Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:15]([CH3:16])=[CH:14][C:10]2[N:11]=[CH:12][S:13][C:9]=2[C:8]=1[C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)(=O)=O.[CH2:26](C([Sn])=C(CCCC)CCCC)[CH2:27]CC.[Li+].[Cl-].C(OCC)(=O)C>CN(C=O)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>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([C:8]2[C:9]3[S:13][CH:12]=[N:11][C:10]=3[CH:14]=[C:15]([CH3:16])[C:7]=2[CH:26]=[CH2:27])=[CH:18][CH:19]=1
Reactant: Cc1cc2ncsc2c(-c2ccc(Cl)cc2)c1OS(=O)(=O)C(F)(F)F
Reactant: CCCCC([Sn])=C(CCCC)CCCC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: C=Cc1c(C)cc2ncsc2c1-c1ccc(Cl)cc1
Temperature: 120 °C
Reaction time: 0.5 h

Procedure:
7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl trifluoromethanesulfonate (5F) from above reaction was dissolved in DMF (3 ml). Tributylvinyltin (130 uL), PdCl2(PPh3)2 (27 mg, 0.039 mmol) and LiCl (49 mg, 1.17 mmol) were added. The reaction mixture was stirred at 120° C. in microwave for 30 min. The reaction mixture was diluted by ethyl acetate, washed with saturated NaHCO3 solution and extracted with ethyl acetate. The organic layer was dried over MgSO4, filtered, concentrated and purified by silica gel column (0-50% ethyl acetate/hexanes). LCMS-ESI+: calc'd for C16H20ClNS: 286.0 (M+H+). Found: 286.1 (M+H+).
Reaction SMILES: [N+](=[CH2:3])=[N-].[C:4]([NH:12][C@H:13]1[C:20](=[O:21])[N:19]2[C@@H:14]1[O:15][CH2:16][C:17]([OH:29])=[C:18]2[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])(=[O:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>CCOCC.C(Cl)Cl>[C:4]([NH:12][C@H:13]1[C:20](=[O:21])[N:19]2[C@@H:14]1[O:15][CH2:16][C:17]([O:29][CH3:3])=[C:18]2[C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])(=[O:11])[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1
Reactant: C=[N+]=[N-]
Reactant: CC(C)(C)OC(=O)C1=C(O)CO[C@@H]2[C@@H](NC(=O)c3ccccc3)C(=O)N12
Solvent: ClCCl
Solvent: CCOCC
Product: COC1=C(C(=O)OC(C)(C)C)N2C(=O)[C@H](NC(=O)c3ccccc3)[C@H]2OC1
Yield: 62 %

Procedure:
A solutin of diazomethane in ether was added to a solution of 260 mg (0.72 mmol) of tert.-butyl (6R, 7R)-7-benzoylamino-3-hydroxy-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate in 3 ml of anhydrous methylene chloride at room temperature until a yellow coloration remained. The solvent and excess diazomethane were then evaporated off in vacuo and the residue was chromatographed on 18 g of silica gel (toluene:ethyl acetate 2:3). 169 mg (62%) of the title compound were obtained as a colorless rigid foam.
Reaction SMILES: [Br:1][CH2:2][CH2:3][OH:4].[C:5]([Si:9]([CH3:12])([CH3:11])Cl)([CH3:8])([CH3:7])[CH3:6].N1C=CN=C1>CN(C)C=O.C(OCC)(=O)C>[Br:1][CH2:2][CH2:3][O:4][Si:9]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:12])[CH3:11]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OCCBr
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)OCCBr
Temperature: 25 °C
Reaction time: 3 h
Yield: 91.9 %

Procedure:
2-Bromoethanol (3.44 g, 27.53 mmol), t-butyldimethylchlorosilane (4.23 g, 28.07 mmol), and imidazole (3.97 g, 58.31 mmol) was dissolved in dimethylformamide (20 ml) and the solution was stirred at room temperature for 3 hours. The reaction mixture was diluted with ethyl acetate and washed with water and then with saturated brine, and dried over magnesium sulfate. Insoluble solids were removed by filtration, and then the filtrate was concentrated under reduced pressure to obtain t-butyldimethylsilyl 2-bromoethyl ether (6.05 g) as crude product. The crude product (1.83 g), 2-phenylimidazole (1.11 g, 7.70 mmol), and potassium carbonate (1.50 g, 10.9 mmol) was added in dimethylformamide (10 ml), and the mixture was heated at 80° C. for 10 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed with water and then with saturated brine, and dried over sodium sulfate. Insoluble solids were removed by filtration and the filtrate was evaporated under reduced pressure. The resulting oil was purified by silica gel column chromatography (ethyl acetate-hexane) to obtain the title compound as pale yellow oil (1.16 g, yield: 50%).
Reaction SMILES: [CH2:1]([N:5]1[C:10](=[O:11])[C:9]2[C:12]([NH:15][CH3:16])=[N:13][NH:14][C:8]=2[N:7]([CH2:17][CH2:18]O)[C:6]1=[O:20])[CH2:2][CH2:3][CH3:4].S(Cl)([Cl:23])=O>C(Cl)(Cl)Cl.N1C=CC=CC=1>[CH2:1]([N:5]1[C:10](=[O:11])[C:9]2[C:12]([NH:15][CH3:16])=[N:13][NH:14][C:8]=2[N:7]([CH2:17][CH2:18][Cl:23])[C:6]1=[O:20])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCn1c(=O)c2c(NC)n[nH]c2n(CCO)c1=O
Reactant: O=S(Cl)Cl
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: CCCCn1c(=O)c2c(NC)n[nH]c2n(CCCl)c1=O
Yield: 94 %

Procedure:
To a suspension of 5-butyl-7-(2-hydroxyethyl)-3-methylaminopyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dione (2.5 g, 8.9 mM) in chloroform (30 ml) and pyridine (4 ml, 50 mM) was added thionyl chloride (3,7 ml, 50 mM) at room temperature. The solution was refluxed for 2 hours and concentrated to dryness under reduced pressure to give a syrup. The syrup was poured onto ice-water to give colorless powder. Recrystallization from DMF/methanol/water gave colorless crystals (2.5 g, 94%), m.p. 270°-272° C.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]#[N:16])=[CH:5][CH:4]=1.C([O-])(=[O:19])C.[Na+]>C(O)(=O)C>[OH:19][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]#[N:16])=[CH:5][CH:4]=1
Reactant: CC(=O)[O-]
Reactant: N#Cc1ccccc1-c1ccc(CBr)cc1
Agent: [Na+]
Solvent: CC(=O)O
Product: N#Cc1ccccc1-c1ccc(CO)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
250 g of 4-bromomethyl-2'-cyanobiphenyl (EP 253,310), 150 g of sodium acetate and 2.5 litres of glacial acetic acid are heated to reflux overnight and the mixture is then concentrated in a high vacuum. The residue is taken up in ethyl acetate, extracted with water, sodium bicarbonate and brine and the solvent is evaporated on a rotary evaporator. The crude product is dissolved in 3.1 litres of ethanol, treated with 430 ml of 2N NaOH and stirred overnight at room temperature. The reaction mixture is concentrated, taken up in ethyl acetate, washed with water and sodium carbonate and concentrated. The residue is suspended in hexane, filtered off with suction, washed and dried at 60° in a high vacuum for 20 hours. 4-Hydroxymethyl-2'-cyanobiphenyl is obtained as a white powder. 1H-NMR (DMSO): 4.58 ppm (d, 2 H), 5.3 ppm (t, 1 H), 7.6-8 ppm (aromatics, 8 H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([C@@H:15]3[CH2:19][CH2:18][NH:17][C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:5][C:4]=1[CH3:23].Cl[CH2:25][C:26]1[NH:27][C:28](=[O:36])[C:29]2[CH2:35][O:34][CH2:33][CH2:32][C:30]=2[N:31]=1.[H-].[Na+]>C1COCC1.CCOCC>[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([C@H:15]3[CH2:19][CH2:18][N:17]([CH2:25][C:26]4[NH:27][C:28](=[O:36])[C:29]5[CH2:35][O:34][CH2:33][CH2:32][C:30]=5[N:31]=4)[C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:5][C:4]=1[CH3:23]
Reactant: COc1ccc(C(=O)C2CCN([C@@H]3CCNC3=O)CC2)cc1C
Reactant: O=c1[nH]c(CCl)nc2c1COCC2
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: COc1ccc(C(=O)C2CCN([C@H]3CCN(Cc4nc5c(c(=O)[nH]4)COCC5)C3=O)CC2)cc1C
Temperature: 70 °C
Yield: 79 %

Procedure:
To a solution of (R)-3-[4-(4-methoxy-3-methyl-benzoyl)-piperidin-1-yl]-pyrrolidin-2-one (0.79 mmol, 250 mg) and 2-chloromethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (0.87 mmol, 174 mg) in THF (10 mL) was added sodium hydride (60%, 2.77 mmol, 111 mg) and heated to 70° C. for 1 hour. The reaction was allowed to cool to ambient temperature, diluted with 100 mL of ether, and the resulting solid in suspension was filtered and dried under vacuum provided the title compound as an off-white solid (300 mg). Chiral resolution of 2-3-[4-(4-methoxy-3-methyl-benzoyl)-piperidin-1-yl]-2-oxo-pyrrolidin-1-ylmethyl}-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (300 mg) via chiral SFC chromatography on a AS-H column (60 g/min, 21×250 mm) eluting 40% IPA/0.2% DEA/CO2 (v/v) afforded 77 mg of pure material. HRMS calculated for C26H32N4O5=480.5687. found (ESI, [M+H]+) 481.2455. 1H NMR (400 MHz, MeOD) δ ppm 1.69-1.90 (m, 4H) 2.10-2.20 (m, 1H) 2.20-2.31 (m, 4H) 2.48-2.58 (m, 1H) 2.59-2.65 (m, 2H) 2.77-2.88 (m, 1H) 2.90-3.06 (m, 1H) 3.10-3.20 (m, 1H) 3.32-3.42 (m, 3H) 3.46-3.54 (m, 2H) 3.63 (t, J=8.53 Hz, 1H) 3.88-3.94 (m, 5H) 4.39 (s, 2H) 4.47 (s, 2H) 6.99 (d, J=8.53 Hz, 1H) 7.77 (s, 1H) 7.87 (dd, J=8.53, 2.01 Hz, 1H), analytical RP-HPLC (Novapak 150×3.9 mm C18 column: mobile phase: 10-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 5 min.) retention time=2.731 min.
Reaction SMILES: [C:1]1([NH2:8])[C:2]([NH2:7])=[CH:3][CH:4]=[CH:5][CH:6]=1.[Cl:9][C:10]1[CH:18]=[CH:17][C:13]([C:14](O)=O)=[C:12]([O:19][CH3:20])[CH:11]=1>>[Cl:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]2[NH:8][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=3[N:7]=2)=[C:12]([O:19][CH3:20])[CH:11]=1
Reactant: COc1cc(Cl)ccc1C(=O)O
Reactant: Nc1ccccc1N
Product: COc1cc(Cl)ccc1-c1nc2ccccc2[nH]1

Procedure:
The title compound was prepared in analogy to Example 19, intermediate c, from benzene-1,2-diamine (CAS Reg. No. 95-54-5) and 4-chloro-2-methoxy-benzoic acid (CAS Reg. No. 57479-70-6). Colorless powder (59%). MS (Turbo Spray): m/z=259.4 (M+H).
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[OH-].[Na+].Br[C:27]([CH3:32])([CH3:31])[C:28]([NH2:30])=[O:29].Cl>CN1CCCN(C)C1=O.O>[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:12]=[CH:13][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:15][CH:16]=3)=[CH:9][N:8]([C:27]([CH3:32])([CH3:31])[C:28]([NH2:30])=[O:29])[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: Nc1ncnc2[nH]cc(-c3ccc(Oc4ccccc4)cc3)c12
Reactant: CC(C)(Br)C(N)=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CN1CCCN(C)C1=O
Solvent: O
Product: CC(C)(C(N)=O)n1cc(-c2ccc(Oc3ccccc3)cc2)c2c(N)ncnc21
Reaction time: 18 h

Procedure:
4-Amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine (200 mg) was dissolved in 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinone (1.5 ml) with stirring and sodium hydroxide (0.158 g) was added at ambient temperature and the mixture stirred for 15 minutes. 2-Bromo-2-methylpropanamide (0.5 g) was added and the mixture was stirred vigorously for 18 hours at ambient temperature under a water-free atmosphere, then further 2-bromo-2-methylpropanamide (0.15 g) was added and stirred for a further 24 hours. Water (3 ml) was added to the reaction mixture together with dilute hydrochloric acid (5M) to adjust the pH to 0. The suspension was added to water (60 ml) and the mixture left to stand for 18 hours at ambient temperature. The solid was collected by filtration, washed well with water and dried under high vacuum at 50° C. The solid was purified by preparative HPLC (reverse phase). Appropriate fractions were collected and combined and extracted with dichloromethane. Evaporation of the dichloromethane gave 2-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-2-methylpropionamide, m.p. 227-228° C.
Reaction SMILES: [H-].[Na+].C(COC)OC.P(=O)([O-])O[CH2:11][C:12](=[O:20])[CH2:13][CH2:14][CH2:15][CH2:16][CH:17](C)C.[C:23]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][C:33]1[C:38]([CH:39]=O)=[C:37]([O:41][CH3:42])[CH:36]=[CH:35][C:34]=1[O:43][CH3:44])([O:25][CH3:26])=[O:24]>C(O)(=O)C>[CH3:44][O:43][C:34]1[CH:35]=[CH:36][C:37]([O:41][CH3:42])=[C:38](/[CH:39]=[CH:11]/[C:12](=[O:20])[CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[C:33]=1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][C:23]([O:25][CH3:26])=[O:24]
Reactant: CC(C)CCCCC(=O)CO[PH](=O)[O-]
Reactant: COC(=O)CCCCCCc1c(OC)ccc(OC)c1C=O
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Solvent: CC(=O)O
Product: CCCCCC(=O)/C=C/c1c(OC)ccc(OC)c1CCCCCCC(=O)OC
Temperature: 85 °C

Procedure:
To a slurry of 278 mg. of a dispersion of sodium hydride in mineral oil in 40 ml. of dimethoxyethane is added a solution of 1.33 g. of dimethyl(2-oxoheptyl) phosphonate in 40 ml. of dimethoxyethane and the mixture is stirred for one hour. 1.41 g. of the aldehyde in 40 ml. of dimethoxyethane is added and the mixture heated at 85° C. for eighteen hours. The mixture is then cooled and neutralized with acetic acid and the solvent is removed in vacuo. The residue is then chromatographed on a silica gel column to yield 1,4-dimethoxy-2-(6-carbomethoxyhexyl)-3-(3-oxo-trans-1-octenyl)benzene as a yellow oil.
Reaction SMILES: [CH3:1][C:2]1([CH3:13])[O:6][C@@H:5]2[O:7][C@H:8]([CH:10]([OH:12])[CH3:11])[CH2:9][C@@H:4]2[O:3]1.[C:14](Cl)(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOC(C)=O>[C:14]([O:12][CH:10]([C@H:8]1[O:7][C@H:5]2[O:6][C:2]([CH3:1])([CH3:13])[O:3][C@H:4]2[CH2:9]1)[CH3:11])(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: CC(O)[C@@H]1C[C@@H]2OC(C)(C)O[C@@H]2O1
Reactant: O=C(Cl)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(OC(=O)c1ccccc1)[C@@H]1C[C@@H]2OC(C)(C)O[C@@H]2O1
Temperature: 25 °C
Reaction time: 8 h
Yield: 54.9 %

Procedure:
To a cooled solution of 1-[(3aS,5S,6aS)-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]ethanol (compound 25g, 200 mg, 1.06 mmol) in DCM (8 mL) was added benzoyl chloride (178 mg, 1.28 mmol) and DMAP (259 mg, 2 mmol). After the addition, the mixture was warmed naturally to room temperature and stirred at room temperature overnight. The resulting mixture was diluted with EtOAc and washed with a saturated aqueous solution of NH4Cl. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 1:3 EtOAc in petroleum ether) to afford 170 mg of 1-[(3aS,5S,6aS)-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]ethyl benzoate (compound 25h).
Reaction SMILES: C(=O)(OC)O[CH2:3]/[CH:4]=[CH:5]/[C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1.C1([C@@H]([N:24]([C@H:48]([C:50]2[CH:55]=[CH:54]C=CC=2)C)P2OC3C=CC4C=CC=CC=4C=3C3C4C(C=CC=3O2)=CC=CC=4)C)C=CC=CC=1.C1(NC)CC1.CC1C=CC(S(O)(=O)=O)=CC=1>C1COCC1.CCO>[CH:50]1([CH2:48][NH:24][C@H:5]([C:6]2[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=2)[CH:4]=[CH2:3])[CH2:55][CH2:54]1
Reactant: COC(=O)OC/C=C/c1ccc(F)cc1
Reactant: C[C@@H](c1ccccc1)N([C@@H](C)c1ccccc1)p1oc2ccc3ccccc3c2c2c(ccc3ccccc32)o1
Agent: CNC1CC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCO
Solvent: C1CCOC1
Product: C=C[C@H](NCC1CC1)c1ccc(F)cc1
Reaction time: 2.5 h
Yield: 851.9 %

Procedure:
A mixture of (2E)-3-(4-fluorophenyl)prop-2-en-1-yl methyl carbonate (420 mg), N,N-bis[(1S)-1-phenylethyl]dinaphtho[1,2-f:2′,1′-d][1,3,2]dioxaphosphepin-4-amine (108 mg), [Ir(COD)Cl]2 (27 mg), cyclopropyl methyl amine (374 μL) and EtOH (5 mL) was stirred under refluxing EtOH for 6H under N2. The progress of the reaction was monitered by HPLC. At the end of the reaction, addition of co-solvent (20 ml EtOH and 20 ml THF) and MP-TsOH resin (6 g) and the mixture was allowed to stirred at RT with swilling every 15 mins for 2-3 hours. Filtered the resin and washed the resin with plenty of EtOH, THF, DCM. The resin was taken up in 3.5N NH3 in MeOH (20 mL) and let it stir for overnight. Filtered the resin and washed the resin excessively with EtOH, THF and DCM. Combined the filtrate and evaporated all the solvent. The crude product was purified by flash chromatography (10% EtOAc/Hexane) to afford the title compound as a viscous oil (350 mg, 88%). 1H NMR (300 MHz, CDCl3) revealed branched/linear ratio (9:1) 0.27 (m, 2H), 0.47 (m, 2H), 1.10 (m, 1H), 2.40 (m, 2H), 4.51(m, 1H), 5.25-5.39 (m, 3H), 7.02-7.22 (m, 4H). MS APCI, m/z=206 (M+1). LC/MS 0.85 min., Method A. 94% ee was determined by NMR in the presence of TFAE-d11
Reaction SMILES: [C:1]([C:3](=[CH2:9])[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].C1CC=CC=1.[C:15]1([CH3:21])[CH:20]=CC=[CH:17][CH:16]=1>>[C:1]([C:3]1([C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH2:20][CH:15]2[CH2:21][CH:9]1[CH:17]=[CH:16]2)#[N:2]
Reactant: C=C(C#N)C(=O)OCC
Reactant: Cc1ccccc1
Agent: C1=CCC=C1
Product: CCOC(=O)C1(C#N)CC2C=CC1C2
Reaction time: 1 h

Procedure:
Specifically, 50 g (0.33 mol) of ethyl 2-cyanoacrylate (6a) was dissolved in 200 ml of toluene, and 45 g (0.68 mol) of 1,3-cyclopentadiene (5a) was added dropwise to the solution with cooling temperatures of 35° C. or below. Stirring for one hour and subsequent enrichment yielded 72 g of ethyl 5-cyanobicyclo[2.2.1]hept-2-ene-5-carboxylate represented by Formula (7a) (crude product).
Reaction SMILES: [Na+].[CH3:2][C:3]([C:11]1[CH:12]=[C:13]([S:17]([O-:20])(=O)=[O:18])[CH:14]=[CH:15][CH:16]=1)([CH3:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.S(Cl)([Cl:23])=O.C>CN(C=O)C.CCCCCC>[CH3:2][C:3]([C:11]1[CH:12]=[C:13]([S:17]([Cl:23])(=[O:20])=[O:18])[CH:14]=[CH:15][CH:16]=1)([CH3:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CC(C)(c1ccccc1)c1cccc(S(=O)(=O)[O-])c1
Reactant: O=S(Cl)Cl
Agent: [Na+]
Solvent: CCCCCC
Solvent: CN(C)C=O
Product: CC(C)(c1ccccc1)c1cccc(S(=O)(=O)Cl)c1
Temperature: 10 °C
Reaction time: 1 h

Procedure:
3-(α,α-Dimethylbenzyl)benzenesulphonic acid sodium salt (9.6 g) is dissolved in DMF (16 ml) and cooled to 10° C. Thionyl chloride (12ml) is added dropwise maintaining the temperature below 20° C. The mixture is allowed to warm to room temperature and stirred one hour. The solution is poured onto ice/water (100 ml) and the mixture is extracted with ether (3×8 ml). The combined extracts are dried (MgSO4) and the solvent evaporated to give pale yellow waxy crystals which are dissolved in hexane (200 ml) and decolourised (charcoal). Evaporation produces white crystals of 3-(α,α-dimethylbenzyl)benzenesulphonyl chloride which are dried at room temperature under vacuum, m.p. 47.5°-49° C.
Reaction SMILES: C1CCNCC1.[CH:7]([C:10]1[CH:15]=[CH:14][C:13]([S:16](Cl)(=[O:18])=[O:17])=[CH:12][CH:11]=1)([CH3:9])[CH3:8].[Cl:20][C:21]1[CH:39]=[CH:38][C:24]([CH2:25][N:26]2[CH2:31][CH2:30][CH:29]([CH2:32][NH:33][C:34](=[O:37])[CH2:35][NH2:36])[CH2:28][CH2:27]2)=[CH:23][CH:22]=1>C(Cl)(Cl)Cl>[Cl:20][C:21]1[CH:39]=[CH:38][C:24]([CH2:25][N:26]2[CH2:27][CH2:28][CH:29]([CH2:32][NH:33][C:34](=[O:37])[CH2:35][NH:36][S:16]([C:13]3[CH:14]=[CH:15][C:10]([CH:7]([CH3:9])[CH3:8])=[CH:11][CH:12]=3)(=[O:18])=[O:17])[CH2:30][CH2:31]2)=[CH:23][CH:22]=1
Reactant: CC(C)c1ccc(S(=O)(=O)Cl)cc1
Reactant: NCC(=O)NCC1CCN(Cc2ccc(Cl)cc2)CC1
Solvent: C1CCNCC1
Solvent: ClC(Cl)Cl
Product: CC(C)c1ccc(S(=O)(=O)NCC(=O)NCC2CCN(Cc3ccc(Cl)cc3)CC2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A (piperidinomethyl)polystyrene resin (28 mg, 2.8 mmol/g) and 4-isopropylbenzenesulfonyl chloride (1.5 equivalents) were added to a chloroform (2 mL) solution of 1-(4-chlorobenzyl)-4-[(glycylamino)methyl]piperidine (14.8 mg, 0.05 mmol). The resulting mixture was stirred at 25° C. for 16 hours, then filtered and concentrated to thereby afford 1-(4-chlorobenzyl)-4-[[N-(4-isopropylphenylsulfonyl)glycyl]aminomethyl]piperidine (Compd. No. 869) (22.1 mg, 92%). The purity was determined by RPLC/MS (86%). ESI/MS m/e 478 (M++H, C24H32N3O3S).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[O:23]1[CH2:26][C:25](=O)[CH2:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:9][CH2:10][N:11]([CH:25]3[CH2:26][O:23][CH2:24]3)[CH2:12][CH2:13]2)=[CH:4][CH:3]=1
Reactant: Brc1ccc(C2CCNCC2)cc1
Reactant: O=C1COC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: Brc1ccc(C2CCN(C3COC3)CC2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 56.8 %

Procedure:
In a round-bottomed, single-necked, 100-mL flask were placed 4-(4-bromophenyl)piperidine (500.0 mg, 2.08 mmol), N,N-diisopropylethylamine (0.36 mL, 2.08 mmol), 3-oxetanone (0.27 mL, 4.16 mmol), and sodium triacetoxyborohydride (1544.5 mg, 7.3 mmol) in THF (15 mL). The mixture was stirred at room temperature for 16 h. Then, it was quenched with water and the organic layers extracted with EtOAc (3×5 mL). The combined organic layers were washed with water (2×5 mL) and brine (1×5 mL), dried (Na2SO4), concentrated, and purified by flash chromatography (100% Hexane to 100% EtOAc) to give 350.0 mg (57%) of 4-(4-bromophenyl)-1-(oxetan-3-yl)piperidine.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH2:10])=[CH:5][CH:4]=1.C(O)(=O)C.[F:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=1[F:24])[CH:19]=O.C([BH3-])#N>ClCCl>[F:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=1[F:24])[CH2:19][NH:10][CH2:9][C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1
Reactant: O=Cc1ccc(F)c(F)c1
Reactant: COc1ccc(CN)cc1
Agent: [BH3-]C#N
Solvent: CC(=O)O
Solvent: ClCCl
Product: COc1ccc(CNCc2ccc(F)c(F)c2)cc1
Temperature: 100 °C
Reaction time: 16 h
Yield: 79.5 %

Procedure:
To (4-methoxyphenyl)methanamine (1.77 mL, 13.6 mmol) and acetic acid (2.7 mL, 45 mmol) in dichloromethane (15 mL) was added 3,4-difluorobenzaldehyde (1.0 m, 9.08 mmol). This mixture was heated in the microwave at 100° C. for 15 min. The reaction was cooled to room temperature and macroporous cyanoborohydride resin (9.8 g, 22.7 mmol) was added in portions. This mixture was stirred at room temperature for 16 hours. The resin was filtered off and rinsed with dichloromethane and the organics were washed with saturated sodium bicarbonate until bubbling ceased. The organics were dried over sodium sulfate and concentrated via rotovap. The resulting crude material was purified by silica gel chromatography using methanol dichloromethane gradient as eluent to afford N-(3,4-difluorobenzyl)(4-methoxyphenyl)methanamine as a yellowish oil (1.9 g, 80% yield). MS (M+H, 264); 1H NMR (400 MHz, DMSO-d6): δ, ppm: 2.63 (br s, 1H), 3.56 (s, 2H), 3.61 (s, 2H), 3.71 (s, 3H), 6.84 (d, J=8.8 Hz, 2H), 7.14 (m, 1H), 7.21 (d, J=8.4 Hz, 2H), 7.34 (m, 2H).
Reaction SMILES: [CH:1]1[C:14]2[CH:13]=[CH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][C:2]=1[CH:15]=[O:16].C(C1C=CC2C3C(=CC=CC=3)C=CC=2C=1)(=[O:19])C.C(C1C=CC2C=CC3C(C=2C=1)=CC=CC=3)(=O)C>>[CH:4]1[C:5]2[CH:6]=[CH:7][C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:14]=2[CH:1]=[C:2]([C:15]([OH:16])=[O:19])[CH:3]=1
Reactant: O=Cc1ccc2c(ccc3ccccc32)c1
Reactant: CC(=O)c1ccc2c(ccc3ccccc32)c1
Agent: CC(=O)c1ccc2ccc3ccccc3c2c1
Product: O=C(O)c1ccc2ccc3ccccc3c2c1
Yield: 51 %

Procedure:
Using the procedure outlined in 2A for 2-acetylphenanthrene, 3-acetylphenanthrene (Aldrich, technical grade), 25 g, 0.114 mol) gave 13 g (51%) of phenanthrene-3-carboxylic acid. 15.6 (0.07 mol) of this acid was converted to the corresponding acid chloride, then to 8.37 g (58%) of phenanthrene-3-carboxaldehyde mp 78°-80° (lit. 79.5°-80°, E. Mosettig and J. van de Kamp, J. Amer. Chem. Soc. 55 2395 (1933)), (C,H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8](=[O:10])[NH:7][C:6]=2[CH:11]=1.[Cl:12][C:13]1[N:18]=[C:17](Cl)[C:16]([CH3:20])=[CH:15][N:14]=1.CO>O>[Cl:12][C:13]1[N:18]=[C:17]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[O:9][C:8](=[O:10])[NH:7][C:6]=3[CH:11]=2)[C:16]([CH3:20])=[CH:15][N:14]=1
Reactant: Cc1cnc(Cl)nc1Cl
Reactant: Nc1ccc2oc(=O)[nH]c2c1
Solvent: CO
Solvent: O
Product: Cc1cnc(Cl)nc1Nc1ccc2oc(=O)[nH]c2c1
Temperature: 25 °C
Reaction time: 64 h
Yield: 71 %

Procedure:
To a vial with 5-aminobenzo[d]oxazol-2(3H)-one (300.1 mg, 2.0 mmol) and 2,4-dichloro-5-methylpyrimidine (423.8 mg, 2.6 mmol), MeOH (8 mL) and H2O (2 mL) were added. The turbid mixture was stirred at room temperature for 64 h. Precipitate from reaction mixture was collected by filtration, washing with EtOAc (3 mL×2), and was further dried in vacuo. 5-(2-Chloro-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one was obtained as an off-white solid: 394 mg (71% yield); 1H NMR (300 MHz, DMSO) δ 11.68 (br s, 1H), 8.62 (s, 1H), 7.94 (d, J=0.8, 1H), 6.97 (d, J=2.0, 1H), 6.82 (d, J=8.1, 1H), 6.74 (dd, J=2.0, 8.1, 1H), 2.15 (s, 3H); LCMS (M+) m/z 277.10.