Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:12]=[CH:11][C:10]2[NH:9][C:8]3[CH2:13][CH2:14][N:15]([CH3:17])[CH2:16][C:7]=3[C:6]=2[CH:5]=1.Br[CH2:19][CH2:20][CH2:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]([F:31])([F:30])[F:29])=[N:26][CH:27]=1.O>CN(C=O)C>[Cl:3][C:4]1[CH:12]=[CH:11][C:10]2[N:9]([CH2:19][CH2:20][CH2:21][C:22]3[CH:27]=[N:26][C:25]([C:28]([F:31])([F:29])[F:30])=[CH:24][CH:23]=3)[C:8]3[CH2:13][CH2:14][N:15]([CH3:17])[CH2:16][C:7]=3[C:6]=2[CH:5]=1
Reactant: FC(F)(F)c1ccc(CCCBr)cn1
Reactant: CN1CCc2[nH]c3ccc(Cl)cc3c2C1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CN1CCc2c(c3cc(Cl)ccc3n2CCCc2ccc(C(F)(F)F)nc2)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 32.7 %

Procedure:
To a suspension of sodium hydride (0.014 g, 0.00054 mol) in dry DMF (3 mL), 8-Chloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.1 g, 0.00045 mol) was added at ice cold temp and stirred for 2 h at room temperature. Reaction mix was cooled to −20° c. and 5-(3-Bromo-propyl)-2-trifluoromethyl-pyridine (0.183 g, 0.00068 mol) was added, stirred for 1 h at 15° c., Reaction was monitor by TLC. After completion (TLC), reaction mix was cooled to 0° C. and water (10 mL) was added, extracted with ethyl acetate (3×100 mL). The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure using rotary evaporator. The crude was purified through column chromatography (4% Methanol:DCM in silica 100-200 mesh, Diameter of column—2.5 cm, Height of silica—approx. 5 inch) to provide desired compound as brown oil (0.06 g, 32% yield). 8-Chloro-2-methyl-5-[3-(6-trifluoromethyl-pyridin-3-yl)-propyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.06 g, 0.000147 mol) was dissolved in THF (1.0 mL), A solution of oxalic acid dihydrate (0.016 g, 0.000126 mol) in THF (1.0 mL) was added and stirred for 30 min at RT. The precipitate was filtered and dried to give oxalate salt as off white solid (0.050 g, 68% yield).
Reaction SMILES: C([Cl:4])(=O)C.C(OC([N:12]1[CH2:17][CH2:16][CH:15]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([NH:25][C:26](=[O:35])[C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=3[Cl:34])[CH:20]=2)[CH2:14][CH2:13]1)=O)(C)(C)C>CO>[ClH:4].[ClH:34].[Cl:34][C:28]1[CH:29]=[C:30]([F:33])[CH:31]=[CH:32][C:27]=1[C:26]([NH:25][C:21]1[CH:22]=[CH:23][CH:24]=[C:19]([NH:18][CH:15]2[CH2:14][CH2:13][NH:12][CH2:17][CH2:16]2)[CH:20]=1)=[O:35]
Reactant: CC(=O)Cl
Reactant: CC(C)(C)OC(=O)N1CCC(Nc2cccc(NC(=O)c3ccc(F)cc3Cl)c2)CC1
Solvent: CO
Product: Cl
Product: O=C(Nc1cccc(NC2CCNCC2)c1)c1ccc(F)cc1Cl
Reaction time: 1 h

Procedure:
Combine acetyl chloride (5 mL) and dried methanol (10 mL) at 0° C. under a nitrogen atmosphere. Stir for 1 hr. at 0° C. Add a solution of 4-(3-(2-Chloro-4-fluorobenzoylamino)phenylamino)piperidine-1-carboxylic acid t-butyl ester (Preparation 56, 72 mg, 0.161 mmol) in methanol (2 mL). Stir overnight. Concentrate under reduced pressure. Triturate with diethyl ether (1 mL) to provide a pale yellow foam of the title compound: mp 255–7° C.; mass spectrum (ion spray): m/z=348.2 (M+1). Analysis calc'd for C18H21Cl3FN3O.1.0H2O: C, 49.28; H, 5.28; N, 9.58. Found: C, 49.15; H, 4.96; N, 9.56.
Reaction SMILES: [O-]CC.[Na+].[C:5]([O:13][CH2:14][CH3:15])(=[O:12])[CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8].Br[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.Cl>C(O)C>[CH2:24]([O:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[C:5]([O:13][CH2:14][CH3:15])=[O:12])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: CCOC(=O)CC(=O)OCC
Reactant: BrCCCCCCOCc1ccccc1
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)C(CCCCCCOCc1ccccc1)C(=O)OCC
Reaction time: 2 h
Yield: 98.9 %

Procedure:
First, 2.7 g of sodium ethoxide and 100 ml of dry ethanol were placed in a 200 ml flask. Then, 20 ml of an ethanol solution containing 7 g of diethyl malonate was added dropwise to the reaction mixture at 60° C., and the resultant reaction mixture was stirred for 2 hours. Then, 20 ml of an ethanol solution containing 9 g of 1-bromo-6-benzyloxyhexane was added dropwise to the reaction mixture, and the resultant reaction mixture was stirred under reflux for 3 hours. The reaction mixture was poured into diluted hydrochloric acid, and an organic layer was extracted with ether. The ether layer was washed with water and dried over anhydrous sodium sulfate. Thereafter, the solvent was distilled away. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=9/1) to obtain 11.5 g of diethyl 2-(6-benzyloxyhexyl)malonate (Y: 98%). The compound thus obtained had a purity of 86.3% by GC.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]=[C:11]=[O:12])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[ClH:13].Cl.[Cl:15][C:16]1[CH:32]=[CH:31][C:19]([CH2:20][N:21]2[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][CH2:29][SH:30])[CH2:23][CH2:22]2)=[CH:18][CH:17]=1.C(N(CC)CC)C>C(Cl)Cl>[OH2:3].[ClH:15].[ClH:13].[C:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[SH:30][CH2:29][CH2:28][CH2:27][N:24]2[CH2:25][CH2:26][N:21]([CH2:20][C:19]3[CH:18]=[CH:17][C:16]([Cl:15])=[CH:32][CH:31]=3)[CH2:22][CH2:23]2)[OH:12])=[CH:6][CH:5]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)c1ccc(N=C=O)cc1
Reactant: SCCCN1CCN(Cc2ccc(Cl)cc2)CC1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)c1ccc(NC(O)=[SH]CCCN2CCN(Cc3ccc(Cl)cc3)CC2)cc1
Product: O
Yield: 55.1 %

Procedure:
The procedure described in Example 2 was followed, using 1.0 g of 4-acetylphenyl isocyanate, 2.0 g of 3-[4-(4-chlorobenzyl)piperazin-1-yl]propanethiol dihydrochloride, 0.7 g of triethylamine and 50 ml of methylene chloride, to give 0.83 g (29% of theory) of N-(4-acetylphenyl)-S-{3-[4-(4-chlorobenzyl)piperazin-1-yl]propyl}thiocarbamate dihydrochloride monohydrate as a white crystalline solid, M.p. 235°-237° C.
Reaction SMILES: [CH2:1]([CH:3]1[O:5][CH2:4]1)[Br:2].[F:6][C:7]([F:15])([F:14])[C:8]([C:10]([F:13])([F:12])[F:11])=[O:9]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[F:6][C:7]([F:15])([F:14])[C:8]1([C:10]([F:13])([F:12])[F:11])[O:5][CH:3]([CH2:1][Br:2])[CH2:4][O:9]1
Reactant: O=C(C(F)(F)F)C(F)(F)F
Reactant: BrCC1CO1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Solvent: O
Product: FC(F)(F)C1(C(F)(F)F)OCC(CBr)O1

Procedure:
This compound was prepared from epibromohydrin and hexafluoroacetone (HFA) (1:1 mole ratio) in the presence of catalytic amounts of tetrabutylammonium bromide and water at 125° C. in 95% isolated yield. Compound 7 has a boiling point 56° C./2 mm. 1H NMR (neat): δ 4.88 (m, 1H), 4.73 (t, J=7.5 Hz, 1H), 4.22 (t, J=7.5 Hz, 1H), 3.60 (m, 2H); 19F NMR (neat: -80.5 (q, J=8.5 Hz, 3F), -81.0 (q, J=8.5 Hz, 3F). Anal. Calc. for C6H5BrF6O2 : C: 23.78, H: 1.66, Br: 26.37, F: 37.62; Found; C: 23.91, H: 1.64, Br: 26.87, F: 37.84.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[CH:12][C:11]=1[C:26](=[O:30])[CH:27]([CH3:29])[CH3:28].[CH3:31][Si]([N-][Si](C)(C)C)(C)C.[Li+].I[CH2:42][CH2:43]C>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[CH:12][C:11]=1[C:26](=[O:30])[C:27]([CH3:31])([CH3:28])[CH2:29][CH2:42][CH3:43]
Reactant: COc1ccc(COc2ccc(-c3cc(OC)ccc3F)c(C(=O)C(C)C)c2)cc1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: CCCI
Agent: [Li+]
Solvent: C1CCOC1
Product: CCCC(C)(C)C(=O)c1cc(OCc2ccc(OC)cc2)ccc1-c1cc(OC)ccc1F
Reaction time: 0.17 h

Procedure:
Under a nitrogen atmosphere, to a solution of 1-(2′-fluoro-5′-methoxy-4-((4-methoxybenzyl)oxy)-[1,1′-biphenyl]-2-yl)-2-methylpropan-1-one (128.6 mg) in THF (1574 μL) was added a solution (409 μL) of lithium bis(trimethylsilyl)amide in THF at 0° C., and the mixture was stirred for 10 min. To the reaction mixture was added 1-iodopropane (61.4 μL), and the mixture was stirred at room temperature for 2.5 hr. To the reaction mixture was added, at 0° C., saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (65.9 mg) as a pale-yellow oil.
Reaction SMILES: [C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[NH2:13][CH2:14][C:15]1[CH:37]=[CH:36][C:18]([C:19]([N:21]2[C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=3[NH:25][C:24]3[N:32]([CH3:35])[N:33]=[CH:34][C:23]=3[CH2:22]2)=[O:20])=[CH:17][C:16]=1[CH3:38].[OH:39][CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1>CN(C=O)C>[OH:39][CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][N:45]([C:1]([NH:13][CH2:14][C:15]2[CH:37]=[CH:36][C:18]([C:19]([N:21]3[C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[NH:25][C:24]4[N:32]([CH3:35])[N:33]=[CH:34][C:23]=4[CH2:22]3)=[O:20])=[CH:17][C:16]=2[CH3:38])=[O:2])[CH2:44][CH2:43]1
Reactant: Cc1cc(C(=O)N2Cc3cnn(C)c3Nc3ccccc32)ccc1CN
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: OCCN1CCNCC1
Solvent: CN(C)C=O
Product: Cc1cc(C(=O)N2Cc3cnn(C)c3Nc3ccccc32)ccc1CNC(=O)N1CCN(CCO)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
1,1′-Carbonyldiimidazole (20 mg, 0.19 mmol) was added to a solution of 5-(4-(aminomethyl)-3-methylbenzoyl)-1-methyl-4,10-dihydropyrazolo-[5,4-b][1,5]benzodiazepine (31 mg, 0.09 mmol) in DMF (3 ml). The solution was stirred at room temperature for 1 h, a solution of 1-(2-hydroxyethyl)-piperazine (13 mg, 0.10 mmol) in DMF (2 ml) was added and stirring was continued for 72 h. The solution was concentrated in vacuo and the residue was partitioned between chloroform and brine. The organic layer was separated and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant 7% methanol/chloroform) to give a white solid identified as 5-(4-(4-(2-hydroxyethyl)piperazine-1-carbonylaminomethyl)-3-methylbenzoyl)-1-methyl-4,10-dihydropyrazolo[5,4-b][1,5](22 mg, 48%).
Reaction SMILES: [CH2:1]([O:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][OH:20])[CH2:2][CH:3]([CH3:5])[CH3:4].[CH2:21](Br)[C:22]1[CH:30]=[CH:29][C:28]2[O:27][CH2:26][O:25][C:24]=2[CH:23]=1.C(=O)(O)[O-].[Na+].N1C=CC=CC=1>CCOCC>[CH2:1]([O:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][O:20][CH2:21][C:22]1[CH:30]=[CH:29][C:28]2[O:27][CH2:26][O:25][C:24]=2[CH:23]=1)[CH2:2][CH:3]([CH3:4])[CH3:5]
Reactant: CC(C)CCOCCCCCCOCCCCCCO
Reactant: BrCc1ccc2c(c1)OCO2
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: CCOCC
Product: CC(C)CCOCCCCCCOCCCCCCOCc1ccc2c(c1)OCO2
Reaction time: 18 h

Procedure:
2.88 g (0.010 mol) of 6-(6-Isopentyloxyhexyloxy)-hexanol are mixed with 2.15 g (0.010 mol) of piperonyl bromide and 1.26 g (0.015 mol) of sodium bicarbonate and the mixture is stirred at 80° for 18 hours and then at 120° C. for 6 hours. 1.0 cc of pyridine is added to the reaction mixture which is heated to 80° over the course of 2 hours. The reaction mixture is cooled, taken up in ether, washed with 2N sulphuric acid, water and saturated sodium chloride solution, dried over magnesium sulphate and evaporated. After chromatography of the residue on silica gel with hexane/acetone (98:2) and (96:4), [6-(6-Isopentyloxyhexyloxy)-hexyl]-piperonyl ether is obtained as a colourless oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH2:9].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:20]([O:23][C:24]1[CH:29]=[C:28]([F:30])[C:27]([F:31])=[C:26](F)[C:25]=1[N+:33]([O-:35])=[O:34])[CH:21]=[CH2:22]>C1COCC1.C(OCC)(=O)C>[CH2:20]([O:23][C:24]1[C:25]([N+:33]([O-:35])=[O:34])=[C:26]([NH:9][C:3]2[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=2[F:1])[C:27]([F:31])=[C:28]([F:30])[CH:29]=1)[CH:21]=[CH2:22]
Reactant: Nc1ccc(I)cc1F
Reactant: C=CCOc1cc(F)c(F)c(F)c1[N+](=O)[O-]
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: C=CCOc1cc(F)c(F)c(Nc2ccc(I)cc2F)c1[N+](=O)[O-]
Temperature: -78 °C
Reaction time: 1 h
Yield: 43.5 %

Procedure:
To a solution of 2-fluoro-4-iodo-phenylamine (1.1 g, 4.6 mmol) in THF (50 mL) was dropwise added LHMDS solution (6.0 mL, 6.0 mmol, 1 M in THF) at −78° C. After stirring for 1 h at −78° C., a solution of 1-allyloxy-3,4,5-trifluoro-2-nitrobenzene (1.2 g, 5.1 mmol) in THF (10 mL) was dropwise added into the reaction mixture. The reaction mixture was stirred at −78° C. for additional 1 h and brought to room temperature and stirred for 16 h. The progress of reaction was monitored by 1H NMR. After completion, the solvent was removed under reduced pressure. The residue obtained was dissolved in ethyl acetate, washed with water, dried over anhydrous Na2SO4 and concentrated. The residue was triturated with hexane to yield (3-allyloxy-5,6-difluoro-2-nitro-phenyl)-(2-fluoro-4-iodo-phenyl)-amine as a yellow solid (900 mg). 1H-NMR (400 MHz, CDCl3): δ 4.62 (2H, d, J=4.8), 5.33-5.36 (1H, d, J=10), 5.48 (1H, d, J=17.2), 5.98-6.02 (1H, m), 6.22 (1H, dd, J=2.4, 9.6), 6.36 (1H, dd, J=2, 10.4), 7.04-7.08 (1H, m), 7.45-7.52 (2H, m), 7.79 (1H, s).
Reaction SMILES: [C:1]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[CH:9]=[C:10](Br)[CH2:11]2.[CH:23]1([Mg]Br)[CH2:25][CH2:24]1.O1CCCC1>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.C1(C)C=CC=CC=1>[C:1]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[CH:9]=[C:10]([CH:23]1[CH2:25][CH2:24]1)[CH2:11]2
Reactant: Br[Mg]C1CC1
Reactant: BrC1=Cc2c(cccc2-c2ccccc2-c2ccccc2)C1
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: C1=C(C2CC2)Cc2cccc(-c3ccccc3-c3ccccc3)c21
Temperature: 60 °C
Reaction time: 0.17 h
Yield: 37 %

Procedure:
A solution of compound 6 (10 g, 28.8 mmol, 1 equiv) and anhydrous toluene (100 mL) was treated with bis(triphenylphosphine)-palladium(II)dichloride (2.35 g, 2.9 mmol, 0.1 equiv). After stirring for 10 minutes, 0.5 M cyclopropylmagnesium bromide in tetrahydrofuran (300 mL, 149.7 mmol, 5.2 equiv) was added dropwise. The reaction was heated at 60° C. overnight. Additional bis(triphenylphosphine)-palladium(II)dichloride (2.35 g, 2.9 mmol, 0.1 equiv) was added and the reaction heated at 60° C. for an additional 24 hours. The reaction was concentrated under reduced pressure and the residue partitioned between water (1 L) and ethyl acetate (1 L). The layers were separated and the aqueous layer washed with ethyl acetate (1 L). The combined organic layers were washed with saturated brine (1 L), dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified over silica gel (200 g) eluting with heptanes to give compound 7 (3.3 g, 37% yield) as a light yellow oil.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([C:13]([CH3:16])([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:30][O:31][NH:32][CH3:33]>ClCCl>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([C:10](=[O:12])[N:32]([O:31][CH3:30])[CH3:33])[C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:2])([CH3:3])[CH3:4]
Reactant: CNOC
Reactant: CC(C)(C)OC(=O)N[C@H](C(=O)O)C(C)(C)C
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Product: CON(C)C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C
Reaction time: 8 h
Yield: 74.3 %

Procedure:
To a solution of 2(S)-tert-butoxycarbonylamino-3,3-dimethyl-butyric acid (30 g, 0.13 mol) in dichloromethane (400 mL) was added portionwise 1,1′-carbonyldiimidazole (63.3 g, 0.39 mol). After addition was complete the reaction was allowed to stir for 15 minutes before N-methoxy-N-methylamine hydrochloride (38 g, 0.39 mol) was added and the reaction allowed to stir overnight. The solvents were removed in vacuo and the residue partitioned between ethyl acetate (250 mL) and 1M HCl (150 mL). The organic phase was washed with 1M HCl solution (2×100 mL), saturated sodium bicarbonate solution (2×100 mL) and brine (100 mL). The organic phase was dried over MgSO4, filtered and the solvents removed in vacuo to give a crude yellow oil. Purification by column chromatography (SiO2, 30% ethyl acetate in hexanes) afforded the title product as a pale yellow oil (26.5 g, 74%).
Reaction SMILES: CS([C:4]1[N:9]=[CH:8][C:7]2=[CH:10][CH:11]=[C:12]([C:13]3[N:14]([CH2:18][CH2:19][C:20]#[N:21])[CH:15]=[CH:16][CH:17]=3)[N:6]2[N:5]=1)=O.[NH2:22][C:23]1[CH:24]=[C:25]([N:29]2[CH2:33][CH2:32][CH2:31][C:30]2=[O:34])[CH:26]=[CH:27][CH:28]=1>>[O:34]=[C:30]1[CH2:31][CH2:32][CH2:33][N:29]1[C:25]1[CH:24]=[C:23]([NH:22][C:4]2[N:9]=[CH:8][C:7]3=[CH:10][CH:11]=[C:12]([C:13]4[N:14]([CH2:18][CH2:19][C:20]#[N:21])[CH:15]=[CH:16][CH:17]=4)[N:6]3[N:5]=2)[CH:28]=[CH:27][CH:26]=1
Reactant: Nc1cccc(N2CCCC2=O)c1
Reactant: CS(=O)c1ncc2ccc(-c3cccn3CCC#N)n2n1
Product: N#CCCn1cccc1-c1ccc2cnc(Nc3cccc(N4CCCC4=O)c3)nn12

Procedure:
Following the synthetic and purification procedures described in Example 1293d, 3-[2-(2-methanesulfinyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-pyrrol-1-yl]-propionitrile (93 mg, 0.31 mmol) was coupled to 1-(3-amino-phenyl)-pyrrolidin-2-one (77 mg, 0.44 mmol) at 120° C. for 96 h to afford the title compound. Yield of TFA salt: 23 mg (15%) of brown powder. LC/MS: 412 (M+H); HPLC: 97% pure, RT=2.16 min; mp: 60-67° C.; 1H NMR: (DMSO, δ) 9.55 (s, 1H), 8.99 (s, 1H), 7.89 (s, 1H), 7.51 (d, J=8.2, 1H), 7.28 (d, J=8.2, 1H), 7.20 (t, J=8.1, 1H), 7.14 (m, 1H), 6.95 (d, J=4.5, 1H), 6.88 (d, J=4.4, 1H), 6.49 (dd, J=3.6, 1.5 1H), 6.27 (t, J=3.6, 1H), 4.19 (t, J=6.3, 2H), 3.49 (t, J=7.0, 2H), 2.77 (t, J=6.3, 2H), 2.47 (t, J=7.0, 2H), 2.02 (p, J=7.0, 2H).
Reaction SMILES: C([O:8][C:9]1[CH:14]=[C:13]([C:15]([CH3:23])([CH3:22])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH:12]=[CH:11][C:10]=1[CH2:24][CH2:25][CH:26]([OH:28])[CH3:27])C1C=CC=CC=1.C(=O)(O)[O-].[Na+].[H][H]>[Pd].C(O)C>[CH3:23][C:15]([C:13]1[CH:12]=[CH:11][C:10]([CH2:24][CH2:25][CH:26]([OH:28])[CH3:27])=[C:9]([OH:8])[CH:14]=1)([CH3:22])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCCCC(C)(C)c1ccc(CCC(C)O)c(OCc2ccccc2)c1
Reactant: [H][H]
Agent: [Pd]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: CCCCCCC(C)(C)c1ccc(CCC(C)O)c(O)c1

Procedure:
A mixture of 390 mg. (1.02 mmols.) of 4-[2-benzyloxy-4-(1,1-dimethylheptyl)phenyl]-2-butanol, 360 mg. of solid sodium bicarbonate, 100 mg. of 10% palladium-on-carbon and 10 ml. of ethanol is stirred under one atmosphere of hydrogen for 20 minutes. The reaction mixture is filtered through diatomaceous earth with ethyl acetate and evaporated to an oil. The oil is purified via rapid column chromatography on silica gel eluted with ether to give a quantitative yield of the title compound as an oil.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]2[C:14]([C:15]3[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][CH:16]=3)=[C:13]([CH3:22])[S:12][C:11]=2[CH:23]=1.[CH3:24][NH:25][CH3:26]>>[Br:21][C:18]1[CH:19]=[CH:20][C:15]([C:14]2[C:10]3[CH:9]=[CH:8][C:7]([O:6][CH2:5][CH2:4][CH2:3][CH2:2][N:25]([CH3:26])[CH3:24])=[CH:23][C:11]=3[S:12][C:13]=2[CH3:22])=[CH:16][CH:17]=1
Reactant: Cc1sc2cc(OCCCCBr)ccc2c1-c1ccc(Br)cc1
Reactant: CNC
Product: Cc1sc2cc(OCCCCN(C)C)ccc2c1-c1ccc(Br)cc1

Procedure:
According to the method in example 31, 6-(4-Bromo-butoxy)-3-(4-bromo-phenyl)-2-methyl-benzo[b]thiophene and dimethylamine were converted to yield {4-[3-(4-Bromo-phenyl)-2-methyl-benzo[b]thiophen-6-yloxy]-butyl}-dimethyl-amine as yellowish oil, MS: 418 (MH+, 1Br).
Reaction SMILES: [CH2:1]([O:4][N:5]=[C:6]1[CH2:10][N:9]([C:11]([O:13]C(C)(C)C)=O)[C@H:8]([C:18]([OH:20])=O)[CH2:7]1)[CH:2]=[CH2:3].[C:21]([C:23]1[CH:31]=[CH:30][C:26](C(Cl)=O)=[CH:25][CH:24]=1)#[N:22].[N:32]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[NH2:43])[CH:36]=[CH:35][CH:34]=[CH:33]1>>[CH2:1]([O:4][N:5]=[C:6]1[CH2:10][N:9]([C:11](=[O:13])[C:26]2[CH:25]=[CH:24][C:23]([C:21]#[N:22])=[CH:31][CH:30]=2)[C@H:8]([C:18]([NH:43][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[N:32]2[CH:36]=[CH:35][CH:34]=[CH:33]2)=[O:20])[CH2:7]1)[CH:2]=[CH2:3]
Reactant: N#Cc1ccc(C(=O)Cl)cc1
Reactant: C=CCON=C1C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)C1
Reactant: Nc1ccccc1-n1cccc1
Product: C=CCON=C1C[C@@H](C(=O)Nc2ccccc2-n2cccc2)N(C(=O)c2ccc(C#N)cc2)C1

Procedure:
Following the general method as outlined in Example 22, starting from (2S,4EZ)-4-[(allyloxy)-imino]-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid, 4-cyanobenzoyl chloride, and 2-(1H-pyrrol-1-yl)phenylamine the title compound was obtained in 51% purity by LC/MS. MS(ESI+): m/z=454.4.
Reaction SMILES: C(=O)(OCC)[O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[C:19]([F:22])[CH:20]=3)[N:15]3[CH:24]=[CH:25][CH:26]=[C:14]3[CH:13]2[CH3:27])(=[O:11])=[O:10])=[CH:5][CH:4]=1.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:42])(=O)=O)=CC=1>C(#N)C>[F:42][C:24]1[N:15]2[C:16]3[C:21]([N:12]([S:9]([C:6]4[CH:7]=[CH:8][C:3]([OH:2])=[CH:4][CH:5]=4)(=[O:10])=[O:11])[CH:13]([CH3:27])[C:14]2=[CH:26][CH:25]=1)=[CH:20][C:19]([F:22])=[C:18]([F:23])[CH:17]=3
Reactant: CCOC(=O)Oc1ccc(S(=O)(=O)N2c3cc(F)c(F)cc3-n3cccc3C2C)cc1
Reactant: O=S(=O)(c1ccccc1)N(F)S(=O)(=O)c1ccccc1
Solvent: CC#N
Product: CC1c2ccc(F)n2-c2cc(F)c(F)cc2N1S(=O)(=O)c1ccc(O)cc1
Yield: 52.8 %

Procedure:
To a 250 ml round bottom flask equipped with condenser was added 3.2 g (7.2 mmol) of the product from Example 9, 3.5 g (10.8 mmol) of N-fluorobenzenesulfonimide and 100 ml of acetonitrile. The solution was heated to reflux for 4 hours. At the end of this time the solution was concentrated and the residue washed with saturated potassium carbonate solution and extracted with ethyl acetate (3×50 ml). The organic layers were combined dried (MgSO4) and concentrated and the resulting crude material chromatographed with 20% ethyl acetate:hexane to yield 1.5 g of material. The enantiomers can be separated (see below) or this material can be hydrolyzed by dissolving in 50 ml of MeOH and 2 ml of 2N NaOH added. After 0.5 hr the solution was concentrated and neutralized with 2N HCL then extracted with ethyl acetate (3×50 ml). The organic layers were combined dried (MgSO4) and concentrated and the solid once again chromatographed with 40% ethyl acetate:hexane. The solid so obtained was recrystallized from ethyl acetate:hexane to yield 0.45 g of product, mp 184-186° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:21]=[CH:22][C:23]=1[O:24][CH3:25])[C:6]([C:8]1[N:12]([CH3:13])[C:11]([CH2:14][C:15]([O:17]CC)=[O:16])=[CH:10][C:9]=1[CH3:20])=[O:7].C(I)CC>>[CH2:14]([C:11]1[N:12]([CH3:13])[C:8]([C:6](=[O:7])[C:5]2[CH:21]=[CH:22][C:23]([O:24][CH3:25])=[C:3]([O:2][CH3:1])[CH:4]=2)=[C:9]([CH3:20])[CH:10]=1)[CH3:15].[CH2:11]([CH2:14][C:15]([O-:17])=[O:16])[CH2:10][CH3:9]
Reactant: CCOC(=O)Cc1cc(C)c(C(=O)c2ccc(OC)c(OC)c2)n1C
Solvent: CCCI
Product: CCCCC(=O)[O-]
Product: CCc1cc(C)c(C(=O)c2ccc(OC)c(OC)c2)n1C

Procedure:
The alkylation procedure of Example 77A is performed upon ethyl 5-(3′,4′-dimethoxybenzoyl)-1,4-dimethylpyrrole-2-acetate (from Example 90), using an equivalent quantity of n-propyl iodide instead of methyl iodide used in Example 77A to yield ethyl 5-(3′,4′-dimethoxybenzoyl)-1,4-dimethylpyrrole-2-(α-n-propyl)-acetate.