Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O=[C:2]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4][NH:3]1.F[B-](F)(F)F.[CH3:21][O+](C)C.[NH2:25][NH2:26]>ClCCl>[C:12]([O:11][C:9]([N:6]1[CH2:7][CH2:8][C:2]2[N:3]([CH:21]=[N:25][N:26]=2)[CH2:4][CH2:5]1)=[O:10])([CH3:15])([CH3:14])[CH3:13]
Reactant: CC(C)(C)OC(=O)N1CCNC(=O)CC1
Reactant: NN
Reactant: C[O+](C)C
Agent: F[B-](F)(F)F
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCc2nncn2CC1
Reaction time: 16 h
Yield: 61.1 %

Procedure:
To a stirred solution of tert-butyl 5-oxo-1,4-diazepane-1-carboxylate (1000 mg, 4.67 mmol) in dichloromethane (10 mL) was added trimethyloxonium tetrafluoroborate (690 mg, 4.67 mmol) under nitrogen and the reaction mixture was stirred for 16 hours. At this point, formic hydrazine (280 mg, 4.67 mmol) in dichloromethane (8 mL) was added, and the reaction was stirred for an additional 16 hours. The reaction mixture was then concentrated under reduced pressure, resuspended in methanol (10 mL), and heated to reflux for 16 hours. The reaction mixture was concentrated and purified via flash chromatography on silica gel (0-50% 2N NH3 in methanol in CH2Cl2) to afford 4,5,7,8-tetrahydro-1,2,3a,6-tetraaza-azulene-6-carboxylic acid tert-butyl ester (680 mg, 61% yield). MS [m/z; (M+1)30 ]: 319.3
Reaction SMILES: [C:1]([NH:4][C:5]1[S:9][C:8]2[CH2:10][CH2:11][CH2:12][CH2:13][C:7]=2[C:6]=1[C:14](=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:3])[CH3:2].[H-].[Na+].[CH3:24]I.O>CN(C)C=O>[CH3:24][CH2:2][C:1]([NH:4][C:5]1[S:9][C:8]2[CH2:10][CH2:11][CH2:12][CH2:13][C:7]=2[C:6]=1[C:14](=[O:21])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:3]
Reactant: CI
Reactant: CC(=O)Nc1sc2c(c1C(=O)c1ccccc1)CCCC2
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCC(=O)Nc1sc2c(c1C(=O)c1ccccc1)CCCC2
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 5.0 g of 2-acetylamino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b ]thiophene in 60 ml of dimethylformamide is added 0.9 g of 63% sodium hydride. The mixture is stirred at room temperature for 30 minutes. Then 71.3 g of methyl iodide in 20 ml of dimethylformamide is added thereto. The mixture is stirred at room temperature for 3 hours, then poured into water, and extracted with benzene. The benzene extracts are washed with water, dried over sodium sulfate, and the solvent is removed under reduced pressure to give 2-(N-methylacetylamino)-3-benzoyl-4,5,6,7-tetrahydrobenzo[b] thiophene as an oil. This layer chromatography (Kiesel gel) shows the Rf value of 0.44 using a mixture of ethyl acetate and chloroform (1 : 1 V/V).
Reaction SMILES: [CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].O[N:15]1[C:19](=[O:20])[C:18]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:17]2[C:16]1=[O:25].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[O:25]=[C:16]1[C:17]2[C:18](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19](=[O:20])[N:15]1[O:13][CH:10]1[CH2:9][CH2:8][N:7]([C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[O:6])[CH2:12][CH2:11]1
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: CC(C)OC(=O)N1CCC(O)CC1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)OC(=O)N1CCC(ON2C(=O)c3ccccc3C2=O)CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 58.6 %

Procedure:
4-Hydroxy-piperidine-1-carboxylic acid isopropyl ester (3.09 g, 17 mmol), N-hydroxyphthalimide (2.69 g, 17 mmol), and triphenylphosphine (4.32 g, 17 mmol) were combined in THF (30 mL). DEAD (2.6 mL, 17 mmol) was added and the mixture was stirred at room temperature for 18 h. The mixture was then concentrated under vacuum and the residue was purified by flash LC(elution with 10-50% ethyl acetate and 0.1% TEA in hexanes) to afford 3.31 g (60%) of 2a as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 7.85-7.81 (m, 2 H), 7.83-7.29 (m, 2 H), 4.91 (quintet, J=6.3 Hz, 1 H), 4.43 (septet, J=3.9 Hz, 1 H), 3.94-3.86 (m, 2 H), 3.32-3.23 (m, 2 H), 1.99-1.78 (m, 4 H), 1.24 (d, J=6.6 Hz, 6 H); LC-MS 333.1 (MH+).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH:5]1[CH:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:7]([Si](C(C)(C)C)(C)C)C1=O.[C:23](=[O:26])(O)[O-:24].[Na+].[CH3:28]COCC>S(=O)(=O)(O)O>[Cl:1][CH2:2][CH2:3][CH2:4][CH:5]([C:23]([O:24][CH3:28])=[O:26])[CH:8]([NH2:7])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CC(C)(C)[Si](C)(C)N1C(=O)C(CCCCl)C1c1ccccc1
Reactant: O=C([O-])O
Reactant: CCOCC
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: COC(=O)C(CCCCl)C(N)c1ccccc1

Procedure:
3-(3'-Chloropropyl)-4-phenyl-1-(tert.-butyldimethylsilyl)azetidin-2-one (3.07 gm, 9.0 mmole) was dissolved in 10% methanolic sulfuric acid and refluxed for 16 hours. At the end of this period, the reaction mixture was cooled, the sulfuric acid was neutralized with sodium bicarbonate and the mixture was taken up in ether (2×200 ml). The ethereal solution was washed with water (2×50 ml) and dried (anhyd. magnesium sulfate). Evaporation afforded essentially pure 5-chloro-2-carbomethoxy-1-phenylpent-1-ylamine as an oil (2.11 gms). The 5-chloro-2-carbomethoxy-1-phenylpent-1-ylamine thus obtained was dissolved in the dimethylformamide ("DMF") (20 ml) and sodium iodide (2.11 gm) and sodium bicarbonate (2.11 gm) were added. The resulting mixture was refluxed for 15 min. At the end of this period, the reaction mixture was cooled and taken up in ether (200 ml). The ethereal solution was washed with water (2×50 ml) and dried (anhyd. magnesium sulfate). Evaporation of the ether afforded chromatographically pure cis-methyl 2-phenylpiperidine-3-carboxylate as an oil (1.54 gm, 78%).
Reaction SMILES: Br[C:2]1[N:7]=[CH:6][C:5]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[CH3:22][S:23]([C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][CH:30]=[CH:29]2)(=[O:25])=[O:24]>>[CH3:22][S:23]([C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[N:31]([C:2]1[N:7]=[CH:6][C:5]([NH:8][CH:9]3[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]3)=[CH:4][CH:3]=1)[CH:30]=[CH:29]2)(=[O:25])=[O:24]
Reactant: CS(=O)(=O)c1ccc2[nH]ccc2c1
Reactant: CC(C)(C)OC(=O)N1CCC(Nc2ccc(Br)nc2)CC1
Product: CC(C)(C)OC(=O)N1CCC(Nc2ccc(-n3ccc4cc(S(C)(=O)=O)ccc43)nc2)CC1

Procedure:
The title compound was prepared by following the similar procedure as described in Intermediate-27 using tert-butyl 4-((6-bromopyridin-3-yl)amino)piperidine-1-carboxylate and 5-(methylsulfonyl)-1H-indole; MS: 415.2 (M−56).
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:24])=[C:4](/[CH:17]=[CH:18]/[C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:5]([O:14][CH2:15][CH3:16])=[C:6]([C:8]2([CH3:13])[O:12][CH2:11][CH2:10][O:9]2)[CH:7]=1.N12CCCN=C1CCCCC2.O.[N+:37]([CH3:40])([O-:39])=[O:38]>>[Cl:1][C:2]1[C:3]([F:24])=[C:4]([CH:17]([CH2:40][N+:37]([O-:39])=[O:38])[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:5]([O:14][CH2:15][CH3:16])=[C:6]([C:8]2([CH3:13])[O:9][CH2:10][CH2:11][O:12]2)[CH:7]=1
Reactant: C[N+](=O)[O-]
Reactant: CCOC(=O)/C=C/c1c(F)c(Cl)cc(C2(C)OCCO2)c1OCC
Solvent: C1CCC2=NCCCN2CC1
Solvent: O
Product: CCOC(=O)CC(C[N+](=O)[O-])c1c(F)c(Cl)cc(C2(C)OCCO2)c1OCC
Temperature: 60 °C
Reaction time: 15 h

Procedure:
A solution ethyl (2E)-3-[3-chloro-6-ethoxy-2-fluoro-5-(2-methyl-1,3-dioxolan-2-yl\) phenyl]acrylate (10 g, 28 mmol) (from Step 2) in nitromethane (100 mL) was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (4.6 mL, 31 mmol) and stirred at 60° C. for 15 h. The reaction mixture was poured into water (400 mL) and extracted with ethyl acetate (2×300 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated to a crude orange oil. The crude material was purified by flash column chromatography using ethyl acetate in hexanes (0%-30%) to give the desired product as a mixture of enantiomers (10.4 g, 89%). 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J=9.1 Hz, 1H), 4.82 (ddd, J=12.5, 7.6, 1.4 Hz, 1H), 4.68 (dd, J=12.5, 7.2 Hz, 1H), 4.54-4.40 (m, 1H), 4.15-3.90 (m, 6H), 3.89-3.75 (m, 2H), 2.85 (ddd, J=16.0, 8.6, 1.4 Hz, 1H), 2.73 (dd, J=16.1, 6.2 Hz, 1H), 1.70 (s, 3H), 1.47 (t, J=7.0 Hz, 3H), 1.21 (t, J=7.1 Hz, 3H). LCMS for C18H24ClFNO7 (M+H)+: m/z=420.1; Found: 420.1.
Reaction SMILES: [NH2:1][CH:2]([CH2:38][CH3:39])[C:3]([N:5]1[CH2:10][CH2:9][C:8]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=2)([CH2:11][CH2:12][N:13]2[CH:18]3[CH2:19][CH2:20][CH:14]2[CH2:15][CH:16]([N:21]2[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=4[N:23]=[C:22]2[CH3:30])[CH2:17]3)[CH2:7][CH2:6]1)=[O:4].[Cl:40][CH:41]([Cl:45])[C:42](Cl)=[O:43].CCN(C(C)C)C(C)C>>[Cl:40][CH:41]([Cl:45])[C:42]([NH:1][CH:2]([C:3]([N:5]1[CH2:10][CH2:9][C:8]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=2)([CH2:11][CH2:12][N:13]2[CH:18]3[CH2:19][CH2:20][CH:14]2[CH2:15][CH:16]([N:21]2[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=4[N:23]=[C:22]2[CH3:30])[CH2:17]3)[CH2:7][CH2:6]1)=[O:4])[CH2:38][CH3:39])=[O:43]
Reactant: O=C(Cl)C(Cl)Cl
Reactant: CCC(N)C(=O)N1CCC(CCN2C3CCC2CC(n2c(C)nc4ccccc42)C3)(c2cccc(F)c2)CC1
Solvent: CCN(C(C)C)C(C)C
Product: CCC(NC(=O)C(Cl)Cl)C(=O)N1CCC(CCN2C3CCC2CC(n2c(C)nc4ccccc42)C3)(c2cccc(F)c2)CC1
Yield: 67 %

Procedure:
2,2-Dichloro-N-[1-(4-(3-fluoro-phenyl)-4-{2-[3-(2-methyl-benzoimidazol-1-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-ethyl}-piperidine-1-carbonyl)-propyl]-acetamide was obtained from treating[1-(4-(3-Fluoro-phenyl)-4-{2-[3-(2-methyl-benzoimidazol-1-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-ethyl}-piperidine-1-carbonyl)-propyl]-carbamic acid tert-butyl ester (0.580 g, 0.92 mmol) with HCl as outlined in the procedure for example 890 to form 2-Amino-1-(4-(3-fluoro-phenyl)-4-{2-[3-(2-methyl-benzoimidazol-1-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-ethyl}-piperidin-1-yl)-butan-1-one (0.488 g, 99%). 2-Amino-1-(4-(3-fluoro-phenyl)-4-{2-[3-(2-methyl-benzoimidazol-1-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-ethyl}-piperidin-1-yl)-butan-1-one (0.049 g, 0.09 mmol, Dichloro-acetyl chloride (0.013 g, 0.09 mmol) and DIEA (0.034 g, 0.534 mmol) were reacted following the procedure outlined in example 890 to give the title compound, 2,2-Dichloro-N-[1-(4-(3-fluoro-phenyl)-4-{2-[3-(2-methyl-benzoimidazol-1-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-ethyl}-piperidine-1-carbonyl)-propyl]-acetamide (0.039 g, 67%) as an oil. ES-LCMS m/z 642 (M+1).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:15])OCC(Cl)(Cl)Cl.[F:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:23]1[N:24]=[C:25]([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[S:26][CH:27]=1.C(N(C(C)C)CC)(C)C.O>CS(C)=O>[F:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:23]1[N:24]=[C:25]([N:28]2[CH2:29][CH2:30][N:31]([C:8]([NH:7][C:2]3[CH:3]=[N:4][CH:5]=[CH:6][N:1]=3)=[O:15])[CH2:32][CH2:33]2)[S:26][CH:27]=1
Reactant: Fc1ccccc1-c1csc(N2CCNCC2)n1
Reactant: O=C(Nc1cnccn1)OCC(Cl)(Cl)Cl
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: O=C(Nc1cnccn1)N1CCN(c2nc(-c3ccccc3F)cs2)CC1
Temperature: 70 °C
Reaction time: 84 h
Yield: 5.5 %

Procedure:
A mixture of 2,2,2-trichloroethyl pyrazin-2-ylcarbamate (226 mg, 0.835 mmol), 4-[4-(2-fluorophenyl)-1,3-thiazol-2-yl]piperazine (200 mg, 0.760 mmol) and diisopropylethylamine (0.265 ml, 1.52 mmol) in dimethylsulfoxide (2.5 ml) was stirred at 70° C. for 3.5 days. Water was poured into the reaction solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) and recrystallized from a mixed solvent of hexane and ethyl acetate to give the desired product (16.0 mg, 5.5%) as a solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:21]=[CH:22][C:23]=1[O:24][CH3:25])[CH2:6][CH:7]1[C:16]2[C:11](=[CH:12][C:13]([O:19][CH3:20])=[CH:14][C:15]=2[O:17][CH3:18])[CH2:10][CH2:9][NH:8]1.Br[CH2:27][C:28](Br)=[O:29].[NH2:31][C@H:32]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][CH2:33]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:21]=[CH:22][C:23]=1[O:24][CH3:25])[CH2:6][CH:7]1[C:16]2[C:11](=[CH:12][C:13]([O:19][CH3:20])=[CH:14][C:15]=2[O:17][CH3:18])[CH2:10][CH2:9][N:8]1[CH2:27][C:28]([NH:31][C@H:32]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][CH2:33]1)=[O:29]
Reactant: O=C(Br)CBr
Reactant: COc1cc2c(c(OC)c1)C(Cc1ccc(OC)c(OC)c1)NCC2
Reactant: N[C@@H]1CCc2ccccc21
Product: COc1cc2c(c(OC)c1)C(Cc1ccc(OC)c(OC)c1)N(CC(=O)N[C@@H]1CCc3ccccc31)CC2

Procedure:
prepared by reaction of 1-(3,4-Dimethoxy-benzyl)-6,8-dimethoxy-1,2,3,4-tetrahydroisoquinoline and 2-bromoacetyl bromide with (1R)-1-amino-indane
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1.[Br:12]N1C(=O)CCC1=O.Br>COC(C)(C)C.C(O)(=O)C>[Br:12][C:5]1[S:1][C:2]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=2)=[CH:3][CH:4]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: c1ccc(-c2cccs2)nc1
Agent: Br
Solvent: CC(=O)O
Solvent: COC(C)(C)C
Product: Brc1ccc(-c2ccccn2)s1
Temperature: 35 °C
Yield: 81.7 %

Procedure:
A solution of 2-thienylpyridine (1.924 kg) and N-bromosuccinimide (2.759 kg) in tert-butyl methyl ether (20.0 kg) was agitated for 15 minutes, treated with 30% HBr in acetic acid (125 g), heated to 35° C. for about 6 hours, and filtered. The wetcake was washed with tert-butyl methyl ether (12.6 kg) while maintaining the temperature of the filtrate at 30° C. to 35° C. The filtrate was washed with 5% Na2SO3 (21 kg) and 10% Na2CO3 (22 kg), concentrated to about 20 L, and diluted with isopropanol (11 kg), which caused the product to crystallize. This procedure was repeated twice more, when NMR analysis of the mother liquor indicated absence of tert-butyl methyl ether. The suspension was concentrated to about 12 L, cooled to 0° C., and filtered. The wetcake was washed with chilled (0° C.) isopropanol (7 kg) and dried in a vacuum oven with a nitrogen purge at 60° C. to provide 2.34 kg (82%) of the desired product. MS m/z 241 (M+H)+; 1H NMR δ 8.53 (m, 1H), 7.68 (m, 1H), 7.57 (m, 1H), 7.30 (m, 1H), 7.15 (m, 1H), 7.06 (m, 1H); Anal. calcd for C9H6BrNS: C, 45.01; H, 2.50; N, 5.83. Found: C, 45.14; H, 2.45; N, 5.72.
Reaction SMILES: O[CH2:2][C:3]1[CH:16]=[N:15][C:6]2[C:7]3[N:8]([CH:12]=[CH:13][CH:14]=3)[C:9](=[O:11])[NH:10][C:5]=2[CH:4]=1.[F:17][C:18]1[CH:19]=[C:20]([CH:25]=[CH:26][C:27]=1[N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)[C:21]([NH:23][CH3:24])=[O:22].[I-].C(C[P+](C)(C)C)#N.C(N(C(C)C)C(C)C)C>C(#N)CC>[F:17][C:18]1[CH:19]=[C:20]([CH:25]=[CH:26][C:27]=1[N:28]1[CH2:29][CH2:30][N:31]([CH2:2][C:3]2[CH:16]=[N:15][C:6]3[C:7]4[N:8]([CH:12]=[CH:13][CH:14]=4)[C:9](=[O:11])[NH:10][C:5]=3[CH:4]=2)[CH2:32][CH2:33]1)[C:21]([NH:23][CH3:24])=[O:22]
Reactant: O=c1[nH]c2cc(CO)cnc2c2cccn12
Reactant: CNC(=O)c1ccc(N2CCNCC2)c(F)c1
Agent: C[P+](C)(C)CC#N
Agent: [I-]
Solvent: CCC#N
Solvent: CCN(C(C)C)C(C)C
Product: CNC(=O)c1ccc(N2CCN(Cc3cnc4c(c3)[nH]c(=O)n3cccc43)CC2)c(F)c1
Temperature: 95 °C
Reaction time: 15 h
Yield: 80.2 %

Procedure:
To a suspension of 3-(hydroxymethyl)pyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-6(5H)-one (50.00 mg, 0.232 mmol), 3-fluoro-N-methyl-4-(piperazin-1-yl)benzamide (68.9 mg, 0.290 mmol) and (cyanomethyl)trimethylphosphonium iodide (90 mg, 0.372 mmol) in Propiononitrile (Volume: 1.00 mL) was added N-ethyl-N-isopropylpropan-2-amine (0.202 mL, 1.162 mmol) at 23° C. The reaction was stirred at 95° C. for 15 hr. The suspension was cooled to 23° C., concentrated via rotary evaporation, re-constituted in ACN (2.0 mL), stirred for 15 min, filtered, rinsed with ACN (3×1 mL) and dried in vacuo. The crude solid was re-suspended in ACN (2.0 mL), heated to reflux, cooled to 23° C., filtered, rinsed with ACN (3×2.0 mL) to provide 3-fluoro-N-methyl-4-(4-((6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-3-yl)methyl)piperazin-1-yl)benzamide (0.081 g, 0.186 mmol, 80.0% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.54-2.63 (m, 4H) 2.75 (d, J=4.55 Hz, 3 H) 3.08-3.17 (m, 4 H) 3.63 (s, 2 H) 6.71-6.75 (m, 1 H) 7.02-7.10 (m, 2 H) 7.53-7.63 (m, 3 H) 7.67 (dd, J=3.03, 1.52 Hz, 1 H) 8.29 (q, J=4.29 Hz, 1 H) 8.33-8.38 (m, 1 H) 11.56 (br. s., 1 H). ESI-MS: m/z 435.4 (M+H)+. mp=288.0-294.5° C.
Reaction SMILES: [NH2:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[CH:6][CH:7]=1.[NH2:9][C:10]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:11]=1[C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[Cl:20])=[O:13].CO.C1C=CC=CC=1>C(Cl)Cl>[NH2:1][C:2]1[C:3]([NH:9][C:10]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:11]=2[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[Cl:20])=[O:13])=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1ccc(Cl)cc1C(=O)c1ccccc1Cl
Reactant: Nc1cccnc1Cl
Solvent: c1ccccc1
Solvent: ClCCl
Solvent: CO
Product: Nc1cccnc1Nc1ccc(Cl)cc1C(=O)c1ccccc1Cl
Temperature: 190 °C
Reaction time: 8 h
Yield: 5.4 %

Procedure:
A stirred mixture of 20.0 g (0.156 mole) of 3-amino-2-chloropyridine and 37.3 g (0.14 mole) of 2-amino-2',5-dichlorobenzophenone was heated at 190° C. under nitrogen atmosphere for 5.5 hr. Thin layer chromatography (5% methyl alcohol-benzene on silica gel) indicated reaction had not substantially occurred. The mixture was stirred overnight at 190° C., cooled somewhat, and 100 ml methylene chloride was added cautiously. The suspension was stirred for two hr and the black solid which formed was separated by filtration. The solid was suspended in 500 ml of methylene chloride and 300 ml of dilute sodium hydroxide was added. An emulsion formed and the mixture was filtered which allowed separation of layers. The methylene chloride layer was washed with two 250 ml portions of water by extraction, dried over magnesium sulfate and evaporated under reduced pressure. The residue was dissolved in benzene and filtered through a 300 g column of florisil to remove low Rf material. All fractions were combined and evaporated under reduced pressure. Thin layer chromatography showed presence of two major components with lower Rf spot predominating. The residue was dissolved in benzene and chromatographed on a 600 g column of florisil packed in benzene. The higher Rf material was eluted with 1% acetone-benzene. On evaporation, the residue was triturated in benzene and recrystallized from benzene-isooctane to give 2.7 g product; m.p. 162°-4° C.
Reaction SMILES: Br[CH:2]([CH2:6][S:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)[C:3]([OH:5])=[O:4].[CH3:17][SH:18].[OH-].[Na+]>C(O)C>[CH3:16][O:15][C:12]1[CH:13]=[CH:14][C:9]([CH2:8][S:7][CH2:6][CH:2]([S:18][CH3:17])[C:3]([OH:5])=[O:4])=[CH:10][CH:11]=1
Reactant: CS
Reactant: COc1ccc(CSCC(Br)C(=O)O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COc1ccc(CSCC(SC)C(=O)O)cc1

Procedure:
A solution of 2-bromo-3-(4-methoxybenzylmercapto)propanoic acid (15 g.), methylmercaptan (3 g.) and sodium hydroxide (4.6 g.) in 95% ethanol (25 ml.) is refluxed for twelve hours. The sodium bromide is filtered off and the filtrate is concentrated to dryness in vacuo. The residue is dissolved in water, acidified with concentrated hydrochloric acid and extracted with ethyl acetate. The organic layer is dried and concentrated to dryness to yield 3-(4-methoxybenzylmercapto)-2-(methythio)propanoic acid.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]([C:12]2[CH2:13][CH2:14][N:15]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:16][CH:17]=2)[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](=[O:30])[N:7]2[C:22]1[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=1[Cl:29].[F:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[C:36](F)[CH:37]=1.C(O)(C(F)(F)F)=O>>[C:18]([N:15]1[CH2:14][CH2:13][CH:12]([C:10]2[CH:9]=[C:8]3[C:3]([CH:4]=[CH:5][C:6](=[O:30])[N:7]3[C:22]3[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:29])=[C:2]([C:35]3[CH:34]=[CH:33][C:32]([F:31])=[CH:37][CH:36]=3)[CH:11]=2)[CH2:17][CH2:16]1)([CH3:19])([CH3:21])[CH3:20]
Reactant: CC(C)(C)N1CC=C(c2cc(Br)c3ccc(=O)n(-c4c(Cl)cccc4Cl)c3c2)CC1
Reactant: OB(O)c1cc(F)cc(F)c1
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)N1CCC(c2cc(-c3ccc(F)cc3)c3ccc(=O)n(-c4c(Cl)cccc4Cl)c3c2)CC1

Procedure:
The title compound was prepared from 5-bromo-7-(1-tert-butyl-1,2,3,6-tetrahydropyridin-4-yl)-1-(2,6-dichlorophenyl)quinolin-2(1H)-one (INTERMEDIATE ABA5) and using 3,5-difluorophenylboronic acid as described in EXAMPLE ABA11. 1H NMR (CD3OD, 500 MHz) TFA salt: δ 1.416 (s, 9H), 1.827 (m, 2H), 2.119 (d, J=14.7 Hz, 2H), 2.948 (m, 1H), 3.063 (t, J=11.0 Hz, 2H), 3.675 (d, J=12.6 Hz, 2H), 6.497 (s, 1H), 6.747 (d, J=9.9 Hz, 1H). 7.122 (m, 3H), 7.249 (s, 1H), 7.619 (t, J=7.6 Hz, 1H), 7.728 (m, 2H), 7.987 (d, J=10.1 Hz, 1H). Mass spectrum (ES): 541.5 (M+1).
Reaction SMILES: Br[C:2]1[CH2:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2.CCN([CH2:16][CH3:17])CC.[C:18]([PH2:22])([CH3:21])([CH3:20])[CH3:19]>C1(C)C=CC=CC=1.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>[C:18]([P:22]([C:7]1[CH2:8][C:9]2[C:17]([CH:16]=1)=[CH:4][CH:3]=[CH:2][CH:10]=2)[C:2]1[CH2:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2)([CH3:21])([CH3:20])[CH3:19]
Reactant: CCN(CC)CC
Reactant: CC(C)(C)P
Reactant: BrC1=Cc2ccccc2C1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: CC(C)(C)P(C1=Cc2ccccc2C1)C1=Cc2ccccc2C1
Temperature: 25 °C

Procedure:
To 15.61 g (0.080 mol) of 2-bromo-1H-indene and 1.38 g (1.19 mmol) of Pd(PPh3)4 in 60 ml of toluene, 22.3 ml (16.19 g, 0.160 mol) of Et3N and 3.60 g (0.040 mol) of tBuPH2 were added. This mixture was refluxed for 24 hours, cooled to room temperature, and passed through short column with Silica Gel using 200 ml of toluene as eluent. The filtrate was evaporated to dryness to give oil, which after treatment with 150 ml of hot ethanol gave a gray precipitate. This precipitate was separated (G3), washed with 3×5 ml of cold ethanol and dried in vacuum. Yield 10.83 g (85%) of 15.
Reaction SMILES: [C:1]1([C:7]2[C:13]3[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:12]=3[N:11]3C(C=O)=[N:20][N:21]=[C:10]3[CH2:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C-:24]#N.[Na+].[C:27]([OH:30])(=[O:29])[CH3:28]>CO.[O-2].[O-2].[Mn+4]>[CH3:24][O:29][C:27]([C:28]1[N:11]2[C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[N:8][CH2:9][C:10]2=[N:21][N:20]=1)=[O:30]
Reactant: O=Cc1nnc2n1-c1ccc(Cl)cc1C(c1ccccc1)=NC2
Reactant: [C-]#N
Reactant: CC(=O)O
Agent: [Mn+4]
Agent: [Na+]
Agent: [O-2]
Solvent: CO
Product: COC(=O)c1nnc2n1-c1ccc(Cl)cc1C(c1ccccc1)=NC2

Procedure:
A mixture of 1.62 g (0.005 mole) of 6-phenyl-8-chloro-4H-s-triazolo[4,3-a][1,4]benzodiazepine-1-carboxaldehyde [cp. Example 1 a)], 20 ml of methanol, 1.225 g (0.025 mole) of sodium cyanide, 8.70 g (0.10 mole) of manganese dioxide and 0.40 g of glacial acetic acid is stirred for 16 hours at 25°. The reaction mixture is diluted with methanol, filtered through a layer of kieselguhr and the filtrate concentrated by evaporation. The residue is dissolved in methylene chloride, this solution washed with water and saturated sodium chloride solution, dried over magnesium sulphate and concentrated by evaporation. The oily residue is chromatographed on silica gel (Merck, 0.063 - 0.2 mm particle size) with ethyl acetate/methanol (9:1) as eluant. The fractions containing the desired product [Rf = 0.7 in the eluant system ethyl acetate/isopropanol (7:1)] are combined, concentrated by evaporation, and the residue crystallised from ethyl acetate to obtain 6-phenyl-8-chloro-4H-s-triazolo[4,3-a] [1,4]benzodiazepine-1-carboxylic acid methyl ester, M.P. 216°-217°.