Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:3]1[N:4]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:5]2[C:10]([C:11]=1[CH2:12][C:13]([NH2:15])=[O:14])=[CH:9][C:8]([O:16][CH2:17][CH2:18][CH2:19][C:20]([NH:22]N)=[O:21])=[CH:7][CH:6]=2)[CH3:2].CO.CCOC(C)=O>C(O)C.[Ni]>[NH2:22][C:20](=[O:21])[CH2:19][CH2:18][CH2:17][O:16][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[N:4]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:3]([CH2:1][CH3:2])=[C:11]2[CH2:12][C:13]([NH2:15])=[O:14]
Reactant: CCc1c(CC(N)=O)c2cc(OCCCC(=O)NN)ccc2n1Cc1ccccc1
Agent: [Ni]
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: CO
Product: CCc1c(CC(N)=O)c2cc(OCCCC(N)=O)ccc2n1Cc1ccccc1
Yield: 47.4 %

Procedure:
A mixture of 150 mg (0.37 mmol) of 2-ethyl-5-(4-hydrazino-4-oxobutoxy)-1-(phenylmethyl)-1H-indole-3-acetamide and 200 mg of Raney Ni in 15 mL of ethanol was heated to maintain reflux for 2 hours. After cooling, the EtOH was poured off and the Raney Ni washed twice with methylene chloride. The combined washes were filtered, concentrated at reduced pressure and the residue chromatographed on silica eluting with EtOAc, then 10% MeOH/EtOAc to give 69 mg (47% yield) of 5-(4-amino-4-oxobutoxy)-2-ethyl-1-(phenylmethyl)-1H-indole-3-acetamide, mp 176-179° C.
Reaction SMILES: Br[C:2]1[S:6][C:5]([C:7]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)([OH:9])[CH3:8])=[N:4][CH:3]=1.O.[NH2:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[NH2:24][C:25]1[CH:30]=[C:29]([C:2]2[S:6][C:5]([C:7]([CH:10]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]3)([OH:9])[CH3:8])=[N:4][CH:3]=2)[CH:28]=[CH:27][CH:26]=1
Reactant: Nc1cccc(B(O)O)c1
Reactant: CC(C)(C)OC(=O)N1CCC(C(C)(O)c2ncc(Br)s2)CC1
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: COCCOC
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(C(C)(O)c2ncc(-c3cccc(N)c3)s2)CC1
Yield: 91.9 %

Procedure:
The product of Step 2 (87 mg, 0.222 mmol), 3-aminophenylboronic acid monohydrate (41.3 mg, 0.267 mmol), Pd(Ph3P)4 (12.85 mg, 0.011 mmol) and Na2CO3 (0.333 mL, 0.667 mmol) were stirred in DME at 100° C. overnight under N2. The reaction mixture was filtered through a pre-pack pad of celica with dichloromethane. The filtrate was concentrated and the residue was purified by flash chromatography to give tert-butyl 4-{1-[5-(3-aminophenyl)-1,3-thiazol-2-yl]-1-hydroxyethyl}piperidine-1-carboxylate (82.4 mg, 0.204 mmol, 92%) as a yellow oil.
Reaction SMILES: FC(F)(F)C([O-])=O.[CH2:8]([O:10][C:11]([C:13]1[N:17]2[CH2:18][C:19](=O)[N:20]([C:21]3[C:26]([CH3:27])=[CH:25][C:24]([CH3:28])=[CH:23][C:22]=3[CH3:29])[C:16]2=[NH+:15][C:14]=1[CH3:31])=[O:12])[CH3:9].P(Cl)(Cl)([Cl:34])=O>>[CH2:8]([O:10][C:11]([C:13]1[N:17]2[CH:18]=[C:19]([Cl:34])[N:20]([C:21]3[C:26]([CH3:27])=[CH:25][C:24]([CH3:28])=[CH:23][C:22]=3[CH3:29])[C:16]2=[N:15][C:14]=1[CH3:31])=[O:12])[CH3:9]
Reactant: O=P(Cl)(Cl)Cl
Reactant: CCOC(=O)c1c(C)[nH+]c2n1CC(=O)N2c1c(C)cc(C)cc1C
Agent: O=C([O-])C(F)(F)F
Product: CCOC(=O)c1c(C)nc2n(-c3c(C)cc(C)cc3C)c(Cl)cn12

Procedure:
A solution of 3-ethoxycarbonyl-2-methyl-6-oxo-7-(2,4,6-trimethyl-phenyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazolium trifluoroacetate (22.2 mg, 0.050 mmol) in phosphorus oxychloride (1 mL) was heated at 150° C. for 48 h. The excess of phosphorus oxychloride was removed under reduced pressure, the residue was dissolved in saturated aqueous solution of sodium bicarbonate (20 mL) and extracted with ethyl acetate (5×20 mL). The combined organic extracts were dried with MgSO4. The solvent was removed under reduced pressure and the crude product was dried under pump vacuum overnight. Yield—23.3 mg (99%). LC/MS: tR=1.93 min., MS: [M+H]=346.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].CN(C)C1C=CC=CC=1.C([O:21][C:22]1[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]2[CH:35]=[C:34]([O:36]CC3C=CC=CC=3)[CH:33]=[C:32]([O:44]CC3C=CC=CC=3)[CH:31]=2)=[CH:24][CH:23]=1)C1C=CC=CC=1>ClCCl>[OH:36][C:34]1[CH:35]=[C:30](/[CH:29]=[CH:28]/[C:25]2[CH:26]=[CH:27][C:22]([OH:21])=[CH:23][CH:24]=2)[CH:31]=[C:32]([OH:44])[CH:33]=1
Reactant: C(=C/c1cc(OCc2ccccc2)cc(OCc2ccccc2)c1)\c1ccc(OCc2ccccc2)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: CN(C)c1ccccc1
Product: Oc1ccc(/C=C/c2cc(O)cc(O)c2)cc1
Temperature: 45 °C
Yield: 90 %

Procedure:
Into a 3 lit. round-bottomed flask equipped with a thermometer were added aluminum chloride (390.35 gm) and N,N-dimethylaniline (413.10 gm) maintaining the temperature at 40-50° C. To this solution, a solution of (E)-1-(4-(benzyloxy)phenyl)-2-(3,5-bis(benzyloxy)phenyl)ethene (243 gm) prepared according to example 1 in dichloromethane was added and stirred well. After the reaction was over, the reaction mixture was acidified, extracted into ethyl acetate and concentrated to get pure (E)1-(3,5-dihydroxyphenyl)-2-(4-hydroxyphenyl)ethene (E-Resveratrol) in the exclusive E- form in 90% yield. 1H NMR (DMSO-d6, Bruker 400 MHz Avarice): δ 6.11 (t, J=1.8 Hz), 6.38 (d, J=1.8 Hz, 2H), 6.75 (d, J=8.5 Hz, 2H), 6.82 (d, J=16.3 Hz, 1H), 6.92 (d, J=16.3 Hz), 7.39 (d, J=8.4 Hz, 2H); Mass m/e: 228.2.
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[Cl:5][CH2:6][C:7](Cl)=[O:8].[F:10][C:11]([F:25])([F:24])[C:12]([NH:14][C@H:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][CH2:16]1)=[O:13]>ClCCCl>[Cl:5][CH2:6][C:7]([C:21]1[CH:22]=[C:23]2[C:18]([CH2:17][CH2:16][C@H:15]2[NH:14][C:12](=[O:13])[C:11]([F:24])([F:10])[F:25])=[CH:19][CH:20]=1)=[O:8]
Reactant: O=C(N[C@@H]1CCc2ccccc21)C(F)(F)F
Reactant: O=C(Cl)CCl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCCl
Product: O=C(CCl)c1ccc2c(c1)[C@H](NC(=O)C(F)(F)F)CC2
Temperature: 22.5 °C
Reaction time: 0.5 h
Yield: 32.7 %

Procedure:
To a suspension of AlCl3 (89.2 g, 0.67 mol) in 1,2-dichloroethane (600 ml) was added chloroacetyl chloride (55.7 ml. 78.9 g, 0.7 mol) dropwise at 0-5° C. under nitrogen for 20 minutes and it was then left to warm up to 20-25° C. To this mixture was added N-trifluoroacetyl-(R)-1-aminoindan (34.4 g, 0.15 mol) for 3 hours at 20-25° C. The resulting mixture was then stirred or an additional 30 minutes and poured into a mixture of ice-cold water (1.5 l) and 1,2-dichloroethane (11). The mixture was stirred for 5 minutes and the layers were separated. The aqueous layer was extracted with 1,2-dichloroethane (2×750 ml). The combined organic layers were washed with water (2×900 ml) and 5% aqueous NaHCO3 solution (3×900 ml). The organic layer was dried (Na2SO4) and the solvent was removed under reduced pressure to give a solid, which was recrystallized from ethanol to give 15 g (48%) of a white solid mp: 166-167° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:23]([N:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[O:24])=[C:8]([NH:10][S:11]([C:14]2[C:19]3=[N:20][S:21][N:22]=[C:18]3[CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])[CH:9]=1)([O-])=O.O>CCOC(C)=O.C(Cl)Cl.Cl[Sn]Cl>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([C:23]([N:25]2[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]2)=[O:24])=[C:8]([NH:10][S:11]([C:14]2[C:19]3=[N:20][S:21][N:22]=[C:18]3[CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])[CH:9]=1
Reactant: O=C(c1ccc([N+](=O)[O-])cc1NS(=O)(=O)c1cccc2nsnc12)N1CCCCC1
Agent: Cl[Sn]Cl
Solvent: O
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: Nc1ccc(C(=O)N2CCCCC2)c(NS(=O)(=O)c2cccc3nsnc23)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 85 %

Procedure:
A solution of benzo[1,2,5]thiadiazole-4-sulfonic acid [5-nitro-2-(piperidine-1-carbonyl)-phenyl]-amide (EXAMPLE 2; 90 mg, 2.0 mmol) was dissolved in 1:1 EtOAc/DCM (10 mL), and SnCl2.2 H2O (2.3 g, 10 mmol) was added. The mixture was stirred overnight at ambient temperature then concentrated in vacuo. The resulting oil was suspended in DCM and neutralized by shaking with aqueous NaHCO3. The organic layer was dried (MgSO4), filtered and concentrated in vacuo to afford the title compound (69 mg, 1.7 mmol, 82%). TLC (silica gel, 3:1 EtOAc/hexanes): Rf=0.42. MS (ESI): m/z 418 [M+H]+, 440 [M+Na]+. HPLC (reversed-phase): RT=8.15 min (single peak). 1H NMR (400 MHz, CDCl3): (rotameric broadening) 9.80 (s, 1H), 8.40 (m, 2H), (dd, J=8.8 Hz, 1.0 Hz, 1H), 8.15 (dd, J=7.0 Hz, 1.0 Hz, 1H), 7.82 (dd, J=8.8 Hz, 1.0 Hz, 1H), 6.77 (d, J=8.4 Hz, 1H), 6.74 (d, J=2.2 Hz, 1H), 6.19 (dd, J=8.4 Hz, 2.3 Hz, 1H), 5.75 (d, J=2.3 Hz, 2H), 2.96 (bs, 4H), 1.45 (bs, 2H), 1.24 (bs, 4H).
Reaction SMILES: [Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[Si]([O:20][CH:21]([C:52](C)(C)C)[CH2:22][N:23]1[C:28](=[O:29])[C:27]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([C:37]3[C:38]([C:43]#[N:44])=[CH:39][CH:40]=[CH:41][CH:42]=3)=[CH:33][CH:32]=2)=[C:26]([CH2:45][CH2:46][CH3:47])[N:25]2[N:48]=[C:49]([CH3:51])[N:50]=[C:24]12)(C(C)(C)C)(C)C>O.C(OCC)(=O)C>[OH:20][CH:21]([CH3:52])[CH2:22][N:23]1[C:28](=[O:29])[C:27]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[C:43]3[NH:3][C:4](=[O:7])[O:5][N:44]=3)=[CH:33][CH:32]=2)=[C:26]([CH2:45][CH2:46][CH3:47])[N:25]2[N:48]=[C:49]([CH3:51])[N:50]=[C:24]12
Reactant: O=C([O-])O
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(CC(O[Si](C)(C)C(C)(C)C)C(C)(C)C)c2nc(C)nn12
Reactant: [NH3+]O
Agent: [Cl-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CS(C)=O
Product: CCCc1c(Cc2ccc(-c3ccccc3-c3noc(=O)[nH]3)cc2)c(=O)n(CC(C)O)c2nc(C)nn12
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 78.3 %

Procedure:
A mixture of hydroxylammonium chloride (1.6 g), sodium hydrogen carbonate (2.5 g) and dimethyl sulfoxide (10 mL) was stirred at 50° C. for 30 min, 4′-{[4-(2-{[tert-butyl(dimethyl)silyl]oxy}-3,3-dimethylbutyl)-2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (0.9 g) was added, and the mixture was stirred at 90° C. for 20 hr. After allowing to cool to room temperature, ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography, and dissolved in tetrahydrofuran (15 mL). N,N′-Carbonyldiimidazole (0.29 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.25 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 N hydrochloric acid and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (15 mL). Tetrabutylammonium fluoride (1 M tetrahydrofuran solution, 7.5 mL) was added and the mixture was stirred at 70° C. for 5 hr. The reaction mixture was extracted with ethyl acetate and water, and the organic layer was washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as a colorless amorphous solid (0.59 g, 72%).
Reaction SMILES: [N:1]([CH:4]([C:7]1[N:8]=[C:9]2[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[N:10]2[C:11](=[O:19])[C:12]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:5][CH3:6])=[N+]=[N-].CP(C)C.C(Cl)Cl>O1CCCC1.O>[NH2:1][CH:4]([C:7]1[N:8]=[C:9]2[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[N:10]2[C:11](=[O:19])[C:12]=1[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[CH2:5][CH3:6]
Reactant: CCC(N=[N+]=[N-])c1nc2cccc(C)n2c(=O)c1-c1ccccc1
Agent: CP(C)C
Solvent: C1CCOC1
Solvent: ClCCl
Solvent: O
Product: CCC(N)c1nc2cccc(C)n2c(=O)c1-c1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution of 2-(1-azidopropyl)-6-methyl-3-phenyl-4H-pyrido[1,2-a]pyrimidin-4-one (0.030 g, 0.094 mmol) in tetrahydrofuran (0.24 mL) and water (0.06 mL) was added 1.0 M of trimethylphosphine in tetrahydrofuran (0.11 mL) at room temperature and the mixture was stirred at room temperature for 1 hour. To the mixture was added methylene chloride and the mixture was washed with brine, dried over magnesium sulfate, and evaporated to dryness under reduced pressure. The crude residue was used directly in next step. LCMS calculated for C18H20N3O (M+H)+: m/z=294.2. Found: 294.3.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9](=O)[C:10]([OH:12])=[O:11])[CH:6]=[CH:7][CH:8]=1.C(=O)(O)[O-].[Na+].Cl.[CH2:20]([O:22][NH2:23])[CH3:21].Cl>O>[CH2:20]([O:22][N:23]=[C:9]([C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=1)[C:10]([OH:12])=[O:11])[CH3:21]
Reactant: COc1cccc(C(=O)C(=O)O)c1
Reactant: CCON
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: CCON=C(C(=O)O)c1cccc(OC)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 98.6 %

Procedure:
A solution of 2-(3-methoxyphenyl)glyoxylic acid (1.8 g.) in an aqueous solution of sodium bicarbonate was adjusted to pH 7.0. On the other hand, a solution of O-ethylhydroxylamine hydrochloride (1.4 g.) in water (20 ml.) was adjusted to pH 7.0 with sodium bicarbonate. Two solutions were combined together, adjusted to pH 5.5 with 10% hydrochloric acid and stirred overnight at ambient temperature. The reaction mixture was adjusted to pH 7.5 with sodium bicarbonate and washed with ethyl acetate. The aqueous layer was adjusted to pH 1.0 with conc. hydrochloric acid under ice-cooling and extracted with ethyl acetate. The extract was washed with ice-water and dried over magnesium sulfate. The solvent was distilled off under reduced pressure to give oil of 2-ethoxyimino-2-(3-methoxyphenyl)acetic acid (syn isomer) (2.2 g.).
Reaction SMILES: [C:1](#[N:5])[CH2:2][C:3]#[N:4].CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].[N:17]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[C:18]=[S:19].Br[CH2:27][C:28]([C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=1)=[O:29]>C(OCC)(=O)C>[NH2:4][C:3]1[C:2]([C:1]#[N:5])=[C:18]([NH:17][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[S:19][C:27]=1[C:28](=[O:29])[C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=1
Reactant: S=C=Nc1ccccc1
Reactant: Cc1ccc(C(=O)CBr)cc1
Reactant: N#CCC#N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1ccc(C(=O)c2sc(Nc3ccccc3)c(C#N)c2N)cc1

Procedure:
Malononitrile (0.661 g, 0.0100 mol) was dissolved in N,N-dimethylformamide (50 mL, 0.6 mol) and was stirred under an atmosphere of Argon. Potassium carbonate (1.52 g, 0.0110 mol) was added and was stirred for 30 minutes. Isothiocyanatobenzene (1.49 g, 0.0110 mol) was added and the reaction mixture was stirred for 2 hours. 2-Bromo-1-(4-methylphenyl)-ethanone, (2.34 g, 0.0110 mol) was added and the reaction mixture was allowed to stir overnight. The resultant dark red solution was diluted with 150 mL ethyl acetate and washed successively with 100 mL each of 1/2 saturated NaHCO3 solution, 1N LiCl (2×) and 1N Na2S2O3. The combined aqueous layers were discarded and the organic layer was dried, filtered, and evaporated to collect 1.46 g of the desired product as pale yellow-orange crystals. MS(ESI) [M+H+]+=334.2.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([S:21]([N:24](CC2C=CC(OC)=CC=2OC)[C:25]2[CH:30]=[CH:29][N:28]=[CH:27][N:26]=2)(=[O:23])=[O:22])[CH:6]=[CH:7][C:8]=1[O:9][C@H:10]1[CH2:14][CH2:13][CH2:12][C@@H:11]1[C:15]1[N:19]([CH3:20])[N:18]=[CH:17][CH:16]=1)#[N:2].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[C:1]([C:3]1[CH:4]=[C:5]([S:21]([NH:24][C:25]2[CH:30]=[CH:29][N:28]=[CH:27][N:26]=2)(=[O:23])=[O:22])[CH:6]=[CH:7][C:8]=1[O:9][C@H:10]1[CH2:14][CH2:13][CH2:12][C@@H:11]1[C:15]1[N:19]([CH3:20])[N:18]=[CH:17][CH:16]=1)#[N:2]
Reactant: COc1ccc(CN(c2ccncn2)S(=O)(=O)c2ccc(O[C@H]3CCC[C@@H]3c3ccnn3C)c(C#N)c2)c(OC)c1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cn1nccc1[C@H]1CCC[C@@H]1Oc1ccc(S(=O)(=O)Nc2ccncn2)cc1C#N
Yield: 78.5 %

Procedure:
The reaction and aftertreatment were conducted in the same manner as in Example 1b by using 3-cyano-N-(2,4-dimethoxybenzyl)-4-{[(1S*,2R*)-2-(1-methyl-1H-pyrazol-5-yl)cyclopentyl]oxy}-N-(pyrimidin-4-yl)benzenesulfonamide (91.0 mg, 0.16 mmol) prepared in Example 26b, triethylsilane (0.10 mL), trifluoroacetic acid (1.0 mL) and dichloromethane (1.0 mL), to yield the title compound (53.3 mg, 79%) as a colorless solid.
Reaction SMILES: O[Li].O.[NH:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5]1.Br[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16].[Cl:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Br)=[CH:23][CH:22]=1>CN(C=O)C>[Cl:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][CH:14]([N:4]2[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[CH2:6][CH2:5]2)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:23][CH:22]=1
Reactant: c1ccc2c(c1)CCN2
Reactant: Clc1ccc(CBr)cc1
Reactant: CCOC(=O)CBr
Agent: [Li]O
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)C(Cc1ccc(Cl)cc1)N1CCc2ccccc21
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
In an oven-dried flask under an atmosphere of nitrogen, 1.1 g LiOH.H2O (26.25 mmol) in DMF (20 mL) was added to a stirring suspension of 4 angstrom molecular sieves. After 30 minutes of stirring at room temperature 2.8 mL (25 mmol) indoline was added dropwise. After one hour at room temperature 2.9 mL (26.25 mmol) Ethyl bromoacetate was added dropwise. After 1.5 h the solid material was filtered and the residue was washed with copious amounts of EtOAc. The organics were washed 3 times with water and the organic material was dried over MgSO4. The solvents were evaporated under reduced pressure. The crude material was then dissolved in 75 mL anhydrous THF, charged into an oven dried round bottom under an atmosphere of nitrogen, cooled to −78° C., and then treated with 26.25 mL a 1M solution of NaHMDS. The solution was allowed to stir for 30 minutes at −78° C. after which the enolate was quenched with 5.4 g (26.25 mmol) of parachlorobenzyl bromide (solution in 25 mL anhydrous THF). The reaction was allowed to warm to room temperature overnight. The next day the reaction was quenched with water. The aqueous layer was extracted with 3 large portions of EtOAc. The combined organics were dried over MgSO4. The solvents were removed under reduced pressure and the residue was purified by flash chromatography which yielded the title compound as a yellow oil. LC/MS m/e=331 (M+1). TLC Rf=0.22 (20:1 hexanes:EtOAc). 1H NMR (500 MHz, CDCl3): δ 1.11 (t, J=3.55 Hz, 3H), 2.96 (m, 2H), 3.06 (m, 1H), 3.25 (m, 1H), 3.60 (t, 2H), 4.07 (m, 2H), 4.36 (t, J=3.75 Hz, 1H).
Reaction SMILES: [NH3:1].[Cl:2][C:3]1[N:8]=[C:7]([Cl:9])[CH:6]=[C:5](OC(F)(F)F)[N:4]=1>C(OC)(C)(C)C>[NH2:1][C:7]1([Cl:9])[CH:6]=[CH:5][N:4]=[C:3]([Cl:2])[NH:8]1
Reactant: N
Reactant: FC(F)(F)Oc1cc(Cl)nc(Cl)n1
Solvent: COC(C)(C)C
Product: NC1(Cl)C=CN=C(Cl)N1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 32.5 %

Procedure:
At -50° to -45° C. and over a period of 45 minutes, 4.3 g (0.25 mol) of gaseous ammonia was passed, while stirring, into a mixture of 23.3 g (0.1 mol) of 2,4-dichloro-6-trifluoromethoxypyrimidine in 150 ml of methyl tert-butyl ether. The mixture was stirred for 30 minutes at -50° C., 1 hour at -30° C. and for 1 hour at 25° C. The precipitate was suction filtered, washed with water and dried, giving 5.4 g (33.1% of theory) of 4-amino-2,4-dichloropyrimidine of melting point 270°-272° C. as byproduct. The filtrate was washed with water, dried, evaporated down partially under reduced pressure, and fractionally chromatographed with a 5:1 ligroin/ether mixture, the first fractions giving 3 g (12.81% of theory) of the starting material as a colorless oil and the last runnings 9 g (42% of theory) of the title compound as colorless crystals of melting point 55°-56° C. The conversion was 48.3%.
Reaction SMILES: [C:1]([O:5][C:6](=[O:35])[CH:7]=[CH:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][Si:16]([C:29]([CH3:32])([CH3:31])[CH3:30])([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:11][C:10]=1[CH:33]=[O:34])([CH3:4])([CH3:3])[CH3:2].C1COCC1.CO.[H][H]>[Pd].C(N(CC)CC)C>[C:1]([O:5][C:6](=[O:35])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][Si:16]([C:29]([CH3:32])([CH3:31])[CH3:30])([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:11][C:10]=1[CH2:33][OH:34])([CH3:4])([CH3:2])[CH3:3]
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)C=Cc1ccc(O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)cc1C=O
Agent: [Pd]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)(C)OC(=O)CCc1ccc(O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)cc1CO

Procedure:
A 500 mL Parr hydrogenation bottle was charged with 3-[4-(tert-butyldiphenylsilanyloxy)-2-formylphenyl]acrylic acid tert-butyl ester (18.3 g, 37.6 mmol), THF (60 mL), and methanol (120 mL). Triethylamine (2 mL) and then 5% Pd/C (5.9 g) were added. The mixture was shaken with hydrogen at 60 psi pressure for 48 h. The mixture was filtered through Celite and concentrated to an oil. This oil was purified using the Biotage medium pressure chromatography (EtOAc:hexanes 15:85) to a pale yellow oil (12.8 g, 69%). 1H NMR (400 MHz, CDCl3) δ 1.09 (s, 9H), 1.35 (s, 9H), 2.49 (t, J=7.6 Hz, 2H), 2.83 (t, J=7.6 Hz, 2H), 4.55 (s, 2H), 6.56 (dd, J=8.3, 2.4 Hz, 1H), 6.83 (d, J=2.9 Hz, 1H), 6.87 (d, J=8.3 Hz, 1H), 7.33-7.44 (m, 6H), 7.70 (dd, J=7.8, 1.5 Hz, 4H). MS (ES) m/e 508 (M+NH4).
Reaction SMILES: N1C=CC=CC=1.[C:7]1([C:13]#[C:14][C:15]#[C:16][C:17]#[C:18][C@@H:19]2[O:21][C@H:20]2[CH2:22][OH:23])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>C(Cl)Cl.[O-2].[O-2].[O-2].[Cr+6]>[C:7]1([C:13]#[C:14][C:15]#[C:16][C:17]#[C:18][C@@H:19]2[O:21][C@H:20]2[CH:22]=[O:23])[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: OC[C@@H]1O[C@H]1C#CC#CC#Cc1ccccc1
Agent: [Cr+6]
Agent: [O-2]
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C[C@@H]1O[C@H]1C#CC#CC#Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 43.7 %

Procedure:
Chromium trioxide (951 mg, 9.51 mmole; dried in vacuo over phosphorous pentoxide) was added to a stirred solution of 1.49 g (18.88 mmole) of dry pyridine in 25 ml of dry methylene chloride. The deep red solution was stirred for 15 minutes at room temperature. A solution of (trans)-3-(6-phenyl-1,3,5-hexatriynyl)oxiranemethanol (300 mg, 1.35 mmole; see example 3) in 5 ml of dry methylene chloride was then added in one portion. A tarry, black deposit separated immediately. After stirring for 20 minutes at room temperature, the solution was decanted and filtered through a pad of silica gel. Several portions of ether were then passed through the silica gel. Solvent was removed from the combined filtrates and the residue was chromatographed on silica gel (ether-hexane) to afford 130 mg of the title compound.
Reaction SMILES: [N:1]([C@@H:4]([CH3:22])[CH2:5][N:6]1[C:10]2=[CH:11][C:12]3[C:17]([C:16]([CH3:19])([CH3:18])[CH:15]=[CH:14][C:13]=3[O:20][CH3:21])=[C:9]2[CH:8]=[N:7]1)=[N+]=[N-].[C:23]([OH:30])(=[O:29])/[CH:24]=[CH:25]/[C:26]([OH:28])=[O:27]>C(O)C.C(OCC)C.CO.[Pt]=O>[C:23]([OH:30])(=[O:29])/[CH:24]=[CH:25]/[C:26]([OH:28])=[O:27].[CH3:21][O:20][C:13]1[CH:14]=[CH:15][C:16]([CH3:19])([CH3:18])[C:17]2[C:12]=1[CH:11]=[C:10]1[C:9]=2[CH:8]=[N:7][N:6]1[CH2:5][C@@H:4]([NH2:1])[CH3:22]
Reactant: COC1=C2C=c3c(cnn3C[C@H](C)N=[N+]=[N-])=C2C(C)(C)C=C1
Agent: O=[Pt]
Agent: O=C(O)/C=C/C(=O)O
Solvent: CO
Solvent: CCO
Solvent: CCOCC
Product: COC1=C2C=c3c(cnn3C[C@H](C)N)=C2C(C)(C)C=C1
Temperature: 25 °C
Reaction time: 18 h
Yield: 69 %

Procedure:
1.38 g (4.6 mmol) of (S)-1-(2-azido-propyl)-7-methoxy-4,4-dimethyl-1,4-dihydro-indeno[2,1-c]pyrazole dissolved in 50 ml of anhydrous ethanol were hydrogenated over 140 mg of platinum oxide for 1.5 hours. The catalyst was subsequently filtered off, rinsed with ethanol and the solvent was removed in a vacuum. The colorless oil obtained was dissolved in 80 ml of anhydrous diethyl ether, filtered and treated while stirring with a solution of 534 mg (4.6 mmol) of fumaric acid in 10 ml of methanol. The mixture was stirred at room temperature for 18 hours and the white crystals were subsequently filtered off. 1.23 g (69%) of (S)-2-(7-methoxy-4,4-dimethyl-1,4-dihydroindeno[2,1-c]pyrazol-1-yl)-1-methyl-ethylamine fumarate (1:1) with m.p. 160°-162° were obtained.