Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[N:28]=[CH:27][CH:26]=[CH:25][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[N+:22]([O-])=O)=[CH:10][CH:9]=1)=[O:5].[Cl-].[NH4+]>C(O)C.O1CCCC1.O.[Fe]>[NH2:1][C:2]1[N:28]=[CH:27][CH:26]=[CH:25][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[NH2:22])=[CH:10][CH:9]=1)=[O:5]
Reactant: Nc1ncccc1C(=O)NCc1ccc(OCc2ccccc2[N+](=O)[O-])cc1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: C1CCOC1
Solvent: O
Product: Nc1ccccc1COc1ccc(CNC(=O)c2cccnc2N)cc1
Reaction time: 8 h
Yield: 98 %

Procedure:
2-Amino-N-(4-(2-nitrobenzyloxy)-benzyl)-nicotinamide described in Example A-15 was dissolved in a mixture solvent of ethanol-tetrahydrofuran-water (3:1:1.5), iron powder (4 mg) and ammonium chloride (85 mg) were added thereto, and the solution was stirred overnight under reflux. In addition, iron powder (10 mg) and ammonium chloride (20 mg) were added, and the solution was stirred under reflux for 2 hours. The reaction solution was allowed to room temperature, filtered through Celite pad to remove insoluble matter, and the filtrate was concentrated in vacuo. The residue was purified by NH silica gel chromatography (hexane:ethyl acetate), and the title compound (9 mg, 98%) was obtained as a pale brown solid.
Reaction SMILES: Br[C:2]1[C:3](=[O:16])[N:4]([CH3:15])[C:5](=[O:14])[C:6]=1[N:7]1[CH2:12][CH2:11][C:10](=[O:13])[CH2:9][CH2:8]1.CC1(C)C(C)(C)OB([C:25]2[CH:42]=[CH:41][C:28]([O:29][CH2:30][C:31]3[CH:40]=[CH:39][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[N:32]=3)=[CH:27][CH:26]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:15][N:4]1[C:3](=[O:16])[C:2]([C:25]2[CH:26]=[CH:27][C:28]([O:29][CH2:30][C:31]3[CH:40]=[CH:39][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[N:32]=3)=[CH:41][CH:42]=2)=[C:6]([N:7]2[CH2:12][CH2:11][C:10](=[O:13])[CH2:9][CH2:8]2)[C:5]1=[O:14]
Reactant: CC1(C)OB(c2ccc(OCc3ccc4ccccc4n3)cc2)OC1(C)C
Reactant: CN1C(=O)C(Br)=C(N2CCC(=O)CC2)C1=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: CN1C(=O)C(c2ccc(OCc3ccc4ccccc4n3)cc2)=C(N2CCC(=O)CC2)C1=O
Reaction time: 0.5 h
Yield: 53.3 %

Procedure:
To a room temperature, stirred solution of 3-bromo-1-methyl-4-(4-oxopiperidin-1-yl)-1H-pyrrole-2,5-dione (100 mg, 0.34 mmol) in 1,4-dioxane (10 mL) was added 2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline (151 mg, 0.41 mol) under a N2 atmosphere. The reaction mixture was stirred for 30 minutes and then Na2CO3 (87 mg, 1.04 mmol), water (4 mL) and Pd(PPh3)4 (40 mg, 0.03 mmol) were added also under a N2 atmosphere. The resulting mixture was then refluxed for 16 h, diluted with water and extracted with ETOAc (2×20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude material was purified via silica gel column chromatography eluting with 60% EtOAc hexanes to afford 1-methyl-3-(4-oxopiperidin-1-yl)-4-(4-(quinolin-2-ylmethoxy)phenyl)-1H-pyrrole-2,5-dione (80 mg, 52%) as a solid. 1H NMR (500 MHz, d6-DMSO): δ 8.45 (d, J=7.4 Hz, 1 H), 8.12 (t, J=7.2 Hz, 2 H) 7.79 (t, J=7.2 Hz, 1 H), 7.72 (d, J=7.8 Hz, 1 H), 7.64 (t, J=7.6 Hz, 1 H), 7.18 (d, J=7.2 Hz, 2 H), 7.12 (d, J=7.2 Hz, 2 H), 5.38 (s, 2 H), 3.62-3.58 (m, 4 H), 2.96-2.85 (m, 4 H), 2.56 (s,4 H). MS: M+: m/z=441.6; M+H: m/z=442.7. HPLC: 97%, (Condition-B).
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][C:12]([F:15])([F:14])[F:13])[CH:8]=[CH:7][C:5]=2[N:6]=1.Cl[CH2:17][CH2:18][NH:19][C:20](=[O:22])[CH3:21].[I-].[Na+]>C(C(C)=O)C>[C:20]([NH:19][CH2:18][CH2:17][N:6]1[C:5]2[CH:7]=[CH:8][C:9]([O:11][C:12]([F:15])([F:13])[F:14])=[CH:10][C:4]=2[S:3][C:2]1=[NH:1])(=[O:22])[CH3:21]
Reactant: CC(=O)NCCCl
Reactant: Nc1nc2ccc(OC(F)(F)F)cc2s1
Agent: [I-]
Agent: [Na+]
Solvent: CCC(C)=O
Product: CC(=O)NCCn1c(=N)sc2cc(OC(F)(F)F)ccc21
Temperature: 20 °C
Yield: 21.1 %

Procedure:
2-Amino-6-trifluoromethoxybenzothiazole (9.4 g), N-(2-chloroethyl)acetamide (9.7 g) and sodium iodide (13.5 g) in methyl ethyl ketone (30 cc) are heated for 40 hours to boiling. After cooling to a temperature in the region of 20° C., the reaction medium is added to distilled water (200 cc), treated with 1N sodium hydroxide (40 cc) and then extracted with ethyl acetate (200 cc). After drying over magnesium sulphate and then concentration to dryness at 40° C. under reduced pressure (20 mm Hg; 2.7 kPa), the residue is purified by chromatography on a silica column with a mixture of ethyl acetate and methanol (90:10 by volume) as eluent. 3-(2-Acetamidoethyl)-2-imino-6-trifluoromethoxybenzothiazoline (2.7 g) is obtained, which product is converted to a hydrochloride subliming at about 180° C.
Reaction SMILES: [CH3:1][C:2]([CH3:6])=[CH:3][CH2:4]O.C[O:8][C:9](OC)([N:11]([CH3:13])[CH3:12])[CH3:10].CN(C)C(OC)=C>>[CH3:12][N:11]([CH3:13])[C:9](=[O:8])[CH2:10][C:2]([CH3:6])([CH3:1])[CH:3]=[CH2:4]
Reactant: COC(C)(OC)N(C)C
Reactant: CC(C)=CCO
Agent: C=C(OC)N(C)C
Product: C=CC(C)(C)CC(=O)N(C)C
Yield: 90 %

Procedure:
147 g of 3-methyl-but-2-en-1-ol are added to 180 g of a mixture of 72.5% by weight of N,N-dimethylacetamide-dimethylacetal and 27.5% by weight of 1-dimethylamino-1-methoxyethylene, and the batch is brought to 144° C. in the course of 80 minutes, whilst at the same time distilling the resulting methanol from the reaction mixture. The batch is then heated for 100 minutes at 144°-154° C. Distillation through a short column gives 205 g (90%) of 3,3-dimethyl-pent-4-enoic acid N,N-dimethylamide (of boiling point 70° C./2.6 mbar), corresponding to a yield of 90% of theory.
Reaction SMILES: [S:1](CCCCCCCC)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=S.[P:32](Cl)([Cl:35])([Cl:34])=[S:33]>>[CH2:2]([S:1][P:32]([Cl:35])([Cl:34])=[S:33])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCCCCCSCCCCCCCC
Reactant: S=P(Cl)(Cl)Cl
Agent: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Product: CCCCCCCCSP(=S)(Cl)Cl
Yield: 97.4 %

Procedure:
Following the procedure of the preceding Examples, 64.5 grams (0.25 mole) of (n-C8H17)2S, 18.5 grams (0.0416 mole) of P4S10 and 90 grams (0.53 mole) of PSCl3 were reacted at 190° C for 10 hours. The crude reaction mixture was distilled twice to provide 68 grams (49% yield) of n-C8H17SP(S)Cl2 having the following properties:
Reaction SMILES: Cl.[C:2]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:19])[CH2:10][C:11](=[O:18])[N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[C:40]([F:43])([F:42])[F:41]>CN(C=O)C.O>[C:2]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:19])[CH2:10][C:11](=[O:18])[N:12]2[CH2:13][CH2:14][N:15]([CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[C:40]([F:41])([F:42])[F:43])[CH2:16][CH2:17]2)=[CH:6][CH:7]=1
Reactant: FC(F)(F)c1ccccc1CBr
Reactant: O=C(CC(=O)N1CCNCC1)Nc1ccc(-c2ccccc2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C(CC(=O)N1CCN(Cc2ccccc2C(F)(F)F)CC1)Nc1ccc(-c2ccccc2)cc1
Temperature: 0 °C
Reaction time: 6 h
Yield: 88.3 %

Procedure:
A solution of N-Biphenyl-4-yl-3-oxo-3-piperazin-1-yl-propionamide hydrochloride (75 mg, 0.2 mmol) and K2CO3 (58 mg, 0.42 mmol) in DMF (2 mL) was stirred for 15 minutes at room temperature, then cooled to 0° C. and 1-bromomethyl-2-trifluoromethyl-benzene (50 mg, 0.21 mmol) was added. The resulting mixture was stirred at room temperature for 6 hours then diluted with water. The resulting precipitate was filtered to afford 85 mg (85%) of N-biphenyl-4-yl-3-oxo-3-[4-(2-trifluoromethyl-benzyl)-piperazin-1-yl]-propionamide. LCMS: 482.2 (M+1)+, 98.8%, 1H NMR: (CDCl3): δ 10.0 (s, 1H), 7.76 (d, 1H), 7.66 (d, 3H), 7.58 (m, 5H), 7.44 (t, 2H), 7.34 (m, 2H), 3.7 (m, 4H), 3.6 (t, 2H), 3.48 (s, 2H).
Reaction SMILES: [CH2:1]([N:3]([CH2:18][CH3:19])[CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13](=[O:17])[CH2:14][CH2:15][CH3:16])=[CH:9][CH:8]=1)[CH3:2].Cl.ClCCN1CCCC1>>[N:3]1([CH2:4][CH2:5][O:6][C:7]2[CH:8]=[CH:9][C:10]([C:13](=[O:17])[CH2:14][CH2:15][CH3:16])=[CH:11][CH:12]=2)[CH2:1][CH2:2][CH2:19][CH2:18]1
Reactant: CCCC(=O)c1ccc(OCCN(CC)CC)cc1
Agent: Cl
Agent: ClCCN1CCCC1
Product: CCCC(=O)c1ccc(OCCN2CCCC2)cc1
Yield: 87 %

Procedure:
The title compound was prepared by using a similar procedure as described for the preparation of 21 except that 1-(2-chloroethyl)pyrrolidine hydrochloride was used instead of 2-(diethylamino)ethyl chloride hydrochloride. This produced a crude oil, which was purified by flash silica gel column chromatography, eluting with 3:1 hexanes/ethyl acetate, to give 23 (455 mg, 87%) as a clear oil: MS (ES+) m/z 262.1 (M+H)+.
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C([Li])CCC.[C:15]1([P:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)Cl)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[CH2:29]([Sn:33](Cl)([CH2:38][CH2:39][CH2:40][CH3:41])[CH2:34][CH2:35][CH2:36][CH3:37])[CH2:30][CH2:31][CH3:32]>C(OCC)C.CCCCCC>[CH2:38]([Sn:33]([C:2]1[CH:3]([P:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:4]2[C:9]([CH:1]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2)([CH2:29][CH2:30][CH2:31][CH3:32])[CH2:34][CH2:35][CH2:36][CH3:37])[CH2:39][CH2:40][CH3:41]
Reactant: ClP(c1ccccc1)c1ccccc1
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Reactant: C1=Cc2ccccc2C1
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: CCCCCC
Product: CCCC[Sn](CCCC)(CCCC)C1=Cc2ccccc2C1P(c1ccccc1)c1ccccc1
Temperature: -20 °C
Yield: 92.5 %

Procedure:
10 g (0.086 mol) of indene were introduced into a round-bottomed flask, diluted with 200 ml of diethyl ether and cooled to -20° C. 36 ml of a 2.36 molar solution of butyl-lithium (0.085 mol) in n-hexane were added to this solution, the solution immediately assuming a yellow color. The cooling bath was removed and the reaction mixture was allowed to warm to room temperature and was stirred for a further hour. Thereafter, the reaction mixture was cooled again to 0° C. and 19 g (15.9 ml, 0.086 mol) of diphenylchlorophosphine were added, a precipitate being formed. The cooling bath was removed again and the solution was allowed to warm to room temperature while being subsequently stirred for a further hour. The solution was then cooled again to -20° C. and 36 ml (0.085 mol) of butyl-lithium in n-hexane were added dropwise. When the addition had ended, the cooling bath was removed again and the temperature rose to room temperature; the solution was subsequently stirred for a further 1.5 hours. The suspension was then cooled again to 0° C. and 28 g (0.086 mol) of tributyltin chloride were added dropwise. The resulting suspension was warmed to room temperature and stirred for a further 1.5 hours and subsequently filtered through a frit, and the solvent was removed in vacuo. 46.9 g of the compound 8 (92% of the theoretical yield) remained as a heavy yellow oil.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:24])[CH2:4][CH2:5][C:6]([CH3:23])=[CH:7][CH2:8][C:9]1[C:10]([OH:22])=[C:11]2[C:15](=[C:16]([CH3:20])[C:17]=1[O:18][CH3:19])[CH2:14][O:13][C:12]2=[O:21].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[CH3:56][Si:57]([CH3:62])([CH3:61])[CH2:58][CH2:59]O>C1COCC1>[CH3:1][O:2][C:3](=[O:24])[CH2:4][CH2:5][C:6]([CH3:23])=[CH:7][CH2:8][C:9]1[C:10]([O:22][CH2:59][CH2:58][Si:57]([CH3:62])([CH3:61])[CH3:56])=[C:11]2[C:15](=[C:16]([CH3:20])[C:17]=1[O:18][CH3:19])[CH2:14][O:13][C:12]2=[O:21]
Reactant: C[Si](C)(C)CCO
Reactant: COC(=O)CCC(C)=CCc1c(O)c2c(c(C)c1OC)COC2=O
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)CCC(C)=CCc1c(OC)c(C)c2c(c1OCC[Si](C)(C)C)C(=O)OC2
Temperature: 25 °C
Reaction time: 8 h
Yield: 86.5 %

Procedure:
To a solution of 6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic acid methyl ester (222 mg, 0.66 mmol), triphenylphosphine (260 mg, 0.996 mmol), and diethyl azodicarboxylate (173 mg, 0.996 mmol) in THF (3 mL) at 0° C. was added a solution of 2-trimethylsilylethanol (142 μL, 0.996 mmol) in THF (3 mL). The resulting yellow solution was allowed to warm to room temperature and stirred overnight. The reaction was concentrated to dryness and ether and hexanes were added. Triphenylphosphine oxide was removed by filtration and the filtrate was concentrated and purified by silica gel chromatography to provide 248 mg of the desired product as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 0.03 (s, 9H), 1.18-1.30 (m, 2H), 1.81 (s, 3H), 2.18 (s, 3H), 2.25-2.33 (m, 2H), 2.37-2.45 (m, 2H), 3.42 (d, 2H, J=7 Hz), 3.62 (s, 3H), 3.77 (s, 3H), 4.25-4.35 (m, 2H), 5.13 (s, 2H), 5.12-5.22 (m, 1H) ppm.
Reaction SMILES: [O:1]1[C:10]2[C:5](=[CH:6][C:7](B3OC(C)(C)C(C)(C)O3)=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.Cl[C:21]1[C:30]([N:31]([CH:33]([CH3:35])[CH3:34])[CH3:32])=[N:29][C:28]2[C:23](=[CH:24][CH:25]=[C:26]([C:36]([O:38][CH3:39])=[O:37])[CH:27]=2)[N:22]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(OCC)(=O)C>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:1]1[C:10]2[C:5](=[CH:6][C:7]([C:21]3[C:30]([N:31]([CH:33]([CH3:35])[CH3:34])[CH3:32])=[N:29][C:28]4[C:23](=[CH:24][CH:25]=[C:26]([C:36]([O:38][CH3:39])=[O:37])[CH:27]=4)[N:22]=3)=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1
Reactant: CC1(C)OB(c2ccc3c(c2)CCCO3)OC1(C)C
Reactant: COC(=O)c1ccc2nc(Cl)c(N(C)C(C)C)nc2c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1COCCO1
Product: COC(=O)c1ccc2nc(-c3ccc4c(c3)CCCO4)c(N(C)C(C)C)nc2c1
Temperature: 95 °C
Reaction time: 4 h
Yield: 54.4 %

Procedure:
To a solution of 2-(chroman-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (320 mg, 1.23 mmol) in dioxane (5.0 mL) was added methyl 2-chloro-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate (Scheme I, 180 mg, 0.61 mmol), K3PO4 (392 mg, 1.86 mmol), Pd(PPh3)4 (35.8 mg, 0.03 mmol) and water (3 drops) with stirring for 4 h at 95° C. maintained with an inert atmosphere of nitrogen in an oil bath. The reaction mixture was concentrated under vacuum to give the residue, which was applied onto a silica gel column with 2% ethyl acetate in petroleum ether to afford methyl 2-(chroman-6-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate as a light yellow solid (130 mg, 51%).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](/[CH:8]=[CH:9]/[N:10](C)[CH3:11])[C:5]2[C:13]([I:35])=[N:14][N:15]([C:16]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:4]=2[CH:3]=1.C(N)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.[C:44](O[BH-](OC(=O)C)OC(=O)C)(=[O:46])C.[Na+]>CCO.CC(O)=O.ClCCCl>[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][CH2:9][NH:10][CH2:11][C:40]2[CH:41]=[CH:42][C:37]([O:46][CH3:44])=[CH:38][CH:39]=2)[C:5]2[C:13]([I:35])=[N:14][N:15]([C:16]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:4]=2[CH:3]=1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Reactant: NCc1ccccc1
Reactant: CN(C)/C=C/c1nc(Cl)cc2c1c(I)nn2C(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Na+]
Solvent: ClCCCl
Solvent: CCO
Solvent: CC(=O)O
Product: COc1ccc(CNCCc2nc(Cl)cc3c2c(I)nn3C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
(E)-2-(6-chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridin-4-yl)-N,N-dimethylethenamine (2.2 g, 3.73 mmol) and benzylamine (1.02 g, 7.46 mmol) were stirred in a 3:1:1 solution of DCE:AcOH:EtOH (10 ml) at 85° C. for 3 hrs. Solvent removed by vacuum and residue taken in DCE (15 ml), added sodium triacetoxyborohydride (3.16 g, 14.9 mmol), acetic acid (0.9 g, 14.9 mmol) and stirred at room temperature for 6 hours. Reaction was partitioned between DCM and aqueous sodium bicarbonate and the organics was separated, washed with brine, dried with sodium sulfate and concentrated. Purification of the residue by flash column (0-10% MeOH-EtOAc) gave 2-(6-chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridin-4-yl)-N-(4-methoxybenzyl)ethanamine MS ESI calc'd. for C34H28ClIN4 [M+H]+ 685. found 685.
Reaction SMILES: Br[C:2]1[C:6]([Br:7])=[CH:5][Se:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[I-].C(NCC)C.[CH3:33][Si:34]([C:37]#[CH:38])([CH3:36])[CH3:35]>CC(OC)(C)C.[Cu].CN(C=O)C>[Br:7][C:6]1[C:2]([C:38]#[C:37][Si:34]([CH3:36])([CH3:35])[CH3:33])=[CH:3][Se:4][CH:5]=1
Reactant: Brc1c[se]cc1Br
Reactant: C#C[Si](C)(C)C
Agent: [Cu]
Agent: [I-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: COC(C)(C)C
Solvent: CCNCC
Solvent: CN(C)C=O
Product: C[Si](C)(C)C#Cc1c[se]cc1Br
Temperature: 90 °C
Yield: 79.5 %

Procedure:
To a pressure vessel purged with N2 was added 3,4-dibromo-selenophene (3.69 g, 12.77 mmol), DMF (10.0 mL), triphenylphosphine (0.669 g, 2.55 mmol), copper(l) iodide (0.161 g, 0.843 mmol), diethylamine (dried over KOH, 20.0 mL, 191.55 mmol), (trimethylsilyl)acetylene (0.910 mL, 6.39 mmol), and palladium dichloride-bis-triphenylphosphine (0.592 g, 0.843 mmol). The reaction vessel was sealed and the mixture heated to 90° C. for 1 h. Upon cooling to room temperature, the reaction mixture was diluted with MTBE (100.0 mL) and was washed with 0.1 M HCl (3×50.0 mL). The combined aqueous layers were extracted with MTBE (50.0 mL). The combined MTBE extracts were quenched with saturated sodium bicarbonate (50.0 mL), dried over magnesium sulfate, and concentrated to an oil. The crude oil was purified by column chromatography (silica gel, cyclohexane) to provide (4-Bromo-selenophen-3-ylethynyl)-trimethyl-silane (1.55 g, 5.08 mmol, 79.5 mol %): 500 MHz 1H NMR (CDCl3) δ 8.15 (d, J =2.9 Hz, 1 H), 7.58 (d, J =2.9 Hz, 1 H), 0.26 (S, 9h); 125 MHz 13C NMR (CDCl3) δ 135.4, 127.0, 126.4, 114.1, 99.8, 96.8, 0.2.
Reaction SMILES: [CH3:1][N:2]([CH3:32])[C:3]([C:5]1[N:26]([CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[C:8]2[N:9]=[C:10]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)=[CH:16][N:15]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4].[CH:33]1([C:36](Cl)=[O:37])CC1.CC[N:41](CC)CC>C(Cl)Cl>[CH3:1][N:2]([CH3:32])[C:3]([C:5]1[N:26]([CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[C:8]2[N:9]=[C:10]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH2:21][CH2:22][N:23]([CH2:33][C:36](=[O:37])[NH2:41])[CH2:24][CH2:25]4)=[CH:16][N:15]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4]
Reactant: CCN(CC)CC
Reactant: O=C(Cl)C1CC1
Reactant: CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n1C1CCCC1
Solvent: ClCCl
Product: CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCN(CC(N)=O)CC4)cn3)nc2n1C1CCCC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 71.6 %

Procedure:
To a solution of 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (100 mg, 0.230 mmol) and cyclopropanecarbonyl chloride (22 mL, 0.690 mmol) in 5 mL of CH2Cl2 is added a solution of Et3N (64 mL, 0.459 mmol) and stirred at rt for 18 h. The resulting mixture is concentrated and diluted with saturated NaHCO3 and extracted with ethyl acetate (3×100 mL). The combine organics are dried over Na2CO3 and preparative HPLC to give 2-[5-(4-carbamoylmethyl-piperazin-1-yl)-pyridin-2-ylamino]-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (81 mg, 68%). MS (ESI) m/z 503.3 (M+H)+
Reaction SMILES: [F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:3]=1[CH2:4][N:5]=[N+:6]=[N-:7].[OH2:13]>>[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:3]=1[CH2:4][N:5]1[CH:2]=[C:3]([C:4]([NH2:5])=[O:13])[N:7]=[N:6]1
Reactant: O
Reactant: [N-]=[N+]=NCc1c(F)cccc1F
Product: NC(=O)c1cn(Cc2c(F)cccc2F)nn1
Temperature: 82 °C
Reaction time: 24 h

Procedure:
A mixture of 2,6-difluorobenzylazide (9,22 g), 2-chloroacryonitrile (6,68 g) and water is stirred at about 82° C. for about 24 hours. 2-Chloroacrylnitrile is distilled off by raising the external temperature to about 113° C. excess. The mixture is cooled to about 40° C. and toluene (10 ml) is added. Within about 40 minutes at about 80° C. sodium hydroxide (5,5 ml—30%) is added the amide being crystallized. By raising the external temperature to 112° C., toluene is distilled off. The suspension is cooled to 20° C. and the product is isolated by filtration, washed with water (200 ml) and dried at about 60° C. in vacuo.
Reaction SMILES: [C:1]([C:9]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:10]=1[C:11]([OH:13])=[O:12])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:23])=O>>[Cl:23][CH:17]1[C:9]2[C:10](=[CH:14][C:15]([N+:18]([O-:20])=[O:19])=[CH:16][C:1]=2[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:11](=[O:12])[O:13]1
Reactant: O=C(O)c1cc([N+](=O)[O-])ccc1C(=O)c1ccccc1
Reactant: O=S(Cl)Cl
Product: O=C1OC(Cl)c2c1cc([N+](=O)[O-])cc2-c1ccccc1
Reaction time: 3 h

Procedure:
To 20 ml of thionyl chloride was added 25 g of 2-benzoyl-5-nitrobenzoic acid. The mixture was heated and stirred for 3 hours on the oil bath kept at a temperature of 60° C. Excess thionyl chloride was distilled away under reduced pressure, and 27.5 g of 3-chloro-4-phenyl-6-nitrophthalide was obtained as a brown oily substance. Separately, 4.48 g (0.04 mol.) of potassium tert-butoxide and 5.34 g (0.03 mol.) of 1-phenyl-5-mercaptotetrazole were added to 200 ml of dried dimethylformamide, and stirred for 20 minutes at room temperature. The resulting mixture was cooled to 5° C. and thereto, was added dropwise gradually the previously prepared solution containing 9.0 g (0.03 mol.) of 3-chloro-3-phenyl 6-nitrophthalide in 75 ml of dried dimethylformamide as the mixture was maintained at 5° C. After the conclusion of the dropwise addition, the reaction mixture was stirred for 30 minutes at 5° C. and further, for 2 hours at room temperature. Thereto, 200 ml of a saturated aqueous solution of ammonium chloride was added. The reaction mixture was extracted with ethyl acetate repeatedly. The extract was washed with water, and the resulting organic layer was dried over anhydrous sodium sulfate. Sodium sulfate was filtered off with suction, and the filtrate was concentrated to yield 9.2 g of crude crystals. These crude crystals were separated and purified by flash column chromatography (silica gel: 400 g, eluate: hexane-ethyl acetate (3:1 by volume) mixture). Thus, the intended compound, 3-(1-phenyltetrazole-5-ylthio)-3-phenyl-6-nitrophthalide (4), was obtained. It was recrystallized from an ethyl acetate-hexane mixture. Yield 5.5 g, Melting Point 176° to 179° C.