63 (bs, 1H), 8.29 (d, 1H), 8.20 (d, 1H), 7.85-7.91 (m, 2H), 7.74 (d, 2H), 7.42 (d, 2H), 7.09 (t, 2H), 1.25 (s, 9H); MS (ES) M+Na expect 469.1. found 469.4.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]3[CH:21]=[N:22][NH:23][CH:24]=3)=[CH:7][N:8]2S(C2C=CC=CC=2)(=O)=O)=[CH:4][CH:3]=1.I[CH:26]1[CH2:29][N:28]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:27]1.[H-].[Na+].[OH-].[Na+]>CN(C=O)C.O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]3[CH:24]=[N:23][N:22]([CH:26]4[CH2:27][N:28]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:29]4)[CH:21]=3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1
Reactant: O=S(=O)(c1ccccc1)n1cc(-c2cn[nH]c2)c2ccc(F)cc21
Reactant: CC(C)(C)OC(=O)N1CC(I)C1
Agent: [H-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CC(n2cc(-c3c[nH]c4cc(F)ccc34)cn2)C1
Temperature: 120 °C
Reaction time: 0.5 h
Yield: 61.7 %

Procedure:
A mixture of 6-fluoro-1-(phenylsulfonyl)-3-(1H-pyrazol-4-yl)-1H-indole (Intermediate 5; 346 mg; 1.0 mmol), tert-butyl 3-iodoazetidine-1-carboxylate (283 mg; 1.0 mmol) and NaH (100 mg; 2.5 mmol; 60% w/w) in DMF (5 mL) was heated to 120° C. for 0.5 hour in a microwave reactor. The reaction mixture was added NaOH (100 mg; 2.50 mmol) in water (0.5 mL) and stirred for 0.5 hour at 85° C. The mixture was concentrated and purified by a silica gel chromatography (petroleum ether/EtOAc=1/1) to afford 220 mg (62%) of the title compound as a yellow solid.
Reaction SMILES: [C:1]1([CH2:7][OH:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.CS(C)=O.[H-].[Na+].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>O>[CH2:7]([O:8][CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH:18]=[CH:17]1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: BrCc1ccccc1
Reactant: OCC1=CCCCC1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: C1=CC(COCc2ccccc2)CCC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A 500 mL round bottom flask equipped with a mechanical stirrer was charged with 19.8 g (0.177 mol) cyclohexene-1-methanol, and 150 mL of DMSO. Sodium hydride (4.90 g, 95% in purity; 0.194 mol) was slowly added to above mixture in an ice bath over 20 min. After the above mixture was reacted at room temperature for 1 hr, 30.2 g (0.177 mol) of benzylbromide was slowly added to the above mixture over 15 min. The reaction was carried out at 60° C. for 2 hrs. The reaction mixture was cooled to room temperature and was added to water (200 mL), and then extracted with chloroform (3×200 mL), washed with water (2×250 mL) and dried with sodium sulfate. The solvent was evaporated and the residue distilled to give pure product.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH2:4][S:5][C@@H:6]2[CH:13]([NH:14][C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=3)=[O:16])[C:12](=[O:28])[N:7]2[C:8]=1[C:9]([OH:11])=[O:10].ClS([N:33]=[C:34]=[O:35])(=O)=O>C(#N)C>[C:34]([O:1][CH2:2][C:3]1[CH2:4][S:5][C@@H:6]2[CH:13]([NH:14][C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=3)=[O:16])[C:12](=[O:28])[N:7]2[C:8]=1[C:9]([OH:11])=[O:10])(=[O:35])[NH2:33]
Reactant: O=C=NS(=O)(=O)Cl
Reactant: O=C(NC1C(=O)N2C(C(=O)O)=C(CO)CS[C@H]12)OCc1ccc([N+](=O)[O-])cc1
Solvent: CC#N
Product: NC(=O)OCC1=C(C(=O)O)N2C(=O)C(NC(=O)OCc3ccc([N+](=O)[O-])cc3)[C@H]2SC1

Procedure:
3-Hydroxymethyl-7-(p-nitrobenzyloxycarbonylamino) 3-cephem-4-carboxylic acid (2.0 g.; 5 m. mole) was suspended in dry acetonitrile (100 ml) and with stirring was cooled to 0°-5° C. under nitrogen. Chlorosulphonylisocyanate (1.1 ml.; 12.5 m. mole) was added dripwise under nitrogen giving a clear solution almost immediately after the addition. The solution was stirred for 1 hour at 0°-5° C. and evaporated to dryness. The resulting gum was dissolved in aqueous sodium bicarbonate such that the final solution was at pH 1.5. This aqueous solution (150 ml) was layered with ethyl acetate (200 ml) and the mixture was stirred at 20° C. for 18 hours. The ethyl acetate layer was separated, washed with brine, dried over magnesium sulphate and evaporated to dryness to give 3-carbamoyloxymethyl-7-(p-nitrobenzyloxycarbonylamino)-3-cephem-4-carboxylic acid as a cream powder (1.73 g.; 77% of theory). Thin layer chromatography in chloroform, acetone, acetic acid (50:50:7) revealed a single spot at Rf =0.11. δ (DMSO) 8.64 (1H, d, CONH), AA'BB' 8.3 and ##STR13## 6.54 (2H, S, --CONH2 exchanges D2O), 5.55 (2H, m, H7 and α-protons), 5.28 (2H, s, benzylic CH2), 5.12 (1H, d, H6), AB quartet 4.9 and 4.6 (2H, 3-CH2), and 3.55 (2H, s, S-CH2 --), γ max (nujol) 1780 (β-lactam C=O) 1710 (broad), 1520 (NO2)cm-1 ; λ max (EtOH) 266 nm (εm 16220).
Reaction SMILES: [CH3:1][C:2]1[N:6]([CH3:7])[C:5]2[CH:8]=[C:9]([C:22](O)=[O:23])[C:10]3[CH2:11][CH2:12][CH:13]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[O:14][C:15]=3[C:4]=2[N:3]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH2:47]([CH2:49][NH2:50])[OH:48].O>ClCCl>[OH:48][CH2:47][CH2:49][NH:50][C:22]([C:9]1[C:10]2[CH2:11][CH2:12][CH:13]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[O:14][C:15]=2[C:4]2[N:3]=[C:2]([CH3:1])[N:6]([CH3:7])[C:5]=2[CH:8]=1)=[O:23]
Reactant: NCCO
Reactant: Cc1nc2c3c(c(C(=O)O)cc2n1C)CCC(c1ccccc1)O3
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: ClCCl
Solvent: O
Product: Cc1nc2c3c(c(C(=O)NCCO)cc2n1C)CCC(c1ccccc1)O3
Temperature: 25 °C
Reaction time: 64 h
Yield: 15.6 %

Procedure:
To a suspension of 0.3 g (0.93 mmol) 2,3-dimethyl-8-phenyl-3,6,7,8-tetrahydro-chromeno[7,8-d]imidazole-5-carboxylic acid in dichloromethane (9 ml) were added 0.45 g (1.4 mmol) O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU) and the suspension was stirred for 64 h at room temperature. 284 μl (4.7 mmol) Ethanolamine were added and the mixture was stirred for 24 h at room temperature. The reaction was poured into water and the precipitate filtered off. The residue was purified by chromatography on silica gel (dichloromethane/methanol=15:1) to afford 53 mg (17%) of the title compound as a yellow solid. m.p. 228°-229° C.
Reaction SMILES: [CH:1]([C:3]1[S:7][C:6]([C:8]([OH:10])=O)=[CH:5][CH:4]=1)=[O:2].[C:11](N1C=CN=C1)([N:13]1C=CN=[CH:14]1)=O.CNC>O1CCCC1>[CH3:11][N:13]([C:8]([C:6]1[S:7][C:3]([CH:1]=[O:2])=[CH:4][CH:5]=1)=[O:10])[CH3:14]
Reactant: O=Cc1ccc(C(=O)O)s1
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: CNC
Solvent: C1CCOC1
Product: CN(C)C(=O)c1ccc(C=O)s1
Reaction time: 0.5 h
Yield: 75 %

Procedure:
To a solution of 5-formyl-2-thiophenecarboxylic acid (prepared according to Carpenter, A. J., et al., Tetrahedron 41:3808 (1985)) (2.75 g, 17.61 mmoles) in 75 ml of tetrahydrofuran was added 1,1′-carbonyl-diimidazole (3.71 g, 22.88 mmoles), the solution stirred under dry argon for ½ hours and treated with excess gaseous dimethylamine. The solution was concentrated in vacuo to an oil which was dissolved in ethyl acetate (100 ml) and extracted with 1N hydrochloric acid (2×50 ml) followed by 5% sodium bicarbonate (2×50 ml). Each of the aqueous layers was backwashed with ethyl acetate (2×50 ml) and the combined organic layers were dried (magnesium sulfate). Concentration in vacuo furnished a pale yellow solid (2.42 g, 75%). EIMS (m/z): 183 (M+, 82%), 154 (M+—CHO, 7%), 139 (M+—(CH3)2N, base) and 111 (M+—(CH3)2NCO, 59%); 1HNMR (CDCl3) delta, 9.91 (1H, s), 7.67 (1H, d, J=4.0 Hz), 7.35 (1H, d, J=4.0 Hz), 3.13 (6H, br s). This material was used directly without further purification.