Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([C:5](=[C:20]([CH2:24][CH2:25][OH:26])[CH2:21][CH2:22][OH:23])[O:6][SiH:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(C)(C)C.[CH3:27][S:28](Cl)(=[O:30])=[O:29]>CCOCC>[CH3:27][S:28]([O:26][CH2:25][CH2:24][C:20](=[CH:5][O:6][Si:7]([C:20]([CH3:24])([CH3:21])[CH3:5])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[CH2:21][CH2:22][O:23][S:28]([CH3:27])(=[O:30])=[O:29])(=[O:30])=[O:29]
Reactant: CC(C)(C)C(O[SiH](c1ccccc1)c1ccccc1)=C(CCO)CCO
Reactant: CS(=O)(=O)Cl
Solvent: CCOCC
Product: CC(C)(C)[Si](OC=C(CCOS(C)(=O)=O)CCOS(C)(=O)=O)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 9.5 h
Yield: 169.9 %

Procedure:
To a 0° C. ether (300 mL) solution of 3-(tertbutyldiphenylsilyloxymethylene)-pentane-1,5-diol (6.9 g, 19 mmol) was added methanesulfonyl chloride (4.3 mL, 56 mmol) followed by Et3 N (7.7 mL, 56 mmol). After 3-16 hours, gradually warming to ambient temperature, the reaction was washed with water, brine, dried over MgSO4, and concentrated to give the 1,5-bis(methanesulfonyloxy)-3-(tert-butyldiphenylsilyoxymethylene)-pentane 8.5g (90%) as a colorless oil that was used without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][CH:4]=1.O=[C:11]1[CH2:16][CH2:15][N:14]([C@H:17]([CH3:21])[CH2:18][C:19]#[N:20])[CH2:13][CH2:12]1>>[NH2:20][CH2:19][CH2:18][C@H:17]([N:14]1[CH2:15][CH2:16][CH:11]([NH:9][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH2:12][CH2:13]1)[CH3:21]
Reactant: COc1ccc(N)cc1
Reactant: C[C@H](CC#N)N1CCC(=O)CC1
Product: COc1ccc(NC2CCN([C@H](C)CCN)CC2)cc1

Procedure:
Using general procedure A with p-anisidine (738 mg, 6.00 mmol) and (R)-3-(4-oxo-piperidin-1-yl)-butyronitrile (1.11 g, 6.67 mmol) followed by general procedure J gave [1-((R)-3-amino-1-methyl-propyl)-piperidin-4-yl]-(4-methoxy-phenyl)-amine as an orange oil (1.43 g, 86% over 2 steps).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([O:12][CH2:13][CH3:14])[CH:11]=1)[CH:7]=O)[CH3:2].[C:15](#[N:19])[CH2:16][C:17]#[N:18]>C(O)CC.[OH-].[K+]>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([O:12][CH2:13][CH3:14])[CH:11]=1)[CH:7]=[C:16]([C:15]#[N:19])[C:17]#[N:18])[CH3:2]
Reactant: N#CCC#N
Reactant: CCOc1cc(C=O)cc(OCC)c1
Agent: [K+]
Agent: [OH-]
Solvent: CCCO
Product: CCOc1cc(C=C(C#N)C#N)cc(OCC)c1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To an amount of 56c (1.0 g, 5.15 mmole) of 3,5-diethoxybenzaldehyde dissolved in 10 mL of propanol, was added malononitrile (375 mg, 5.67 mmole) and 2 drops of sat. KOH. The mixture was stirred at r.t. for 10 mins. Precipitates was filtered to yield 1.0 g of 2-(3,5-diethoxybenzylidene)malononitrile (56d). MS [m+H] calc'd for C14H14N2O2, 243.11; found 243.11.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][NH2:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:10](Cl)(=[O:12])[CH3:11].O>C(Cl)Cl>[CH2:8]([NH:9][C:10](=[O:12])[CH3:11])[CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NCCc1ccccc1
Reactant: CC(=O)Cl
Solvent: O
Solvent: ClCCl
Product: CC(=O)NCCc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 90 %

Procedure:
To a solution of 2-phenylethanamine (5.00 g, 41.32 mmol) and TEA (6.26 g, 61.98 mmol) in anhydrous DCM (50 mL) was added dropwise acetyl chloride (3.57 g, 45.45 mmol) at 0° C. The resulting reaction mixture was stirred at room temperature for 30 min. Water was added and the mixture was extracted with DCM. The combined organic layers were washed with saturated aqueous ammonium chloride, brine and concentrated to give the title product as a yellow oil (6.06 g, 37.19 mmol, 90% yield). MS (ESI) m/z 164.1 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([CH3:10])=[CH:7][C:6]=2[CH:11]=1.C1C(=O)N([Br:19])C(=O)C1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:19][CH2:10][C:8]1[S:9][C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:11][C:6]=2[CH:7]=1
Reactant: Cc1cc2cc(Cl)ccc2s1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: Clc1ccc2sc(CBr)cc2c1
Yield: 97.2 %

Procedure:
A solution of 2.73 g (14.95 mmol) 5-chloro-2-methylbenzothiophene and 2.67 g (15.0 mmol) NBS in 100 ml carbon tetrachloride was heated to 70° C. and a catalytic amount of dibenzoyl peroxide was added. After 30 min reflux solids were removed by filtration. The solvent was removed in vacuo and the residue was suspended in 100 ml hot hexane and filtered. The filtrate was evaporated to dryness to give 3.8 g (97%) of the title compound as a colorless solid.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:21]([CH3:23])[CH3:22])[C:6]2[O:10][C:9]([C:11]3[CH:19]=[CH:18][C:14]([C:15](O)=[O:16])=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:20]=1)#[N:2].[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34]([CH:37]([NH2:42])[C:38]([O:40][CH3:41])=[O:39])[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34]([CH:37]([NH:42][C:15](=[O:16])[C:14]2[CH:13]=[CH:12][C:11]([C:9]3[O:10][C:6]4[C:5]([CH:21]([CH3:23])[CH3:22])=[CH:4][C:3]([C:1]#[N:2])=[CH:20][C:7]=4[N:8]=3)=[CH:19][CH:18]=2)[C:38]([O:40][CH3:41])=[O:39])[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25]
Reactant: COC(=O)C(N)C1CCN(C(=O)OC(C)(C)C)CC1
Reactant: CC(C)c1cc(C#N)cc2nc(-c3ccc(C(=O)O)cc3)oc12
Agent: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)C(NC(=O)c1ccc(-c2nc3cc(C#N)cc(C(C)C)c3o2)cc1)C1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
At room temperature, a 2-dram vial equipped with a magnetic stirrer was charged with 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoic acid (INTERMEDIATE 2), 4-(amino-methoxycarbonyl-methyl)-piperidine-1-carboxylic acid tert-butyl ester, bromo-tris-pyrrolidino phosphonium hexafluorophosphate, and dimethylformamide (5 ml). To this mixture was added of N,N-diisopropylethylamine, dropwise. The reaction mixture was allowed to stir at room temperature for 3 d. The residue was purified by flash chromatography using a Biotage SP 1, 40M silica cartridge, eluting with a linear gradient of 20% to 100% hexanes in ethyl acetate over 15 column volumes to provide the title compound. Mass spectrum (ESI) 559.3 (M+1).
Reaction SMILES: C1(C)C=CC=CC=1.[CH3:8][C:9]1[CH:14]=[C:13]([CH3:15])[C:12]([S:16][CH2:17][C:18]([F:21])([F:20])[F:19])=[CH:11][C:10]=1B1OC(C)(C)C(C)(C)O1.C[N+]1([O-])CC[O:35]CC1.CCCCCC>C(OCC)(=O)C>[CH3:8][C:9]1[CH:14]=[C:13]([CH3:15])[C:12]([S:16][CH2:17][C:18]([F:21])([F:20])[F:19])=[CH:11][C:10]=1[OH:35]
Reactant: C[N+]1([O-])CCOCC1
Reactant: Cc1cc(C)c(B2OC(C)(C)C(C)(C)O2)cc1SCC(F)(F)F
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Solvent: CCCCCC
Product: Cc1cc(C)c(SCC(F)(F)F)cc1O
Temperature: 25 °C
Yield: 76.3 %

Procedure:
To 200 ml of toluene were added 20.24 g (58.5 mmol) of [2,4-dimethyl-5-(2,2,2-trifluoroethylthio)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (a compound described in PCT International Publication No. WO 2012/176856 as Compound No. 55-47) and 8.22 g (70.16 mmol) of N-methylmorpholine-N-oxide. The mixture was refluxed for 2 hours under heating. The reaction mixture was allowed to cool to room temperature, washed and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (developing solvent: a mixed solvent of n-hexane:ethyl acetate=20:1), to obtain 10.54 g (yield: 76%) of an intended product.
Reaction SMILES: [C:1]([O:5][C:6](=[O:28])[CH2:7][C@H:8]([C:18]1[O:22][N:21]=[C:20]([C:23](OCC)=[O:24])[N:19]=1)[CH2:9][CH2:10][CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[N:31]1[C:40]2[CH2:39][CH2:38][NH:37][CH2:36][C:35]=2[CH:34]=[CH:33][CH:32]=1.C(N(CC)CC)C>C(O)C>[CH:12]1([CH2:11][CH2:10][CH2:9][C@@H:8]([C:18]2[O:22][N:21]=[C:20]([C:23]([N:37]3[CH2:38][CH2:39][C:40]4[N:31]=[CH:32][CH:33]=[CH:34][C:35]=4[CH2:36]3)=[O:24])[N:19]=2)[CH2:7][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:28])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]1
Reactant: c1cnc2c(c1)CNCC2
Reactant: CCOC(=O)c1noc([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)n1
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)C[C@@H](CCCC1CCCCC1)c1nc(C(=O)N2CCc3ncccc3C2)no1
Temperature: 60 °C
Yield: 76.6 %

Procedure:
A solution of ethyl 5-{(1R)-1-[2-(tert-butoxy)-2-oxoethyl]-4-cyclohexylbutyl}-1,2,4-oxadiazole-3-carboxylate (Preparation 3) (300 mg, 0.76 mmol) in ethanol (4 ml) was treated with 5,6,7,8-tetrahydro[1,6]naphthyridine dihydrochloride (Chem.Pharm.Bull.; 32; 7; 1984; 2522-2529) (0.79 g, 3.80 mmol) and triethylamine (1.27 ml, 9.13 mmol) and the resulting mixture was heated at 60° C. under a nitrogen atmosphere for 16 hours. The mixture was cooled and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:ethyl acetate (90:10) gradually changing to dichloromethane:ethyl acetate (50:50) to afford the title compound (281 mg).
Reaction SMILES: [NH2:1][C:2]1[NH:3][C:4]([C:9]#[N:10])=[C:5]([C:7]#[N:8])[N:6]=1.Cl.N([O-])=O.[Na+].S([O-])([O-])=O.[Na+].[Na+].[N+:22](=[C:24]1[N:28]=[C:27]([C:29]#[N:30])[C:26]([C:31]#[N:32])=[N:25]1)=[N-]>O>[N:22]([C:24]1[NH:25][C:26]([C:31]#[N:32])=[C:27]([C:29]#[N:30])[N:28]=1)=[N:1][C:2]1[NH:3][C:4]([C:9]#[N:10])=[C:5]([C:7]#[N:8])[N:6]=1
Reactant: N#Cc1nc(N)[nH]c1C#N
Reactant: N#CC1=NC(=[N+]=[N-])N=C1C#N
Agent: Cl
Agent: O=N[O-]
Agent: O=S([O-])[O-]
Solvent: O
Product: N#Cc1nc(N=Nc2nc(C#N)c(C#N)[nH]2)[nH]c1C#N
Reaction time: 1 h

Procedure:
In a glass reactor 7.98 g (60 mmol) 2-amino-4,5-dicyanoimidazole was dissolved in 200 ml water plus 45 ml conc. hydrochloric acid. At 0° the stirred solution was diazotized over ~ 10 minutes by the slow addition of 6.0 g sodium nitrite dissolved in 15 ml water. The mixture was stirred for 1 hour at 0° to insure complete reaction. Then 7.52 g (60 mmol) anhydrous sodium sulfite dissolved in ~40 ml of water was added at once to the vigorously stirred suspension of 2-diazo-4,5-dicyanoimidazole. The bright yellow mixture was stirred for 30 minutes at 0° and filtered. The yellow cake was washed with a little cold water and air dried. This procedure was repeated two more times giving a total of 15.4 g of crude material. The crude product was recrystallized from boiling water (~600 ml). The hot solution was filtered. The yellow filtrate deposited golden plates on cooling. The product was collected at 0°, washed with a little ice water and dried in a vacuum oven at 70°. This gave 9.6g (41%) of 2,2'-azobis(4,5-imidazoledicarbonitrile); mp >300°.
Reaction SMILES: [CH:1]1([C:6]([O:8][CH3:9])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].CC([N-]C(C)C)C.Br.Br[CH2:20][CH2:21][N:22]([CH2:25][CH3:26])[CH2:23][CH3:24]>C1COCC1.O>[CH2:21]([N:22]([CH2:25][CH3:26])[CH2:23][CH2:24][C:1]1([C:6]([O:8][CH3:9])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1)[CH3:20]
Reactant: CCN(CC)CCBr
Reactant: COC(=O)C1CCCC1
Agent: Br
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: CCN(CC)CCC1(C(=O)OC)CCCC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 79 %

Procedure:
To methyl cyclopentanecarboxylate (1 g) in THF (8 ml) at −61° C. is added a solution of 2M LDA (9.8 ml). The mixture is stirred at room temperature for 15 minutes, then 2-bromo-N,N-diethylethanamine hydrobromide (2.04 g) is added at −61° C. The mixture is stirred for 5 minutes at this temperature, then at room temperature. The solution became yellow and was diluted with water (30 ml). The organic phase is extracted twice with a brine solution (30 ml). The pH of the organic phase is adjusted to 4 with 6N HCl. After decantation, the aqueous phase is extracted with CH2Cl2 (20 ml) and the pH of aqueous phase adjusted to 12 with 6 N NaOH. After decantation, the organic phase is dried over MgSO4 and concentrated. The residue is treated with diethyl ether (10 ml) and the white solid is filtrated. Methyl 1-[2-(diethylamino)ethyl]cyclopentanecarboxylate 280 is obtained as a yellow liquid after concentration of the ether solution.
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:15])[CH2:10][CH2:11][C:12](O)=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C([Cl:19])=O>C1C=CC=CC=1>[Cl:19][C:12]([CH2:11][CH2:10][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:15])=[O:13]
Reactant: O=C(O)CCC(=O)OCc1ccccc1
Reactant: O=C(Cl)C(=O)Cl
Solvent: c1ccccc1
Product: O=C(Cl)CCC(=O)OCc1ccccc1
Reaction time: 5 h

Procedure:
To a solution of 5 g of succinic acid monobenzyl ester in 60 ml of benzene was added 11 ml of oxalyl chloride. After 5 hrs at 20° C., gas evolution ceased and the solvent and excess oxalyl chloride was evaporated at 20° C. The residue was held at 1 torr for 1 hr to yield 5.19 g of crude benzyl 3-chloroformylpropionate; ir 1788 and 1735 cm-1.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[O:12])[N:10]([CH2:13][CH3:14])[C:8](=[O:9])[C:7]2=[CH:15][CH:16]=1)([O-])=O.[H][H]>N.O[V](=O)=O.[O-2].[O-2].[Ti+4].[Pd].O>[NH2:1][C:4]1[CH:5]=[C:6]2[C:11](=[O:12])[N:10]([CH2:13][CH3:14])[C:8](=[O:9])[C:7]2=[CH:15][CH:16]=1
Reactant: [H][H]
Reactant: CCN1C(=O)c2ccc([N+](=O)[O-])cc2C1=O
Agent: O=[V](=O)O
Agent: [Pd]
Agent: [Ti+4]
Solvent: O
Product: CCN1C(=O)c2ccc(N)cc2C1=O
Temperature: 65 °C
Reaction time: 42 h
Yield: 84.2 %

Procedure:
0.001 g of ammonium vanadate and 0.5 g of titanium dioxide extrudate containing 1% by weight of metallic palladium and having a particle size of 3 mm (from Johnson Matthey) are added to a suspension consisting of 50 ml of water and 2.2 g of 4-nitro-N-ethylphthalimide. After displacing the air with nitrogen, the latter is replaced by hydrogen at atmospheric pressure and the suspension is stirred at 65° C. for 42 hours. During this time, 95% of the theoretical amount of hydrogen, based on the 4-nitro-N-ethylphthalimide, is absorbed. The resulting suspension is then sieved through a sieve having a mesh width of 1 mm. The material remaining on the sieve is washed with 50 ml of water and the combined aqueous phases are then filtered through a paper filter and washed with 250 ml of water. Drying at 80° C. under reduced pressure (125 mbar) gives 1.6 g (84%) of 4-amino-N-ethylphthalimide.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:10]=[C:11]=[O:12])[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8].[F:13][C:14]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:15]=1[C:16]([NH2:18])=[O:17]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]([NH:18][C:16](=[O:17])[C:15]2[C:14]([F:13])=[CH:22][CH:21]=[CH:20][C:19]=2[F:23])=[O:12])[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8]
Reactant: O=C=Nc1cc(Cl)c(Cl)c(Cl)c1
Reactant: NC(=O)c1c(F)cccc1F
Solvent: Cc1ccccc1
Product: O=C(NC(=O)c1c(F)cccc1F)Nc1cc(Cl)c(Cl)c(Cl)c1

Procedure:
A solution of 3,4,5-trichloro-phenyl isocyanate (22.3 g), 2,6-difluoro-benzamide (15.7 g) in toluene (200 ml) was heated for eight hours at 90°-95° C. The title compound slowly crystallized out of the initially clear solution and was isolated by suction filtration after cooling of the reaction mixture.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([S:21][CH3:22])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[CH2:24][C:25]1[CH:30]=[CH:29][N:28]=[C:27]([C:31]2[CH:36]=[C:35]([O:37][CH3:38])[C:34]([O:39][CH3:40])=[C:33]([O:41][CH3:42])[CH:32]=2)[CH:26]=1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([C:15]2[CH:20]=[CH:19][C:18]([S:21][CH3:22])=[CH:17][CH:16]=2)[CH2:24][C:25]2[CH:30]=[CH:29][N:28]=[C:27]([C:31]3[CH:36]=[C:35]([O:37][CH3:38])[C:34]([O:39][CH3:40])=[C:33]([O:41][CH3:42])[CH:32]=3)[CH:26]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1cc(-c2cc(CCl)ccn2)cc(OC)c1OC
Reactant: CSc1ccc(NC2CCN(C(=O)OC(C)(C)C)CC2)cc1
Product: COc1cc(-c2cc(CN(c3ccc(SC)cc3)C3CCN(C(=O)OC(C)(C)C)CC3)ccn2)cc(OC)c1OC

Procedure:
1-(tert-Butoxycarbonyl)-4-[[4-(methylthio)phenyl]amino]piperidine (644 mg) and 4-chloromethyl-2-(3,4,5-trimethoxyphenyl)pyridine (588 mg) was treated in the same manner as described in Example 9 to give light yellow amorphous of the title compound.
Reaction SMILES: Br[C:2]1[C:3]2[C:8]([CH:9]=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[CH3:16][Si:17]([C:20]#[CH:21])([CH3:19])[CH3:18]>C(NC(C)C)(C)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I>[CH3:16][Si:17]([CH3:19])([CH3:18])[C:20]1[C:4]2[C:3]([CH:2]=[C:15]3[C:21]=1[C:11]([C:10]#[CH:9])=[CH:12][CH:13]=[CH:14]3)=[CH:8][CH:7]=[CH:6][CH:5]=2
Reactant: Brc1c2ccccc2cc2ccccc12
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: I[Cu]I
Solvent: CC(C)NC(C)C
Product: C#Cc1cccc2cc3ccccc3c([Si](C)(C)C)c12
Temperature: 80 °C
Yield: 75.2 %

Procedure:
Under an argon atmosphere, 40 g (0.155 mol) of 9-bromoanthracene, 3.3 g (4.6 mmol) of bis(triphenylphosphine)palladium(II) dichloride and 0.87 g (3 mmol) of copper Iodide were dissolved in 500 ml of diisopropylamine in a 1 L 3-necked flask equipped with a stirrer, thermometer and reflux condenser. 23 g (0.233 mol) of trimethylsilyl acetylene was then slowly dropped into the resulting mixture at room temperature. The reaction mixture was slowly heated to 80° C. and refluxed for 12 hours. After the reaction was completed, the reaction mixture was cooled down to room temperature, and then the precipitated salt was filtered off. The solvent was removed under a reduced pressure, and then the residue was dissolved in methylene chloride. The organic layer was washed with water several times and then dried with anhydrous magnesium sulfate. The solvent was removed to obtain orange-colored liquid, which was purified by silica gel column chromatography using hexane as an eluent, and then recrystallized from ethanol to give yellow crystal. The yellow crystal was recovered and sufficiently dried in a vacuum oven at 40° C., to give 32 g (83.3% yield) of the desired product having a melting point of 66-68° C.
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1(Cl)[CH2:9][CH2:8][CH2:7][C:6]([Cl:11])([F:10])[CH:5]1O.CC[O:16]CC>O>[Cl:3][C:4]12[O:16][CH:9]1[CH2:8][CH2:7][C:6]([Cl:11])([F:10])[CH2:5]2
Reactant: CCOCC
Reactant: OC1C(F)(Cl)CCCC1(Cl)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: FC1(Cl)CCC2OC2(Cl)C1
Reaction time: 0.25 h

Procedure:
0.85 g (21.3 mmol) of sodium hydroxide pellets were added in three portions to 1.6 g (7.22 mmol) of pure alcohol 1f in suspension in 22 cm3 of distilled water at 15°-20° C. The reaction mixture was kept at room temperature for 1 h 15 min, 10 cm3 of ether were then added, stirring was continued for 5 min and then the aqueous phase was separated off and extracted with ether (5×25 cm3). The ether phases were combined, dried over magnesium sulfate and filtered, and the solvent was evaporated off. 1.28 g of a liquid, the epoxide 2e, were obtained; the crude yield was 96% (macrobore GC purity>98%).
Reaction SMILES: C(OC[C@H:10]1[C@@H:14]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH2:13][C@H:12]([NH:23][CH:24]2[N:29]([C@@H:30]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH2:32][C@@H:31]3[O:39][CH3:40])[C:28]([NH2:41])=[N:27][C:26](Cl)=[N:25]2)[CH2:11]1)C1C=CC=CC=1.[C:43]([O-:46])(O)=O.[Na+]>CO.C(Cl)Cl.[Pd]>[Si:16]([O:15][C@H:14]1[CH2:13][C@H:12]([NH:23][C:24]2[N:41]=[C:28]([NH:29][C@@H:30]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH2:32][C@@H:31]3[O:39][CH3:40])[N:27]=[CH:26][N:25]=2)[CH2:11][C@H:10]1[CH2:43][OH:46])([C:19]([CH3:21])([CH3:20])[CH3:22])([CH3:18])[CH3:17]
Reactant: O=C([O-])O
Reactant: CO[C@H]1Cc2ccccc2[C@H]1N1C(N)=NC(Cl)=NC1N[C@@H]1C[C@@H](COCc2ccccc2)[C@@H](O[Si](C)(C)C(C)(C)C)C1
Agent: [Pd]
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: CO[C@H]1Cc2ccccc2[C@H]1Nc1ncnc(N[C@@H]2C[C@@H](CO)[C@@H](O[Si](C)(C)C(C)(C)C)C2)n1
Reaction time: 48 h
Yield: 57 %

Procedure:
A suspension of N-((1R,3S,4S)-3-[(benzyloxy)methyl]-4-{[tert-butyl(dimethyl)-silyl]oxy}cyclopentyl)-6-chloro-M-[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]-1,3,5-triazine-2,4-diamine (250 mg, 0.00041 mol) and 10% Pd/C (44 mg, 0.000041 mol) in methanol (1.61 mL) was stirred under an atmosphere of hydrogen for 2 days. The reaction was purged with nitrogen and filtered through celite with EtOAc. The filtrate was concentrated to obtain a yellow oil. The oil was taken up in CH2Cl2 and saturated NaHCO3. The layers were separated and the aqueous was extracted with CH2Cl2 (1×). The combined organics were dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography (0 to 10% MeOH/CH2Cl2) to obtain 114 mg (57%) of the title compound. LC/MS: Rt=1.68 min, ES+ 486 (FA standard).
Reaction SMILES: [CH3:1][N:2]([CH3:16])[C:3]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]1.[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([Mg]Br)=[CH:21][CH:20]=1.[NH4+].[Cl-]>O1CCCC1.O=O>[CH3:1][N:2]([CH3:16])[C:3]1([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:8][CH2:7][C:6]([C:22]2[CH:23]=[CH:24][C:19]([O:18][CH3:17])=[CH:20][CH:21]=2)([OH:9])[CH2:5][CH2:4]1
Reactant: CN(C)C1(c2ccccc2)CCC(=O)CC1
Reactant: COc1ccc([Mg]Br)cc1
Agent: O=O
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: COc1ccc(C2(O)CCC(c3ccccc3)(N(C)C)CC2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
4-(dimethylamino)-4-phenylcyclohexanone (4.34 g, 20 mmol) was dissolved in absolute tetrahydrofuran (60 ml) with the exclusion of oxygen, mixed with 4-methoxy phenyl magnesium bromide solution (90 ml, 45 mmol, 0.5N) with ice cooling and boiled for 2 h with reflux. For work up the batch was mixed with saturated NH4Cl solution (50 ml) with ice cooling and stirred for 10 min at room temperature. The aqueous phase was separated off and extracted with ethyl acetate (3×25 ml). The combined organic phases were dried over Na2SO4 and then concentrated to low volume. A raw product was isolated that was purified by chromatography [silica gel 60 (50 g); ethyl acetate (1000 ml), methanol (1000 ml)]. 2.016 g (31%, mp 174-175° C.) of more non-polar and 2.51 g (39%, mp 149-151° C.) of more polar product were obtained. Both could be recrystallised from ethyl acetate.
Reaction SMILES: C(=O)([O-])O.[Na+].[CH3:6][N:7]([CH2:9][CH2:10][CH:11]=[C:12]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[CH:20]=[CH:19][C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]1=2)C.Cl.ClC(OCC)=O.[OH-].[K+]>C(Cl)(Cl)Cl.O.C(O)CCC>[CH:17]1[C:18]2[CH:19]=[CH:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:12](=[CH:11][CH2:10][CH2:9][NH:7][CH3:6])[C:13]=2[CH:14]=[CH:15][CH:16]=1
Reactant: CN(C)CCC=C1c2ccccc2C=Cc2ccccc21
Agent: CCOC(=O)Cl
Agent: Cl
Agent: O=C([O-])O
Solvent: ClC(Cl)Cl
Solvent: CCCCO
Solvent: O
Product: CNCCC=C1c2ccccc2C=Cc2ccccc21
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
20 ml of saturated aqueous sodium hydrogencarbonate solution was added to 2.467 g (7.91 mmol) of cyclobenzaprine hydrochloride in 20 ml of chloroform, and they were stirred at room temperature for 10 minutes. After extracting with chloroform, the organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. 15 ml of toluene was added to the residue, and they were heated at 80° C. 4.0 ml (41.8 mmol) of ethyl chloroformate was added thereto, and they were stirred at 80° C. overnight. 4.0 ml (41.8 mmol) of ethyl chloroformate was added to the reaction mixture, and they were stirred under heating for 2 days. Water was added to the reaction mixture. After extracting with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by the silica gel chromatography (hexane:ethyl acetate=1:1). 11.4 ml of 1-butanol and 1.97 g (35.1 mmol) of powdery potassium hydroxide were added to the obtained product, and they were stirred under heating at 120° C. for 4 hours. The reaction mixture was poured in water at room temperature. After the extraction with chloroform, the organic layer was dried over anhydrous sodium sulfate and then concentrated under reduce pressure to obtain the title compound.