Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12](=[O:40])[O:13][CH2:14][C@@H:15]([N:26]([CH3:39])[C:27]([NH:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[C:32]=2[Cl:38])=[O:28])[CH2:16][CH2:17][C:18](=[O:25])[N:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[N:2]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[CH3:55][C:56]([CH3:58])=O>C(Cl)Cl.C(O)(=O)C>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12](=[O:40])[O:13][CH2:14][C@@H:15]([N:26]([CH3:39])[C:27]([NH:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[C:32]=2[Cl:38])=[O:28])[CH2:16][CH2:17][C:18]([N:19]2[CH2:20][CH2:21][N:22]([CH:56]([CH3:58])[CH3:55])[CH2:23][CH2:24]2)=[O:25])[N:2]=1
Reactant: CN(C(=O)NCc1cccc(F)c1Cl)[C@@H](CCC(=O)N1CCNCC1)COC(=O)Nc1cc2ccccc2cn1
Reactant: CC(C)=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Product: CC(C)N1CCN(C(=O)CC[C@@H](COC(=O)Nc2cc3ccccc3cn2)N(C)C(=O)NCc2cccc(F)c2Cl)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 82 %

Procedure:
To a solution of (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-oxo-5-(piperazin-1-yl)pentyl isoquinolin-3-ylcarbamate (610 mg, 1.07 mmol) in acetone (1 mL) and DCM (1 mL) was added acetic acid (4 drops, ˜0.2 mL). The reaction mixture was stirred at RT for 30 min. To this mixture was added solid NaBH(OAc)3 and the resulting mixture was stirred at RT for 1 h and concentrated. The residue was purified on RP-HPLC using a mixture of acetonitrle and water (0.1% HCOOH buffer). The fractions was collected, concentrated to dryness, and re-dissolved in EtOAc. The organic mixture was washed with Na2CO3, dried over Na2SO4, filtered, and concentrated to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(4-isopropylpiperazin-1-yl)-5-oxopentyl isoquinolin-3-ylcarbamate (540 mg, 82%) as white solid. LRMS (M+H+) m/z 613.3.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH:11]1[S:17][CH2:16][CH2:15][N:14]=[C:13]([C:18]2[C:19](=[O:26])[O:20][C:21]([CH3:25])=[CH:22][C:23]=2[OH:24])[CH2:12]1.C(N(C(C)C)CC)(C)C.[C:36](Cl)(Cl)=[O:37]>C(Cl)CCl.CN(C)C1C=CN=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH:11]1[CH:12]=[C:13]2[C:18]3[C:19](=[O:26])[O:20][C:21]([CH3:25])=[CH:22][C:23]=3[O:24][C:36](=[O:37])[N:14]2[CH2:15][CH2:16][S:17]1
Reactant: COc1ccc(C2CC(c3c(O)cc(C)oc3=O)=NCCS2)c(OC)c1
Reactant: O=C(Cl)Cl
Agent: CN(C)c1ccncc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCCl
Product: COc1ccc(C2C=C3c4c(cc(C)oc4=O)OC(=O)N3CCS2)c(OC)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
3-[7-(2,4-Dimethoxyphenyl)-2,3,6,7-tetrahydro-[1,4]thiazepin-5-yl]-4-hydroxy-6-methyl-pyran-2-one (63 mg, 0.168 mmol), prepared as in Reference 5, was dissolved in ethylene dichloride (2 mL) and then 4-(dimethylamino)pyridine (0.020 g), di-iso-propylethylamine (0.5 mL) and phosgene (0.4 ml, 2 M in toluene) were added at room temperature. The reaction was monitored by analytical HPLC. After stirring at room temperature for 30 minutes, the solvent was removed in vacuo. Product was purified by HPLC (RPC18 column, 2-70% acetonitrile/water containing 0.1% HCl) to provide 10-(2,4-dimethoxy-phenyl)-3-methyl-7,8-dihydro-10H-2,5-dioxa-9-thia-6a-aza-cyclohepta[a]naphthalene-1,6-dione (20 mg) as an off-white powder. LCMS: M+ 401.0.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=O.C([O:15][C:16](=[O:22])[C@H:17]([CH:19]([CH3:21])[CH3:20])[NH2:18])C.C([O-])([O-])=O.[K+:27].[K+]>CO>[K+:27].[F:1][C:2]([F:12])([F:11])[C:3](=[N:18][C@H:17]([C:16]([O-:22])=[O:15])[CH:19]([CH3:21])[CH3:20])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: O=C(c1ccccc1)C(F)(F)F
Reactant: CCOC(=O)[C@@H](N)C(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: CC(C)[C@H](N=C(c1ccccc1)C(F)(F)F)C(=O)[O-]
Temperature: 50 °C

Procedure:
2,2,2-Trifluoroacetophenone (4.24 g, 24.3 mmol) was added to a mixture of L-valine ethyl ester (3.21 g, 22.1 mmol) and K2CO3 (2.90 g, 20.9 mmol) in MeOH (50 mL). The mixture was warmed to 50° C. for 18 h. The mixture was cooled to 20–25° C., filtered and concentrated. The residue was suspended in TBME (100 ml) and filtered to give the title compound as a white solid.
Reaction SMILES: [H-].[Li+].[Cl:3][C:4]1[CH:5]=[C:6]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH:7]=[C:8]([Cl:10])[CH:9]=1.[CH3:17][C:18]1[CH:19]=[C:20]([C:29](=[O:31])[CH3:30])[S:21][C:22]=1[C:23]#[C:24][Si:25]([CH3:28])([CH3:27])[CH3:26].CC(OC)(C)C>C1COCC1>[Cl:3][C:4]1[CH:5]=[C:6]([C:11]([OH:16])([C:12]([F:13])([F:14])[F:15])[CH2:30][C:29]([C:20]2[S:21][C:22]([C:23]#[C:24][Si:25]([CH3:28])([CH3:26])[CH3:27])=[C:18]([CH3:17])[CH:19]=2)=[O:31])[CH:7]=[C:8]([Cl:10])[CH:9]=1
Reactant: CC(=O)c1cc(C)c(C#C[Si](C)(C)C)s1
Reactant: O=C(c1cc(Cl)cc(Cl)c1)C(F)(F)F
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: COC(C)(C)C
Product: Cc1cc(C(=O)CC(O)(c2cc(Cl)cc(Cl)c2)C(F)(F)F)sc1C#C[Si](C)(C)C
Reaction time: 0.5 h
Yield: 56.1 %

Procedure:
LiH (1.72 g) is added to a solution of 3′,5′-dichloro-2,2,2-trifluoroacetophenone (26.6 g) and 1-(4-methyl-5-trimethylsilanylethynyl-thiophen-2-yl)-ethanone (18.2 g) in THF (100 ml). After 30 minutes at 60° C. MTBE is added (200 ml) and the reaction mixture is poured onto water (30 ml) at 5° C. The organic phase is extracted with water and a saturated aqueous solution of NaCl, dried over Na2SO4 and concentrated in vacuo to yield 3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-3-hydroxy-1-(4-methyl-5-trimethylsilanylethynyl-thiophen-2-yl)-butan-1-one (20.7 g). The crude product is used without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH3:10].[Te:11](Cl)([Cl:14])([Cl:13])[Cl:12]>C(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([Te:11]([Cl:14])([Cl:13])[Cl:12])[CH:6]=[CH:5][C:4]=1[O:9][CH3:10]
Reactant: COc1ccccc1OC
Reactant: Cl[Te](Cl)(Cl)Cl
Solvent: ClC(Cl)Cl
Product: COc1ccc([Te](Cl)(Cl)Cl)cc1OC
Reaction time: 0.5 h

Procedure:
1,2-Dimethoxybenzene (veratrole, 13.8 g=0.1 mole) and tellurium tetrachloride (26.9 g=0.1 mole) were heated in chloroform (120 ml) for 2 hours under reflux and with stirring. After 30 minutes yellow crystals started to precipitate. The product (25.2 g, 67.9% of theory) was collected by filtration and dried in a vacuum oven, m.p. 162°-163° C. (dec. with gas evolution). The mass spectra were in agreement with that of the structural formula.
Reaction SMILES: FC(F)(F)C(O)=O.B1([O-])OO1.[OH2:12].[OH2:13].O.O.[Na+].[NH2:17][C:18]1[C:27]([F:28])=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[C:20]([F:29])[C:19]=1[CH3:30]>C(O)(=O)C>[F:29][C:20]1[C:19]([CH3:30])=[C:18]([N+:17]([O-:13])=[O:12])[C:27]([F:28])=[CH:26][C:21]=1[C:22]([O:24][CH3:25])=[O:23]
Reactant: O
Reactant: COC(=O)c1cc(F)c(N)c(C)c1F
Agent: [Na+]
Agent: [O-]B1OO1
Solvent: CC(=O)O
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)c1cc(F)c([N+](=O)[O-])c(C)c1F
Temperature: 60 °C
Reaction time: 24 h
Yield: 70.8 %

Procedure:
Trifluoroacetic acid (50 ml), acetic acid (50 ml) and sodium perborate tetrahydrate (26.6 g) were added to methyl 4-amino-2,5-difluoro-3-methylbenzoate (7.5 g), and the mixture was stirred at 60° C. for 24 hours. Impurities in the reaction mixture was removed by filtration, chloroform was added to the resultant filtrate, and the resultant mixture was washed with water. After an organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain the title compound (6.1 g) as a reddish brown oil.
Reaction SMILES: [H-].[Na+].[C:3]1([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br.[NH2:17][C:18]1[N:27]=[C:26]([NH2:28])[C:25]2[C:20](=[N:21][CH:22]=[C:23]([CH2:29]Br)[N:24]=2)[N:19]=1.CO>C1COCC1>[NH2:17][C:18]1[N:27]=[C:26]([NH2:28])[C:25]2[C:20](=[N:21][CH:22]=[C:23]([CH2:29][N:9]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:24]=2)[N:19]=1
Reactant: c1ccc(Nc2ccccc2)cc1
Reactant: Nc1nc(N)c2nc(CBr)cnc2n1
Agent: Br
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: Nc1nc(N)c2nc(CN(c3ccccc3)c3ccccc3)cnc2n1
Reaction time: 0.17 h

Procedure:
Powdered NaH (50 mg, 2.1 mmol) is added to a stirred solution of diphenylamine (1.3 g, 0.77 mmol) in dry THF (10 mL) at 0° C. under N2. After 10 min, 2,4-diamino-6-bromomethylpteridine hydrobromide (100 mg, 0.3 mmol) is added and the reaction mixture is allowed to come to room temperature and left to stir for 2 days. The excess NaH is decomposed with MeOH (1 mL) and the mixture is concentrated to dryness by rotary evaporation. Flash chromatography on silica gel with 95:5 CHCl3-MeOH as the eluent affords the product, N-(2,4-diaminopteridin-6-yl)methyl-N,N-diphenylamine, as a bright-yellow powder (56 mg, 54% yield); mp >250° C. dec.; MS (FAB) m/z (M+1)=344; IR (KBr) v 3450, 3340, 3170, 1630, 1590, 1550, 1490, 1450, 1360, 1220 cm−1; 1H NMR(d6-DMSO) δ 5.10 (s, 2H, CH2), 6.70 (m, 10H, aromatic), 8.60 (s, 1H, C7-H. Anal. Calcd for C19H17N7.0.8H2O: C, 63.73; H, 5.23; N, 27.40. Found: C, 64.15; H, 4.85; N, 27.07.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:30]([O-])=O)[C:18]([NH:19][CH:20]4[CH2:25][CH2:24][CH2:23][CH:22]([O:26][C:27](=[O:29])[CH3:28])[CH2:21]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl-].[NH4+].O>C(O)C.[Fe]>[NH2:30][C:17]1[C:18]([NH:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH:22]([O:26][C:27](=[O:29])[CH3:28])[CH2:21]2)=[C:13]2[CH:12]=[CH:11][N:10]([S:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)(=[O:9])=[O:8])[C:14]2=[N:15][CH:16]=1
Reactant: CC(=O)OC1CCCC(Nc2c([N+](=O)[O-])cnc3c2ccn3S(=O)(=O)c2ccccc2)C1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: CC(=O)OC1CCCC(Nc2c(N)cnc3c2ccn3S(=O)(=O)c2ccccc2)C1
Temperature: 80 °C

Procedure:
A mixture of Acetic acid 3-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclohexyl ester (trans racemic) (9.72 g, 21.2 mmol), ammonium chloride (2.26 g, 42.40 mmol), iron powder (5.92 g, 106 mmol), and water (15.0 mL) in ethanol (150 ml) was heated at 80° C. overnight. The reaction was followed by LC/MS to completion. On completion, the reaction mixture was used as is for the next step without any workup. LCMS (Method M, ESI): RT=1.90 min, m+H=428.9.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3](=[O:10])[C:2]1=[N:11][OH:12].[H-].[Na+].Br[CH2:16][CH2:17][OH:18].O>CN(C)C=O>[OH:18][CH2:17][CH2:16][O:12][N:11]=[C:2]1[C:3](=[O:10])[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[O:1]1
Reactant: OCCBr
Reactant: O=C1C(=NO)Oc2ccccc21
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=C1C(=NOCCO)Oc2ccccc21
Temperature: 0 °C
Reaction time: 1 h
Yield: 76.6 %

Procedure:
11.8 g (0.0725 mol) of benzofuran-2,3-dione 2-oxime (XI-1) (Stoermer, Kahlert, B. 35, 1644) are dissolved in 75 ml of dimethylformamide. With cooling, 3 g (0.075 mol) of 60% strength sodium hydride (mineral oil suspension) are added a little at a time and stirring is continued at a temperature of 25° C. for about one hour until the formation of gas has ceased. The mixture is then cooled to 0° C., and at this temperature 9.3 g (0.0744 mol) of 2-bromoethanol are added dropwise and stirring is continued at 25° C. for a further 24 hours. The reaction mixture is poured into water and the resulting mixture is extracted with ethyl acetate, the organic phase is dried over sodium sulphate and the solvent is distilled off under reduced pressure. The residue is recrystallized from a mixture of 150 ml of toluene and 100 ml of cyclohexane. 11.5 g (64% of theory) of benzofuran-2,3-dione 2-[O-(2-hydroxy-ethyl)-oxime] (VII-1) are obtained (content according to HPLC analysis: 83.5%). A sample recrystallized from toluenes has a melting point of 110-111° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:17]2[C:22](=[O:23])[NH:21][C:20](=[O:24])[CH:19]=[N:18]2)[CH:5]=[CH:6][C:7]=1[CH:8](Cl)[C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=1.[Cu](C#N)[C:26]#[N:27]>ClC(Cl)Cl.CO>[Cl:1][C:2]1[CH:3]=[C:4]([N:17]2[C:22](=[O:23])[NH:21][C:20](=[O:24])[CH:19]=[N:18]2)[CH:5]=[CH:6][C:7]=1[CH:8]([C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=1)[C:26]#[N:27]
Reactant: N#C[Cu]C#N
Reactant: O=c1cnn(-c2ccc(C(Cl)c3ccc(Cl)cc3)c(Cl)c2)c(=O)[nH]1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: N#CC(c1ccc(Cl)cc1)c1ccc(-n2ncc(=O)[nH]c2=O)cc1Cl
Temperature: 180 °C
Yield: 11.2 %

Procedure:
A mixture of 12 parts of 2-[3-chloro-4-[chloro(4-chlorophenyl)methyl]phenyl]-1,2,4-triazine-3,5(2H,4H)-dione and 5.4 parts of copper cyanide was stirred and heated first for 3 hours at 130° C. and for 3 hours at 180° C. After cooling, the precipitated product was dissolved in a mixture of trichloromethane and methanol (90:10 by volume). The inorganic precipitate was filtered off and the filtrate was evaporated in vacuo. The residue was purified four times by column chromatography over silica gel using first a mixture of trichloromethane and acetonitrile (90:10 by volume), second a mixture of tetrachloromethane and methanol (93:7 by volume) and then twice a mixture of tetrachloromethane and acetonitrile (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was further purified by column chromatography (HPLC) over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The pure fractions were collected and the eluent was evaporated in vacuo. The residue was dried, yielding 1.3 parts (11.2%) of 2-chloro-α-(4-chlorophenyl)-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)benzeneacetonitrile; mp. 196.8° C. (compound 22).
Reaction SMILES: [C:1]([C:9]1[CH:13]=[CH:12][S:11][C:10]=1[C:14]([OH:16])=O)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:17][NH:18][NH2:19]>C(O)C>[CH3:17][N:18]1[C:14](=[O:16])[C:10]2[S:11][CH:12]=[CH:13][C:9]=2[C:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[N:19]1
Reactant: O=C(c1ccccc1)c1ccsc1C(=O)O
Reactant: CNN
Solvent: CCO
Product: Cn1nc(-c2ccccc2)c2ccsc2c1=O

Procedure:
A solution of 31.2 g (0.134 mol) of 3-benzoyl-2-thiophenecarboxylic acid in 400 mL of ethanol was treated with 9.3 (0.2 mol) of methylhydrazine at room temperature for 18 hours, refluxed 3 hours, cooled and 30.7 g of the product filtered off, mp 174-175.
Reaction SMILES: [C:1](=[S:20])([S-:19])[S:2][CH2:3][CH2:4][NH:5][C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=1)=[O:7].[K+].C(O[C@@H:26]1[NH:29][C:28](=[O:30])[C@H:27]1[O:31][CH3:32])(=O)C.O1CCOCC1>O.P([O-])([O-])([O-])=O>[N+:16]([C:13]1[CH:14]=[CH:15][C:10]([CH2:9][O:8][C:6]([NH:5][CH2:4][CH2:3][S:2][C:1]([S:19][C@H:26]2[NH:29][C:28](=[O:30])[C@@H:27]2[O:31][CH3:32])=[S:20])=[O:7])=[CH:11][CH:12]=1)([O-:18])=[O:17]
Reactant: CO[C@@H]1C(=O)N[C@H]1OC(C)=O
Reactant: O=C(NCCSC(=S)[S-])OCc1ccc([N+](=O)[O-])cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: CO[C@H]1C(=O)N[C@@H]1SC(=S)SCCNC(=O)OCc1ccc([N+](=O)[O-])cc1
Reaction time: 0.5 h

Procedure:
A solution of 422 mg of potassium 2-p-nitrobenzyloxycarbonylaminoethyl trithiocarbonate in 1 ml of water is added dropwise at room temperature under, a nitrogen atmosphere to a solution of 159 mg (1 mmole) of (3S,4S)-4-acetoxy-3-methoxy-2-oxoazetidine in 3 ml of phosphate buffer of a pH of 7 and 0.2 ml of dioxan, and the mixture is stirred at the same temperature for 30 minutes. The reaction mixture is exhaustively extracted with methylene chloride. The combined organic phases are dried over sodium sulphate and concentrated by evaporation in vacuo. The residue is chromatographed over silica gel and yields the title compound with the following
Reaction SMILES: [CH:1]1([N:7]2[CH2:11][CH:10]([CH2:12]O)[C:9]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:8]2=[O:26])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.S(Cl)([Cl:29])=O.N1C=CC=CC=1>C(Cl)(Cl)Cl>[Cl:29][CH2:12][CH:10]1[CH2:11][N:7]([CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[C:8](=[O:26])[C:9]1([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=S(Cl)Cl
Reactant: O=C1N(C2CCCCC2)CC(CO)C1(c1ccccc1)c1ccccc1
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: O=C1N(C2CCCCC2)CC(CCl)C1(c1ccccc1)c1ccccc1
Yield: 55 %

Procedure:
To 60.0 g. (0.17 mole) of 1-cyclohexyl-4-hydroxymethyl-3,3-diphenyl-2-pyrrolidinone in 400 ml. of chloroform was added 48.0 g. (0.40 mole) of thionylchloride with stirring. To this solution was added dropwise with ice bath cooling 40 g. (0.52 mole) of dry pyridine and the solution was refluxed for two hours. After concentrating in vacuo the residue was dissolved in chloroform and washed successively with dilute hydrochloric acid solution and dilute sodium hydroxide solution. The chloroform solution was dried (sodium sulfate), filtered, and concentrated in vacuo. The residue was recrystallized from isopropyl ether and after drying weighed 34.5 g. (55% yield) and melted at 124°-126° C.
Reaction SMILES: [CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].[Li]CCCC.C([O:15][C:16](=O)[CH2:17][CH2:18][C:19]1[CH:28]=[CH:27][C:26]2[CH2:25][CH2:24][CH2:23][NH:22][C:21]=2[N:20]=1)C>C1COCC1>[CH3:4][O:3][P:2]([CH2:1][C:16](=[O:15])[CH2:17][CH2:18][C:19]1[CH:28]=[CH:27][C:26]2[CH2:25][CH2:24][CH2:23][NH:22][C:21]=2[N:20]=1)(=[O:7])[O:5][CH3:6]
Reactant: CCOC(=O)CCc1ccc2c(n1)NCCC2
Reactant: COP(C)(=O)OC
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COP(=O)(CC(=O)CCc1ccc2c(n1)NCCC2)OC
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a stirred solution of dimethyl methylphosphonate (1.9 mL, 17.08 mmol) in THF (20 mL) at −78° C. was added nBuLi (10.94 mL, 17.5 mmol). After 30 minutes, 2-9 (1 g , 4.27 mmol) in THF (5 mL) was added. After 1 hour, the reaction was quenched with saturated NH4Cl (10 mL) and warmed to ambient temperature. The mixture was diluted with ethyl acetate, washed with sat. NaHCO3, brine, and dried over MgSO4. Following evaporative removal of the solvent, the residue was chromatographed (silica gel, 70/25/5 CHCl3/EtOAc/MeOH) to give 2-10 as a yellow oil.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[C:12]2[N:13]([N:17]=[C:18]([NH2:20])[N:19]=2)[CH:14]=[CH:15][CH:16]=1)(=[O:4])=[O:3].Br[C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]2)=[CH:24][CH:23]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[C:12]2[N:13]([N:17]=[C:18]([NH:20][C:22]3[CH:23]=[CH:24][C:25]([N:28]4[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]4)=[CH:26][CH:27]=3)[N:19]=2)[CH:14]=[CH:15][CH:16]=1)(=[O:3])=[O:4]
Reactant: CS(=O)(=O)c1ccccc1-c1cccn2nc(N)nc12
Reactant: CN1CCN(c2ccc(Br)cc2)CC1
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: CN1CCN(c2ccc(Nc3nc4c(-c5ccccc5S(C)(=O)=O)cccn4n3)cc2)CC1

Procedure:
[8-(2-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine was prepared from 8-(2-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (75.0 mg, 0.260 mmol) and 1-(4-bromo-phenyl)-4-methyl-piperazine (80.0 mg, 0.314 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (30.0 mg, 0.0549 mmol) as the ligand in a manner analogous to Step 2d. The title compound was isolated as a yellow foam (0.067 g, 56%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.47 (d, J=6.6 Hz, 1H), 8.24 (d, J=7.7 Hz, 1H), 7.74 (t, J=7.0 Hz, 1H), 7.67 (t, J=7.4 Hz, 1H), 7.47 (t, J=8.0 Hz, 2H), 7.41 (d, J=7.8 Hz, 2H), 6.99-6.91 (m, 3H), 6.57 (s, 1H), 3.17-3.12 (m, 4H), 2.97 (s, 3H), 2.61-2.56 (m, 4H), 2.36 (s, 3H). MS=463 (MH)+.