Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]=[S:2]1(=[O:28])[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[NH:5][C:4]([C:12]2[C:17](=[O:18])[N:16]([N:19]=[CH:20][CH:21]([CH3:23])[CH3:22])[C:15]3[CH:24]=[CH:25][S:26][C:14]=3[C:13]=2[OH:27])=[N:3]1.CO.[BH4-].[Li+].Cl.O1C[CH2:37][CH2:36][CH2:35]1>O>[CH:21]1([CH2:20][NH:19][N:16]2[C:17](=[O:18])[C:12]([C:4]3[NH:5][C:6]4[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=4[S:2](=[O:1])(=[O:28])[N:3]=3)=[C:13]([OH:27])[C:14]3[S:26][CH:25]=[CH:24][C:15]2=3)[CH2:22][CH2:37][CH2:36][CH2:35][CH2:23]1
Reactant: CC(C)C=Nn1c(=O)c(C2=NS(=O)(=O)c3ccccc3N2)c(O)c2sccc21
Reactant: C1CCOC1
Agent: Cl
Agent: [BH4-]
Agent: [Li+]
Solvent: O
Solvent: CO
Product: O=c1c(C2=NS(=O)(=O)c3ccccc3N2)c(O)c2sccc2n1NCC1CCCCC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
The product of Example 269A (0.12 g, 0.26 mmol) in tetrahydrofuran (5 mL) and methanol (0.021 mL, 0.52 mmol) at 0° C. was treated dropwise with a 2.0M solution of lithium borohydride in tetrahydrofuran (0.195 mL, 0.39 mmol). The reaction was stirred at 25° C. for 1 hour, acidified with 1M hydrochloric acid a pH of approximately 2-4, diluted with water (15 mL), and the resulting precipitate was collected by filtration and dried. The crude product was chromatographed on silica gel with 97:3 dichloromethane/methanol to give the title compound. The sodium salt of the title compound was prepared according to the procedure of Example 1D. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.04 (m, 2 H) 1.23 (m, 3 H) 1.52 (m, 1 H) 1.68 (m, 3 H) 1.87 (m, 2 H) 2.69 (m, 2 H) 5.95 (t, J=7.17 Hz, 1 H) 7.07 (d, J=5.52 Hz, 1 H) 7.19 (d, J=8.09 Hz, 1 H) 7.26 (t, J=7.72 Hz, 1 H) 7.53 (t, J=7.17 Hz, 1 H) 7.65 (d, J=6.99 Hz, 1 H) 7.78 (d, J=5.15 Hz, 1 H) 15.91 (s, 1 H). MS (APCI+) m/z 459 (M+H)+.
Reaction SMILES: [CH3:1][P:2](Cl)([CH3:4])=[O:3].[H-].[Na+].[CH:8]1[C:13]([N+:14]([O-:16])=[O:15])=[CH:12][CH:11]=[C:10]([OH:17])[CH:9]=1>O1CCCC1>[N+:14]([C:13]1[CH:12]=[CH:11][C:10]([O:17][P:2]([CH3:4])([CH3:1])=[O:3])=[CH:9][CH:8]=1)([O-:16])=[O:15]
Reactant: O=[N+]([O-])c1ccc(O)cc1
Reactant: CP(C)(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CP(C)(=O)Oc1ccc([N+](=O)[O-])cc1
Yield: 26 %

Procedure:
The dimethylphosphinic acid 4-nitrophenyl ester reactant is prepared according to procedure E using 500 mg of dimethylphosphinic chloride, 214 mg of sodium hydride (50% in oil), and 618 mg of p-nitrophenol in solution in 10 ml of tetrahydrofuran. 700 mg of expected product are collected. Yield=26%.
Reaction SMILES: [NH2:1][C:2]1[S:14][C:5]2[CH2:6][N:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:8][C:4]=2[C:3]=1[C:15]([O:17]CC)=O.C([O-])=O.[NH4+].[CH:24]([NH2:26])=O>O>[O:17]=[C:15]1[NH:26][CH:24]=[N:1][C:2]2[S:14][C:5]3[CH2:6][N:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:8][C:4]=3[C:3]1=2
Reactant: NC=O
Reactant: CCOC(=O)c1c(N)sc2c1CN(C(=O)OCC)C2
Agent: O=C[O-]
Agent: [NH4+]
Solvent: O
Product: CCOC(=O)N1Cc2sc3nc[nH]c(=O)c3c2C1
Temperature: 140 °C
Yield: 52 %

Procedure:
Diethyl 2-amino-4,6-dihydro-5H-thieno[2,3-c]pyrrole-3,5-dicarboxylate from Example 19A (3.60 g, 12.7 mmol) was dissolved in formamide (72 mL), and ammonium formiate (2.11 g, 20.3 mmol) was added. The mixture was heated to 140° C. overnight, then diluted with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The precipitate in the aqueous layer was collected by suction filtration and combined with the organic extracts. The product was purified by column chromatography on silica gel (eluent: DCM/MeOH 100:3) and subsequently triturated with tert-butyl methyl ether to yield 1.74 g (52%) of the title compound.
Reaction SMILES: C([NH:8][C@H:9]([C:24]([NH:26][C@H:27]([C:30]1[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=1)[CH2:28][OH:29])=[O:25])[CH2:10][CH2:11][CH2:12][NH:13][C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])(OC(C)(C)C)=O.[ClH:38].CCOC(C)=O>CCOC(C)=O>[ClH:38].[C:14]([NH:13][CH2:12][CH2:11][CH2:10][C@@H:9]([C:24]([NH:26][C@H:27]([C:30]1[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=1)[CH2:28][OH:29])=[O:25])[NH2:8])([O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:15]
Reactant: COc1ccc([C@H](CO)NC(=O)[C@H](CCCNC(=O)OCc2ccccc2)NC(=O)OC(C)(C)C)cc1
Agent: Cl
Solvent: CCOC(C)=O
Product: COc1ccc([C@H](CO)NC(=O)[C@@H](N)CCCNC(=O)OCc2ccccc2)cc1

Procedure:
Prepared according to the method described in Example 1(b) above from crude (R)-N2 -(Boc)-N5 -(Cbz)-(S)-N-[2-hydroxy-l-(4-methoxyphenyl)ethyl]-ornithine amide (4.0 g; from step (a) above), EtOAc (100 mL) and HCl/EtOAc (100 mL), 18 hours reaction time. The hydrochloride salt was precipitated by the addition of diethyl ether, collected and dried to give the sub-title compound as a white solid (2.3 g).
Reaction SMILES: [Cl:1][C:2]1[O:6][C:5]([C:7]([NH:9][C@@H:10]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]([F:33])([F:32])[F:31])[CH2:11][N:12]2C(=O)C3C(=CC=CC=3)C2=O)=[O:8])=[CH:4][C:3]=1[C:34]1[N:38]([CH3:39])[N:37]=[CH:36][C:35]=1[Cl:40].NN>O1CCCC1.CO>[NH2:12][CH2:11][C@@H:10]([NH:9][C:7]([C:5]1[O:6][C:2]([Cl:1])=[C:3]([C:34]2[N:38]([CH3:39])[N:37]=[CH:36][C:35]=2[Cl:40])[CH:4]=1)=[O:8])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]([F:33])([F:32])[F:31]
Reactant: Cn1ncc(Cl)c1-c1cc(C(=O)N[C@@H](Cc2ccccc2C(F)(F)F)CN2C(=O)c3ccccc3C2=O)oc1Cl
Agent: NN
Solvent: C1CCOC1
Solvent: CO
Product: Cn1ncc(Cl)c1-c1cc(C(=O)N[C@H](CN)Cc2ccccc2C(F)(F)F)oc1Cl
Yield: 65 %

Procedure:
To a solution of 5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-furancarboxamide (116 mg, 0.20 mmol) in tetrahydrofuran (1 ml) and methanol (1 ml) at 25° C. was added hydrazine (0.04 ml, 1.37 mmol) dropwise. After 12 h the solution was concentrated, dry loaded onto silica and purified by column chromatography (2% MeOH in DCM (1% NH4OH)). The free base was transferred to the HCl salt by addition of excess 2M HCl in Ether (2 ml) to the residue in DCM (2 ml) affording the HCl salt of N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-furancarboxamide (68 mg, 0.13 mmol, 65% yield) as a yellow solid: LCMS (ES) m/z=461, 463 (M, M+2)+, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.80 (d, J=9.09 Hz, 1H) 8.03 (br. s., 3H) 7.66-7.73 (m, 2H) 7.58-7.61 (m, 1H) 7.52-7.59 (m, 2H) 7.40-7.48 (m, 1H) 4.5-4.57 (m, 1H) 3.77 (s, 3H) 2.98-3.09 (m, 4H).
Reaction SMILES: C(N(CC)CC)C.[C:8](Cl)(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[NH2:17][C:18]1[CH:19]=[C:20]([CH:29]=[CH:30][C:31]=1[CH3:32])[C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:22]>C(Cl)Cl>[C:21]([C:20]1[CH:29]=[CH:30][C:31]([CH3:32])=[C:18]([NH:17][C:8](=[O:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:19]=1)(=[O:22])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Cc1ccc(C(=O)c2ccccc2)cc1N
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc(C(=O)c2ccccc2)cc1NC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
0.67 mL of triethylamine and 0.34 ml of benzoyl chloride was added to 5 mL of methylene chloride solution containing 0.51 g of 3-amino-4-methylbenzophenone while ice-cooled and stirred at room temperature for 2 hours. The solvent of the reaction mixture was evaporated under reduced pressure and ethyl acetate and 1.0 mol/L hydrochloric acid were added. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with a saturated sodium hydrogen carbonate aqueous solution and a saturated sodium chloride aqueous solution sequentially, and the solvent was evaporated under reduced pressure. Hexane and diisopropyl ether were added to the obtained residue and a solid substance was separated by filtration to obtain 0.71 g of N-(5-benzoyl-2-methylphenyl)benzamide as white solid.
Reaction SMILES: [NH2:1][CH2:2][CH:3]([OH:5])[CH3:4].Cl[C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8].C(=O)([O-])[O-].[Na+].[Na+]>O>[CH2:10]([O:9][C:7]([NH:1][CH2:2][CH:3]([OH:5])[CH3:4])=[O:8])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CC(O)CN
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: CC(O)CNC(=O)OCc1ccccc1
Temperature: 0 °C
Reaction time: 3 h
Yield: 99.8 %

Procedure:
A mixture of 1-amino-2-propanol (1) (4.6 g, 61.8 mmol), benzyl chloroformate (11.5 g, 67.6 mmol), and sodium carbonate (7.16 g, 67.7 mmol) in water (50 mL) was stirred at 0° C. for 3 h. Water (50 mL) was added to the reaction mixture, the product was extracted with CH2Cl2 (3×20 mL), dried over Na2SO4 and concentrated. The residue was purified by a flash chromatography on SiO2 eluting with 10:1 hex:EtOAc, followed by EtOAc to afford 1-benzyloxycarbonylamino-2-propanol (12.9 g, 100%) as an oil. 1H NMR (CDCl3): □ 7.30 (m, 5H), 5.90 (s, 1H), 5.06 (s, 2H), 3.95 (s, 1H), 3.31 (m, 1H), 3.04 (m, 1H), 1.2 (d, 3H)
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:19]=[CH:18][C:7]([O:8][CH2:9][CH:10]([OH:17])[CH2:11][N:12]2[CH:16]=[CH:15][N:14]=[CH:13]2)=[CH:6][CH:5]=1.CN(C)P(N(C)C)(N(C)C)=O.Br[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41]>O>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([O:8][CH2:9][CH:10]([O:17][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])[CH2:11][N:12]2[CH:16]=[CH:15][N:14]=[CH:13]2)=[CH:18][CH:19]=1
Reactant: OC(COc1ccc(Cl)cc1)Cn1ccnc1
Reactant: CCCCCCCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: O
Product: CCCCCCCCCCOC(COc1ccc(Cl)cc1)Cn1ccnc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A 56% dispersion of sodium hydride in mineral oil (480 mg.) is added under nitrogen to a solution of 2.52 g. of 1-[3'-(4"-chlorophenoxy)-2'-hydroxypropyl]imidazole in 6 ml. dry hexamethylphosphoramide. After stirring for 1 hours at room temperature, the temperature is increased to 45° C. and stirring is continued for 2 hours. The solution is then cooled in an ice bath and 2.5 g. of 1-bromodecane in 1 ml. of hexamethylphosphoramide is added. Thereafter, the solution is stirred for 2 hours at room temperature and then for 16 hours at 50° C. The reaction mixture is poured into water and the resultant aqueous mixture extracted with ether and the ether extracts washed with water. The organic phase is dried over magnesium sulfate and evaporated. The resulting residue is chromatographed on silica gel. Elution with 20% acetone in dichloromethane yields 1-[3'-(4"-chlorophenoxy)-2'-(n-decyloxy)propyl]imidazole.
Reaction SMILES: [CH:1]([CH:4]1[CH2:9][CH2:8][CH2:7][CH:6]([CH:10]([CH3:15])[C:11](=[CH2:14])[CH:12]=[O:13])[CH2:5]1)([CH3:3])[CH3:2]>CO.[Pd]>[CH:1]([CH:4]1[CH2:9][CH2:8][CH2:7][CH:6]([CH:10]([CH3:15])[CH:11]([CH3:14])[CH:12]=[O:13])[CH2:5]1)([CH3:3])[CH3:2]
Reactant: C=C(C=O)C(C)C1CCCC(C(C)C)C1
Agent: [Pd]
Solvent: CO
Product: CC(C)C1CCCC(C(C)C(C)C=O)C1
Temperature: 42.5 °C
Reaction time: 0.67 h
Yield: 66 %

Procedure:
5% Pd/C (250 mg, 5% w/w) was charged into a 25 mL autoclave vessel with 3-(3-isopropylcyclohexyl)-2-methylenebutanal (4.5 g, 21.6 mmol) in methanol (5 mL). The mixture was vigorously stirred under an hydrogen atmosphere (10 Bar) at 40-45° C. for 40 minutes. The catalyst was filtered over celite and the solution was concentrated. The resulting crude product was distilled with a bulb-to-bulb distillation (2.5 mBar, 117° C.) to give 3-(3-isopropylcyclohexyl)-2-methylbutanal (3 g, gc purity>90%; yield=67%).
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])C.[NH2:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([NH2:14])=[O:13]>C(O)=O>[CH:1]([NH:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([NH2:14])=[O:13])=[O:3]
Reactant: NC(=O)c1cccc(N)c1
Reactant: CC(=O)OC(C)=O
Solvent: O=CO
Product: NC(=O)c1cccc(NC=O)c1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 78 %

Procedure:
A mixture of 40 ml of acetic anhydride and 40 ml of 98 to 100% formic acid was heated at 50° to 60° C. for 90 minutes. The solution was cooled to room temperature and 10 gm of 3-aminobenzamide was added in small aliquots over 15 minutes. The temperature was kept below 30° C. by occasional cooling in an ice-bath during the addition of the 3-aminobenzamide. The solution was stirred at room temperature for 2.5 hours, and then it was evaporated under vacuum to a viscous oil. Traces of acetic anhydride and of formic acid were removed by the repeated addition of water and evaporation until a white solid product was obtained. The solid product was crystallized from water. The white, round crystals were filtered off and washed with cold water and then dried under a vacuum. The overall yield was 78% and the melting point of the final material was 175° C. to 177° C. Mass spectrum analysis indicated a molecular weight of 164.
Reaction SMILES: N[C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[C:16]([Br:17])=[CH:15][CH:14]=[C:13]3[C:8]=2[CH2:9][CH2:10][C@H:11]([CH3:21])[N:12]3[C:18](=[O:20])[CH3:19])=[C:4]([F:24])[CH:3]=1.C(O)(=O)C.N([O-])=O.[Na+].S(=O)(O)[O-].[Na+]>C(O)C>[Br:17][C:16]1[C:7]([O:6][C:5]2[CH:22]=[CH:23][CH:2]=[CH:3][C:4]=2[F:24])=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]([C:18](=[O:20])[CH3:19])[C@@H:11]([CH3:21])[CH2:10][CH2:9]2
Reactant: CC(=O)N1c2ccc(Br)c(Oc3ccc(N)cc3F)c2CC[C@@H]1C
Agent: O=N[O-]
Agent: O=S([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: CC(=O)O
Product: CC(=O)N1c2ccc(Br)c(Oc3ccccc3F)c2CC[C@@H]1C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 86.2 %

Procedure:
A 100-mL round-bottom flask was charged with 1-[(2S)-5-(4-amino-2-fluorophenoxy)-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-1-yl]ethan-1-one (370 mg, 0.92 mmol) and acetic acid (5 mL). Sodium nitrite (1.3 g, 18.8 mmol) was added in portions, and the mixture stirred at room temperature for 30 minutes. Sodium bisulfite (2.0 g, 18.8 mmol) and ethanol (5 mL) were added, and the resulting mixture stirred for 12 h at room temperature. The reaction mixture was concentrated under vacuum, diluted with dichloromethane, washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified via column chromatography on silica gel (eluting with 5:1, ethyl acetate/petroleum ether) to afford 1-[(2S)-6-bromo-5-(2-fluorophenoxy)-2-methyl-1,2,3,4-tetrahydroquinolin-1-yl]ethan-1-one (300 mg, 86%) of as yellow oil. MS (ESI, pos. ion) m/z 378, 380 [M+H]+.
Reaction SMILES: [CH3:1][C:2]([OH:18])([CH3:17])[CH2:3][O:4][CH:5]1[CH2:10][CH2:9][CH:8]([NH:11][C:12]2[N:16]=[CH:15][NH:14][N:13]=2)[CH2:7][CH2:6]1.[C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH:34]([C:40](=O)[CH2:41][CH2:42][CH3:43])[C:35](OCC)=[O:36])=[CH:29][CH:28]=1)#[N:20]>ClC1C=CC(Cl)=CC=1Cl>[OH:18][C:2]([CH3:1])([CH3:17])[CH2:3][O:4][C@@H:5]1[CH2:6][CH2:7][C@H:8]([N:11]2[C:35](=[O:36])[C:34]([CH2:33][C:30]3[CH:31]=[CH:32][C:27]([C:22]4[C:21]([C:19]#[N:20])=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:28][CH:29]=3)=[C:40]([CH2:41][CH2:42][CH3:43])[N:13]3[N:14]=[CH:15][N:16]=[C:12]23)[CH2:9][CH2:10]1
Reactant: CCCC(=O)C(Cc1ccc(-c2ccccc2C#N)cc1)C(=O)OCC
Reactant: CC(C)(O)COC1CCC(Nc2nc[nH]n2)CC1
Solvent: Clc1ccc(Cl)c(Cl)c1
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@@H](OCC(C)(C)O)CC2)c2ncnn12
Temperature: 25 °C

Procedure:
A solution of 2-methyl-1-{[4-(1H-1,2,4-triazol-3-ylamino)cyclohexyl]oxy}propan-2-ol (2.80 g) and ethyl 2-[(2′-cyanobiphenyl-4-yl)methyl]-3-oxohexanoate (7.69 g) in 1,2,4-trichlorobenzene (15 mL) was stirred at 195° C. for 2 days. The reaction mixture was cooled to room temperature, and purified by silica gel chromatography [eluent: hexane/ethyl acetate=70/30→50/50 (volume ratio)] to give the title compound as a brown amorphous compound (620 mg, 10%).
Reaction SMILES: C([O:3][C:4](=[O:29])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[CH2:22][N:23]2[CH2:27][CH2:26][O:25][C:24]2=[O:28])[CH:7]=1)C.[OH-].[Li+].O>O1CCOCC1>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([O:14][C:8]2[CH:7]=[C:6]([CH2:5][C:4]([OH:29])=[O:3])[CH:11]=[CH:10][C:9]=2[O:12][CH3:13])=[C:16]([CH2:22][N:23]2[CH2:27][CH2:26][O:25][C:24]2=[O:28])[CH:17]=1
Reactant: CCOC(=O)Cc1ccc(OC)c(Oc2ccc(Cl)cc2CN2CCOC2=O)c1
Agent: [Li+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: COc1ccc(CC(=O)O)cc1Oc1ccc(Cl)cc1CN1CCOC1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To {3-[4-chloro-2-(2-oxo-oxazolidin-3-ylmethyl)-phenoxy]-4-methoxy-phenyl}-acetic acid ethyl ester (0.36 mmol) in 1,4-dioxane was added lithium hydroxide and H2O, and the reaction was stirred overnight at room temperature. The mixture was worked-up, and the residue was purified by preparative HPLC to give the title compound.
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[O-]S([O-])(=S)=O.[Na+].[Na+]>C(Cl)Cl>[O:1]=[CH:2][CH2:3][C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1
Reactant: N#Cc1ccc(CCO)cc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Product: N#Cc1ccc(CC=O)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 4-(2-Hydroxyethyl)benzonitrile (0.38 g, 2.6 mmol) in DCM (5 mL) was added Dess-Martin reagent (1.7 g, 3.9 mmol). The mixture was allowed to stir at RT for 1 hour. TLC showed no starting material at that point. The reaction was diluted with DCM, worked up with Na2S2O3, washed with sodium bicarbonate, dried over sodium sulfate, and concentrated. The crude 4-(2-Oxoethyl)benzonitrile was used in the next step without further purification.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][C:8]([Cl:14])=[CH:9][CH:10]=2)[N:5]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:4]=1.[C:21]([C:24]1[CH:29]=[CH:28][C:27]([S:30]([NH2:33])(=[O:32])=[O:31])=[CH:26][CH:25]=1)(O)=[O:22]>>[Cl:14][C:8]1[CH:7]=[C:6]2[C:11]([C:12](=[O:13])[C:3]([CH2:2][NH:1][C:21](=[O:22])[C:24]3[CH:29]=[CH:28][C:27]([S:30](=[O:32])(=[O:31])[NH2:33])=[CH:26][CH:25]=3)=[CH:4][N:5]2[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[CH:10][CH:9]=1
Reactant: NS(=O)(=O)c1ccc(C(=O)O)cc1
Reactant: NCc1cn(-c2ccccc2)c2cc(Cl)ccc2c1=O
Product: NS(=O)(=O)c1ccc(C(=O)NCc2cn(-c3ccccc3)c3cc(Cl)ccc3c2=O)cc1

Procedure:
N-(7-Chloro-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-4-sulfamoyl-benzamide was prepared starting from intermediate D and 4-carboxybenzenesulfonamide. MS calcd. for C23H18ClN3O4S [(M+H)+] 467.9, obsd. 468.0.
Reaction SMILES: C(O[C@@H:5]1[O:22][C@H:21]([CH2:23][O:24][C:25](=[O:27])[CH3:26])[C@@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@@H:6]1[O:7][C:8](=[O:10])[CH3:9])(=O)C.[CH:28]1[C:33]([N+:34]([O-:36])=[O:35])=[CH:32][CH:31]=[C:30]([OH:37])[CH:29]=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Zn+2].C([O-])(=O)C>[C:8]([O:7][C@H:6]1[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@@H:21]([CH2:23][O:24][C:25](=[O:27])[CH3:26])[O:22][C@H:5]1[O:37][C:30]1[CH:31]=[CH:32][C:33]([N+:34]([O-:36])=[O:35])=[CH:28][CH:29]=1)(=[O:10])[CH3:9]
Reactant: O=[N+]([O-])c1ccc(O)cc1
Reactant: CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: CC(=O)[O-]
Agent: [Zn+2]
Solvent: Cc1ccccc1
Product: CC(=O)OC[C@H]1O[C@@H](Oc2ccc([N+](=O)[O-])cc2)[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Yield: 52 %

Procedure:
A 19.5 g (0.05 mole) quantity of penta-O-acetyl-β-D-mannopyranose and 13.9 g (0.10 mole) of p-nitrophenol were heated at 130° C. under reduced pressure of 20 mmHg. To the melt obtained were added 0.25 g of 12-molybdophosphoric acid and 0.05 g of zinc acetate and the mixture was reacted under reduced pressure for 30 minutes. The reaction mixture was dissolved in 100 ml of toluene and the solution was washed with 6 portions of 50 ml of 1.0M-NaoH aqueous solution and with 2 portions of 50 ml of water. After the toluene layer was evaporated to dryness under reduced pressure, the semisolid obtained was purified by silica gel column chromatography using toluene-acetone (20 : 1, v/v) as an eluent, giving 12.2 g of p-nitrophenyl 2,3,4,6-tetra-O-acetyl-β-D-mannopyranoside in a yield of 52.0%. M.p. 142° to 143° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:23])[NH:7][CH2:8][CH2:9][CH2:10][NH:11][C:12]([C:14]1[C:18]([CH3:19])=[C:17]([CH:20]=O)[NH:16][C:15]=1[CH3:22])=[O:13])([CH3:4])([CH3:3])[CH3:2].[F:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:29](=[O:34])[CH2:28]2.N1CCCC1>C(O)C>[C:1]([O:5][C:6](=[O:23])[NH:7][CH2:8][CH2:9][CH2:10][NH:11][C:12]([C:14]1[C:18]([CH3:19])=[C:17](/[CH:20]=[C:28]2\[C:29](=[O:34])[NH:30][C:31]3[C:27]\2=[CH:26][C:25]([F:24])=[CH:33][CH:32]=3)[NH:16][C:15]=1[CH3:22])=[O:13])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1[nH]c(C=O)c(C)c1C(=O)NCCCNC(=O)OC(C)(C)C
Reactant: O=C1Cc2cc(F)ccc2N1
Solvent: CCO
Solvent: C1CCNC1
Product: Cc1[nH]c(/C=C2\C(=O)Nc3ccc(F)cc32)c(C)c1C(=O)NCCCNC(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 93.6 %

Procedure:
A solution of {3-[(5-Formyl-2,4-dimethyl-1H-pyrrole-3-carbonyl)-amino]-propyl}-carbamic acid tert-butyl ester (0.200 g, 0.62 mmol) and 5-Fluoro-1,3-dihydro-indol-2-one (0.011 g, 0.62 mmol), pyrrolidine (0.003 ml) in ethanol (2 ml) was heated at 78° C. for 3 hours. The reaction was cooled to 0° C. and the resulting precipitate filtered, washed with cold ethanol. The product was suspended in ethanol (4 ml) and stirred at 72° C. for 30 minutes. The reaction was filtered, the precipitate dried in a vacuum oven at 40° C. to yield the desired compound as a solid (0.265 g, 94%). 1H NMR (400 MHz, DMSO-d6) δ 13.8 (s, 1H); 11.00 (s, 1H); 7.80 (m, 2H); 7.70 (m, 1H); 7.0 (m, 1H); 6.9 (m, 2H); 3.30 (q, 2H); 3.10 (q, 2H); 2.50 (dd, 6H) 1.60 (m, 2H)); 1.40 (s, 9H). LCMS: method D, RT=2.86 min, [M+Na+=479], and [M−Boc+Na+=379].
Reaction SMILES: [C:1]1([C:7]#[C:8][C:9]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([C:18]4[CH:23]=[C:22]([O:24][CH3:25])[C:21]([O:26][CH3:27])=[C:20]([O:28][CH3:29])[CH:19]=4)[N:16]=3)[N:11]([S:30]([C:33]3[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=3)(=[O:32])=[O:31])[CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(=O)(=O)(O)[OH:41].CC(C)=O>S([O-])([O-])(=O)=O.[Hg+2].O>[C:1]1([C:7](=[O:41])[CH2:8][C:9]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([C:18]4[CH:19]=[C:20]([O:28][CH3:29])[C:21]([O:26][CH3:27])=[C:22]([O:24][CH3:25])[CH:23]=4)[N:16]=3)[N:11]([S:30]([C:33]3[CH:34]=[CH:35][C:36]([CH3:39])=[CH:37][CH:38]=3)(=[O:32])=[O:31])[CH:10]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=S(=O)(O)O
Reactant: COc1cc(-c2cnc3c(n2)c(C#Cc2ccccc2)cn3S(=O)(=O)c2ccc(C)cc2)cc(OC)c1OC
Agent: O=S(=O)([O-])[O-]
Agent: [Hg+2]
Solvent: CC(C)=O
Solvent: O
Product: COc1cc(-c2cnc3c(n2)c(CC(=O)c2ccccc2)cn3S(=O)(=O)c2ccc(C)cc2)cc(OC)c1OC
Temperature: 110 °C
Yield: 61.8 %

Procedure:
7-Phenylethynyl-5-(toluene-4-sulfonyl)-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine (154 mg, 0.29 mmol), mercury(II) sulfate (127 mg, 0.43 mmol), concentrated sulfuric acid (0.031 ml, 0.58 mmol) and 3 ml of a 3:1 mixture of acetone and water were added to a 5 ml microwave vial. The reaction was heated in a microwave reactor at 110° C. for one hour. The solvent was evaporated and ethyl acetate and aqueous sodium carbonate were added to the residue. The aqueous layer was removed using a reparatory funnel, the organic layer was washed with water twice, then dried and concentrated. The residue was purified by flash chromatography using a gradient of 0% ethyl acetate in hexanes up to 30% to give 100 mg of 1-phenyl-2-[5-(toluene-4-sulfonyl)-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-ethanone as the major product. MS: (M+H)+=558.