Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([C@H:5]([NH:17]C(=O)OCC1C=CC=CC=1)[CH2:6][C:7]1[CH:8]=[CH:9][C:10]2[NH:14][C:13](=[O:15])[NH:12][C:11]=2[CH:16]=1)=[O:4].[H][H]>[Pd].CO>[NH2:17][C@H:5]([CH2:6][C:7]1[CH:8]=[CH:9][C:10]2[NH:14][C:13](=[O:15])[NH:12][C:11]=2[CH:16]=1)[C:3]([O:2][CH3:1])=[O:4]
Reactant: COC(=O)[C@@H](Cc1ccc2[nH]c(=O)[nH]c2c1)NC(=O)OCc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: COC(=O)[C@H](N)Cc1ccc2[nH]c(=O)[nH]c2c1
Yield: 99.2 %

Procedure:
Benzyl (R)-1-(methoxycarbonyl)-2-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-6-yl)ethylcarbamate (265 mg, 0.72 mmol) and 10% palladium on carbon (30 mg) in methanol (15 mL) were agitated for 1.5 h under 50 psi hydrogen using a Parr apparatus. The reaction mixture was purged with 3 vacuum/nitrogen purge cycles. The reaction mixture was then filtered through a pad of Celite® and the pad was rinsed with several portions of methanol. The methanol filtrate was evaporated to give the title compound (168 mg, quantitative yield). 1H-NMR (CD3OD, 300 MHz) δ 6.97 (d, J=8.1 Hz, 1H), 6.87 (s, 1H), 6.86 (d, J=8.2 Hz, 1H), 3.71–3.64 (m, 1H), 3.67 (s, 3H), 3.04–2.89 (m, 2H). LC/MS: tR=0.87 min, 236 (MH)+.
Reaction SMILES: [F:1][C:2]1[C:11]([F:12])=[CH:10][CH:9]=[CH:8][C:3]=1[C:4](=[N:6][OH:7])[NH2:5].Cl.[C:14](Cl)(=O)[C:15]1[CH:20]=[CH:19][CH:18]=[N:17][CH:16]=1.N>>[F:1][C:2]1[C:11]([F:12])=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]1[N:5]=[C:14]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[O:7][N:6]=1
Reactant: NC(=NO)c1cccc(F)c1F
Reactant: O=C(Cl)c1cccnc1
Agent: Cl
Agent: N
Product: Fc1cccc(-c2noc(-c3cccnc3)n2)c1F

Procedure:
The title compound was prepared according to the procedure of Example 1 using 2,3-difluoro-N′-hydroxybenzimidamide (Tyger Scientific) and nicotinoyl chloride hydrochloride (Aldrich). 1H NMR (300 MHz, DMSO-d6) δ 7.42-7.61 (m, 1H), 7.67-7.85 (m, 2H), 7.91-8.04 (m, 1H), 8.57 (dt, J=8.1, 1.9 Hz, 1H), 8.92 (dd, J=4.8, 1.6 Hz, 1H), 9.36 (dd, J=2.4, 0.8 Hz, 1H) ppm; MS (DCl/NH3) m/z 260 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:3]([O:14]C)=[CH:4][C:5]2[CH:9]=[C:8]([CH2:10][CH3:11])[S:7][C:6]=2[C:12]=1[Cl:13].Cl.N1C=CC=CC=1>>[Cl:1][C:2]1[C:3]([OH:14])=[CH:4][C:5]2[CH:9]=[C:8]([CH2:10][CH3:11])[S:7][C:6]=2[C:12]=1[Cl:13]
Reactant: CCc1cc2cc(OC)c(Cl)c(Cl)c2s1
Agent: Cl
Solvent: c1ccncc1
Product: CCc1cc2cc(O)c(Cl)c(Cl)c2s1
Reaction time: 1.5 h
Yield: 73.7 %

Procedure:
A mixture of 2.15 g of 6,7-dichloro-2-ethyl-5-methoxybenzo[b]thiophene and 15 g of pyridine hydrochloride is stirred at 170°-180° C. for 90 min. The mixture is cooled, triturated with water and extracted three times with dichloromethane. The combined organic extracts are washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo to an oily residue. Purification by column chromatography (silica gel-ether-pentane 50:50) affords 1.5 g of 6,7-dichloro-2-ethyl-5-hydroxybenzo[b]thiophene as off-white crystals, mp 69°-70°.
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[C:4]([C:19]2[O:20][CH:21]=[CH:22][CH:23]=2)[N:3]=1.[CH3:24][NH:25][CH3:26]>C(O)(C)C.O>[CH3:24][N:25]([CH3:26])[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[C:4]([C:19]2[O:20][CH:21]=[CH:22][CH:23]=2)[N:3]=1
Reactant: C[Si](C)(C)CCOCn1cnc2c(-c3ccco3)nc(Cl)nc21
Reactant: CNC
Solvent: CC(C)O
Solvent: O
Product: CN(C)c1nc(-c2ccco2)c2ncn(COCC[Si](C)(C)C)c2n1
Yield: 86 %

Procedure:
A solution of 2-chloro-6-(2-furyl)-9-(2-trimethylsilylethoxymethyl)-9H-purine (488 mg, 1.4 mmol) in isopropanol (5 mL) was treated with 40% dimethylamine in water (1 mL), refluxed for 2 h, concentrated in vacuo and purified by chromatography [SiO2; EtOAc Heptane, (1:1)] to give the title compound (431 mg, 86%) as a white solid.
Reaction SMILES: ON1[C:6](=O)[CH2:5][CH2:4][C:3]1=[O:8].[CH3:9]C1CCCC=1.[C:15](=[O:17])=[O:16].O=O>C(O)(=O)C.O.O.O.O.C([O-])(=O)C.[Co+2].C([O-])(=O)C>[O:8]=[C:3]([CH3:9])[CH2:4][CH2:5][CH2:6][C:15]([OH:17])=[O:16]
Reactant: O=C=O
Reactant: O=C1CCC(=O)N1O
Reactant: CC1=CCCC1
Agent: [Co+2]
Agent: CC(=O)[O-]
Agent: O=O
Solvent: CC(=O)O
Solvent: O
Product: CC(=O)CCCC(=O)O
Temperature: 100 °C
Reaction time: 1 h
Yield: 60 %

Procedure:
This reaction was performed with a solution of 0.1191 g (1.03 mmol) of N-hydroxysuccinimide, 2.0 g (24.3 mmol) of 1-methylcyclopentene and 0.1330 g (0.53 mmol) of cobalt acetate tetrahydrate in 40 ml of acetic acid was heated to 100° C. in a Parr Hastelloy reactor with temperature and pressure transducer. After the temperature reached 100° C., 745 psi of CO2 was introduced into the reactor, then 120 psi of O2 was added slowly to the reactor. The mixture was stirred under pressure for one hour at 100° C., then the pressure was released, and the mixture was cooled to room temperature. The solution was extracted with ethyl acetate then with a saturated NaCl solution in water and, dried over Na2SO4 to give, as the major 60% 5-ketohexanoic acid.
Reaction SMILES: [C:1]([C:5]1[C:10]([F:11])=[C:9](S(C)=O)[N:8]=[C:7]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([Cl:24])[CH:22]=3)[NH:17][CH:16]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:25][C@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@@H:27]1[C:32]([OH:34])=[O:33].C([O-])([O-])=O.[Na+].[Na+].CCN(C(C)C)C(C)C.Cl>C1COCC1.CC#N>[C:1]([C:5]1[N:6]=[C:7]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([Cl:24])[CH:22]=3)[NH:17][CH:16]=2)[N:8]=[C:9]([NH:25][C@H:26]2[CH2:31][CH2:30][CH2:29][CH2:28][C@@H:27]2[C:32]([OH:34])=[O:33])[C:10]=1[F:11])([CH3:4])([CH3:3])[CH3:2]
Reactant: N[C@H]1CCCC[C@@H]1C(=O)O
Reactant: CS(=O)c1nc(-c2c[nH]c3ncc(Cl)cc23)nc(C(C)(C)C)c1F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)c1nc(-c2c[nH]c3ncc(Cl)cc23)nc(N[C@H]2CCCC[C@@H]2C(=O)O)c1F
Temperature: 140 °C

Procedure:
A mixture of 3-(tert-butyl-5-fluoro-6-(methylsulfinyl)pyrimidin-2-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridine, 40c, (0.05 g, 0.14 mmol), (1S,2S)-2-amino-cyclohexanecarboxylic acid (0.04 g, 0.27 mmol), freshly ground Na2CO3 (0.04 g, 0.41 mmol), and iPr2NEt (0.37 mL, 0.27 mmol) in THF (1 mL) and CH3CN (0.5 mL) was heated in a sealed vessel to 140° C. for 30 minutes under microwave irradiation. The mixture was cooled to room temperature. A solution of 1N HCl (0.5 mL, 0.5 mmol) was added and the mixture was concentrated to give a yellow solid, which was purified by reverse phase HPLC (0%-50% methanol in water) to afford the desired product, 629, as off-white solid.
Reaction SMILES: C([O:3][C:4]([C:6]1[S:7][CH:8]=[C:9]([CH:11]([CH3:13])[CH3:12])[N:10]=1)=O)C.CC(C[AlH]CC(C)C)C.O>C(Cl)Cl>[CH:11]([C:9]1[N:10]=[C:6]([CH:4]=[O:3])[S:7][CH:8]=1)([CH3:13])[CH3:12]
Reactant: CCOC(=O)c1nc(C(C)C)cs1
Agent: CC(C)C[AlH]CC(C)C
Solvent: O
Solvent: ClCCl
Product: CC(C)c1csc(C=O)n1
Reaction time: 1 h

Procedure:
A solution of 2.1 g (11 mmol) of 4-isopropyl-thiazole-2-carboxylic acid ethyl ester (J. Med. Chem., 1998:602-617) in CH2Cl2 (50 mL) was cooled to −78° C. under nitrogen and treated dropwise with DIBAL (12 mL of 1.0 M in CH2Cl2; 12 mmol). The mixture was stirred at low temperature for 1 hour and then treated with another 7 mL of DIBAL. The solution was stirred for 30 minutes at −78° C. H2O was added, and the mixture was extracted with EtOAc (3×100 mL). The combined extracts were washed with brine, dried (MgSO4), and concentrated. Chromatography of the residue over silica gel, eluting with 3:1 hexane:EtOAc, gave the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].C(Cl)(=O)[C:12](Cl)=[O:13]>ClCCCl>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([N:6]=[C:12]=[O:13])=[O:5]
Reactant: NC(=O)c1ccccc1Cl
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCCl
Product: O=C=NC(=O)c1ccccc1Cl
Temperature: 100 °C
Reaction time: 8 h

Procedure:
0.39 g (2.5 mmol) of 2-chlorobenzamide and 0.38 g (3.0 mmol, 1.2 eq) of oxalyl chloride were added to 10 ml of 1,2-dichloroethane and then the mixture was stirred for 8 hours at 100° C. The reaction solution was cooled down to room temperature. The reaction solvent and excessive oxalyl chloride were removed by distillation under reduced pressure to obtain 2-chlorobenzoyl isocyanate in an oily state. 10 ml of fresh 1,2-dichloroethane and 0.69 g (2.5 mmol) of 2-bromo-4-chloro-5-trifluoromethyl aniline were successively added thereto, reacted for 2 hours and filtered to obtain 0.61 g (Yield 53%) of the title compound as a solid.
Reaction SMILES: [CH:1]([O:4][C:5]([C:7]1[N:8]=[CH:9][C:10]2[NH:11][C:12]3[C:17]([C:18]=2[C:19]=1[CH2:20][CH3:21])=[CH:16][C:15]([NH:22][C:23](=O)[CH3:24])=[CH:14][CH:13]=3)=[O:6])([CH3:3])[CH3:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:35])=CC=1.C(OCC)(=O)C>O1CCOCC1>[CH:1]([O:4][C:5]([C:7]1[N:8]=[CH:9][C:10]2[NH:11][C:12]3[C:17]([C:18]=2[C:19]=1[CH2:20][CH3:21])=[CH:16][C:15]([NH:22][C:23](=[S:35])[CH3:24])=[CH:14][CH:13]=3)=[O:6])([CH3:3])[CH3:2]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CCc1c(C(=O)OC(C)C)ncc2[nH]c3ccc(NC(C)=O)cc3c12
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CCc1c(C(=O)OC(C)C)ncc2[nH]c3ccc(NC(C)=S)cc3c12
Yield: 53.7 %

Procedure:
2741 mg of 6-acetylamino-4-ethyl-β-carboline-3-carboxylic acid isopropyl ester is heated to 70° C. in 110 ml of dioxane with 3915 mg of Lawesson's reagent while being stirred. After cooling, it is mixed with 100 ml of ethyl acetate and washed with saturated sodium chloride solution. The organic phases are dried and concentrated by evaporation in a vacuum. The residue is chromatographed on silica gel with toluene+methanol=8+2. 1541 mg of 4-ethyl-6-thioacetylamino-β-carboline-3-carboxylic acid isopropyl ester with a melting point of 158-160° C. is obtained from the desired fractions.
Reaction SMILES: [CH:1]1([C:6]2[CH:10]=[CH:9][S:8][C:7]=2[C:11]2([OH:24])[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.C[O:26][C:27](=[O:50])[C@H:28]([C@@H:47]([CH3:49])O)[NH:29]C(OCC1C2C=CC=CC=2C2C1=CC=CC=2)=O.OS(O)(=O)=O>FC(F)(F)C(O)=O>[CH:1]1([C:6]2[CH:10]=[CH:9][S:8][C:7]=2[C:11]2([O:24][C@H:47]([CH3:49])[C@@H:28]([C:27]([OH:50])=[O:26])[NH2:29])[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: OC1(c2sccc2C2CCCC2)c2ccccc2-c2ccccc21
Reactant: COC(=O)[C@@H](NC(=O)OCC1c2ccccc2-c2ccccc21)[C@@H](C)O
Agent: O=S(=O)(O)O
Solvent: O=C(O)C(F)(F)F
Product: C[C@@H](OC1(c2sccc2C2CCCC2)c2ccccc2-c2ccccc21)[C@H](N)C(=O)O

Procedure:
from 9-(3-cyclopentylthien-2-yl)-9H-fluoren-9-ol and Nα -(9 fluorenylmethoxycarbonyl)-L-threonine methyl ester following method A, using trifluoroacetic acid as catalyst in place of H2SO4 ;
Reaction SMILES: [O:1]1[CH2:16][CH:2]1[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[N:13][S:14][CH:15]=2)=[CH:7][CH:6]=1.[C:17]([NH2:21])([CH3:20])([CH3:19])[CH3:18]>C(O)(C)(C)C>[C:17]([NH:21][CH2:16][CH:2]([OH:1])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[N:13][S:14][CH:15]=2)=[CH:7][CH:6]=1)([CH3:20])([CH3:19])[CH3:18]
Reactant: CC(C)(C)N
Reactant: c1cc(-c2csnn2)ccc1OCC1CO1
Solvent: CC(C)(C)O
Product: CC(C)(C)NCC(O)COc1ccc(-c2csnn2)cc1

Procedure:
To a solution of 660 mg. of 4-[4(2,3-epoxypropoxy)phenyl]-1,2,3-thiadiazole in 29.7 ml. of t-butylamine is added 3.3 ml. of t-butanol and the reaction mixture is stirred at room temperature for 24 hours. It is then evaporated to dryness under vacuo and the residue taken up in methylene chloride. The resulting solution is extracted with dilute hydrochloric acid and the aqueous phase made alkaline with sodium carbonate. It is then extracted with ethyl acetate and the organic extracts washed to neutrality, dried over sodium sulfate and evaporated to dryness. The solid residue is purified by two recrystallizations from methylene chloridehexane (after decolorization with charcoal) and then by three crystallizations from benzene, thus obtaining the pure 4-[4(3-t-butylamino-2-hydroxypropoxy)phenyl]-1,2,3-thiadiazole, m.p. 124°-125° C; λmax 256, 304 nm, (ε 20,000;2,000) ir 3340, 1615, 1580, 1535, 835 cm-1.
Reaction SMILES: [N+:1]([C:4]1[N:5]([CH2:9][CH:10]([OH:13])[CH2:11]Cl)[CH:6]=[CH:7][N:8]=1)([O-:3])=[O:2].Cl.[CH2:15]([NH2:19])[CH2:16][C:17]#[CH:18].C(=O)([O-])[O-].[K+].[K+]>CO>[CH2:15]([NH:19][CH2:11][CH:10]([OH:13])[CH2:9][N:5]1[CH:6]=[CH:7][N:8]=[C:4]1[N+:1]([O-:3])=[O:2])[CH2:16][C:17]#[CH:18]
Reactant: O=[N+]([O-])c1nccn1CC(O)CCl
Reactant: C#CCCN
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: C#CCCNCC(O)Cn1ccnc1[N+](=O)[O-]
Yield: 70.5 %

Procedure:
A mixture of 5 (2.67 g, 13.1 mmol), but-3-ynylamine HCl salt (2.76 g, 26.2 mmol) and potassium carbonate (3.62 g) in 40 ml of methanol was refluxed for 5 h. After the workup, the residue was purified by column chromatography (THF-EtOH=9:0.5) to give 2.2 g of yellow solid (6, 70% yield). 1H NMR (DMSO-d6, δppm): 2.26 (dt, 2H, ≡C—CH2—, J=7.2 Hz, 2.7 Hz), 2.50 (d, 2H, J=5.7 Hz), 2.63 (t, 2H, J=7.2 Hz), 2.78 (t, 1H, CH≡C—, J=2.7 Hz), 3.82 (m, 1H, HO—CH—), 4.25 (dd, 1H, imidazole-CHa—, J=13.8 Hz, 8.4 Hz), 4.54 (dd, 1H, imidazole-CHb—, J=13.8 Hz, 3.6 Hz), 5.13 (d, 1H, OH, J=5.1 Hz), 7.13 (s, 1H, —CH═), 7.55 (s, 1H, —CH═). 13C NMR (DMSO-d6, δppm): 18.80, 47.79, 52.04, 52.89, 68.09, 71.60, 82.87, 126.98, 128.19, 144.83.
Reaction SMILES: Cl[C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[NH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.C(N(CC)CC)C>C(O)C>[N:11]1([C:2]2[S:3][C:4]3[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=3[N:6]=2)[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1
Reactant: Clc1nc2ccccc2s1
Reactant: C1CNCCN1
Solvent: CCO
Solvent: CCN(CC)CC
Product: c1ccc2sc(N3CCNCC3)nc2c1

Procedure:
A solution of 1.7 g (0.01 mol) of 2-chlorobenzothiazole, 4.76 g (0.05 mol) of piperazine and 7 ml (0.05 mol) of triethylamine in 50 ml of ethanol is stirred for 48 hours at ambient temperature. The reaction mixture is concentrated by evaporation, mixed with water and extracted twice with dichloromethane. The combined organic phases are dried over sodium sulphate, the drying agent is filtered off and the filtrate is concentrated by evaporation. The residue is washed with diethylether.
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-])=O)=[C:6]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][C:18]([NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=3)=[O:19])[CH2:13][CH2:12]2)[C:5]([Cl:28])=[CH:4][N:3]=1.[CH3:29][N:30]([CH3:39])[C:31]1[CH:38]=[CH:37][C:34]([CH:35]=O)=[CH:33][CH:32]=1.[O-]S(S([O-])=O)=O.[Na+].[Na+]>C(O)C>[Cl:28][C:5]1[C:6]([N:11]2[CH2:12][CH2:13][N:14]([CH2:17][C:18]([NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=3)=[O:19])[CH2:15][CH2:16]2)=[C:7]2[N:8]=[C:35]([C:34]3[CH:37]=[CH:38][C:31]([N:30]([CH3:39])[CH3:29])=[CH:32][CH:33]=3)[NH:1][C:2]2=[N:3][CH:4]=1
Reactant: CN(C)c1ccc(C=O)cc1
Reactant: Nc1ncc(Cl)c(N2CCN(CC(=O)Nc3cccc(Cl)c3)CC2)c1[N+](=O)[O-]
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: CCO
Product: CN(C)c1ccc(-c2nc3c(N4CCN(CC(=O)Nc5cccc(Cl)c5)CC4)c(Cl)cnc3[nH]2)cc1
Temperature: 70 °C

Procedure:
To a mixture of 2-(4-(2-amino-5-chloro-3-nitropyridin-4-yl)piperazin-1-yl)-N-(3-chlorophenyl)acetamide (0.036 g, 0.08 mmol), ethanol (3.5 ml), and 4-dimethylaminobenzaldehyde (0.017 g, 0.11 mmol) was added a freshly prepared aqueous solution of Na2S2O4 (1M; 0.35 ml, 0.35 mmol). The reaction mixture was heated at 70° C. for 3 h, then allowed to cool to room temperature and the solvents were removed in vacuo. The residue was absorbed on silica gel and the free running powder was placed on a 10 g isolute silica column which was eluted with 30% ethyl acetate in dichloromethane and then 1.5% methanol in ethyl acetate/dichloromethane (v/v; 1:1). The title compound was obtained as a pale yellow solid after trituration with diethyl ether (0.004 g, 7%); 1H-NMR (500 MHz, DMSO-d6) 2.78 (br s, 4H, piperazine N(CH2)2), 3.00 (s, 6H, N(CH3)2), 3.24 (s, 2H, NCH2CO), 3.76 (br s, 4H, piperazine N(CH2)2), 6.82 (d, J=8.96 Hz, 2H) and 8.01 (d, J=8.91 Hz, 2H) (3,5-C6H4NMe2 and 2,6-C6H4—NMe2), 7.12 (d, J=7.62 Hz, 1H) and 7.60 (d, J=9.25 Hz, 1H) (4-ArH and 6-ArH), 7.34 (t, J=6.85 Hz, 1H, 5-ArH), 7.90 (s, 1H, 2-ArH), 8.03 (s, 1H, imidazo[4,5-b]pyridine 5-H), 9.96 (s, 1H, CONH), 13.09 (s, 1H, imidazo[4,5-b]pyridine N—H);
Reaction SMILES: [NH2:1][C:2]([CH3:24])([CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)[C:3]([NH:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4].[C:25]([N:29]=[C:30]=[O:31])([CH3:28])([CH3:27])[CH3:26]>ClCCl>[CH3:26][C:25]([NH:29][C:30]([NH:1][C:2]([CH3:24])([CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)[C:3]([NH:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4])=[O:31])([CH3:28])[CH3:27]
Reactant: CC(N)(Cc1c[nH]c2ccccc12)C(=O)NCCc1ccccc1
Reactant: CC(C)(C)N=C=O
Solvent: ClCCl
Product: CC(C)(C)NC(=O)NC(C)(Cc1c[nH]c2ccccc12)C(=O)NCCc1ccccc1

Procedure:
The product of Example 12 (0.25 g, 0.78 mmol) was dissolved in 1.5 ml of dichloromethane and treated with 90 μl (0.78 mmol) of tert-butylisocyanate, and then heated under reflux overnight. The crystalline product, (±)-α-[[[(1,1-dimethylethyl)amino]carbonyl]-amino ]-α-methyl-N-(2-phenylethyl)-1H-indole-3-propanamide, separated and was collected by filtration and dried.
Reaction SMILES: [F:1][C:2]([F:40])([F:39])[C@H:3]([N:26]1[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:27]1)[C:4]1[CH:5]=[N:6][C:7]([NH:10]/[N:11]=[CH:12]/[C:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][C:17]([O:24][CH3:25])=[C:18]([CH3:23])[CH:19]=3)[N:14]=2)=[CH:8][CH:9]=1.C(O)(=O)C.C(O)(=O)C.I(C1C=CC=CC=1)=O>C(Cl)Cl>[F:40][C:2]([F:39])([F:1])[C@H:3]([N:26]1[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:36])([CH3:37])[CH3:35])[CH2:27]1)[C:4]1[CH:9]=[CH:8][C:7]2[N:6]([C:12]([C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][C:17]([O:24][CH3:25])=[C:18]([CH3:23])[CH:19]=4)[N:14]=3)=[N:11][N:10]=2)[CH:5]=1
Reactant: COc1cc2nc(/C=N/Nc3ccc([C@@H](N4CC[C@H](NC(=O)OC(C)(C)C)C4)C(F)(F)F)cn3)ccc2cc1C
Agent: O=Ic1ccccc1
Solvent: ClCCl
Solvent: CC(=O)O
Product: COc1cc2nc(-c3nnc4ccc([C@@H](N5CC[C@H](NC(=O)OC(C)(C)C)C5)C(F)(F)F)cn34)ccc2cc1C
Temperature: 25 °C
Reaction time: 2 h
Yield: 46.9 %

Procedure:
To tert-butyl (S)-1-((R)-2,2,2-trifluoro-1-(6-((E)-2-((7-methoxy-6-methylquinolin-2-yl)methylene)hydrazinyl)pyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamate (278 mg, 0.498 mmol) in DCM was added iodosobenzene diacetate (208 mg, 0.647 mmol) and the reaction was stirred at ambient temperature for 2 hours. After concentration, the residue was purified by reverse phase chromatography (SP4, 25M, eluting with a gradient of water/ACN 100:0 to 0:100, 25 column volumes) to yield tert-butyl (S)-1-((R)-2,2,2-trifluoro-1-(3-(7-methoxy-6-methylquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate (130 mg, 46.9% yield) as a beige solid
Reaction SMILES: [OH:1][CH2:2][C:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])O)[OH:8])[OH:6])=[O:4].[NH2:13][C@H:14]([C:20]([OH:22])=[O:21])[CH2:15][CH2:16][C:17]([OH:19])=[O:18]>[Ni]>[OH:12][CH2:11][CH:9]([NH:13][C@H:14]([C:20]([OH:22])=[O:21])[CH2:15][CH2:16][C:17]([OH:19])=[O:18])[CH:7]([OH:8])[CH:5]([OH:6])[CH:3]([OH:4])[CH2:2][OH:1]
Reactant: N[C@@H](CCC(=O)O)C(=O)O
Reactant: O=C(CO)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: [Ni]
Product: O=C(O)CC[C@H](NC(CO)C(O)C(O)C(O)CO)C(=O)O

Procedure:
The product was made from D-fructose and L-(+)-glutamic acid using Raney nickel as a catalyst and heating for 2 hours to 50° C. and for 3 hours to 70° C. The reaction product had a melting point of 149° C. (decomposition) and an RF -value of 0.62 (determined as indicated under Example T).
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Br)=[C:4]([F:10])[CH:3]=1.C([O-])C.[Na+].[CH2:15]([O:17][C:18](=[O:33])[CH:19]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH3:16]>C(O)C>[CH2:15]([O:17][C:18](=[O:33])[C:19]([CH2:6][C:5]1[CH:8]=[CH:9][C:2]([Br:1])=[CH:3][C:4]=1[F:10])([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH3:16]
Reactant: Fc1cc(Br)ccc1CBr
Reactant: CCCCCCCCC(C(=O)OCC)C(=O)OCC
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: CCCCCCCCC(Cc1ccc(Br)cc1F)(C(=O)OCC)C(=O)OCC

Procedure:
4-bromo-2-fluoro-benzylbromide [76283-09-5] is reacted in ethanol with stoichiometric compounds of natrium ethanolate and octylmalonic acid diethylester to form 2-(4-bromo-2-fluoro phenyl)methyl-2-octyl malonic acid diethylester. After usual post-treatment and distillation a 50% aqueous potassium hydroxide solution is added to the methanolic solution and heated until the saponification has ended. After cooling sulfuric acid is added to adjust the pH to a value of 1-2. The 4-fold volume of water is added followed by multiple extraction of methyl-tert.-butylether. The combined organic phases are dried and the solvent is removed under vacuum, finally at 60° C. in the heating bath. The 2-(4-bromo-2-fluoro phenyl)methyl-2-octyl-malonic acid thus obtained after heating for several hours at 150-170° C. is decarboxylated to obtain 3-(4-bromo-2-fluoro phenyl)-2-octyl-propionic acid.
Reaction SMILES: Cl[C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[CH:5]=[C:4]([C:11]2[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=2)[N:3]=1.[CH3:17][C:18]1[C:22](B2OC(C)(C)C(C)(C)O2)=[CH:21][NH:20][N:19]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].COCCOC>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO>[CH3:16][N:14]1[CH:15]=[C:11]([C:4]2[N:3]=[C:2]([C:22]3[C:18]([CH3:17])=[N:19][NH:20][CH:21]=3)[N:7]3[CH:8]=[CH:9][N:10]=[C:6]3[CH:5]=2)[CH:12]=[N:13]1
Reactant: Cc1n[nH]cc1B1OC(C)(C)C(C)(C)O1
Reactant: Cn1cc(-c2cc3nccn3c(Cl)n2)cn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: COCCOC
Product: Cc1n[nH]cc1-c1nc(-c2cnn(C)c2)cc2nccn12
Temperature: 100 °C
Reaction time: 8 h
Yield: 27.7 %

Procedure:
To a flask charged with 5-chloro-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (Preparation J; 0.650 g, 2.78 mmol), 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.868 g, 4.17 mmol), and 2 M K3PO4 (4.17 mL, 8.35 mmol) was added 20 mL of DME and argon was bubbled through for 15 minutes before tetrakis(triphenylphosphine)palladium (0) (0.321 g, 0.278 mmol) was added. The flask was sealed and the reaction was heated to 100° C. for 4 hours, then allowed to cool to ambient temperature and stirred overnight. The reaction mixture was diluted with EtOAc (300 mL) and washed with aqueous saturated sodium bicarbonate (50 mL). The organic layer was washed with brine (50 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The crude material was taken up in DCM in preparation for chromatography when a precipitate began to form and continued to thicken over time. The addition of minimal MeOH (0.5 mL) did not dissolve the precipitate. The solid was collected by vacuum filtration and retained. The rinse was purified by means of silica gel chromatography eluting with a gradient of 5-10% MeOH in EtOAc containing 1% NH4OH. This was successful at generating material that was combined with the solid above to afford 7-(1-methyl-1H-pyrazol-4-yl)-5-(3-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (0.215 g, 0.770 mmol, 27.7% yield). MS (apci) m/z=280.1 (M+H).