Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][C:15]([OH:17])=O)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Li][CH3:19]>CCOCC>[C:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][C:15](=[O:17])[CH3:19])[CH2:9]1)([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]
Reactant: CC(C)(C)OC(=O)N1CCCC(CC(=O)O)C1
Reactant: [Li]C
Solvent: CCOCC
Product: CC(=O)CC1CCCN(C(=O)OC(C)(C)C)C1
Reaction time: 8 h

Procedure:
A solution of 2-2 (13.4 g, 55 mmol) in ether (500 mL) at 0° C. was treated dropwise with MeLi (87 mL, 121 mmol; 1.4 M/ether). After addition was complete, the cooling bath was removed and the reaction mixture was stirred overnight. The reaction mixture was then poured into an ice/water mixture and then extracted with ether. The ether extracts were washed with brine, dried (MgSO4), and concentrated. Flash chromatography (silica, 30% EtOAc/hexanes) gave 2-3 as a colorless oil.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:5]([C:7]([N:9]2[CH2:14][C@H:13]3[C@H:11]([CH2:12]3)[C@H:10]2[CH2:15][NH2:16])=[O:8])[N:6]=1.[CH3:24][O:25][C:26]1[CH:27]=[C:28]([CH:32]=[C:33]([O:35][CH3:36])[CH:34]=1)[C:29](O)=[O:30]>>[NH2:1][C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:5]([C:7]([N:9]2[CH2:14][C@H:13]3[C@H:11]([CH2:12]3)[C@H:10]2[CH2:15][NH:16][C:29](=[O:30])[C:28]2[CH:32]=[C:33]([O:35][CH3:36])[CH:34]=[C:26]([O:25][CH3:24])[CH:27]=2)=[O:8])[N:6]=1
Reactant: NC[C@@H]1[C@H]2C[C@H]2CN1C(=O)c1nc(N)sc1-c1cccc(F)c1
Reactant: COc1cc(OC)cc(C(=O)O)c1
Product: COc1cc(OC)cc(C(=O)NC[C@@H]2[C@H]3C[C@H]3CN2C(=O)c2nc(N)sc2-c2cccc(F)c2)c1

Procedure:
prepared by reaction of [2-Amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((1S,2S,5R)-2-aminomethyl-3-aza-bicyclo[3.1.0]hex-3-yl)-methanone with 3,5-dimethoxy-benzoic acid. LC-MS (basic): tR=0.80 min; [M+H]+=497.3.
Reaction SMILES: C([N:8](CC1C=CC=CC=1)[C:9]1([CH2:13][NH:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([CH3:25])[CH:23]=3)[N:18]=[C:17]([N:26]3[CH2:32][C:31]4[CH:33]=[CH:34][CH:35]=[CH:36][C:30]=4[S:29](=[O:38])(=[O:37])[CH2:28][CH2:27]3)[N:16]=2)[CH2:12][O:11][CH2:10]1)C1C=CC=CC=1>CO.[OH-].[Pd+2].[OH-]>[NH2:8][C:9]1([CH2:13][NH:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([CH3:25])[CH:23]=3)[N:18]=[C:17]([N:26]3[CH2:32][C:31]4[CH:33]=[CH:34][CH:35]=[CH:36][C:30]=4[S:29](=[O:38])(=[O:37])[CH2:28][CH2:27]3)[N:16]=2)[CH2:10][O:11][CH2:12]1
Reactant: Cc1ccc2nc(N3CCS(=O)(=O)c4ccccc4C3)nc(NCC3(N(Cc4ccccc4)Cc4ccccc4)COC3)c2c1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: Cc1ccc2nc(N3CCS(=O)(=O)c4ccccc4C3)nc(NCC3(N)COC3)c2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 30.2 %

Procedure:
To a solution of N-{[3-(dib enzylamino)oxetan-3-yl]methyl}-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-amine (1.4 g, 2.26 mmol) in methanol was added palladium hydroxide (20% on carbon, 200 mg). After being stirred at room temperature overnight under a hydrogen atmosphere, the resulting mixture was filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography on silica gel to afford 300 mg of the product as off-white foam. MS obsd. (ESI+) [(M+H)+] 440, 1H NMR (400 MHz, CD3OD) δ ppm 7.97 (d, J=7.6 Hz, 1 H), 7.86 (d, J=7.2 Hz, 1 H), 7.69 (s, 1 H), 7.58 (t, J=7.2 Hz, 1 H), 7.44-7.34 (m, 3 H), 5.21 (s, 2 H), 4.66 (d, J=6.4 Hz, 2 H), 4.60 (br.s., 2 H), 4.56 (d, J=6.4 Hz, 2 H), 4.10 (s, 2 H), 3.52 (t, J=5.2 Hz, 2 H), 2.39 (s, 3 H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:25]#[N:26])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:10](=[O:24])[CH:9]=2)[CH:7]=1.[O:27]1[CH2:31][CH2:30][CH:29]([CH:32]=[O:33])[CH2:28]1.[Cl-].[NH4+]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:25]#[N:26])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH:32]([OH:33])[CH:29]3[CH2:30][CH2:31][O:27][CH2:28]3)[C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[C:10](=[O:24])[CH:9]=2)[CH:7]=1
Reactant: COc1cn(CC(=O)OC(C)(C)C)c(=O)cc1-c1cc(Cl)ccc1C#N
Reactant: O=CC1CCOC1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: COc1cn(C(C(=O)OC(C)(C)C)C(O)C2CCOC2)c(=O)cc1-c1cc(Cl)ccc1C#N
Temperature: -70 °C
Reaction time: 0.17 h

Procedure:
At −70° C., 6.94 ml (6.94 mmol, 1.3 eq.) of bis(trimethylsilyl)lithium amide (1M in THF) were added dropwise to a solution of 2.00 g (5.34 mmol) of tert-butyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]acetate in 50 ml of tetrahydrofuran, the mixture was stirred at −70° C. for 10 min, a solution of 801 mg (8.00 mmol, 1.5 eq.) of tetrahydrofuran-3-carbaldehyde in 4 ml of tetrahydrofuran was added and the mixture was stirred at −70° C. for 90 min. The reaction mixture was warmed to −20° C., and 25 ml of semisaturated aqueous ammonium chloride solution were added. After phase separation, the aqueous phase was extracted with diethyl ether. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried (sodium sulphate), filtered, concentrated under reduced pressure and dried. The crude product was purified by flash chromatography (KP-SIL, petroleum ether/ethyl acetate 33-75%). Yield: 1.49 g (56% of theory)
Reaction SMILES: [N+:1]([C:4]1[CH:20]=[CH:19][C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][C:10]=2[N+:16]([O-:18])=[O:17])=[CH:6][CH:5]=1)([O-:3])=[O:2].Cl[C:22]([O:24][CH2:25][CH3:26])=[O:23]>N1C=CC=CC=1>[N+:1]([C:4]1[CH:20]=[CH:19][C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:22](=[O:23])[O:24][CH2:25][CH3:26])=[CH:11][C:10]=2[N+:16]([O-:18])=[O:17])=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: Nc1ccc(Oc2ccc([N+](=O)[O-])cc2)c([N+](=O)[O-])c1
Reactant: CCOC(=O)Cl
Solvent: c1ccncc1
Product: CCOC(=O)Nc1ccc(Oc2ccc([N+](=O)[O-])cc2)c([N+](=O)[O-])c1
Temperature: 5 °C
Reaction time: 0.5 h

Procedure:
4-(4-Nitrophenoxy)-3-nitrobenzenamine (0.1 mole) and pyridine (50 ml) are charged into a glass reaction vessel fitted with a mechanical stirrer and thermometer and are cooled to about 5° C. Ethyl chloroformate (0.125 mole) is added, with stirring, at about 5° C. Stirring is continued for a period of about 30 minutes at about 5° C., then for an additional 16 hours at room temperature. The mixture is then washed with 2 portions of water (50 ml), dried and the solvent is then removed to yield the desired product ethyl [4-(4-nitrophenoxy)-3-nitrophenyl]carbamate.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13](OS(C(F)(F)F)(=O)=O)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:24])[CH:11]=2)[CH:6]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:45][C:46]1[CH:51]=[CH:50][C:49]([NH:52][S:53]([C:56]2[CH:61]=[CH:60][C:59](B(O)O)=[CH:58][CH:57]=2)(=[O:55])=[O:54])=[CH:48][CH:47]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[C:14]([CH3:13])=[C:15]([C:59]2[CH:58]=[CH:57][C:56]([S:53](=[O:54])(=[O:55])[NH:52][C:49]3[CH:50]=[CH:51][C:46]([F:45])=[CH:47][CH:48]=3)=[CH:61][CH:60]=2)[C:8]2[C:7](=[CH:12][CH:11]=[C:10]([F:24])[CH:9]=2)[CH:6]=1
Reactant: COC(=O)Cc1cc2ccc(F)cc2c(OS(=O)(=O)C(F)(F)F)c1C
Reactant: O=S(=O)(Nc1ccc(F)cc1)c1ccc(B(O)O)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: COCCOC
Product: COC(=O)Cc1cc2ccc(F)cc2c(-c2ccc(S(=O)(=O)Nc3ccc(F)cc3)cc2)c1C
Temperature: 25 °C
Yield: 12 %

Procedure:
A stirred solution of (6-fluoro-3-methyl-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester (0.10 g, 0.26 mmol) in dimethoxyethane (5 mL) was purged with argon for 5 minutes at room temperature. Triphenylphosphine (0.016 g, 0.06 mmol), palladium (II) acetate (0.007 g, 0.03 mmol), 4-(N-(4-fluorophenyl)sulfamoyl)phenylboronic acid (0.105 g, 0.35 mmol) and a 2 M aqueous solution of sodium carbonate (0.5 mL, 1.0 mmol) were added simultaneously to the reaction mixture at room temperature under argon. The reaction mixture was refluxed for 2 hours and then cooled to room temperature. Water was added and the mixture was extracted twice with ethyl acetate. The collected organic extracts were washed with water and then brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the crude product, which was finally purified using flash chromatography (Biotage, 5-10% ethyl acetate-hexane) to obtain {6-fluoro-4-[4-(4-fluoro-phenylsulfamoyl)-phenyl]-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (0.015 g, 12%) as a solid. MS calcd. for C26H20F2NO4S [(M−H)−] 480, obsd. 480.3.
Reaction SMILES: [N+:1]([C:4]1[C:5](O)=[N:6][CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1)([O-:3])=[O:2].P(Cl)(Cl)([Cl:17])=O>CN(C=O)C>[Cl:17][C:5]1[C:4]([N+:1]([O-:3])=[O:2])=[CH:9][C:8]([C:10]([F:13])([F:12])[F:11])=[CH:7][N:6]=1
Reactant: O=[N+]([O-])c1cc(C(F)(F)F)cnc1O
Reactant: O=P(Cl)(Cl)Cl
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1cc(C(F)(F)F)cnc1Cl
Temperature: 105 °C

Procedure:
To a mixture of 3-nitro-5-trifluoromethylpyridin-2-ol (3.2 g) and DMF (1 drop), phosphorous oxychloride (8.2 ml) was added at room temperature. The mixture was heated to 105° C., and stirred with heating for 2 days. The reaction mixture was cooled to room temperature, and then the reaction mixture was poured into ice, and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure to give 2.5 g of 2-chloro-3-nitro-5-trifluoromethylpyridine.
Reaction SMILES: [Cl:1][C:2]1[CH:34]=[CH:33][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:15](=[O:17])(=[O:16])[N:14]([CH3:18])[C:13]3[S:19][C:20]([C:22]#[C:23][CH2:24][O:25]C4CCCCO4)=[CH:21][C:12]=3[C:11]=2[OH:32])=[O:9])=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:1][C:2]1[CH:34]=[CH:33][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:15](=[O:16])(=[O:17])[N:14]([CH3:18])[C:13]3[S:19][C:20]([C:22]#[C:23][CH2:24][OH:25])=[CH:21][C:12]=3[C:11]=2[OH:32])=[O:9])=[CH:4][CH:3]=1
Reactant: CN1c2sc(C#CCOC3CCCCO3)cc2C(O)=C(C(=O)NCc2ccc(Cl)cc2)S1(=O)=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: O
Product: CN1c2sc(C#CCO)cc2C(O)=C(C(=O)NCc2ccc(Cl)cc2)S1(=O)=O
Temperature: 60 °C
Yield: 51.8 %

Procedure:
To a stirring suspension of N-(4-chlorobenzyl)-4-hydroxy-1-methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)prop-1-ynyl)-1H-thieno[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide (Preparation 36, 0.20 g) in MeOH (20 mL) at ambient temperature is added p-toluenesulfonic acid monohydrate (0.030 g). The resulting solution is heated at 60° C. for 45 min. The mixture is cooled to 0° C. and the resulting solid is filtered to afford 0.087 g (52%) of the title compound as a white solid. Physical characteristics; 1H NMR (DMSO-d6) δ3.44, 4.30, 4.48, 7.35, 7.37, 8.50; IR (diffuse reflectance) 3354, 1618, 1570, 1538, 1493, 1436, 1367, 1351, 1304, 1291, 1189, 1151, 1092, 1015, 815 cm−1; MS (EI) m/z 438 (M+). Anal. Found: C, 49.23; H, 3.49; N, 6.38.
Reaction SMILES: N[C@H](C(O)=O)C[SeH].[Li]CCCC.CN(C)CCN(C)C.[CH2:21]([N:23]([CH2:34][CH3:35])[C:24](=[O:33])[C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=1)[CH3:22].[CH3:36][S:37]C>C1COCC1>[CH2:34]([N:23]([CH2:21][CH3:22])[C:24](=[O:33])[C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][C:26]=1[S:37][CH3:36])[CH3:35]
Reactant: CCN(CC)C(=O)c1ccc(OC)cc1
Reactant: CSC
Agent: CN(C)CCN(C)C
Agent: N[C@@H](C[SeH])C(=O)O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCN(CC)C(=O)c1ccc(OC)cc1SC
Reaction time: 1 h

Procedure:
Sec-BuLi (1.4 M in cyclohexane, 11.34 mL, 15 mmol) was carefully added to a mixture of N,N,N′,N′-tetramethylethane-1,2-diamine (2.2 mL, 15 mmol) in anhydrous THF at −78° C. N,N-Diethyl-4-methoxybenzamide (3 g, 14.4 mmol) dissolved in 5 mL of anhydrous THF was added dropwise to the reaction mixture which was allowed to stir for 1 h. Dimethyl sulfide (2.5 mL, 28.8 mmol) was then added to the reaction. After stirring for 15 min, the cooling bath was removed and the mixture was stirred overnight. The reaction was diluted with ethyl acetate and washed with a solution of saturated sodium bicarbonate, water and then brine. The organic layer was then dried with sodium sulfate, concentrated and purified by flash chromatography using a gradient of 20 to 80% ethyl acetate in hexanes to obtain the product as a light yellow oil. Yield=2.51 g. MS (M+H)+ 254.
Reaction SMILES: C[N:2](C)[CH:3]=[C:4]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N+:13]([O-:15])=[O:14])[CH:5]=O.[NH2:17]N>C(O)C>[N+:13]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[C:4]1[CH:3]=[N:2][NH:17][CH:5]=1)([O-:15])=[O:14]
Reactant: CN(C)C=C(C=O)c1ccccc1[N+](=O)[O-]
Reactant: NN
Solvent: CCO
Product: O=[N+]([O-])c1ccccc1-c1cn[nH]c1

Procedure:
3-Dimethylamino-2-(2-nitrophenyl)propenal (Maybridge) in ethanol was treated with hydrazine via syringe and heated to reflux for 16 hours. Concentration in vacuo afforded crude 4-(2-nitrophenyl)pyrazole, which was reduced as in Example 64 and coupled with CMI to give the fumaric acid salt of N-(4,5-dihydro-1H-imidazol-2-ylmethyl)-2-(1H-pyrazol-4-yl)aniline.
Reaction SMILES: [Br:1][C:2]1[N:6]2[N:7]=[C:8](Cl)[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[CH3:12][NH:13][CH2:14][CH2:15][CH2:16][CH3:17].CCN(C(C)C)C(C)C>>[Br:1][C:2]1[N:6]2[N:7]=[C:8]([N:13]([CH2:14][CH2:15][CH2:16][CH3:17])[CH3:12])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1
Reactant: CCCCNC
Reactant: Clc1ccc2ncc(Br)n2n1
Solvent: CCN(C(C)C)C(C)C
Product: CCCCN(C)c1ccc2ncc(Br)n2n1
Yield: 138.2 %

Procedure:
A neat solution of 3-bromo-6-chloro-imidazo[1,2-b]pyridazine [13526-66-4] (522.9 mg, 2.3 mmol) in N-methyl butylamine [110-68-9] (3.0 mL, 24.3 mmol) and Hunig's base [7087-68-5] (0.6 mL, 3.5 mmol) was stirred under N2 blanket at 65° C. overnight then evaporated to provide 0.9 g of yellow solid, used in the next step without further purification. LRMS (ESI) m/z 283.1/285.1 [(M+H)]+, calc'd for C11H15BrN4: 283.17.
Reaction SMILES: [CH3:1][C:2]1([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3]1.[ClH:14]>CO.C(OCC)C.[Pt](=O)=O>[ClH:14].[CH:8]1([C:2]2([CH3:1])[CH2:7][CH2:6][CH2:5][NH:4][CH2:3]2)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1
Reactant: CC1(c2ccccc2)CCCNC1
Agent: O=[Pt]=O
Agent: Cl
Solvent: CO
Solvent: CCOCC
Product: CC1(C2CCCCC2)CCCNC1
Reaction time: 3 h
Yield: 66 %

Procedure:
To a solution of 3-methyl-3-phenylpiperidine (500 mg, 2.85 mmol) in methanol (8 ml) was added concentrated hydrochloric acid (1 ml) and platinum (IV) oxide (500 mg). The reaction mixture was hydrogenated at 50 psi for 3 h before filtering through Celite® and concentrating. The crude residue was dissolved in dichloromethane and washed with sodium carbonate and concentrated to give a crude semi solid. The crude product was dissolved in diethyl ether (15 ml) and methanol (5 ml) and hydrogen chloride (1M in diethyl ether, 30 ml) was added to afford a white solid which was filtered to give the pure product (0.41 g, 66%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:20]2[C@H:9]3[CH2:10][CH2:11][C@@:12]4([CH2:18][CH3:19])[C@H:16]([C@@H:8]3[CH2:7][CH:6]([CH3:23])[C:5]=2[CH:4]=1)[CH2:15][CH2:14][C:13]4=[O:17].[BH4-].[Na+].C(O)(=O)C>CO.[Cl-].[Na+].O>[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:20]2[C@H:9]3[CH2:10][CH2:11][C@@:12]4([CH2:18][CH3:19])[C@H:16]([C@@H:8]3[CH2:7][CH:6]([CH3:23])[C:5]=2[CH:4]=1)[CH2:15][CH2:14][C@@H:13]4[OH:17]
Reactant: CC[C@]12CC[C@@H]3c4ccc(OC)cc4C(C)C[C@H]3[C@@H]1CCC2=O
Agent: [BH4-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Solvent: O
Solvent: CC(=O)O
Product: CC[C@]12CC[C@@H]3c4ccc(OC)cc4C(C)C[C@H]3[C@@H]1CC[C@@H]2O
Yield: 96.5 %

Procedure:
Dissolve dl-3-methoxy-6-methyl- 13-ethylgona-1,3,5(10)-trien-17-one (7.0 g) in methanol (300 cc) and treat with sodium borohydride (3.0 g). After spontaneous reflux ceases, make acid with 50% aqueous acetic acid (20 cc). Pour into brine, extract with acid and isolate the dl-3-methoxy-17β-hydroxy-6-methyl-13-ethylgona-1,3,5(10)-triene (6.8 g), m.p. 158°-160°C, λmax. KBr 3.05, 6.45 μ.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[CH:9]([F:14])[N+:8]([O-])=[C:7]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:6]=2[CH:22]=1.P(OC)(OC)OC>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[CH:9]([F:14])[N:8]=[C:7]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:6]=2[CH:22]=1
Reactant: CN1C(=O)C(F)[N+]([O-])=C(c2ccccc2)c2cc(Cl)ccc21
Agent: COP(OC)OC
Solvent: ClCCl
Product: CN1C(=O)C(F)N=C(c2ccccc2)c2cc(Cl)ccc21
Yield: 98.5 %

Procedure:
A solution of 15.93 g (0.05 mole) of 7-chloro-3-fluoro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide and 20 ml (0.16 mole) of trimethyl phosphite in 250 ml of methylene chloride was allowed to remain at room temperature (about 25° C.) for 3 days, and then evaporated to dryness under reduced pressure. The residue was suspended in water, collected on a filter, washed thoroughly with water, and dried in air to give 14.91 g (98.5% yield) of crude 7-chloro-3-fluoro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one as a white powder. Analysis by high pressure liquid chromatography indicated the product was 98.9% pure. Recrystallization from ethanol gave colorless crystals: mp 145°-147°; 19F nmr (CDCl3) δ -161.7 ppm (d, J=57 Hz); 1H nmr (CDCl3) δ 3.43 ppm (s, 3H), 5.54 ppm (d, J=57 Hz, 1H) and 7.5 ppm (m, 8H).
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[CH:17]=[CH:16][NH:15][C:12]3=[N:13][CH:14]=2)O1.Cl[C:20]1[N:25]=[C:24]([NH:26][CH2:27][CH2:28][N:29]([CH3:31])[CH3:30])[CH:23]=[N:22][CH:21]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C(Cl)(Cl)Cl>[NH:15]1[C:12]2=[N:13][CH:14]=[C:9]([C:20]3[N:25]=[C:24]([NH:26][CH2:27][CH2:28][N:29]([CH3:31])[CH3:30])[CH:23]=[N:22][CH:21]=3)[CH:10]=[C:11]2[CH:17]=[CH:16]1
Reactant: CC1(C)OB(c2cnc3[nH]ccc3c2)OC1(C)C
Reactant: CN(C)CCNc1cncc(Cl)n1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: ClC(Cl)Cl
Solvent: C1COCCO1
Product: CN(C)CCNc1cncc(-c2cnc3[nH]ccc3c2)n1
Temperature: 100 °C

Procedure:
The starting material 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (124) (70 mg, 0.286 mmol, 1 eq) and N1-(6-chloropyrazin-2-yl)-N2,N2-dimethylethane-1,2-diamine (66) (457 mg, 0.286 mmol, 1 eq) in 1,4-dioxane (5 mL) was degassed and purged under argon atmosphere for 10 min. To this reaction mixture was charged Cs2CO3 (150 mg, 0.614 mmol, 1.5 eq) followed by addition of Pd(dpp)Cl2 (6.2 mg, 0.0086 mmol, 0.03 eq) and degassing and purging under argon for additional 10 min. The reaction mixture was heated at 100° C. for 12 h in a sealed tube. After completion of the reaction, the reaction mixture was diluted with CHCl3 and filtered through oCelite. The solvents were distilled off and the crude material was submitted for flash column purification in neutral alumina using 1% MeOH/CHCl3 to obtain pale yellow solid compound N1-(6-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazin-2-yl)-N2,N2-dimethylethane-1,2-diamine 127 in 10 mg quantity. The compound 127 was confirmed by 1HNMR and LCMS. 1H NMR (400 MHz, CDCl3) δ: 11.78 (s, 1H), 8.90 (d, J=1.82, 1H), 8.57 (s, 1H), 8.30 (s, 1H), 7.89 (s, 1H), 7.51 (m, J=151.58, 1H), 7.01 (m, J=201.21, 1H), 6.53 (m, J=191.45, 1H), 3.48 (m, J=5.85, 2H), 2.22 (s, 6-H); MS m/z 283 (M+H)+.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[CH:7]2)([O-:3])=[O:2].[I:13]C1CC(=O)NC1=O.O.C(OCC)C>CN(C)C=O>[I:13][C:7]1[C:6]2[C:10](=[CH:11][CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[NH:9][N:8]=1
Reactant: O=[N+]([O-])c1ccc2[nH]ncc2c1
Reactant: O=C1CC(I)C(=O)N1
Solvent: CCOCC
Solvent: O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccc2[nH]nc(I)c2c1

Procedure:
To a solution of 17.0 g of 5-nitroindazole in 100 ml dimethylformamide was added 24.6 g of N-.iodosuccinimide at room temperature, and the mixture was stirred at 80° C. for 7 hours. After standing to cool, to the reaction mixture were added 150 ml of water and 200 ml of diethyl ether, and the resulting crystals were collected by filtration. The crystals were sequentially washed with water, isopropanol and diethyl ether, to give 27.5 g of the title compound as colorless crystals.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH2:11][S:12]([NH2:15])(=[O:14])=[O:13])[CH:5]=[CH:6][C:7]=1[N+:8]([O-])=O.CCO.CC(O)=O>[Pd].C1COCC1>[NH2:8][C:7]1[CH:6]=[CH:5][C:4]([CH2:11][S:12]([NH2:15])(=[O:13])=[O:14])=[CH:3][C:2]=1[CH3:1]
Reactant: Cc1cc(CS(N)(=O)=O)ccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: Cc1cc(CS(N)(=O)=O)ccc1N
Reaction time: 3 h

Procedure:
The sulfonamide 14 (31.7 g, 138 mmol) was dissolved into boiling EtOH (600 ml) containing some AcOH (80 ml). To this solution was added 10% Pd/C (1.4 g) and this mixture was stirred under hydrogen (40 psi) for 3 h. THF (50 ml) was then added and this mixture heated to dissolve the precipitated product. This solution was filtered through celite and concentrated. The resulting solid was triturated with ether:hexane 1:1 (200 ml) to yield 27.28 g (99%) of pure 15.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:44]=[CH:45][CH:46]=1)[CH2:12][C@@H:13]1[C@@H:17](/[CH:18]=[CH:19]/[C@@H:20]([O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[C@H:16]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[CH2:15][C@@H:14]1[CH2:42][OH:43])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:54]1([CH3:64])[CH:59]=[CH:58][C:57]([S:60](Cl)(=[O:62])=[O:61])=[CH:56][CH:55]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH3:64][C:54]1[CH:59]=[CH:58][C:57]([S:60]([O:43][CH2:42][C@H:14]2[CH2:15][C@@H:16]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[C@H:17](/[CH:18]=[CH:19]/[C@@H:20]([O:26][Si:27]([C:30]([CH3:31])([CH3:32])[CH3:33])([CH3:28])[CH3:29])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[C@H:13]2[CH2:12][C:11]2[CH:44]=[CH:45][CH:46]=[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:10]=2)(=[O:62])=[O:61])=[CH:56][CH:55]=1
Reactant: CCCCC[C@@H](/C=C/[C@@H]1[C@@H](Cc2cccc(OCc3ccccc3)c2)[C@@H](CO)C[C@H]1O[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCC[C@@H](/C=C/[C@@H]1[C@@H](Cc2cccc(OCc3ccccc3)c2)[C@@H](COS(=O)(=O)c2ccc(C)cc2)C[C@H]1O[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C
Reaction time: 0.5 h
Yield: 85 %

Procedure:
A solution of ((1S,2S,3R,4R)-2-(3-(benzyloxy)benzyl)-4-(tert-butyldimethylsilyoxy)-3-((S,E)-3-(tert-butyl dimethylsilyoxy)oct-1-enyl)cyclopentyl)methanol (15 g, 0.023 mol) in dry CH2Cl2 (500 ml) was cooled to 0° C. under nitrogen and treated with triethylamine (9.6 ml, 0.068 mol), then with p-Toluenesulfonic chloride (8.77 g, 0.046 mol). The mixture was poured to saturated sodium bicarbonate aqueous and stirred for 30 minutes. The reaction mixture was phase separated and the aqueous layer was extracted with 500 ml ethyl acetate. The organic layers were combined and dried over anhydrous magnesium sulfate. The solid was filtered off. The solvent was evaporated off under vacuum. The crude product was purified by chromatography on silica gel using a mixture of hexane and ethyl acetate as a gradient eluent. Yield: 85%.