Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[N:10]=[CH:9][C:8]([C:11]2[N:12]([C:32]([N:34]3[CH2:39][CH2:38][CH:37]([CH2:40][C:41](O)=[O:42])[CH2:36][CH2:35]3)=[O:33])[C@@:13]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)([CH3:24])[C@@:14]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)([CH3:16])[N:15]=2)=[C:7]([O:44][CH2:45][CH3:46])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH:47]([C:50]1[CH:51]=[C:52]([CH:54]=[CH:55][CH:56]=1)[NH2:53])([CH3:49])[CH3:48]>>[C:1]([C:5]1[N:10]=[CH:9][C:8]([C:11]2[N:12]([C:32]([N:34]3[CH2:39][CH2:38][CH:37]([CH2:40][C:41]([NH:53][C:52]4[CH:54]=[CH:55][CH:56]=[C:50]([CH:47]([CH3:49])[CH3:48])[CH:51]=4)=[O:42])[CH2:36][CH2:35]3)=[O:33])[C@@:13]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)([CH3:24])[C@@:14]([C:17]3[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=3)([CH3:16])[N:15]=2)=[C:7]([O:44][CH2:45][CH3:46])[CH:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCC(CC(=O)O)CC1
Reactant: CC(C)c1cccc(N)c1
Product: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCC(CC(=O)Nc2cccc(C(C)C)c2)CC1

Procedure:
In a manner analogous to the method described in example 163, {1-[(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidin-4-yl}-acetic acid was reacted with 3-isopropylaniline (Aldrich) to give the title product. LC-MS (ES+) 782 [(M+H)+].
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([Cl:9])[C:3]=1[NH2:4].[NH:10]1[CH2:14][CH2:13][N:12]=[C:11]1S(O)(=O)=O.C(O)C(C)C>C(Cl)(Cl)Cl>[CH:7]1[CH:8]=[C:2]([Cl:1])[C:3]([NH:4][C:11]2[NH:12][CH2:13][CH2:14][N:10]=2)=[C:5]([Cl:9])[CH:6]=1
Reactant: O=S(=O)(O)C1=NCCN1
Reactant: Nc1c(Cl)cccc1Cl
Solvent: CC(C)CO
Solvent: ClC(Cl)Cl
Product: Clc1cccc(Cl)c1NC1=NCCN1
Temperature: 125 °C
Yield: 64 %

Procedure:
A mixture of 2,6-dichloroaniline (0.162 g, 1 mmol), imidazoline-2-sulfonic acid (0.30 g, 2 mmol) and isobutanol (3 ml) was heated to 125° C. and maintained at this temperature for 16 hours. The mixture was then cooled to room temperature, diluted with CHCl3 (10 ml) and washed twice with 2 ml of aqueous 1 N NaOH. The organic extracts were combined, dried over MgSO4 and concentrated in vacuo to yield a solid which was chromatographed (silica gel, 10:1 CHCl3 /CH3OH saturated with NH3 (g)) to yield 0.147 g (a yield of 64%) of the title compound as a white solid, which was characterized spectroscopically.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[Br:6][C:7]1[N:8]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([CH:27]3[CH2:29][CH2:28]3)=[CH:19][CH:18]=2)[C:9]([S:12][CH2:13][C:14]([OH:16])=[O:15])=[N:10][N:11]=1.[OH:30][CH:31]1[O:37][C@H:36]([C@@H:38]([CH2:40][OH:41])[OH:39])[C@H:34](O)[C@H:32]1[OH:33]>N1C=CC=CC=1>[Br:6][C:7]1[N:8]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([CH:27]3[CH2:29][CH2:28]3)=[CH:19][CH:18]=2)[C:9]([S:12][CH2:13][C:14]([O:16][CH:34]2[CH:32]([OH:33])[CH:31]([OH:30])[O:37][CH:36]2[CH:38]([OH:39])[CH2:40][OH:41])=[O:15])=[N:10][N:11]=1
Reactant: OC[C@@H](O)[C@H]1OC(O)[C@H](O)[C@H]1O
Reactant: O=C(O)CSc1nnc(Br)n1-c1ccc(C2CC2)c2ccccc12
Solvent: O=P(Cl)(Cl)Cl
Solvent: c1ccncc1
Product: O=C(CSc1nnc(Br)n1-c1ccc(C2CC2)c2ccccc12)OC1C(O)C(O)OC1C(O)CO
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Phosphorus oxychloride (2.4 mmol) is added dropwise over 5 mins to a solution of 2-(5-bromo-4-(1-cyclopropylnaphthalen-4-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid (810 mg, 2.0 mmol) in pyridine (20 mL) at 0° C. The mixture is stirred at 0° C. for a further 1 hour and then a solution of 1,2:5,6-Di-O-isopropilydene-□-D-glucofuranose (320 mg, 2.0 mmol) in pyridine (5 mL) is added dropwise over 5 mins. The mixture is stirred at 0° C. for a further 1 hour and 1 hour at 20° C. and then is quenched by addition of water (1 mL). Volatile solvents are removed in vacuo and DCM (200 mL) added. The organic phase is washed with water (1×50 mL), saturated sodium carbonate solution (1×50 mL) and brine (1×50 mL), dried over Na2SO4 and concentrated to dryness. Ethanol and water are added to produce a solid which is collected by filtration. Additional product is recovered by extraction of the filtrate with DCM. Combined product is concentrated, dried and purified by column chromatography (acetone/DCM eluent). The combined solids are dissolved in acetic acid (25 mL) and water (5 mL) mixture, heated at 60° C. for 3 hours. Volatile solvents are removed in vacuo. Ethanol and water are added to produce a solid which is collected by filtration.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.C(OC(OC(C)C)OC(C)C)(C)C.C1(S(O)(=O)=O)C=CC=CC=1.C(NC(C)C)(C)C.CON(C)[C:43](=[O:63])[C:44]1[CH:49]=[CH:48][C:47]([O:50][C:51]2[C:56]([CH:57]3[CH2:62][CH2:61][S:60][CH2:59][CH2:58]3)=[N:55][CH:54]=[CH:53][N:52]=2)=[CH:46][CH:45]=1.[Li+].CC([N-]C(C)C)C>C1(C)C=CC=CC=1.C1COCC1>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:43]([C:44]1[CH:49]=[CH:48][C:47]([O:50][C:51]2[C:56]([CH:57]3[CH2:62][CH2:61][S:60][CH2:59][CH2:58]3)=[N:55][CH:54]=[CH:53][N:52]=2)=[CH:46][CH:45]=1)=[O:63]
Reactant: c1ccc2[nH]cnc2c1
Reactant: CON(C)C(=O)c1ccc(Oc2nccnc2C2CCSCC2)cc1
Agent: CC(C)OC(OC(C)C)OC(C)C
Agent: CC(C)[N-]C(C)C
Agent: O=S(=O)(O)c1ccccc1
Solvent: CC(C)NC(C)C
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: O=C(c1ccc(Oc2nccnc2C2CCSCC2)cc1)c1nc2ccccc2[nH]1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
A mixture of 1H-benzo[d]imidazole (0.039 g, 0.334 mmol), triisopropoxymethane (0.529 g, 2.78 mmol), benzenesulfonic acid (2.200 mg, 0.014 mmol) in toluene (5 mL) was heated at reflux for 3 h. The mixture was cooled, neutralized with diisopropylamine (0.1 ml), concentrated to dryness and diluted with 1 ml THF. The above solution was added to a stirred mixture of N-methoxy-N-methyl-4-(3-(tetrahydro-2H-thiopyran-4-yl)pyrazin-2-yloxy)benzamide (0.100 g, 0.278 mmol) in THF (3 mL). The resulting mixture was cooled to 0° C. and LDA (0.167 mL, 0.334 mmol) was added dropwise. The reaction mixture was stirred at RT overnight, quenched with saturated NH4Cl, extracted with EtOAc (3×), dried over MgSO4, concentrated and purified by ISCO (0-5% MeOH/DCM) to give the title compound as a white solid. MS (ESI, pos. ion) m/z: 416.1 (M+1). IC50 (uM) +++++.
Reaction SMILES: [CH2:1]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][N:19]3[CH2:23][C:22]4([CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)[O:21][C:20]3=[O:29])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1)[CH:2]=C.NC(N)=S.C(Cl)Cl.C[OH:38]>C(=O)=O.CC(C)=O>[O:29]=[C:20]1[N:19]([CH2:18][C:15]2[CH:14]=[CH:13][C:12]([C:9]3[CH:8]=[CH:7][C:6]([CH2:5][O:4][CH2:1][CH:2]=[O:38])=[CH:11][CH:10]=3)=[CH:17][CH:16]=2)[CH2:23][C:22]2([CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[O:21]1
Reactant: C=CCOCc1ccc(-c2ccc(CN3CC4(CCCCC4)OC3=O)cc2)cc1
Reactant: CO
Agent: NC(N)=S
Agent: O=C=O
Solvent: ClCCl
Solvent: CC(C)=O
Product: O=CCOCc1ccc(-c2ccc(CN3CC4(CCCCC4)OC3=O)cc2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 41 %

Procedure:
3-(4′-Allyloxymethyl-biphenyl-4-ylmethyl)-1-oxa-3-aza-spiro[4.5]decan-2-one (200 mg, 0.51 mmol) was dissolved in DCM/methanol (4:1, 7.5 mL) and was cooled to −78° C. in dry ice-acetone bath. O3 was bubbled through the solution for 15 min. Thin layer chromatography (TLC) confirmed the completion of the reaction at this stage. Thiourea was added to the reaction mixture and stirred at low temperature for 0.5 hr. The cooling bath was removed and the reaction mixture was allowed to warm to room temperature, and stirred overnight. The reaction mixture was concentrated, and the residue was purified on silica gel eluting with 5˜20% ethyl acetate in hexane to give the product as a white solid (80 mg, 41%). 1H NMR (300 MHz, CDCl3): δ (ppm) 9.76 (s, 1H), 7.63 (m, 4H), 7.44 (d, 2H), 7.35 (d, 2H), 4.7 (s, 2H), 4.47 (s, 2H), 4.16 (s, 2H), 3.14 (s, 2H), 1.78 (m, 4H), 1.45 (m, 6H).
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]2[C:9]([N:10]([CH3:18])[C@H:11]([CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:12][OH:13])=[N:8][C:7]([S:19]CC3C=CC=CC=3)=[N:6][C:5]=2[N:27]=1.[Na].[NH4+].[Cl-]>>[NH2:1][C:2]1[S:3][C:4]2[C:9]([N:10]([CH3:18])[C@H:11]([CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:12][OH:13])=[N:8][C:7]([SH:19])=[N:6][C:5]=2[N:27]=1
Reactant: CC(C)C[C@H](CO)N(C)c1nc(SCc2ccccc2)nc2nc(N)sc12
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na]
Product: CC(C)C[C@H](CO)N(C)c1nc(S)nc2nc(N)sc12
Yield: 80.4 %

Procedure:
A three-neck round-bottomed flask was immersed in a dry ice/ethanol cooling bath and equipped with a dry ice/ethanol condenser. The system was flushed with nitrogen and ammonia (approximately 50 mL) was condensed into the flask. (2R)-2-[[2-Amino-5-(benzylthio)[1,3]thiazolo[4,5-d]pyrimidin-7-yl](methyl)amino]-4-methylpentan-1-ol (1 g, 2.5 mmol) was added to the flask, resulting in a clear yellow solution. Small pieces of sodium metal (size 2-3 mm) were added one by one to the reaction mixture. When a persistent blue colour (>20 sec) appeared, a spoon of solid NH4Cl was added to quench the reaction. The ammonia was evaporated off. Water (50 mL) was added and the mixture was neutralized with 1M HCl (aq.) to pH 7. The precipitated yellow solid was collected by filtration, washed with water and dried in vacuo to yield 630 mg of the title compound (80% yield).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH:5]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)[C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=1.[Cl:20][C:21]1[CH:36]=[CH:35][C:24]2[N:25]([CH:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)[C:26](=[O:28])[NH:27][C:23]=2[CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+].CC(C)CC(=O)C>O>[Cl:20][C:21]1[CH:36]=[CH:35][C:24]2[N:25]([CH:29]3[CH2:30][CH2:31][N:32]([CH2:2][CH2:3][CH2:4][CH:5]([C:13]4[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=4)[C:6]4[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=4)[CH2:33][CH2:34]3)[C:26](=[O:28])[NH:27][C:23]=2[CH:22]=1
Reactant: ClCCCC(c1ccc(Cl)cc1)c1ccc(Cl)cc1
Reactant: O=c1[nH]c2cc(Cl)ccc2n1C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)CC(C)C
Product: O=c1[nH]c2cc(Cl)ccc2n1C1CCN(CCCC(c2ccc(Cl)cc2)c2ccc(Cl)cc2)CC1

Procedure:
A mixture of 4.7 parts of 4-chloro-1,1'-butylidene bis[4-chlorobenzene], 3 parts of 5-chloro-1-(4-piperidyl)- 2-benzimidazolinone, 3.7 parts of sodium carbonate and 100 parts of 4-methyl-2-pentanone is stirred and refluxed overnight with water-separator. The reaction mixture is cooled, water is added and the layers are separated. The organic layer is dried, filtered and evaporated. The residue is purified by column-chromatography over silicagel, using a mixture of trichloromethane and 5% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from a mixture of 2-propanol and 2,2'-oxybispropane, yielding 5-chloro-1-{1-[4,4-bis(4-chlorophenyl)butyl]-4-piperidinyl}-1,3-dihydro-2H-benzimidazol-2-one; mp. 165.4° C.
Reaction SMILES: [Mn]([O-])(=O)(=O)=O.[K+].[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[CH:19]=[CH:18][C:17]([CH:20]([S:22]([CH2:24][C:25]([N:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)=[O:26])=[O:23])[CH3:21])=[CH:16][CH:15]=1.S(=O)(O)[O-:34].[Na+]>O.C(O)(=O)C.[O-2].[O-2].[Mn+4]>[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[CH:15]=[CH:16][C:17]([CH:20]([S:22]([CH2:24][C:25]([N:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)=[O:26])(=[O:34])=[O:23])[CH3:21])=[CH:18][CH:19]=1
Reactant: O=S([O-])O
Reactant: CC(c1ccc(-c2ccccc2F)cc1)S(=O)CC(=O)N1CCCCC1
Agent: O=[Mn](=O)(=O)[O-]
Agent: [Mn+4]
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Product: CC(c1ccc(-c2ccccc2F)cc1)S(=O)(=O)CC(=O)N1CCCCC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 65 %

Procedure:
A suspension of 2.1 gm (13.4 millimols) of potassium permanganate in 15 ml of water was added in small portions to a slution of 5.0 gm (13.4 millimols) of [1-(2'-fluoro-4-biphenylyl)-ethylsulfinyl]-acetic acid piperidide in 30 ml of glacial acetic acid. The temperature was maintained at 15°-20° C. The mixture was stirred for 1 hour at room temperature, then diluted with water, the manganese dioxide was reduced with sodium bisulfite, and the reaction product was extracted with ethyl acetate. After washing, drying and evaporation of the ethyl acetate extract, the residue was recrystallized from isopropanol. Yield: 65% of theory; m.p. 126° C.
Reaction SMILES: [OH-].[NH4+:2].S(F)([O:6][C:7](F)(F)[C:8]([F:14])([I:13])[C:9]([F:12])([F:11])[F:10])(=O)=O>C(Cl)Cl>[I:13][C:8]([F:14])([C:9]([F:12])([F:11])[F:10])[C:7]([NH2:2])=[O:6]
Reactant: [NH4+]
Reactant: O=S(=O)(F)OC(F)(F)C(F)(I)C(F)(F)F
Agent: [OH-]
Solvent: ClCCl
Product: NC(=O)C(F)(I)C(F)(F)F
Temperature: 12.5 °C
Yield: 68.3 %

Procedure:
Into a glass flask was placed a mixture of aqueous ammonium hydroxide (28 wt. %, 40.5 mL, 0.6 mol) and methylene chloride (80 mL) which was cooled to 10-15° C. 2-Iodohexafluoropropyl fluorosulfate from Experiment 5 (37.6 g, 0.1 mol) was added slowly with vigorous stirring while the reaction temperature was kept at <15° C. After addition, the mixture was warmed to ambient temperature, the bottom organic layer was separated, washed with aqueous sodium bisulfite solution, dried over MgSO4. The solvent was removed in vacuo to give the title product as a white solid (18.5 g, 68.3 % yield), mp. 75-77° C., 1H NMR (300 MHz, CDCl3): δ6.98, 6.53 (2 broad singlets); 19F NMR (188.24 MHz, CDCl3): -76.3 (2 singlets, 3F), -138.5 (m, 1F); IR: 1690 cm-1 (C=O); Anal. Calcd. for C3H2F4INO: C: 13.30, H: 0.74, F: 28.05, N: 5.17. Found: C: 13.68, H: 0.83, F: 28.43, N: 5.21. Mass. Calcd. for [M+ ]: 270.9117; Found: 270.9093.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:8][OH:9])[CH:5]=[N:6][CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].I[CH2:21][CH3:22].CN(C=O)C>C1COCC1.[Cl-].[Na+].O>[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][OH:9])[CH:5]=[N:6][CH:7]=1.[Br:1][C:2]1[CH:7]=[N:6][CH:5]=[C:4]([CH2:8][O:9][CH2:21][CH3:22])[CH:3]=1
Reactant: CCI
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: OCc1cncc(Br)c1
Agent: [Cl-]
Solvent: CN(C)C=O
Solvent: O
Solvent: C1CCOC1
Product: CCOCc1cncc(Br)c1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 120.4 %

Procedure:
(5-Bromopyridin-3-yl)methanol was prepared according to the published procedure (Zhang, N. et al, J. Med. Chem., 45, 2832–2840 (2002)). A solution of (5-bromopyridin-3-yl)methanol (7.39 g, 39.3 mmol) in THF was cooled to 0° C. Sodium bis(trimethylsilyl)amide (39.3 mL of a 1.0 M solution in THF) was added, and the reaction was stirred for 20 minutes. Iodoethane (3.46 mL, 43.2 mmol) and DMF were added, and the reaction was allowed to warm to ambient temperature and stirred overnight. Brine was added, and the aqueous layer was extracted twice with hexanes. The combined organic fractions were concentrated under reduced pressure, and the residue was purified by HPFC (eluting with hexanes:ethyl acetate in a gradient from 100:0 to 70:30) to provide 5.11 g of 3-bromo-5-ethoxymethylpyridine as a colorless oil.
Reaction SMILES: [N:1]([CH2:4][CH:5]1[O:21][C:8]2=[C:9]3[C:14](=[C:15]([CH3:17])[CH:16]=[C:7]2[CH2:6]1)[NH:13][C:12](=[O:18])[C:11]([CH3:19])=[C:10]3[CH3:20])=[N+]=[N-].[H][H]>O1CCCC1.CO.[Pd]>[NH2:1][CH2:4][CH:5]1[O:21][C:8]2=[C:9]3[C:14](=[C:15]([CH3:17])[CH:16]=[C:7]2[CH2:6]1)[NH:13][C:12](=[O:18])[C:11]([CH3:19])=[C:10]3[CH3:20]
Reactant: [H][H]
Reactant: Cc1c(C)c2c3c(cc(C)c2[nH]c1=O)CC(CN=[N+]=[N-])O3
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: Cc1c(C)c2c3c(cc(C)c2[nH]c1=O)CC(CN)O3
Yield: 69 %

Procedure:
The compound obtained in Example 255 (1.05 g, 3.69 mmol) was dissolved in a solvent mixture of tetrahydrofuran (50 ml) and methanol (20 ml). To the solution, 10% palladium-on-carbon (1 g) was added, followed by stirring at 50° C. for 4 hours in the atmosphere of hydrogen. The catalyst was removed by filtration, and the catalyst was evaporated under reduced pressure. As a result, 658 mg of the title compound was obtained as colorless powder (69.1%). The obtained powder was dissolved in methanol (20 ml), to which 4N-HCl in 1,4-dioxane (0.7 ml) was added. Recrystallization from chloroform--methanol--ether yielded 536 mg of the title compound as pale yellow powder (49.3%).
Reaction SMILES: [F:1][C:2]([F:8])([F:7])[S:3]([O-:6])(=[O:5])=[O:4].[CH3:9][C:10]1[Te:11][C:12]2[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=2[N+:14]=1[CH3:15].[CH3:20][N:21]([CH3:30])[C:22]1[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][CH:23]=1>C(O)C.N1CCCCC1>[F:1][C:2]([F:8])([F:7])[S:3]([O-:6])(=[O:5])=[O:4].[CH3:20][N:21]([CH3:30])[C:22]1[CH:29]=[CH:28][C:25]([CH:26]=[CH:9][C:10]2[Te:11][C:12]3[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=3[N+:14]=2[CH3:15])=[CH:24][CH:23]=1
Reactant: CN(C)c1ccc(C=O)cc1
Reactant: Cc1[te]c2ccccc2[n+]1C
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: CCO
Solvent: C1CCNCC1
Product: CN(C)c1ccc(C=Cc2[te]c3ccccc3[n+]2C)cc1

Procedure:
2,3-Dimethylbenzotellurazolium trifluoromethanesulfonate (Example 30) (0.80 g, 0.002 mole) and 4-dimethylaminobenzaldehyde (0.30 g, 0.002 mole) were heated together in ethanol (about 30 ml), with one drop of piperidine present, to boiling and maintained at boiling for ten minutes. An intense red color developed. The dye separated as crystals on cooling. After overnight chilling they were isolated by filtration and recrystallized from ethanol, using diethyl ether to aid in reprecipitation. Yield 0.21 g (19% of theory).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH3:22])[C:10]([NH:12][N:13]1[CH:17]=[CH:16][CH:15]=[C:14]1[C:18]([O:20]C)=O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:23][O:24][C:25]1[CH:37]=[CH:36][C:28]([CH2:29][N:30]2[CH:34]=[C:33]([NH2:35])[CH:32]=[N:31]2)=[CH:27][CH:26]=1>>[CH3:23][O:24][C:25]1[CH:26]=[CH:27][C:28]([CH2:29][N:30]2[CH:34]=[C:33]([NH:35][C:18]([C:14]3[N:13]([NH:12][C:10](=[O:11])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH3:22])[CH:17]=[CH:16][CH:15]=3)=[O:20])[CH:32]=[N:31]2)=[CH:36][CH:37]=1
Reactant: COc1ccc(Cn2cc(N)cn2)cc1
Reactant: COC(=O)c1cccn1NC(=O)[C@H](C)NC(=O)OC(C)(C)C
Product: COc1ccc(Cn2cc(NC(=O)c3cccn3NC(=O)[C@H](C)NC(=O)OC(C)(C)C)cn2)cc1
Yield: 73 %

Procedure:
This compound was prepared starting from (S)-methyl 1-(2-(tert-butoxycarbonylamino)propanamido)-1H-pyrrole-2-carboxylate (900 mg, 2.89 mmol) and 1-(4-methoxybenzyl)-1H-pyrazol-4-amine (1.24 g, 6.10 mmol) following the experimental procedure described in Preparation 27a to afford 1.02 g (100% purity, 73% yield) of the title compound after purification by flash chromatography (0% to 100% AcOEt/hexanes).
Reaction SMILES: [CH:1]([C:3]1[CH:20]=[CH:19][C:6]([O:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[CH2:14][C:15]([O:17][CH3:18])=[O:16])=[C:5]([CH3:21])[CH:4]=1)=[O:2].[BH4-].[Na+]>CO>[OH:2][CH2:1][C:3]1[CH:20]=[CH:19][C:6]([O:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[CH2:14][C:15]([O:17][CH3:18])=[O:16])=[C:5]([CH3:21])[CH:4]=1
Reactant: COC(=O)Cc1ccccc1Oc1ccc(C=O)cc1C
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COC(=O)Cc1ccccc1Oc1ccc(CO)cc1C
Yield: 65.5 %

Procedure:
A stirred solution of 1.00 g (3.52 mmol) of the product of Step A dissolved in 14 mL of methanol was treated with 0.067 g (1.8 mmol) of sodium borohydride at room-temperature. After 15 minutes the reaction mixture was partitioned between ethyl acetate and 1N hydrochloric acid, and the organic layer was separated. The product was washed with water, brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified on a silica gel flash chromatography column eluted with 30% ethyl acetate/hexane to afford 0.660 g (66%) of the title compound.
Reaction SMILES: [OH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.[N+:14]([C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20](O)=[CH:19][CH:18]=1)([O-:16])=[O:15]>>[N+:14]([C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]([O:1][C@@H:2]2[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]2)=[CH:19][CH:18]=1)([O-:16])=[O:15]
Reactant: O=[N+]([O-])c1ccc(O)c2ccccc12
Reactant: CC(C)(C)OC(=O)N1CC[C@H](O)C1
Product: CC(C)(C)OC(=O)N1CC[C@@H](Oc2ccc([N+](=O)[O-])c3ccccc23)C1
Yield: 49.1 %

Procedure:
The compound was prepared from tert-butyl (3S)-3-hydroxypyrrolidine-1-carboxylate (3.56 g, 19 mmol) and 4-nitro-1-naphthol (3 g, 15.9 mmol). Yield: 2.8 g (49%) of the title compound as yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.46 (d, J=7.03 Hz, 9H) 2.26-2.38 (m, 2H) 3.55-3.81 (m, 4H) 5.20 (br s, 1H) 6.77 (d, J=8.53 Hz, 1H) 7.59 (t, J=7.53 Hz, 1H) 7.72-7.76 (m, 1H) 8.32 (d, J=8.03 Hz, 1H) 8.37 (d, J=8.53 Hz, 1H) 8.76 (d, J=8.53 Hz, 1H). HPLC 95%, RT=2.775 min (System A1, 10-97% MeCN over 3 min).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][C:4]=1[O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26].[N:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH2:33][NH:34][C:35](=[O:37])[CH3:36].[H-].[Na+]>O1CCCC1>[C:35]([N:34]([CH2:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][N:27]=1)[C:7](=[O:8])[C:6]1[CH:10]=[CH:11][C:3]([O:2][CH3:1])=[C:4]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH:5]=1)(=[O:37])[CH3:36]
Reactant: CC(=O)NCc1ccccn1
Reactant: CCCCCCCCCCCCCCOc1cc(C(=O)Cl)ccc1OC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCCCCCCCCCCCCOc1cc(C(=O)N(Cc2ccccn2)C(C)=O)ccc1OC
Yield: 30.6 %

Procedure:
The title compound is prepared by the procedure of Example 27 using 1.19 g of product from Example 43, 0.490 g of product from Example 12, 0.157 g of washed 50% sodium hydride and 12 ml of tetrahydrofuran. The residue is purified by column chromatography (silica gel:35% ethyl acetate/hexane) to give 0.472 g of the desired product as yellow crystals.
Reaction SMILES: [N:1]([O-])=O.[Na+].[CH3:5][O:6][C:7]([C:9]1[S:13][CH:12]=[N:11][C:10]=1[NH2:14])=[O:8].[Sn](Cl)Cl>Cl>[CH3:5][O:6][C:7]([C:9]1[S:13][CH:12]=[N:11][C:10]=1[NH:14][NH2:1])=[O:8]
Reactant: O=N[O-]
Reactant: COC(=O)c1scnc1N
Agent: Cl
Agent: Cl[Sn]Cl
Agent: [Na+]
Product: COC(=O)c1scnc1NN
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 69.2 %

Procedure:
An aqueous solution (10 ml) of sodium nitrite (7.32 g) was added dropwise to a concentrated hydrochloric acid solution (90 ml) of 4-aminothiazole-5-carboxylic acid methyl ester (15.3 g) at 0-10° C. The mixture was then stirred at 0° C. for 30 minutes. To this mixture there was added dropwise a concentrated hydrochloric acid solution (100 ml) containing tin(II) chloride (73.2 g) at 0-10° C., and the mixture was stirred at the same temperature for 2 hours. The mixture was filtered and the filtrate was carefully added to a suspension of potassium carbonate and Celite in ethyl acetate (3 l) while stirring, with regular addition of potassium carbonate to prevent solution acidity. After adding the filtered substance to this ethyl acetate suspension, it was rendered basic with a 5N aqueous sodium hydroxide solution. The mixture was allowed to stand, and then most of the supernatant (organic layer A) was separated off. The remaining suspension was filtered through Celite and the filtrate was separated into organic layer B and aqueous layer A. Ethyl acetate (500 ml) and anhydrous magnesium sulfate were added to the filtered substance, and the mixture was stirred and then filtered. Aqueous layer A was re-extracted with the resulting filtrate. Washing of the filtered substance and re-extraction of aqueous layer A were repeated 4 times in the same manner. Organic layer A and organic layer B were combined with the obtained organic layer, and the mixture was dried over anhydrous magnesium sulfate. The desiccant was filtered out and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate-methanol system) to obtain the target compound (11.6 g) as an off-white solid.