Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:9]1(S(OCCCCCCCCCCCC)(=O)=O)C=CC=C[CH:10]=1.[Na]>>[CH2:7]1[CH:8]2[CH:3]([CH2:2][CH2:1][CH2:9][CH2:10]2)[CH2:4][CH2:5][CH2:6]1
Reactant: CCCCCCCCCCCCOS(=O)(=O)c1ccccc1
Reactant: C=Cc1ccccc1
Agent: [Na]
Product: C1CCC2CCCCC2C1

Procedure:
Except for changing the amount of the styrene from 150 parts to 100 parts and not using sodium dodecyl benzenesulfonate when performing the polymerization, the same procedure was followed as in Example 6 to obtain a decalin dispersion of the polymer particles J which do not have a core-shell structure. The obtained polymer particles J had an average particle size of 500 nm. Further, except for using the obtained decalin dispersion of polymer particles J not having a core-shell structure, the same procedure was followed as in Example 1 to prepare the slurries and produce the all-solid state secondary cell and the same procedure was followed as in Example 1 to evaluate it. The results are shown in Table 1.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:5]([NH:6][C:7](=[O:9])[CH3:8])=[CH:4][CH:3]=1.F[C:13]1[C:18]([C:19]2[N:27]=[C:26]([CH3:28])[N:25]=[C:24]3[C:20]=2[N:21]=[CH:22][N:23]3[CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][O:30]2)=[CH:17][CH:16]=[CH:15][N:14]=1.C[Si](N[Si](C)(C)C)(C)C.[Li]>C1COCC1.[NH4+].[Cl-]>[CH3:28][C:26]1[N:25]=[C:24]2[C:20]([N:21]=[CH:22][N:23]2[CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][O:30]2)=[C:19]([C:18]2[C:13]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([NH:6][C:7](=[O:9])[CH3:8])=[CH:10][CH:11]=3)=[N:14][CH:15]=[CH:16][CH:17]=2)[N:27]=1
Reactant: CC(=O)Nc1ccc(N)cc1
Reactant: Cc1nc(-c2cccnc2F)c2ncn(C3CCCCO3)c2n1
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: [Cl-]
Agent: [Li]
Solvent: C1CCOC1
Product: CC(=O)Nc1ccc(Nc2ncccc2-c2nc(C)nc3c2ncn3C2CCCCO2)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 67.6 %

Procedure:
A glass microwave reaction vessel was charged with 4′-aminoacetanilide (69.0 mg, 0.460 mmol, Aldrich, St. Louis, Mo.) and 6-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (120 mg, 0.383 mmol) in THF (5 mL), Ar was bubbled in for 2 minutes and the reaction was sealed. The reaction mixture was cooled to 0° C., lithium bis(trimethylsilyl)amine (1 N in THF, 1.2 mL, 1.2 mmol) was added dropwise and the solution was stirred at 0° C. for 1 h. After warming to room temperature, the reaction mixture was diluted with saturated NH4Cl (10 mL) and extracted with EtOAc (3×). The organic extracts were washed with brine and dried over Na2SO4. The solution was filtered and concentrated in vacuum. The crude material was purified by chromatography through a RediSep®, Teledyne ISCO, Lincoln, Nebr., pre-packed silica gel column (25 g), eluting with a gradient of 2% to 10% 2 M NH3/MeOH in CH2Cl2, to provide N-(4-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)acetamide (115 mg, 0.259 mmol, 67.7% yield) as a yellow solid. MS (ESI positive ion) m/z 444 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.68 (s, 1H); 9.86 (s, 1H); 9.72 (d, J=8.02 Hz, 1H); 8.86 (s, 1H); 8.34 (d, J=2.15 Hz, 1H); 7.75 (d, J=7.82 Hz, 2H); 7.56 (d, J=7.63 Hz, 2H); 6.98 (s, 1H); 5.84 (d, J=10.95 Hz, 1H); 3.92-4.22 (m, 1H); 3.64-3.87 (m, 1H); 2.90 (s, 3H); 2.30-2.33 (m, 1H); 2.03 (s, 3H); 1.99-2.01 (m, 2H); 1.79-1.82 (m, 1H); 1.48-1.71 (m, 2H).
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=CC(S(Cl)(=O)=O)=C[CH:2]=1.[Br:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]([OH:21])=[O:20])=[N:17][CH:18]=1.N1C=CC=CC=1.C(=O)([O-])O.[Na+]>C(O)(C)(C)C.C(OCC)C>[C:1]([O:20][C:19]([C:16]1[CH:15]=[CH:14][C:13]([Br:12])=[CH:18][N:17]=1)=[O:21])([CH3:11])([CH3:6])[CH3:2]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: O=C(O)c1ccc(Br)cn1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Solvent: CC(C)(C)O
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)c1ccc(Br)cn1
Temperature: 40 °C
Reaction time: 2 h
Yield: 73 %

Procedure:
para-Toluene sulfonyl chloride (262 mg, 1.38 mmol) was added to a solution of 5-bromo-2-carboxypyridine (118 mg, 0.58 mmol) and pyridine (0.3 mL, 0.39 mmol) in tert-butanol (1 mL) and the mixture was stirred at 40° C. for 10 minutes and room temperature for 2 hours. Saturated sodium hydrogen carbonate solution (4 mL) was then added and the mixture was stirred for 5 minutes. Diethyl ether was next added and the bi-phasic mixture was stirred for a further 10 minutes. The organic layer was then separated, washed with brine, dried over magnesium sulfate and concentrated in vacuo. Purification of the residue by column chromatography on silica gel, eluting with pentane:ethyl acetate, 100:0 to 80:20, afforded the title compound as a colourless solid in 73% yield, 110 mg.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[C:33]([O:37][C:38](=[O:46])[NH:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][NH2:45])([CH3:36])([CH3:35])[CH3:34].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[C:33]([O:37][C:38]([NH:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][NH:45][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2)=[O:46])([CH3:36])([CH3:35])[CH3:34]
Reactant: CC(C)(C)OC(=O)NCCCCCN
Reactant: Brc1cccc2cnccc12
Agent: CC(C)(C)P(c1ccccc1-c1ccccc1)C(C)(C)C
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)NCCCCCNc1cccc2cnccc12
Temperature: 70 °C
Yield: 84.3 %

Procedure:
Under nitrogen atmosphere, a suspension of 5-bromoisoquinoline (245 mg), tris(dibenzylideneacetone)palladium(0) (56 mg), 2-(di-tert-butylphosphino)biphenyl (69 mg), N-(5-aminopentyl)carbamic acid tert-butyl ester (282 mg, Tokyo Kasei Kogyo) and sodium tert-butoxide (160 mg) in toluene was stirred with heating at 70° C. for 4.5 hours. The reaction mixture was cooled to room temperature and purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1) to obtain the title compound (327 mg).
Reaction SMILES: F[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[C:5]#[N:6].[Br:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[OH:20].C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[Br:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[O:20][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[C:5]#[N:6]
Reactant: Oc1ccccc1Br
Reactant: N#Cc1ccc([N+](=O)[O-])c(F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: N#Cc1ccc([N+](=O)[O-])c(Oc2ccccc2Br)c1
Temperature: 25 °C
Reaction time: 5 h
Yield: 92.5 %

Procedure:
To a solution of 3-fluoro-4-nitrobenzonitrile (6.3 g; 37.93 mmol) and 2-bromophenol (4.4 mL; 37.94 mmol) in DMF (50 mL) was added potassium carbonate (6.29 g; 45.51 mmol). The mixture was stirred for 5 h at rt. Water (100 mL) was added, and a precipitate formed. The solid was separated via filtration, washed with water, and dried to yield 11.20 g (92.5%) of 3-(2-bromo-phenoxy)-4-nitrobenzonitrile, 1a.
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:11][O:12][C:13]1[CH:14]=[C:15]([C:21]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([N+:31]([O-:33])=[O:32])[CH:24]=2)=O)[CH:16]=[C:17]([O:19][CH3:20])[CH:18]=1.[CH2:34]1COC[CH2:35]1>[Br-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C>[CH3:11][O:12][C:13]1[CH:14]=[C:15]([C:21]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([N+:31]([O-:33])=[O:32])[CH:24]=2)=[CH:34][CH3:35])[CH:16]=[C:17]([O:19][CH3:20])[CH:18]=1
Reactant: COc1cc(OC)cc(C(=O)c2ccc(OC)c([N+](=O)[O-])c2)c1
Reactant: C1CCOC1
Agent: CC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Br-]
Product: CC=C(c1cc(OC)cc(OC)c1)c1ccc(OC)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 97 %

Procedure:
Lithium bis(trimethylsilyl)amide (8.8 mL, 8.8 mmol) was added dropwise to a stirred suspension of (ethyl)triphenylphosphonium bromide (3.28 g, 8.8 mmol) in anhydrous THF (30 mL) at 0° C. After 10 min at cold, the reaction mixture was stirred at room temperature for 40 min. The Wittig reagent was then added dropwise to a stirred solution of (3,5-dimethoxy-phenyl)-(4-methoxy-3-nitro-phenyl)-methanone (1.40 g, 4.4 mmol) in THF (30 mL) at 0° C. The reaction mixture was stirred at room temperature for 1 h. The solution was poured into ice water (100 mL) and extracted with CH2Cl2 (4×40 mL). The combined organic layers were washed with water (2×40 mL), brine (40 mL) and dried (MgSO4). Removal of solvent and chromatography (Silica Gel) gave a mixture of (E/Z) 4-[1-(3,5-dimethoxy-phenyl)-propenyl]-1-methoxy-2-nitro-benzene as an oil (1.40 g, 97% yield): 1H NMR (CDCl3) δ 1.76-1.79 (d, J=6.5 Hz, 6H, 2CH3), 3.75-3.78 (2s, 12H, 4OCH3), 3.93-3.99 (2s, 6H, 2OCH3), 6.12-6.22 (m, 2H, 2CH), 6.29-7.75 (m, 12H, Ar); 13C NMR (CDCl3) δ 15.68, 15.71, 55.33, 56.57, 99.04, 99.29, 105.82, 107.91, 113.09, 113.27, 123.68, 125.01, 125.92, 127.04, 132.21, 132.48, 135.34, 135.80, 139.92, 140.83, 144.27, 151.63, 151.85, 160.63, 160.85.
Reaction SMILES: [CH3:1]OP(C)(=O)OC.[P:8]([O:25]C1C=CC(C)=CC=1)([O:17][C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=1)[O:9][C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=1.CI>>[C:10]1([O:9][P:8]([CH3:1])(=[O:25])[O:17][C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=1
Reactant: Cc1ccc(OP(Oc2ccc(C)cc2)Oc2ccc(C)cc2)cc1
Reactant: COP(C)(=O)OC
Solvent: CI
Product: Cc1ccc(OP(C)(=O)Oc2ccc(C)cc2)cc1
Temperature: 245 °C
Reaction time: 0.5 h
Yield: 263.8 %

Procedure:
A mixture of 64 g of methane phosphonic acid dimethyl ester (0.516 mol), 352 g of tris-p-cresyl phosphite (1.00 mol) and 2 ml of methyl iodide is slowly heated to 245° C. and tempered at this temperature for 30 minutes. Vacuum distillation yields 376 g of methane phosphonic acid di-p-cresyl ester (Bp1 mm 144° C.), 98.6% pure.
Reaction SMILES: C[N:2](C)[CH:3]=[C:4]([C:10]1[CH:15]=[CH:14][N:13]=[C:12]([F:16])[CH:11]=1)[C:5](=O)[CH:6]([CH3:8])[CH3:7].[NH2:18]N>CO.CCOC(C)=O>[F:16][C:12]1[CH:11]=[C:10]([C:4]2[CH:3]=[N:2][NH:18][C:5]=2[CH:6]([CH3:8])[CH3:7])[CH:15]=[CH:14][N:13]=1
Reactant: NN
Reactant: CC(C)C(=O)C(=CN(C)C)c1ccnc(F)c1
Solvent: CO
Solvent: CCOC(C)=O
Product: CC(C)c1[nH]ncc1-c1ccnc(F)c1
Reaction time: 4 h
Yield: 69.9 %

Procedure:
To a solution of 1-dimethylamino-2-(2-fluoro-pyridin-4-yl)-4-methyl-pent-1-en-3-one (crude, 26.5 mmol) in methanol (50 mL) is added hydrazine (0.84 mL, 26.5 mmol) at 0° C. The reaction mixture is stirred for 4 h, diluted with EtOAc, and washed with water. The organic layer is washed with brine, dried over sodium sulfate, and concentrated in vacuo. Purification by flash chromatography (SiO2, EtOAc/heptan 5:1) afforded 3.8 g of 2-fluoro-4-(5-isopropyl-1H-pyrazol-4-yl)-pyridine as a white solid.
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:15][C@@H:14]3[CH2:16][C@@:17]4([CH2:20][O:19]4)[CH2:18][N:13]3[C:12]2=[O:21])=[CH:7][CH:6]=1.[H-].[Na+].[CH2:26]([OH:30])[CH2:27][CH2:28][CH3:29]>>[CH2:26]([O:30][CH2:20][C@@:17]1([OH:19])[CH2:18][N:13]2[C:12](=[O:21])[N:11]([C:8]3[CH:7]=[CH:6][C:5]([O:4][CH2:3][C:2]([F:23])([F:1])[F:22])=[CH:10][CH:9]=3)[CH2:15][C@@H:14]2[CH2:16]1)[CH2:27][CH2:28][CH3:29]
Reactant: CCCCO
Reactant: O=C1N(c2ccc(OCC(F)(F)F)cc2)C[C@@H]2C[C@@]3(CO3)CN12
Agent: [H-]
Agent: [Na+]
Product: CCCCOC[C@]1(O)C[C@H]2CN(c3ccc(OCC(F)(F)F)cc3)C(=O)N2C1
Yield: 24 %

Procedure:
To a stirred solution of (2S,7a′S)-2′-[4-(2,2,2-trifluoroethoxy)phenyl]tetrahydro-3′H-spiro[oxirane-2,6′-pyrrolo[1,2-c]imidazol]-3′-one (40 mg, 0.121 mmol) in butanol (5 mL) was added NaH (60% in oil, 7.3 mg, 0.18 mmol) and heated to reflux for 12 h. The reaction mixture quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over Na2SO4 and concentrated. The residue purified by column chromatography on silica eluting with ethyl acetate/hexane to yield 12 mg (24%) of the title compound as white solid. LC-MS: 403.0 [M+1]+.
Reaction SMILES: C([O:5][C:6](=[O:49])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](=[O:48])[C@H:13]([CH2:36][CH2:37][CH2:38][CH2:39][NH:40]C(OC(C)(C)C)=O)[NH:14][C@H:15]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][NH:23]C(OC(C)(C)C)=O)(C)(C)C>C(O)=O>[CH2:34]([O:33][C:31]([C@@H:15]([NH:14][C@H:13]([C:12]([N:8]1[CH2:9][CH2:10][CH2:11][C@H:7]1[C:6]([OH:49])=[O:5])=[O:48])[CH2:36][CH2:37][CH2:38][CH2:39][NH2:40])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][NH2:23])=[O:32])[CH3:35]
Reactant: CCOC(=O)[C@H](CCCCCCCNC(=O)OC(C)(C)C)N[C@@H](CCCCNC(=O)OC(C)(C)C)C(=O)N1CCC[C@H]1C(=O)OC(C)(C)C
Solvent: O=CO
Product: CCOC(=O)[C@H](CCCCCCCN)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)O
Temperature: 37 °C
Reaction time: 48 h

Procedure:
Nα -[1(S)-ethoxycarbonyl-8-tertiary butoxycarbonylaminooctyl]-Nε -tertiary butoxycarbonyl-L-lysyl-L-proline tertiary butylester obtained by Example VII b) (480 mg) is added into 100 ml of formic acid and dissolved. This solution is stirred at 37° C. for 48 hours. The formic acid is distilled off and the residue is dried under reduced pressure to obtain 320 mg of colorless oil.
Reaction SMILES: [CH2:1]([NH:8][C:9]1[N:14]2[N:15]=[CH:16][C:17]([C:18](O)=[O:19])=[C:13]2[N:12]=[CH:11][C:10]=1[C:21]([N:23]1[CH2:28][CH2:27][C:26]2([C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:30](=[O:37])[O:29]2)[CH2:25][CH2:24]1)=[O:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:38][S:39]([NH2:42])(=[O:41])=[O:40]>>[CH2:1]([NH:8][C:9]1[N:14]2[N:15]=[CH:16][C:17]([C:18]([NH:42][S:39]([CH3:38])(=[O:41])=[O:40])=[O:19])=[C:13]2[N:12]=[CH:11][C:10]=1[C:21]([N:23]1[CH2:24][CH2:25][C:26]2([C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:30](=[O:37])[O:29]2)[CH2:27][CH2:28]1)=[O:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1OC2(CCN(C(=O)c3cnc4c(C(=O)O)cnn4c3NCc3ccccc3)CC2)c2ccccc21
Reactant: CS(N)(=O)=O
Product: CS(=O)(=O)NC(=O)c1cnn2c(NCc3ccccc3)c(C(=O)N3CCC4(CC3)OC(=O)c3ccccc34)cnc12
Yield: 85.7 %

Procedure:
In the same manner as in Example 1, step 6 and using 7-benzylamino-6-(3-oxo-3H-spiro[isobenzofuran-1,4′-piperidine]-1′-ylcarbonyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (0.100 g, 0.201 mmol) obtained in step 4 and methanesulfonamide (0.096 g, 1.01 mmol), the title compound (0.099 g, 85%) was obtained.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([O:13][CH3:14])=[CH:11][C:10]([C:15]([OH:17])=[O:16])=[N:9]1.C([O-])(=O)C.[Na+].[Br:23]Br>C(O)(=O)C>[Br:23][C:11]1[C:10]([C:15]([OH:17])=[O:16])=[N:9][N:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[C:12]=1[O:13][CH3:14]
Reactant: COc1cc(C(=O)O)nn1-c1ccccc1F
Reactant: BrBr
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: COc1c(Br)c(C(=O)O)nn1-c1ccccc1F
Reaction time: 1 h
Yield: 90.7 %

Procedure:
50 mg (0.21 mmol) of 1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid were dissolved in 1.5 ml of acetic acid, sodium acetate (35 mg, 0.42 mmol) and bromine (50 mg, 0.21 mmol) were added and the mixture was stirred for 60 min. The solvent was removed in vacuo and the residue subjected to an aqueous work-up. The obtained crude title compound (60 mg) was used in the next step without further purification.
Reaction SMILES: [C:1]([N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9][CH:10]=[CH2:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].B1(B2C3CCCC2CCC3)C2CCCC1CCC2.Br[C:38]1[CH:39]=[CH:40][C:41]2[O:45][CH:44]([CH2:46][CH3:47])[CH2:43][C:42]=2[CH:48]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCCC1.CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1(C)C=CC=CC=1>[C:15]([O:14][C:12]([N:8]([CH2:9][CH2:10][CH2:11][C:38]1[CH:39]=[CH:40][C:41]2[O:45][CH:44]([CH2:46][CH3:47])[CH2:43][C:42]=2[CH:48]=1)[C:1]([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2])=[O:13])([CH3:18])([CH3:17])[CH3:16]
Reactant: CCC1Cc2cc(Br)ccc2O1
Reactant: C=CCN(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: C1CC2CCCC(C1)B2B1C2CCCC1CCC2
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CCC1Cc2cc(CCCN(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)ccc2O1
Temperature: 0 °C
Reaction time: 3 h
Yield: 46 %

Procedure:
N,N-Bis-Boc-N-allylamine (2.99 g, 11.6 mmol) was azeotroped with toluene (2×50 mL) then dissolved in tetrahydrofuran (12 mL). The solution was cooled to 0° C., 9-borabicyclo[3.3.1]nonane dimer (0.5M in tetrahydrofuran, 46.5 mL, 23.2 mmol) was added and the mixture was stirred at 0° C. for 3 hours. A mixture of 5-bromo-2-ethyl-2,3-dihydro-benzofuran (preparation 98, enantiomer 2), (2.9 g, 12.8 mmol), tripotassium phosphate (7.7 mL, 23.2 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (4.74 mg, 0.58 mmol) in N,N-dimethylformamide (12 mL) was added and the reaction mixture was stirred at room temperature for 18 hours. The reaction was then quenched with 2M sodium hydroxide solution (30 mL) and water (10 mL) and stirred for 1 hour at room temperature. The mixture was then extracted with diethyl ether, dried over magnesium sulfate and concentrated in vacuo. The residue was suspended in ethyl acetate:petroleum ether, 25:75, filtered and the filtrate was concentrated in vacuo. The residue was purified by column chromatography on silica gel, eluting with ethyl acetate:petroleum ether, 7:93, to afford the title compound as a clear oil in 46% yield, 2.15 g.
Reaction SMILES: [CH3:1]/[C:2](=[CH:5]\[C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1)/[CH:3]=O.[C:15]([O:19][C:20]([CH:22]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>C(#N)C>[CH3:1]/[C:2](=[CH:5]\[C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1)/[CH:3]=[CH:22]/[C:20]([O:19][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:21]
Reactant: C/C(C=O)=C\c1ccc([N+](=O)[O-])cc1
Reactant: CC(C)(C)OC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CC#N
Product: CC(/C=C/C(=O)OC(C)(C)C)=C\c1ccc([N+](=O)[O-])cc1
Temperature: 65 °C
Yield: 53.2 %

Procedure:
(E)-2-Methyl-3-(4-nitrophenyl)prop-2-enal (3.0 g, 15.6 mmol), (tert-butoxycarbonyl methylene)triphenylphosphorane (8.85 g, 23.4 mmol) and dry acetonitrile (60 ml) were stirred and heated at 65° C. until reaction was complete (ca. 1 h, HPLC monitoring). The mixture was cooled, filtered to remove some insoluble by-product, and the filtrate concentrated in vacuo to ca. 15 ml volume. On cooling the product deposited, was collected by filtration and washed with cold acetonitrile to give a yellow solid (2.4 g), mp 120-122° C. The mother liquors were evaporated to dryness, the residue stirred in ether (20 ml) and the insoluble material removed by filtration. The filtrate was concentrated in vacuo and the residue crystallised from acetonitrile (5 ml) to give a second crop of product (1.3 g). Total yield=3.7 g (87%)
Reaction SMILES: [NH2:1][CH2:2][C:3]([N:5]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:4].[CH3:18][O:19][C:20]1[CH:21]=[C:22]([N:26]=[C:27]=[O:28])[CH:23]=[CH:24][CH:25]=1>>[CH3:18][O:19][C:20]1[CH:21]=[C:22]([NH:26][C:27](=[O:28])[NH:1][CH2:2][C:3]([N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:4])[CH:23]=[CH:24][CH:25]=1
Reactant: COc1cccc(N=C=O)c1
Reactant: NCC(=O)N(c1ccccc1)c1ccccc1
Product: COc1cccc(NC(=O)NCC(=O)N(c2ccccc2)c2ccccc2)c1
Yield: 79.5 %

Procedure:
Working in a manner similar to that described in Example 1, but starting with 2-amino-N,N-diphenylacetamide (2 g) and 3-methoxyphenyl isocyanate (1.3 g), and after recrystallization in acetonitrile, 2-[3-(3-methoxyphenyl)ureido]-N,N-diphenylacetamide (2.6 g), m.p. 182° C., is obtained.
Reaction SMILES: [C:1]1([N:7]([CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:8]([C:10]2[CH:11]=[CH:12][C:13]3[S:17][C:16]([CH2:18]OC)=[N:15][C:14]=3[CH:21]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.B(Br)(Br)[Br:30]>ClCCl>[C:1]1([N:7]([CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:8]([C:10]2[CH:11]=[CH:12][C:13]3[S:17][C:16]([CH2:18][Br:30])=[N:15][C:14]=3[CH:21]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: BrB(Br)Br
Reactant: CCOC(=O)CCN(C(=O)c1ccc2sc(COC)nc2c1)c1ccccc1
Solvent: ClCCl
Product: CCOC(=O)CCN(C(=O)c1ccc2sc(CBr)nc2c1)c1ccccc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A mixture of 2.05 g (5.14 mmol) of 2-methoxymethylbenzothiazole-5-carboxylic acid-N-phenyl-N-(2-ethoxycarbonylethyl)amide and 5.7 mL (5.7 mmol) of a 1M solution of boron tribromide in dichloromethane was dissolved in a further 60 mL of dichloromethane and stirred for 16 hours at room temperature. Then the mixture was washed with 40 mL of saturated sodium hydrogen carbonate solution, the organic phase was dried with sodium sulfate, and the solvent was distilled off. The crude 2-bromomethylbenzothiazole-5-carboxylic acid-N-phenyl-N-(2-ethoxycarbonylethyl)amide thus obtained (2.4 g) was taken up in 5.0 mL of N,N-diisopropylethylamine and mixed with 0.64 g (5.4 mmol) of 4-aminobenzonitrile. After 1 hour's heating to 130° C., the solvent was distilled off in vacuo and the crude product obtained was purified by flash chromatography (silica gel; gradient: ethyl acetate/petroleum ether=1:3 to 1:1), whilst an orange foam was obtained when the eluates were evaporated down. Yield: 1.1 g (44% of theory); Rf value: 0.35 (silica gel; ethyl acetate/petroleum ether=7:3).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([OH:8])[CH:7]=1.[CH3:10][N:11]([CH3:15])[CH2:12][CH2:13]Cl.Cl.C([O-])([O-])=O.[K+].[K+].C([O-])(O)=O.[Na+]>CC(C)=O.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([CH:7]=1)[O:8][CH2:13][CH2:12][N:11]([CH3:15])[CH3:10]
Reactant: CN(C)CCCl
Reactant: Oc1cc(Br)ccc1F
Agent: Cl
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: CC(C)=O
Product: CN(C)CCOc1cc(Br)ccc1F
Temperature: 25 °C
Reaction time: 72 h

Procedure:
5-Bromo-2-fluoro-phenol (5.0 g, 26.2 mmol), 2-Dimethylaminoethylchlorid×HCl (5.66 g, 39.3 mmol) and K2CO3 (11.0 g, 78.5 mmol) are suspended/dissolved in 260 ml dry acetone and stirred at room temperature for 72 hours. Addition of aqueous NaHCO3 solution and extraction into ethyl acetate yields a crude product which is further purified by chromatography on silica. 1H-NMR (400 MHz; DMSO-d6): 7.41 (d, 1H), 7.20 (dd, 1H), 7.08-7.14 (m, 1H), 4.15 (t, 2H), 2.63 (t, 2H), 2.22 (s, 6H). MS (m/z, ES+): 262 (MH+).
Reaction SMILES: N[C@@H]1CCN(C2N=C3C(N=CN3[C@@H]3C[C@H](N4N=NC(CC)=N4)[C@@H](O)[C@H]3O)=C(NCC(C3C=CC=CC=3)C3C=CC=CC=3)N=2)C1.[ClH:45].[C:46]1([CH:52]([C:94]2[CH:99]=[CH:98][CH:97]=[CH:96][CH:95]=2)[CH2:53][NH:54][C:55]2[N:63]=[C:62]([N:64]3[CH2:68][CH2:67][C@@H:66]([NH:69][C:70](NCC4C=CC=CN=4)=[O:71])[CH2:65]3)[N:61]=[C:60]3[C:56]=2[N:57]=[CH:58][N:59]3[C@@H:80]2[CH2:84][C@H:83]([N:85]3[N:89]=[N:88][C:87]([CH2:90][CH3:91])=[N:86]3)[C@@H:82]([OH:92])[C@H:81]2[OH:93])[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.[N:100]1[C:109]2[C:104](=[CH:105][CH:106]=[CH:107][CH:108]=2)[C:103]([CH2:110][NH2:111])=[CH:102][CH:101]=1>>[ClH:45].[C:94]1([CH:52]([C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)[CH2:53][NH:54][C:55]2[N:63]=[C:62]([N:64]3[CH2:68][CH2:67][C@@H:66]([NH:69][C:70]([NH:111][CH2:110][C:103]4[C:104]5[C:109](=[CH:108][CH:107]=[CH:106][CH:105]=5)[N:100]=[CH:101][CH:102]=4)=[O:71])[CH2:65]3)[N:61]=[C:60]3[C:56]=2[N:57]=[CH:58][N:59]3[C@@H:80]2[CH2:84][C@H:83]([N:85]3[N:89]=[N:88][C:87]([CH2:90][CH3:91])=[N:86]3)[C@@H:82]([OH:92])[C@H:81]2[OH:93])[CH:99]=[CH:98][CH:97]=[CH:96][CH:95]=1
Reactant: NCc1ccnc2ccccc12
Reactant: CCc1nnn([C@H]2C[C@@H](n3cnc4c(NCC(c5ccccc5)c5ccccc5)nc(N5CC[C@@H](NC(=O)NCc6ccccn6)C5)nc43)[C@H](O)[C@@H]2O)n1
Agent: CCc1nnn([C@H]2C[C@@H](n3cnc4c(NCC(c5ccccc5)c5ccccc5)nc(N5CC[C@@H](N)C5)nc43)[C@H](O)[C@@H]2O)n1
Agent: Cl
Product: CCc1nnn([C@H]2C[C@@H](n3cnc4c(NCC(c5ccccc5)c5ccccc5)nc(N5CC[C@@H](NC(=O)NCc6ccnc7ccccc67)C5)nc43)[C@H](O)[C@@H]2O)n1

Procedure:
This compound is prepared from ((1R,2S,3R,5S)-3-[2-((R)-3-amino-pyrrolidin-1-yl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-5-(5-ethyl-tetrazol-2-yl)-cyclopentane-1,2-diol (Example 48) using a procedure analogous to that of 1-((R)-1-{6-(2,2-diphenyl-ethylamino)-9-[(1R,2S,3R,4S)-4-(5-ethyl-tetrazol-2-yl)-2,3-dihydroxy-cyclopentyl]-9H-purin-2-yl}-pyrrolidin-3-yl)-3-pyridin-2-ylmethyl-urea hydrochloride (Example 113) by replacing 2-aminomethyl pyridine with C-quinolin-4-yl-methylamine. MS (ES+) m/e 780.55 (MH+).