Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[C:11]2[CH:10]=[C:9]([C:12]([OH:14])=O)[O:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.[CH2:15]([NH2:18])[C:16]#[CH:17].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C)C=O.C(N(CC)CC)C>[CH2:15]([NH:18][C:12]([C:9]1[O:8][C:7]2[CH:6]=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[C:11]=2[CH:10]=1)=[O:14])[C:16]#[CH:17]
Reactant: COc1cccc2oc(C(=O)O)cc12
Reactant: C#CCN
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: C#CCNC(=O)c1cc2c(OC)cccc2o1
Temperature: 0 °C
Reaction time: 4 h
Yield: 90.1 %

Procedure:
4-Methoxybenzo(b)furan-2-carboxylic acid (44.0 g) and propargylamine (12 g) were dissolved in dimethylformamide (200 ml), and WSC (48.0 g), HOBt (43.0 g) and triethylamine (50 ml) were added thereto at room temperature. The mixture was stirred for 4 hr. The reaction mixture was poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous solution of ammonium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound as yellow crystals (45.0 g)
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH3:12])[C:5]([O:7][CH3:8])=[O:6].BrN1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(N(CC)CC)C.[CH3:46][O:47][C:48]1[CH:55]=[CH:54][C:51]([CH2:52][NH2:53])=[CH:50][CH:49]=1>C(Cl)(Cl)(Cl)Cl.C1COCC1>[CH3:46][O:47][C:48]1[CH:55]=[CH:54][C:51]([CH2:52][N:53]2[CH2:1][C:2]3[C:11](=[CH:10][CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[CH:3]=3)[CH2:12]2)=[CH:50][CH:49]=1
Reactant: COC(=O)c1ccc(C)c(C)c1
Reactant: COc1ccc(CN)cc1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Agent: O=C1CCC(=O)N1Br
Solvent: CCN(CC)CC
Solvent: ClC(Cl)(Cl)Cl
Solvent: C1CCOC1
Product: COC(=O)c1ccc2c(c1)CN(Cc1ccc(OC)cc1)C2
Temperature: 25 °C
Reaction time: 8 h
Yield: 49 %

Procedure:
A mixture of methyl 3,4-dimethylbenzoate (1.334 g, 8.13 mmol), N-bromosuccinimide (3.173 g, 17.83 mmol) and benzoyl peroxide (0.143 g, 0.592 mmol) in carbon tetrachloride (5 mL) was heated at reflux for 1.5 hours. Upon cooling to room temperature, the solids present were removed by vacuum filtration and the resulting solution concentrated in vacuo. The residue obtained was re-dissolved in THF (30 mL). To the solution was added triethylamine (2.265 mL, 16.25 mmol) and a solution of 4-methoxy benzylamine (1.05 mL, 8.13 mmol) in THF (20 mL). The resulting reaction mixture was stirred overnight at room temperature. The precipitate was removed via filtration and the solution obtained was concentrated in vacuo. The residue obtained was purified via flash chromatography (15-30% EtOAc/hexane) to afford a light yellow oil (1.185 g). LCMS: (FA) ES+ 298; 1H NMR (CDCl3, 400 MHz) 7.89 (dd, J=7.8, 1.5 Hz, 1H), 7.84 (s, 1H), 8.74 (d, J=8.7 Hz, 2H), 7.313 (d, J=8.7 Hz 2H), 7.22 (d, J=7.2 Hz, 2H), 6.89 (d, J=8.7 Hz, 2H), 3.93 (s, 4H), 3.89 (s, 3H), 3.85 (s, 2H), 3.82 (s, 3H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([C:16]3[CH:20]=[CH:19][S:18][CH:17]=3)=[C:11]([CH2:13][CH2:14][OH:15])[N:12]=2)=[CH:4][CH:3]=1.[CH3:21][S:22](Cl)(=[O:24])=[O:23].C(N(CC)CC)C.O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([C:16]3[CH:20]=[CH:19][S:18][CH:17]=3)=[C:11]([CH2:13][CH2:14][O:15][S:22]([CH3:21])(=[O:24])=[O:23])[N:12]=2)=[CH:4][CH:3]=1
Reactant: CS(=O)(=O)Cl
Reactant: OCCc1nc(-c2ccc(F)cc2)oc1-c1ccsc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: CS(=O)(=O)OCCc1nc(-c2ccc(F)cc2)oc1-c1ccsc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Under argon atmosphere, to a solution of 2-(4-fluoro-phenyl)-4-(2-hydroxyethyl)-5-(3-thienyl)oxazole (300 mg) in methylene chloride (10 ml) were successively added methane-sulfonyl chloride (96 μl) and triethylamine (188 μl) under ice-cooling, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into water and extracted with methylene chloride. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to obtain a crude product of 2-(4-fluorophenyl)-4-(2-methanesulfonyloxyethyl)-5-(3-thienyl)oxazole.
Reaction SMILES: [Br:1][C:2]1[CH:18]=[CH:17][C:5]2[N:6]=[C:7]([C:9]3[CH:14]=[CH:13][C:12]([CH2:15]Br)=[CH:11][CH:10]=3)[O:8][C:4]=2[CH:3]=1.[N:19]1([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>>[Br:1][C:2]1[CH:18]=[CH:17][C:5]2[N:6]=[C:7]([C:9]3[CH:14]=[CH:13][C:12]([CH2:15][N:22]4[CH2:21][CH2:20][N:19]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:24][CH2:23]4)=[CH:11][CH:10]=3)[O:8][C:4]=2[CH:3]=1
Reactant: BrCc1ccc(-c2nc3ccc(Br)cc3o2)cc1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Product: CC(C)(C)OC(=O)N1CCN(Cc2ccc(-c3nc4ccc(Br)cc4o3)cc2)CC1

Procedure:
Preparation is carried out analogously to 4.1.g-2 from 6-bromo-2-(4-bromomethyl-phenyl)-benzoxazole and tert.-butyl piperazine-1-carboxylate.
Reaction SMILES: C(N(CC)CC)C.[CH:8]#[C:9][CH2:10][CH2:11][CH2:12][CH3:13].[NH2:14][C:15]1[NH:16][C:17](=[O:33])[C:18]2[C:23](I)=[CH:22][N:21]([C@@H:25]3[O:30][C@H:29]([CH2:31][OH:32])[C@@H:27]([OH:28])[CH2:26]3)[C:19]=2[N:20]=1>[Cu](I)I>[NH2:14][C:15]1[NH:16][C:17](=[O:33])[C:18]2[C:23]([C:8]#[C:9][CH2:10][CH2:11][CH2:12][CH3:13])=[CH:22][N:21]([C@@H:25]3[O:30][C@H:29]([CH2:31][OH:32])[C@@H:27]([OH:28])[CH2:26]3)[C:19]=2[N:20]=1
Reactant: Nc1nc2c(c(I)cn2[C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]1
Reactant: C#CCCCC
Agent: I[Cu]I
Solvent: CCN(CC)CC
Product: CCCCC#Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c2nc(N)[nH]c(=O)c12
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Copper iodide (38.1 mg, 0.2 mmol), triethylamine (2.8 ml, 2 mmol), tetrakis(triphenylphsophine)palladium(0) (40.5 mg, 0.1 mmol) and 1-hexyne (492 mg, 6 mmol) are added to an argon-flushed solution of compound (58) (390 mg, 1 mmol in 5 ml of dried DMF), and the solution is stirred at room temperature for 24 h. It is then evaporated and the residue is loaded onto a silica gel column (5×25 cm). Title compound (65) is obtained following stepwise elution with 5%, 10% and 20% MeOH in CH2Cl2. Recrystallization from MeCN affords a colorless solid (120 mg, 35%). 1H-NMR ([(D6] DMSO): δ=0.94 (m, CH3), 1.49, 2.38 (m, CH2), 2.0 (M, Hα—C(2′)), 2.35 (m, Hβ—C(2′)), 3.50 (m, H2—C(5′)), 3.76 (m, H—C(4′)), 4. (m, H—C(3′)), 4.88 (t, 5′-OH), 5.18 (d, J=3.5, 3′-OH), 6.27 (m, H—C(1′) +NH2), 7.13 (s, H—C(6)), 10.34 (br., NH). MS: m/e 346 (M+).
Reaction SMILES: [C:1]1([CH2:7][C:8]([NH:10][C@@H:11]2[CH2:15][O:14][N:13]([C:16]3([C:22]([O:24][CH3:25])=[O:23])[CH:20]=[CH:19][C:18](=[O:21])[O:17]3)[C:12]2=[O:26])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>O1CCCC1.[H][H].[C].[Pd]>[C:1]1([CH2:7][C:8]([NH:10][C@@H:11]2[CH2:15][O:14][N:13]([C:16]3([C:22]([O:24][CH3:25])=[O:23])[CH2:20][CH2:19][C:18](=[O:21])[O:17]3)[C:12]2=[O:26])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)C1(N2OC[C@@H](NC(=O)Cc3ccccc3)C2=O)C=CC(=O)O1
Reactant: [H][H]
Agent: [Pd]
Solvent: C1CCOC1
Product: COC(=O)C1(N2OC[C@@H](NC(=O)Cc3ccccc3)C2=O)CCC(=O)O1
Yield: 79.6 %

Procedure:
In 3 ml of tetrahydrofuran was dissolved 30 mg of the Compound (30) obtained in Example 30. To the solution was added 30 mg of 10% palladium-carbon, and the mixture was stirred at room temperature for 30 minutes in hydrogen streams. The catalyst was filtered off and washed with tetrahydrofuran. The filtrate and the washing were combined, then the solvent was evaporated off. The residue was subjected to a silica gel column chromatography, followed by elution with hexane-ethyl acetate (2:3) to give 24 mg of the subject Compound (31) as colorless oil.
Reaction SMILES: C(=O)(O)[O-].[Na+].[NH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.Br[CH2:14][C:15]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1)=O.O>C(O)C>[CH3:24][O:23][C:20]1[CH:21]=[CH:22][C:17]([C:15]2[N:6]=[C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][N:8]3[CH:14]=2)=[CH:18][CH:19]=1
Reactant: COc1ccc(C(=O)CBr)cc1
Reactant: Nc1ccccn1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: COc1ccc(-c2cn3ccccc3n2)cc1

Procedure:
A mixture of 25.2 g. of sodium bicarbonate, 12.3 g. of 2-aminopyridine and 30 g. of α-bromo-p-methoxyacetophenone in 100 ml. of water and 550 ml. of absolute ethanol is heated at reflux temperatures for 1.5 hrs. The reaction mixture is concentrated under reduced pressure to a yellow solid, which is partitioned between chloroform and water. The organic layer is separated, dried over sodium sulfate. Removal of the chloroform in vacuo leaves the crude intermediate as a yellow solid. Recrystallization from ethanol-water give 15.2 g. of the desired material, m.p. 131°-134° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[NH2:11])[NH:7][C:6](=[O:12])[C:5]2([CH3:14])[CH3:13].[CH3:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21](O)=O.C>C(O)C>[CH2:16]([C:15]1[NH:11][C:10]2[CH:9]=[C:8]3[NH:7][C:6](=[O:12])[C:5]([CH3:14])([CH3:13])[C:4]3=[CH:3][C:2]=2[N:1]=1)[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CC1(C)C(=O)Nc2cc(N)c(N)cc21
Reactant: CCCCCCC(=O)O
Solvent: CCO
Product: CCCCCCc1nc2cc3c(cc2[nH]1)NC(=O)C3(C)C

Procedure:
Analogously to Example 11, from 0.48 g. 5,6-diamino-3,3-dimethylindolin-2-one and 0.36 g. oenanthic acid, after heating with 4.5 g. polyphosphoric acid for 30 minutes at a bath temperature of 200° C., there is obtained 0.7 g. of crude product which is dissolved in 35 ml. ethanol, treated with active charcoal, filtered and the clear filtrate evaporated in a vacuum. The evaporation residue, after trituration with diethyl ether, gives 0.37 g. of the title compound in the form of the monohydrate; m.p. 233°-234° C.
Reaction SMILES: [CH:1]1([C:4]([C:6]2[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=2)=O)[CH2:3][CH2:2]1.[CH2:13]([C:15]1[NH:16][CH:17]=[C:18]([CH3:20])[N:19]=1)[CH3:14]>>[Cl:12][C:9]1[CH:8]=[CH:7][C:6]([C:4]2[C:1]3[N:16]([C:15]([CH2:13][CH3:14])=[N:19][C:3]=3[CH3:2])[CH2:17][CH2:18][CH:20]=2)=[CH:11][CH:10]=1
Reactant: CCc1nc(C)c[nH]1
Reactant: O=C(c1ccc(Cl)cc1)C1CC1
Product: CCc1nc(C)c2n1CCC=C2c1ccc(Cl)cc1

Procedure:
Combine 25 g (0.14 mol) of 4-chlorophenyl cyclopropyl ketone with 50 g (0.45 mol) of 2-ethyl-4-methylimidazole, and heat to 175° C. under argon for 40 hr. Isolate the title compound by column chromatography on 500 g of silica gel using 1% methanol/methylene chloride as solvent.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[Cl:12][C:13]1[CH:18]=[C:17](I)[CH:16]=[CH:15][C:14]=1[CH3:20]>>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:17]2[CH:16]=[CH:15][C:14]([CH3:20])=[C:13]([Cl:12])[CH:18]=2)[CH:3]=1
Reactant: Cc1ccc(I)cc1Cl
Reactant: Clc1ccnc2ccccc12
Product: Cc1ccc(-c2cc(Cl)c3ccccc3n2)cc1Cl

Procedure:
The title compound, m. p. 115-116° C., MS: m/e=288 (M+), was prepared from 4-chloroquinoline and 2-chloro-4-iodo-toluene.
Reaction SMILES: [CH:1]1([NH:6][C:7]2[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][C:8]=2[C:9]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([O:21]CC)=[O:20])=[CH:15][CH:14]=2)=[O:10])[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].Cl>C(O)C>[C:19]([C:16]1[CH:15]=[CH:14][C:13]([CH2:12][NH:11][C:9](=[O:10])[C:8]2[CH:24]=[C:25]([N+:28]([O-:30])=[O:29])[CH:26]=[CH:27][C:7]=2[NH:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[CH:18][CH:17]=1)([OH:21])=[O:20]
Reactant: CCOC(=O)c1ccc(CNC(=O)c2cc([N+](=O)[O-])ccc2NC2CCCC2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)c1ccc(CNC(=O)c2cc([N+](=O)[O-])ccc2NC2CCCC2)cc1
Yield: 90 %

Procedure:
A mixture of 2-(cyclopentylamino)-N-(4-ethoxycarbonylbenzyl)-5-nitrobenzamide (645 mg), ethanol (30 mL) and 1N-sodium hydroxide solution (5 mL) was heated for 2 hours under reflux. The mixture was acidified with 1 N-hydrochloric acid to pH 4 and the organic solvent was removed by evaporation. The resulting precipitates were collected by filtration and washed with water and diethyl ether to give N-(4-carboxybenzyl)-2-(cyclopentylamino)-5-nitrobenzamide as yellow powders (541 mg).
Reaction SMILES: [NH2:1][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[Na].[C:12]([NH:14][C:15]([NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=S)#[N:13]>>[NH2:13][C:12]1[N:1]=[C:2]2[N:6]([C:15](=[N:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[N:14]=1)[C:5]1[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=1[NH:3]2
Reactant: N#CNC(=S)Nc1ccccc1
Reactant: Nc1nc2ccccc2[nH]1
Agent: [Na]
Product: Nc1nc(=Nc2ccccc2)n2c(n1)[nH]c1ccccc12
Reaction time: 16 h
Yield: 27.8 %

Procedure:
A suspension of 2-aminobenzimidazole (10.0 g) and the sodium salt of N-cyano-N'-phenyl thiourea (7.5 g) was stirred at room temperature for 30 minutes. Mercuric chloride (10.2 g) was added and stirring continued for 16 h. The mixture was filtered and the filtrate evaporated to a gum. A solution of the gum in methanol soon yielded a solid (3.25 g). The solid was collected, suspended in tetrahydrofuran and hydrogen sulphide added until no further black precipitate formed. The mixture was filtered and the filtrate evaporated to give a yellow solid which showed several components on thin layer chromatography. The components were separated on a column of silica gel to give the sub-title compound as white crystals (1.22 g) mp, 271°-3°.
Reaction SMILES: [C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:43]/[OH:44])/[C:27]([O:29][CH:30]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:46]1([C:52]([O:54][CH3:55])=[O:53])[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1>C(OCC)(=O)C.CCCCCC>[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:43]/[O:44][C:46]2([C:52]([O:54][CH3:55])=[O:53])[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]2)/[C:27]([O:29][CH:30]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(OC(c1ccccc1)c1ccccc1)/C(=N\O)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Reactant: COC(=O)C1(Br)CCCCC1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: COC(=O)C1(O/N=C(\C(=O)OC(c2ccccc2)c2ccccc2)c2csc(NC(c3ccccc3)(c3ccccc3)c3ccccc3)n2)CCCCC1
Yield: 69 %

Procedure:
Benzhydryl 2-(2-tritylaminothiazol-4-yl)-(Z)-2-(hydroxyimino)acetate (2.0 g) was treated with methyl 1-bromocyclohexane carboxylate as described in Example 5a to give the title compound (1.7 g, 69%) as a white solid, m.p. 180°-182° C. (ethyl acetate/hexane). [Found: C: 73.73; H: 5.60; N: 5.69. C45H41N3O5S requires C: 73.45; H: 5.62; N: 5.71%] νmax (KBr) 3406, 2945, 1751, and 1528cm-1, δH (CDCl3) 1.36 (5H, m), 1.72 (3H, m), 2.00 (2H, m), 3.69 (3H, s), 6.46 (1H, s), 6.71 (1H, s), 7.15 (1H, s), 7.29 and 7.34 (25H, m).
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]1[CH:9]=[C:8]([F:10])[C:7]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[C:6]([C:16]#[CH:17])[CH:5]=1.C(N(CC)CC)C.[Br:25][C:26]1[N:31]=[CH:30][C:29]([CH:32]=[CH:33][C:34](O)=[O:35])=[CH:28][CH:27]=1.C[N+]1(C2N=C(OC)N=C(OC)N=2)CCOCC1.[Cl-]>C1COCC1.CCOC(C)=O>[Br:25][C:26]1[N:31]=[CH:30][C:29]([CH:32]=[CH:33][C:34]([NH:2][CH2:3][C:4]2[CH:9]=[C:8]([F:10])[C:7]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[C:6]([C:16]#[CH:17])[CH:5]=2)=[O:35])=[CH:28][CH:27]=1
Reactant: C#Cc1cc(CN)cc(F)c1NS(C)(=O)=O
Reactant: O=C(O)C=Cc1ccc(Br)nc1
Agent: COc1nc(OC)nc([N+]2(C)CCOCC2)n1
Agent: Cl
Agent: [Cl-]
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C#Cc1cc(CNC(=O)C=Cc2ccc(Br)nc2)cc(F)c1NS(C)(=O)=O
Reaction time: 0.17 h
Yield: 71.7 %

Procedure:
N-(4-Aminomethyl-2-ethynyl-6-fluoro-phenyl)-methanesulfonamide HCl salt (63 mg, 0.219 mmol) was suspended in THF and treated with triethylamine (25 mg, 0.241 mmol) and then the resulting mixture was stirred for 10 mins. 3-(6-bromo-pyridin-3-yl)-acrylic acid (50 mg, 0.219 mmol) was added to the reaction mixture followed by DMTMM (66 mg, 0.241 mmol) after 10 mins. The resulting mixture was stirred overnight at ambient temperature and then diluted with EtOAc. The resulting solution was washed successively with water, sat'd NaHCO3 (×2), and brine, and then dried over anhyd. Na2SO4, filtered and concentrated under reduced pressure. The crude residue was recrystallized (EtOAc/n-Hexane) to yield the title compound (71 mg, 72%).
Reaction SMILES: N1CCCCC1.C1C2C(COC(=O)[NH:23][CH:24]([CH2:48][C:49]3[CH:54]=[CH:53][C:52]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[CH:51][CH:50]=3)[C:25](=[O:47])[N:26]3[CH:35]([C:36]4[NH:37][CH:38]=[C:39]([C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=5)[N:40]=4)[CH2:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH2:27]3)C3C(=CC=CC=3)C=2C=CC=1>CO>[NH2:23][CH:24]([CH2:48][C:49]1[CH:54]=[CH:53][C:52]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[CH:51][CH:50]=1)[C:25]([N:26]1[CH:35]([C:36]2[NH:37][CH:38]=[C:39]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[N:40]=2)[CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:27]1)=[O:47]
Reactant: CC(C)(C)Oc1ccc(CC(NC(=O)OCC2c3ccccc3-c3ccccc32)C(=O)N2Cc3ccccc3CC2c2nc(-c3ccccc3)c[nH]2)cc1
Solvent: C1CCNCC1
Solvent: CO
Product: CC(C)(C)Oc1ccc(CC(N)C(=O)N2Cc3ccccc3CC2c2nc(-c3ccccc3)c[nH]2)cc1

Procedure:
Piperidine in methanol (20%; 2 mL) was added to {1-(4-tert-butoxy-benzyl)-2-oxo-2-[3-(4-phenyl-1H-imidazol-2-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-ethyl}-carbamic acid 9H-fluoren-9-ylmethyl ester (0.20 g, 0.28 mmol) at room temperature. After 30 minutes the reaction was concentrated under reduced pressure, and the residual 200 mg of desired product 2-amino-3-(4-tert-butoxy-phenyl)-1-[3-(4-phenyl-1H-imidazol-2-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-propan-1-one was used as is without further purification (LC/MS; Measured MW (MH+): 495).
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=[C:11]2[CH:19]([C:21]2[CH:26]=[CH:25][C:24]([S:27][CH3:28])=[CH:23][CH:22]=2)[OH:20])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=[C:11]2[C:19]([C:21]2[CH:22]=[CH:23][C:24]([S:27][CH3:28])=[CH:25][CH:26]=2)=[O:20])(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CSc1ccc(C(O)c2cc3cccnc3n2S(=O)(=O)c2ccccc2)cc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: CSc1ccc(C(=O)c2cc3cccnc3n2S(=O)(=O)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 96.3 %

Procedure:
To a solution of (1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-(4-methylsulfanyl-phenyl)-methanol (7.0 g, 17.1 mmol) in dichloromethane (600 ml) was added Dess-Martin periodinane (21.8 g, 51.3 mmol) at 25° C. The reaction mixture was stirred at 25° C. for 1 h and then quenched with a saturated aqueous sodium bicarbonate solution (100 mL). The mixture was extracted with ethyl acetate (500 mL), washed with a saturated aqueous sodium bicarbonate solution (3×80 mL), brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by flash column chromatography (silica gel from QingDao, 200-300 mesh, 30% ethyl acetate/hexanes) afforded (1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-(4-methylsulfanyl-phenyl)-methanone (6.73 g, 97%) as a white solid: LC/MS m/e calcd for C21H16N2O3S2 [M+H]+ 409.50, observed 409.2.
Reaction SMILES: [O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][C:8]([O:10]CC)=O.[CH3:13][N:14]1[CH2:19][CH2:18][N:17]([CH:20]([CH3:23])[CH2:21][NH2:22])[CH2:16][CH2:15]1>>[CH3:13][N:14]1[CH2:19][CH2:18][N:17]([CH:20]([CH3:23])[CH2:21][NH:22][C:8](=[O:10])[CH2:7][N:3]2[CH2:4][CH2:5][CH2:6][C:2]2=[O:1])[CH2:16][CH2:15]1
Reactant: CCOC(=O)CN1CCCC1=O
Reactant: CC(CN)N1CCN(C)CC1
Product: CC(CNC(=O)CN1CCCC1=O)N1CCN(C)CC1

Procedure:
From 7.0 g. of ethyl 2-oxo-1-pyrrolidineacetate and 6.3 g. of 2-(4-methyl-1-piperazinyl)propylamine, following the procedure of Example 9, there is obtained (±)-N-[2-(4-methyl-1-piperazinyl)propyl]-2-oxo-1-pyrrolidineacetamide; m.p. 84°-85° C. after recrystallization from cyclohexane and from heptane.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1.[N-:13]=[N+:14]=[N-:15].[Na+]>CC(C)=O.O>[N:13]([CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1)=[N+:14]=[N-:15]
Reactant: [N-]=[N+]=[N-]
Reactant: O=C(O)Cc1ccc(CBr)cc1
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: [N-]=[N+]=NCc1ccc(CC(=O)O)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 71.7 %

Procedure:
A solution of p-bromomethylphenylacetic acid (3.64 g, 15.9 mmol) in acetone (100 ml) was treated with a solution of sodium azide (1.04 g, 16.0 mmol) in H2O (15 ml). The mixture was stirred at room temperature overnight (ca. 20 h). After evaporation of the acetone, the residual solution was cooled in an ice-bath. The white gelatinous precipitate that formed was collected, washed with cold water and dried yielding 2.175 g (11.4 mmol, 71.5%) of p-azidomethylphenylacetic acid as a white solid: 1Hmr (DMSO-d6) δ: 3.59 (2H, s,--CH2CO2), 4.42 (2H, s,--CH2N3) and 7.32 ppm (4H, s, aromatic Hs); ir (nujol) νmax : 2500-3400 (b, --CO2H), 2070 (s, --N3) and 1690 cm-1 (s, C=O).
Reaction SMILES: [NH2:1][CH2:2][CH:3]([C:9]1([CH3:14])[O:13][CH2:12][CH2:11][O:10]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5].[Cl:15][C:16]1[CH:17]=[C:18]2[C:23](=O)[O:22][C:20](=[O:21])[C:19]2=[CH:25][CH:26]=1>>[Cl:15][C:16]1[CH:17]=[C:18]2[C:19](=[CH:25][CH:26]=1)[C:20](=[O:21])[N:1]([CH2:2][CH:3]([C:9]1([CH3:14])[O:10][CH2:11][CH2:12][O:13]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:23]2=[O:22]
Reactant: O=C1OC(=O)c2cc(Cl)ccc21
Reactant: CCOC(=O)C(CN)C1(C)OCCO1
Product: CCOC(=O)C(CN1C(=O)c2ccc(Cl)cc2C1=O)C1(C)OCCO1

Procedure:
Ethyl 3-(5-chloro-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(2-methyl-[1,3]dioxolan-2-yl)propionate was prepared (0.37 g, 50%) in the same manner as described in the above example 5 (20) from ethyl 3-amino-2-(2-methyl-[1,3]dioxolan-2-yl)propionate (0.40 g, 1.97 mmol) and 4-chlorophthalic anhydride (0.47 g, 2.56 mmol), and the obtained product was identified with the following NMR data.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][NH:3][C:2]1=[O:6].C([O-])([O-])=O.[K+].[K+].[Br:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18]Br)=[CH:16][CH:15]=1.O>CS(C)=O>[Br:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18][N:1]2[CH2:5][CH2:4][NH:3][C:2]2=[O:6])=[CH:16][CH:15]=1
Reactant: BrCc1ccc(Br)cc1
Reactant: O=C1NCCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: O=C1NCCN1Cc1ccc(Br)cc1
Reaction time: 1.8 h
Yield: 100 %

Procedure:
A 12.4 g (0.14 mole) portion of 2-imidazolidinone in 125 ml of dimethylsulfoxide treated with 19.9 g (0.14 mole) of K2CO3, 11.5 g (0.069 mole) of KI and 36.0 g (0.14 mole) of 4-bromobenzylbromide. The reaction mixture was heated to 105° over 0.3 hours, held at 105° with stirring for 1.8 hours, and poured into 1.51 of cold water. The aqueous mixture was extracted with 1.3 l of chloroform. The chloroform extract was washed with 500 ml of water, dried over MgSO4 overnight and filtered. The filtrate was concentrated under reduced pressure to give 36 g (100%) of a light yellow semisolid. The crude product was crystallized using 150 ml of ether, filtered, air dried and dried at 60° for 4 hours to give 15 (42%) of a white solid m.p. 163°-167°. Recrystallization from acetonitrile gave an analytical sample, m.p. 166°-168°.
Reaction SMILES: [Cl:1][C:2]1[C:3]2[C:12]([F:13])=[CH:11][CH:10]=[CH:9][C:4]=2[S:5][C:6]=1[CH2:7][OH:8]>C1C=CC=CC=1.O=[Mn]=O>[Cl:1][C:2]1[C:3]2[C:12]([F:13])=[CH:11][CH:10]=[CH:9][C:4]=2[S:5][C:6]=1[CH:7]=[O:8]
Reactant: OCc1sc2cccc(F)c2c1Cl
Agent: O=[Mn]=O
Solvent: c1ccccc1
Product: O=Cc1sc2cccc(F)c2c1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 88.5 %

Procedure:
A suspension of (3-chloro-4-fluoro-benzo[b]thiophen-2-yl)methanol (1.00 g, 4.63 mmol) and MnO2 (3.10 g, 35.2 mmol) in benzene (50 mL) was stirred at room temperature overnight. The solution was filtered through diatamaceous earth and the was filtrate was concentrated to give the title compound (880 mg, 87%) as an off-white solid: 1H NMR (500 MHz, CDCl3) δ 10.32 (s, 1H), 7.63 (dd, J=8.2, 0.4 Hz, 1H), 7.50 (ddd, J=8.1, 8.1, 4.7 Hz, 1H), 7.13 (ddd, J=11.0, 7.9, 0.4 Hz, 1H).