Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8][CH3:9])[C:3]=1[CH:10]=[O:11].[BH4-].[Na+]>CCO>[I:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8][CH3:9])[C:3]=1[CH2:10][OH:11]
Reactant: COc1nccc(I)c1C=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: COc1nccc(I)c1CO
Yield: 97.2 %

Procedure:
Following the procedure in Example 1, the reaction was carried out with 1b (1.88 g, 7.1 mmol) and NaBH4 (0.135 g, 3.56 mmol) in EtOH (40 mL) to afford 2b as a pale yellow oil (1.83 g, 97%). The crude product was sufficiently pure for the subsequent reaction. IR (CH2Cl2, NaCl,cm−1) 3391, 2946, 1561, 1459, 1380, 1019, 805; 1H NMR (300 MHz, CDCl3) δ2.43 (t, J=7 Hz,1H), 3.99 (s, 3H), 4.82 (d, J=7 Hz, 2H), 7.35 (d, J=5.4 Hz, 1H), 7.7 (d, J=5.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ54.29, 64.90, 112.12, 126.50, 128.15, 146.59, 161.71; HRMS (EI) m/z calcd for C7H8NO2I (M+) 264.9600, found 264.9598; LRMS (EI) m/z 265 (M+, 53), 250(84), 138(30), 84(100), 78(30).
Reaction SMILES: [C:1](Cl)(Cl)=[O:2].[C:5]1([C:11]2([C:18]3[CH:27]=[C:26]([O:28][CH2:29][C:30]4[CH:39]=[CH:38][C:37]5[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=5)[N:31]=4)[CH:25]=[CH:24][C:19]=3[C:20]([NH:22][NH2:23])=[O:21])[CH2:16][CH:15]3[CH2:17][CH:12]2[CH2:13][CH2:14]3)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(Cl)Cl>[C:5]1([C:11]2([C:18]3[CH:27]=[C:26]([O:28][CH2:29][C:30]4[CH:39]=[CH:38][C:37]5[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=5)[N:31]=4)[CH:25]=[CH:24][C:19]=3[C:20]3[O:21][C:1](=[O:2])[NH:23][N:22]=3)[CH2:16][CH:15]3[CH2:17][CH:12]2[CH2:13][CH2:14]3)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: NNC(=O)c1ccc(OCc2ccc3ccccc3n2)cc1C1(c2ccccc2)CC2CCC1C2
Reactant: O=C(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: O=c1[nH]nc(-c2ccc(OCc3ccc4ccccc4n3)cc2C2(c3ccccc3)CC3CCC2C3)o1
Reaction time: 0.75 h

Procedure:
Phosgene (751 μL of a −20% w/v solution in toluene, 1.42 mmol) was added dropwise via syringe to a stirred solution of 4d (365 mg, 0.79 mmol) in methylene chloride (20 mL) at −78° C. After approximately 45 minutes, the reaction mixture was poured into saturated aqueous sodium bicarbonate and extracted three times with methylene chloride. The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo. The crude residue was purified by preparative reversed phase HPLC on YMC Pack Pro C18 stationary phase (gradient elution; 0-75% acetonitrile/water as eluent, 0.1% TFA as modifier). Lyophilization of the purified fractions afforded the title compound 4e, m/z (ES) 490 (MH)+.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1C=O.[NH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[BH3-]C#N.[Na+]>CO.[Cl-].[Cl-].[Zn+2]>[C:14]1([NH:13][C:3]2[CH:2]=[N:1][C:10]3[C:5]([CH:4]=2)=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=Cc1ccc2ccccc2n1
Reactant: Nc1ccccc1
Agent: [BH3-]C#N
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Product: c1ccc(Nc2cnc3ccccc3c2)cc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of quinoline-3-carbaldehyde 11 (79 mg, 0.5 mmol) in MeOH (5 mL) was added aniline (0.05 mL, 0.55 mmol) and ZnCl2 (136 mg, 2.0 mmol) and the reaction was stirred at room temperature for 15 min. Then NaCNBH3 (62.8 mg, 2.0 mmol) was added and to the reaction was stirred overnight at room temperature. The solvent was removed by rotary evaporation and the residue suspended in EtOAc. The organic layers were combined and washed with NaHCO3, water, and brine and then dried over MgSO. Concentration in vacuo gave the crude product, which was used in the next step without further purification. 1H NMR (CDCl3): 9.05 (s, 1H), 8.23 (d, J=7.6 Hz, 2H), 7.77 (d, J=8.0 Hz, 1H), 7.71-7.66 (m, 1H), 7.54-7.51 (m, 1H), 7.21-7.16 (m, 2H), 6.76-6.72 (m, 1H), 6.68-6.60 (m, 2H), 4.54 (s, 2H), 4.16 (s, br, 1H).
Reaction SMILES: [N:1]12[CH2:9][CH2:8][CH2:7][CH:6]1[CH2:5][NH:4][CH2:3][CH2:2]2.[I-].[K+].[OH-].[K+].C[O:15][C:16](OC)([C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[CH2:17][CH2:18][CH2:19]Cl.Cl.[OH-].[NH4+]>C(Cl)Cl.C(O)C.C(OCC)C.O>[N:1]12[CH2:9][CH2:8][CH2:7][CH:6]1[CH2:5][N:4]([CH2:19][CH2:18][CH2:17][C:16]([C:21]1[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=1)=[O:15])[CH2:3][CH2:2]2
Reactant: COC(CCCCl)(OC)c1ccc(F)cc1
Reactant: C1CC2CNCCN2C1
Agent: Cl
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Solvent: CCO
Product: O=C(CCCN1CCN2CCCC2C1)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 49 %

Procedure:
To a heated slurry of 2.90 parts of 1,4-diazabicyclo[4.3.0]nonane, 1.91 parts of potassium iodide, and 25 parts of deionized water is added 1.65 parts potassium hydroxide and 6.17 parts of 1,1-dimethoxy-1-(4-fluorophenyl)-4-chlorobutane under nitrogen. The mixture is heated to reflux and held at that temperature for 4.5 hours. After cooling to room temperature, 18 parts of ethyl ether and a sufficient quantity of concentrated hydrochloric acid to bring the pH of the aqueous phase to about 2 are added. The aqueous layer is separated and basified to pH 12 with 50% sodium hydroxide solution. The resultant oil which forms is extracted into chloroform. The solvent is removed under reduced pressure to afford an orange oil. Chromatography of this oil using silica gel as an adsorbant and mixtures of ethanol (0.5 - 20%) in methylene chloride with 0.25% ammonium hydroxide as eluants affords 4-(1,4-diazabicyclo[4.3.0]non-4-yl)-4'-fluorobutyrophenone as an orange oil, in yield of 49%. This compound is represented by the following structural formula. ##STR18##
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1C=O.[CH:8]([O:15][CH2:16][CH3:17])([O:12][CH2:13][CH3:14])OCC.C([O-])([O-])=O.[K+].[K+]>C(O)C.Cl>[CH2:16]([O:15][CH:8]([O:12][CH2:13][CH3:14])[C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[CH3:17]
Reactant: CCOC(OCC)OCC
Reactant: O=Cc1cccs1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CCOC(OCC)c1cccs1
Yield: 89.9 %

Procedure:
A solution of 22.4 g (200 mmol) of 2-thiophene carboxaldehyde and 44.4 g (300 mmol) of triethyl orthoformate in ethanol (200 mL) with 3-5 drops of concentrated HCl was heated at reflux for 4 hrs. The reaction mixture was then neutralized with K2CO3. After filtered and concentrated, 33.5 g (90% yield) of 2-(diethoxymethyl)-thiophene was distilled under reduced pressure (bp 156° C./1 torr).
Reaction SMILES: [BH4-].[Na+].[C:3]([C:5]1[CH:6]=[CH:7][C:8]([O:31][CH3:32])=[C:9]([CH:30]=1)[C:10]([NH:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][CH:18]([C:21](=[O:29])[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:17][CH2:16]1)=[O:11])#[N:4].CC(C)=O>C(O)C>[C:3]([C:5]1[CH:6]=[CH:7][C:8]([O:31][CH3:32])=[C:9]([CH:30]=1)[C:10]([NH:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][C:18](=[C:21]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[OH:29])[CH2:17][CH2:16]1)=[O:11])#[N:4]
Reactant: COc1ccc(C#N)cc1C(=O)NCCN1CCC(C(=O)c2ccc(F)cc2)CC1
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: CCO
Product: COc1ccc(C#N)cc1C(=O)NCCN1CCC(=C(O)c2ccc(F)cc2)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
0.38 g (0.01 mol) of sodium borohydride are added, while stirring, to a suspension of 4.1 g (0.01 mol) of 5-cyano-N-[2-[4-(p-fluorobenzoyl)-piperidinyl]ethyl]-2-methoxybenzamide in 50 ml of ethanol and the whole is stirred for 1 hour at room temperature. There is added to the resulting clear solution 1 ml of acetone and the whole is then concentrated in a water-jet vacuum. The residue is taken up in methylene chloride and water, the layers are separated in a separating funnel and, after being dried over magnesium sulphate, the organic phase is concentrated by evaporation. 5-Cyano-N-[2-[4-[(4-fluorophenyl)hydroxymethylene]-piperidinyl]-ethyl]-2-methoxybenzamide of melting point 135°-137° is obtained as residue.
Reaction SMILES: [CH2:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[Cl:13])[C:6]([C:14]2[CH:19]=[CH:18][C:17]([O:20]C)=[CH:16][C:15]=2[O:22]C)=[N:5]1)[CH:2]=[CH2:3].B(Br)(Br)Br.C1CCCCC=1>>[CH2:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[Cl:13])[C:6]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][C:15]=2[OH:22])=[N:5]1)[CH:2]=[CH2:3]
Reactant: C=CCn1nc(-c2ccc(OC)cc2OC)c2cccc(Cl)c21
Agent: BrB(Br)Br
Solvent: C1=CCCCC1
Product: C=CCn1nc(-c2ccc(O)cc2O)c2cccc(Cl)c21
Yield: 53.2 %

Procedure:
Prepared according to Method D step C from 1-allyl-7-chloro-3-(2,4-dimethoxyphenyl)-1H-indazole (0.101 g, 0.30 mmol), boron tribromide (0.226 mL, 2.4 mmol) and 1.0 mL of cyclohexene to give the product (0.048 g) as a white solid.
Reaction SMILES: [ClH:1].Cl.C([O:7][CH:8](OCCCC)[C@H:9]([CH2:36][CH2:37][CH2:38][NH:39][C:40](=[NH:42])[NH2:41])[NH:10][C:11](=[O:35])[C@@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[C:17](=[O:34])[C@@H:18]1[CH2:22][CH2:21][C:20](=[O:23])[N:19]1[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])CCC.[OH-].[Na+]>C(#N)C>[ClH:1].[CH2:27]([O:26][C:24]([N:19]1[C:20](=[O:23])[CH2:21][CH2:22][C@H:18]1[C:17]([N:13]1[CH2:14][CH2:15][CH2:16][C@H:12]1[C:11]([NH:10][C@H:9]([CH:8]=[O:7])[CH2:36][CH2:37][CH2:38][NH:39][C:40](=[NH:41])[NH2:42])=[O:35])=[O:34])=[O:25])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: CCCCOC(OCCCC)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCC(=O)N1C(=O)OCc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC#N
Product: N=C(N)NCCC[C@@H](C=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCC(=O)N1C(=O)OCc1ccccc1
Yield: 80 %

Procedure:
After 1N hydrochloric acid aqueous solution (30 ml) was added to a solution of N-benzyloxycarbonyl-L-pyroglutamyl-L-prolyl-L-argininal dibutylacetal hydrochloride (0.40 g, 0.60 mmol) in acetonitrile (60 ml), the mixture was reacted at 36° C. for an hour with stirring. After completion of the reaction, pH of the reaction mixture was adjusted to 4.8 with 1N sodium hydroxide aqueous solution. The solvent was distilled off under reduced pressure and chloroform was added to the residue. Insoluble matters were removed by filtration. After the filtrate was concentrated, the residue was recrystallized from chloroform-hexane to give 0.26 g (80%) of N-benzyloxycarbonyl-L-pyroglutamyl-L-prolyl-L-argininal hydrochloride.
Reaction SMILES: CSC.C([O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([S:25][CH3:26])=[CH:21][CH:20]=1)C1C=CC=CC=1.O>C(Cl)Cl>[CH3:26][S:25][C:22]1[CH:23]=[CH:24][C:19]([CH2:18][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[OH:11])=[CH:20][CH:21]=1
Reactant: CSc1ccc(Cc2ccccc2OCc2ccccc2)cc1
Solvent: CSC
Solvent: O
Solvent: ClCCl
Product: CSc1ccc(Cc2ccccc2O)cc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 87.6 %

Procedure:
In a nitrogen stream, dimethylsulfide (7.25 mL, 138 mmol) and a boron trifluoride-diethyl ether complex (2.1 mL, 8.8 mmol) were added to a solution of 1-benzyloxy-(4-methylsulfanylbenzyl)benzene (1.9 g, 5.9 mmol) in methylene chloride (15 mL) under cooling with ice, and the reaction mixture was stirred for 48 hours while gradually raising its temperature to room temperature. Water was added thereto under cooling with ice and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated sodium chloride aqueous solution and dried (anhydrous magnesium sulfate), and then the solvent was distilled under reduced pressure. The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:5)] to obtain the title compound (1.19 g, 91%).
Reaction SMILES: [F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH:6]=[C:7]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[CH2:11][CH2:10][C:9]2[CH:18]=[CH:19][CH:20]=[CH:21][C:8]1=2.C(OCC)(=O)C.[H][H]>C(O)C.[Pd]>[F:1][C:2]([F:29])([F:30])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:26])[F:27])[CH:24]=1)[CH2:6][CH:7]1[C:8]2[CH:21]=[CH:20][CH:19]=[CH:18][C:9]=2[CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]1=2
Reactant: [H][H]
Reactant: FC(F)(F)c1cc(C=C2c3ccccc3CCc3ccccc32)cc(C(F)(F)F)c1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: FC(F)(F)c1cc(CC2c3ccccc3CCc3ccccc32)cc(C(F)(F)F)c1
Reaction time: 17 h

Procedure:
Add 5-(3,5-bis-trifluoromethyl-benzylidene)-10,11-dihydro-5H-dibenzo [a,d]cycloheptene (0.28 g, 0.67 mmol) to a mixture of 10% Pd/C (0.08 g) suspended in absolute ethanol (4.0 mL) and ethyl acetate (4.0 mL) and hydrogenate under a balloon of hydrogen at room temperature and pressure. Stir for 17 h, remove the catalyst via filtration through a pad of Celite. Evaporate the filtrate and pass through a plug of silica gel equilibrated with hexanes. Concentrate the filtrate to give the title product. MS (m/e): 420 (M+); Analysis for C24H18F6: Calcd: C, 68.56 H, 4.31. Found: C, 68.55 H. 4.01.
Reaction SMILES: C([Li])(C)(C)C.Br[C:7]1[CH:32]=[CH:31][C:10]([O:11][C@H:12]([C@H:14]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:15][CH2:16][C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)[CH3:13])=[CH:9][CH:8]=1.C([O:36][B:37](OC(C)C)[O:38]C(C)C)(C)C>O1CCCC1>[Si:24]([O:23][C@H:14]([CH2:15][CH2:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1)[C@H:12]([CH3:13])[O:11][C:10]1[CH:31]=[CH:32][C:7]([B:37]([OH:38])[OH:36])=[CH:8][CH:9]=1)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]
Reactant: C[C@H](Oc1ccc(Br)cc1)[C@@H](CCc1cccnc1)O[Si](C)(C)C(C)(C)C
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Product: C[C@H](Oc1ccc(B(O)O)cc1)[C@@H](CCc1cccnc1)O[Si](C)(C)C(C)(C)C
Temperature: -78 °C
Reaction time: 2 h

Procedure:
A solution of tert-butyllithium (3.95 ml, 1.7M in hexanes) was added over a 1 hour period to a solution of (2S,3R)-2-(4-bromophenoxy)-3-tert-butyldimethylsilyloxy-5-pyridin-3-ylpentane (2.518 g, Example 15e)) and tri-isopropylborate (1.68 ml) in tetrahydrofuran (20 ml) at -78° C. The resulting solution was stirred at -78° C. for 2 hours and was then quenched by the addition of a saturated solution of ammonium chloride in water (50 ml). The mixture was poured into water (50 ml) and extracted into ethyl acetate (2×50 ml). The combined extracts were dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified by chromatography on silica gel eluting with ethyl acetate and then ethyl acetate:methanol (4:1) to afford the sub-title compound as a foam (1.22 g).
Reaction SMILES: [Cl:1][C:2]1[C:7]2[C:8](=[O:24])[N:9]([CH3:23])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[O:17][C:18]([CH2:21]Cl)=[N:19][N:20]=3)[C:6]=2[CH:5]=[CH:4][C:3]=1[F:25].[CH2:26]([NH:29][CH2:30][CH2:31][CH3:32])[CH2:27][CH3:28]>CN(C)C=O>[Cl:1][C:2]1[C:7]2[C:8](=[O:24])[N:9]([CH3:23])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[O:17][C:18]([CH2:21][N:29]([CH2:30][CH2:31][CH3:32])[CH2:26][CH2:27][CH3:28])=[N:19][N:20]=3)[C:6]=2[CH:5]=[CH:4][C:3]=1[F:25]
Reactant: CCCNCCC
Reactant: CN1Cc2c(-c3nnc(CCl)o3)ncn2-c2ccc(F)c(Cl)c2C1=O
Solvent: CN(C)C=O
Product: CCCN(CCC)Cc1nnc(-c2ncn3c2CN(C)C(=O)c2c-3ccc(F)c2Cl)o1
Temperature: 25 °C
Reaction time: 17 h
Yield: 41.2 %

Procedure:
A suspension of 0.193 g (0.51 mmol) of 7-chloro-3-(5-chloromethyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one in 2 ml of N,N-dimethylformamide was treated with 0.26 g (2.55 mmol) of dipropylamine. After stirring at room temperature for 17 hrs. the solution obtained was completely freed from the solvents. The residue was chromatographed over silica gel with methylene chloride/methanol 39:1 as the eluent. The product was recrystallized from ether/n-hexane at 0°. There were obtained 0.094 g (41%) of 7-chloro-3-(5-dipropylaminomethyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one as white crystals; m.p. 128°-130°.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][N:3]=1.[C:10](=[N:23][NH2:24])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[C:11]1([C:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[N:23][NH:24][C:2]2[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][N:3]=2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: COc1ccnc(Cl)c1
Reactant: NN=C(c1ccccc1)c1ccccc1
Product: COc1ccnc(NN=C(c2ccccc2)c2ccccc2)c1
Yield: 71.9 %

Procedure:
According to the process described in Example 2.2, starting with 0.5 g of 2-chloro-4-methoxypyridine and 0.75 g of benzophenone hydrazone, 0.76 g of 2-[2-(diphenylmethylidene)hydrazino]-4-methoxypyridine is obtained in the form of a yellow solid, which is used without further purification in the following step.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH3:17])[C@H:9]([C:14]([OH:16])=O)[CH2:10][CH:11]([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.C(N=C=NCCCN(C)C)C.[CH:30]1[C:40]2[CH:39]=[CH:38][C:37]3[CH:41]=[CH:42][CH:43]=[CH:44][C:36]=3[C:35](=[CH:45][CH2:46][CH2:47][NH:48][CH3:49])[C:34]=2[CH:33]=[CH:32][CH:31]=1.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>ClCCl>[CH:30]1[C:40]2[CH:39]=[CH:38][C:37]3[CH:41]=[CH:42][CH:43]=[CH:44][C:36]=3[C:35](=[CH:45][CH2:46][CH2:47][N:48]([CH3:49])[C:14]([C@@H:9]([N:8]([CH3:17])[C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:10][CH:11]([CH3:12])[CH3:13])=[O:16])[C:34]=2[CH:33]=[CH:32][CH:31]=1
Reactant: CNCCC=C1c2ccccc2C=Cc2ccccc21
Reactant: CC(C)C[C@@H](C(=O)O)N(C)C(=O)OC(C)(C)C
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)C[C@@H](C(=O)N(C)CCC=C1c2ccccc2C=Cc2ccccc21)N(C)C(=O)OC(C)(C)C

Procedure:
280 mg (1.14 mmol) of t-butoxycarbonyl-N-methyl-L-leucine, 204 mg (1.06 mmol) of 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride, 271 mg (1.04 mmol) of 3-(5H-dibenzo[a,d][7]annulen-5-ylidene)-N-methyl-1-propanamine and 0.15 ml (1.08 mmol) of triethylamine were stirred in 10 ml of dichloromethane at room temperature overnight. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture. After extracting with dichloromethane, 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=82:18) to obtain the title compound.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([OH:34])[CH2:16][NH:17][C:18]([CH3:33])([CH3:32])[CH2:19][CH2:20][N:21]2[CH:25]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:23]=[CH:22]2)=[CH:11][C:10]=1[N+:35]([O-])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H][H]>O1CCCC1.C1(C)C=CC=CC=1.[Pt](=O)=O>[NH2:35][C:10]1[CH:11]=[C:12]([C@@H:15]([OH:34])[CH2:16][NH:17][C:18]([CH3:32])([CH3:33])[CH2:19][CH2:20][N:21]2[CH:25]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:23]=[CH:22]2)[CH:13]=[CH:14][C:9]=1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: [H][H]
Reactant: CC(C)(CCn1cnc(-c2ccccc2)c1)NC[C@H](O)c1ccc(OCc2ccccc2)c([N+](=O)[O-])c1
Agent: O=[Pt]=O
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CC(C)(CCn1cnc(-c2ccccc2)c1)NC[C@H](O)c1ccc(OCc2ccccc2)c(N)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 100 %

Procedure:
0.025 g (0.11 mmol) platinum(IV)oxide were added to a solution of 0.15 g (0.28 mmol) (R)-1-(4-benzyloxy-3-nitrophenyl)-2-[1,1-dimethyl-3-(4-phenylimidazol-1-yl)-propylamino]-ethanol in 10 mL tetrahydrofuran/toluene (1:1). The reaction mixture was shaken in an autoclave under a hydrogen pressure of 10 psi at ambient temperature for 16 h. The hydrogen pressure was released, the platinum(IV)oxide was filtered off and the filtrate was freed from solvent. 0.14 g (0.28 mmol, 99%) (R)-1-(3-amino-4-benzyloxyphenyl)-2-[1,1-dimethyl-3-(4-phenylimidazol-1-yl)-propylamino]-ethanol were obtained as a brown oil.
Reaction SMILES: Cl[SiH:2]1[CH2:7][CH2:6][CH:5]([C@H:8]2[CH2:13][CH2:12][C@H:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[C:18]([F:23])[CH:17]=3)[CH2:10][CH2:9]2)[CH2:4][CH2:3]1>C1COCC1>[F:23][C:18]1[CH:17]=[C:16]([CH2:15][CH2:14][C@H:11]2[CH2:12][CH2:13][C@H:8]([C@H:5]3[CH2:6][CH2:7][Si@H:2]([CH2:3][CH2:4][CH:5]([CH3:8])[CH3:6])[CH2:3][CH2:4]3)[CH2:9][CH2:10]2)[CH:21]=[CH:20][C:19]=1[F:22]
Reactant: Fc1ccc(CC[C@H]2CC[C@H](C3CC[SiH](Cl)CC3)CC2)cc1F
Solvent: C1CCOC1
Product: CC(C)CC[Si@H]1CC[C@H]([C@H]2CC[C@H](CCc3ccc(F)c(F)c3)CC2)CC1

Procedure:
3.0 g (20 mmol) of 3-methylbutyl bromide was dripped into a mixture of 0. 5 g (21 mmol) of magnesium and 50 ml of THF to obtain a Grignard's reagent. This solution was then dripped into a 50 ml THF solution of 7.1 g of 1-chloro-4-(trans-4-(2-(3,4-difluorophenyl) ethyl) cyclohexyl)-1-silacyclohexane. The silacyclohexane rings of the reacted mixture thus obtained were a mixture of trans isomers and cis isomers. After a conventional after treatment, they were separated by means of chromatography to obtain 6.9 g (yield 88%) of trans-4-(trans-4-(2-(3,4-difluorophenyl) ethyl) cyclohexyl)-1-(3-methylbutyl)-1-silacyclohexane.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.ClCCl.[CH2:20]([C@@:27]1([OH:50])[C@@:31]2([CH2:41][O:42][C@H:28]1[C@H:29]([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[OH:49])[O:30]2)[CH2:32][O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O>[C:1]([O:49][C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=1[C@@H:29]1[O:30][C@:31]2([CH2:32][O:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C@@:27]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)([OH:50])[C@H:28]1[O:42][CH2:41]2)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Oc1ccccc1[C@@H]1O[C@@]2(COCc3ccccc3)CO[C@@H]1[C@@]2(O)Cc1ccccc1
Reactant: O=C(Cl)c1ccccc1
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(Oc1ccccc1[C@@H]1O[C@@]2(COCc3ccccc3)CO[C@@H]1[C@@]2(O)Cc1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 100 %

Procedure:
Benzoyl chloride (0.06 ml, 0.52 mmol) and anhydrous triethylamine (0.073 ml, 0.52 mmol) were added to an anhydrous dichloromethane (3 ml) solution of the compound (24) (168 mg, 0.40 mmol), and the mixture was stirred for 3 hours at room temperature. After water was added to the reaction solution, the system was extracted with ethyl acetate 3 times. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (n-hexane:ethyl acetate=7:1) to obtain a colorless oily substance (25) (209 mg, 93%).
Reaction SMILES: [Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([C:12]3[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=3)[C:15]#[N:16])[C:7](=[O:20])[C@@H:6]([CH2:21]O)[N:5]([CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[C:4]=2[N:3]=1.C(N(S(F)(F)[F:34])CC)C>C(Cl)Cl>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([C:12]3[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=3)[C:15]#[N:16])[C:7](=[O:20])[C@@H:6]([CH2:21][F:34])[N:5]([CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[C:4]=2[N:3]=1
Reactant: N#Cc1cccc(N2C(=O)[C@@H](CO)N(C3CCCC3)c3nc(Cl)ncc32)c1
Reactant: CCN(CC)S(F)(F)F
Solvent: ClCCl
Product: N#Cc1cccc(N2C(=O)[C@@H](CF)N(C3CCCC3)c3nc(Cl)ncc32)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 25.9 %

Procedure:
To a stirred solution of 3-[(7R)-2-chloro-8-cyclopentyl-7-(hydroxymethyl)-6-oxo-7,8-dihydropteridin-5(6H)-yl]benzonitrile (94 mg, 0.24 mmol) in anhydrous DCM (3 mL) was added diethylaminosulfur trifluoride (39 μL, 0.29 mmol) at −78° C. under nitrogen. The mixture was allowed to warm to rt and stirred for 18 h. The mixture was then cooled to 0° C. and quenched by saturated aqueous NaHCO3 solution. The mixture was extracted with DCM (30 mL×2) and the combined organic layers were dried over Na2SO4, concentrated in vacuo to give a crude residue, which was purified using a silica gel flash chromatography [eluent: 0-50% EtOAc/Heptane] to afford the desired compound (24 mg, 25%). 1H NMR (400 MHz, CD3OD): δ 7.89-7.94 (m, 1H), 7.74-7.80 (m, 2H), 7.61-7.66 (m, 1H), 7.01 (s, 1H), 4.87-5.00 (m, 1H), 4.70-4.83 (m, 1H), 4.31 (quin, J=8.4 Hz, 1H), 2.08-2.19 (m, 2H), 1.97-2.07 (m, 4H), 1.61-1.76 (m, 2H). MS (ES+): m/z=386.32/388.29 [MH+]. UPLC: tR=1.33 min (TOF: polar_2 min).