Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH2:9])[CH:3]=1.C([Li])CCC.CCCCCC.CN(C)[CH:29]=[O:30].[Cl-].[NH4+]>O1CCCC1>[C:10]1([C:8]([C:4]2[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=2)[CH:29]=[O:30])=[CH2:9])[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: CN(C)C=O
Reactant: C=C(c1ccccc1)c1cccc(Br)c1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: C=C(c1ccccc1)c1cccc(C=O)c1
Reaction time: 1 h
Yield: 77.9 %

Procedure:
A solution of 1-bromo-3-(1-phenylvinyl)benzene (1.00 g, 3.86 mmol) in tetrahydrofuran (5 mL) was stirred under a nitrogen atmosphere at −78° C., and 1.6 M n-butyllithium/hexane solution (3 mL, 4.8 mmol) was added dropwise. After 1 hr, N,N-dimethylformamide (0.372 mL, 4.80 mmol) was added, and the mixture was further stirred at the same temperature for 2 hrs. Aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-20% ethyl acetate/hexane) to give the title compound (0.626 g, yield 78%) as a colorless oil.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[C:9]([C:11]([OH:13])=O)[N:10]=[C:4]2[CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[CH:37]([C:39]1[CH:40]=[C:41]([N:48]2[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]2)[CH:42]=[CH:43][C:44]=1[N+:45]([O-:47])=[O:46])=[O:38]>C(N(CC)CC)C.CN(C)C=O>[CH:37]([C:39]1[CH:40]=[C:41]([N:48]2[CH2:53][CH2:52][N:51]([C:11]([C:9]3[N:10]=[C:4]4[CH:3]=[C:2]([CH3:1])[CH:7]=[CH:6][N:5]4[CH:8]=3)=[O:13])[CH2:50][CH2:49]2)[CH:42]=[CH:43][C:44]=1[N+:45]([O-:47])=[O:46])=[O:38]
Reactant: Cc1ccn2cc(C(=O)O)nc2c1
Reactant: O=Cc1cc(N2CCNCC2)ccc1[N+](=O)[O-]
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1ccn2cc(C(=O)N3CCN(c4ccc([N+](=O)[O-])c(C=O)c4)CC3)nc2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 98.1 %

Procedure:
A mixture of 7-methylimidazo[1,2-a]pyridine-2-carboxylic acid (10.56 g), 1-hydroxybenzotriazole (8.1 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (11.46 g) and N,N-dimethylformamide (360 ml) was stirred for 1 hour at ambient temperature. 1-(3-Formyl-4-nitrophenyl)piperazine hydrochloride (16.2 g) and triethylamine (9.1 g) were added thereto and the mixture was stirred for 1 hour. The resulting precipitates were collected, washed with ethyl acetate (100 ml×2) and water (100 ml×2), and dried to give 1-(3-formyl-4-nitrophenyl)-4-(7-methylimidazo[1,2-a]pyridine-2-carbonyl)piperazine (23.0 g).
Reaction SMILES: CS([Cl:5])(=O)=O.CCN(CC)CC.[CH3:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([N+:23]([O-:25])=[O:24])=[C:19]([CH:22]=1)[CH2:20]O>C(Cl)Cl>[CH3:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([N+:23]([O-:25])=[O:24])=[C:19]([CH:22]=1)[CH2:20][Cl:5]
Reactant: CS(=O)(=O)Cl
Reactant: COc1ccc([N+](=O)[O-])c(CO)c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc([N+](=O)[O-])c(CCl)c1
Yield: 94.9 %

Procedure:
MsCl (1.9 mL, 24 mmol) was added to Et3N (4.5 mL, 32 mmol) and 5-methoxy-2-nitrobenzyl alcohol (1.48 g, 8.1 mmol) in CH2Cl2 (80 mL) and the ni-xture kept at reflux for 12 h. The solution was cooled, washed with dilute HCl (2N, 2×50 mL), dried (Na2SO4), concentrated, and filtered through a short column of silica (eluting with 9:1 petroleum ether:EtOAc) to give 5-methoxy-2-nitrobenzyl chloride as a yellow liquid (1.55 g, 95%). 1H N (CDCl3) δ 8.17 (d, J=9.1 Hz, 1 H, H-3), 7.20 (d, J=2.8Hz, 1 H, H-6), 6.93 (dd, J=9.1, 2.8 Hz, 1 H, H-4), 5.03 (s, 2 H, ArCH2Cl), 3.93 (s, 3 H, ArOCH3); 13C NMR (CDCl3) δ 163.7 (C-2), 140.7, 135.5, 128.2, 116.5, 113.7 (C-1,3,4,5,6), 56.1 (OCH3), 43.7 (CH2Cl); MS (EI) m/z 201 [70%, M+ (35Cl)], 184 (100%), 166 (60%, M - Cl), 156 (50%), 106 (70%); HRMS (EI) Calcd. for C8H8ClNO3 203.0163 (35Cl). Found 203.0165.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:10]=[CH:9][C:8]2[C:11](Br)=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[S:13][C:7]=2[C:6]=1[OH:22])=[O:4].[F:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C[O-].[Na+]>O1CCOCC1.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]([C:5]1[N:10]=[CH:9][C:8]2[C:11]([C:27]3[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=3)=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[S:13][C:7]=2[C:6]=1[OH:22])=[O:4]
Reactant: OB(O)c1ccc(F)cc1
Reactant: COC(=O)c1ncc2c(Br)c(-c3ccc(F)cc3)sc2c1O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: COC(=O)c1ncc2c(-c3ccc(F)cc3)c(-c3ccc(F)cc3)sc2c1O
Temperature: 120 °C
Yield: 50.6 %

Procedure:
3-Bromo-2-(4-fluoro-phenyl)-7-hydroxy-thieno[3,2-c]pyridine-6-carboxylic acid methyl ester (0.34 g, 0.89 mmol), example 36-g, 4-fluoro-phenyl boronic acid (0.373 mg, 2.67 mmol), sodium methoxide (0.433 g, 8.01 mmol), and tetrakis(triphenylphosphine)palladium(0) (257 mg, 0.22 mmol) were suspended in 15 mL of 1,4-dioxane. The reaction mixture was heated at 120° C. for 30 min. using a CEM microwave reactor (CEM, Matthews, N.C.). The reaction mixture was diluted with ethyl acetate, and washed with saturated sodium bicarbonate and brine solutions. The organic fraction was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by flash chromatography eluting from silica gel with a gradient of 0-60% ethyl acetate in hexanes to produce 0.179 g of a yellow solid. MS: (+) m/z 398.0 (M+1).
Reaction SMILES: C(O)(=O)C.OO.[C:7]([C:10]1[C:11]([CH3:24])=[C:12]2[C:17](=[C:18]([Cl:20])[CH:19]=1)S[CH2:15][C:14]([CH3:22])([CH3:21])[C:13]2=[O:23])(=[O:9])[CH3:8].[S:25]([O-:28])(O)=[O:26].[Na+]>O>[C:7]([C:10]1[C:11]([CH3:24])=[C:12]2[C:17](=[C:18]([Cl:20])[CH:19]=1)[S:25](=[O:28])(=[O:26])[CH2:22][C:14]([CH3:21])([CH3:15])[C:13]2=[O:23])(=[O:9])[CH3:8]
Reactant: O=S([O-])O
Reactant: CC(=O)c1cc(Cl)c2c(c1C)C(=O)C(C)(C)CS2
Agent: OO
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: CC(=O)c1cc(Cl)c2c(c1C)C(=O)C(C)(C)CS2(=O)=O
Reaction time: 2.5 h
Yield: 88 %

Procedure:
4 Milliliters of acetic acid and 2.12 g (18.71 mmol) of a 30 wt % hydrogen peroxide aqueous solution were added to 2.20 g (7.79 mmol) of 6-acetyl-8-chloro-3,3,5-trimethylthiochroman-4-one in a 100-ml round-bottomed flask, and the mixture was reached at 80° C. for 2.5 hours. The reaction mixture was diluted with about 50 ml of water, and a sodium hydrogensulfite aqueous solution was added to decompose excess hydrogen peroxide. Then, the reaction mixture was extracted with ethyl acetate. An organic layer was washed with a saturated sodium hydrogencarbonate aqueous solution and with a saturated sodium chloride aqueous solution, and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to give 2.16 g (yield 88%) of 6-acetyl-8-chloro-3,3,5-trimethylthiochroman-4-one-1,1-dioxide.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][S:5]([O:8][CH2:9][C:10]([CH3:24])([CH3:23])[C@@H:11]([O:15][Si:16]([CH3:22])([CH3:21])[C:17]([CH3:20])([CH3:19])[CH3:18])[C:12]([OH:14])=[O:13])(=[O:7])=[O:6].[C:25]([O:33][CH:34](Cl)[CH3:35])(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Ag+2]>[Cl:1][CH2:2][CH2:3][CH2:4][S:5]([O:8][CH2:9][C:10]([CH3:24])([CH3:23])[C@@H:11]([O:15][Si:16]([CH3:22])([CH3:21])[C:17]([CH3:19])([CH3:18])[CH3:20])[C:12]([O:14][CH2:35][CH2:34][O:33][C:25](=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:13])(=[O:7])=[O:6]
Reactant: CC(C)(COS(=O)(=O)CCCCl)[C@@H](O[Si](C)(C)C(C)(C)C)C(=O)O
Reactant: CC(Cl)OC(=O)c1ccccc1
Agent: [Ag+2]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: CC(C)(COS(=O)(=O)CCCCl)[C@@H](O[Si](C)(C)C(C)(C)C)C(=O)OCCOC(=O)c1ccccc1
Yield: 110 %

Procedure:
Following the general procedure for the preparation of acyloxyalkyl/alkoxycarbonyloxyalkyl carboxylic esters from carboxylic acids of Description 22, (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(1,1,2,2-tetramethyl-1-silapropoxy)butanoic acid (15) (0.4 g, 0.99 mmol) dissolved in 5 mL of anhydrous toluene was reacted with 0.55 g (3.0 mmol) of 1-chloroethyl benzoate (23) in the presence of 0.33 g (1.1 mmol) of silver carbonate (Ag2CO3). After work-up, the crude material was purified by silica gel column chromatography using a mixture of ethyl acetate (EtOAc) and hexane (Hxn) (EtOAc/Hxn=1:2) as eluent to provide 0.6 g of a mixture of the title compound (38a) and (3R)-4,4-dimethyl-3-(1,1,2,2-tetramethyl-1-silapropoxy)-3,4,5-trihydrofuran-2-one (4a). MS (ESI) m/z 573.01 (M+Na)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5](F)=[C:6]([CH:9]=1)[CH:7]=[O:8].[F:11][C:12]([F:22])([F:21])[O:13][C:14]1[CH:19]=[CH:18][C:17](O)=[CH:16][CH:15]=1.C(=O)([O-])[O-:24].[K+].[K+]>[Cu]=O.N1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:24][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[O:13][C:12]([F:22])([F:21])[F:11])=[C:6]([CH:9]=1)[CH:7]=[O:8]
Reactant: O=C([O-])[O-]
Reactant: Oc1ccc(OC(F)(F)F)cc1
Reactant: O=Cc1cc(Br)ccc1F
Agent: O=[Cu]
Agent: [K+]
Solvent: c1ccncc1
Product: O=Cc1cc(Br)ccc1Oc1ccccc1OC(F)(F)F
Temperature: 180 °C
Reaction time: 6 h
Yield: 82.9 %

Procedure:
A mixture of 5-bromo-2-fluorobenzaldehyde (1.07 g, 5.280 mmol), 4-(trifluoromethoxy)phenol (940 mg, 5.280 mmol), potassium carbonate (1.46 g, 10.560 mmol), copper(II) oxide (420 mg, 5.280 mmol) and pyridine (10 ml) was stirred at 180° C. for 6 hours. The reaction mixture was cooled to room temperature and filtered through celite. The filtrate was diluted with water, extracted with water and saturated brine, and dried over anhydrous sodium sulfate. The residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel (n-hexane:ethyl acetate=6:1) to give the title compound (1.58 g, 83.1%) as a brown oil.
Reaction SMILES: [CH:1]1[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C([Li])CCC.Br[CH2:20][CH2:21][CH:22]1[O:26][CH2:25][CH2:24][O:23]1>C1COCC1>[C:1]1([CH2:20][CH2:21][CH:22]2[O:26][CH2:25][CH2:24][O:23]2)[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: c1ccc2c(c1)Cc1ccccc1-2
Reactant: BrCCC1OCCO1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: c1ccc2c(c1)Cc1c(CCC3OCCO3)cccc1-2
Reaction time: 0.33 h
Yield: 71.1 %

Procedure:
A solution of fluorene (5.04 g; 30.32 mmol) in THF (50 mL) was cooled to 0° C. and treated with n-butyllithium (12.13 mL of a 2.5M solution in hexanes; 30.32 mL). After stirring the resulting dark red mixture for 20 minutes, a solution of 2-(2-bromoethyl)-1,3-dioxolane (6.03 g; 33.35 mmol) in 20 mL of THF was added, and the resulting mixture was stirred overnight, allowing it to come to room temperature. It was quenched by the addition of saturated ammonium chloride (50 mL) and extracted into ethyl acetate (50 mL). The organic phase was washed with brine, dried and freed of solvent. The crude residue was purified on a flash chromatography column, eluting with 20% ethyl acetate in hexane, to obtain 5.74 g (72%) of the product as an oil. 1H NMR (CDCl3): δ 1.43 (m, 2H); 2.18 (m, 2H); 3.82, 3.86 (m, 2H each); 4.15 (t, 1H); 4.77 (t, 1H); 7.31 (m, 4H); 7.51 (dd, 2H); 7.68 (dd, 2H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][CH:3]=1.Cl[C:11]1[CH:19]=[CH:18][C:14]([C:15]([OH:17])=[O:16])=[CH:13][N:12]=1.C(O)(=[O:22])C>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:18]2[CH2:19][C:11](=[O:22])[NH:12][CH:13]=[C:14]2[C:15]([OH:17])=[O:16])=[CH:4][CH:3]=1
Reactant: Fc1ccc([Mg]Br)cc1
Reactant: CC(=O)O
Reactant: O=C(O)c1ccc(Cl)nc1
Solvent: C1CCOC1
Product: O=C1CC(c2ccc(F)cc2)C(C(=O)O)=CN1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
4-Fluorophenylmagnesium bromide (2M in THF; 130 ml) was added dropwise at 0° C. to a stirring solution of 6-chloronicotinic acid (12.92 g) in 150 mL of THF. After the addition was complete the reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was cooled to −60° C. and acetic acid (105 ml) was added dropwise, resulting in formation of a solid. After the addition was complete the reaction mixture was warmed to ambient temperature. The reaction mixture was then cooled to 0° C. and quenched by addition of saturated aqueous ammonium chloride solution. The mixture was partitioned between water and ethyl acetate, and the organic layer was separated, washed with water and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was dissolved in hot ethyl acetate. Upon standing a solid precipitate formed, which was collected and dried to give 10.04 g of 4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid as a white solid.
Reaction SMILES: Br[C:2]1[C:3]([N:7]2[C:15]3[CH:14]=[CH:13][C:12]([CH3:16])=[CH:11][C:10]=3[C:9]3[CH2:17][N:18]([CH3:21])[CH2:19][CH2:20][C:8]2=3)=[CH:4][S:5][CH:6]=1.[N:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.O>[CH3:21][N:18]1[CH2:19][CH2:20][C:8]2[N:7]([C:3]3[C:2]([C:25]4[CH:26]=[CH:27][N:22]=[CH:23][CH:24]=4)=[CH:6][S:5][CH:4]=3)[C:15]3[CH:14]=[CH:13][C:12]([CH3:16])=[CH:11][C:10]=3[C:9]=2[CH2:17]1
Reactant: Cc1ccc2c(c1)c1c(n2-c2cscc2Br)CCN(C)C1
Reactant: OB(O)c1ccncc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc2c(c1)c1c(n2-c2cscc2-c2ccncc2)CCN(C)C1
Temperature: 95 °C

Procedure:
To a de-aerated solution of 5-(4-bromo-thiophen-3-yl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (160 mg, 0.44 mmol), 4-pyridinylboronic acid (81.9 mg, 0.66 mmol) and K3PO4 (235 mg, 1.11 mmol) in DMF-water (4.5:0.5 mL) was added dichlorobis(triphenylphosphine) palladium (II) (15.5 mg, 5 mol %). The reaction mixture was heated at 95° C. for 30 min under nitrogen atmosphere. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford crude material, which was purified by reverse phase HPLC to yield 2,8-dimethyl-5-(4-pyridin-4-yl-thiophen-3-yl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole as an off white solid (90 mg). 1H NMR (Oxalate salt, CD3OD) δ (ppm): 8.4-8.3 (bs, 2H), 8.19 (s, 1H), 7.8 (s, 1H), 7.35 (s, 1H), 7.05-6.9 (m, 4H), 4.7-4.5 (m, 2H), 3.7-3.5 (m, 2H), 3.1 (s, 3H), 3.05-3.0 (m, 1H), 2.7-2.59 (m, 1H), 2.4 (s, 3H).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][CH:3]=1.S(Cl)([Cl:21])(=O)=O.[ClH:23]>CCOCC>[Cl:23][C:7]1[CH:6]=[C:5]([C:8]([C:11]2[CH:12]=[CH:13][C:14]([OH:17])=[C:15]([Cl:21])[CH:16]=2)([CH3:10])[CH3:9])[CH:4]=[CH:3][C:2]=1[OH:1]
Reactant: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Reactant: Cl
Reactant: O=S(=O)(Cl)Cl
Solvent: CCOCC
Product: CC(C)(c1ccc(O)c(Cl)c1)c1ccc(O)c(Cl)c1
Temperature: 25 °C
Yield: 95 %

Procedure:
Bisphenol A (17.2 g; 75 mmol) dissolved in 100 mL of anhydrous ether was treated with sulfuryl chloride (22.25 g; 165 mmol) and stirred at room temperature. The reaction was exothermic, and the temperature initially rose to 30° C. However, HCl and SO2 gases that were given off cooled the system and maintained it below 30° C. After the gas evolution had stopped, the reaction mixture was refluxed for 1 hour. The work-up procedure involved washing with saturated NaHCO3 solution and water followed by drying (Na2SO4) and concentration. The product 2,2-bis(3-chloro,-4-hydroxyphenyl)propane was formed in 95% yield.
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH2:4][CH2:5][C:6]1([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[C:10]2[CH:11]=[CH:12][C:13]([C:15]#[N:16])=[CH:14][C:9]=2CO1.Cl.[C:25]1([C:31](=[NH:34])OC)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[C:35](=[O:38])([O-])[O-].[K+].[K+]>CN1CCCC1=O>[C:15]([C:13]1[CH:14]=[CH:9][C:10]2[C:6]([CH2:5][CH2:4][CH2:3][N:2]([CH3:1])[C:31]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[NH:34])([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[O:38][CH2:35][C:11]=2[CH:12]=1)#[N:16]
Reactant: O=C([O-])[O-]
Reactant: COC(=N)c1ccccc1
Reactant: CNCCCC1(c2ccc(F)cc2)OCc2cc(C#N)ccc21
Agent: Cl
Agent: [K+]
Solvent: CN1CCCC1=O
Product: CN(CCCC1(c2ccc(F)cc2)OCc2cc(C#N)ccc21)C(=N)c1ccccc1
Temperature: 80 °C
Yield: 29.4 %

Procedure:
A mixture of 0.350 g (1.13 mmol) of 1-[3-(methylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile (Preparation 1) and methyl benzenecarboximidoate hydrochloride (0.213 g, 1.24 mmol, 1.1 equiv.) in 0.7 mL of N-methyl-pyrrolidinone was treated with potassium carbonate (0.11 g, 0.79 mmol, 0.7 equiv.) and heated to 80° C. for 15 hr. The solvent was then removed and the crude product purified by column chromatography to give the title compound 0.096 g (19%) as a white solid.
Reaction SMILES: [Li]CCCC.CO[CH:8](OC)[CH2:9][NH2:10].[S:13]1[CH:17]=[CH:16][N:15]=[C:14]1[C:18]#[N:19].N>CCCCCC.C1COCC1>[NH:10]1[CH:9]=[CH:8][N:19]=[C:18]1[C:14]1[S:13][CH:17]=[CH:16][N:15]=1
Reactant: COC(CN)OC
Reactant: N#Cc1nccs1
Agent: N
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: c1c[nH]c(-c2nccs2)n1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A 2.5 M solution of nBuLi (2.0 eq) in hexane was added under argon to a solution of 2,2-dimethoxyethanamine (2.0 eq) in THF at −78° C. After stirring for 30 min, thiazole-2-carbonitrile (2-Im-2, 3.0 g, 1.0 eq) was added and the resulting solution was stirred at 0° C. for 2 h, then quenched with 20 mL of 5% MeOH in water. The volatiles were removed and 6N HCl was added to adjust to pH=1. The acidic solution was refluxed overnight, cooled to rt then poured into a mixture of ice and aqueous Na2CO3. This was extracted with EtOAc and the organic layer was concentrated to give Imadazole 2. LCMS (0.01% Ammonia): 152.1 m/z (M+H)+; 1H-NMR (DMSO-d6, 500 MHz): δ: 13.19 (bs, 1H), 7.98 (d, 1H, J=3.0 Hz), 7.82 (d, 1H, J=3.0 Hz), 7.36 (s, 1H), 7.14 (s, 1H).
Reaction SMILES: P(Cl)(OC1C=CC=CC=1)(OC1C=CC=CC=1)=O.C(N(C(C)C)CC)(C)C.[OH:27][C@@H:28]([C@H:30]1[C:51](=[O:52])[N:32]2[CH:33]([C:38]([O:40][CH2:41][C:42]3[CH:47]=[CH:46][C:45]([N+:48]([O-:50])=[O:49])=[CH:44][CH:43]=3)=[O:39])[C:34](=O)[C@H:35]([CH3:36])[C@H:31]12)[CH3:29].FC(F)(F)S(O)(=O)=O.[C:61]([O:64][CH2:65][CH2:66][N:67]1[CH2:73][CH2:72][CH2:71][N:70]([C:74]([C@@H:76]2[CH2:80][C@H:79]([SH:81])[CH2:78][N:77]2[C:82]([O:84][CH2:85][C:86]2[CH:91]=[CH:90][C:89]([N+:92]([O-:94])=[O:93])=[CH:88][CH:87]=2)=[O:83])=[O:75])[CH2:69][CH2:68]1)(=[O:63])[NH2:62]>C(#N)C>[C:61]([O:64][CH2:65][CH2:66][N:67]1[CH2:73][CH2:72][CH2:71][N:70]([C:74]([C@@H:76]2[CH2:80][C@H:79]([S:81][C:34]3[C@H:35]([CH3:36])[C@@H:31]4[C@@H:30]([C@H:28]([OH:27])[CH3:29])[C:51](=[O:52])[N:32]4[C:33]=3[C:38]([O:40][CH2:41][C:42]3[CH:47]=[CH:46][C:45]([N+:48]([O-:50])=[O:49])=[CH:44][CH:43]=3)=[O:39])[CH2:78][N:77]2[C:82]([O:84][CH2:85][C:86]2[CH:87]=[CH:88][C:89]([N+:92]([O-:94])=[O:93])=[CH:90][CH:91]=2)=[O:83])=[O:75])[CH2:69][CH2:68]1)(=[O:63])[NH2:62]
Reactant: NC(=O)OCCN1CCCN(C(=O)[C@@H]2C[C@H](S)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)CC1
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)C(=O)[C@H](C)[C@H]12
Agent: O=P(Cl)(Oc1ccccc1)Oc1ccccc1
Agent: O=S(=O)(O)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](C(=O)N4CCCN(CCOC(N)=O)CC4)N(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)[C@H](C)[C@H]12
Reaction time: 1 h
Yield: 31.8 %

Procedure:
88 μl of diphenyl chlorophosphate and 74 μl of diisopropylethylamine were added dropwise, whilst ice-cooling, to a solution of 145 mg of 4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 2 ml of anhydrous acetonitrile, and the resulting mixture was stirred at the same temperature for 1 hour. 202 μl of diisopropylethylamine and a solution of 310 mg of (2S,4S)-2-[4-(2-carbamoyloxyethyl)-1-homopiperazinylcarbonyl]-4-mercapto-1-(4-nitrobenzyloxycarbonyl)pyrrolidine trifluoromethanesulfonate [prepared as described in step (1) above] in 2.0 ml of anhydrous acetonitrile were then added dropwise to the mixture, whilst ice-cooling, and the resulting mixture was allowed to stand overnight at the same temperature. At the end of this time, the reaction mixture was worked up and purified in a similar manner to that described in Example 32(2), to afford 107 mg of the title compound as a powder.
Reaction SMILES: [CH3:1][C:2]1[N:6]([CH2:7][CH2:8][CH3:9])[C:5]2[CH:10]=[CH:11][C:12]([CH2:14]O)=[CH:13][C:4]=2[N:3]=1.[ClH:16].S(Cl)([Cl:19])=O>ClC(Cl)Cl>[ClH:19].[Cl:16][CH2:14][C:12]1[CH:11]=[CH:10][C:5]2[N:6]([CH2:7][CH2:8][CH3:9])[C:2]([CH3:1])=[N:3][C:4]=2[CH:13]=1
Reactant: O=S(Cl)Cl
Reactant: CCCn1c(C)nc2cc(CO)ccc21
Agent: Cl
Solvent: ClC(Cl)Cl
Product: CCCn1c(C)nc2cc(CCl)ccc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 36 parts of 2-methyl-1-propyl-1H-benzimidazole-5-methanol in 150 parts of trichloromethane is acidified with an excess of gaseous hydrogen chloride. Then there are added dropwise 32 parts of thionyl chloride. Upon completion, the whole is stirred for one hour at room temperature. The reaction mixture is evaporated and the residue is crystallized from 2-propanone. The product is filtered off, washed with 2-propanone and dried, yielding 40.9 parts of 5-(chloromethyl)-2-methyl-1-propyl-1H-benzimidazole monohydrochloride; m.p. 180° C.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C:13]([OH:15])=O)[CH:7]=[CH:6]2)#[N:2].S(Cl)([Cl:18])=O.S([O-])([O-])(=O)=O.[Ca+2]>CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C:13]([Cl:18])=[O:15])[CH:7]=[CH:6]2)#[N:2]
Reactant: O=S(Cl)Cl
Reactant: N#Cc1ccc2cc(C(=O)O)ccc2c1
Agent: O=S(=O)([O-])[O-]
Agent: [Ca+2]
Solvent: CN(C)C=O
Product: N#Cc1ccc2cc(C(=O)Cl)ccc2c1

Procedure:
A mixture of 6-cyano-naphthalene-2-carboxylic acid (250.00 mg, 1.27 mmol), thionyl chloride (15 mL), and a few drops of DMF was refluxed for two hours under a condenser equipped with a drying tube containing anhydrous calcium sulfate. The thionyl chloride was then removed by high vacuum distillation, yielding a quantitative yield of a yellow solid. This material was not characterized, and was carried on without further purification.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10]O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(=O)(=O)(O)O.[BrH:17]>>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][Br:17])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Br
Reactant: OCCCCc1ccccc1
Agent: O=S(=O)(O)O
Product: BrCCCCc1ccccc1
Temperature: 0 °C

Procedure:
To 3.2 g of 4-phenyl-1-butanol, were added 1.0 g of concentrated sulfuric acid and 5.5 g of 47% aqueous solution of hydrobromic acid, and the resultant solution was stirred for 5 hours at 140-150° C. while applying heating. After completed the reaction, the solution was then poured into ice-water and extracted with ethyl acetate. The organic layer resulted was dried with anhydrous magnesium sulfate, and the solvent used was distillated under reduced pressure, thereby affording 2.7 g of 4-phenyl-1-bromobutane.