Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[CH2:11](Br)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH2:11]([O:10][C:8]1[CH:7]=[CH:6][C:3]([CH:4]=[O:5])=[C:2]([F:1])[CH:9]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: BrCc1ccccc1
Reactant: O=Cc1ccc(O)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=Cc1ccc(OCc2ccccc2)cc1F
Temperature: 25 °C
Reaction time: 12 h
Yield: 85.6 %

Procedure:
To a solution of 2-fluoro-4-hydroxy-benzaldehyde (1.0 g, 7.1 mmol) in DMF (70 mL) was added benzylbromide (0.85 mL, 1.2 g, 7.1 mmol) and K2CO3 (1.1 g, 7.9 mmol) and the reaction mixture was stirred (rt, 12 h). The reaction mixture was treated with H2O (50 mL) and filtered to afford the title compound as a colorless solid (1.4 g, 85%). MS (ESI): mass calcd. for C14H11FO2, 230.1; m/z found, 231.1 [M+H]+. 1H NMR (400 MHz, CDCl3): 10.21 (s, 1H), 7.82 (t, J=8.8, 1H), 7.48-7.32 (m, 5H), 6.85 (dd, J=8.8, 2.3, 1H), 6.71 (dd, J=12.3, 2.3, 1H), 5.11 (d, J=14.8, 2H).
Reaction SMILES: [Si]([O:8][C:9]1[CH:10]=[CH:11][C:12]([N:32]2[C:36](=[O:37])[C:35]3=[CH:38][CH:39]=CC=[C:34]3[C:33]2=O)=[C:13]([CH:31]=1)[NH:14][C:15]([O:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22](C2C=CN=CC=2)[CH2:21][CH2:20]1)=[O:16])(C(C)(C)C)(C)C.[CH2:43]([Cl:45])Cl>NN.CO>[Cl:45][C:43]1[CH:39]=[CH:38][C:35]([C:36]([NH:32][C:12]2[C:13]([NH:14][C:15]([O:17][CH:18]([CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[C:19]3[CH:20]=[CH:21][N:22]=[CH:23][CH:24]=3)=[O:16])=[CH:31][C:9]([OH:8])=[CH:10][CH:11]=2)=[O:37])=[CH:34][CH:33]=1
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(N2C(=O)c3ccccc3C2=O)c(NC(=O)OCC2CCN(c3ccncc3)CC2)c1
Reactant: ClCCl
Agent: NN
Solvent: CO
Product: O=C(Nc1cc(O)ccc1NC(=O)c1ccc(Cl)cc1)OC(c1ccncc1)C1CCNCC1
Yield: 86 %

Procedure:
A solution of 5-(tert-butyldimethylsilyloxy)-2-phthalimido-N-[[1-(4-pyridyl)piperidin-4-yl]methoxycarbonyl]aniline (1.34 g, 2.28 mmol) in 1 M hydrazine in methanol (6 mL) was stirred at ambient temperature for 40 h during which time a white precipitate formed. The mixture was further diluted with methylene chloride and cooled with an ice bath then filtered. The filtrate was washed once with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to yield 890 mg (86%) of the title compound as a tan powder.
Reaction SMILES: Br[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=[C:6]2[C:5]([Br:19])=[CH:4][N:3]=1.[CH3:20][C:21]1[N:26]=[CH:25][N:24]=[C:23]([NH2:27])[CH:22]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:19][C:5]1[C:6]2[C:7](=[CH:8][N:9]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=2)[C:2]([NH:27][C:23]2[CH:22]=[C:21]([CH3:20])[N:26]=[CH:25][N:24]=2)=[N:3][CH:4]=1
Reactant: Cc1cc(N)ncn1
Reactant: Clc1cccc(Cl)c1-n1cc2c(Br)ncc(Br)c2n1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: Cc1cc(Nc2ncc(Br)c3nn(-c4c(Cl)cccc4Cl)cc23)ncn1
Yield: 63.7 %

Procedure:
A suspension of 4,7-dibromo-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine (317 mg, 0.75 mmol), 6-methylpyrimidin-4-ylamine (90 mg, 0.83 mmol), Pd2(dba)3 (17 mg, 0.019 mmol), Xantphos (43 mg, 0.075 mmol) and cesium carbonate (489 mg, 1.5 mmol) in dioxane (11 mL) was sealed in a microwave vial, purged with nitrogen, and irradiated in a microwave reactor at 150° C. for 1 hour. The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (50-60% ethyl acetate in cyclohexane), to afford the title compound as a yellow solid (215 mg, 64% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.80 (s, 1H), 9.29 (s, 1H), 8.72 (d, J=1.3 Hz, 1H), 8.40 (s, 1H), 8.17 (s, 1H), 7.85 (d, J=0.9 Hz, 1H), 7.82 (s, 1H), 7.74 (dd, J=7.1 and 9.0 Hz, 1H), 2.46 (s, 3H). LCMS (Method B): RT=3.60 min, m/z: 449 [M+H+].
Reaction SMILES: [C:1]([CH2:4][CH2:5][CH2:6]/[CH:7]=[C:8]1\[CH2:9][C@@H:10]2[C@H:14]([CH2:15]\1)[C@@H:13]([CH2:16][CH2:17][CH:18]([OH:25])[CH:19]([F:24])[CH2:20][CH2:21][CH2:22][CH3:23])[C@H:12]([O:26][CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][O:28]1)[CH2:11]2)([OH:3])=[O:2].CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O>C(O)(C)C>[C:1]([CH2:4][CH2:5][CH2:6]/[CH:7]=[C:8]1\[CH2:9][C@@H:10]2[C@H:14]([CH2:15]\1)[C@@H:13]([CH2:16][CH2:17][C:18](=[O:25])[CH:19]([F:24])[CH2:20][CH2:21][CH2:22][CH3:23])[C@H:12]([O:26][CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][O:28]1)[CH2:11]2)([OH:3])=[O:2]
Reactant: CCCCC(F)C(O)CC[C@@H]1[C@H]2C/C(=C/CCCC(=O)O)C[C@H]2C[C@H]1OC1CCCCO1
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)O
Solvent: CC(C)=O
Product: CCCCC(F)C(=O)CC[C@@H]1[C@H]2C/C(=C/CCCC(=O)O)C[C@H]2C[C@H]1OC1CCCCO1
Reaction time: 0.67 h

Procedure:
(1S,2R,3R,5S)-7(E)-(4-Carboxybutylidene)-2-[4(RS)-fluoro-3(RS)-hydroxyoctyl]-3 -tetrahydropyranyloxybicyclo[3.3.0]octane (13) (0.184 g) was oxidized with Jones reagent between about -15° and -5° C. After stirring for 40 minutes, isopropyl alcohol (0.43 ml) was added, and the mixture was treated by a usual work-up. Obtained crude product was purified on column chromatography (hexane/ethyl acetate=15/1-10/1) using silica gel treated with an acid (CC-4: available from Mallineckrodt Co., Ltd.) to give (1S,2R,3R,5S)-7(E)-(4-carboxybutylidene)-2-[4(RS)-fluoro-3-oxooctyl]-3-tetrahydropyranyloxybicyclo[3.3.0]octane (14) as a colorless oily product. Yield: 0.072 g (40%)
Reaction SMILES: Br[CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.[O:13]1[C:17]2([CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[CH2:16][NH:15][C:14]1=[O:23].C(N(CC)CC)C.CN(C)C=O>O>[NH:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:4]([CH2:3][CH2:2][N:20]2[CH2:19][CH2:18][C:17]3([O:13][C:14](=[O:23])[NH:15][CH2:16]3)[CH2:22][CH2:21]2)=[CH:5]1
Reactant: O=C1NCC2(CCNCC2)O1
Reactant: BrCCc1c[nH]c2ccccc12
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: O=C1NCC2(CCN(CCc3c[nH]c4ccccc34)CC2)O1
Temperature: 25 °C
Reaction time: 16 h
Yield: 44.7 %

Procedure:
A mixture of 3.94 g of 3-(2-bromoethyl)indole, 2.74 g of 1-oxa-3,8-diazaspiro[4.5]decan-2-one, 2 g of triethylamine and 10 ml N,N-dimethylformamide is stirred at 50° for 16 hours. The mixture is cooled to room temperature and 150 ml of water is added with stirring The aqueous layer is decanted from the residue which adheres to the walls of the flask. The residue is washed with 100 ml water following by 100 ml diethyl ether. The residue is dissolved in a minimum amount of 10% (v/v) methanol-dichloromethane and the resulting solution is filtered through 25 g silica gel with 150 ml of 10% (v/v) methanol-dichloromethane. Evaporation of the filtrate followed by crystallization with diethyl ether affords 2.35 g of 8-[2-(3-indolyl)ethyl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one, mp 183°-186° (d).
Reaction SMILES: C1(CC([NH:10][C@@H:11]2[C:34](=[O:35])[N:13]3[C:14]([C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=4)=[O:23])=[C:15](/[CH:18]=[CH:19]\[CH2:20][Cl:21])[CH2:16][S:17][C@H:12]23)=O)C=CC=CC=1.N1C=CC=CC=1.CO.C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:10][C@@H:11]1[C:34](=[O:35])[N:13]2[C:14]([C:22]([O:24][CH2:25][C:26]3[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=3)=[O:23])=[C:15](/[CH:18]=[CH:19]\[CH2:20][Cl:21])[CH2:16][S:17][C@H:12]12
Reactant: COc1ccc(COC(=O)C2=C(/C=C\CCl)CS[C@@H]3[C@H](NC(=O)Cc4ccccc4)C(=O)N23)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Solvent: c1ccncc1
Product: COc1ccc(COC(=O)C2=C(/C=C\CCl)CS[C@@H]3[C@H](N)C(=O)N23)cc1
Temperature: -40 °C
Yield: 50.7 %

Procedure:
2.56 g of 4-methoxybenzyl 7β-phenylacetamido-3-[(Z)-3-chloro-1-propenyl]-3-cephem-4-carboxylate [IR υ max(Nujol)cm-1 : 3265, 1759, 1719, 1661, 1612, 1250, 1221, 1175, 1101, 1036, 824. NMR δ(CDCl3)ppm: 3.20, 3.44(2 H, ABq, J=18), 3.56(2 H, s), 3.71(3 H, s), 3.72(2 H, m), 4.87(1 H, d, J=4.5), 5.03(2 H, s), 5.4-5.9(2 H, m), 6.12(1 H, d, J=11), 6.30(1 H, d, J=9), 6.73(2 H, d, J=8.5), 7.15(5 H, s), 7.17(2 H, d, J=8.5)] was dissolved in 75 ml of dry methylene chloride and the solution was cooled to -40 ° C. 0.68 ml of pyridine and 1.35 g of PCL5 were successively added thereto with stirring. The resulting solution was stirred at room temperature for 2.5 hours and cooled to -40° C. and 46.5 ml of MeOH was dropwise added thereto. The resulting solution was stirred at room temperature for 1.5 hours, and neutralized with an aqueous NaHCO3 solution. The organic layer was washed with brine and water and dried over Na2SO4. After evaporation of the solvent, the residue was purified by silica gel column chromatography (60 g) with a mixture of benzene and ethyl acetate (1/1 volume) to give 1.0 g (51% yield) of 4-methoxybenzyl 7β-amino-3-[(Z)-3-chloro-1-propenyl]-3-cephem-4-carboxylate.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][C@@H:16]([NH:18][C:19]([C:21]3[N:22]=[C:23]([CH2:26]Cl)[O:24][CH:25]=3)=[O:20])[CH3:17])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].C(=O)([O-])[O-].[K+].[K+].[C:34]1(=[O:40])[NH:38][C:37](=[O:39])[CH2:36][CH2:35]1.C(Cl)Cl>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][C@@H:16]([NH:18][C:19]([C:21]3[N:22]=[C:23]([CH2:26][N:38]4[C:34](=[O:40])[CH2:35][CH2:36][C:37]4=[O:39])[O:24][CH:25]=3)=[O:20])[CH3:17])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]
Reactant: O=C1CCC(=O)N1
Reactant: C[C@@H](Cn1ccc(-c2ccc(C#N)c(Cl)c2)n1)NC(=O)c1coc(CCl)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: C[C@@H](Cn1ccc(-c2ccc(C#N)c(Cl)c2)n1)NC(=O)c1coc(CN2C(=O)CCC2=O)n1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 16.92 %

Procedure:
(S)—N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(chloromethyl)oxazole-4-carboxamide (0.132 g, 0.327 mmol) and potassium carbonate (0.068 g, 0.490 mmol) were dissolved in dry DMF under nitrogen atmosphere. Succinimide (0.036 g, 0.359 mmol) was added and the mixture was stirred in RT for 4.5 h. DCM was added and the organic phase was washed with water. The product was triturated using diethyl ether, DCM and finally by Flash-chromatography. Yield 16.92%. %. 1H-NMR (400 MHz; CDCl3): δ 1.23 (d, 3H), 2.83 (s, 4H), 4.29 (dd, 1H), 4.39 (dd, 1H), 4.51-4.59 (m, 1H), 4.83 (s, 2H), 6.63 (d, 1H), 7.47 (d, 1H), 7.52 (d, 1H), 7.74 (d, 1H), 7.87 (dd, 1H), 7.98 (d, 1H), 8.11 (s, 1H).
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[N:14]([C:16]([O:20]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C)C[C@@H]1CC[C@H](C2C=CC=CC=2)N1>CN(C=O)C.CCOC(C)=O>[C:1]1([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:6]([C:16]([NH2:14])=[O:20])=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Reactant: c1ccc(-c2ccccc2)cc1
Agent: CN(C)C[C@@H]1CC[C@H](c2ccccc2)N1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: NC(=O)c1ccccc1-c1ccccc1
Reaction time: 2 h
Yield: 45 %

Procedure:
Biphenyl acid 10 (40 mg, 0.064 mmol, 1 eq) and HBTU (49 mg, 0.13 mmol, 2 eq) were dissolved in DMF (1 mL) followed by the addition of N,N-dimethyl-1-((2S,5R)-5-phenylpyrrolidin-2-yl)methanamine 250 (23 mg, 0.13 mmol, 2 eq). The reaction mixture was stirred for 2 h, diluted with EtOAc and quenched with a saturated aqueous NaHCO3 solution. The reaction mixture was extracted with EtOAc (3×100 mL) and the combined organics were dried over MgSO4, filtered and concentrated in vacuo to afford an oil. The crude oil was purified by silica gel chromatography (2-5% MeOH/DCM, 0.1% Et3N) to afford 23 mg of biphenyl amide 247. Yield 45%.
Reaction SMILES: C(OC([NH:11][C@H:12]([C:17]([NH:19][C@@H:20]([CH2:41][OH:42])[C@@H:21]([OH:40])[C@@H:22]([OH:39])[C@H:23]([OH:38])[C:24]([NH:26][C@H:27]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:28][C:29](O)=[O:30])=[O:25])=[O:18])[CH2:13][CH:14]([CH3:16])[CH3:15])=O)C1C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O:61][C:62](=[O:66])[C@H:63]([CH3:65])[NH2:64])C1C=CC=CC=1.C1(N=C=NC2CCCCC2)CCCCC1.C(N(CC)CC)C>C(#N)C.CO.[Pd]>[OH:38][C@@H:23]([C@H:22]([OH:39])[C@H:21]([OH:40])[C@@H:20]([NH:19][C:17](=[O:18])[C@H:12]([CH2:13][CH:14]([CH3:16])[CH3:15])[NH2:11])[CH2:41][OH:42])[C:24]([NH:26][C@H:27]([C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[CH2:28][C:29]([NH:64][C@H:63]([C:62]([OH:66])=[O:61])[CH3:65])=[O:30])=[O:25]
Reactant: CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](CO)[C@@H](O)[C@@H](O)[C@H](O)C(=O)N[C@@H](CC(=O)O)c1ccccc1
Reactant: C[C@H](N)C(=O)OCc1ccccc1
Agent: [Pd]
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CC(C)C[C@H](N)C(=O)N[C@@H](CO)[C@@H](O)[C@@H](O)[C@H](O)C(=O)N[C@@H](CC(=O)N[C@@H](C)C(=O)O)c1ccccc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 32.5 %

Procedure:
To absolution of (S)-3-[(2S,3R,4R,5S)-5-(N-benzyloxycarbonyl-L-leucyl)amino-2,3,4,6-tetrahydroxyhexanoyl]amino-3-phenylpropionic acid (200 mg), L alanine benzyl ester p-toluenesulfonate (238 mg) and N-hydroxy-5-norbornene-2,3-dicarboxyimide (183 mg) in acetonitrile (10 ml) were added N,N′-dicyclohexylcarbodimide (140 mg) and triethylamine (0.094 ml) and the mixture was stirred at room temperature for 15 hours. The formed insoluble solid was filtrated off and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with saturated brine, followed by drying over anhydrous sodium sulfate. Removal of the organic solvent gave a residue, which was dissolved in methanol (10 ml) and stirred at room temperature with 10% palladium on activated carbon (60 mg) under hydrogen atmosphere for 3 hours. After filtration, the filtrate was concentrated under reduced pressure to give a residue, which was passed through a column of DIAION HP-20SS (Mitsubishi kasei corporation), followed by elution with water-acetonitrile. The effective fractions were combined and concentrated under reduced pressure. The residue was recrystallized from methanol-ethyl acetate to afford the title compound (58 mg).
Reaction SMILES: Br[C:2]1[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=1[CH2:4][NH:5][C:6](=[O:11])[C:7]([F:10])([F:9])[F:8].[NH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:2]2[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=2[CH2:4][NH:5][C:6](=[O:11])[C:7]([F:10])([F:9])[F:8])=[CH:19][CH:18]=1
Reactant: Nc1ccccc1
Reactant: O=C(NCc1ccccc1Br)C(F)(F)F
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Product: Nc1ccc(-c2ccccc2CNC(=O)C(F)(F)F)cc1
Temperature: 80 °C
Yield: 48.6 %

Procedure:
A mixture of N-(2-bromo-benzyl)-2,2,2-trifluoro-acetamide (282 mg, 1.0 mmol), 444,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (284 mg, 1.3 mmol), Pd(OAc)2 (20 mg, 0.09 mmol) and PS—PPh3 (40 mg, 3 mmol/g, 0.12 mmol) was dissolved in DMF (5 mL) and 4M K2CO3 solution (0.5 mL) was added. The reaction was heated at 80° C. overnight. The mixture was filtered, concentrated and purified by column chromatography (0-50% ethyl acetate-hexanes) to yield N-(4′-amino-biphenyl-2-ylmethyl)-2,2,2-trifluoro-acetamide (1-1) (143 mg, 49%).
Reaction SMILES: [CH2:1]([N:8]([CH3:33])[C:9]1[CH:14]=[CH:13][C:12]([C:15]([CH3:29])([CH2:23]OS(C)(=O)=O)[C:16]([N:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[O:17])=[CH:11][C:10]=1[N+:30]([O-:32])=[O:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:34]=[N+:35]=[N-:36].[Na+]>CN(C)C=O>[CH2:1]([N:8]([CH3:33])[C:9]1[CH:14]=[CH:13][C:12]([C:15]([CH3:29])([CH2:23][N:34]=[N+:35]=[N-:36])[C:16]([N:18]2[CH2:19][CH2:20][CH2:21][CH2:22]2)=[O:17])=[CH:11][C:10]=1[N+:30]([O-:32])=[O:31])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CN(Cc1ccccc1)c1ccc(C(C)(COS(C)(=O)=O)C(=O)N2CCCC2)cc1[N+](=O)[O-]
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN(Cc1ccccc1)c1ccc(C(C)(CN=[N+]=[N-])C(=O)N2CCCC2)cc1[N+](=O)[O-]

Procedure:
Prepared analogously to Example 6b from 2-[4-(N-benzyl-methylamino)-3-nitro-phenyl]-2-methyl-3-methanesulphonyloxy-1-pyrrolidino-propan-1-one and sodium azide in dimethylformamide.
Reaction SMILES: [CH3:1][CH:2]([CH2:24][CH3:25])[CH2:3][O:4][C:5]1[N:13]=[C:12]2[C:8]([N:9]=[C:10]([O:21]C)[N:11]2[CH2:14][CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[C:7]([NH2:23])[N:6]=1.Cl.[OH-].[Na+]>CO.O1CCOCC1>[NH2:23][C:7]1[N:6]=[C:5]([O:4][CH2:3][CH:2]([CH3:1])[CH2:24][CH3:25])[N:13]=[C:12]2[C:8]=1[NH:9][C:10](=[O:21])[N:11]2[CH2:14][CH:15]1[CH2:16][CH2:17][O:18][CH2:19][CH2:20]1
Reactant: CCC(C)COc1nc(N)c2nc(OC)n(CC3CCOCC3)c2n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CO
Product: CCC(C)COc1nc(N)c2[nH]c(=O)n(CC3CCOCC3)c2n1
Temperature: 25 °C
Reaction time: 3 h
Yield: 50.8 %

Procedure:
To a solution of 2-[(2-methylbutyl)oxy]-8-methoxy-9-(tetrahydro-2H-pyran-4-ylmethyl)-9H-purin-6-amine (41 mg) in dry MeOH (4.5 mL) was added 4N HCl in 1,4-dioxane (0.766 mL) and the reaction mixture was stirred at room temperature for 3 h. The reaction was neutralised with 2M sodium hydroxide solution and concentrated in vacuo. The resulting white residue was taken up in water (20 mL) and was filtered under reduced pressure to give the title compound as an off-white solid (20 mg).
Reaction SMILES: [Cl:1][CH2:2][C:3](Cl)=[O:4].C(N(CC)CC)C.[CH3:13][N:14]1[C:23]2[C:22](=[O:24])[NH:21][C:20]3[CH:25]=[CH:26][CH:27]=[CH:28][C:19]=3[NH:18][C:17]=2[C:16]([CH3:29])=[N:15]1>O1CCOCC1>[Cl:1][CH2:2][C:3]([N:18]1[C:19]2[CH:28]=[CH:27][CH:26]=[CH:25][C:20]=2[NH:21][C:22](=[O:24])[C:23]2[N:14]([CH3:13])[N:15]=[C:16]([CH3:29])[C:17]1=2)=[O:4]
Reactant: O=C(Cl)CCl
Reactant: Cc1nn(C)c2c1Nc1ccccc1NC2=O
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: Cc1nn(C)c2c1N(C(=O)CCl)c1ccccc1NC2=O
Reaction time: 3 h
Yield: 65.1 %

Procedure:
2 g of chloroacetyl chloride and 2 g of triethylamine are added dropwise at the same time over the course of 40 minutes to a boiling solution of 2.3 g of 1,3-dimethyl-1,4,9,10-tetrahydropyrazolo[4,3-b][1,5]benzodiazepin-10-one in 30 ml of absolute dioxane, and the mixture is stirred for a further 3 hours. It is then allowed to cool and is filtered; the filtrate is concentrated to dryness and chromatographed over a silica gel column by means of a 1:1 mixture of petroleum ether and ethyl acetate, and the product is recrystallized from toluene to yield 2.0 g of 4-chloroacetyl-1,3-dimethyl-1,4,9,10-tetrahydropyrazolo[4,3-b][1,5]benzodiazepin-10-one, mp 246° to 248° C. (dec.).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][CH2:8][C:9]2=[O:12])=[CH:5][CH:4]=1.[CH:13](=O)[CH2:14][CH2:15][CH3:16].[OH-].[K+].Cl>C(O)C.O>[CH:13](=[C:8]1[CH2:7][C:6]2[C:10](=[CH:11][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C:9]1=[O:12])[CH2:14][CH2:15][CH3:16]
Reactant: COc1ccc2c(c1)C(=O)CC2
Reactant: CCCC=O
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCCC=C1Cc2ccc(OC)cc2C1=O
Reaction time: 1 h

Procedure:
To a 0° C. mixture of 9.66 g (59.6 mmol) of 6-methoxy-1-indanone and 4.29 g (59.6 mmol) of butyr-aldehyde in 10 ml ethanol is added 9.66 ml of a 4% KOH in ethanol solution. The reaction is stirred 1 hour and then added to 300 ml water and the pH of the quench adjusted to 2 with 1N hydrochloric acid. The resultant mixture is extracted with 3×300 ml ether, and the extracts combined, dried over MgSO4, evaporated and the residue triturated with ether to yield present title compound.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[S:15](Cl)(=[O:18])(=[O:17])[NH2:16].[Cl-].[Na+]>CN(C)C(=O)C>[S:15](=[O:18])(=[O:17])([O:14][C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:1][S:15](=[O:18])(=[O:17])[NH2:16])=[CH:7][CH:6]=2)=[CH:9][CH:10]=1)[NH2:16]
Reactant: NS(=O)(=O)Cl
Reactant: Nc1ccc(-c2ccc(O)cc2)cc1
Agent: [Cl-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: NS(=O)(=O)Nc1ccc(-c2ccc(OS(N)(=O)=O)cc2)cc1
Temperature: 25 °C
Reaction time: 2.4 h
Yield: 52.7 %

Procedure:
43 mg of 4′-aminobiphenyl-4-ol was dissolved in 0.7 ml of N,N-dimethylacetamide, and 107 mg of sulfamoyl chloride was added thereto under cooling with ice, followed by stirring at room temperature for 2.4 hours. After the reaction mixture was poured into a saturated aqueous solution of sodium chloride, the product was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the resulting crude product was purified by TLC (using a 17:10 mixture of chloroform and tetrahydrofuran as the developing solvent) to obtain 42 mg of 4′-(sulfamoylamino)biphenyl-4-yl sulfamate.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:11][CH:10]2[C:12]([O:14][CH3:15])=[O:13])=[CH:5][CH:4]=1)#[CH:2].I[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[CH:18]=1>>[C:19]1([CH3:23])[CH:20]=[CH:21][C:22]([C:2]#[C:1][C:3]2[CH:8]=[CH:7][C:6]([CH:9]3[CH2:11][CH:10]3[C:12]([O:14][CH3:15])=[O:13])=[CH:5][CH:4]=2)=[CH:17][CH:18]=1
Reactant: C#Cc1ccc(C2CC2C(=O)OC)cc1
Reactant: Cc1cccc(I)c1
Product: COC(=O)C1CC1c1ccc(C#Cc2ccc(C)cc2)cc1

Procedure:
The title compound was prepared from methyl 2-(4-ethynylphenyl)cyclopropanecarboxylate (80 mg, 0.40 mmol) and 1-iodo-3-methylbenzene (97 mg, 0.44 mmol) according to the general procedure IF to give 57 mg (49%) of a white after purification by flash chromatography (SiO2, EtOAc:PE, 1:9): Rf=0.43 (EtOAc:PE, 1:4); 1H NMR (CDCl3) δ 7.46-7.38 (m, 4H), 7.14 (d, J=7.9 Hz, 2H), 7.06 (d, J=8.2 Hz, 2H), 3.72 (s, 3H), 2.59-2.47 (m, 1H), 2.36 (s, 3H), 1.92 (ddd, J=8.5, 5.3, 4.2 Hz, 1H), 1.63 (dt, J=9.9, 5.0 Hz, 1H), 1.33 (ddd, J=8.4, 6.5, 4.7 Hz, 1H); 13C NMR (CDCl3) δ 173.6, 140.2, 138.4, 131.6, 131.5, 129.1, 126.1, 121.6, 120.2, 89.6, 88.5, 52.0, 26.2, 24.2, 21.5, 17.2; ESI-MS m/z 313.1 (M+Na+).