Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1([C:6]2[CH:11]=[CH:10][C:9]([N:12]3[CH:21]=[C:20]4[C:14]([CH2:15][CH2:16][NH:17][CH2:18][CH2:19]4)=[N:13]3)=[CH:8][CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:22]1(=O)[CH2:25][CH2:24][CH2:23]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C.CO>[CH:22]1([N:17]2[CH2:18][CH2:19][C:20]3=[CH:21][N:12]([C:9]4[CH:10]=[CH:11][C:6]([N:1]5[CH2:2][CH2:3][CH2:4][CH2:5]5)=[CH:7][CH:8]=4)[N:13]=[C:14]3[CH2:15][CH2:16]2)[CH2:25][CH2:24][CH2:23]1
Reactant: O=C1CCC1
Reactant: c1cc(-n2cc3c(n2)CCNCC3)ccc1N1CCCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Solvent: ClCCl
Product: c1cc(-n2cc3c(n2)CCN(C2CCC2)CC3)ccc1N1CCCC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 2-[4-(1-pyrrolidinyl)phenyl]-2,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine (may be prepared as described in Description 45) (25 mg, 0.09 mmol) in dichloromethane (4 ml) was added cyclobutanone (30 μl, 0.45 mmol) followed by acetic acid (3 drops). The mixture was stirred at room temperature for 30 min, then treated with sodium triacetoxyborohydride (95 mg, 0.45 mmol). The mixture was stirred at room temperature for 4 hours, then it was diluted with methanol and purified by SCX cartridge to afford the title compound (E41). MS (ES+) m/e 337 [M+H]+.
Reaction SMILES: [CH2:1]([N:8]1[C:12]([C:13]([F:16])([F:15])[F:14])=[C:11](Br)[C:10]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[C:9]1[C:25]([N:27]([CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH3:28])=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:34][S:35]([O-:37])=[O:36].[Na+].CS(C)=O.CNCCNC>ClCCl.O>[CH2:1]([N:8]1[C:12]([C:13]([F:16])([F:15])[F:14])=[C:11]([S:35]([CH3:34])(=[O:37])=[O:36])[C:10]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[C:9]1[C:25]([N:27]([CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH3:28])=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CS(=O)[O-]
Reactant: CN(CC(C)(C)C)C(=O)c1c(-c2ccc(Cl)cc2)c(Br)c(C(F)(F)F)n1Cc1ccccc1
Agent: CNCCNC
Agent: [Na+]
Solvent: ClCCl
Solvent: CS(C)=O
Solvent: O
Product: CN(CC(C)(C)C)C(=O)c1c(-c2ccc(Cl)cc2)c(S(C)(=O)=O)c(C(F)(F)F)n1Cc1ccccc1
Temperature: 140 °C
Yield: 50 %

Procedure:
1-Benzyl-4-bromo-3-(4-chlorophenyl)-N-(2,2-dimethylpropyl)-N-methyl-5-(trifluoromethyl)pyrrole-2-carboxamide (100 mg, 0.18 mmol) followed by SODIUM METHANESULFINATE (4.0 equiv., 0.078 g, 0.74 mmol), COPPER(I) TRIFLATE BENZENE COMPLEX (0.1 equiv., 0.010 g, 0.018 mmol), DIMETHYL SULFOXIDE (0.6 mL) and N,N′-DIMETHYLETHYLENEDIAMINE (0.2 equiv., 0.003 g, 0.037 mmol) added to reactivial. Flushed with Nitrogen and heated at 140° C. for 18 hours (overnight). Black solid residue formed. Work Up: Diluted with 50 ml Dichloromethane and 100 ml Water then filtered to remove solids. Dichloromethane/Water shaken and separated. Aqueous extracted 2×50 ml Dichloromethane. Organics combined and filtered through hydrophobic frit, then reduced under vacuum. Purification: Purified via Preparative HPLC over 2 injections using 50-95% acetonitrile/water (0.1% Formic Acid) over 15 minutes collecting at 254 nm. Pure fractions combined and reduced under vacuum to yield product as 51.4 mg (0.09 mmol) beige solid.
Reaction SMILES: [Br:1][C@@H:2]1[C@H:9]([O:10][C:11](=[O:17])[NH:12][C:13](=[O:16])[CH2:14][Cl:15])[CH2:8][CH2:7][C@@:4]2([O:6][CH2:5]2)[C@@:3]1([OH:21])[C:18]([CH3:20])=[CH2:19].ClC1C=CC=C(C(OO)=[O:30])C=1.CCCCCC.C(OCC)(=O)C>ClCCl>[Br:1][C@@H:2]1[C@H:9]([O:10][C:11](=[O:17])[NH:12][C:13](=[O:16])[CH2:14][Cl:15])[CH2:8][CH2:7][C@@:4]2([O:6][CH2:5]2)[C@@:3]1([OH:21])[C:18]1([CH3:20])[CH2:19][O:30]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: C=C(C)[C@@]1(O)[C@H](Br)[C@H](OC(=O)NC(=O)CCl)CC[C@]12CO2
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: CC1([C@@]2(O)[C@H](Br)[C@H](OC(=O)NC(=O)CCl)CC[C@]23CO3)CO1

Procedure:
By proceeding in accordance with the method of operation described in Example 2, starting from 2.14 g (5.6 mmol) of the crude compound obtained in Example 3 and 1.93 g (11.2 mmol) of 72% 3-chloroperbenzoic acid in 55 ml of dichloromethane, 0.9 g (2.26 mmol) of a mixture of the two expected diastereoisomers (73/27) is obtained in the form of a mousse after chromatography on silica gel twice (eluant: hexane/ethyl acetate, 3:1).
Reaction SMILES: O=C1N[C:6](=[O:8])[CH:5](C#N)[C:4]2([CH2:15][CH2:14][CH:13]([CH:16]3[CH2:21][CH2:20][CH:19]([CH2:22][CH2:23][CH3:24])[CH2:18][CH2:17]3)[CH2:12][CH2:11]2)C1C#N.S(=O)(=O)(O)[OH:28].[C:32]([OH:35])(=[O:34])[CH3:33]>>[C:32]([CH2:33][C:4]1([CH2:5][C:6]([OH:28])=[O:8])[CH2:15][CH2:14][CH:13]([CH:16]2[CH2:21][CH2:20][CH:19]([CH2:22][CH2:23][CH3:24])[CH2:18][CH2:17]2)[CH2:12][CH2:11]1)([OH:35])=[O:34]
Reactant: CC(=O)O
Reactant: O=S(=O)(O)O
Reactant: CCCC1CCC(C2CCC3(CC2)C(C#N)C(=O)NC(=O)C3C#N)CC1
Product: CCCC1CCC(C2CCC(CC(=O)O)(CC(=O)O)CC2)CC1
Temperature: 122.5 °C
Reaction time: 120 h

Procedure:
A mixture of 50 g (0.14 mol) of 2,4-dioxo-9-(4-propylcyclohexyl)-3-aza-spiro[5.5]undecane-1,5-dicarbonitrile, 800 ml of glacial acetic acid and 1.51 of 60% sulfuric acid is stirred at 120-125° C. for 5 days. After cooling, the batch is added to ice-water and extracted a number of times with THF/MTBE (1:1). The combined organic phases are washed with saturated sodium chloride solution and dried using sodium sulfate. The solution is concentrated to dryness, and the residue is recrystallised from acetonitrile/THF (2:1), giving (4-carboxymethyl-4′-propylbicyclohexyl-4-yl)acetic acid as a beige solid.
Reaction SMILES: [CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10](B3OC(C)(C)C(C)(C)O3)=[CH:11][CH:12]=2)[CH2:7][CH2:6]1)=[O:4].[NH2:23][C:24]1[N:25]=[CH:26][C:27]([C:31]2[CH:36]=[CH:35][C:34]([S:37]([N:40]([CH:42]3[CH2:44][CH2:43]3)[CH3:41])(=[O:39])=[O:38])=[CH:33][CH:32]=2)=[N:28][C:29]=1Br>>[NH2:23][C:24]1[C:29]([C:10]2[CH:9]=[C:8]3[C:13](=[CH:12][CH:11]=2)[N:5]([C:3]([NH:2][CH3:1])=[O:4])[CH2:6][CH2:7]3)=[N:28][C:27]([C:31]2[CH:36]=[CH:35][C:34]([S:37](=[O:39])(=[O:38])[N:40]([CH:42]3[CH2:43][CH2:44]3)[CH3:41])=[CH:33][CH:32]=2)=[CH:26][N:25]=1
Reactant: CNC(=O)N1CCc2cc(B3OC(C)(C)C(C)(C)O3)ccc21
Reactant: CN(C1CC1)S(=O)(=O)c1ccc(-c2cnc(N)c(Br)n2)cc1
Product: CNC(=O)N1CCc2cc(-c3nc(-c4ccc(S(=O)(=O)N(C)C5CC5)cc4)cnc3N)ccc21
Yield: 28.1 %

Procedure:
Method C was applied to N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline-1-carboxamide (85 mg, 0.28 mmol) and 4-(5-amino-6-bromopyrazin-2-yl)-N-cyclopropyl-N-methylbenzenesulfonamide (100 mg, 0.26 mmol). The organic layer was decanted then triturated with Et2O to provide 5-(3-amino-6-(4-(N-cyclopropyl-N-methylsulfamoyl)phenyl)pyrazin-2-yl)-N-methylindoline-1-carboxamide as a yellow solid (35 mg, 28% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.58-8.66 (m, 1H), 8.20-8.31 (m, 1H), 7.92-7.99 (m, 1H), 7.79-7.88 (m, 2H), 7.47-7.64 (m, 2H), 6.61-6.71 (m, 1H), 6.60-6.65 (m, 1H), 6.58-6.71 (m, 2H), 6.42-6.49 (m, 2H), 3.88-3.98 (m, 2H), 3.13-3.25 (m, 2H), 2.68 (s, 3H), 2.08 (s, 3H), 1.79-1.88 (m, 1H), 0.62-0.81 (m, 4H); MS (EI) m/z=479.1[M+1]+.
Reaction SMILES: [Cl:1][C:2]1[C:7]([S:8][CH3:9])=[C:6]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[N:5]=[C:4]([C:16]2[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=2)[N:3]=1.Cl[C:24]([O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:25]>CC(=O)OCC.C([O-])(O)=O.[Na+]>[C:27]1([O:26][C:24](=[O:25])[NH:22][C:19]2[CH:20]=[CH:21][C:16]([C:4]3[N:3]=[C:2]([Cl:1])[C:7]([S:8][CH3:9])=[C:6]([N:10]4[CH2:15][CH2:14][O:13][CH2:12][CH2:11]4)[N:5]=3)=[CH:17][CH:18]=2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: CSc1c(Cl)nc(-c2ccc(N)cc2)nc1N1CCOCC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Product: CSc1c(Cl)nc(-c2ccc(NC(=O)Oc3ccccc3)cc2)nc1N1CCOCC1
Temperature: 25 °C

Procedure:
A mixture of 4-(4-chloro-5-methylsulfanyl-6-morpholin-4-yl-pyrimidin-2-yl)-phenylamine (915 mg, 2.717 mmol.) in EA (20 ml) and NaHCO3 (20 ml) the reaction was stirred at r.t. then added dropwise to slurry of phenyl chloroformate (851 mg, 0.543 mmol, 2.0 eq) at reaction for 2 hr. The reaction mixture was partitioned between EA/NaHCO3, the organic layer was washed with brine, dried over MgSO4, filtered and evaporated in vacuo. The residue was recrystallized by (Hexane/EtOAc) to give a pale yellow product of 1056 mg (85.1%).
Reaction SMILES: [CH:1]([C:3]1[CH:17]=[CH:16][C:6]([O:7][CH2:8][CH2:9][CH2:10][C:11]([O:13]CC)=[O:12])=[C:5]([O:18][CH3:19])[CH:4]=1)=[O:2].C(=O)([O-])[O-].[K+].[K+]>CO.O>[CH:1]([C:3]1[CH:17]=[CH:16][C:6]([O:7][CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12])=[C:5]([O:18][CH3:19])[CH:4]=1)=[O:2]
Reactant: CCOC(=O)CCCOc1ccc(C=O)cc1OC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CO
Product: COc1cc(C=O)ccc1OCCCC(=O)O
Yield: 58.3 %

Procedure:
4-(4-Formyl-2-methoxyphenoxy)butanoic acid, ethyl ester (240 mg, 0.90 mmol) is dissolved in 3 mL of methanol/water (3:2) and treated with 435 mg. (3.15 mmol) of potassium carbonate according to the procedure described for Example 4 to give 125 mg (58%) of 4-(4-formyl-2-methoxyphenoxy) butanoic acid as a white powder: m.p. 143°-148°; the 1 H NMR (300 MHz, CDCl3) is consistent with the desired product; IR (KBr) 3575, 3500, 1720, 1700, 1680, 1600, 1585 cm-1 ; MS (CI (low res))m/e 239 (M+H), 221, 207, 153.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:10][CH2:11][CH2:12][N:13]([CH3:15])[CH3:14])=[N:8][CH:9]=1)([O-])=O.[H][H]>CO.[Pd]>[CH3:14][N:13]([CH3:15])[CH2:12][CH2:11][O:10][C:7]1[N:8]=[CH:9][C:4]([NH2:1])=[CH:5][CH:6]=1
Reactant: CN(C)CCOc1ccc([N+](=O)[O-])cn1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CN(C)CCOc1ccc(N)cn1
Temperature: 25 °C
Reaction time: 16 h
Yield: 98.5 %

Procedure:
2-(5-Nitropyridin-2-yloxy)-N,N-dimethylethanamine (295 mg, 1.40 mmol) was dissolved in 5 mL of methanol and placed under a nitrogen atmosphere. A catalytic amount of 10% palladium on carbon was added and a hydrogen balloon was connected to the reaction flask. The flask was flushed five times with hydrogen and stirred at room temperature under hydrogen atmosphere for 16 hours. The solid was filtered and washed with methanol. The filtrate was evaporated under reduced pressure yielding 6-[2-(dimethylamino)ethoxy]pyridin-3-amine as a brown oil (250 mg, 99%). LC/MS (m/z): 182.1 (MH+), Rt 0.36 minutes.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4](O)=[O:5].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[F:47][C:48]([F:62])([F:61])[C:49]1[N:53]2[CH2:54][CH2:55][NH:56][CH2:57][C:52]2=[C:51]([C:58]([NH2:60])=[O:59])[N:50]=1.C(N(CC)C(C)C)(C)C>CN(C)C=O.O>[F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([N:56]1[CH2:55][CH2:54][N:53]2[C:49]([C:48]([F:62])([F:47])[F:61])=[N:50][C:51]([C:58]([NH2:60])=[O:59])=[C:52]2[CH2:57]1)=[O:5]
Reactant: O=C(O)c1cc(Cc2n[nH]c(=O)c3ccccc23)ccc1F
Reactant: NC(=O)c1nc(C(F)(F)F)n2c1CNCC2
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: NC(=O)c1nc(C(F)(F)F)n2c1CN(C(=O)c1cc(Cc3n[nH]c(=O)c4ccccc34)ccc1F)CC2
Reaction time: 12 h
Yield: 19.4 %

Procedure:
2-Fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoic acid 1a (150 mg, 0.50 mmol) was dissolved in 10 mL of N,N-dimethylformamide, followed by addition of O-(1-benzotriazolyl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (285 mg, 0.75 mmol), crude 3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamide 10a (130 mg, 0.55 mmol) and N,N-diisopropylethylamine (0.2 mL, 1 mmol). After stirring for 12 hours, the reaction mixture was added with 50 mL of H2O and extracted with dichloromethane (60 mL×3). The organic phase was combined, concentrated under reduced pressure, added with 100 mL of ethyl acetate, washed successively with H2O (40 mL) and saturated sodium chloride solution (40 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by thin layer chromatography with elution system A to obtain 7-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]-3-(trifluoromethyl)-6,8-dihydro-5H-imidazo[1,5-a]pyrazine-1-carboxamide 10 (50 mg, yield 20.0%) as a white solid.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10]([NH2:15])=[N:11][CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:17][C:18](=O)[CH2:19][CH2:20][C:21]#[C:22][Si:23]([CH3:26])([CH3:25])[CH3:24]>>[CH2:1]([O:8][C:9]1[C:10]2[N:11]([CH:17]=[C:18]([CH2:19][CH2:20][C:21]#[C:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[N:15]=2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1ncccc1OCc1ccccc1
Reactant: C[Si](C)(C)C#CCCC(=O)CBr
Product: C[Si](C)(C)C#CCCc1cn2cccc(OCc3ccccc3)c2n1

Procedure:
The title compound was prepared in accordance with the general method of Example 223(D), from 3-(benzyloxy)pyridin-2-amine (274 mg, 1.37 mmol) and 1-bromo-6-(trimethylsilyl)hex-5-yn-2-one (compound 223(C), 750 mg, 3.0 mmol). The crude residue was purified over silicagel chromatography (prepacked 25 g silicagel column, DCM/MeOH: from 98/2 to 95/5 as eluent) to afford 331 mg of 8-(benzyloxy)-2-(4-(trimethylsilyl)but-3-ynyl)H-imidazo[1,2-a]pyridine (Yield: 69%) as a yellow oil.
Reaction SMILES: [F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:10]1[N:14]([S:15]([C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)(=[O:17])=[O:16])[CH:13]=[C:12]([CH2:24][N:25](C)[C:26](=O)[O:27][C:28]([CH3:31])(C)C)[CH:11]=1.[C:34]([O:37]CC)(=[O:36])[CH3:35].Cl.C[OH:42]>>[C:28]([OH:42])(=[O:27])/[CH:31]=[CH:35]/[C:34]([OH:37])=[O:36].[F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:10]1[N:14]([S:15]([C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)(=[O:17])=[O:16])[CH:13]=[C:12]([CH2:24][NH:25][CH3:26])[CH:11]=1
Reactant: CO
Reactant: CCOC(C)=O
Reactant: COc1cccc(-c2cc(CN(C)C(=O)OC(C)(C)C)cn2S(=O)(=O)c2cccnc2)c1F
Agent: Cl
Product: CNCc1cc(-c2cccc(OC)c2F)n(S(=O)(=O)c2cccnc2)c1
Product: O=C(O)/C=C/C(=O)O
Temperature: 70 °C
Reaction time: 0.33 h
Yield: 63 %

Procedure:
tert-Butyl {[5-(2-fluoro-3-methoxyphenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate (475 mg) was dissolved in methanol (20 mL), a 4 mol/L hydrogen chloride-ethyl acetate solution (2 mL) was added and the mixture was stirred at 70° C. for 20 min. The reaction mixture was concentrated under reduced pressure, a saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in ethanol (13 mL), fumaric acid (116 mg) was added, and the obtained crystals were collected by filtration to give the title compound as colorless crystals (yield 310 mg, 63%).
Reaction SMILES: [Si]([O:8][C@@H:9]([C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][C:66]=1[C:71]1[CH:76]=[CH:75][C:74]([Cl:77])=[CH:73][CH:72]=1)[CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:64]=[CH:63][C:19]([C:20]([NH:22][S:23]([C:26]3[CH:31]=[CH:30][C:29]([NH:32][C@H:33]([CH2:42][CH2:43][N:44]4[CH2:49][CH2:48][O:47][CH2:46][C@@H:45]4[CH2:50][N:51]([CH2:54][CH3:55])[CH2:52][CH3:53])[CH2:34][S:35][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[C:28]([S:56]([C:59]([F:62])([F:61])[F:60])(=[O:58])=[O:57])[CH:27]=3)(=[O:25])=[O:24])=[O:21])=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>>[Cl:77][C:74]1[CH:75]=[CH:76][C:71]([C:66]2[CH:67]=[CH:68][CH:69]=[CH:70][C:65]=2[C@H:9]([OH:8])[CH:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:17]=[CH:18][C:19]([C:20]([NH:22][S:23]([C:26]4[CH:31]=[CH:30][C:29]([NH:32][C@H:33]([CH2:42][CH2:43][N:44]5[CH2:49][CH2:48][O:47][CH2:46][C@@H:45]5[CH2:50][N:51]([CH2:54][CH3:55])[CH2:52][CH3:53])[CH2:34][S:35][C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)=[C:28]([S:56]([C:59]([F:62])([F:61])[F:60])(=[O:57])=[O:58])[CH:27]=4)(=[O:24])=[O:25])=[O:21])=[CH:63][CH:64]=3)[CH2:12][CH2:11]2)=[CH:72][CH:73]=1
Reactant: CCN(CC)C[C@H]1COCCN1CC[C@H](CSc1ccccc1)Nc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCC([C@@H](O[Si](C)(C)C(C)(C)C)c4ccccc4-c4ccc(Cl)cc4)CC3)cc2)cc1S(=O)(=O)C(F)(F)F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Product: CCN(CC)C[C@H]1COCCN1CC[C@H](CSc1ccccc1)Nc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCC([C@@H](O)c4ccccc4-c4ccc(Cl)cc4)CC3)cc2)cc1S(=O)(=O)C(F)(F)F
Yield: 48 %

Procedure:
A solution of 4-(4-((R)-(tert-butyldimethylsilyloxy)(4′-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)-N-(4-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide, (INTERMEDIATE 89, 100 mg, 0.09 mmol) and TBAF (3.5 ml 3.46 mmol, 1 M in THF) was stirred for 45 minutes at room temperature. The solvent was removed under reduced pressure and the residue was taken up in DCM (50 ml). The organic layer was washed successively with 50 ml of water (50 ml) and saturated aqueous sodium bicarbonate (50 ml). The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography (ISCO, eluting with 0→100% DCM/[10% 2N ammonia in MeOH in DCM] over 19 minutes and then eluting with 0→20% MeOH/DCM) to give the title product (43.0 mg, yield: 48%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])=[C:5]2[NH:17][C@H:18]1[CH2:23][CH2:22][C@H:21]([CH2:24][NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:20][CH2:19]1.[Cl:33][C:34]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:37]=[C:36]([F:49])[C:35]=1[OH:50]>>[Cl:33][C:34]1[CH:39]=[C:38]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][C:6]([C:12]([CH:14]2[CH2:15][CH2:16]2)=[O:13])=[C:5]3[NH:17][C@H:18]2[CH2:19][CH2:20][C@H:21]([CH2:24][NH:25][C:26](=[O:32])[O:27][C:28]([CH3:29])([CH3:30])[CH3:31])[CH2:22][CH2:23]2)[CH:37]=[C:36]([F:49])[C:35]=1[OH:50]
Reactant: CC(C)(C)OC(=O)NC[C@H]1CC[C@H](Nc2c(C(=O)C3CC3)cnc3ccc(Br)cc23)CC1
Reactant: CC1(C)OB(c2cc(F)c(O)c(Cl)c2)OC1(C)C
Product: CC(C)(C)OC(=O)NC[C@H]1CC[C@H](Nc2c(C(=O)C3CC3)cnc3ccc(-c4cc(F)c(O)c(Cl)c4)cc23)CC1

Procedure:
Following general procedure F, tert-butyl {trans-4-[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-ylamino]cyclohexyl}methylcarbamate (62 mg, 0.123 mmol) was reacted with 2-chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (50 mg, 0.185 mmol) to afford the crude product (69 mg) as a yellow-green solid.
Reaction SMILES: [CH2:1]=[CH:2][CH:3]=[CH2:4].[H-].[CH2:6]([Al+]CC(C)C)C(C)C.[Nd].C(Br)C=C>[Nd].CCCCCC.C(O)CCC>[CH2:1]=[CH:2][C:3](=[CH2:6])[CH3:4].[CH2:1]=[CH:2][CH:3]=[CH2:4]
Reactant: CC(C)C[Al+]CC(C)C
Agent: C=CC=C
Agent: [H-]
Agent: [Nd]
Solvent: CCCCCC
Solvent: C=CCBr
Solvent: CCCCO
Product: C=CC(=C)C
Temperature: 20 °C
Reaction time: 1 h

Procedure:
In this experiment, an isoprene-butadiene copolymer was synthesized using an alcohol modified neodymium catalyst system with a different catalyst component molar ratio than that described in Example 3. In this procedure, a one gallon (3.78 liter) reactor was charged with 1,088 grams of hexane containing 93.5 grams of butadiene and 668 grams of 1.23 molar diisobutylaluminum hydride (DIBAH) in hexane (i.e., 25% weight percent DIBAH). To this solution was added 26.22 grams of n-butanol with stirring and with temperatures maintained at 20° C. After stirring for thirty minutes, 107.5 grams of a 10.1% neodymium solution (neodymium neodecanoate), dilute with 158 grams of dry hexane, was charged to the reactor. The solution was stirred for another thirty minutes after which time 21.4 grams of allyl bromide was added. The cooling was stopped and the mixture allowed to warm up to ambient (and above) temperature. After the exotherm subsided, requiring about one hour, the catalyst solution was heat aged at 65° C. for ninety minutes. The aged catalyst was then cooled and stored in a dry container under nitrogen. The catalyst prepared had a [butanol-DIBAH] Nd-allyl bromide-butadiene molar component ratio of [4.7-15.5]-1-2.35-23, respectively, and a concentration of 0.025 molarity with respect to the neodymium.
Reaction SMILES: C[Si]([C:5]#[C:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][Si](C)(C)C)=[CH:15][N:14]=2)=[N:11][CH:12]=1)(C)C.[F-].[K+]>CO.C1COCC1>[C:19]([C:16]1[CH:17]=[CH:18][C:13]([C:10]2[CH:9]=[CH:8][C:7]([C:6]#[CH:5])=[CH:12][N:11]=2)=[N:14][CH:15]=1)#[CH:20]
Reactant: C[Si](C)(C)C#Cc1ccc(-c2ccc(C#C[Si](C)(C)C)cn2)nc1
Agent: [F-]
Agent: [K+]
Solvent: CO
Solvent: C1CCOC1
Product: C#Cc1ccc(-c2ccc(C#C)cn2)nc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4 (390 mg, 1.12 mmol) was dissolved in a mixture of 40 ml MeOH and 10 ml THF; then KF powder (400 mg, 6.88 mmol) was added and the solution was stirred at room temperature overnight. Subsequently, the solvents were removed under reduced pressure. The residue was redissolved in 200 ml CH2Cl2 and washed four times with 100 ml H2O each, in order to remove inorganic salts. The organic phase was dried over Na2SO4, concentrated under reduced pressure and purified by silica flash column chromatography (eluent: CH2Cl2) to yield a colorless powder of 204 mg (1.0 mmol, 81%) pure 5. 1H NMR (CDCl3, 250 MHz): δ=8.76 (d, 2H, JHH=1.0 Hz, bpy-H), 8.39 (d, 2H, JHH=6.0 Hz, bpy-H), 7.90 (dd, 2H, JHH=1.1 Hz, 5.1 Hz, bpy-H), 3.31 (s, 2H, bpy-CCH).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[C:10](=[O:11])[O:9][CH2:8]2.COC1C=CC=CC=1C=O.C1(P(=[CH:42][C:43]([O:45][CH3:46])=[O:44])(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)(Cl)Cl>[OH:11][CH:10]1[C:12]2[C:3]([O:2][CH3:1])=[CH:4][CH:5]=[CH:6][C:7]=2[CH2:8][O:9]1.[OH:9][CH2:8][C:7]1[CH:6]=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[C:12]=1/[CH:10]=[CH:42]/[C:43]([O:45][CH3:46])=[O:44]
Reactant: COc1cccc2c1C(=O)OC2
Reactant: COC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: COc1ccccc1C=O
Solvent: ClC(Cl)Cl
Product: COC(=O)/C=C/c1c(CO)cccc1OC
Product: COc1cccc2c1C(O)OC2
Temperature: 50 °C
Reaction time: 0.67 h

Procedure:
1-Hydroxy-7-methoxy-1,3-dihydrobenzo[c]furan (1.08 g), which was prepared with using 7-methoxyphthalide which was synthesized with using 2-methoxybenzaldehyde by the method described in Journal of Organic Chemistry, 1980, 45, 1835-1838, was dissolved in chloroform (20 ml). Methyl (triphenylphosphoranylidene)acetate (2.68 g) was added to the solution. The mixture was stirred for 40 min. at 50° C. A temperature of the reaction mixture was down to room temperature. The reaction solution was purified by column chromatography on silica gel (n-hexane:ethyl acetate=2:1) to give the title compound (1.25 g) having the following physical data.
Reaction SMILES: [CH:1]([CH2:3][CH2:4][CH2:5][C:6]1[CH:15]=[C:14]([O:16][CH3:17])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]=1[O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)=[O:2].[BH4-].[Na+]>CO>[CH3:17][O:16][C:14]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)=[C:6]([CH2:5][CH2:4][CH2:3][CH2:1][OH:2])[CH:15]=1
Reactant: COc1cc(CCCC=O)c(OC2CCCCO2)c2ccccc12
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COc1cc(CCCCO)c(OC2CCCCO2)c2ccccc12
Reaction time: 0.5 h

Procedure:
The starting 2-(3-formylpropyl)-4-methoxy-1-[(tetrahydro-2H-pyran-2-yl)-oxy]naphthalene (0.587 g) is dissolved in 5 ml methanol. This solution is placed under a nitrogen atmosphere and then cooled to 0°-5° C. and solid sodium borohydride (0.10 g) is added in one portion. Vigorous gas evolution ensues and after stirring for 30 min TLC analysis indicates the reduction is complete. The reaction is quenched with saturated aqueous ammonium chloride and then poured into water. The pH is adjusted to 2--3 (10% aqueous sodium bisulfate) and the mixture extracted with ether. The pH of the aqueous phase is raised to 7 (saturated aqueous sodium bicarbonate), excess solid sodium chloride is added and the mixture reequilibrated. The organic extract is dried with magnesium sulfate, filtered and concentrated to give the crude product as an orange colored oil.