Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].FC(F)(F)S(Cl)(=O)=O.FC(F)(F)S([O:16][CH2:17][C:18]([F:21])([F:20])[F:19])(=O)=O.[Cl:24][C:25]1[C:26]([CH3:43])=[C:27]([S:31]([NH:34][C:35]2[S:36][CH:37]=[C:38]([CH2:40][CH2:41]O)[N:39]=2)(=[O:33])=[O:32])[CH:28]=[CH:29][CH:30]=1.Cl>C1COCC1>[Cl:24][C:25]1[C:26]([CH3:43])=[C:27]([S:31]([NH:34][C:35]2[S:36][CH:37]=[C:38]([CH2:40][CH2:41][O:16][CH2:17][C:18]([F:19])([F:20])[F:21])[N:39]=2)(=[O:33])=[O:32])[CH:28]=[CH:29][CH:30]=1
Reactant: Cc1c(Cl)cccc1S(=O)(=O)Nc1nc(CCO)cs1
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Agent: Cl
Agent: O=S(=O)(Cl)C(F)(F)F
Agent: [H-]
Solvent: C1CCOC1
Product: Cc1c(Cl)cccc1S(=O)(=O)Nc1nc(CCOCC(F)(F)F)cs1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Sodium hydride (95% dry, 253 mg, 10.00 mmol) was added to a stirred solution of 2,2,2-tirluoroethanol (1.00 g, 10.00 mmol) in THF (15 mL) at 0° C. under nitrogen atmosphere. After stirring for 15 minutes at room temperature, the temperature was lowered to −80° C. using an ethanol-dry ice bath. Trifluoromethanesulfonyl chloride (1.69 g, 10.00 mmol) dissolved in THF (5 mL) was then added in small portions, and the mixture was then left to reach room temperature over night. The reaction mixture was centrifuged and the white precipitate was separated. The solvent was diluted with THF to 25 mL (assumed concentration: 0.4 M). The prepared 2,2,2-trifluoroethyl trifluoromethanesulfonate solution (7.5 mL, 0.4 M) was added to a mixture of EXAMPLE 181A (500 mg, 1.5 mmol) and sodium hydride (95% dry, 94 mg, 3.73 mmol) in THF (10 mL) at 0° C. under nitrogen atmosphere. After stirring at 0° C. for 1.5 h an additional amount of sodium hydride (95% dry, 76 mg, 3.00 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate solution (7.5 mL) was added. After 1 h at 0° C. was die mixture poured on to ice and neutralized with 2.0 M HCl and extracted with DCM. Evaporation of the organic solvent gave a residue which was purified by flash chromatography on silica gel eluting with a 2-5% acetone gradient in DCM. This gave 174 mg (28%) of a white solid: MS (Ionspray, [M+H]+) m/z 414. Anal. Calcd. (found) for C14H14ClF3N2O3S2: C, 40.5 (40.5)%; H, 3.4 (3.4)%; N, 6.7 (6.7)%.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:22])[CH:4]([C:13]1[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[CH:15][C:14]=1[Cl:21])[N:5]1[C:9]([CH2:10][CH2:11][OH:12])=[CH:8][N:7]=[CH:6]1.CCN(CC)CC.[CH3:30][S:31](Cl)(=[O:33])=[O:32]>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:22])[CH:4]([C:13]1[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[CH:15][C:14]=1[Cl:21])[N:5]1[C:9]([CH2:10][CH2:11][O:12][S:31]([CH3:30])(=[O:33])=[O:32])=[CH:8][N:7]=[CH:6]1
Reactant: COC(=O)C(c1ccc(C#N)cc1Cl)n1cncc1CCO
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)C(c1ccc(C#N)cc1Cl)n1cncc1CCOS(C)(=O)=O

Procedure:
The crude (2-chloro-4-cyanophenyl)-[5-(2-hydroxyethyl)imidazol-1-yl]acetic acid methyl ester (2.06 g, 6.46 mmol) is dissolved in CH2Cl2 (25 mL) and stirred at 0° C. before Et3N (1.4 mL, 9.69 mmol) and methanesulfonyl chloride (0.6 mL, 7.75 mmol) are added. After completion of the reaction, the solution is partitioned between CH2Cl2 and aqueous saturated NaHCO3. The organic layer is dried (Na2SO4) and evaporated to give the crude (2-chloro-4-cyanophenyl)-[5-(2-methanesulfonyloxyethyl)imidazol-1-yl]-acetic acid methyl ester that is used without further purification. MS (ESI) m/z 398.2, 400.2 (M+H).
Reaction SMILES: Cl[C:2]1[C:10]2[NH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[N:7][C:6]=2[C:5]([N+:15]([O-:17])=[O:16])=[CH:4][C:3]=1[C:18]([F:21])([F:20])[F:19].[Na].[CH:23]1([OH:29])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>>[CH:23]1([O:29][C:2]2[C:10]3[NH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[N:7][C:6]=3[C:5]([N+:15]([O-:17])=[O:16])=[CH:4][C:3]=2[C:18]([F:21])([F:20])[F:19])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1
Reactant: OC1CCCCC1
Reactant: O=[N+]([O-])c1cc(C(F)(F)F)c(Cl)c2[nH]c(C(F)(F)F)nc12
Agent: [Na]
Product: O=[N+]([O-])c1cc(C(F)(F)F)c(OC2CCCCC2)c2[nH]c(C(F)(F)F)nc12

Procedure:
4-Chloro-7-nitro-2,5-bis(trifluoromethyl)benzimidazole is reacted with the sodium sale of cyclohexanol to obtain 4-cyclohexyloxy-7-nitro-2,5-bis(trifluoromethyl)benzimidazole, m.w., 397.3.
Reaction SMILES: [OH:1][C@:2]1([C:30]([F:36])([F:35])[C:31]([F:34])([F:33])[F:32])[C@:18]2([CH3:19])[C@H:5]([C@H:6]3[C:15]([C@@H:16]([C:20]4[CH:25]=[CH:24][C:23]([C@H:26]([OH:28])[CH3:27])=[CH:22][CH:21]=4)[CH2:17]2)=[C:14]2[C:9](=[CH:10][C:11](=[O:29])[CH2:12][CH2:13]2)[CH2:8][CH2:7]3)[CH2:4][CH2:3]1.[CH2:37]([O:40][C:41]([NH:43][C@@H:44]([CH3:48])[C:45](O)=[O:46])=[O:42])[CH:38]=[CH2:39]>>[OH:1][C@:2]1([C:30]([F:35])([F:36])[C:31]([F:32])([F:33])[F:34])[C@:18]2([CH3:19])[C@H:5]([C@H:6]3[C:15]([C@@H:16]([C:20]4[CH:21]=[CH:22][C:23]([C@H:26]([O:28][C:45](=[O:46])[C@@H:44]([NH:43][C:41]([O:40][CH2:37][CH:38]=[CH2:39])=[O:42])[CH3:48])[CH3:27])=[CH:24][CH:25]=4)[CH2:17]2)=[C:14]2[C:9](=[CH:10][C:11](=[O:29])[CH2:12][CH2:13]2)[CH2:8][CH2:7]3)[CH2:4][CH2:3]1
Reactant: C=CCOC(=O)N[C@@H](C)C(=O)O
Reactant: C[C@@H](O)c1ccc([C@H]2C[C@@]3(C)[C@@H](CC[C@@]3(O)C(F)(F)C(F)(F)F)[C@@H]3CCC4=CC(=O)CCC4=C32)cc1
Product: C=CCOC(=O)N[C@@H](C)C(=O)O[C@H](C)c1ccc([C@H]2C[C@@]3(C)[C@@H](CC[C@@]3(O)C(F)(F)C(F)(F)F)[C@@H]3CCC4=CC(=O)CCC4=C32)cc1
Yield: 72 %

Procedure:
In analogy to Example 5, 150 mg (0.29 mmol) of (8S,11R,13S,14S,17S)-17-hydroxy-11-[4-((R)-1-hydroxyethyl)phenyl]-1 3-methyl-17-pentafluoroethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one were converted using (S)-2-allyloxycarbonylaminopropanoic acid and, after workup and purification, 140 mg (72%) of the title compound were isolated as a colourless foam.
Reaction SMILES: [NH2:1][C:2]1[C:3]([Cl:12])=[C:4]([C:8]([Cl:11])=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[Br:13]N1C(=O)CCC1=O>C(#N)C>[NH2:1][C:2]1[C:3]([Cl:12])=[C:4]([C:8]([Cl:11])=[CH:9][C:10]=1[Br:13])[C:5]([OH:7])=[O:6]
Reactant: Nc1ccc(Cl)c(C(=O)O)c1Cl
Reactant: O=C1CCC(=O)N1Br
Solvent: CC#N
Product: Nc1c(Br)cc(Cl)c(C(=O)O)c1Cl
Temperature: 90 °C
Reaction time: 0.75 h
Yield: 73.1 %

Procedure:
A mixture of 3-amino-2,6-dichloro-benzoic acid (5 g, 24 mmol, Step b) in acetonitrile (50 mL) was treated with N-bromosuccinimide (5.1 g, 29 mmol) and the reaction mixture was stirred at 90° C. for 45 minutes. Acetonitrile was removed under vacuum and the residue was partitioned between water (200 mL) and ethyl acetate (200 mL). Organic layer was separated and the aqueous layer was again extracted with ethyl acetate (2×100 mL). The combined organic layer was dried over anhydrous sodium sulphate and concentrated to yield 3-amino-4-bromo-2,6-dichloro-benzoic acid (5 g, 73%).
Reaction SMILES: Cl[C:2](=[O:8])[C:3]([O:5]CC)=O.[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([CH3:22])=[C:14]([NH:16][C:17]([NH:19][CH2:20][CH3:21])=[S:18])[CH:15]=1>C(Cl)(Cl)Cl>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([CH3:22])=[C:14]([N:16]2[C:2](=[O:8])[C:3](=[O:5])[N:19]([CH2:20][CH3:21])[C:17]2=[S:18])[CH:15]=1
Reactant: CCOC(=O)C(=O)Cl
Reactant: CCNC(=S)Nc1cc(Cl)ccc1C
Solvent: ClC(Cl)Cl
Product: CCN1C(=O)C(=O)N(c2cc(Cl)ccc2C)C1=S
Yield: 83.1 %

Procedure:
Ethyl chlorooxoacetate (12.3 g; 0.09 mol) was added dropwise to the solution N-(5-chloro-2-methylphenyl)-N′-ethylthiourea (13.7 g; 0.06 mol) in chloroform (300 mL). The mixture was heated at reflux for 3 hour then evaporated to dryness. The residue was dissolved in ethyl acetate (400 mL) and washed with saturated sodium bicarbonate solution (300 mL), then with water (300 mL). ). The organic phase was dried over anhydrous magnesium sulfate and evaporated to dryness. The residual solid was slurried in ether and filtered. The solid was washed with ether and air dried to give 1-(5-Chloro-2-methylphenyl)-3-ethyl-2-thioxo-4,5-imidazolidinedione (14.1 g), m.p. 173–174° C. Mass spectrum; (El, M.+) m/z 382/384. 1 H-NMR (DMSO-d6; 300 MHz): δ 7.49–7.40 (m, 3H), 3.92 (m, 2H), 2.15 (s, 3H), and 1.23 ppm (t, 3H).
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([I:10])=[C:7]([OH:9])[CH:8]=1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].I[CH:18]([CH3:20])[CH3:19]>O>[CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([I:10])=[C:7]([O:9][CH:18]([CH3:20])[CH3:19])[CH:8]=1)[CH3:2]
Reactant: CCc1ccc(I)c(O)c1
Reactant: CC(C)I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: CCc1ccc(I)c(OC(C)C)c1
Temperature: 25 °C
Yield: 80.1 %

Procedure:
A mixture of 5-ethyl-2-iodophenol (1.0 g, 4 mmol), potassium carbonate (1.10 g, 8 mmol) and 2-iodopropane (0.80 mL, 8 mmol) was heated at reflux for 6 h. The reaction mixture was cooled to room temperature and water was added. The mixture was extracted with diethyl ether. The combined organic extracts were washed with brine and dried over anhydrous magnesium sulfate. The solid was then filtered off, and the filtrate was concentrated in vacuo. Purification of the residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with hexanes, 5% ethyl acetate in hexanes yielded 4-ethyl-1-iodo-2-isopropoxy-benzene (0.93 g, 80%).
Reaction SMILES: [CH:1]1([CH2:7][C:8]2[CH:33]=[CH:32][C:11]([CH2:12][O:13][C:14]3[CH:22]=[CH:21][C:20]4[NH:19][C:18]5[CH:23]([CH2:26][C:27]([O:29]CC)=[O:28])[CH2:24][CH2:25][C:17]=5[C:16]=4[CH:15]=3)=[CH:10][C:9]=2[C:34]([F:37])([F:36])[F:35])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].[OH-]>O1CCOCC1>[CH:1]1([CH2:7][C:8]2[CH:33]=[CH:32][C:11]([CH2:12][O:13][C:14]3[CH:22]=[CH:21][C:20]4[NH:19][C:18]5[CH:23]([CH2:26][C:27]([OH:29])=[O:28])[CH2:24][CH2:25][C:17]=5[C:16]=4[CH:15]=3)=[CH:10][C:9]=2[C:34]([F:37])([F:35])[F:36])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CCOC(=O)CC1CCc2c1[nH]c1ccc(OCc3ccc(CC4CCCCC4)c(C(F)(F)F)c3)cc21
Agent: [Li+]
Agent: [OH-]
Solvent: C1COCCO1
Product: O=C(O)CC1CCc2c1[nH]c1ccc(OCc3ccc(CC4CCCCC4)c(C(F)(F)F)c3)cc21
Temperature: 25 °C
Reaction time: 5 h
Yield: 51.5 %

Procedure:
To a stirred solution of ethyl 2-(7-(4-(cyclohexylmethyl)-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate (40 mg, 0.078 mmol) in dioxane was added 1 M LiOH aqueous solution (0.39 mL, 0.39 mmol). The reaction mixture was stirred at room temperature for 5 h. The solvent was partly removed, then diluted with water, acidified with HCl solution. The pinkish solid was collect and dried to give the title compound (19.5 mg). LCMS m/z=486.3 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 0.96-1.06 (m, 2H), 1.14-1.22 (m, 3H), 1.55-1.70 (m, 6H), 2.05-2.10 (m, 1H), 2.40 (dd, J=16.0 and 9.0 Hz, 1H), 2.62-2.75 (m, 6H), 3.42-3.50 (m, 1H), 5.12 (s, 2H), 6.72 (dd, J=8.7 and 2.4 Hz, 1H), 6.94 (d, J=2.4 Hz, 1H), 7.21 (d, J=8.8 Hz, 1H), 7.45 (d, J=8.0 Hz, 1H), 7.66 (d, J=7.8 Hz, 1H), 7.75 (s, 1H), 10.48 (s, 1H), 12.20 (br, 1H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:18]2[C:13](=[CH:14][C:15]([F:21])=[C:16](F)[C:17]=2[F:19])[C:12](=[O:22])[C:11]([C:23]([OH:25])=[O:24])=[CH:10]1.[CH2:26]([NH:28][CH2:29][CH2:30][CH:31]1[O:36][CH2:35][CH2:34][NH:33][CH2:32]1)[CH3:27]>>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:18]2[C:13](=[CH:14][C:15]([F:21])=[C:16]([N:33]3[CH2:34][CH2:35][O:36][CH:31]([CH2:30][CH2:29][NH:28][CH2:26][CH3:27])[CH2:32]3)[C:17]=2[F:19])[C:12](=[O:22])[C:11]([C:23]([OH:25])=[O:24])=[CH:10]1
Reactant: O=C(O)c1cn(-c2ccc(F)cc2F)c2c(F)c(F)c(F)cc2c1=O
Reactant: CCNCCC1CNCCO1
Product: CCNCCC1CN(c2c(F)cc3c(=O)c(C(=O)O)cn(-c4ccc(F)cc4F)c3c2F)CCO1

Procedure:
By the use of 1-(2,4-difluorophenyl)-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid and 2-(2ethylaminoethyl)morpholine, the reaction is similarly carried out as Example 26 to give 1-(2,4-difluorophenyl)-7-[2-(2ethylaminoethyl)morpholino]-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid.
Reaction SMILES: [C:1]([N:5]1[C:9](=[O:10])[CH:8]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][C@H:18]([NH:27][C:28](=[O:49])[C@@H:29]([NH:37][C:38](=[O:48])[CH2:39][C:40]3[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=3)[CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:19]([NH:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[O:20])=[CH:13][CH:12]=2)[S:6]1(=[O:51])=[O:50])([CH3:4])([CH3:3])[CH3:2]>C(O)C.CO.ClCCl.[Pd].[O-]S([O-])(=O)=O.[Ba+2]>[C:1]([N:5]1[C:9](=[O:10])[CH2:8][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][C@H:18]([NH:27][C:28](=[O:49])[C@@H:29]([NH:37][C:38](=[O:48])[CH2:39][C:40]3[CH:41]=[CH:42][C:43]([O:46][CH3:47])=[CH:44][CH:45]=3)[CH2:30][C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:19]([NH:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[O:20])=[CH:13][CH:12]=2)[S:6]1(=[O:51])=[O:50])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCCCCNC(=O)[C@H](Cc1ccc(C2=CC(=O)N(C(C)(C)C)S2(=O)=O)cc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)Cc1ccc(OC)cc1
Agent: [Pd]
Agent: O=S(=O)([O-])[O-]
Agent: [Ba+2]
Solvent: ClCCl
Solvent: CO
Solvent: CCO
Product: CCCCCNC(=O)[C@H](Cc1ccc(C2CC(=O)N(C(C)(C)C)S2(=O)=O)cc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)Cc1ccc(OC)cc1
Yield: 95.4 %

Procedure:
A solution of 401-A (50 mg, 0.07 mmol) and 5% Pd/BaSO4 (5 mg, 10 wt %) in ethanol (1.5 mL), methanol (1.0 mL) and dichloromethane (2 drops) was stirred under an atmosphere of hydrogen for 5 h. The reaction mixture was filtered and concentrated to yield the 401-B (48 mg, 96%) as a white solid. 1H NMR (500 MHz, CDCl3): δ 7.30–7.26 (m, 4H), 7.22–7.16 (m, 4H), 7.00–6.94 (m, 4H), 6.85–6.81 (m, 2H), 6.43 (dd, J=8.3, 4.9 Hz, 1H), 5.90–5.84 (m, 1H), 5.79 (dd, J=8.8, 6.8 Hz, 1H), 4.75 (ddd, J=10.7, 9.3, 2.0 Hz, 1H), 4.61–4.57 (m, 1H), 4.50 (dd, J=12.2, 6.3 Hz, 1H), 3.82 (s, 3H), 3.43–3.35 (m, 2H), 3.22–3.09 (m, 4H), 3.05–3.03 (m, 1H), 3.00–2.90 (m, 1H), 2.90–2.80 (m, 1H), 1.66 (s, 9H), 1.40–1.35 (m, 2H), 1.35–1.23 (m, 2H), 1.23–1.17 (m, 2H), 0.88 (t, J=7.1 Hz, 3H); LCMS found for C39H51N4O7S (M+H)+: m/z=719.
Reaction SMILES: C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O.[C:12]([O:20][C@@H:21]1[C@H:27]([O:28][C:29](=[O:36])[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@@H:26]([O:37][C:38](=[O:45])[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C@H:25]([CH3:46])[O:24][CH:22]1[OH:23])(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CCOCC>C(Cl)Cl>[C:12]([O:20][C@@H:21]1[C@H:27]([O:28][C:29](=[O:36])[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@@H:26]([O:37][C:38](=[O:45])[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[C@H:25]([CH3:46])[O:24][C:22]1=[O:23])(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: C[C@@H]1OC(O)[C@H](OC(=O)c2ccccc2)[C@H](OC(=O)c2ccccc2)[C@H]1OC(=O)c1ccccc1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: CCOCC
Solvent: ClCCl
Product: C[C@@H]1OC(=O)[C@H](OC(=O)c2ccccc2)[C@H](OC(=O)c2ccccc2)[C@H]1OC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 84.9 %

Procedure:
PCC (30 g, 0.139 mmol) and well-dried 4 Å molecular shives (25 g) are added into a flask under N2 current. Dry CH2Cl2 (250 ml) is added to the flask and the flask is stirred for 1 hour at a room temperature and cooled to 0° C. The compound (VI) (16 g, 33.6 mmol) dissolved in dry CH2Cl2 (250 ml) is added to and stirred 4 hours at a room temperature. The reaction is finished with adding cool Et2O (200 ml) and filtered by silica gel. The solvent is vacuum concentrated, and then the compound (VII) (13.54 g, 85%) is isolated using flash column chromatography (toluene/EtOAc, 10:1, v/v).
Reaction SMILES: [CH2:1]([CH:3]([CH2:32][CH2:33][CH2:34][CH3:35])[CH2:4][Si:5]1([CH2:24][CH:25]([CH2:30][CH3:31])[CH2:26][CH2:27][CH2:28][CH3:29])[C:9]2[CH:10]=[C:11]([Si](C)(C)C)[S:12][C:8]=2[C:7]2[S:17][C:18]([Si](C)(C)C)=[CH:19][C:6]1=2)[CH3:2].FC(F)(F)C(O)=O.O>C(Cl)(Cl)Cl>[CH2:30]([CH:25]([CH2:26][CH2:27][CH2:28][CH3:29])[CH2:24][Si:5]1([CH2:4][CH:3]([CH2:1][CH3:2])[CH2:32][CH2:33][CH2:34][CH3:35])[C:9]2[CH:10]=[CH:11][S:12][C:8]=2[C:7]2[S:17][CH:18]=[CH:19][C:6]1=2)[CH3:31]
Reactant: CCCCC(CC)C[Si]1(CC(CC)CCCC)c2cc([Si](C)(C)C)sc2-c2sc([Si](C)(C)C)cc21
Solvent: ClC(Cl)Cl
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: CCCCC(CC)C[Si]1(CC(CC)CCCC)c2ccsc2-c2sccc21
Reaction time: 3.5 h
Yield: 94 %

Procedure:
4,4-bis(2-ethylhexyl)-2,6-bis(trimethylsilyl)-dithieno[3,2-b:2′,3′-d]silole (Compound G1, synthesized in accordance with Non-patent Document J. Am. Chem. Soc. 2008, 130, 16144-16145, 1.03 g, 1.786 mmol) was placed in a 200 mL four-necked recovery flask in a nitrogen atmosphere, and dissolved in chloroform (50 mL). Trifluoroacetic acid (0.265 mL, 3.573 mmol) was added dropwise, and the mixture was agitated for about 3.5 hours. Water was added to the reaction solution, and the lower layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressure. This was dissolved in hexane and subjected to silica gel column chromatography (solvent: hexane) to obtain 4,4-bis(2-ethylhexyl)-dithieno[3,2-b:2′,3′-d]silole (Compound G2) as a light yellow oily substance (702 mg, yield 94%).
Reaction SMILES: C([N:4]([CH:7]([CH3:9])[CH3:8])CC)(C)C.[Cl:10][C:11]1[N:16]=[C:15]([C:17]2[S:21][C:20]3[CH:22]=[CH:23][CH:24]=[C:25]([C:26]([OH:28])=O)[C:19]=3[CH:18]=2)[C:14]([Cl:29])=[CH:13][N:12]=1.C1(N)CC1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>ClCCl.C(OCC)C>[CH:7]1([NH:4][C:26]([C:25]2[C:19]3[CH:18]=[C:17]([C:15]4[C:14]([Cl:29])=[CH:13][N:12]=[C:11]([Cl:10])[N:16]=4)[S:21][C:20]=3[CH:22]=[CH:23][CH:24]=2)=[O:28])[CH2:9][CH2:8]1
Reactant: CCN(C(C)C)C(C)C
Reactant: O=C(O)c1cccc2sc(-c3nc(Cl)ncc3Cl)cc12
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: NC1CC1
Solvent: CCOCC
Solvent: ClCCl
Product: O=C(NC1CC1)c1cccc2sc(-c3nc(Cl)ncc3Cl)cc12
Temperature: 0 °C
Reaction time: 2 h

Procedure:
Diisopropylethylamine (1.42 mL) is added to a stirred suspension of 2-(2,5-dichloro-pyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid (2.55 g, 7.84 mmol) in anhydrous dichloromethane (40 mL) at 0° C. under nitrogen to form a solution, followed by sequentially addition of cyclopropylamine (0.570 mL, 8.23 mmol) and powdered 1H-benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (3.64 g, 8.23 mmol). The resultant mixture is allowed to stir at 0° C. for 2 hours, then at ambient temperature for 3 hours. Diethyl ether (35 mL) is added in small portions to the mixture, the mixture is stirred for another 20 minutes before filtration. After drying, the crude title compound (2.45 g) is obtained as a tan solid. It is used without further purification.
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][C:7]([O:8][C:9]2[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:18]([S-:20])#[N:19].[K+].BrBr.[NH4+].[OH-]>CC(O)=O.O>[N+:1]([C:4]1[CH:17]=[CH:16][C:7]([O:8][C:9]2[CH:15]=[CH:14][C:12]3[N:13]=[C:18]([NH2:19])[S:20][C:11]=3[CH:10]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: N#C[S-]
Reactant: Nc1ccc(Oc2ccc([N+](=O)[O-])cc2)cc1
Agent: BrBr
Agent: [K+]
Agent: [NH4+]
Solvent: O
Solvent: CC(=O)O
Product: Nc1nc2ccc(Oc3ccc([N+](=O)[O-])cc3)cc2s1
Temperature: 0 °C
Reaction time: 8 h
Yield: 65.5 %

Procedure:
To a solution of 4-(4-nitrophenoxy)aniline (Intermediate 10–1.15 g, 5.0 mmol) in AcOH (5 mL) was added KSCN (729 mg, 7.5 mmol). The mixture was cooled to 0° C. and added a solution of Br2 (256 μL, 5.0 mmol) in AcOH (6 mL) then stirred at room temperature overnight. The mixture was poured into H2O, basified with NH4OH (aq), then extracted with ethyl acetate. The organic layer was washed with water and brine, dried over Na2SO4 then evaporated. Sequence purification on SiO2 column chromatography gave Intermediate 10A (941.5 mg, 66%): MS m/e 288 (M+1) and Intermediate 10B (223.7 mg, 12%): MS m/e 366, 368 (M+1).
Reaction SMILES: Cl[CH2:2][C:3]1[N:15]2[C:6]([C:7]3[CH:8]=[C:9]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:10]([C:16]4[CH:30]=[CH:29][C:19]([CH2:20][NH:21]C(=O)OC(C)(C)C)=[CH:18][CH:17]=4)=[N:11][C:12]=3[CH:13]=[CH:14]2)=[N:5][N:4]=1.[NH:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1>CS(C)=O>[C:31]1([C:9]2[C:10]([C:16]3[CH:17]=[CH:18][C:19]([CH2:20][NH2:21])=[CH:29][CH:30]=3)=[N:11][C:12]3[CH:13]=[CH:14][N:15]4[C:3]([CH2:2][N:37]5[CH2:41][CH2:40][CH2:39][CH2:38]5)=[N:4][N:5]=[C:6]4[C:7]=3[CH:8]=2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: C1CCNC1
Reactant: CC(C)(C)OC(=O)NCc1ccc(-c2nc3ccn4c(CCl)nnc4c3cc2-c2ccccc2)cc1
Solvent: CS(C)=O
Product: NCc1ccc(-c2nc3ccn4c(CN5CCCC5)nnc4c3cc2-c2ccccc2)cc1
Temperature: 150 °C
Reaction time: 24 h

Procedure:
To a solution of 26-1 (0.05 g, 0.1 mmol) in DMSO (1 ml) was added pyrrolidine. The solution was heated at 150° C. for 30 min. The reaction mixture was purified using reverse phase HPLC. The residue was dissolved in MeOH (0.5 ml) and was treated with 1N HCl (0.4 ml). The reaction mixture was stirred at 35° C. for 1 day. Solvent removal afforded the desired product 26-2 as a solid.
Reaction SMILES: FC(F)(F)C(O)=O.[S:8]([O:12][N:13]1[C:19](=[O:20])[N:18]2[CH2:21][CH:14]1[CH2:15][CH2:16][CH:17]2[CH2:22][NH2:23])([OH:11])(=[O:10])=[O:9]>C(O)(C)C.O>[S:8]([O:12][N:13]1[C:19](=[O:20])[N:18]2[CH2:21][C@H:14]1[CH2:15][CH2:16][C@H:17]2[CH2:22][NH2:23])([OH:11])(=[O:9])=[O:10]
Reactant: NCC1CCC2CN1C(=O)N2OS(=O)(=O)O
Solvent: O
Solvent: O=C(O)C(F)(F)F
Solvent: CC(C)O
Product: NC[C@@H]1CC[C@@H]2CN1C(=O)N2OS(=O)(=O)O

Procedure:
The compound of Formula (IX) was reacted with trifluoroacetic acid in a suitable solvent such as dichloromethane to provide trifluoroacetic acid and sodium salt of 6-sulfooxy-2-(amino methyl)-7-oxo-1,6-diazabicyclo[3.2.1]octane (X). This trifluoroacetic acid and sodium salt (X) was further treated with water isopropyl alcohol mixture to obtain zwitterion form, (2S, 5R)-6-sulfooxy-2-(aminomethyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane (XI).
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([NH2:10])=[NH:9])=[CH:6][CH:5]=1.[Na].[N:14]([CH2:17][C:18]1[CH:19]=[C:20]([CH:25]=[CH:26][CH:27]=1)[C:21]([NH:23]N)=O)=[N+:15]=[N-:16]>C(O)C>[N:14]([CH2:17][C:18]1[CH:19]=[C:20]([C:21]2[N:10]=[C:8]([C:7]3[CH:11]=[CH:12][C:4]([O:3][CH3:2])=[CH:5][CH:6]=3)[NH:9][N:23]=2)[CH:25]=[CH:26][CH:27]=1)=[N+:15]=[N-:16]
Reactant: COc1ccc(C(=N)N)cc1
Reactant: [N-]=[N+]=NCc1cccc(C(=O)NN)c1
Agent: Cl
Agent: [Na]
Solvent: CCO
Product: COc1ccc(-c2nc(-c3cccc(CN=[N+]=[N-])c3)n[nH]2)cc1
Reaction time: 0.5 h
Yield: 56.7 %

Procedure:
To an ethanolic suspension of 4-methoxybenzamidine hydrochloride salt (1:1) (2.01 g, 10.8 mmol, 1.5 eq.) was added sodium (331 mg, 14.4 mmol, 2 eq.) in ethanol (60 ml), stirring was then continued for 30 min. at r.t. 3-azidomethyl-benzoic acid hydrazide (1.37 g, 7.2 mmol) in ethanol was then added at 20° C. and the mixture heated at reflux for 18 hrs. Upon cooling the product mixture was filtered, the solvent was evaporated and the residue chromatographed over 20 g SiO2 (Merck 230-400 mesh) with CH2Cl2, affording a solid after evaporation of the solvent. The residue was dried under high vacuum overnight at 20° C. affording the title compound (1.25 g, 57% yield) as a white solid. MS: m/e=306 (M+).
Reaction SMILES: [C:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]2[N:9]([CH2:22][CH3:23])[C:10]3[C:15]([C:16]=2[CH:17]=1)=[CH:14][C:13]([O:18][C:19](=O)[CH3:20])=[CH:12][CH:11]=3)(=O)[CH3:2].[ClH:24].C([N:27]([CH2:31][CH3:32])[CH2:28][CH2:29][Cl:30])C.C[O-].[Na+]>ClC1C=CC=CC=1>[ClH:30].[ClH:24].[CH2:31]([N:27]([CH2:28][CH3:29])[CH2:2][CH2:1][O:4][C:5]1[CH:17]=[CH:16][C:8]2[N:9]([CH2:22][CH3:23])[C:10]3[C:11]([C:7]=2[CH:6]=1)=[CH:12][C:13]([O:18][CH2:19][CH2:20][N:9]([CH2:10][CH3:11])[CH2:8][CH3:7])=[CH:14][CH:15]=3)[CH3:32]
Reactant: CCN(CC)CCCl
Reactant: CCn1c2ccc(OC(C)=O)cc2c2cc(OC(C)=O)ccc21
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: Clc1ccccc1
Product: CCN(CC)CCOc1ccc2c(c1)c1cc(OCCN(CC)CC)ccc1n2CC

Procedure:
A mixture of 15.5 g (0.05 mole) of N-ethyl-3,6-carbazolediol diacetate, 17.2 g (0.1 mole) of 2-diethylaminoethylchloride hydrochloride, 10.8 g (0.2 mole) of sodium methoxide and 400 ml of chlorobenzene is refluxed for 24 hours. Upon cooling, the reaction mixture is filtered, and the filtrate is washed with several portions of water, dried over anhydrous magnesium sulfate, diluted with ether and acidified with ethereal HCl. The resulting precipitate is separated and recrystallized from methanol-ethyl acetate to give 3,6-bis(2-diethylaminoethoxy)-N-ethylcarbazole dihydrochloride. M.P. 208°-210°C.