Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[C:10]2[O:9][CH:8]=[CH:7][C:6]=2[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1.C([Sn](CCCC)(CCCC)[C:19]1[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=1)CCC.CN(C=O)C.[OH-].[Na+]>[Cu]I.C(Cl)(Cl)Cl>[N+:11]([C:4]1[CH:3]=[C:2]([C:19]2[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=2)[C:10]2[O:9][CH:8]=[CH:7][C:6]=2[CH:5]=1)([O-:13])=[O:12]
Reactant: O=[N+]([O-])c1cc(I)c2occc2c1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccncc1
Agent: [Cu]I
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: ClC(Cl)Cl
Product: O=[N+]([O-])c1cc(-c2ccncc2)c2occc2c1
Temperature: 100 °C
Reaction time: 0.25 h

Procedure:
7-Iodo-5-nitrobenzofuran (2.00 g, 0.00692 mol), 4-tributylstannylpyridine (2.80 g, 0.00761 mol), copper(I)iodide (132 mg, 0.692 mmol) and dichlorobis(triphenylphosphine) palladium(II) (49 mg, 0.0692 mmol) were added to a 50 mL test tube followed by DMF (20 mL). The mixture was heated at 100° C. overnight in a StemBlock. After cooling to room temperature, aqueous sodium hydroxide (2 M; 4 mL) was added and the solution was stirred for 15 min. Chloroform (20 mL) was added and the mixture was filtered through Celite. The aqueous layer was then extracted with chloroform (3×) and the combined organic phases were evaporated. The residue was then triturated with ether and the precipitate was dried in vacuo overnight to yield a light brown solid. Yield: 686 mg (41%); HLPC (System A) purity=99%, m/z=241 (M+H)+, 1H NMR (270 MHz, DMSO-d6) δ ppm 7.33 (d, J=2.23 Hz, 1H) 7.98 (m, 2H) 8.38 (d, J=2.23 Hz, 1H) 8.50 (d, J=2.47 Hz, 1H) 8.75 (d, J=2.23 Hz, 1H) 8.79 (m, 2H).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[N:7][C:8]2[C:13]([C:14]=1Cl)=[CH:12][CH:11]=[CH:10][C:9]=2[O:16][CH2:17][CH2:18][CH2:19][S:20][CH2:21][CH2:22][CH3:23])(=[O:4])[CH2:2][CH3:3].[NH2:24][C:25]1[C:26]([CH3:31])=[CH:27][CH:28]=[CH:29][CH:30]=1>C(#N)C>[C:1]([C:5]1[CH:6]=[N:7][C:8]2[C:13]([C:14]=1[NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH3:31])=[CH:12][CH:11]=[CH:10][C:9]=2[O:16][CH2:17][CH2:18][CH2:19][S:20][CH2:21][CH2:22][CH3:23])(=[O:4])[CH2:2][CH3:3]
Reactant: CCCSCCCOc1cccc2c(Cl)c(C(=O)CC)cnc12
Reactant: Cc1ccccc1N
Solvent: CC#N
Product: CCCSCCCOc1cccc2c(Nc3ccccc3C)c(C(=O)CC)cnc12
Yield: 54 %

Procedure:
3-Propanoyl-4-chloro-8-(3-propylthiopropoxy)quinoline (2.0 g, 5.7 mmol) and o-toluidine (0.7 g, 6.5 mmol) was refluxed in acetonitrile (10 ml) for 2 h. The solvent was evaporated and the residue was partitioned between methylene chloride and 10% Na2CO3 solution. The organic layer was dried over Na2SO4 and evaporated. The residue was purified by column chromatography (methylene chloride: ethyl acetate 70:30). 1.3 g (54%) of the title compound was obtained. (1H-NMR, 300 MHz, CDCl3) 0.94 (t, 3H), 1.26 (t, 3H), 1.57 (m, 2H), 2.25 (m, 2H), 2.34 (s, 3H), 2.49 (t, 2H), 2.75 (t, 2H), 3.15 (q, 2H), 4.27 (t, 2H) 6.83-7.23 (m, 7H), 9.22 (s, 1H), 11.73 (s, 1H).
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]([OH:11])=O)[CH2:4][CH2:3]1.[NH2:12][C@@H:13]([CH3:37])[C:14]([NH:16][C@@H:17]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=1)[C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])=[O:15].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>ClCCl.O>[OH:1][CH:2]1[CH2:3][CH2:4][N:5]([CH2:8][C:9]([NH:12][C@@H:13]([CH3:37])[C:14]([NH:16][C@@H:17]([CH2:28][C:29]2[CH:30]=[CH:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=2)[C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])=[O:15])=[O:11])[CH2:6][CH2:7]1
Reactant: COc1ccc(C[C@H](NC(=O)[C@H](C)N)C(=O)OCc2ccccc2)cc1
Reactant: O=C(O)CN1CCC(O)CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN1CCOCC1
Solvent: O
Solvent: ClCCl
Product: COc1ccc(C[C@H](NC(=O)[C@H](C)NC(=O)CN2CCC(O)CC2)C(=O)OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 85 %

Procedure:
To a solution of 2-(4-hydroxypiperidin-1-yl)acetic acid (0.41 g, 2.6 mmol) and (S)-benzyl 2-((S)-2-aminopropanamido)-3-(4-methoxyphenyl)propanoate (HCl salt, 0.93 g, 2.6 mmol) in dichloromethane (30 mL) at 0° C. was added HATU (1.1 g, 2.9 mmol) followed by N-methylmorpholine (1.05 g, 10.4 mmol). The reaction mixture was allowed to warm to ambient temperature and stirred for 1 h. Water (30 mL) was added and the resulting mixture was extracted with dichloromethane (30 mL×3). The organic extracts were combined, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (petroleum ether/dichloromethane=5:1 to 1:1) to afford (S)-benzyl 2-((S)-2-(2-(4-hydroxypiperidin-1-yl)acetamido)propanamido)-3-(4-methoxyphenyl)propanoate (1.1 g, 87% yield) as a colorless solid.
Reaction SMILES: [CH2:1]([C:3]1[C:8]([O:9][C:10]2[C:11]([NH:23][C:24]3[S:28][N:27]=[C:26]([C@H:29]4[C@H:33]([CH2:34][O:35][CH3:36])[O:32]C5(CCCCC5)[O:30]4)[N:25]=3)=[N:12][CH:13]=[C:14]([S:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[CH:15]=2)=[CH:7][CH:6]=[CH:5][N:4]=1)[CH3:2].[ClH:42]>CCO>[ClH:42].[CH2:1]([C:3]1[C:8]([O:9][C:10]2[C:11]([NH:23][C:24]3[S:28][N:27]=[C:26]([C@H:29]([OH:30])[C@@H:33]([OH:32])[CH2:34][O:35][CH3:36])[N:25]=3)=[N:12][CH:13]=[C:14]([S:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[CH:15]=2)=[CH:7][CH:6]=[CH:5][N:4]=1)[CH3:2]
Reactant: CCc1ncccc1Oc1cc(Sc2ccccn2)cnc1Nc1nc([C@@H]2OC3(CCCCC3)O[C@H]2COC)ns1
Agent: Cl
Solvent: CCO
Product: CCc1ncccc1Oc1cc(Sc2ccccn2)cnc1Nc1nc([C@H](O)[C@@H](O)COC)ns1
Temperature: 50 °C
Yield: 64.6 %

Procedure:
N-(3-(2-ethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-((2S,3S)-3-(methoxymethyl)-1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine (1.6 g, 2.70 mmol) was dissolved in EtOH (30 mL) and 4N HCl (1 mL) added and heated to 50° C. overnight. Additional 4N HCl was added (1 mL) and heated for 4 hours. The reaction was cooled to ambient temperature, partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate, extracted with CH2Cl2, dried over sodium sulfate, filtered and concentrated. The residue was purified over silica gel (10% methanol in EtOAc) to afford (1S,2S)-1-(5-(3-(2-ethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)-3-methoxypropane-1,2-diol hydrochloride (0.957 g, 1.74 mmol, 64.6% yield) as a tan solid after HCl salt formation. Mass Spectrum (apci) m/z=513.1 (M+H−HCl).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][N:12]=2)=[O:10])=[CH:4][C:3]=1[C:18]12[CH2:25][CH:24]1[CH2:23][O:22][CH2:21][C:20](=S)[NH:19]2.[NH3:27].C(OO)(C)(C)C>CO>[NH2:27][C:20]1[CH2:21][O:22][CH2:23][CH:24]2[C:18]([C:3]3[CH:4]=[C:5]([NH:8][C:9]([C:11]4[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][N:12]=4)=[O:10])[CH:6]=[CH:7][C:2]=3[F:1])([CH2:25]2)[N:19]=1
Reactant: N
Reactant: O=C(Nc1ccc(F)c(C23CC2COCC(=S)N3)c1)c1ccc(Cl)cn1
Agent: CC(C)(C)OO
Solvent: CO
Product: NC1=NC2(c3cc(NC(=O)c4ccc(Cl)cn4)ccc3F)CC2COC1
Temperature: 23 °C
Reaction time: 20 h
Yield: 132 %

Procedure:
To mixture of 5-chloro-pyridine-2-carboxylic acid [4-fluoro-3-((1SR,7RS)-3-thioxo-5-oxa-2-aza-bicyclo[5.1.0]oct-1-yl)-phenyl]-amide (intermediate B14A) (142 mg, 0.36 mmol) and 7 N ammonia in methanol (3.1 ml) in methanol (15 ml) at 23° C. was added tert-butylhydroperoxide (70% in water, 0.50 ml, 3.62 mmol) and the mixture was stirred at 23° C. for 20 h. The reaction mixture was extracted with water and dichloromethane. The organic layer was washed with water and brine, the aqueous layers were reextracted with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and evaporated to give a light yellow oil (180 mg, 132%), which was purified by silica gel column chromatography with dichloromethane to dichloromethane/methanol/ammonium hydroxide 65:10:1 to give the title compound as a white solid (10 mg, 7.4%). MS (ISP): m/z=375.3 [(M+H)+] and 377.3 [(M+2+H)+].
Reaction SMILES: [Cl:1][C:2]1[N:3]=[CH:4][C:5]([C:8]([NH:10][CH2:11][CH2:12][NH:13]C(=O)OC(C)(C)C)=[O:9])=[N:6][CH:7]=1>FC(F)(F)C(O)=O>[ClH:1].[NH2:13][CH2:12][CH2:11][NH:10][C:8]([C:5]1[CH:4]=[N:3][C:2]([Cl:1])=[CH:7][N:6]=1)=[O:9]
Reactant: CC(C)(C)OC(=O)NCCNC(=O)c1cnc(Cl)cn1
Solvent: O=C(O)C(F)(F)F
Product: Cl
Product: NCCNC(=O)c1cnc(Cl)cn1

Procedure:
A solution of 1.6 g of t-butyl [2-(5-chloropyrazine-2-carboxamido)ethyl]carbamate in 6 ml of trifluoroacetic acid was stirred at 20° for 20 minutes. The mixture was thereafter evaporated to dryness on a rotary evaporator, the residue was dissolved in methanol and the solution was treated with hydrogen chloride in methanol (6N). After recrystallization from methanol/diethyl ether there was obtained N-(2-aminoethyl)-5-chloropyrazine-2-carboxamide hydrochloride, m.p. 225°.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]2[S:8][C:9]([NH:11][C:12](=[O:14])[CH3:13])=[N:10][C:5]2=[CH:4][CH:3]=1.O.[NH2:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1>[NH2:16][C:17]1[CH:22]=[C:21]([C:2]2[N:7]=[C:6]3[S:8][C:9]([NH:11][C:12](=[O:14])[CH3:13])=[N:10][C:5]3=[CH:4][CH:3]=2)[CH:20]=[CH:19][CH:18]=1
Reactant: CC(=O)Nc1nc2ccc(Br)nc2s1
Reactant: Nc1cccc(B(O)O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: CC(=O)Nc1nc2ccc(-c3cccc(N)c3)nc2s1
Temperature: 94.5 °C
Reaction time: 4 h
Yield: 77.6 %

Procedure:
N-(5-bromothiazolo[5,4-b]pyridin-2-yl)acetamide (1.504 g, 5.527 mmol), 3-aminophenylboronic acid monohydrate (1.316 g, 8.493 mmol), Pd(dppf)C12-DCM complex (604.4 mg, 0.7401 mmol), and potassium carbonate (2.292 g, 16.58 mmol) were suspended in 1,4-dioxane (45 ml) and water (15 ml) was added. Argon was bubbled through the solution for about 30 seconds, and then the flask was fit with a reflux condensor and placed in a preheated oil bath (90-99° C.) and stirred under argon for 4 hours. The reaction was cooled to room temperature, filtered, and the solid was washed with DCM and MeOH. The filtrate was concentrated, treated with DCM and MeOH, and filtered. The solid was collected and set aside, and the filtrate was concentrated, treated with Et2O, and filtered. Solid washed with Et2O. This solid was combined with the first batch and dried under high vacuum first at room temperature, and then at ˜50° C. This solid was treated with deionized water and filtered, and the solid was washed with water, collected, and dried under high vacuum in water bath (˜50° C.) to afford N-(5-(3-aminophenyl)thiazolo[5,4-b]pyridin-2-yl)acetamide (1.22 g, 78% yield). MS (ESI pos. ion) m/z: 285. Calculated exact mass for C14H12N4OS 284.
Reaction SMILES: C(N(CC)CC)C.Br[CH2:9][CH:10]=[CH:11][CH:12]=[CH:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1.[OH:21][N:22]1[C:26](=[O:27])[C:25]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]2[C:23]1=[O:32].CN1CCCC1=O>O>[F:20][C:17]1[CH:18]=[CH:19][C:14](/[CH:13]=[CH:12]/[CH:11]=[CH:10]/[CH2:9][O:21][N:22]2[C:23](=[O:32])[C:24]3=[CH:31][CH:30]=[CH:29][CH:28]=[C:25]3[C:26]2=[O:27])=[CH:15][CH:16]=1
Reactant: Fc1ccc(C=CC=CCBr)cc1
Reactant: O=C1c2ccccc2C(=O)N1O
Solvent: CN1CCCC1=O
Solvent: O
Solvent: CCN(CC)CC
Product: O=C1c2ccccc2C(=O)N1OC/C=C/C=C/c1ccc(F)cc1
Reaction time: 24 h
Yield: 57 %

Procedure:
8.3 ml (60 mmol ) of triethylamine were added dropwise at about 20° C. to a mixture of 10.4 g (43 mmol) of 1-bromo-5- (4-fluorophenyl)-2,4-pentadiene, 9.8 g (60 mmol) of N-hydroxyphthalimide and 45 ml of N-methyl-pyrrolidone. The mixture was stirred for 24 hours and then poured into 200 ml of water and extracted several times with ethyl acetate, after which the combined organic phases were washed with 5% by weight aqueous sodium hydroxide solution and then with saturated aqueous sodium chloride solution. After drying with magnesium sulfate and removal of the solvent, the residue was recrystallized from 70 ml of ethanol. Yield: 57%. Melting point: 155°-157° C.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:8]1(C)[C:9]([S:14]([N:17]=[C:18]=[O:19])(=[O:16])=[O:15])=[CH:10][CH:11]=[CH:12][CH:13]=1.[C:21]1(C)C=CC=CC=1>>[C:12]1([CH3:21])[CH:13]=[CH:8][C:9]([S:14]([NH:17][C:18]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:19])(=[O:15])=[O:16])=[CH:10][CH:11]=1
Reactant: Cc1ccccc1
Reactant: Cc1ccccc1S(=O)(=O)N=C=O
Reactant: Nc1ccccc1
Product: Cc1ccc(S(=O)(=O)NC(=O)Nc2ccccc2)cc1
Temperature: 90 °C

Procedure:
A three-necked flask equipped with a dropping funnel, a thermometer, and a reflux condenser was charged with 18.6 g of aniline and the aniline was dissolved in 200 ml of toluene. While the resultant reaction solution was stirred with a magnetic stirrer, 42.0 g of toluenesulfonylisocyanate were added dropwise from the dropping funnel to the reaction solution. During the stirring, an exothermic reaction occurred and a large amount of white solid was precipitated. The resultant reaction mixture was heated at a temperature of 90° C. for one hour, cooled, and then filtered. White crystals were obtained in an amount of 58.0 g. The crystals had a melting point of 166° C.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[CH3:12])[C:6]([OH:8])=[O:7])=[O:2].I[C:14]1C(C)=CC(C)=C(C=1)C(O)=O>>[CH:1]([C:3]1[C:11]([CH3:12])=[CH:10][C:9]([CH3:14])=[C:5]([CH:4]=1)[C:6]([OH:8])=[O:7])=[O:2]
Reactant: Cc1cc(C)c(C(=O)O)cc1I
Reactant: Cc1ccc(C(=O)O)cc1C=O
Product: Cc1cc(C)c(C(=O)O)cc1C=O

Procedure:
The title compound was prepared using standard chemical manipulations and procedures similar to those used for the preparation of compound 4.1, except 5-iodo-2,4-dimethylbenzoic acid (compound 1.3) was used in place of 3-bromo-4-methylbenzoic acid.
Reaction SMILES: C(N(CCCC)CCCC)CCC.[CH2:14]=[CH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.Cl[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>>[C:16]1(/[CH:15]=[CH:14]/[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Clc1ccccc1
Reactant: C=Cc1ccccc1
Solvent: CCCCN(CCCC)CCCC
Product: C(=C/c1ccccc1)\c1ccccc1
Temperature: 25 °C

Procedure:
In a 100 mL Schlenk flask, the NAIL (3.23 g, 10 mmol)(NBu4Br) was heated to melt (130° C.) and degassed with nitrogen and vacuum prior to the addition of other reagents. After cooling the NAIL to room temperature, LDH-Pd0 (3 mol %), tri-n-butyl amine (222 mg, 1.2 mmol) were added. The styrene (1.2 mmol) and chlorobenzene (1 mmol) were then added and the reaction was heated to 130° C. and stirred for 10–40 h under nitrogen atmosphere, After completion of the reaction, the LDH-Pd0 catalyst was filtered and washed with water and dichloromethane. After removing the solvent, the crude material was chromatographed on silica gel or recrystallized from ethanol to afford the trans-stilbene.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8][CH2:7]2)([O-:3])=[O:2].Cl.Cl[CH2:17][CH2:18][N:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH2:17][CH2:18][N:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1)[C:9](=[O:14])[CH2:8][CH2:7]2)([O-:3])=[O:2]
Reactant: O=C1CCc2cc([N+](=O)[O-])ccc2N1
Reactant: ClCCN1CCCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C1CCc2cc([N+](=O)[O-])ccc2N1CCN1CCCC1
Temperature: 25 °C
Reaction time: 96 h

Procedure:
A suspension of 6-nitro-3,4-dihydroquinolin-2(1H)-one (230 mg, 1.06 mmol), 1-(2-chloroethyl)pyrrolidine hydrochloride (234 mg, 1.37 mmol) and potassium carbonate (440 mg, 3.18 mmol) in 5 mL DMF was stirred at room temperature for 4 days. After this time, the mixture was poured into 20 mL H2O then extracted with 2×30 mL CH2Cl2. The organic layers were combined together, washed with brine (20 mL) and concentrated. Product was subjected to flash chromatography on the biotage using 5% 2M NH3 in MeOH/CH2Cl2 to give a yellow solid. Yield: 218 mg of yellow solid (71%). 1H NMR (CDCl3) δ: 8.14 (dd, J=2.7, 9 Hz, 1H), 8.06 (d, J=2.4 Hz, 1H), 7.20 (d, J=9.0 Hz, 1H), 4.13 (t, J=7.5 Hz, 2H), 3.00 (t, J=6.9 Hz, 2H), 2.73-2.68 (m, 4H), 2.63-2.60 (m, 4H), 1.82-1.78 (m, 4H). MS (ESI): 290.2 (M+1, 100%).
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[NH:7][C@H:8]([C:17](F)=[O:18])[C@H:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])([CH3:4])([CH3:3])[CH3:2].[NH2:21][C:22]1[S:23][CH:24]=[C:25]([C:27](=[O:29])[CH3:28])[N:26]=1.CN1CCOCC1>O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:20])[NH:7][C@H:8]([C:17](=[O:18])[NH:21][C:22]1[S:23][CH:24]=[C:25]([C:27](=[O:29])[CH3:28])[N:26]=1)[C@H:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])([CH3:4])([CH3:3])[CH3:2]
Reactant: C[C@@H](c1ccccc1)[C@H](NC(=O)OC(C)(C)C)C(=O)F
Reactant: CC(=O)c1csc(N)n1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CN1CCOCC1
Product: CC(=O)c1csc(NC(=O)[C@@H](NC(=O)OC(C)(C)C)[C@@H](C)c2ccccc2)n1
Yield: 99.1 %

Procedure:
Crude ((1S,2S)-1-fluorocarbonyl-2-phenyl-propyl)-carbamic acid tert-butyl ester (2.2 g, ≈6.93 mol), 1-(2-amino-thiazol-4-yl)-ethanone (1.0 g, 7.0 mmol), 4-methyl morpholine (1.56 mL, 14 mmol) and N,N-dimethylaminopyridine (10 mg, 0.082 mmol) were dissolved in tetrahydrofuran (20 mL). The mixture was microwaved at 120° C. for 15 minutes. The solution was diluted with ethyl acetate and washed with 1.5 M aqueous potassium hydrogen sulfate, water and brine. After drying (sodium sulfate), filtration and evaporation of the solvents, [(1S,2S)-1-(4-acetyl-thiazol-2-ylcarbamoyl)-2-phenyl-propyl]-carbamic acid tert-butyl ester (2.8 g, 89%) was obtained as a yellow foam.
Reaction SMILES: NCC[N:4]1[CH:8]=[C:7]([NH:9][C:10]([C:12]2[N:13]=[CH:14][O:15][C:16]=2[C:17]2[CH:18]=[C:19]([CH3:23])[CH:20]=[CH:21][CH:22]=2)=[O:11])[CH:6]=[N:5]1.C([NH:31][CH2:32][CH2:33][CH2:34]Br)(OC(C)(C)C)=O>>[NH2:31][CH2:32][CH2:33][CH2:34][N:4]1[CH:8]=[C:7]([NH:9][C:10]([C:12]2[N:13]=[CH:14][O:15][C:16]=2[C:17]2[CH:18]=[C:19]([CH3:23])[CH:20]=[CH:21][CH:22]=2)=[O:11])[CH:6]=[N:5]1
Reactant: Cc1cccc(-c2ocnc2C(=O)Nc2cnn(CCN)c2)c1
Reactant: CC(C)(C)OC(=O)NCCCBr
Product: Cc1cccc(-c2ocnc2C(=O)Nc2cnn(CCCN)c2)c1

Procedure:
The title compound was synthesized according to above mentioned procedure for N-(1-(2-aminoethyl)-1H-pyrazol-4-yl)-5-(m-tolyl)oxazole-4-carboxamide, using 3-(Boc-amino)propyl bromide. LC-MS conditions B: tR=0.56 min, [M+H]+=326.19.
Reaction SMILES: [CH:1]1([CH:7]([NH:24][C:25]2[CH:33]=[CH:32][C:28](C(O)=O)=[CH:27][CH:26]=2)[C:8]2[CH:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][S:21][CH3:22])=[CH:15][CH:14]=3)[O:10][C:9]=2[CH3:23])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CNC[CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39].Cl.C(N=C=NCCCN(C)C)C.O.OC1C2N=NNC=2C=CC=1.[CH3:66][N:67]([CH3:70])[CH:68]=[O:69]>C(OCC)(=O)C.C(N(CC)CC)C>[CH:1]1([CH:7]([NH:24][C:25]2[CH:26]=[CH:27][C:28]([C:68]([N:67]([CH3:70])[CH2:66][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])=[O:69])=[CH:32][CH:33]=2)[C:8]2[CH:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][S:21][CH3:22])=[CH:15][CH:14]=3)[O:10][C:9]=2[CH3:23])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CCOC(=O)CCNC
Reactant: CSCOc1ccc(-c2cc(C(Nc3ccc(C(=O)O)cc3)C3CCCCC3)c(C)o2)cc1
Reactant: CN(C)C=O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: Oc1cccc2[nH]nnc12
Solvent: CCN(CC)CC
Solvent: O
Solvent: CCOC(C)=O
Product: CCOC(=O)CCN(C)C(=O)c1ccc(NC(c2cc(-c3ccc(OCSC)cc3)oc2C)C2CCCCC2)cc1

Procedure:
A solution of 4-{[cyclohexyl(2-methyl-5-{4-[(methylsulfanyl)methoxy]phenyl}furan-3-yl)methyl]amino}benzoic acid (408 mg), ethyl 3-(methylamino)propanoate (134 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (196 mg), hydroxybenzotriazole monohydrate (156 mg) and triethylamine (142 μL) in N,N-dimethylformamide (10 mL) was stirred at room temperature for 4 hr. Ethyl acetate was added, the mixture was washed with saturated aqueous sodium hydrogen carbonate solution and water, and the organic layer was dried over magnesium sulfate. The solvent was evaporated under reduced pressure, and the organic layer was dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give ethyl 3-{[(4-{[cyclohexyl(2-methyl-5-{4-[(methylsulfanyl)methoxy]phenyl}furan-3-yl)methyl]amino}phenyl)carbonyl](methyl)amino}propanoate. To ethyl 3-{[(4-{[cyclohexyl(2-methyl-5-{4-[(methylsulfanyl)methoxy]phenyl}furan-3-yl)methyl]amino}phenyl)carbonyl](methyl)amino}propanoate (119 mg) were added ethanol (2 mL), tetrahydrofuran (2 mL) and 1N lithium hydroxide (0.4 mL), and the mixture was stirred at room temperature for 1 hr. The solvent was evaporated under reduced pressure, and water (10 mL) was added. The mixture was neutralized with 1N hydrochloric acid under ice-cooling, and stirred for 1 hr. The resulting precipitate was collected by filtration and dried to give the title compound (82 mg, 72%).
Reaction SMILES: [C:1]([CH2:3][N:4]1[C:12]2[C:13](=[O:23])[N:14]([CH2:21][CH3:22])[C:15]3[C:20]([C:11]=2[C:10]2[CH:9]=[C:8]([Cl:24])[CH:7]=[CH:6][C:5]1=2)=[CH:19][CH:18]=[CH:17][CH:16]=3)#[N:2].CN(C)C=O.O1CCCC1>[Ni].C(O)C>[NH2:2][CH2:1][CH2:3][N:4]1[C:12]2[C:13](=[O:23])[N:14]([CH2:21][CH3:22])[C:15]3[C:20]([C:11]=2[C:10]2[CH:9]=[C:8]([Cl:24])[CH:7]=[CH:6][C:5]1=2)=[CH:19][CH:18]=[CH:17][CH:16]=3
Reactant: CCn1c(=O)c2c(c3ccccc31)c1cc(Cl)ccc1n2CC#N
Agent: [Ni]
Solvent: CN(C)C=O
Solvent: CCO
Solvent: C1CCOC1
Product: CCn1c(=O)c2c(c3ccccc31)c1cc(Cl)ccc1n2CCN

Procedure:
5 g. of 7-cyanomethyl-10-chloro-5-ethyl-7H-indolo[2,3-c]-quinolin-6(5H)-one was dissolved in 200 ml. of boiling dimethylformamide. After cooling, 200 ml. of tetrahydrofuran, 100 ml. of ethanol and Raney nickel were added. The mixture was hydrogenated for 21/2 hours at atmospheric pressure. The catalyst was separated by filtration and the filtrate was evaporated. Crystallization of the residue from ethanol yielded 2.9 g. (57 percent) of 7-(2-aminoethyl)-10-chloro-5-ethyl-7H-indolo[2,3-c]quinolin-6(5H)-one, which after recrystallization from ethanol had a melting point of 166°-169°.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:14]([NH2:16])=[O:15])=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([Cl:13])[CH:8]=2)[N:6]=1.[CH3:17][O:18][CH:19]([O:30][CH3:31])[C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[C:22](F)[CH:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O>C(OCC)(=O)C.O>[Cl:13][C:9]1[CH:8]=[C:7]([C:5]2[N:6]=[C:2]([NH:1][C:22]3[CH:21]=[C:20]([CH:19]([O:30][CH3:31])[O:18][CH3:17])[CH:25]=[CH:24][C:23]=3[N+:26]([O-:28])=[O:27])[S:3][C:4]=2[C:14]([NH2:16])=[O:15])[CH:12]=[CH:11][CH:10]=1
Reactant: COC(OC)c1ccc([N+](=O)[O-])c(F)c1
Reactant: NC(=O)c1sc(N)nc1-c1cccc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: COC(OC)c1ccc([N+](=O)[O-])c(Nc2nc(-c3cccc(Cl)c3)c(C(N)=O)s2)c1
Yield: 47.5 %

Procedure:
A mixture of 3.6 g (15 mmole) of 2-amino-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid amide (V.2), 3.9 g (17.9 mmole) of 4-(dimethoxymethyl)-2-fluoro-1-nitro-benzene (IV.2a), 7.3 g (22.5 mmole) cesium carbonate, and 30 mL of dimethylformamide was heated at 70 degrees for 18 hours. The mixture was cooled, diluted with 150 mL of ethyl acetate and 100 mL of water. The ethyl acetate layer was washed once with 100 mL of brine and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with hexanes-ethyl acetate (50:50) to give 3.2 g of 4-(3-chloro-phenyl)-2-(5-dimethoxymethyl-2-nitro-phenylamino)-thiazole-5-carboxylic acid amide (VI.2a).