Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:23][C:24](=[O:28])[N:25]([CH3:27])[CH3:26])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH2:10][CH2:11][C:12]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)OCC[O:13]1.O1CCCC1.Cl>[Cl-].[Na+].O>[C:12]([CH2:11][CH2:10][CH2:9][O:8][C:7]1[CH:6]=[CH:5][C:4]([NH:23][C:24](=[O:28])[N:25]([CH3:27])[CH3:26])=[CH:3][C:2]=1[Cl:1])(=[O:13])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: CN(C)C(=O)Nc1ccc(OCCCC2(c3ccccc3)OCCO2)c(Cl)c1
Agent: Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CN(C)C(=O)Nc1ccc(OCCCC(=O)c2ccccc2)c(Cl)c1
Reaction time: 8 h

Procedure:
A mixture of 3-{3-chloro-4-[3-(2-phenyl-1,3-dioxolan-2-yl)propoxy]phenyl}-1,1-dimethylurea (2.03 g; 0.005 mol), tetrahydrofuran (10 ml) and 10% aqueous hydrochloric acid (2 ml) is stirred overnight. The reaction mixture is poured into brine (100 ml) and extracted with methylene chloride. The organic layer is washed with water, dried and evaporated to afford the product: 1.69 g of an off-white solid. Recrystallization from a toluene-hexane mixture (50 ml) yields 1.33 g of cream colored needles, m.p. 129°-130° C.
Reaction SMILES: [Br:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][NH:7][C:8]([C:10](=[CH:15]N(C)C)[C:11](OC)=[O:12])=[O:9])=[CH:4][CH:3]=1.Cl.[N:22]1([C:27](=[NH:29])[NH2:28])[CH:26]=[CH:25][CH:24]=[N:23]1.C1CCN2C(=NCCC2)CC1>CC(N(C)C)=O.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11]([OH:12])=[N:29][C:27]([N:22]3[CH:26]=[CH:25][CH:24]=[N:23]3)=[N:28][CH:15]=2)=[O:9])=[CH:19][CH:20]=1
Reactant: COC(=O)C(=CN(C)C)C(=O)NCc1ccc(Br)cc1
Reactant: N=C(N)n1cccn1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CC(=O)N(C)C
Solvent: C1CCC2=NCCCN2CC1
Product: O=C(NCc1ccc(Br)cc1)c1cnc(-n2cccn2)nc1O
Reaction time: 0.5 h

Procedure:
All of the unpurified product of step B was diluted with DMA (28 mL) before adding 1H-pyrazole-1-carboximidamide hydrochloride (5.13 g, 35.0 mmol), and DBU (5.28 mL, 35.0 mmol) at rt. The reaction was aged at 110° C. for about 30 min. The reaction was diluted with EtOAc and washed with aq. 2 M HCl and water. The organic portion was concentrated and diluted with EtOH. The mixture was aged for about 30 min at 75° C. and cooled. The solid is isolated by filtration and washed with EtOH to afford the title compound. HPLC/MS: 374.0 (M+1); Rt=2.70 min.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1([CH:21]=[O:22])[C:13]2[C:8](=[CH:9][C:10]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)=[C:11]([Cl:14])[CH:12]=2)[CH2:7][CH2:6]1)=[O:4].[O:23]1CCCC1>[Ag]=O.O>[CH3:1][O:2][C:3]([C:5]1([C:21]([OH:23])=[O:22])[C:13]2[C:8](=[CH:9][C:10]([CH:15]3[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]3)=[C:11]([Cl:14])[CH:12]=2)[CH2:7][CH2:6]1)=[O:4]
Reactant: COC(=O)C1(C=O)CCc2cc(C3CCCCC3)c(Cl)cc21
Reactant: C1CCOC1
Agent: O=[Ag]
Solvent: O
Product: COC(=O)C1(C(=O)O)CCc2cc(C3CCCCC3)c(Cl)cc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 3.0 g of crude 1-formyl-5-cyclohexyl-6-chloro-1-indanecarboxylic acid methyl ester in 30 of tetrahydrofurane and 3 ml of water is treated with 4 equivalents of silver oxide (manufactured according to Corey et al., J. Amer. Chem. Soc., 90, 5616 (1963)) and the mixture is stirred overnight at room temperature. The reaction solution is then filtered through Celite and the filtrate is partitioned between 150 ml of methylene chloride and 100 ml of 0.1 N hydrochloric acid. The organic phase is washed with twice 150 ml of water, dried over sodium sulphate and evaporated in vacuo. Chromatography of the evaporation residue on silica gel, using benzene/ethyl acetate/glacial acetic acid, 90:30:1, as the eluting agent, yields crude 1-methoxycarbonyl-5-cyclohexyl-6-chloro-1-indanecarboxylic acid which can be purified further by fractional crystallisation from benzene-hexane; melting point 139°-142° C.
Reaction SMILES: [CH2:1]1[C:6]2([CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]2)[CH2:5][CH2:4][C:3](=O)[CH2:2]1.S([CH2:23][N+:24]#[C-])(C1C=CC(C)=CC=1)(=O)=O.CCO.CC([O-])(C)C.[K+]>COCCOC>[CH2:1]1[C:6]2([CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]2)[CH2:5][CH2:4][CH:3]([C:23]#[N:24])[CH2:2]1
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Reactant: O=C1CCC2(CCCCC2)CC1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCO
Solvent: COCCOC
Product: N#CC1CCC2(CCCCC2)CC1
Temperature: 0 °C
Reaction time: 1 h
Yield: 72.2 %

Procedure:
To a solution of spiro[5.5]undecan-3-one (1.66 g, 10 mmol) and tosylmethylisocyanide (2.54 g, 13 mmol) in DME (50 ml) and abs. EtOH (1 ml) was added KOtBu (2.69 g, 24 mmol) portionwise during 0.5 hr at −10° C. After addition, the reaction mixture was stirred at 0° C. for 1 hr then 2 hr at ambient temperature. Solvent was removed in vacuo and the resulting residue was extracted with diethyl ether (50 ml×3) and the combined organic layer was washed with water (50 ml×3). The organic layer was dried with anhydrous MgSO4, concentrated under reduced pressure and purified by flash column chromatography (50%-100% CH2Cl2/Hexane) to give the nitrile as colorless solid (1.28 g, 72% Yield). 1H-NMR (360 MHz, CDCl3) δ 2.58-2.53 (m, 1H), 1.83-1.70 (m, 4H), 1.63-1.58 (m, 2H), 1.40-1.26 (m, 8H), 1.28-1.20 (m, 4H); 13C-NMR (90 MHz, CDCl3) δ 122.79, 34.41, 31.88, 28.37, 26.88, 24.73, 21.64, 21.55; ESI-MS: Calculated for C12H19N (M+H)+178.3. Found: 178.2.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:7]2[C:24]([CH3:25])=[N:23][N:22]([CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][O:27]3)[C:8]=2[N:9]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][O:20][CH3:21])=[CH:14][CH:13]=2)[CH:11]=1)=[O:5])C.[OH-].[Na+]>C(O)C>[CH3:21][O:20][CH2:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([C:10]2[CH:11]=[C:6]([C:4]([OH:5])=[O:3])[C:7]3[C:24]([CH3:25])=[N:23][N:22]([CH:26]4[CH2:31][CH2:30][CH2:29][CH2:28][O:27]4)[C:8]=3[N:9]=2)=[CH:13][CH:14]=1
Reactant: CCOC(=O)c1cc(-c2ccc(OCOC)cc2)nc2c1c(C)nn2C1CCCCO1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COCOc1ccc(-c2cc(C(=O)O)c3c(C)nn(C4CCCCO4)c3n2)cc1
Yield: 89.1 %

Procedure:
To 2.09 g 6-(4-methoxymethoxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester in 140 ml ethanol was added 100 ml of 1M aqueous sodium hydroxide solution. After 3 h at r.t. the volatiles were removed in vacuo. The residue was taken up in water and the pH was adjusted to 4-5. The aqueous phase was extracted with ethyl acetate three times. The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica, dichloromethane/MeOH gradient with addition of aqueous ammonia) to obtain 1.74 g (90%) of the title compound.
Reaction SMILES: [CH2:1]([O:8][N:9]1[C:14](=[O:15])[C:13]2[CH:16]=[C:17]([F:21])[C:18](Cl)=[N:19][C:12]=2[N:11]([CH2:22][CH3:23])[C:10]1=[O:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:25]([O:29][C:30]([NH:32][CH:33]1[CH2:37][CH2:36][NH:35][CH2:34]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].C(N(CC)CC)C>ClCCl>[CH2:1]([O:8][N:9]1[C:14](=[O:15])[C:13]2[CH:16]=[C:17]([F:21])[C:18]([N:35]3[CH2:36][CH2:37][CH:33]([NH:32][C:30]([O:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:31])[CH2:34]3)=[N:19][C:12]=2[N:11]([CH2:22][CH3:23])[C:10]1=[O:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)NC1CCNC1
Reactant: CCn1c(=O)n(OCc2ccccc2)c(=O)c2cc(F)c(Cl)nc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCn1c(=O)n(OCc2ccccc2)c(=O)c2cc(F)c(N3CCC(NC(=O)OC(C)(C)C)C3)nc21
Yield: 85.7 %

Procedure:
Following the procedure of Example X-2, the reaction of 3-benzyloxy-7-chloro-1-ethyl-6-fluoro-1H-pyrido[2,3-d]pyrimidine-2,4-dione (Example N-2, 200 mg, 0.572 mmol) with 3-(N-tert-butoxycarbonylamino)pyrrolidine (117 mg, 0.629 mmol) in dichloromethane (5 mL) in the presence of triethylamine (0.087 mL) afforded 245 mg of the title compound as a solid, mp 157-159° C.
Reaction SMILES: Cl.[NH2:2][CH:3]1[CH2:7][CH2:6][N:5]([C:8]2[N:9]=[C:10]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH3:27])[CH:19]=3)[C:11]3[N:16]=[CH:15][S:14][C:12]=3[N:13]=2)[CH2:4]1.[O:28]=[C:29]1[CH2:37][C:36]2[C:31](=[CH:32][C:33]([C:38](O)=[O:39])=[CH:34][CH:35]=2)[NH:30]1.CCN=C=NCCCN(C)C.CN1C=CN=C1>C(Cl)Cl>[CH3:27][O:26][C:20]1[CH:19]=[C:18]([NH:17][C:10]2[C:11]3[N:16]=[CH:15][S:14][C:12]=3[N:13]=[C:8]([N:5]3[CH2:6][CH2:7][CH:3]([NH:2][C:38]([C:33]4[CH:32]=[C:31]5[C:36]([CH2:37][C:29](=[O:28])[NH:30]5)=[CH:35][CH:34]=4)=[O:39])[CH2:4]3)[N:9]=2)[CH:23]=[CH:22][C:21]=1[O:24][CH3:25]
Reactant: COc1ccc(Nc2nc(N3CCC(N)C3)nc3scnc23)cc1OC
Reactant: O=C1Cc2ccc(C(=O)O)cc2N1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: Cn1ccnc1
Solvent: ClCCl
Product: COc1ccc(Nc2nc(N3CCC(NC(=O)c4ccc5c(c4)NC(=O)C5)C3)nc3scnc23)cc1OC
Temperature: 25 °C
Reaction time: 16 h
Yield: 23.5 %

Procedure:
A mixture of 5-(3-aminopyrrolidin-1-yl)-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine hydrochloride (82 mg, 0.2 mmol), 2-oxoindoline-6-carboxylic acid (36 mg, 0.2 mmol), EDCI (76 mg, 0.4 mmol) and N-methylimidazole (50 mg, 0.6 mmol) in 5 mL of DCM was stirred at room temperature for 16 hours. The mixture was washed with water (4 mL), The organic layer was dried over Na2SO4. After filtration and concentration, the residue was purified by preparative TLC (Silica gel, 20 cm×20 cm, separated by EtOAc, eluted by DCM:MeOH=1:20, v/v) to give N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)-2-oxoindoline-6-carboxamide (25 mg, 23.5%). 1H NMR (300 MHz, DMSO): δ 10.52 (s, 1H), 9.56 (s, 1H), 8.81 (s, 1H), 8.61 (d, 1H, J=6.3 Hz), 7.90 (brs, 1H), 7.48-7.46 (m, 2H), 7.28-7.25 (m, 2H), 6.93-6.90 (m, 1H), 4.54 (brs, 1H), 3.77-3.34 (m, 11H), 2.50-2.34 (m, 1H), 2.07-1.99 (m, 2H). LC-MS: 532 [M+H]+, 530 [M−H]−, tR=1.35 min. HPLC: 97.39% at 214 nm, 97.05% at 254 nm, tR=4.54 min.
Reaction SMILES: [CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:26]([OH:28])=O)=[C:21]5[C:25]=4[O:24][CH2:23][CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:29])[C:8](=[O:30])[C@H:7]2[CH2:31][CH3:32])[CH2:5][CH2:4][CH2:3][CH2:2]1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH3:64][N:65]1[CH2:70][CH2:69][N:68]([C@H:71]2[CH2:76][CH2:75][C@H:74]([NH2:77])[CH2:73][CH2:72]2)[CH2:67][CH2:66]1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:26]([NH:77][C@H:74]5[CH2:73][CH2:72][C@H:71]([N:68]6[CH2:67][CH2:66][N:65]([CH3:64])[CH2:70][CH2:69]6)[CH2:76][CH2:75]5)=[O:28])=[C:21]5[C:25]=4[O:24][CH2:23][CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:29])[C:8](=[O:30])[C@H:7]2[CH2:31][CH3:32])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)O)c4c3OCC4)nc2N1C1CCCC1
Reactant: CN1CCN([C@H]2CC[C@H](N)CC2)CC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: O=C([O-])[O-]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)N[C@H]4CC[C@H](N5CCN(C)CC5)CC4)c4c3OCC4)nc2N1C1CCCC1
Reaction time: 3 h

Procedure:
7-[[(7R)-8-Cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 1q (200 mg, 0.46 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (147 mg, 0.46 mmol) were dissolved in 25 mL of anhydrous dichloromethane followed by the addition of diisopropylethylamine (0.2 mL, 1 mmol) and (trans)-4-(4-methylpiperazin-1-yl)cyclohexanamine 17b (90 mg, 0.46 mmol) successively. The reaction solution was stirred for 3 hours. The resulting solution was added with 20 mL of saturated sodium carbonate solution and extracted with dichloromethane (30 mL×3). The combined organic phase was washed with saturated sodium carbonate solution (30 mL×2), water (30 mL) and saturated sodium chloride solution (30 mL) successively, then dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-[(trans)-4-(4-methylpiperazin-1-yl)cyclohexyl]-2,3-dihydrobenzofuran-4-carboxamide 19 (190 mg, yield: 67.0%) as a white solid.
Reaction SMILES: [CH3:1][C:2]([N:5]([O:10])[C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:4])[CH3:3].[C:11]([OH:19])(=[O:18])[CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16].C1(C)C=CC(S([O-])(=O)=O)=CC=1.CN(C)C1C=C[NH+]=CC=1.CC(C)N=C=NC(C)C>C(O)(C)C.C(Cl)Cl>[CH3:1][C:2]([N:5]([O:10])[C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:4])[CH3:3].[C:11]([O-:19])(=[O:18])[CH2:12][CH2:13][CH2:14][C:15]([O-:17])=[O:16]
Reactant: O=C(O)CCCC(=O)O
Agent: CC(C)(C)N([O])C(C)(C)C
Agent: CC(C)N=C=NC(C)C
Agent: *CC(*)C
Solvent: CC(C)O
Solvent: ClCCl
Product: O=C([O-])CCCC(=O)[O-]

Procedure:
DTBn (0.5 mol, 209.66 g), glutaric acid (0.5 mol, 66.06 g), DPTS (0.2 mol, 58.84 g) were placed in a 3 L flask equipped with an overhead stirrer and condenser. Methylene chloride (1.2 L) was added to the flask and the contents stirred until all the solids were dispersed. DIPC (1.5 mol, 189.3 g, 234.2 mL) was added and stirring continued for 20-22 h by which time reaction mixture was viscous. The polymer was isolated by repeated precipitations from methylene chloride and isopropanol (IPA). The solid polymer was transferred to a polypropylene tray and left to dry in the hood overnight, transferred to a vacuum oven at 50° C. and dried to constant weight. The yield of poly(DTBn-glutarate) was 203 g (76%). The polymer had a molecular weight of 100 kDa and a Tg of 66° C.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[O:11][C:12](=[O:27])[C@H:13]([CH2:16][CH2:17][CH2:18][NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[NH:14][CH3:15].[C:28]([NH:35][C@H:36]([C:45](O)=[O:46])[CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29]>>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[O:11][C:12](=[O:27])[C@H:13]([CH2:16][CH2:17][CH2:18][NH:19][C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[N:14]([C:45](=[O:46])[C@H:36]([CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[NH:35][C:28]([O:30][C:31]([CH3:34])([CH3:32])[CH3:33])=[O:29])[CH3:15]
Reactant: CC(C)(C)OC(=O)N[C@@H](CCc1ccccc1)C(=O)O
Reactant: CN[C@@H](CCCNC(=O)OC(C)(C)C)C(=O)Oc1ccc2ccccc2c1
Product: CN(C(=O)[C@H](CCc1ccccc1)NC(=O)OC(C)(C)C)[C@@H](CCCNC(=O)OC(C)(C)C)C(=O)Oc1ccc2ccccc2c1

Procedure:
Using Procedure D, coupling of Nδ-Boc-Nα-methylornithinyl 2-naphthyl ether (E) and Boc-homophenylalanine afforded titled compound as a glassy solid: 1H NMR (400 MHz, CDCl3) δ1.44 (2s, 18H), 1.58-1.70 (m, 4H), 1.98 (m, 2H), 2.73 (m, 2H), 2.83 (s, 3H), 3.18 (m, 2H), 4.08 (m, 2H), 4.61 (m, 1H), 7.09 (m, 2H), 7.35 (m, 5H), 7.49 (t, J=9.1 Hz, 1H), 7.59 (t, J=9.0 Hz, 1H), and 7.81 (3H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:13])=[N:11][N:12]=2)=[CH:4][C:3]=1[C:14]1[CH:19]=[CH:18][C:17]([C:20](O)=[O:21])=[CH:16][CH:15]=1.C1C=CC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.[CH3:45][CH:46]([CH:48]([NH2:52])[CH:49]([CH3:51])[CH3:50])[CH3:47]>CN(C=O)C>[CH3:45][CH:46]([CH:48]([NH:52][C:20]([C:17]1[CH:18]=[CH:19][C:14]([C:3]2[CH:4]=[C:5]([C:8]3[O:9][C:10]([CH3:13])=[N:11][N:12]=3)[CH:6]=[CH:7][C:2]=2[CH3:1])=[CH:15][CH:16]=1)=[O:21])[CH:49]([CH3:51])[CH3:50])[CH3:47]
Reactant: Cc1nnc(-c2ccc(C)c(-c3ccc(C(=O)O)cc3)c2)o1
Reactant: CC(C)C(N)C(C)C
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: Cc1nnc(-c2ccc(C)c(-c3ccc(C(=O)NC(C(C)C)C(C)C)cc3)c2)o1
Reaction time: 18 h

Procedure:
2′-Methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxylic acid (11.3 mg, 0.034 mmol), HOBT (6.0 mg, 0.044 mmol), 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (8.0 mg, 0.042 mmol) and 2,4-dimethyl-3-pentylamine (0.34 mmol) were mixed in DMF (0.7 ml) and the reaction left at room temperature for 18 h. The DMF was evaporated under vacuum and the residue partitioned between DCM (0.4 ml) and water (0.4 ml). The organic phase was washed with aqueous sodium hydroxide (0.5M, 0.2 ml) and the DCM evaporated under vacuum. The residue was purified by mass directed HPLC to give N-(2,4-dimethyl-3-pentyl)-2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxamide.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:27]=[CH:26][C:9]([C:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][CH2:22][CH2:23][CH:24]=[CH2:25])=[CH:15][CH:14]=2)=[O:11])=[CH:8][CH:7]=1)[CH2:2][CH:3]=[CH2:4].[CH3:28][SiH:29]([CH3:31])[CH3:30]>ClCCl.C1([Pt](Cl)(Cl)C2C=CC=C2)C=CC=C1>[CH3:28][Si:29]([CH3:31])([CH3:30])[CH:1]([O:5][C:6]1[CH:27]=[CH:26][C:9]([C:10]([O:12][C:13]2[CH:14]=[CH:15][C:16]([O:19][CH:20]([Si:29]([CH3:31])([CH3:30])[CH3:28])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[CH:17][CH:18]=2)=[O:11])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4]
Reactant: C[SiH](C)C
Reactant: C=CCCCCOc1ccc(OC(=O)c2ccc(OCCC=C)cc2)cc1
Agent: Cl[Pt](Cl)(C1C=CC=C1)C1C=CC=C1
Solvent: ClCCl
Product: CCCCCC(Oc1ccc(OC(=O)c2ccc(OC(CCC)[Si](C)(C)C)cc2)cc1)[Si](C)(C)C

Procedure:
0.35 g (0.01 mmol of Pt) of L.5% strength dicyclopentadienylplatinum dichloride solution in dichloromethane was added as catalyst to a solution of 5.00 g (9.71 mmol) of 4-(5-hexenyloxy)phenyl 4-(3-butenyloxy)benzoate in 10 ml of dichloromethane, and 2.02 g (27.2 mmol) of trimethylsilane were passed into the refluxing mixture over the course of 8 hours. After complete hydrosilylation of the olefin, the reaction mixture was flushed with nitrogen, and the dichloromethane was removed by vacuum distillation on a rotary evaporator. The crude product was purified by chromatography on silica gel, to give 4-(1-trimethylsilylhexyloxy)phenyl 4-(1-trimethylsilylbutyloxy)benzoate, phases: c 72 i.
Reaction SMILES: O[CH2:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH2:13][CH2:14][CH2:15][CH2:16][N:17]([CH2:21][CH2:22][CH3:23])[CH2:18][CH2:19][CH3:20])[CH:9]=2)[CH:4]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:43]1(=[O:53])[NH:47][C:46](=[O:48])[C:45]2=[CH:49][CH:50]=[CH:51][CH:52]=[C:44]12.N(C(OCC)=O)=NC(OCC)=O.C1(C)C=CC=CC=1>C1COCC1>[C:43]1(=[O:53])[N:47]([CH2:2][C:3]2[CH:12]=[CH:11][C:10]3[C:5](=[CH:6][CH:7]=[C:8]([CH2:13][CH2:14][CH2:15][CH2:16][N:17]([CH2:21][CH2:22][CH3:23])[CH2:18][CH2:19][CH3:20])[CH:9]=3)[CH:4]=2)[C:46](=[O:48])[C:45]2=[CH:49][CH:50]=[CH:51][CH:52]=[C:44]12
Reactant: O=C1NC(=O)c2ccccc21
Reactant: CCCN(CCC)CCCCc1ccc2cc(CO)ccc2c1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CCCN(CCC)CCCCc1ccc2cc(CN3C(=O)c4ccccc4C3=O)ccc2c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 75.9 %

Procedure:
The compound (70.0 mg) obtained in Example 124-2 was added with triphenylphosphine (76.1 mg) and phthalimide (36.1 mg), and then dissolved in anhydrous THF (1.0 ml). Subsequently, the solution was added with a 40% diethyl azodicarboxylate/toluene solution (0.132 ml) in an ice bath and stirred at room temperature for 3 hours under a nitrogen atmosphere. After completion of the reaction, the solvent was distilled off and the residue was then purified through silica gel column chromatography (hexane/ethyl acetate), thereby obtaining the subject compound (75.0 mg) as a white solid.
Reaction SMILES: Cl/[CH:2]=[CH:3]\Cl.[C:5]1([S-:11])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[Na+]>CN(P(N(C)C)(N(C)C)=O)C>[C:5]1([S:11]/[CH:6]=[CH:5]\[S:11][C:3]2[CH:2]=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: Cl/C=C\Cl
Reactant: [S-]c1ccccc1
Agent: [Na+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: C(=C\Sc1ccccc1)\Sc1ccccc1

Procedure:
A solution of (Z)-1,2-dichloroethene (0.49 g, 5.04 mmol) and compound 43 (2.0 g, 15.15 mmol) in HMPA (10 mL) was stirred under nitrogen for 1 h. The solvent was removed under reduced pressure to give the crude product that was then purified by column chromatography using 100% hexane as a solvent to give control (1.04 g, 85%). 1H NMR (400 MHz, CDCl3) δ 6.55 (s, 2H), 7.29 (m, 2H), 7.35 (t, J=7.7 Hz, 4H), 7.43 (s, 2H), 7.44 (m, 2H). HRMS ESI (m/z): Calculated for C14H12S2 [M]+: 244.0380. found: 244.0377.
Reaction SMILES: [C:1]([N:6]1[C@@H:10]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:9][O:8][C:7]1=[O:18])(=[O:5])/[CH:2]=[CH:3]/[CH3:4].C(N(CC)CC)C.[O-]S(C(F)(F)F)(=O)=O.C([B+]CCCC)CCC.[CH:43](=[O:46])[CH2:44][CH3:45]>C(Cl)Cl.CCCCCC.C(OCC)(=O)C>[CH:3]([C@@H:2]([C@H:43]([OH:46])[CH2:44][CH3:45])[C:1]([N:6]1[C@@H:10]([CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:9][O:8][C:7]1=[O:18])=[O:5])=[CH2:4]
Reactant: CCC=O
Reactant: C/C=C/C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Agent: CCCC[B+]CCCC
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: C=C[C@H](C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)[C@H](O)CC
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 65 %

Procedure:
A solution of 2.45 g of (4S)-N-crotonyl-4-benzyl-2-oxazolidinone in 10 ml of anhydrous CH2Cl2 was cooled to −78° C., and 1.7 ml of triethylamine was added followed by 10.5 ml of a 1 M solution of dibutylboron triflate in CH2Cl2. After 30 minutes, the reaction was warmed to 0° C., kept for 20 minutes, then recooled to −78° C. Propionaldehyde (0.9 ml) was added, and the reaction was allowed to slowly warm to ambient temperature over 16 hours. Standard oxidative workup yielded the product (1.98 g, 65% yield) after chromatography (2:1 hexane/ethyl acetate). 1H-NMR (360 MHz, CDCl3): δ 7.2–7.35 (m,5H); 6.02 (1H,m); 5.41 (m,2H); 4.72 (m,1H); 4.58 (dd,1H); 4.20 (m,2H); 3.92 (m,1H); 3.25 (dd,1H); 2.98 (br s, 1H); 2.76 (dd,1H); 1.53 (m,2H); 0.98 (t,3H).
Reaction SMILES: CCOCC.[OH:6][CH2:7][P:8](=[O:17])([O:13][CH:14]([CH3:16])[CH3:15])[O:9][CH:10]([CH3:12])[CH3:11].C(N(CC)CC)C.[F:25][C:26]([F:38])([F:37])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[S:33](Cl)(=[O:35])=[O:34]>C(OCC)(=O)C>[F:38][C:26]([F:25])([F:37])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[S:33]([O:6][CH2:7][P:8](=[O:17])([O:9][CH:10]([CH3:12])[CH3:11])[O:13][CH:14]([CH3:16])[CH3:15])(=[O:34])=[O:35]
Reactant: O=S(=O)(Cl)c1ccccc1C(F)(F)F
Reactant: CC(C)OP(=O)(CO)OC(C)C
Solvent: CCOC(C)=O
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: CC(C)OP(=O)(COS(=O)(=O)c1ccccc1C(F)(F)F)OC(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 64.2 %

Procedure:
A solution of 30 ml of ether, 13.3 g of diisopropyl P-(hydroxymethyl)phosphonate, prepared in Example 17, and 10.5 ml of triethylamine was added dropwise over 60 minutes to a solution of 15.35 g of 2-(trifluoromethyl)benzenesulfonyl chloride and 50 ml of ether. After the mild exotherm, the reaction was allowed to stir at room temperature overnight and then was diluted with 200 ml of ethyl acetate, the ethyl acetate solution washed with two 100 ml portions of water, dried with magnesium sulfate, filtered, and concentrated to yield 16.3 g of the desired product as an oil.