Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][N:5]2[C:10]=1[CH2:11]O.[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([SH:20])=[CH:16][CH:15]=1.[OH-].[Na+]>Cl>[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([S:20][CH2:11][C:10]2[N:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]3=[N:3][C:2]=2[CH3:1])=[CH:16][CH:15]=1
Reactant: Nc1ccc(S)cc1
Reactant: Cc1nc2ccccn2c1CO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: Cc1nc2ccccn2c1CSc1ccc(N)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 22.2 %

Procedure:
Under nitrogen atmosphere, to a suspension of aluminum lithium hydride (1.6 g) in THF (100 ml) was added dropwise a solution of ethyl 2-methylimidazo[1,2-a]pyridine-3-carboxylate (8.56 g) in THF (100 ml) at 0° C. under nitrogen atmosphere. The mixture was stirred for 1 hour at 0° C., water (1.6 ml), 15% aqueous solution of sodium hydroxide (1.6 ml) and water (4.8 ml) were sequentially and slowly added dropwise to the solution, and the mixture was stirred for 2 hours at room temperature. To the reaction solution was added magnesium sulfate, and the precipitates were removed by filtration. The mixture was concentrated under reduced pressure, to give 2-methylimidazo[1,2-a]pyridine-3-methanol (6.45 g) as pale yellow amorphous. A mixture of 2-methylimidazo[1,2-a]pyridine-3-methanol (1 g) and 4-aminothiophenol (0.65 g) in concentrated hydrochloric acid (10 ml) was stirred for 18 hours at room temperature. 8N aqueous solution of sodium hydroxide was added to adjust pH to 10 at 0° C. and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was separated and purified by column chromatography (ethanol:ethyl acetate 1:4), to give 3-(4-aminophenylthiomethyl)-2-methylimidazo[1,2-a]pyridine (311 mg) as colorless crystals.
Reaction SMILES: C([O:5][C:6](=[O:19])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][C:10]=1[C:17]#[CH:18])(C)(C)C.Br[C:21]1[CH:22]=[C:23]([S:28]([CH2:31][CH2:32][OH:33])(=[O:30])=[O:29])[CH:24]=[CH:25][C:26]=1[CH3:27]>>[C:15]([C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:7][C:6]([OH:5])=[O:19])=[C:10]([C:17]#[C:18][C:21]2[CH:22]=[C:23]([S:28]([CH2:31][CH2:32][OH:33])(=[O:30])=[O:29])[CH:24]=[CH:25][C:26]=2[CH3:27])[CH:11]=1)#[N:16]
Reactant: C#Cc1cc(C#N)ccc1OCC(=O)OC(C)(C)C
Reactant: Cc1ccc(S(=O)(=O)CCO)cc1Br
Product: Cc1ccc(S(=O)(=O)CCO)cc1C#Cc1cc(C#N)ccc1OCC(=O)O

Procedure:
Following the general method as outlined in Example 37, starting from tert-butyl(4-cyano-2-ethynyl phenoxy)acetate (Intermediate 46) and 2-[(3-bromo-4-methylphenyl)sulfonyl]ethanol (Intermediate 67), the title compound was obtained as a yellow solid.
Reaction SMILES: [CH3:1][N:2]([CH3:8])[CH:3]1[CH2:7][CH2:6][NH:5][CH2:4]1.F[C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[CH:12][CH:11]=1>>[NH2:16][C:13]1[CH:14]=[CH:15][C:10]([N:5]2[CH2:6][CH2:7][CH:3]([N:2]([CH3:8])[CH3:1])[CH2:4]2)=[CH:11][CH:12]=1
Reactant: CN(C)C1CCNC1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Product: CN(C)C1CCN(c2ccc(N)cc2)C1

Procedure:
Dimethylpyrrolidin-3-ylamine was reacted with 4-fluoronitrobenzene by method C, and the product was subsequently hydrogenated by method B. This resulted in the product with the molecular weight of 205.31 (C12H19N3); MS (ESI): 206 (M+H+).
Reaction SMILES: [O:1]=[C:2]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=[O:8])[CH2:3]1.S(=O)(=O)(O)O.[CH3:15]O>>[O:1]=[C:2]1[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH3:15])=[O:8])[CH2:3]1
Reactant: O=C1CCC(C(=O)O)C1
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)C1CCC(=O)C1
Reaction time: 1.5 h
Yield: 84 %

Procedure:
A solution of 3-oxocyclopentanecarboxylic acid (13.2 g, 103 mmol), MeOH (130 ml) and 98% sulfuric acid (0.1 ml) was heated under reflux with stirring for 1.5 h. The MeOH was evaporated in vacuo. The residue was dissolved in CH2Cl2 (100 ml) and was washed with 1% sodium bicarbonate (50 ml). The solvent was evaporated in vacuo to give the title compound as a liquid, 12.2 g (84% yield); ir (liq.) νmax : 1730-1740 cm-1 ; 1Hmr (CDCl3) δ: 3.71 (s, 3H, OMe), 3.2 (m, 1H, H-1) and 2.5-1.9 ppm (m, 6H, CH2).
Reaction SMILES: [C:1]([N:3]=[C:4]1[NH:9][CH2:8][CH2:7][CH2:6][N:5]1[C@@H:10]1[C:15]2[CH:16]=[C:17]([C:20]#[N:21])[CH:18]=[CH:19][C:14]=2[O:13][C:12]([CH3:23])([CH3:22])[C@H:11]1[OH:24])#[N:2].[C:25](OC(=O)C)(=[O:27])[CH3:26]>N1C=CC=CC=1>[C:25]([O:24][C@H:11]1[C@H:10]([N:5]2[CH2:6][CH2:7][CH2:8][NH:9][C:4]2=[N:3][C:1]#[N:2])[C:15]2[CH:16]=[C:17]([C:20]#[N:21])[CH:18]=[CH:19][C:14]=2[O:13][C:12]1([CH3:22])[CH3:23])(=[O:27])[CH3:26]
Reactant: CC1(C)Oc2ccc(C#N)cc2[C@@H](N2CCCNC2=NC#N)[C@@H]1O
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)O[C@H]1[C@H](N2CCCNC2=NC#N)c2cc(C#N)ccc2OC1(C)C
Temperature: 25 °C
Reaction time: 168 h

Procedure:
A mixture of trans-4-(2-cyanoiminohexahydropyrimidin-1-yl)-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (651 mg) and acetic anhydride (0.76 ml) in pyridine (2 ml) was stirred for 7 days at room temperature. The mixture was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate, washed twice with water and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo and the residue was pulverized with diisopropyl ether to give trans-3-acetoxy-4-(2-cyanoiminohexahydropyrimidin-1-yl)-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6carbonitrile (0.76 g).
Reaction SMILES: [NH2:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][C@@H:7]2[CH2:11][CH2:10][C@H:9]([C@H:12]([OH:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:8]2C(OC(C)(C)C)=O)=[CH:4][CH:3]=1.[N:29]([C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=1)=[C:30]=[O:31].C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:19][C@H:12]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C@@H:9]1[NH:8][C@H:7]([CH2:6][C:5]2[CH:27]=[CH:28][C:2]([NH:1][C:30]([NH:29][C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=3)=[O:31])=[CH:3][CH:4]=2)[CH2:11][CH2:10]1
Reactant: CC(C)(C)OC(=O)N1[C@H](Cc2ccc(N)cc2)CC[C@@H]1[C@H](O)c1ccccc1
Reactant: COc1cccc(N=C=O)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1cccc(NC(=O)Nc2ccc(C[C@@H]3CC[C@H]([C@H](O)c4ccccc4)N3)cc2)c1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
To a solution of 30 mg (0.078 mmol) of tert-butyl (2S,5R)-2-(4-aminobenzyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidine-1-carboxylate (i-13a) in CH2Cl2 (0.5 mL) was added 14 mg (0.094 mmol) of 1-isocyanato-3-methoxybenzene. The reaction mixture was stirred at ambient temperature for 2.5 h. It was then added TFA (0.4 mL) and was stirred at ambient temperature for another 3 h. After removal of the volatiles, it was purified by reverse-phase HPLC (TMC Pro-Pac C18; 10-80% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient). The pure fractions were lyophilized overnight to give the title compound as a white solid. LC/MS 432.3 (M+1).
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([C:13]1[CH:18]=[CH:17][C:16]([C:19]([NH:21][NH:22][C:23]([O:25]C(C)(C)C)=O)=[S:20])=[CH:15][CH:14]=1)[CH:7]=[CH:6]2.[Al+3].[Cl-].[Cl-].[Cl-].CCOC(C)=O>C(Cl)Cl>[OH:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([C:13]1[CH:18]=[CH:17][C:16]([C:19]3[S:20][C:23](=[O:25])[NH:22][N:21]=3)=[CH:15][CH:14]=1)[CH:7]=[CH:6]2
Reactant: COc1ccc2nc(-c3ccc(C(=S)NNC(=O)OC(C)(C)C)cc3)ccc2c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: O=c1[nH]nc(-c2ccc(-c3ccc4cc(O)ccc4n3)cc2)s1
Yield: 7 %

Procedure:
A mixture of tert-butyl 2-(4-(6-methoxyquinolin-2-yl)phenylcarbonothioyl)hydrazinecarboxylate (500 mg, 1.49 mmol) and AlCl3 (600 mg, 4.50 mmol) in anhydrous DCM (50 mL) was refluxed overnight. Reaction was cooled, followed by an aqueous/EtOAc workup. The residue was purified by prep-HPLC (0.1% TFA as additive) to give Compound IV-33 (35 mg, yield 7%) as a solid. 1H NMR (DMSO-d6, 400 MHz): δ 13.22 (brs, 1H), 10.22 (brs, 1H), 8.40-8.28 (m, 3H), 8.11 (d, J=8.8 Hz, 1H), 7.98 (d, J=8.8 Hz, 1H), 7.86 (d, J=8.4 Hz, 2H), 7.38 (dd, J=9.2, 2.8 Hz, 1H), 7.22 (d, J=2.8 Hz, 1H). MS (ESI): m/z 321.7 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]2[C:13]3[C:18]([N:19]=[C:20]([CH3:21])[C:11]2=[C:10]([CH3:23])[N:9]=1)=[CH:17][C:16]([OH:22])=[CH:15][CH:14]=3.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O.[N+:35]([C:38]1[CH:39]=[C:40]([CH:43]=[CH:44][CH:45]=1)[CH2:41]Br)([O-:37])=[O:36]>O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]2[C:13]3[C:18]([N:19]=[C:20]([CH3:21])[C:11]2=[C:10]([CH3:23])[N:9]=1)=[CH:17][C:16]([O:22][CH2:41][C:40]1[CH:43]=[CH:44][CH:45]=[C:38]([N+:35]([O-:37])=[O:36])[CH:39]=1)=[CH:15][CH:14]=3
Reactant: Cc1nc(-c2ccccc2Cl)n2c1c(C)nc1cc(O)ccc12
Reactant: O=[N+]([O-])c1cccc(CBr)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1nc(-c2ccccc2Cl)n2c1c(C)nc1cc(OCc3cccc([N+](=O)[O-])c3)ccc12
Temperature: 120 °C
Reaction time: 3 h

Procedure:
1.5 g 1-(2-Chloro-phenyl)-3,4-dimethyl-7-hydroxy-imidazo(1,5-a)quinoxaline, 3.36 g Caesium carbonate, 80 mL N,N-dimethylformamide, and 9 mL water were stirred for 10 min followed by addition of 1.3 g 3-nitro-benzylbromide. After 3 h stirring at 120° C. the reaction mixture was given into 250 mL water, filtered off, washed with water, dried under reduced pressure.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([CH3:14])[CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2[CH:26]=[CH:27][CH:28]=[N:29][C:24]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1CCCC1>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH3:14])[CH2:10][C:11](=[O:13])[N:29]1[CH2:28][CH2:27][CH2:26][CH2:24]1)([CH3:2])([CH3:3])[CH3:4]
Reactant: C[C@H](CC(=O)O)NC(=O)OC(C)(C)C
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCNC1
Solvent: CN(C)C=O
Product: C[C@H](CC(=O)N1CCCC1)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of (R)-3-tert-butoxycarbonylamino-butyric acid (150 mg, 0.74 mmol) and HATU (309 mg, 0.81 mmol) in DMF (2 mL) was added pyrrolidine (0.19 mL, 2.21 mmol). The resultant yellow reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (2×). The combined organics were washed with water (3×) and brine then dried over MgSO4 and concentrated to afford ((R)-1-methyl-3-oxo-3-pyrrolidin-1-yl-propyl)-carbamic acid tert-butyl ester as a colorless oil which was used without further purification.
Reaction SMILES: C[N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:4]=[C:3]1[CH2:13]O.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+].[Cl:42]CCCl>>[Cl:42][CH2:13][C:3]1[NH:2][CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:4]=1
Reactant: ClCCCl
Reactant: Cn1cc(-c2ccccc2)nc1CO
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=C([O-])O
Agent: [Na+]
Product: ClCc1nc(-c2ccccc2)c[nH]1
Temperature: 25 °C
Reaction time: 2 h
Yield: 79 %

Procedure:
To a solution of (1-Methyl-4-phenyl-1H-imidazol-2-yl)-methanol 5 (50.0 mg, 0.266 mmol) in 1,2-dichloroethane (4.0 mL) under Ar was added Dess-Martin periodinane (124 mg, 0.292 mmol), and the mixture was stirred at room temperature for 2 hours. Saturated NaHCO3 solution was added, the organic layer was separated and the aqueous layer was extracted with 1,2-dichloroethane. The combined organic layers were dried over Na2SO4, volatiles were evaporated and the residue was purified by silica gel chromatography on a FlashMaster system (gradient elution; 0-100% ethylacetate in heptane) to afford the title compound as a white solid (39.1 mg, 79%). 1H NMR (500 MHz, DMSO-d6): δ9.76 (s, 1H), 8.11 (s, 1H), 7.84 (d, J=7.7 Hz, 2H), 7.42 (t, J=7.6 Hz, 2H), 7.30 (t, J=7.4 Hz, 1H), 3.99 (s, 3H).
Reaction SMILES: C([O:3][C:4](=O)[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]([F:21])([F:20])[F:19])=[CH:13][CH:12]=2)=[N:7][C:6]=1[C:22]([F:25])([F:24])[F:23])C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[F:21][C:18]([F:19])([F:20])[O:17][C:14]1[CH:15]=[CH:16][C:11]([C:8]2[N:7]=[C:6]([C:22]([F:23])([F:24])[F:25])[C:5]([CH2:4][OH:3])=[CH:10][CH:9]=2)=[CH:12][CH:13]=1
Reactant: CCOC(=O)c1ccc(-c2ccc(OC(F)(F)F)cc2)nc1C(F)(F)F
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: OCc1ccc(-c2ccc(OC(F)(F)F)cc2)nc1C(F)(F)F

Procedure:
In analogy to the procedure described in example 16 c], 6-(4-trifluoromethoxy-phenyl)-2-trifluoromethyl-nicotinic acid ethyl ester was treated with lithium aluminium hydride to give the title compound as colorless crystals.
Reaction SMILES: [Na].[N:2]([CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])=[N+:3]=[N-:4].[CH3:11][O:12][C:13]1[CH:27]=[CH:26][C:16]([O:17][C:18]2[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=2)[CH:21]=O)=[CH:15][CH:14]=1.[NH4+].[Cl-]>C(O)C>[N:2]([C:5](=[CH:21][C:20]1[CH:23]=[CH:24][CH:25]=[C:18]([O:17][C:16]2[CH:26]=[CH:27][C:13]([O:12][CH3:11])=[CH:14][CH:15]=2)[CH:19]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])=[N+:3]=[N-:4]
Reactant: COc1ccc(Oc2cccc(C=O)c2)cc1
Reactant: CCOC(=O)CN=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na]
Solvent: CCO
Product: CCOC(=O)C(=Cc1cccc(Oc2ccc(OC)cc2)c1)N=[N+]=[N-]
Temperature: -5 °C
Reaction time: 4.5 h

Procedure:
Sodium metal (2.01 g, 87.43 mmol) cut into small pieces was dissolved in absolute ethanol (67 mL) and the resulting solution cooled to -5° C. A mixture of ethyl azidoacetate (11.32 g, 87.67 mmol) and 3-(4-methoxyphenoxy) benzaldehyde (5.0 g, 21.91 mmol) was added dropwise over 30 min. On completion of addition the mixture was stirred at -5° C. for 4.5 hr, and then kept at room temperature overnight. The red reaction mixture was poured into saturated aqueous NH4Cl solution and extracted (3×) with Et2O. The ethereal extracts were washed (H2O and then saturated aqueous NaCl), dried (MgSO4) and evaporated to give an orange gum which was chromatographed (silica gel; hexane/Et2O; 0-15%). The product: ethyl 2-azido-3-(3-(4-methoxyphenoxy)phenyl)propenoate, was thus obtained as a light yellow gum, 5.5 g (70%).
Reaction SMILES: [F:1][C:2]1[CH:32]=[CH:31][C:5]([C:6]([NH:8][C:9]2[N:13]([C@H:14]3[CH2:19][CH2:18][C@@H:17]([C:20](=[O:25])[NH:21][CH:22]([CH3:24])[CH3:23])[CH2:16][CH2:15]3)[C:12]3[CH:26]=[C:27]([OH:30])[CH:28]=[CH:29][C:11]=3[N:10]=2)=[O:7])=[CH:4][CH:3]=1.Cl[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN1C(=O)CCC1>CCOC(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:29]=[CH:28][C:27]([O:30][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=4)=[CH:26][C:12]=3[N:13]\2[C@H:14]2[CH2:19][CH2:18][C@@H:17]([C:20](=[O:25])[NH:21][CH:22]([CH3:24])[CH3:23])[CH2:16][CH2:15]2)=[O:7])=[CH:31][CH:32]=1
Reactant: CC(C)NC(=O)[C@H]1CC[C@@H](n2c(NC(=O)c3ccc(F)cc3)nc3ccc(O)cc32)CC1
Reactant: Clc1ccccn1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN1CCCC1=O
Solvent: CCOC(C)=O
Product: CC(C)NC(=O)[C@H]1CC[C@@H](n2/c(=N/C(=O)c3ccc(F)cc3)[nH]c3ccc(Oc4ccccn4)cc32)CC1

Procedure:
A microwave vial was charged with 4-fluoro-N-(6-hydroxy-1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2-yl)benzamide (56 mg, 0.128 mmol), 2-chloropyridine (0.036 mL, 0.383 mmol), cesium carbonate (166 mg, 0.511 mmol), and NMP (0.6 mL) then irradiated in the microwave at 160° C. for 6 hours. The mixture was diluted with EtOAc, washed with water, the water layer back extracted with EtOAc, and the combined organics were washed with brine. The organic layer was dried over Na2SO4 and filtered. The mixture was purified via flash chromatography using a linear gradient of 0% to 10% MeOH in DCM. The material was further purified by reverse-phase preparative HPLC using a 0.1% TFA in ACN/H2O, gradient 10% to 90%. The material was partitioned between saturated aqueous NaHCO3 and 5% IPA/DCM, the organic layer washed with brine, dried over Na2SO4, filtered and evaporated. The title compound was isolated as an off-white solid (32 mg, 35% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.98 (d, J=8.00 Hz, 6H) 1.54-1.82 (m, 4H) 2.01-2.14 (m, 2H) 2.42-2.56 (m, 1H) 2.56-2.77 (m, 2H) 3.75-3.93 (m, 1H) 4.80-4.95 (m, 1H) 6.97 (dd, J=8.56, 2.10 Hz, 1H) 6.95-7.10 (m, 1H) 7.00-7.18 (m, 1H) 7.20-7.29 (m, 2H) 7.48 (d, J=2.05 Hz, 1H) 7.51-7.62 (m, 2H) 7.80-7.90 (m, 1H) 8.07-8.19 (m, 1H) 8.27-8.38 (m, 2H) 12.81 (s, 1H). M/Z calc'd for C29H30FN5O3: 515.58. found 516 [M+H].
Reaction SMILES: [OH:1][C:2]1[CH:14]=[CH:13][C:5]2[N:6]=[C:7]([S:9]([NH2:12])(=[O:11])=[O:10])[S:8][C:4]=2[CH:3]=1.[CH3:15][N:16]([CH3:20])[C:17](Cl)=[O:18].Cl>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[CH3:15][N:16]([CH3:20])[C:17](=[O:18])[O:1][C:2]1[CH:14]=[CH:13][C:5]2[N:6]=[C:7]([S:9](=[O:11])(=[O:10])[NH2:12])[S:8][C:4]=2[CH:3]=1
Reactant: CN(C)C(=O)Cl
Reactant: NS(=O)(=O)c1nc2ccc(O)cc2s1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: c1ccncc1
Product: CN(C)C(=O)Oc1ccc2nc(S(N)(=O)=O)sc2c1
Temperature: 0 °C
Reaction time: 18 h
Yield: 76325.2 %

Procedure:
To a stirred solution of 6-hydroxy-2-benzothiazolesulfonamide (2.3 g, 0.01 mole) and 4-dimethylaminopyridine (200 mg) in pyridine (25 ml) was added dimethylcarbamoyl chloride (0.95 ml, 0.01 mmole). After stirring for 18 hours additional dimethylcarbamoyl chloride (1.5 ml) was added and stirring was continued for 18 hours. The reaction mixture was poured into ice water and excess hydrochloric acid to give 2.3 g of (2-sulfamoyl-6-benzothiazolyl) N,N-dimethylcarbamate which melts at 208°-209° C. after recrystallization from 2-propanol.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[C@@H:3]([OH:9])[C@H:4]([CH:6]1[CH2:8][CH2:7]1)[OH:5].[C:17]([NH:34][C@H:35]([C:40](O)=[O:41])[CH2:36][CH2:37][CH2:38][CH3:39])([O:19][CH2:20][CH:21]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]2[C:22]1=[CH:23][CH:24]=[CH:25][CH:26]=2)=[O:18]>>[CH:11]1([CH2:10][C@H:2]([NH:1][C:40]([C@@H:35]([NH:34][C:17](=[O:18])[O:19][CH2:20][CH:21]2[C:33]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:27]3[C:22]2=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:36][CH2:37][CH2:38][CH3:39])=[O:41])[C@@H:3]([OH:9])[C@H:4]([CH:6]2[CH2:8][CH2:7]2)[OH:5])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1
Reactant: CCCC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Reactant: N[C@@H](CC1CCCCC1)[C@@H](O)[C@@H](O)C1CC1
Product: CCCC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)N[C@@H](CC1CCCCC1)[C@@H](O)[C@@H](O)C1CC1

Procedure:
Analogously to the procedure described in Example 1, paragraph (c), by condensing (1S,2R,3S)-3-amino-4-cyclohexyl-1-cyclopropyl-1,2-butanediol and Fmoc-norleucine there was obtained 9H-fluoren-9-ylmethyl [(S)-1-[[(1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]carbamoyl]pentyl]carbamate which, after reaction with piperidine in methylene chloride, yielded (S)-2-amino-N-[(1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]hexanamide as a colourless foam, MS: 322 (M-H2)+.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O:7][C:8]2[N:13]=[CH:12][C:11]([NH2:14])=[CH:10][CH:9]=2)[CH:2]=1.[NH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]([C:24](O)=[O:25])=[CH:16]1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O:7][C:8]2[N:13]=[CH:12][C:11]([NH:14][C:24]([C:17]3[C:18]4[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=4)[NH:15][CH:16]=3)=[O:25])=[CH:10][CH:9]=2)[CH:2]=1
Reactant: Nc1ccc(Oc2cccnc2)nc1
Reactant: O=C(O)c1c[nH]c2ccccc12
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CN(C)C=O
Product: O=C(Nc1ccc(Oc2cccnc2)nc1)c1c[nH]c2ccccc12
Temperature: 60 °C
Reaction time: 8 h
Yield: 61 %

Procedure:
The 6-(pyridine-3-yloxy)pyridine-3-amine (200 mg, 1.24 mmol) and indole-3-carboxylic acid (200 mg, 1.24 mmol) were dissolved in DMF (5 ml), DCC (280 mg, 1.37 mmol) was added to the solution, and then the mixture was stirred at 60° C. for 8 hours. After the reaction was completed, the product was washed and filtered to yield a target compound as a white solid (250 mg, 61%) by chromatography (methanol:dichloromethane=1:30).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]([CH3:12])[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[C:13](OC(=O)C)(=[O:15])[CH3:14].C1(C)C(C)=CC=CC=1>O>[C:13]([N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([Br:1])[CH:10]=2)[CH:6]([CH3:12])[C:7]1=[O:11])(=[O:15])[CH3:14]
Reactant: CC(=O)OC(C)=O
Reactant: CC1C(=O)Nc2cc(Br)ccc21
Solvent: O
Solvent: Cc1ccccc1C
Product: CC(=O)N1C(=O)C(C)c2ccc(Br)cc21

Procedure:
To 6-bromo-3-methyl-1,3-dihydro-2H-indol-2-one (11.2 g) were added acetic anhydride (12 ml) and xylene (120 ml), and the mixture was refluxed for 5 hours. After the reaction was complete, water was added to the reaction solution, and the mixture was extracted with ethyl acetate solution. This ethyl acetate solution was washed successively with water, a saturated aqueous sodium hydrogen carbonate solution and an aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1) to give the title compound (9.5 g) as a red solid.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:29](=[O:36])[N:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]#[C:18][CH2:19][CH2:20][CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(OCC)(=O)C.[Pd+2]>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:29](=[O:36])[N:30]1[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]1)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])=[CH:13][CH:12]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)CCCC#Cc1ccc(C[C@H](NC(=O)OC(C)(C)C)C(=O)N2CCCCC2)cc1
Agent: [Pd+2]
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)CCCCCc1ccc(C[C@H](NC(=O)OC(C)(C)C)C(=O)N2CCCCC2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
tert-Butyl (S)-6-(4-(2-((tert-butoxycarbonyl)amino)-3-oxo-3-(piperidin-1-yl)propyl)phenyl)hex-5-ynoate (Compound SP425) (5.74 g, 11.51 mmol) was dissolved in ethyl acetate (40 ml), and 10% palladium(II) on carbon (1.72 g) was added under a nitrogen atmosphere. The mixture was then stirred at room temperature for 2 hours under a hydrogen atmosphere. After filtration through celite, the filtrate was concentrated under reduced pressure to afford the title compound SP426 (5.65 g, 98%).
Reaction SMILES: C([O-])(=O)C.[NH4+:5].[CH3:6][C:7]([CH3:44])([CH2:42][CH3:43])[CH2:8][C:9](=O)[CH2:10][NH:11][C:12](=O)[C:13]([NH:29][C:30](=[O:39])[O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][N:23]=2)=[CH:18][CH:17]=1)[CH3:14].C(=O)(O)[O-].[Na+]>>[CH2:32]([O:31][C:30](=[O:39])[NH:29][C:13]([C:12]1[NH:11][CH:10]=[C:9]([CH2:8][C:7]([CH3:6])([CH3:44])[CH2:42][CH3:43])[N:5]=1)([CH3:14])[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][N:23]=2)=[CH:18][CH:17]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1
Reactant: CCC(C)(C)CC(=O)CNC(=O)C(C)(Cc1ccc(-c2ccc(F)cn2)cc1)NC(=O)OCc1ccccc1
Reactant: [NH4+]
Agent: CC(=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Product: CCC(C)(C)Cc1c[nH]c(C(C)(Cc2ccc(-c3ccc(F)cn3)cc2)NC(=O)OCc2ccccc2)n1
Temperature: 160 °C
Reaction time: 1 h

Procedure:
Ammonium acetate (2.53 g, 32.79 mmol) was added to an ambient temperature solution of benzyl {2-[(4,4-dimethyl-2-oxohexyl)amino]-1-[4-(5-fluoropyridin-2-yl)benzyl]-1-methyl-2-oxoethyl}carbamate (350 mg, 0.66 mmol) in xylenes (minimal volume). After stirring in a sealed tube at 160° C. for 1 hr, the reaction mixture was poured into saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (sodium sulfate) and concentrated. High pressure liquid chromatography (KR100-5C18 100×21.2 mm column) eluting with 10-100% acetonitrile/water containing 0.05% trifluoroacetic acid afforded the title compound. (M+H) found: 515.