Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C@H:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[C:13]([OH:15])=[O:14])(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(OC(=O)[C@H](CC1C=CC(O)=CC=1)N)(C)(C)C>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C@@H:12]([CH2:16][C:17]2[CH:18]=[CH:19][C:20]([OH:23])=[CH:21][CH:22]=2)[C:13]([OH:15])=[O:14])(=[O:9])=[O:10])=[CH:4][CH:3]=1
Reactant: O=C(O)[C@@H](Cc1ccc(O)cc1)NS(=O)(=O)c1ccc(F)cc1
Agent: CC(C)(C)OC(=O)[C@@H](N)Cc1ccc(O)cc1
Product: O=C(O)[C@H](Cc1ccc(O)cc1)NS(=O)(=O)c1ccc(F)cc1

Procedure:
Following 19a synthetic method, using B2 (118.65 mg, 0.5 mmol) instead of A2 gave 19b as a colorless oil; (96.03 mg, 56.6%). [α]D25: −13.7 (c=0.23, CHCl3); 1H-NMR (300 MHz, CDCl3): δ 7.78-7.71 (m, 2H), 7.26-7.17 (m, 7H), 6.92 (d, J=9 Hz, 1H), 4.25-4.13 (m, 1H), 3.15-2.90 (m, 2H); 13C NMR (300 MHz, acetone-d6): δ 171.56, 166.28, 162.95, 137.52, 136.53, 129.74, 129.62, 129.39, 128.24, 126.68, 115.94, 115.63, 57.31, 38.48; HRMS (ESI): calcd for: C15H14FNO4S [M+Na]+=346.0520, obsd [M+Na]+=346.0523.
Reaction SMILES: [OH:1][CH2:2][C:3]1[N:4]=[C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[S:6][CH:7]=1>[O-2].[O-2].[Mn+4].C1COCC1>[CH:2]([C:3]1[N:4]=[C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[S:6][CH:7]=1)=[O:1]
Reactant: CCOC(=O)c1nc(CO)cs1
Agent: [Mn+4]
Agent: [O-2]
Solvent: C1CCOC1
Product: CCOC(=O)c1nc(C=O)cs1
Temperature: 50 °C
Yield: 91.2 %

Procedure:
A mixture of ethyl 4-(hydroxymethyl)-1,3-thiazole-2-carboxylate (1.23 g), manganese dioxide (5.71 g) and THF (25 ml) was heated at 50° C. overnight. The inorganic material was removed by filtration, and the filtrate was concentrated in vacuo to give the title compound (1.11 g) as a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][C:10]2[N:11]=[C:12]([CH3:15])[NH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[CH3:16]I>>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][C:10]2[N:11]=[C:12]([CH3:15])[N:13]([CH3:16])[CH:14]=2)[CH:5]=[CH:4][N:3]=1
Reactant: Cc1nc(C#Cc2ccnc(Cl)c2)c[nH]1
Reactant: CI
Product: Cc1nc(C#Cc2ccnc(Cl)c2)cn1C

Procedure:
The title compound, MS: m/e=232.1 (M+H+), was prepared in accordance with the general method of example 1 from 2-chloro-4-(2-methyl-1H-imidazol-4-ylethynyl)-pyridine and methyl iodide.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH:20]2[CH2:29][CH2:28][C:27]3[C:22](=[CH:23][CH:24]=[C:25]([O:30][CH3:31])[CH:26]=3)[CH2:21]2)=[C:7]([CH2:9][NH:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)[CH:8]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:39][CH2:40][N:41]1[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1.O>CN(C)C=O>[N:41]1([CH2:40][CH2:39][O:19][C:16]2[CH:17]=[CH:18][C:13]([CH2:12][CH2:11][NH:10][CH2:9][C:7]3[CH:8]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=3[CH:20]3[CH2:29][CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[C:25]([O:30][CH3:31])[CH:26]=4)[CH2:21]3)=[CH:14][CH:15]=2)[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1
Reactant: ClCCN1CCCCCC1
Reactant: COc1ccc2c(c1)CCC(c1ccc(OC)cc1CNCCc1ccc(O)cc1)C2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc2c(c1)CCC(c1ccc(OC)cc1CNCCc1ccc(OCCN3CCCCCC3)cc1)C2
Temperature: 60 °C
Reaction time: 2 h
Yield: 75.5 %

Procedure:
To a solution of 4-{2-{[5-methoxy-2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenyl]methylamino}ethyl}phenol (160 mg) in N,N-dimethylformamide (3 ml) were sequentially added potassium carbonate (100 mg) and 1-(2-chloroethyl)azepane (110 mg), and the solution was stirred for 2 hours at 60° C. Water was added thereto followed by stirring, the solution was extracted with ethyl acetate, then sequentially washed with water and brine, and the solvent was evaporated in vacuo. The residue was purified by NH silica gel column chromatography (hexane-ethyl acetate system) to provide the title compound (157 mg).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([S:7]([C:10]2[CH:11]=[CH:12][C:13]3[C:14]4[N:22]=[C:21]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[CH:20]=[C:19]([C:29]([O:31]C)=O)[C:15]=4[NH:16][C:17]=3[CH:18]=2)(=[O:9])=[O:8])[CH2:3][CH2:2]1.[NH3:33]>CO>[O:1]1[CH2:6][CH2:5][N:4]([S:7]([C:10]2[CH:11]=[CH:12][C:13]3[C:14]4[N:22]=[C:21]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[CH:20]=[C:19]([C:29]([NH2:33])=[O:31])[C:15]=4[NH:16][C:17]=3[CH:18]=2)(=[O:8])=[O:9])[CH2:3][CH2:2]1
Reactant: COC(=O)c1cc(-c2ccccc2)nc2c1[nH]c1cc(S(=O)(=O)N3CCOCC3)ccc12
Reactant: N
Solvent: CO
Product: NC(=O)c1cc(-c2ccccc2)nc2c1[nH]c1cc(S(=O)(=O)N3CCOCC3)ccc12
Temperature: 80 °C
Yield: 62 %

Procedure:
A suspension of methyl 7-(morpholinosulfonyl)-2-phenyl-5H-pyrido[3,2-b]indole-4-carboxylate (106 mg, 0.235 mmol) in 7 N NH3 in MeOH (5 mL) in a sealed microwave vial was heated at 80° C. overnight. After cooling to RT, the precipitate was collected, washed with MeOH, and dried to leave 7-(morpholinosulfonyl)-2-phenyl-5H-pyrido[3,2-b]indole-4-carboxamide (67 mg, 0.15 mmol, 62% yield) as yellow fluffy solid. MS (ESI) m/z 435.1 (M−H). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.03 (1H, s), 8.70 (1H, s), 8.59 (1H, s), 8.52 (1H, d, J=8.06 Hz), 8.33 (2H, d, J=7.30 Hz), 8.21 (1H, d, J=1.01 Hz), 8.00 (1H, s), 7.52-7.64 (3H, m), 7.46 (1H, t, J=7.30 Hz), 3.60-3.69 (4H, m), 2.88-2.97 (4H, m).
Reaction SMILES: C(NC1C=CC(C2C=C3C(CN([C@@H](C(C)C)C(O)=O)C3=O)=CC=2)=CC=1)(=O)C1C=CC=CC=1.[Cl:33][C:34]1[CH:35]=[C:36]([CH:64]=[CH:65][CH:66]=1)[C:37]([NH:39][C:40]1[CH:45]=[CH:44][C:43]([C:46]2[CH:54]=[C:53]3[C:49]([CH2:50][N:51]([C@@H:56]([CH:61]([CH3:63])[CH3:62])[C:57]([O:59]C)=[O:58])[C:52]3=[O:55])=[CH:48][CH:47]=2)=[CH:42][CH:41]=1)=[O:38]>>[Cl:33][C:34]1[CH:35]=[C:36]([CH:64]=[CH:65][CH:66]=1)[C:37]([NH:39][C:40]1[CH:45]=[CH:44][C:43]([C:46]2[CH:54]=[C:53]3[C:49]([CH2:50][N:51]([C@@H:56]([CH:61]([CH3:63])[CH3:62])[C:57]([OH:59])=[O:58])[C:52]3=[O:55])=[CH:48][CH:47]=2)=[CH:42][CH:41]=1)=[O:38]
Reactant: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(NC(=O)c4cccc(Cl)c4)cc3)cc2C1=O
Agent: CC(C)[C@@H](C(=O)O)N1Cc2ccc(-c3ccc(NC(=O)c4ccccc4)cc3)cc2C1=O
Product: CC(C)[C@@H](C(=O)O)N1Cc2ccc(-c3ccc(NC(=O)c4cccc(Cl)c4)cc3)cc2C1=O
Yield: 81 %

Procedure:
The compound of example 108 was prepared analogous to compound of example 98 by hydrolysis of compound of example 107.
Reaction SMILES: [CH2:1]([C:8]1[N:12]([CH3:13])[C:11]2[CH:14]=[C:15]([C:18]([O:20]CC)=[O:19])[CH:16]=[CH:17][C:10]=2[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].[ClH:25]>C(O)C>[ClH:25].[CH2:1]([C:8]1[N:12]([CH3:13])[C:11]2[CH:14]=[C:15]([C:18]([OH:20])=[O:19])[CH:16]=[CH:17][C:10]=2[N:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1ccc2nc(Cc3ccccc3)n(C)c2c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Cn1c(Cc2ccccc2)nc2ccc(C(=O)O)cc21

Procedure:
To an ethanol (4 ml) solution of 2-benzyl-6-ethoxycarbonyl-1-methylbenzimidazole (0.340 g) (example 10), 5% sodium hydroxide aqueous solution (2.8 g) is added, and the solution is refluxed for 1.5 hours. The solution is made acidic using 1N hydrochloric acid, and is concentrated under reduced pressure. Ethanol is added to the residue and organic materials are extracted. The ethanol is removed under reduced pressure and thus, 2-benzyl-6-carboxy-1-methylbenzimidazole hydrochloride (0.30 g) is obtained. 1H-NMR (DMSO-d6, δ): 4.00 (3H, s), 4.62 (2H, s), 7.33 (1H, m), 7.35-7.45 (4H, m), 7.83 (1H, d, J=8.4 Hz), 8.06 (1H, d, J=8.4 Hz), 8.42 (1H, s), 13.3 (1H, br s).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:26])=[C:8]2[C:14]([Br:15])=[C:13]([Br:16])[N:12]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[O:24][CH3:25])[C:9]2=[CH:10][N:11]=1)=[O:5])[CH3:2].C1C(=O)N([Br:34])C(=O)C1.C(OOC(C1C=CC=CC=1)=O)(C1C=CC=CC=1)=O>C(Cl)(Cl)(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:26])=[C:8]2[C:14]([Br:15])=[C:13]([Br:16])[N:12]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[O:24][CH3:25])[C:9]2=[C:10]([Br:34])[N:11]=1)=[O:5])[CH3:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)c1ncc2c(c1O)c(Br)c(Br)n2Cc1ccccc1OC
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CCOC(=O)c1nc(Br)c2c(c1O)c(Br)c(Br)n2Cc1ccccc1OC

Procedure:
Prepared in analogy to that of Example 103(a) from 2,3-dibromo-1-(2-methoxy-benzyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester, NBS and BzOOBz in carbontetrachloride. The title compound, ESI MS (m/z): 561 (M+H)+.
Reaction SMILES: [OH:1][CH2:2][C:3]1[O:8][CH2:7][N:6]([C:9]([CH3:21])([CH3:20])[C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[C:5](=[O:22])[C:4]=1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>ClCCl>[CH:2]([C:3]1[O:8][CH2:7][N:6]([C:9]([CH3:21])([CH3:20])[C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[C:5](=[O:22])[C:4]=1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:1]
Reactant: CC(C)(C(=O)OCc1ccccc1)N1COC(CO)=C(c2ccccc2)C1=O
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CC(C)(C(=O)OCc1ccccc1)N1COC(C=O)=C(c2ccccc2)C1=O
Reaction time: 1 h
Yield: 42.7 %

Procedure:
A solution of benzyl 2-(2,3-dihydro-6-hydroxymethyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpropanoate (2.0 g) in dichloromethane was added over 5 minutes to a stirred suspension of pyridinium chlorochromate (0.9 g) in dichloromethane at ambient temperature. After stirring for 1 hour the reaction mixture was diluted with dichloromethane and washed with water. The organic solution was dried (magnesium sulphate) and solvent evaporated under reduced pressure to give benzyl 2-(6-formyl-2,3-dihydro-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpropanoate (0.85 g) as an orange gum, NMR (CDCl3) 1.5(s,6H), 5.1(s,2H), 5.3(s,2H), 7.2(bs,5H), 7.3-7.4(m,5H), 9.25(s,1H).
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C@@H:11]([CH3:14])[C@@H:10]([NH:15][C:16]2[C:21]([C:22](=[O:24])[CH3:23])=[CH:20][N:19]=[C:18]3[N:25]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[CH:26]=[CH:27][C:17]=23)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:36]OC(OC)N(C)C>>[CH2:1]([N:8]1[CH2:13][CH2:12][C@@H:11]([CH3:14])[C@@H:10]([N:15]2[C:16]3[C:21](=[CH:20][N:19]=[C:18]4[N:25]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:33])([CH3:35])[CH3:34])[CH:26]=[CH:27][C:17]4=3)[C:22](=[O:24])[CH:23]=[CH:36]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(OC)N(C)C
Reactant: CC(=O)c1cnc2c(ccn2COCC[Si](C)(C)C)c1N[C@H]1CN(Cc2ccccc2)CC[C@H]1C
Product: C[C@@H]1CCN(Cc2ccccc2)C[C@@H]1n1ccc(=O)c2cnc3c(ccn3COCC[Si](C)(C)C)c21
Temperature: 25 °C
Reaction time: 1 h
Yield: 30 %

Procedure:
rac-1-(4-{[(3R,4R)-1-Benzyl-4-methylpiperidin-3-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-5-yl)ethanone (20 mg, 0.041 mmol) in N,N-dimethylformamide dimethyl acetal (1 mL) was stirred at 170° C. for 6 hours under microwave irradiation. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure, and the resulting residue was dissolved in tetrahydrofuran (1 mL) and stirred with 1 M hydrochloric acid (1 mL) at 80° C. for 1 hour. The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous sodium hydrogen carbonate, extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate/methanol=1/1/0→0/5/1 (v/v/v)) to give the title compound as a yellow oil (6.1 mg, yield 30%).
Reaction SMILES: C[O:2][C:3]([C:5]12[CH2:14][CH:9]3[CH2:10][CH:11]([CH2:13][CH:7]([CH2:8]3)[O:6]1)[CH2:12]2)=[O:4].[OH-].[Na+]>CO.O>[C:5]12([C:3]([OH:4])=[O:2])[CH2:14][CH:9]3[CH2:10][CH:11]([CH2:13][CH:7]([CH2:8]3)[O:6]1)[CH2:12]2
Reactant: COC(=O)C12CC3CC(CC(C3)O1)C2
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)C12CC3CC(CC(C3)O1)C2
Temperature: 25 °C
Reaction time: 3 h
Yield: 83.6 %

Procedure:
To a solution of Example 56A (2.5 g, 12.6 mmol) in methanol/water (1:1, 100 mL) was added 5 N aqueous NaOH (3.8 mL, 19 mmol). The mixture was stirred at room temperature for 3 hours and then extracted with methylene chloride to remove unreacted starting material. The aqueous layer was acidified (pH˜2) with 6 N aqueous HCl and then extracted with methylene chloride. The combined acidic extracts were dried (Na2SO4), filtered and concentrated to afford 1.92 g of the title compound. MS (ESI+) m/z 183 (M+H)+.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:20]Br.[O:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[C:24]([CH:31](O)[CH2:32][CH3:33])=[CH:23]1.N1C=CC=CC=1>C(Cl)Cl.C(OCC)C>[Br:20][CH2:33][CH2:32][CH2:31][C:24]1[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[O:22][CH:23]=1
Reactant: CCC(O)c1coc2ccccc12
Reactant: BrBr
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCOCC
Solvent: c1ccncc1
Product: BrCCCc1coc2ccccc12
Temperature: 25 °C
Reaction time: 4 h
Yield: 95.3 %

Procedure:
To a 0° C. solution of triphenylphosphine (2.07 g, 7.90 mmol) in methylene chloride (20 mL) was added bromine (0.4 mL, 7.90 mmol) dropwise. To the resulting cloudy mixture was added a solution of 3-benzofuran-3-yl-propan-1-ol (1.16 g, 6.58 mmol) and pyridine (1.07 mL, 13.2 mmol) in methylene chloride (10 mL). The reaction was stirred at room temperature for 4 hours, then was diluted with diethyl ether (100 mL) and filtered. The ethereal solution was washed with 1 M aqueous potassium hydrogen sulfate (50 mL), then with saturated aqueous sodium bicarbonate (50 mL), and finally with brine (50 mL), then was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuum. Flash chromatography on SiO2 (CH2Cl2) afforded 1.5 g (96%) of the title compound: 1H NMR (CDCl3, 400 MHz) δ 7.56 (d, J=7.8 Hz, 1 H), 7.47 (d, J=8.1 Hz, 1 H), 7.46 (s, 1 H), 7.7.22-7.35 (m, 2 H), 3.45 (t, J=6.4 Hz, 2 H), 2.87 (t, J=7.1 Hz, 2 H), 2.25 (quint, J=7.2 Hz, 2 H).
Reaction SMILES: [S:1]([NH2:11])(=[O:10])([C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][CH:4]=1)=[O:2].C([NH:20][C:21]#[N:22])(=O)C1C=CC=CC=1>C(O)C.Cl>[S:1]([C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:21]([NH2:22])=[NH:20])=[CH:7][CH:8]=1)(=[O:10])(=[O:2])[NH2:11]
Reactant: Nc1ccc(S(N)(=O)=O)cc1
Reactant: N#CNC(=O)c1ccccc1
Agent: Cl
Solvent: CCO
Product: N=C(N)Nc1ccc(S(N)(=O)=O)cc1

Procedure:
A mixture of sulphanilamide (20 g, 0.166 mol), benzoyl cyanamide (34 g, 0.33 mmol) in ethanol (60 ml) and concentrated hydrochloric acid (11 ml) was heated on a steam bath until the solvent had evaporated. Water was added and the mixture heated at reflux for 5 minutes. Sodium hydroxide (14.4 g) was added and the mixture heated at reflux. The mixture was allowed to cool and was adjusted to pH2 with hydrochloric acid and the precipitated solid removed by filtration. The filtrate was neutralised and the solvent removed by evaporation. The residue was recrystallized from water to give crude title product. m/z: 215 [MH]+.
Reaction SMILES: O[CH:2]([C:5]1[CH:9]=[CH:8][S:7][C:6]=1[C:10]([OH:12])=[O:11])[CH2:3][CH3:4].S(Cl)(C1C=CC(C)=CC=1)(=O)=O>ClCCl>[CH2:3]([CH:2]1[O:12][C:10](=[O:11])[C:6]2[S:7][CH:8]=[CH:9][C:5]1=2)[CH3:4]
Reactant: CCC(O)c1ccsc1C(=O)O
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: ClCCl
Product: CCC1OC(=O)c2sccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 296.7 %

Procedure:
A solution of 3-(1-Hydroxy-propyl)-thiophene-2-carboxylic acid (25 mg) in Dichloromethane (4 ml) and triethylamide (1.5 mL) is treated with TsCl (50 mg) and reaction is stirred at room temperature overnight. The reaction mixture is concentrated and the product is purified by chromatography (silica gel, 20% ethyl acetate/hexane) to give the title compound (67 mg, 13% yield).
Reaction SMILES: CCN(C(C)C)C(C)C.[C:10]1([NH:16][C:17]2[CH:25]=[CH:24][C:20]([C:21]([OH:23])=O)=[CH:19][CH:18]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH2:47][CH2:48][C:49]([N:51]1[CH2:56][CH2:55][N:54]([C:57](=[O:66])[C:58]2[CH:63]=[C:62]([Cl:64])[CH:61]=[CH:60][C:59]=2[Cl:65])[CH2:53][CH2:52]1)=[O:50].C(O)(C(F)(F)F)=O>CN(C=O)C.O>[Cl:65][C:59]1[CH:60]=[CH:61][C:62]([Cl:64])=[CH:63][C:58]=1[C:57]([N:54]1[CH2:53][CH2:52][N:51]([C:49](=[O:50])[CH2:48][NH:47][C:21](=[O:23])[C:20]2[CH:19]=[CH:18][C:17]([NH:16][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)=[CH:25][CH:24]=2)[CH2:56][CH2:55]1)=[O:66]
Reactant: O=C(O)c1ccc(Nc2ccccc2)cc1
Reactant: NCC(=O)N1CCN(C(=O)c2cc(Cl)ccc2Cl)CC1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: O
Product: O=C(NCC(=O)N1CCN(C(=O)c2cc(Cl)ccc2Cl)CC1)c1ccc(Nc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 78 %

Procedure:
DIPEA (133 mg, 0.18 mL, 1.0 mmol) was added drop wise to 4-(-phenyl-amino)-benzoic acid (75 mg, 0.35 mmol) in DMF (5 mL). EDCI (167 mg, 0.87 mmol) and HOBT (56 mg, 0.42 mmol) were added consecutively and, after 10 minutes, 2-amino-1-[4-(2,5-dichloro-benzoyl)-piperazin-1-yl]-ethanone in its TFA salt form (148 mg, 0.42 mmol) was added. The resulting mixture was stirred at room temperature overnight. Cold water was then added and filtered the solid to afford 140 mg (78% yield) of N-{2-[4-(2,5-dichloro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-4-phenylamino-benzamide. LC-MS purity: 95.65%. 1H-NMR (DMSO-d6): δ 8.6 (s, 1H), 8.3 (t, 1H), 7.8 (m, 5H), 7.3 (t, 2H), 7.2 (m, 4H), 6.9 (t, 1H), 4.1 (d, 2H), 3.6 (m, 6H), 3.2 (d, 2H).
Reaction SMILES: [C:1]([N:5]1[N:9]=[N:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]([NH:37][C:38](=[O:49])[C@H:39]([C:45]([CH3:48])([CH3:47])[CH3:46])[NH:40][C:41]([O:43][CH3:44])=[O:42])[CH2:18][C@H:19]([OH:36])[C@@H:20]([NH:28]C(OC(C)(C)C)=O)[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:12][CH:11]=2)=[N:6]1)([CH3:4])([CH3:3])[CH3:2].[ClH:50]>C1COCC1>[ClH:50].[C:1]([N:5]1[N:9]=[N:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]([NH:37][C:38](=[O:49])[C@H:39]([C:45]([CH3:48])([CH3:47])[CH3:46])[NH:40][C:41]([O:43][CH3:44])=[O:42])[CH2:18][C@H:19]([OH:36])[C@@H:20]([NH2:28])[CH2:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)=[CH:12][CH:11]=2)=[N:6]1)([CH3:2])([CH3:4])[CH3:3]
Reactant: COC(=O)N[C@H](C(=O)NN(Cc1ccc(-c2nnn(C(C)(C)C)n2)cc1)C[C@H](O)[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C)C(C)(C)C
Agent: Cl
Solvent: C1CCOC1
Product: COC(=O)N[C@H](C(=O)NN(Cc1ccc(-c2nnn(C(C)(C)C)n2)cc1)C[C@H](O)[C@@H](N)Cc1ccccc1)C(C)(C)C
Temperature: 50 °C
Reaction time: 8 h

Procedure:
Under a nitrogen atmosphere, 200 mg (0.293 mmol) of 1-[4-(2-tert-butyl-2H-tetrazol-5-yl)-phenyl]-4(S)-hydroxy-5(S)-N-(tert-butyloxycarbonyl)amino-2-N-[N-methoxycarbonyl-(L)-tert-leucyl]amino-6-phenyl-2-azahexane are dissolved in 2.3 ml of THF; 1.6 ml of aqueous 2N HCl are added and the mixture is stirred at 50° C. for 8 hours. The reaction solution is concentrated by evaporation; the residue is taken up several times in ethanol and concentrated by evaporation again (→title compound): TLC: Rt =0.08 (CH2Cl2 /MeOH 30:1); HPLC20-100(12') : tRet =9.9; 1H-NMR (CD3OD) d 8.03 and 7.50 (2d, J=8, each 2H), 7.32 (m, 5H), 4.18 and 3.91 (2d, J=4, 2H), 3.80 (m, 1H), 3.68 (s, 1H), 3.58 (s, 3H), 3.57 (m, 1H), 3.3-2.9 (m, 4H), 1.81 and 0.75 (2s, each 9H).
Reaction SMILES: [OH:1][CH:2]([C:16]1[CH:17]=[C:18]([NH:22][S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)(=[O:25])=[O:24])[CH:19]=[CH:20][CH:21]=1)[CH2:3][NH:4][C:5]([CH3:15])([CH3:14])[CH2:6][CH2:7][N:8]1[CH:12]=[C:11](I)[N:10]=[CH:9]1.C(=O)([O-])[O-].[Na+].[Na+].O1[CH2:43][CH2:42]OCC1.ClCCl>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH3:14][C:5]([NH:4][CH2:3][CH:2]([C:16]1[CH:17]=[C:18]([NH:22][S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)(=[O:25])=[O:24])[CH:19]=[CH:20][CH:21]=1)[OH:1])([CH3:15])[CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:26]2[S:23][C:42]([CH3:43])=[CH:28][CH:27]=2)[N:10]=[CH:9]1
Reactant: C1COCCO1
Reactant: CC(C)(CCn1cnc(I)c1)NCC(O)c1cccc(NS(=O)(=O)c2ccccc2)c1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: ClCCl
Product: Cc1ccc(-c2cn(CCC(C)(C)NCC(O)c3cccc(NS(=O)(=O)c4ccccc4)c3)cn2)s1
Temperature: 25 °C
Yield: 76 %

Procedure:
0.277 g (0.500 mmol) N-(3-{1-hydroxy-2-[3-(4-iodo-imidazol-1-yl)-1,1-dimethyl-propylamino]-ethyl}-phenyl)-benzenesulphonamide, 0.807 g (0.613 mmol) 5-methylthiophene-2-boric acid, 0.031 g (0.038 mmol) [1,1′-bis(diphenylphosphino)ferrocene]-palladium(II)-chloride (1:1 complex with dichloromethane), 2.00 mL aqueous sodium carbonate solution (2M) and 2 mL dioxane were stirred for 5 min at 150° C. in a sealed reaction vessel in a microwave. The reaction mixture was cooled to ambient temperature and then poured into 20 mL dichloromethane and 20 mL water. The phases were separated, the organic phase was washed twice with 20 mL water, dried over magnesium sulphate and the solvent was eliminated using the rotary evaporator. The residue was purified by flash column chromatography [methylene chloride/methanol (100:0→75:25)]. 0.200 g (0.381 mmol, 76%) N-[3-(2-{1,1-dimethyl-3-[4-(5-methyl-thiophen-2-yl)-imidazol-1-yl]-propylamino}-1-hydroxy-ethyl)-phenyl]-benzenesulphonamide were obtained as a beige solid.
Reaction SMILES: [CH2:1]([O:8][C:9](Cl)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:12][CH2:13][CH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[CH2:1]([O:8][C:9]([N:17]1[CH2:18][CH2:19][CH:14]([CH2:13][OH:12])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: OCC1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: O=C(OCc1ccccc1)N1CCC(CO)CC1
Reaction time: 3 h
Yield: 42.5 %

Procedure:
A solution of benzylchloroformate (17 g, 100 mmol) in 50 mL of 2-butanone was added dropwise to a stirred mixture of 4-hydroxymethylpiperidine (10.3 g, 100 mol) and potassium carbonate (13.8 g, 100 mmol) in 300 mL of 2-butanone. When the addition was complete the stirring was continued for an additional 3 hours. The solids formed were filtered and the filtrate concentrated in vacuo. Pure product was obtained by flash chromatography (hexane-ethyl acetate, 2:1) to give 10.6 g of product as an oil.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][OH:18])=[CH:13][CH:12]=2)=[N:8][CH:9]=1)([O-])=O.C(O)(=O)C.[CH3:23][S:24](Cl)(=[O:26])=[O:25]>N1C=CC=CC=1.[Zn].[O-2].[O-2].[Mn+4]>[CH:17]([C:14]1[CH:15]=[CH:16][C:11]([O:10][C:7]2[N:8]=[CH:9][C:4]([NH:1][S:24]([CH3:23])(=[O:26])=[O:25])=[CH:5][CH:6]=2)=[CH:12][CH:13]=1)=[O:18]
Reactant: CS(=O)(=O)Cl
Reactant: O=[N+]([O-])c1ccc(Oc2ccc(CO)cc2)nc1
Agent: [Mn+4]
Agent: [O-2]
Agent: [Zn]
Solvent: CC(=O)O
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1ccc(Oc2ccc(C=O)cc2)nc1

Procedure:
{4-[(5-nitropyridin-2-yl)oxy]phenyl}methanol was subjected to reduction of nitro group by using zinc and acetic acid, the obtained compound reacted with methanesulfonyl chloride in pyridine, and the obtained compound was subjected to oxidation by using manganese dioxide to give the title compound having the following physical data.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[F:11].[C:12]([CH:14]1[CH2:16][CH2:15]1)#[CH:13]>>[CH:14]1([C:12]#[C:13][C:2]2[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=2[F:11])[CH2:16][CH2:15]1
Reactant: C#CC1CC1
Reactant: O=[N+]([O-])c1ccc(F)c(Br)c1
Product: O=[N+]([O-])c1ccc(F)c(C#CC2CC2)c1

Procedure:
2-Bromo-1-fluoro-4-nitrobenzene and ethynylcyclopropane were reacted by method MA. The product with the molecular weight of 205.19 (C11H8FNO2) was obtained in this way; MS (ESI): 206 (M+H+).