Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[O:9][C:8]([C:10]3[N:11]=[C:12]4[N:16]([CH:17]=3)[N:15]=[C:14]([O:18][CH3:19])[S:13]4)=[CH:7][C:6]2=[C:20]([OH:22])[CH:21]=1.Br[CH2:24][C:25]1[N:26]=[C:27]([CH2:30][O:31][CH2:32][CH2:33][O:34][CH3:35])[S:28][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.ClCCl>[CH3:19][O:18][C:14]1[S:13][C:12]2=[N:11][C:10]([C:8]3[O:9][C:5]4[CH:4]=[C:3]([O:2][CH3:1])[CH:21]=[C:20]([O:22][CH2:24][C:25]5[N:26]=[C:27]([CH2:30][O:31][CH2:32][CH2:33][O:34][CH3:35])[S:28][CH:29]=5)[C:6]=4[CH:7]=3)=[CH:17][N:16]2[N:15]=1
Reactant: COCCOCc1nc(CBr)cs1
Reactant: COc1cc(O)c2cc(-c3cn4nc(OC)sc4n3)oc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COCCOCc1nc(COc2cc(OC)cc3oc(-c4cn5nc(OC)sc5n4)cc23)cs1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
A suspension of 6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)benzofuran-4-ol (Example 1H, 0.10 g, 0.315 mmol) and 4-(bromomethyl)-2-((2-methoxyethoxy)methyl)thiazole (Example 6E, 0.10 g, 0.376 mmol) in DMF (5 mL) was purged under vacuum and nitrogen for 10 minutes. The mixture was then treated with potassium carbonate (0.10 g, 0.724 mmol) and the reaction was stirred at RT for 2.5 hours. The reaction was then diluted with dichloromethane, washed with water (1×), brine (1×), dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (2.5×10 cm, 50% ethyl acetate/CH2Cl2) to give the title material which was crystallized in ethyl acetate and provided the desired title material (0.055 g, 35%) along with non-crystallized material (9 mgs, 6%). LC (Method F): 2.476 min. HRMS (ESI) calcd for C22H23N4O6S2 [M+H]+ m/z 503.1054, found 503.1066. 1H NMR (CDCl3, 400 MHz) δ ppm: 7.82 (s, 1H), 7.35 (s, 1H), 7.05 (s, 1H), 6.68 (broad s, 1H), 6.39 (d, J=1.9 Hz, 1H), 5.28 (s, 2H), 4.86 (s, 2H), 4.19 (s, 3H), 3.82 (s, 3H), 3.74-3.77 (m, 2H), 3.58-3.61 (m, 2H), 3.39 (s, 3H).
Reaction SMILES: [F:1][C:2]1[CH:20]=[C:19]2[C:5]([CH2:6][C:7]3[C:15]4[CH:14]=[CH:13][C:12]([O:16][CH3:17])=[CH:11][C:10]=4[N:9]([CH3:18])[C:8]=32)=[CH:4][CH:3]=1.[Li]CCCC.[CH3:26][Si:27](Cl)([CH3:29])[CH3:28]>CCOCC>[F:1][C:2]1[CH:20]=[C:19]2[C:5]([CH:6]([Si:27]([CH3:29])([CH3:28])[CH3:26])[C:7]3[C:15]4[CH:14]=[CH:13][C:12]([O:16][CH3:17])=[CH:11][C:10]=4[N:9]([CH3:18])[C:8]=32)=[CH:4][CH:3]=1
Reactant: C[Si](C)(C)Cl
Reactant: COc1ccc2c3c(n(C)c2c1)-c1cc(F)ccc1C3
Agent: [Li]CCCC
Solvent: CCOCC
Product: COc1ccc2c3c(n(C)c2c1)-c1cc(F)ccc1C3[Si](C)(C)C
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 62 %

Procedure:
A round bottom flask containing 56 (201 mg, 0.75 mmol) in dry ether (6 mL) was immersed in a 25° C. water bath. n-BuLi (1.5 M in THF, 602 μL, 0.90 mmol) was added via syringe pump over one hour, generating an orange solution. Following addition of base, the reaction mixture was stirred at 25° C. for an additional 1.5 hours and then cooled to −78° C. TMSCl (200 μL, 1.58 mmol) was added rapidly via syringe, and the reaction mixture was stirred an additional 5 minutes at −78° C., then warmed to room temperature over 3.5 hours. The reaction was subsequently diluted with ether, filtered, and concentrated in vacuo. Crude product was purified by flash column chromatography (20:1 hexanes-ethyl acetate) to yield 57 as a solid in 62% yield (159 mg, 0.47 mmol). 1H NMR (600 MHz, CDCl3): δ 7.54 (d, 1H, J=8.4 Hz), 7.39-7.41 (dd, 1H, J=8.4, 4.8 Hz), 7.33-7.35 (dd, 1H, J=9, 2.4 Hz), 6.83-6.89 (m, 3H), 3.98 (s, 3H), 3.93 (s, 3H), −0.02 (s, 9H). 13C NMR (150 MHz, CDCl3): δ 61.4 (d, J=238.5 Hz), 156.2, 144.5 (d, J=2.0), 143.0, 141.5 (d, J=3 Hz), 134.8 (d, J=9.5 Hz), 125.4, 124.79 (d, J=9.15 Hz), 120.9, 118.0, 109.4 (d, J=22.8 Hz), 108.6, 103.9 (d, J=24.3 Hz), 93.5, 5.6, 36.3, 31.0, −2.5; 19F NMR (CD3CD, 376 MHz): δ −117.6 (m); FTIR: cm−12952, 1608, 1523, 1372, 1223, 1163, 1107, 1042, 939, 841.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH:5]=[O:6].C(=O)([O-])[O-].[K+].[K+].Br[CH2:19][CH2:20][CH3:21]>CN(C=O)C.C(OCC)C.[I-].[K+]>[CH2:19]([O:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH:5]=[O:6])[CH2:20][CH3:21]
Reactant: CCCBr
Reactant: COc1ccc(C=O)cc1O
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CCCOc1cc(C=O)ccc1OC
Temperature: 65 °C
Reaction time: 5 h
Yield: 101.4 %

Procedure:
To a suspension of 3-hydroxy-4-methoxybenzaldehyde (2.00 g, 13.2 mmol), potassium carbonate (2.74 g, 19.8 mmol) and potassium iodide (60.0 mg, 0.361 mmol) in DMF (15 mL) was slowly added 1-bromopropane (1.56 mL, 17.2 mmol) via syringe. The reaction mixture was stirred at 65° C. for 5 hours. After cooling to room temperature, the mixture was diluted with diethyl ether (100 mL), and the organic phase was washed with water (2×50 mL). After drying over anhydrous MgSO4, filtration and evaporation of the filtrate in vacuo gave crude 3-(propyloxy)-4-methoxybenzaldehyde (2.60 g) which was used in the next step without further purification.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]([C:13]3[CH:28]=[CH:27][C:16]([NH:17]CC4C=CC(OC)=CC=4)=[C:15]([N+:29]([O-:31])=[O:30])[CH:14]=3)[CH2:11][CH2:10][CH:9]2[C:32]2[CH:47]=[CH:46][C:35]([NH:36]CC3C=CC(OC)=CC=3)=[C:34]([N+:48]([O-:50])=[O:49])[CH:33]=2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH:9]([C:32]3[CH:47]=[CH:46][C:35]([NH2:36])=[C:34]([N+:48]([O-:50])=[O:49])[CH:33]=3)[CH2:10][CH2:11][CH:12]2[C:13]2[CH:28]=[CH:27][C:16]([NH2:17])=[C:15]([N+:29]([O-:31])=[O:30])[CH:14]=2)=[CH:6][CH:7]=1
Reactant: COc1ccc(CNc2ccc(C3CCC(c4ccc(NCc5ccc(OC)cc5)c([N+](=O)[O-])c4)N3c3ccc(F)cc3)cc2[N+](=O)[O-])cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Nc1ccc(C2CCC(c3ccc(N)c([N+](=O)[O-])c3)N2c2ccc(F)cc2)cc1[N+](=O)[O-]

Procedure:
4,4′-(1-(4-Fluorophenyl)pyrrolidine-2,5-diyl)bis(N-(4-methoxybenzyl)-2-nitroaniline) (0.78 g, 1.15 mmol) was dissolved in dichloromethane (10 mL) at room temperature and treated with TFA (1.8 mL, 23.0 mmol) for 3 hours. The residue was concentrated and partitioned between dichloromethane and sodium bicarbonate solution. The organics were concentrated and purified by chromatography on silica gel with a 40 g column, eluting with dichloromethane to give 0.218 g (43%) of the trans isomer.
Reaction SMILES: [C:1]([O:5][CH:6]1[CH2:11][C:10]([CH3:13])([CH3:12])[N:9]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[C:8]([CH3:34])([CH3:33])[CH2:7]1)(=[O:4])[CH:2]=[CH2:3].[C:35]([O:59][CH:60]1[CH2:65][C:64]([CH3:67])([CH3:66])[N:63]([OH:68])[C:62]([CH3:70])([CH3:69])[CH2:61]1)(=[O:58])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][C:44]([O:46][CH:47]1[CH2:52][C:51]([CH3:54])([CH3:53])[N:50]([OH:55])[C:49]([CH3:57])([CH3:56])[CH2:48]1)=[O:45]>>[C:35]([O:59][CH:60]1[CH2:61][C:62]([CH3:70])([CH3:69])[N:63]([O:68][CH2:3][CH2:2][C:1]([O:5][CH:6]2[CH2:7][C:8]([CH3:33])([CH3:34])[N:9]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[C:10]([CH3:12])([CH3:13])[CH2:11]2)=[O:4])[C:64]([CH3:67])([CH3:66])[CH2:65]1)(=[O:58])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][C:44]([O:46][CH:47]1[CH2:48][C:49]([CH3:56])([CH3:57])[N:50]([O:55][CH2:3][CH2:2][C:1]([O:5][CH:6]2[CH2:7][C:8]([CH3:33])([CH3:34])[N:9]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[C:10]([CH3:12])([CH3:13])[CH2:11]2)=[O:4])[C:51]([CH3:53])([CH3:54])[CH2:52]1)=[O:45]
Reactant: C=CC(=O)OC1CC(C)(C)N(OCCCCCCCCCCCCCCCCCC)C(C)(C)C1
Reactant: CC1(C)CC(OC(=O)CCCCCCCCC(=O)OC2CC(C)(C)N(O)C(C)(C)C2)CC(C)(C)N1O
Product: CCCCCCCCCCCCCCCCCCON1C(C)(C)CC(OC(=O)CCON2C(C)(C)CC(OC(=O)CCCCCCCCC(=O)OC3CC(C)(C)N(OCCC(=O)OC4CC(C)(C)N(OCCCCCCCCCCCCCCCCCC)C(C)(C)C4)C(C)(C)C3)CC2(C)C)CC1(C)C

Procedure:
The title compound is prepared from 1-octadecyloxy-2,2,6,6-tetramethylpiperidin-4-yl acrylate and bis(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl) sebacate according to the general procedure of Example 2.
Reaction SMILES: [OH:1][C:2]1[C:11]2[CH2:10][CH:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:8][CH2:7][C:6]=2[O:5][C:4](=[O:16])[C:3]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[O:23]1[CH2:28][CH2:27][N:26]([CH2:29][CH:30]([CH3:33])[CH2:31]Cl)[CH2:25][CH2:24]1>>[O:23]1[CH2:28][CH2:27][N:26]([CH2:29][CH:30]([CH3:33])[CH2:31][O:1][C:2]2[C:11]3[CH2:10][CH:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:8][CH2:7][C:6]=3[O:5][C:4](=[O:16])[C:3]=2[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:25][CH2:24]1
Reactant: CC(CCl)CN1CCOCC1
Reactant: CC(C)(C)C1CCc2oc(=O)c(-c3ccccc3)c(O)c2C1
Product: CC(COc1c2c(oc(=O)c1-c1ccccc1)CCC(C(C)(C)C)C2)CN1CCOCC1

Procedure:
Prepared according to the method of Example 9 from 12.8 g. (0.043 mol) of 4-hydroxy-3-phenyl-6-tert.butyl-5,6,7,8-tetrahydro-coumarin and 10.7 g. (0.061 mol) of 3-morpholino-2-methyl-1-chloropropane. The product is a thick oil which cannot be crystallised.
Reaction SMILES: [CH:1]([S:4]([O-:6])=[O:5])([CH3:3])[CH3:2].[Na+].CN1CCCC1=O.Cl[C:16]1[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=1[N+:23]([O-:25])=[O:24]>O>[Cl:22][C:21]1[C:16]([S:4]([CH:1]([CH3:3])[CH3:2])(=[O:6])=[O:5])=[C:17]([N+:23]([O-:25])=[O:24])[CH:18]=[CH:19][CH:20]=1
Reactant: CC(C)S(=O)[O-]
Reactant: O=[N+]([O-])c1cccc(Cl)c1Cl
Agent: [Na+]
Solvent: O
Solvent: CN1CCCC1=O
Product: CC(C)S(=O)(=O)c1c(Cl)cccc1[N+](=O)[O-]
Temperature: 70 °C
Reaction time: 8 h
Yield: 54.6 %

Procedure:
To a mixture of sodium isopropylsulfinate (3.3 g) and N-methyl-2-pyrrolidinone (20 mL), 2,3-dichloronitrobenzene (4 g) was added and stirred overnight at 70° C. The reaction mixture was diluted with water, and the precipitated solid was collected by filtration and washed with diethyl ether to give 3-chloro-2-isopropylsulfonyl-1-nitrobenzene (3.0 g) as a white solid.
Reaction SMILES: B(O)O.Br[C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][N:12]=1)[CH:8]=[O:9].[O:13]1[CH:17]=[CH:16][CH:15]=[C:14]1B(O)O>>[O:13]1[CH:17]=[CH:16][CH:15]=[C:14]1[C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][N:12]=1)[CH:8]=[O:9]
Reactant: OB(O)c1ccco1
Reactant: O=Cc1ccnc(Br)c1
Agent: OBO
Product: O=Cc1ccnc(-c2ccco2)c1

Procedure:
2-(furan-2-yl)isonicotinaldehyde was prepared using the general boronic acid coupling procedure for 2-bromoisonicotinaldehyde and furan-2-ylboronic acid (39.6 mg, 93.2 mg theoretical, 42.5%). LC-MS m/z 174.2 (M+1).
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH:10][C:11](=[O:13])[CH3:12])=[CH:5][CH:4]=1.[Cl:14][C:15]1[CH:16]=[CH:17][C:18]([N:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)=[N:19][CH:20]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Cl:14][C:15]1[CH:16]=[CH:17][C:18]([N:21]2[CH2:22][CH2:23][N:24]([CH2:2][C:3]3[CH:8]=[CH:7][C:6]([CH2:9][NH:10][C:11](=[O:13])[CH3:12])=[CH:5][CH:4]=3)[CH2:25][CH2:26]2)=[N:19][CH:20]=1
Reactant: Clc1ccc(N2CCNCC2)nc1
Reactant: CC(=O)NCc1ccc(CCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)NCc1ccc(CN2CCN(c3ccc(Cl)cn3)CC2)cc1
Yield: 113.8 %

Procedure:
A solution of N-(4-chloromethylphenylmethyl)acetamide (1.5 g), 1-(5-chloropyridin-2-yl)piperazine (1.5 g) and potassium carbonate (1.6 g) in dimethylformamide (20 ml) was stirred at 70-80° C. for 8.5 hr. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated to give a brown solid (3.1 g). The obtained brown solid was crystallized ethyl acetate to give the title compound (1.3 g) as pale-yellow crystals,
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH:11]=[O:12].[C:13]([C:16]1[CH:25]=[CH:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=1)(=O)[CH3:14]>>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11](=[O:12])[CH:14]=[CH:13][C:16]1[CH:25]=[CH:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=1
Reactant: CC(=O)c1ccc2ccccc2c1
Reactant: O=Cc1ccc2ccccc2c1
Product: O=C(C=Cc1ccc2ccccc2c1)c1ccc2ccccc2c1

Procedure:
By a procedure similar to that of example 1.59.1, starting from 2-naphthaldehyde and 2-acetylnaphthalene, 1,3-di-(2-naphthalenyl)prop-2-en-1-one was obtained as yellow solid.
Reaction SMILES: [CH3:1][N:2]1[C:7]2[S:8][C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]([F:22])([F:21])[F:20])[CH:13]=3)=[C:10]([CH3:11])[C:6]=2[C:5](=[O:23])[N:4]([CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:3]1=[O:31].C1C(=O)N([Br:39])C(=O)C1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl.C(Cl)Cl>[Br:39][CH2:11][C:10]1[C:6]2[C:5](=[O:23])[N:4]([CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:3](=[O:31])[N:2]([CH3:1])[C:7]=2[S:8][C:9]=1[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]([F:20])([F:21])[F:22])[CH:13]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)CCn1c(=O)c2c(C)c(-c3cccc(OC(F)(F)F)c3)sc2n(C)c1=O
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClCCl
Solvent: ClC(Cl)(Cl)Cl
Product: CCOC(=O)CCn1c(=O)c2c(CBr)c(-c3cccc(OC(F)(F)F)c3)sc2n(C)c1=O
Temperature: 25 °C
Yield: 84.9 %

Procedure:
To a solution of ethyl 3-(1,5-dimethyl-2,4-dioxo-6-(3-(trifluoromethoxy)phenyl)-1,2-dihydrothieno[2,3-d]pyrimidin-3(4H)-yl)propanoate (120 mg, 0.22 mmol) in CCl4 (3 mL) was added NBS (39 mg, 0.22 mmol) followed by benzoyl peroxide (5 mg). The reaction was heated at reflux for 4 h, cooled to RT and diluted with DCM (10 mL). The mixture was washed with aq. NaHCO3 (10 mL), and brine (10 mL). The organic layer was dried over Na2SO4 and concentrated to give ethyl 3-(5-(bromomethyl)-1-methyl-2,4-dioxo-6-(3-(trifluoromethoxy)phenyl)-1,2-dihydrothieno[2,3-d]pyrimidin-3(4H)-yl)propanoate (100 mg, 85.7% yield) as an oil. LCMS: MH+ 535 and TR=2.087 min. Used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][CH2:16][CH2:17][C:18]#[N:19])[C:10]([CH2:20][OH:21])=[CH:9]2>C(Cl)Cl.O=[Mn]=O>[Cl:1][C:2]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][CH2:16][CH2:17][C:18]#[N:19])[C:10]([CH:20]=[O:21])=[CH:9]2
Reactant: N#CCCCn1c(CO)cc2cc(OCc3c(Cl)cccc3Cl)ccc21
Agent: O=[Mn]=O
Solvent: ClCCl
Product: N#CCCCn1c(C=O)cc2cc(OCc3c(Cl)cccc3Cl)ccc21
Temperature: 25 °C
Reaction time: 18 h
Yield: 72.7 %

Procedure:
To a solution of 4-[5-(2,6-dichlorobenzyloxy)-2-hydroxymethyl-indol-1-yl]butyronitrile (1.73 g, 4.44 mmol) in CH2Cl2 (100 mL) was added MnO2 (3.09 g, 35.6 mmol) and the reaction was stirred at room temperature for 18 h. The reaction mixture was filtered through Celite and the filtrate was concentrated under reduced pressure. Purification by flash column chromatography (silica gel, ethyl acetate/hexane) yielded the desired aldehyde (1.25 g, 73%) as a white solid. MS(ES) m/e 387.0 [M+H]+.
Reaction SMILES: [C:1]([S:4][C@@H:5]1[CH2:9][N:8]([C:10]([O:12][CH2:13][CH:14]=[CH2:15])=[O:11])[C@H:7]([CH2:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][CH:18]=2)[CH2:6]1)(=O)[CH3:2].O(P(OC1C[C@@H:46]2[C@@H:56]([C@H:57]([OH:59])[CH3:58])[C:55](=[O:60])[N:47]2[C:48]=1[C:49]([O:51][CH2:52][CH:53]=[CH2:54])=[O:50])(OC1C=CC=CC=1)=O)C1C=CC=CC=1.[OH-].[Na+].Cl.C(N(CC)C(C)C)(C)C>>[CH2:13]([O:12][C:10]([N:8]1[C@@H:7]([CH2:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][CH:18]=2)[CH2:6][C@H:5]([S:4][C:1]2[CH2:2][C@@H:46]3[C@@H:56]([C@H:57]([OH:59])[CH3:58])[C:55](=[O:60])[N:47]3[C:48]=2[C:49]([O:51][CH2:52][CH:53]=[CH2:54])=[O:50])[CH2:9]1)=[O:11])[CH:14]=[CH2:15]
Reactant: C=CCOC(=O)N1C[C@@H](SC(C)=O)C[C@H]1Cc1cccc2ccccc12
Reactant: C=CCOC(=O)C1=C(OP(=O)(Oc2ccccc2)Oc2ccccc2)C[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(C(C)C)C(C)C
Product: C=CCOC(=O)C1=C(S[C@H]2C[C@H](Cc3cccc4ccccc34)N(C(=O)OCC=C)C2)C[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12
Yield: 73.5 %

Procedure:
Allyl (5R,6S)-2-[(3S,5S)-N-(allyloxycarbonyl)-5-(1-naphthylmethyl)pyrrolidin-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylate (633 mg, yield: 70.1%) was prepared as a yellow powder, from (2R,4S)-4-acetylthio-N-allyloxycarbonyl-2-(1-naphthylmethyl)pyrrolidine (610 mg, 1.53 mmol), allyl (5R,6S)-2-diphenoxyphosphoryloxy-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylate (743 mg, 1.53 mmol), 1N aqueous sodium hydroxide (1.8 ml, 1.8 mmol), 1N aqueous hydrochloric acid (1.8 ml, 1.8 mmol) and N,N-diisopropylethylamine (800 μl, 4.59 mmol), in the same manner as in Example 135-1.
Reaction SMILES: [O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[N:11][OH:12])[CH2:3][CH2:2]1.C1C=CC=CC=1.[CH2:19]([N:21]=[C:22]=[O:23])[CH3:20]>C(N(CC)CC)C>[CH2:19]([NH:21][C:22]([O:12][N:11]=[C:4]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=2[O:1][CH2:2][CH2:3]1)=[O:23])[CH3:20]
Reactant: ON=C1CCOc2ccccc21
Reactant: CCN=C=O
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: CCNC(=O)ON=C1CCOc2ccccc21
Reaction time: 8 h

Procedure:
4-Chromanone oxime (20 g, 0.12 mole) was added to benzene (260 ml) and refluxed for 45 min. in a flask equipped with a Dean-Stark trap. The solution was cooled to 25°-30°, triethylamine (0.5 ml) was added, followed by ethyl isocyanate (8.5 g, 0.12 mole). The solution was refluxed for 3 hrs. and stored overnight at room temperature. The mixture was filtered and the filtrate was stripped of solvent under reduced pressure. Anhydrous ether (100 ml) was added to the residue and the mixture was cooled for 3 hrs. The product was collected by filtration, yield: 20 g (79%). A sample was recrystallized from isopropanol, m.p. 110°-111°.
Reaction SMILES: C(N1[CH2:8][CH2:7][CH2:6][CH:5]([CH2:9][CH2:10][N:11]2[C:19]([O:20][CH3:21])=[N:18][C:17]3[C:12]2=[N:13][C:14]([O:23][C@@H:24](C)[CH2:25][CH2:26][CH3:27])=[N:15][C:16]=3[NH2:22])C1)C.C(OC1N=[C:41]2[C:37](N=[C:39](OC)[N:40]2[CH2:43][CH2:44]CCCC2CCCNC2)=[C:36](N)N=1)CCC.ICC>>[CH2:24]([O:23][C:14]1[N:13]=[C:12]2[C:17]([N:18]=[C:19]([O:20][CH3:21])[N:11]2[CH2:10][CH2:9][CH2:5][CH2:6][CH2:7][CH:8]2[CH2:36][CH2:37][CH2:41][N:40]([CH2:43][CH3:44])[CH2:39]2)=[C:16]([NH2:22])[N:15]=1)[CH2:25][CH2:26][CH3:27]
Reactant: CCC[C@H](C)Oc1nc(N)c2nc(OC)n(CCC3CCCN(CC)C3)c2n1
Reactant: CCCCOc1nc(N)c2nc(OC)n(CCCCCC3CCCNC3)c2n1
Solvent: CCI
Product: CCCCOc1nc(N)c2nc(OC)n(CCCCCC3CCCN(CC)C3)c2n1

Procedure:
Prepared similarly to Intermediate 46 from 2-(butyloxy)-8-(methyloxy)-9-[5-(3-piperidinyl)pentyl]-9H-purin-6-amine and 2-iodoethane.
Reaction SMILES: [SH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH2:21][CH2:20][CH2:19][N:11]3[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.[C:22](Cl)(=[O:24])[CH3:23]>C(Cl)Cl>[C:22]([S:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]3[CH2:21][CH2:20][CH2:19][N:11]3[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:6][CH:7]=1)(=[O:24])[CH3:23]
Reactant: Sc1ccc(-c2nc3n(c2-c2ccncc2)CCC3)cc1
Reactant: CC(=O)Cl
Solvent: ClCCl
Product: CC(=O)Sc1ccc(-c2nc3n(c2-c2ccncc2)CCC3)cc1
Reaction time: 0.5 h
Yield: 17.5 %

Procedure:
To 1.0 q (3.4 mmole) of 2-(4 mercaptophenyl)-(4 pyridyl)-6,7-dihydro [5H]-pyrrolo[1,2-a]imidazole prepared as in Example 16 in 50 ml methylene chloride at 0° C. was added a solution of 0.3 g (3.7 mmole, 0.26 ml) acetyl chloride in 10 ml CH2Cl2 over a period of 10 minutes. The reaction was allowed to come to room temperature and was stirred for 30 minutes. The mixture was then diluted with methylene chloride and washed with 3N NaHCO3, saturated NaCl, treated with Na2SO4, stripped, then flash chromatographed on silica with methylene chloride containing 1% to 5% MeOH. The isolated material was recrystallized twice from ethyl acetate to give 0.20 g of the titled compound. 17.6% yield, mp 216-217.5 152°-154° C. C19H17N3OS, Calculated, C: 68.03, H: 5.11, N: 12.53; Found, C: 68.25, H: 5.40, N: 12.14.
Reaction SMILES: [CH3:1][C:2]1[N:29]=[C:5]2[NH:6][C:7](=[O:28])[C:8]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]4[C:21]([C:26]#[N:27])=[CH:22][CH:23]=[CH:24][CH:25]=4)=[CH:16][CH:15]=3)=[C:9]([CH2:10][CH2:11][CH3:12])[N:4]2[N:3]=1.[CH3:30][C:31]1([CH2:35]O)[CH2:34][O:33][CH2:32]1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1.C(OCC)(=O)C>[CH3:1][C:2]1[N:29]=[C:5]2[N:6]([CH2:30][C:31]3([CH3:35])[CH2:34][O:33][CH2:32]3)[C:7](=[O:28])[C:8]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]4[C:21]([C:26]#[N:27])=[CH:22][CH:23]=[CH:24][CH:25]=4)=[CH:16][CH:15]=3)=[C:9]([CH2:10][CH2:11][CH3:12])[N:4]2[N:3]=1
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)[nH]c2nc(C)nn12
Reactant: CC1(CO)COC1
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(CC2(C)COC2)c2nc(C)nn12
Temperature: 25 °C
Reaction time: 16 h
Yield: 1.6 %

Procedure:
To a solution of 4′-[(2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (1.5 g), (3-methyloxetan-3-yl)methanol (0.6 g) and tributylphosphine (1.9 mL) in THF (80 mL) was added 1,1′-(azodicarbonyl)dipiperidine (1.9 g) under ice-cooling, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with 5% aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.03 g, 16%).
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[CH:6][N:7]=[C:8]([O:11][CH3:12])[CH:9]=2)[S:4][CH:3]=1.[Li]CCCC.CCCCCC.C(O[B:28]1[O:32][C:31]([CH3:34])([CH3:33])[C:30]([CH3:36])([CH3:35])[O:29]1)(C)C>C1COCC1>[CH3:12][O:11][C:8]1[CH:9]=[C:10]2[C:2]([B:28]3[O:32][C:31]([CH3:34])([CH3:33])[C:30]([CH3:36])([CH3:35])[O:29]3)=[CH:3][S:4][C:5]2=[CH:6][N:7]=1
Reactant: COc1cc2c(Br)csc2cn1
Reactant: CC(C)OB1OC(C)(C)C(C)(C)O1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COc1cc2c(B3OC(C)(C)C(C)(C)O3)csc2cn1
Temperature: -78 °C
Reaction time: 1 h
Yield: 37.7 %

Procedure:
To a cooled (−78° C.) solution of 3-bromo-5-methoxythieno[2,3-c]pyridine (14.7 mg, 0.0602 mmol) in THF (2.5 mL) was added dropwise 1.60 M n-BuLi in hexane (56.4 μL, 0.0903 mmol) in 5 min under an atmosphere of nitrogen. After stirring at −78° C. for 1 h, 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (18.8 μL, 0.0903 mmol) was added dropwise. The combined mixture was stirred at −78° C. for another 1 h. The temperature was then gradually raised to RT in 40 min. The reaction was then quenched by addition of MeOH (5 mL) and purified by ISCO chromatography (0 to 20% EtOAc:hexane) to afford 6.6 mg (38%) of the title compound as a light yellow solid. 1H NMR (400 MHz, dioxane-d8): δ 8.72 (d, J=1.2 Hz, 1 H), 8.29 (s, 1 H), 7.48 (d, J=0.8 Hz, 1 H), 3.93 (s, 3 H), 1.35 (s, 12 H); MS (ESI): 292.11 [M+H]+; HPLC tR=1.71 min (TOF: polar—3 min).
Reaction SMILES: [N+:1]([O-])([OH:3])=[O:2].[CH2:5]([O:12][C:13]1[CH:18]=[C:17](/[CH:19]=[CH:20]/[N+:21]([O-:23])=[O:22])[CH:16]=[CH:15][C:14]=1[O:24][CH3:25])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>C(O)(=O)C>[CH2:5]([O:12][C:13]1[CH:18]=[C:17](/[CH:19]=[CH:20]/[N+:21]([O-:23])=[O:22])[C:16]([N+:1]([O-:3])=[O:2])=[CH:15][C:14]=1[O:24][CH3:25])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: O=[N+]([O-])O
Reactant: COc1ccc(/C=C/[N+](=O)[O-])cc1OCc1ccccc1
Solvent: CC(=O)O
Product: COc1cc([N+](=O)[O-])c(/C=C/[N+](=O)[O-])cc1OCc1ccccc1
Temperature: 40 °C
Reaction time: 3 h
Yield: 91 %

Procedure:
69% Nitric acid (10 mL, 155 mmol) was added to a mixture of (E)-2-(benzyloxy)-1-methoxy-4-(2-nitrovinyl)benzene described in Production Example 1-1 (10 g, 35.1 mmol) and acetic acid (70 mL) under nitrogen atmosphere at 25° C., and the mixture was stirred at 40° C. for 3 hours. The reaction mixture was poured onto ice and the precipitate was collected by filteration and then washed with ethanol to obtain the title compound (10.5 g, 91%).