Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:2]=1[CH:3]=[C:4]1[CH2:13][C@@H:12]([C:14](OC3(C)CCC(C(C)C)CC3)=[O:15])[CH2:11][CH2:10][N:5]12.[H-].[Al+3].[Li+].[H-].[H-].[H-].C(OCC)(=O)C.Cl>O1CCCC1.O>[OH:15][CH2:14][C@H:12]1[CH2:11][CH2:10][N:5]2[C:6]3[C:2]([CH:3]=[C:4]2[CH2:13]1)=[CH:1][CH:9]=[CH:8][CH:7]=3
Reactant: CC(C)C1CCC(C)(OC(=O)[C@H]2CCn3c(cc4ccccc43)C2)CC1
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: OC[C@H]1CCn2c(cc3ccccc32)C1
Reaction time: 0.17 h

Procedure:
A solution of 0.8 g (2.27 mmol) of 1-menthyl 6,7,8,9tetrahydropyrido[1,2-a]indole-8(S)-carboxylate in 15 ml of dry tetrahydrofuran was treated dropwise under a nitrogen atmosphere with 2 ml (2 mmol) of 1M lithium aluminum hydride. After 10 minutes, the mixture was cooled in ice, treated successively with 5 ml of ethyl acetate and 30 ml of water and acidified with 1M hydrochloric acid. The mixture was extracted three times with diethyl ether and the combined extracts were dried over sodium sulfate and evaporated. Flash chromatography on silica gel using ethyl acetate/hexane (1:1) for the elution gave (S)-8-(hydroxymethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indole as a white solid which was dissolved in 5 ml of dichloromethane. Then, 0.43 g (4.21 mmol) of acetic anhydride and 0.9 ml (6.5 mmol) of triethylamine were added and the solution was left to stand for 17 hours. The solvent was evaporated. The residue was partitioned between 5% aqueous sodium bicarbonate solution and diethyl ether. The organic phase was dried over sodium sulfate and evaporated. The residue was crystallized from aqueous ethanol to give 0.518 g (94%) of (S)-8-(acetoxymethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indole as a white solid of melting point 63°-64° C.; [α]589 ;20 =43.7° (c=1% in chloroform).
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([NH:9][CH3:10])=[C:4]([NH:11][C:12](=O)[CH2:13][CH3:14])[CH:3]=1>Cl.CC(O)=O>[Br:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]2[N:9]([CH3:10])[C:12]([CH2:13][CH3:14])=[N:11][C:4]=2[CH:3]=1
Reactant: CCC(=O)Nc1cc(Br)nc(Cl)c1NC
Agent: Cl
Solvent: CC(=O)O
Product: CCc1nc2cc(Br)nc(Cl)c2n1C
Temperature: 100 °C
Reaction time: 2 h

Procedure:
N-(6-bromo-2-chloro-3-(methylamino)pyridin-4-yl)propionamide 2.78 (213 mg, 0.73 mmol) was dissolved in a mixture of HCl (37% aqueous solution) and AcOH 1:5 (12 mL) and the mixture was heated in a sealed tube at 100° C. After 2 h, LC/MS indicated full conversion to desired product. Reaction mixture was evaporated under reduced pressure. Solids were suspended and stirred for 10 min in a basic aqueous solution of NaHCO3 Solids were collected by filtration to isolate 6-bromo-4-chloro-2-ethyl-3-methyl-3H-imidazo[4,5-c]pyridine 2.79. LCMS found for C9H9BrClN3 as (M+H)+ 273.9.
Reaction SMILES: C(OC(=O)[CH:5]([C:11]1[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][CH:14]=[CH:13][N:12]=1)C(OCC)=O)C.Cl>O>[CH3:5][C:11]1[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][CH:14]=[CH:13][N:12]=1
Reactant: CCOC(=O)C(C(=O)OCC)c1ncccc1[N+](=O)[O-]
Agent: Cl
Solvent: O
Product: Cc1ncccc1[N+](=O)[O-]
Temperature: 100 °C
Reaction time: 3 h

Procedure:
A mixture of 43 g (115 mmol) of diethyl(3-nitropyridin-2-yl)malonate (purity approximately 75%; Example 3.a) and 150 ml of 18% strength hydrochloric acid was stirred for 3 hours at 100 ° C. After the mixture had cooled to room temperature (approximately 25° C.), it was diluted with water and extracted using tert-butyl methyl ether. The aqueous phase was evaporated under reduced pressure, and the resulting crystalline residue was taken up in (aqueous) Na2CO3 solution. The Na2CO3 solution was extracted repeatedly using methylene chloride. The organic phases were combined, washed and dried, and the solvent was removed under reduced pressure. This gave 10 g (79%) of the title compound as a yellow oil.
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[CH2:7][NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][C:10]=1[NH2:17])([CH3:4])([CH3:3])[CH3:2].[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH:29]([O:32][C:33]2[CH:38]=[CH:37][C:36]([N:39]([CH2:50][C:51](O)=[O:52])[C:40]([O:42][CH2:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[O:41])=[CH:35][CH:34]=2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].C(OC(N1C2C(=CC=CC=2)C=CC1OCC)=O)C>C(Cl)(Cl)Cl>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH:29]([O:32][C:33]2[CH:38]=[CH:37][C:36]([N:39]([C:40]([O:42][CH2:43][C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=3)=[O:41])[CH2:50][C:51](=[O:52])[NH:17][C:10]3[CH:11]=[C:12]([C:15]#[N:16])[CH:13]=[CH:14][C:9]=3[NH:8][CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:18])=[CH:35][CH:34]=2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2ccc(N(CC(=O)O)C(=O)OCc3ccccc3)cc2)CC1
Reactant: CC(C)(C)OC(=O)CNc1ccc(C#N)cc1N
Agent: CCOC(=O)N1c2ccccc2C=CC1OCC
Solvent: ClC(Cl)Cl
Product: CC(C)(C)OC(=O)CNc1ccc(C#N)cc1NC(=O)CN(C(=O)OCc1ccccc1)c1ccc(OC2CCN(C(=O)OC(C)(C)C)CC2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 71.6 %

Procedure:
To a solution of N-(2-amino-4-cyanophenyl)glycine tert-butyl ester (21.53 g) and N-[4-(1-tert-butoxycarbonylpiperidin-4-yloxy)phenyl]-N-benzyloxycarbonyl-aminoacetic acid (42.18 g) in chloroform (300 ml) was added 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (23.68 g), and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, the solvent was evaporated and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:3) to give the title compound (44.479 g).
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[N:9]1[C:16]2[N:12]([N:13]=[C:14]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)[CH:15]=2)[CH:11]=[CH:10]1.[CH:23]([C:25]1[CH:26]=[C:27]([CH:31]=[C:32]([S:34]([F:39])([F:38])([F:37])([F:36])[F:35])[CH:33]=1)[C:28](O)=[O:29])=[O:24].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.C(=O)(O)[O-].[Na+]>CN(C=O)C>[CH:28]([C:27]1[CH:26]=[C:25]([CH:33]=[C:32]([S:34]([F:38])([F:39])([F:35])([F:36])[F:37])[CH:31]=1)[C:23]([NH:6][C:5]1[CH:7]=[CH:8][C:2]([CH3:1])=[C:3]([N:9]2[C:16]3[N:12]([N:13]=[C:14]([C:17]4[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=4)[CH:15]=3)[CH:11]=[CH:10]2)[CH:4]=1)=[O:24])=[O:29]
Reactant: O=Cc1cc(C(=O)O)cc(S(F)(F)(F)(F)F)c1
Reactant: Cc1ccc(N)cc1-n1ccn2nc(-c3cccnc3)cc12
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C([O-])O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(NC(=O)c2cc(C=O)cc(S(F)(F)(F)(F)F)c2)cc1-n1ccn2nc(-c3cccnc3)cc12
Temperature: 25 °C
Reaction time: 3 h

Procedure:
320 mg (1.11 mmol) of the compound of Example 6A, 336 mg (1.22 mmol) of the compound of Example 36A and 504 mg (1.33 mmol) of HATU were dissolved in 3.3 ml of DMF, 0.23 ml (1.33 mmol) of N,N-diisopropylethylamine were added and the mixture was stirred at RT for 3 h. The reaction was then stirred into 30 ml of semiconcentrated aqueous sodium bicarbonate solution. After 10 min of stirring at RT, the precipitate formed was filtered off, washed with water and dried. The crude product obtained in this manner was purified by preparative HPLC (Method 12). The product fractions were concentrated, the residue was dissolved in ethyl acetate and the mixture was washed successively with saturated sodium bicarbonate solution and saturated sodium chloride solution. The organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure. Drying of the residue gave 100 mg (16% of theory) of the title compound.
Reaction SMILES: S(=O)(=O)(OC1C=CC2[C@@H]3[C@H]([C@H]4[C@@](CC3)(C)[C@@H](C(=O)NCCC)CC4)CCC=2C=1)N.[S:30](=[O:59])(=[O:58])([O:32][C:33]1[CH:50]=[CH:49][C:48]2[C@@H:47]3[C@H:38]([C@H:39]4[C@@:43]([CH2:45][CH2:46]3)([CH3:44])[C:42]([C:51](=[O:57])[NH:52][CH2:53][CH:54]([CH3:56])[CH3:55])=[CH:41][CH2:40]4)[CH2:37][CH2:36][C:35]=2[CH:34]=1)[NH2:31]>>[S:30](=[O:58])(=[O:59])([O:32][C:33]1[CH:50]=[CH:49][C:48]2[C@@H:47]3[C@H:38]([C@H:39]4[C@@:43]([CH2:45][CH2:46]3)([CH3:44])[C@@H:42]([C:51](=[O:57])[NH:52][CH2:53][CH:54]([CH3:56])[CH3:55])[CH2:41][CH2:40]4)[CH2:37][CH2:36][C:35]=2[CH:34]=1)[NH2:31]
Reactant: CC(C)CNC(=O)C1=CC[C@H]2[C@@H]3CCc4cc(OS(N)(=O)=O)ccc4[C@H]3CC[C@]12C
Agent: CCCNC(=O)[C@H]1CC[C@H]2[C@@H]3CCc4cc(OS(N)(=O)=O)ccc4[C@H]3CC[C@]12C
Product: CC(C)CNC(=O)[C@H]1CC[C@H]2[C@@H]3CCc4cc(OS(N)(=O)=O)ccc4[C@H]3CC[C@]12C

Procedure:
In similar manners to those described for the synthesis of compound 7, compound 29d was prepared from compound 11d. TOF-MS m/z 435 (M+H)+; 1H NMR (270 MHz, DMSO-d6) δ 0.60 (s, 3H, CH3), 0.84 (d, 6H, J=6.9 Hz, CH(CH3)2), 2.60-3.16 (m, 2H, NHCH2), 6.95 (d, 1H, J=2.3 Hz, ArH), 7.00 (dd, 1H, J=2.3, 8.6 Hz, ArH), 7.34 (d, 1H, J=8.6 Hz, ArH), 7.49 (brt, 1H, J=5.6 Hz, NHCH2), 7.84 (brs, 2H, NH2).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[C:7]([CH3:21])[C:8]([C:12]3[C:17]([CH3:18])=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=3[CH3:20])=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:22])[C:3]=1[CH2:23][CH2:24]Cl>NC(CC)CC.C1(C)C=CC=CC=1.[O-2].[O-2].[Mn+4]>[CH2:7]([CH:6]([N:5]1[C:2]2[C:11]3[CH:10]=[CH:9][C:8]([C:12]4[C:13]([CH3:20])=[CH:14][C:15]([CH3:19])=[CH:16][C:17]=4[CH3:18])=[C:7]([CH3:21])[C:6]=3[N:5]=[C:4]([CH3:22])[C:3]=2[CH:23]=[CH:24]1)[CH2:11][CH3:10])[CH3:8]
Reactant: Cc1cc(C)c(-c2ccc3c(Cl)c(CCCl)c(C)nc3c2C)c(C)c1
Agent: [Mn+4]
Agent: CCC(N)CC
Agent: [O-2]
Solvent: Cc1ccccc1
Product: CCC(CC)n1ccc2c(C)nc3c(C)c(-c4c(C)cc(C)cc4C)ccc3c21
Reaction time: 48 h
Yield: 11.6 %

Procedure:
A solution of 4-chloro-3-(2-chloroethyl)-7-mesityl-2,8-dimethylquinoline (200 mg, 0.54 mmol) in 3-aminopentane (6.0 mL) was stirred in a sealed tube at 200° C. for 8 hr. After evaporating, activated manganese dioxide (101 mg, 1.16 mmol) was added to a solution of the residue in toluene (9.0 mL) and the mixture was stirred for two days. After filtering through Celite, the mixture was evaporated. The residue was purified by silica gel column chromatography (10% ethyl acetate/hexane) to give the title compound (12 mg) as white crystals.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=1)[C:5]([OH:7])=[O:6].S(=O)(=O)(O)O.[CH3:19]O>>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=1)[C:5]([O:7][CH3:19])=[O:6]
Reactant: CO
Reactant: O=C(O)c1cc(Br)cc([N+](=O)[O-])c1
Agent: O=S(=O)(O)O
Product: COC(=O)c1cc(Br)cc([N+](=O)[O-])c1
Temperature: 0 °C
Yield: 95 %

Procedure:
A solution of 3-bromo-5-nitrobenzoic acid (15.4 g, 62.6 mmol) in methanol (120 mL) and sulfuric acid (1.7 mL, 31 mmol) was heated to reflux overnight. After cooling to 0° C. for 0.5 h, the precipitated solid was filtered to give the desired product as a white solid (15.5 g, 95%). LCMS for C8H7BrNO4 (M+H)+: m/z=260.0, 262.0.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[O:7]=[C:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]([O:15][CH2:16][CH3:17])=[O:14].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CC(C)=O>[CH2:18]([C:9]1([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:10][CH2:11][CH2:12][C:8]1=[O:7])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: CCOC(=O)C1CCCC1=O
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)C1(Cc2ccccc2)CCCC1=O
Temperature: 25 °C
Yield: 66.9 %

Procedure:
38.7 grams of anhydrous potassium carbonate and 90 ml of acetone were mixed, then with stirring, to the resulting mixture was dropwise added a solution of 10.4 ml of ethyl 2-oxocyclopentane carboxylate in 45 ml of acetone. After stirring at room temperature for 35 minutes, 16.7 ml of benzyl bromide was dropwise added thereto, and the reaction was allowed to continue under reflux for 3 hours. Then the reaction mixture was cooled to room temperature, filtered, concentrated, and distilled under reduced pressure. 11.54 g of colorless liquid as the second distillate cut was collected. Yield: 66.9%.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH2:13][C:14]4[S:15][CH:16]=[CH:17][C:18]=4[C:11]=3[N:10]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[N:9]=2)=[CH:4][CH:3]=1.C[N:28]1[CH2:33][CH2:32]N[CH2:30][CH2:29]1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1.C(O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[N:28]1([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[C:12]4[CH2:13][C:14]5[S:15][CH:16]=[CH:17][C:18]=5[C:11]=4[N:10]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[N:9]=3)=[CH:4][CH:3]=2)[CH2:33][CH2:32][CH2:30][CH2:29]1
Reactant: CN1CCNCC1
Reactant: C[Si](C)(C)CCOCn1nc(-c2ccc(Br)cc2)c2c1-c1ccsc1C2
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Solvent: Cc1ccccc1
Solvent: CCO
Product: C[Si](C)(C)CCOCn1nc(-c2ccc(N3CCCC3)cc2)c2c1-c1ccsc1C2
Temperature: 100 °C
Yield: 39 %

Procedure:
A mixture of the corresponding 6-(4-Bromo-phenyl)-4-(2-trimethylsilanyl-ethoxymethyl)-4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalene (0.7 g, 1.5 mmol), 1-Methyl-piperazine (0.2 g, 3 mmol), Cs2CO3 (2 M, 1.5 mL), Xantphos (180 mg, 0.06 mmol) and Pd(OAc)2 (70 mg, 0.06 mmol) in toluene/ethanol (1:1, 10 mL) was heated at 100° C. for 8 hr. The solution was cooled to room temperature and extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give 6-(4-Pyrolidin-1-yl-phenyl)-4-(2-trimethylsilanyl-ethoxymethyl)-4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalene as brown solid in 39% yield.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[CH2:6]([O:8][N:9]=[C:10]([C:14]1[N:15]=[C:16]([NH:19][CH:20]=[O:21])[S:17][CH:18]=1)[C:11]([OH:13])=O)[CH3:7].[CH3:22][CH:23]1[CH:28]=[C:27]([C:29]([OH:31])=[O:30])[N:26]2[C:32](=[O:35])[CH:33]([NH2:34])[C@H:25]2[S:24]1.C[Si](CC(N)=O)(C)C>C(=O)=O.CC(C)=O.C(OCC)(=O)C.O.CN(C)C=O>[CH3:22][CH:23]1[CH:28]=[C:27]([C:29]([OH:31])=[O:30])[N:26]2[C:32](=[O:35])[CH:33]([NH:34][C:11](=[O:13])[C:10](=[N:9][O:8][CH2:6][CH3:7])[C:14]3[N:15]=[C:16]([NH:19][CH:20]=[O:21])[S:17][CH:18]=3)[C@H:25]2[S:24]1
Reactant: CC1C=C(C(=O)O)N2C(=O)C(N)[C@H]2S1
Reactant: CCON=C(C(=O)O)c1csc(NC=O)n1
Agent: CCON=C(C(=O)O)c1csc(=NC=O)[nH]1
Agent: C[Si](C)(C)CC(N)=O
Agent: O=C=O
Solvent: O=P(Cl)(Cl)Cl
Solvent: CC(C)=O
Solvent: CN(C)C=O
Product: CCON=C(C(=O)NC1C(=O)N2C(C(=O)O)=CC(C)S[C@H]12)c1csc(NC=O)n1

Procedure:
To dimethylformamide (0.65 g) was added dried ethyl acetate (3 ml), and the mixture was solidified by dropwise addition of phosphorus oxychloride (1.37 g) under cooling at 0° C. in dry ice-acetone bath over 15 minutes followed by stirring at the same temperature for a while. Dried ethyl acetate (20 ml) was added thereto and 2-ethoxyimino-2-(2-formylaminothiazol-4-yl)acetic acid (syn isomer), which can be represented as 2-ethoxyimino-2-(2-formylimino-2,3-dihydrothiazol-4-yl)acetic acid (syn isomer), (2.00 g) was added thereto. The resulting mixture was stirred for an hour at the same temperature and thereto was added ethyl acetate (30 ml) and stirring was continued at the same temperature for an hour, during which period a homogeneous solution was obtained. Thus obtained solution was added dropwise over 15 minutes at -15° C. to a solution, which was prepared by stirring a mixture of 2-methyl-7-amino-3-cephem-4-carboxylic acid (1.60 g) and trimethylsilylacetamide (6.86 g) in ethyl acetate (100 ml) for an hour at room temperature. The mixture was stirred for an hour at the same temperature and thereto was added water (30 ml) and then the temperature of the mixture was permitted to rise to room temperature. The precipitates were collected by filtration washed with water and then dried over phosphorus pentoxide under reduced pressure to give 2-methyl-7-[2-ethoxyimino-2-(2-formylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer), which can be represented as 2-methyl-7-[2-ethoxyimino-2-(2-formylimino-2,3-dihydrothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer), (1.68 g). The ethyl acetate layer in the mother liquor was separated, washed with water, dried over magnesium sulfate and then concentrated under reduced pressure to give powder of the same compound (1.54 g). Total yield: 3.22 g.
Reaction SMILES: [CH2:1]([C:5]1[CH:6]=[C:7]([CH:23]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:24](O)=[O:25])[CH:8]=[CH:9][C:10]=1[O:11][CH2:12][C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]=1)[CH:2]([CH3:4])[CH3:3].S(Cl)(C)(=O)=O.[CH3:38][S:39]([NH2:42])(=[O:41])=[O:40].C(N(CC)CC)C.CN(C1C=CC=CN=1)C>>[CH3:38][S:39]([NH:42][C:24](=[O:25])[CH:23]([C:7]1[CH:8]=[CH:9][C:10]([O:11][CH2:12][C:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]=2)=[C:5]([CH2:1][CH:2]([CH3:4])[CH3:3])[CH:6]=1)[CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)(=[O:41])=[O:40]
Reactant: CC(C)Cc1cc(C(C(=O)O)C2CCCCC2)ccc1OCc1ccc2ccccc2n1
Reactant: CS(N)(=O)=O
Agent: CN(C)c1ccccn1
Agent: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Product: CC(C)Cc1cc(C(C(=O)NS(C)(=O)=O)C2CCCCC2)ccc1OCc1ccc2ccccc2n1

Procedure:
The title compound is prepared in analogy to the procedure of Example XVI from 3.5 g (0.008 mol) of the compound of Example 81, 1 g (0.008 mol) of mesyl chloride, 0.912 g of methanesulphonamide, 1.62 g (0.016 mol) of triethylamine and 0.98 g (0.008 mol) of dimethylaminopyridine.
Reaction SMILES: [NH:1]1[C:9]2[CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH:5]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:4]=2[N:3]=[CH:2]1.Br[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.O.[Cu-]=O>[N:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[N:1]1[C:9]2[CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])[CH:5]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:4]=2[N:3]=[CH:2]1
Reactant: Brc1ccccn1
Reactant: CCOC(=O)C1c2nc[nH]c2CCN1C(=O)OC(C)(C)C
Agent: O=[Cu-]
Agent: O=C([O-])[O-]
Agent: Oc1cccc2cccnc12
Solvent: CS(C)=O
Solvent: O
Product: CCOC(=O)C1c2ncn(-c3ccccn3)c2CCN1C(=O)OC(C)(C)C
Yield: 39.7 %

Procedure:
A solution of 5-tert-butyl 4-ethyl 6,7-dihydro-1H-imidazo[4,5-c]pyridine-4,5(4H)-dicarboxylate (0.50 g, 1.69 mmol), 2-bromo-pyridine (0.27 g, 1.69 mmol), copper (I) oxide (0.03 g, 0.17 mmol), 8-hydroxyquinoline (0.05 g, 0.34 mmol), and Cs2CO3 (1.10 g, 3.39 mmol) in DMSO (2 mL) was irradiated in a microwave apparatus for 1 hour at 140° C. The reaction was diluted with H2O (100 mL) and extracted with EtOAc (75 mL×3). The organic layers were combined, dried (Na2SO4), and concentrated. Chromatography of the resulting residue (SiO2; MeOH(NH3):DCM) gave the title compound (0.25 g, 40%). MS (ESI): mass calculated for C19H24N4O4, 372.2. m/z found 273.2 [M+H—BOC]+.
Reaction SMILES: [CH2:1]([O:3][C:4]([C@@:6]1([NH:11][C:12]([C@@H:14]2[CH2:18][C@@H:17]([OH:19])[CH2:16][N:15]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:13])[CH2:8][C@H:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2].C(N(C(C)C)CC)(C)C.[N+:36]([C:39]1[CH:47]=[CH:46][C:42]([C:43](Cl)=[O:44])=[CH:41][CH:40]=1)([O-:38])=[O:37]>CN(C)C1C=CN=CC=1.CCOC(C)=O>[CH2:1]([O:3][C:4]([C@@:6]1([NH:11][C:12]([C@@H:14]2[CH2:18][C@@H:17]([O:19][C:43](=[O:44])[C:42]3[CH:41]=[CH:40][C:39]([N+:36]([O-:38])=[O:37])=[CH:47][CH:46]=3)[CH2:16][N:15]2[C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])=[O:13])[CH2:8][C@H:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2]
Reactant: C=C[C@@H]1C[C@]1(NC(=O)[C@@H]1C[C@@H](O)CN1C(=O)OC(C)(C)C)C(=O)OCC
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Agent: CN(C)c1ccncc1
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: C=C[C@@H]1C[C@]1(NC(=O)[C@@H]1C[C@@H](OC(=O)c2ccc([N+](=O)[O-])cc2)CN1C(=O)OC(C)(C)C)C(=O)OCC
Temperature: 5 °C
Reaction time: 2.5 h

Procedure:
To a stirring slurry of (2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate (1.69 kg), 4-dimethylaminopyridine (28.0 g), diisopropylethylamine (946 g) and EtOAc (4.82 kg), at 10° C., was added p-nitrobenzoyl chloride (1.06 kg) as a solution in EtOAc (3.48 kg). After 2.5 h at 10° C., the reaction was cooled to 5° C. and quench by the addition of water (1.85 kg). The resulting layers were separated and the organic layer was washed with a 1.0 N aqueous solution of HCl (3.75 kg), 10% aqueous solution of KHCO3 (2×2.8 kg), water (3.1 kg), and a 10% aqueous solution of NaCl (3.1 kg). The organic layer was washed again with a 1.0 N aqueous solution of HCl (1.88 kg), 10% aqueous solution of KHCO3 (4.2 kg), H2O (1.5 kg), and a 10% aqueous solution of NaCl (2×755 g). The organic layer was concentrated under reduced pressure, diluted with EtOAc (5.6 kg), and then concentrated again. The resulting oil was diluted with EtOAc (10.0 kg), filtered, and then concentrated. EtOAc (10.0 kg) was added and then the resulting solution was concentrated to a mass of 7.9 kg. The assay yield was determined on the product-containing solution to be 98%.
Reaction SMILES: C([O:3][C:4](=[O:34])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[C:15]([CH:17]=[CH:18][C:19]2[C:20]([CH3:32])([CH3:31])[O:21][C:22](=[C:26]([C:29]#[N:30])[C:27]#[N:28])[C:23]=2[C:24]#[N:25])[CH:14]=[CH:13][C:12]=1[NH2:33])C.Cl.O.C(=O)(O)[O-].[Na+]>C(O)(=O)C>[NH2:33][C:12]1[CH:13]=[CH:14][C:15]([CH:17]=[CH:18][C:19]2[C:20]([CH3:32])([CH3:31])[O:21][C:22](=[C:26]([C:29]#[N:30])[C:27]#[N:28])[C:23]=2[C:24]#[N:25])=[CH:16][C:11]=1[O:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][C:4]([OH:34])=[O:3]
Reactant: CCOC(=O)CCCCCOc1cc(C=CC2=C(C#N)C(=C(C#N)C#N)OC2(C)C)ccc1N
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: CC1(C)OC(=C(C#N)C#N)C(C#N)=C1C=Cc1ccc(N)c(OCCCCCC(=O)O)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 74.9 %

Procedure:
To a solution of 6-{2-amino-5-[2-(4-cyano-5-dicyanomethylene-2,2-dimethyl-2,5-dihydro-furan-3-yl)-vinyl]-phenoxy}-hexanoic acid ethyl ester (0.33 g, 0.71 mmol), in acetic acid (6 ml) was added 5 mls of 6M HCl. The mixture was allowed to stir at room temperature for 16 hours. After being poured into 50 mls of water, it was neutralized with a solution of saturated sodium bicarbonate and extracted with ethyl acetate. Both phases of the separatory funnel remained highly colored so solid sodium chloride was added resulting in the decoloration of the aqueous layer. The organic phase was separated and dried over magnesium sulfate and rotovapped to dryness. Purification by column chromatography (60% EtOAc, 35% Hexane, 5% EtOH) provided 6-{2-amino-5-[2-(4-cyano-5-dicyanomethylene-2,2-dimethyl-2,5-dihydro-furan-3-yl)-vinyl]-phenoxy}-hexanoic acid as a shiny green solid (0.23 g, 74%). 1H NMR (400 MHz, CDCl3) δ: 7.57 (d, 1H, J=16.0 Hz), 7.17 (dd, 1H, J=8.4 Hz, J=1.6 Hz), 7.04 (d, 1H, J=1.6 Hz), 6.79 (d, 1H, J=16.0 Hz), 6.72 (d, 1H, J=8.4 Hz), 4.12 (t, 2H, J=7.2 Hz), 2.45 (t, 2H, J=6. Hz), 1.93 (m, 2H), 1.79 (m, 8H), 1.62 (m, 2H). 13C NMR (400 MHz, CDCl3) δ: 176.65, 174.34, 174.17, 148.78, 146.49, 143.21, 127.15, 124.20, 113.86, 112.45, 112.36, 111.64, 111.13, 110.16, 109.82, 97.35, 68.62, 33.27, 30.95, 29.72, 29.28, 28.75, 26.81
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].[C:13](Cl)(=[O:23])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>N1C=CC=CC=1>[C:13]([OH:23])(=[O:1])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4]
Reactant: CCCCCCCCCC(=O)Cl
Agent: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Solvent: c1ccncc1
Product: CCCCCCCCCC(=O)O

Procedure:
Glucose and linear decanoic acid chloride were reacted in pyridine solvent at a reaction temperature of 60° C. for about 30 min. to obtain a crude product of glucose decanoate.