Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:24])([CH2:21][CH:22]=[CH2:23])[CH2:9][CH2:10][NH:11][C@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)[CH3:13])=[CH:4][CH:3]=1.CCN(CC)CC.Cl[C:33](Cl)([O:35]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[CH2:21]([C@@:8]1([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[O:24][C:33](=[O:35])[N:11]([C@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)[CH3:13])[CH2:10][CH2:9]1)[CH:22]=[CH2:23]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: C=CCC(O)(CCN[C@@H](C)c1cccc(F)c1)c1ccc(F)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=CC[C@]1(c2ccc(F)cc2)CCN([C@@H](C)c2cccc(F)c2)C(=O)O1
Yield: 43 %

Procedure:
To a solution of 3-(4-fluorophenyl)-1-((S)-1-(3-fluorophenyl)ethylamino)hex-5-en-3-ol (350 mg, 1.1 mmol) and Et3N (333 mg, 3.3 mmol) in anhydrous CH2Cl2 (6 mL) was added triphosgene (155 mg, 0.52 mmol) in portions at 0° C. under N2. Then the solution was refluxed overnight. After the solvent was removed under reduced pressure, the residue was purified by preparative TLC to afford (R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(3-fluorophenyl)ethyl)-1,3-oxazinan-2-one (80 mg, 21%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[C:14]4[C@:19]([C:21](O)=[O:22])([CH2:20][C:11]=3[CH:10]=[N:9]2)[CH2:18][N:17]([S:24]([C:27]2[CH:28]=[N:29][C:30]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[CH:31][CH:32]=2)(=[O:26])=[O:25])[CH2:16][CH2:15]4)=[CH:4][CH:3]=1.C(Cl)(=O)C([Cl:42])=O>ClCCl.CN(C)C=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[C:14]4[C@:19]([C:21]([Cl:42])=[O:22])([CH2:20][C:11]=3[CH:10]=[N:9]2)[CH2:18][N:17]([S:24]([C:27]2[CH:28]=[N:29][C:30]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[CH:31][CH:32]=2)(=[O:26])=[O:25])[CH2:16][CH2:15]4)=[CH:4][CH:3]=1
Reactant: O=C(O)[C@]12Cc3cnn(-c4ccc(F)cc4)c3C=C1CCN(S(=O)(=O)c1ccc(N3CCOCC3)nc1)C2
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)[C@]12Cc3cnn(-c4ccc(F)cc4)c3C=C1CCN(S(=O)(=O)c1ccc(N3CCOCC3)nc1)C2
Reaction time: 2 h

Procedure:
A solution of (R)-1-(4-fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid (0.29 g) in dry dichloromethane (9 mL) was treated with oxalyl chloride (0.21 g) for 30 minutes. One drop of N,N-dimethylformamide was added and the reaction mixture stirred for a further 2 hours. The reaction mixture was concentrated under reduced pressure and the product used without further purification.
Reaction SMILES: CC1C=CC(S(O[CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[C:21]([C:22]4[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:23]=4[F:29])[C:15]=3[O:14]2)(=O)=O)=CC=1.[N-:30]=[N+:31]=[N-:32].[Na+]>>[F:29][C:23]1[CH:24]=[CH:25][CH:26]=[C:27]([F:28])[C:22]=1[C:21]1[C:15]2[O:14][CH:13]([CH2:12][N:30]=[N+:31]=[N-:32])[CH2:17][C:16]=2[CH:18]=[CH:19][CH:20]=1
Reactant: Cc1ccc(S(=O)(=O)OCC2Cc3cccc(-c4c(F)cccc4F)c3O2)cc1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Product: [N-]=[N+]=NCC1Cc2cccc(-c3c(F)cccc3F)c2O1

Procedure:
Treatment of (±)-[7-(2,6-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanol (3.5 g, 13.35 mmol) with p-toluenesulfonyl chloride (3.05 g, 16.01 mol) generally according to the procedure described for Intermediate 10 gave 3.5 g (64%) of (±)-[7-(2,6-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate. Treatment of (±)-[7-(2,6-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (3.0 g, 7.20 mmol) with sodium azide (1.87 g, 28.8 mmol) generally according to the procedure described for Intermediate 98 gave (±)-[7-(2,6-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl azide. Treatment of the azide with palladium on carbon (0.20 g, 10 wt. %) generally according to the procedure described for Example 1 provided 1.69 g (90%) of (±)-1-[7-(2,6-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt. mp 219-222° C.; Anal. calcd. for C15H13F2NOHCl: C, 60.51; H, 4.74; N, 4.7. Found: C, 60.34; H, 4.87; N, 4.58.
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:22])=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[O:8][CH:7]([C:13]([F:16])([F:15])[F:14])[C:6]([C:17]([O:19]CC)=[O:18])=[CH:5]2.[OH-].[Li+].Cl>C1COCC1.CO.O>[Cl:1][C:2]1[C:3]([F:22])=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[O:8][CH:7]([C:13]([F:16])([F:14])[F:15])[C:6]([C:17]([OH:19])=[O:18])=[CH:5]2
Reactant: CCOC(=O)C1=Cc2c(F)c(Cl)cc(Cl)c2OC1C(F)(F)F
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)C1=Cc2c(F)c(Cl)cc(Cl)c2OC1C(F)(F)F
Temperature: 25 °C
Reaction time: 8 h
Yield: 72.5 %

Procedure:
To a solution of 359 mg (1.0 mmole) of ethyl 6,8-dichloro-5-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate in 7 mLs of THF and 2 mL of methanol was added a solution of 90 mg of lithium hydroxide monohydate in 1.0 mL of water. The mixture was heated to reflux for 60 min and allowed to cool to rt. After stirring overnight, the mixture was treated with 75 mL of 1N HCl and extracted three times with diethyl ether. The combined extracts were concd and purified by reverse phase chromatography to afford 240 mg of an impure white solid. Recrystallization from acetonitrile afforded 51 mg (15%) of a white, crystalline solid: 1H NMR (d6-acetone/400 MHz) 6.08 (q, 1H, J=7.0 Hz), 7.74 (d, 1H, J=7.7 Hz), 7.94 (s, 1H); 19F NMR (d6-acetone/400 MHz) −122.1 (d, 1F, J=7.7 Hz), −79.4 (d, 3F, J=6.8 Hz); MS (ES+) 331 (M+1, 100), 333 (M+3, 57); MS (ES−) 329 (M−1, 100), 331 (79); HRMS (ES−) m/z calcd for (C11H4C12F4O3) 328.9401, found 328.9357.
Reaction SMILES: C(O[C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:16][CH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)=[CH:13][CH:12]=[CH:11][C:10]=2[O:22][CH3:23])=[O:5])C.[N:24]([C:27]1[CH:36]=[CH:35][C:30]2[O:31][CH2:32][CH2:33][O:34][C:29]=2[CH:28]=1)=[C:25]=[O:26]>>[CH:17]1([N:16]2[C:15]3[C:14]4[CH:13]=[CH:12][CH:11]=[C:10]([O:22][CH3:23])[C:9]=4[N:8]=[CH:7][C:6]=3[C:4](=[O:5])[N:24]([C:27]3[CH:36]=[CH:35][C:30]4[O:31][CH2:32][CH2:33][O:34][C:29]=4[CH:28]=3)[C:25]2=[O:26])[CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: CCOC(=O)c1cnc2c(OC)cccc2c1NC1CCCC1
Reactant: O=C=Nc1ccc2c(c1)OCCO2
Product: COc1cccc2c1ncc1c(=O)n(-c3ccc4c(c3)OCCO4)c(=O)n(C3CCCC3)c12
Yield: 40.4 %

Procedure:
1-Cyclopentyl-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione (18 mg) was prepared from 4-cyclopentylamino-8-methoxy-quinoline-3-carboxylic acid ethyl ester (0.1 mmol) and 6-isocyanato-2,3-dihydro-benzo[1,4]dioxine (0.5 mmol) following general procedure C. LCMS: m/z 446 [M+1]+.
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=3)=[CH:13][CH:12]=2)[CH2:3]1.N1(N[C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])CCCC1>>[C:23]([C:20]1[CH:19]=[CH:18][C:17]([C:14]2[CH:15]=[CH:16][C:11]([O:10][CH2:9][CH2:8][CH2:7][N:4]3[CH2:5][CH2:6][CH:2]([NH:1][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:3]3)=[CH:12][CH:13]=2)=[CH:22][CH:21]=1)#[N:24]
Reactant: N#Cc1ccc(-c2ccc(OCCCN3CC[C@@H](N)C3)cc2)cc1
Reactant: CC(C)(C)OC(=O)NN1CCCC1
Product: CC(C)(C)OC(=O)NC1CCN(CCCOc2ccc(-c3ccc(C#N)cc3)cc2)C1

Procedure:
4′-{3-[(3R)-3-Aminopyrrolidinyl]propoxy}[1,1′-biphenyl]-4-carbonitrile and tert-butyl pyrrolidinylcarbamate were processed as described in Examples 9A-9C to provide the title compound.
Reaction SMILES: O.[NH2:2][NH2:3].[N:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]=[CH:11][CH:12]=O)[CH:5]=1>CC(O)(C)C>[N:2]1[NH:3][CH:10]([C:6]2[CH:5]=[N:4][CH:9]=[CH:8][CH:7]=2)[CH2:11][CH:12]=1
Reactant: O=CC=Cc1cccnc1
Reactant: NN
Solvent: CC(C)(C)O
Solvent: O
Product: C1=NNC(c2cccnc2)C1

Procedure:
Under N2 atmosphere, hydrazine hydrate (3.65 mL, 2 equiv.) was added to a solution of 3-(3-pyridyl)acrolein (5.0 g) in t-BuOH (25 mL). The mixture was refluxed for 3 days, followed by evaporation under reduced pressure. The residue was taken up in DCM and washed with 5% aqueous NaHCO3. The organic phase was dried over Na2SO4 and evaporated under reduced pressure. This gave 5.0 g of a red oil, containing 74% of the anticipated product and 26% of the hydrazone intermediate that failed to undergo ring-closure. This material was used in subsequent steps without further purification. Characteristic pyrazoline signals in 1H NMR (400 MHz, CDCl3): δ 2.63-2.75 (m, 1H), 3.13-3.25 (m, 1H), 4.72-4.82 (m, 1H), 6.85 (br s, 1H).
Reaction SMILES: [F:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][CH:3]=1.[CH3:9][C:10]([CH3:15])([CH3:14])[C:11](Cl)=[O:12]>N1C=CC=CC=1>[F:1][C:2]1[N:7]=[C:6]([NH:8][C:11](=[O:12])[C:10]([CH3:15])([CH3:14])[CH3:9])[CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)C(=O)Cl
Reactant: Nc1cccc(F)n1
Solvent: c1ccncc1
Product: CC(C)(C)C(=O)Nc1cccc(F)n1
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 93.2 %

Procedure:
6-fluoropyridin-2-amine (13.1 g, 117 mmol) was dissolved in anhydrous pyridine (100 mL), and cooled to 0° C. followed by fast dropwise addition of trimethylacetyl chloride (15.9 mL, 129 mmol) over 2 min. 5 min later, the resulting slurry was stirred over night at room temperature. Partial of the solvent was removed on rotary vacuum. The residue was partitioned between saturated ammonium chloride (200 mL) and EtOAc(200 mL). After separation, the organic layer was washed with brine (50 mL), dried over MgSO4, concentrated on rotary vacuum, and purified on flash chromatography eluting with 25˜75% EtOAc/Hexanes (1400 mL) to afford the expected product as a white solid(21.4 g, 93% yield); 1H NMR (400 MHz, CDCl3) δppm 1.29 (s, 9H), 6.63 (dd, J=8.06, 2.01 Hz, 1H), 7.76 (q, J=8.14 Hz, 1H) ,7.85 (s, 1H), 8.09 (dd, J=8.06, 1.76 Hz, 1H); Mass spec. 197.15 (MH+), Calc. for C10H13FN2O196.1.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([NH:9][C@H:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH3:11])[N:3]=1.[NH:19]1[CH2:24][CH2:23][NH:22][CH2:21][C:20]1=[O:25].C(N(CC)C(C)C)(C)C>C(O)CCC.C(OCC)(=O)C>[Cl:8][C:6]1[N:5]=[C:4]([NH:9][C@H:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH3:11])[N:3]=[C:2]([N:22]2[CH2:23][CH2:24][NH:19][C:20](=[O:25])[CH2:21]2)[CH:7]=1
Reactant: C[C@H](Nc1nc(Cl)cc(Cl)n1)c1ccc(F)cc1
Reactant: O=C1CNCCN1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CCCCO
Product: C[C@H](Nc1nc(Cl)cc(N2CCNC(=O)C2)n1)c1ccc(F)cc1
Temperature: 60 °C
Reaction time: 20 h
Yield: 106.9 %

Procedure:
To a solution of 150 mg of (S)-4,6-dichloro-N-[1-(4-fluorophenyl)ethyl]pyrimidine-2-amine and 58 mg of piperazin-2-one in 1.5 ml of 1-butanol was added 183 μl of N,N-diisopropylethylamine, and the mixture was stirred at 60° C. for 20 hours. The reaction solution was air-cooled to room temperature, and then diluted with ethyl acetate. The solution was washed in turn with water and brine and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 196 mg of the objective compound as white powder.
Reaction SMILES: [CH2:1]([N:5](C(OC(C)(C)C)=O)[C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:2][CH:3]=[CH2:4].FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:1]([NH:5][C:6](=[O:7])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH2:2][CH:3]=[CH2:4]
Reactant: C=CCCN(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: C=CCCNC(=O)OC(C)(C)C
Reaction time: 0.08 h
Yield: 96.2 %

Procedure:
To a solution of 186 (708 mg, 2.60 mmol) in DCM (20 mL) was added trifluoroacetic acid (593 mg, 5.20 mmol) and the mixture was allowed to stir for 5 min before being quenched with 2M NaOH (25 mL) and extracted with DCM (3×20 mL). The combined organic fractions were dried, and concentrated to yield the title compound (429 mg, 2.50 mmol, 96%) as a light brown oil, which had spectral data in agreement with that reported.104 1H NMR (CDCl3, 300 MHz): δ 5.75 (m, 1H, H3); 5.08 (m, 2H, H4); 4.59 (bs, 1H, NH); 3.20 (dd, J=6.3, 12.6 Hz, 2H, H1); 2.24 (dd, J=6.9, 12.6 Hz, 2H, H2); 1.44 (s, 9H, (CH3)3). Mass Spectrum (ES, +ve) m/z 116 (100%) [MH+ less 56 (Boc rearrangement].
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[B:9]([OH:11])[OH:10].O[C:13]([C:16](O)([CH3:18])[CH3:17])([CH3:15])[CH3:14]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[B:9]1[O:10][C:16]([CH3:18])([CH3:17])[C:13]([CH3:15])([CH3:14])[O:11]1
Reactant: OB(O)c1cc(O)ccc1Cl
Reactant: CC(C)(O)C(C)(C)O
Solvent: Cc1ccccc1
Product: CC1(C)OB(c2cc(O)ccc2Cl)OC1(C)C
Temperature: 120 °C
Yield: 82.9 %

Procedure:
2-chloro-5-hydroxyphenyl boronic acid (409 mg, 2.37 mmol), pinacol (336 mg, 2.85 mmol), toluene (20 ml) and 4 angstrom molecular sieves (400 mg) were combined and heated at 120° C. for 2 h. The reaction mixture was allowed to cool and was then partitioned between EtOAc (2×30 ml) and water (30 ml). The combined organics were washed with brine (20 ml), dried (Na2SO4) and evaporated in vacuo to afford the desired product as a white solid (500 mg, 83%).
Reaction SMILES: ClCC(C)(C)C([NH-])=O.Cl[CH2:10][C:11]([CH3:24])([CH3:23])[C:12]([NH:14]/[C:15](/[CH3:22])=[CH:16]\[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[O:13].[H-].[Na+].CCOCC>CN(C=O)C.C(Cl)Cl>[CH2:20]([O:19][C:17]([CH2:16][C:15]([N:14]1[CH2:10][C:11]([CH3:24])([CH3:23])[C:12]1=[O:13])=[CH2:22])=[O:18])[CH3:21]
Reactant: CCOC(=O)/C=C(/C)NC(=O)C(C)(C)CCl
Agent: CC(C)(CCl)C([NH-])=O
Agent: [H-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCOCC
Product: C=C(CC(=O)OCC)N1CC(C)(C)C1=O

Procedure:
The β-chloropivaloyl amide cyclization to the title β-lactam compound was accomplished by treatment of 209 mg (0.84 mmole) of the amide with 64.5 mg (1.3 mmole) of NaH in 5 mL of DMF-CH2Cl2 (1:4) for 3 hours at room temperature. The reaction mixture was poured into 75 mL of ether and washed with two 25 mL portions of water, 25 mL of brine, dried over MgSO4, filtered and evaporated to yield 177 mg (0.84 mmole, 100%) of the β-lactam title compound as an oil. IR (neat) 1770, 1705 cm-1 ; 1H NMR δ 1.16-1.33 (9H, m), 2.63 (3H, s), 3.26 (2H, s), 4.03-4.26 (2H, q), 5.2 (1H, s).
Reaction SMILES: [C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH3:6].O[C@H:10]1[CH2:15][CH2:14][C@H:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]34[CH2:29][CH2:28][C:25]([CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])([CH2:26][CH2:27]3)[CH2:24][CH2:23]4)=[CH:18][CH:17]=2)[CH2:12][CH2:11]1>ClCCl.CN(C)C1C=CN=CC=1>[C:1]([O:8][C@H:10]1[CH2:15][CH2:14][C@H:13]([C:16]2[CH:17]=[CH:18][C:19]([C:22]34[CH2:27][CH2:26][C:25]([CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])([CH2:24][CH2:23]3)[CH2:28][CH2:29]4)=[CH:20][CH:21]=2)[CH2:12][CH2:11]1)(=[O:7])/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH3:6]
Reactant: CCCCCC12CCC(c3ccc([C@H]4CC[C@H](O)CC4)cc3)(CC1)CC2
Reactant: CCC/C=C/C(=O)O
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CCC/C=C/C(=O)O[C@H]1CC[C@H](c2ccc(C34CCC(CCCCC)(CC3)CC4)cc2)CC1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
A solution of N,N-dicyclohexylcarbodiimide (0.22 g, 1.1 mmol) in dichloromethane (10 cm3) is added to a solution of (E)-hex-2-enoic acid (0.10 g, 0.9 mmol), 1-[4-(trans-4-hydroxycyclohexyl) phenyl]-4-pentylbicyclo[2.2.2]octane (0.32 g, 0.9 mmol), 4-(dimethylamino) pyridine (0.04 g) in dichloromethane (20 cm3), cooled in an ice bath (0° C.) under an atmosphere of nitrogen. The reaction mixture is stirred overnight, filtered to remove precipitated material and the filtrate is evaporated down under reduced pressure. The crude product is purified by column chromatography on silica gel using a 9:1 petroleum ether (40-60° C.)/ethyl acetate mixture as eluent, followed by recrystallization from ethanol to yield the desired ester (0.26 g, 64%).
Reaction SMILES: [O:1]([CH3:13])[C@@H:2]1[O:10][C@H:9]([CH2:11][OH:12])[C@@H:7]([OH:8])[C@H:5]([OH:6])[C@H:3]1[OH:4].CO[CH:16](OC)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(OCC)(=O)C.C(N(CC)CC)C>C(#N)C.CCCCCC.[NH4+].[NH4+].[O-][Mo]([O-])(=O)=O.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>[CH3:13][O:1][C@@H:2]1[O:10][C@@H:9]2[CH2:11][O:12][CH:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[O:8][C@H:7]2[C@H:5]([OH:6])[C@H:3]1[OH:4]
Reactant: CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Reactant: COC(OC)c1ccccc1
Agent: O=[Mo](=O)([O-])[O-]
Agent: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Agent: [NH4+]
Solvent: CCN(CC)CC
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CO[C@@H]1O[C@@H]2COC(c3ccccc3)O[C@H]2[C@H](O)[C@H]1O
Yield: 91.4 %

Procedure:
Using a modification of the procedure as described: Tetrahedron, 1992, 48(47), 10249-10264. Methyl β-D-glucopyranoside (Biosynth International M-3592; 10.2 g, 50 mmol), benzaldehyde dimethylacetal (30 ml, 200 mmol) and 10-camphorsulfonic acid (116 mg, 0.5 mmol) in anhydrous acetonitrile (150 ml) was stirred at room temperature for 4 h. The reaction was checked by TLC to confirm complete conversion to the product (run in hexane: ethyl acetate, 1:2, visualised with ceric ammonium molybdate spray and heating. The reaction was then treated with triethylamine (1 ml) to neutralise the acid. The solution was filtered and the solid was washed with acetonitrile (20 ml). The mother solution was concentrated to about 60 ml, and it was again filtrated, and the filtrate washed with acetonitdrile (10 ml). The combined solid was dried in vacuum, to give 12.9 g (91%) of methyl 4,6-O-benzylidene-β-D-glucopyranoside.
Reaction SMILES: [C:1]([C:5]1[CH:24]=[CH:23][C:8]([CH2:9][NH:10][C:11](=[O:22])[CH:12]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[C:16]([NH2:21])[CH:15]=2)[CH3:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[N:25]([O-])=O.[Na+].O>C(O)(=O)C.CN(C=O)C>[C:1]([C:5]1[CH:24]=[CH:23][C:8]([CH2:9][NH:10][C:11](=[O:22])[CH:12]([C:14]2[CH:19]=[CH:18][C:17]3[NH:20][N:25]=[N:21][C:16]=3[CH:15]=2)[CH3:13])=[CH:7][CH:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: O=N[O-]
Reactant: CC(C(=O)NCc1ccc(C(C)(C)C)cc1)c1ccc(N)c(N)c1
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Solvent: CN(C)C=O
Product: CC(C(=O)NCc1ccc(C(C)(C)C)cc1)c1ccc2[nH]nnc2c1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
N-(4-tert-Butyl-benzyl)-2-(3,4-diamino-phenyl)-propionamide (110 mg, 0.338 mmol) in 5% aq. acetic acid (3 mL) and DMF (2.5 mL) was added sodium nitrite (30 mg, 0.435 mmol) at 0° C. The reaction mixture was stirred for 14 hours at room temperature. The mixture was added water (20 mL) and extracted with methylene chloride. The organic layer was dried with MgSO4 and filtered. Methylene chloride was removed by evaporation. The residue was purified by column chromatography eluting with CH2Cl2/MeOH=10/1.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.I[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1.O>C([O-])([O-])=O.[K+].[K+].CC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([OH:1])[CH:7]=2)=[CH:13][CH:14]=1
Reactant: OB(O)c1cccc(O)c1
Reactant: COc1ccc(I)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: CC(C)=O
Solvent: O
Product: COc1ccc(-c2cccc(O)c2)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 82.1 %

Procedure:
To a solution of 3-hydroxyphenylboronic acid (1.00 g, 7.3 mmol) in 2M aqueous K2CO3 (4 mL) was added a solution of 4-iodoanisole (1.70 g, 7.3 mmol) in acetone (4 mL). A homogeneous mixture was obtained by sequential addition of water (60 mL) and acetone (30 mL). Catalytic Pd(OAc)2 was added (160 mg, 0.73 mmol) and the mixture was stirred for 10 min at room temperature. The acetone was removed from the dark brown solution in vacuo and the resultant aqueous mixture was acidified with 1N HCl (20 mL) and extracted with ethyl acetate (75 mL). The organic layer was washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude product was suspended in dichloromethane and adsorbed onto silica gel and purified by flash chromatography using hexanes-ethyl acetate (3:1) to yield 1.20 g (82%) 56 as a white solid after solvent removal.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][CH3:10])[C:4]=1[N:11]=[C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20](=O)[CH3:21])[N:15]=1)[CH3:13])[CH3:2].[C-:23]1([NH2:28])[CH:27]=[CH:26][CH:25]=[CH:24]1.[CH-:29]1[CH:33]=[CH:32][CH:31]=[CH:30]1.[Fe+2:34]>C1(C)C=CC=CC=1>[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][CH3:10])[C:4]=1[N:11]=[C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20](=[N:28][C-:23]2[CH:27]=[CH:26][CH:25]=[CH:24]2)[CH3:21])[N:15]=1)[CH3:13])[CH3:2].[CH-:29]1[CH:33]=[CH:32][CH:31]=[CH:30]1.[Fe+2:34]
Reactant: CCc1cccc(CC)c1N=C(C)c1cccc(C(C)=O)n1
Reactant: N[c-]1cccc1
Agent: [Fe+2]
Agent: c1cc[cH-]c1
Solvent: Cc1ccccc1
Product: CCc1cccc(CC)c1N=C(C)c1cccc(C(C)=N[c-]2cccc2)n1
Reaction time: 40 h

Procedure:
In an inert atmosphere, monoimine 2-[1-(2,6-diethylphenylimino)ethyl]-6-acetylpyridine (8, 368 mg, 1.25 mmol ) and ferrocenylamine (268 mg, 1.33 mmol) were dissolved in 50 ml of toluene. To this solution, molecular sieves (4 Å) were added. After standing for 40 hours the mixture was filtered. The solvent was removed in vacuo. The residue was recrystallised from ethanol. Yield 160 mg (27%) red crystals of mixed diimine 9.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([CH2:11][O:12][CH3:13])[CH:3]=1.CCO.O.[Cl-].[NH4+]>C(OCC)(=O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([CH2:11][O:12][CH3:13])[CH:3]=1)[NH2:8]
Reactant: COCc1cc(Br)cc([N+](=O)[O-])c1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CCO
Product: COCc1cc(N)cc(Br)c1
Temperature: 90 °C
Reaction time: 4 h
Yield: 62.5 %

Procedure:
To a solution of the product of Step 1 (470 mg, 1.910 mmol) in (EtOH/water) (8.5 mL/4.2 mL) were added iron (533 mg, 9.55 mmol) and ammonium chloride (51 mg, 0.955 mmol). The reaction was stirred at 90° C. for about 4 hours. The reaction was then allowed to come to room temperature and diluted with ethyl acetate. The solution was then filtered through Celite and organic solvent was then removed in vacuo. Flash chromatography (hexane/ethyl acetate: 70/30) was used for purification to afford 3-bromo-5-(methoxymethyl)aniline (258 mg, 1.194 mmol, 62.5% yield). MS ESI: [M+H]+ m/z=216.0.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:9]=[N:10][C:11]([CH:14]([F:16])[F:15])=[CH:12][CH:13]=1)(C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+]>ClCCl>[F:15][CH:14]([F:16])[C:11]1[N:10]=[CH:9][C:8]([NH2:7])=[CH:13][CH:12]=1
Reactant: CC(C)(C)OC(=O)Nc1ccc(C(F)F)nc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Nc1ccc(C(F)F)nc1
Yield: 60.3 %

Procedure:
A solution of the compound obtained in Step C (5.9 g) in dichloromethane (80 ml) was treated with trifluoroacetic acid (3.7 ml) at ambient temperature for 12 hours. The reaction mixture was poured into aqueous sodium hydrogen carbonate (saturated) and washed several times with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate and then concentrated in vacuo. Chromatography on silica gel (eluent: hexane/ethyl acetate 1:1) afforded 6-difluoromethyl-pyridin-3-yl-amine (2.1 g): 1H NMR (400 MHz, CDCl3) 3.98 (br s, 2H), 6.56 (t, 1H), 7.03 (dd, 1H), 7.40 (d, 1H), 8.06 (d, 1H).
Reaction SMILES: [C:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][C:5]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)(=O)[CH3:2].C(=O)(O)O.[NH2:23][NH:24][C:25]([NH2:27])=[NH:26]>C(O)(C)C.Cl>[C:13]1([C:5]2[NH:6][C:7]3[C:12]([C:4]=2[C:1](=[N:23][NH:24][C:25](=[NH:26])[NH2:27])[CH3:2])=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: N=C(N)NN
Reactant: CC(=O)c1c(-c2ccccc2)[nH]c2ccccc12
Agent: Cl
Agent: O=C(O)O
Solvent: CC(C)O
Product: CC(=NNC(=N)N)c1c(-c2ccccc2)[nH]c2ccccc12
Temperature: 80 °C
Yield: 36 %

Procedure:
A mixture of 2-phenylindole (193.3 mg, 1.0 mmol) and acetyl chloride (92 μL, 1.3 mmol) in CH2Cl2 is treated with tin tetrachloride (97.4 μL, 1.9 mmol) at room temperature, shaken for 6 h, quenched with saturated NaHCO3 and extracted with ethyl acetate. The extracts are combined and concentrated in vacuo to afford the 3-acetyl-2-phenylindole intermediate. A suspension of the thus-obtained 3-acetyl-2-phenylindole (47 mg, 0.2 mmol) in isopropanol and concentrated HCl (5 μL) is treated with aminoguanidine bicarbonate, heated at 80° C. for 2 h, cooled to room temperature and concentrated in vacuo. The resultant residue is purified by HPLC to afford the title product, 21.0 mg (36% yield), identified by HPLC1 and mass spectral analyses, (M+H) 292, retention time 3.9 min.