Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([OH:12])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:13]([O-])([O-])=O.[K+].[K+].IC>CC(C)=O>[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][CH3:13])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]
Reactant: COC(=O)c1cc(O)cc(O)c1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CC(C)=O
Product: COC(=O)c1cc(O)cc(OC)c1
Yield: 37 %

Procedure:
A suspension of methyl 3,5-dihydroxybenzoate (2.0 g, 11.9 mmol), K2CO3 (1.6 g, 11.9 mmol), and iodomethane (1.7 g, 11.9 mmol) in acetone (100 mL) was stirred at reflux. After stirring for three hours the mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified by column chromatography to yield the title compound as a white solid (0.813 g, 4.4 mmol). 1H NMR (400 MHz, CDCl3)δ7.16 (m, 1 H), 7.12 (m, 1 H), 6.61 (m, 1 H), 5.04 (s, 1 H), 3.91 (s, 3 H) 3.82 (s, 3 H).
Reaction SMILES: I[C:2]1[N:3]=[C:4]2[C:10]3[CH:11]=[CH:12][C:13]([C:15]([O:17][CH3:18])=[O:16])=[CH:14][C:9]=3[O:8][CH2:7][CH2:6][N:5]2[CH:19]=1.[F:20][C:21]([F:32])([F:31])[C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1.C(#N)C>C(=O)([O-])[O-].[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:20][C:21]([F:32])([F:31])[C:22]1[CH:27]=[C:26]([C:2]2[N:3]=[C:4]3[C:10]4[CH:11]=[CH:12][C:13]([C:15]([O:17][CH3:18])=[O:16])=[CH:14][C:9]=4[O:8][CH2:7][CH2:6][N:5]3[CH:19]=2)[CH:25]=[CH:24][CH:23]=1
Reactant: OB(O)c1cccc(C(F)(F)F)c1
Reactant: COC(=O)c1ccc2c(c1)OCCn1cc(I)nc1-2
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: COC(=O)c1ccc2c(c1)OCCn1cc(-c3cccc(C(F)(F)F)c3)nc1-2
Yield: 40.5 %

Procedure:
Methyl 2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-9-carboxylate (80 mg, 1 eq), 3-(trifluoromethyl)phenylboronic acid (76 mg, 1.75 eq), and tetrakis(triphenylphosphine)palladium (10 mg, 0.05 eq), in 1.0 M aqueous sodium carbonate (1.0 mL) and acetonitrile (1.0 mL) were heated to 140° C. for 10 min in a sealed microwave reactor. The crude reaction mixture was concentrated and purified using reverse phase HPLC to yield 299 (34 mg). ESI-MS: 389.1(M)+
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[CH:15]=[CH:14][C:11]([CH:12]=[O:13])=[CH:10][CH:9]=2)[N:3]=1.[F:16][C:17]([F:29])([F:28])[O:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1>[Pd]>[F:16][C:17]([F:28])([F:29])[O:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([C:8]3[CH:15]=[CH:14][C:11]([CH:12]=[O:13])=[CH:10][CH:9]=3)[N:3]=2)=[CH:21][CH:20]=1
Reactant: OB(O)c1ccc(OC(F)(F)F)cc1
Reactant: O=Cc1ccc(-c2nccc(Cl)n2)cc1
Agent: [Pd]
Product: O=Cc1ccc(-c2nccc(-c3ccc(OC(F)(F)F)cc3)n2)cc1

Procedure:
The compound was prepared by palladium-catalyzed arylation of the product of Step 1 with 4-trifluoromethoxyphenyl boronic acid: 1H NMR (400 MHz, CDCl3) δ 10.14 (s, 1H), 8.91 (d, J=4.2 Hz, 1H), 8.63 (d, J=8.5 Hz, 2H), 8.37 (d, J=8.4 Hz, 2H), 8.06 (d, J=8.8 Hz, 2H), 7.67 (d, J=5.4 Hz, 1H), 7.35 (d, J=8.7 Hz, 2H); EIMS m/z 344 (M+).
Reaction SMILES: [N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:16]=[CH:17][CH:18]=2)[O:11][CH2:12][CH2:13][CH2:14][NH2:15])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.I.[CH3:20][N:21]1[CH2:25][C:24](=[O:26])[N:23]=[C:22]1SC.C(N(CC)CC)C>C(O)C>[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:16]=[CH:17][CH:18]=2)[O:11][CH2:12][CH2:13][CH2:14][NH:15][C:22]2[N:21]([CH3:20])[CH2:25][C:24](=[O:26])[N:23]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: NCCCOc1cccc(CN2CCCCC2)c1
Reactant: CSC1=NC(=O)CN1C
Agent: I
Solvent: CCO
Solvent: CCN(CC)CC
Product: CN1CC(=O)N=C1NCCCOc1cccc(CN2CCCCC2)c1

Procedure:
3-(3-Piperidinomethylphenoxy)propylamine (2.61 g), 1-methyl-2-methylthioimidazolin-4-one hydroiodide (2.85 g) and triethylamine (3.635 g) were refluxed in ethanol (25 ml) for 5 hours.
Reaction SMILES: [N:1]([C:10]1[CH:16]=[CH:15][C:13]([NH2:14])=[CH:12][CH:11]=1)=[N:2][C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[CH:5][CH:4]=1.[C:17](OCC)(=[O:19])[CH3:18]>ClCCl>[C:17]([NH:14][C:13]1[CH:15]=[CH:16][C:10]([N:1]=[N:2][C:3]2[CH:4]=[CH:5][C:6]([NH2:7])=[CH:8][CH:9]=2)=[CH:11][CH:12]=1)(=[O:19])[CH3:18]
Reactant: CCOC(C)=O
Reactant: Nc1ccc(N=Nc2ccc(N)cc2)cc1
Solvent: ClCCl
Product: CC(=O)Nc1ccc(N=Nc2ccc(N)cc2)cc1
Yield: 73 %

Procedure:
Following the general monoacylation procedure, 4,4′-azodianiline (25 mg, 120 μmol) was treated with acetyl choloride (8.5 μl, 120 μmol). Silica gel chromatography through a wide column (20% ethyl acetate in dichloromethane, gradient to 66%) provided S1 as an orange solid (22 mg, 90 μmol, 73% yield): 1H (CD3CN, 500 MHz): 1.98 (s, 3H); 4.77 (s, 21-1); 6.74 (d, 2H, J=8.5); 7.70 (d, 4H. J=8.5); 7.77 (d, 21-1, J=8.5); 8.53 (s, 1H). 13C(CD3CN, 125 MHz): 23.4, 113.9, 119.3, 122.7, 124.7, 140.6, 144.3, 148.6, 151.5, 168.7. HRMS (FAB+): calc'd for C14H14N4O—254.1168. found—254.1171 (M+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[C:20]1([CH2:26][C:27](Cl)=[O:28])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:13][CH2:14]2)[C:27](=[O:28])[CH2:26][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:4][CH:3]=1
Reactant: O=C(Cl)Cc1ccccc1
Reactant: CCOC(=O)N1CCC(Nc2ccc(Cl)cc2)CC1
Solvent: c1ccccc1
Product: CCOC(=O)N1CCC(N(C(=O)Cc2ccccc2)c2ccc(Cl)cc2)CC1

Procedure:
To a stirred solution of 58 parts of ethyl 4-[(4-chlorophenyl)amino]-1-piperidinecarboxylate in 240 parts of benzene is added dropwise a solution of 46.2 parts of benzeneacetyl chloride in 80 parts of benzene at a temperature between 40°-70° C. Upon completion, the whole is stirred and refluxed for 6h.15. The reaction mixture is cooled and filtered. The filtrate is washed successively with water, sodium hydrogen carbonate solution and water, then dried and evaporated in vacuo. The residue is crystallized from 1,1'-oxybisethane, yielding 47 parts of ethyl 4-[N-(4-chlorophenyl)-N-(phenylacetyl)amino]-1-piperidinecarboxylate; mp. 108° C.
Reaction SMILES: [H-].[Na+].Cl.[CH2:4]([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([OH:17])[CH2:12]1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.Cl[C:19]1[N:20]=[N:21][C:22]([N:25]2[CH:29]=[CH:28][N:27]=[CH:26]2)=[CH:23][CH:24]=1>CN(C=O)C>[N:25]1([C:22]2[N:21]=[N:20][C:19]([O:17][CH:13]3[CH2:14][CH2:15][CH2:16][N:11]([CH2:4][C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=4)[CH2:12]3)=[CH:24][CH:23]=2)[CH:29]=[CH:28][N:27]=[CH:26]1
Reactant: OC1CCCN(Cc2ccccc2)C1
Reactant: Clc1ccc(-n2ccnc2)nn1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: c1ccc(CN2CCCC(Oc3ccc(-n4ccnc4)nn3)C2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 36.1 %

Procedure:
To a suspension of NaH (0.21 g, 8.31 mmol) in DMF (5 mL) was added 1-benzyl-3-hydroxypiperidine hydrochloride (0.78 g, 3.3 mmol) in DMF (5 mL), and the resulting reaction mixture was stirred at ambient temperature for 30 minutes. 3-chloro-6-(imidazol-1-yl)pyridazine (0.6 g, 3.3 mmol) in DMF (5 mL) was then added dropwise. The reaction mixture was stirred at ambient temperature for 30 minutes. After removal of DMF in vacuo, the black oil was dissolved in CH2Cl2 (50 mL), washed with water and brine. Purification using column chromatography afforded 3-[(6-(imidazol-1-yl)pyridazin-3-yl)oxy]-1-benzylpiperidine (400 mg) as a yellow oil.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18](=O)[CH3:19])=[CH:15][CH:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:21][OH:22].Cl>CCO>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18](=[N:21][OH:22])[CH3:19])=[CH:15][CH:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(=O)c1ccc2c(c1)CCCN2C(=O)OC(C)(C)C
Reactant: NO
Agent: Cl
Solvent: CCO
Product: CC(=NO)c1ccc2c(c1)CCCN2C(=O)OC(C)(C)C
Yield: 96.4 %

Procedure:
A solution of 6-acetyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester (1.38 g, 5 mmol) in EtOH (20 mL) was treated with NH2OH.HCl (695 mg, 10 mmol). The resulting solution was stirred at 23° C. for 3 hours in the presence of Amberlist A-21 (2.0). Then the mixture was filtered and the solvent evaporated. The residue was dissolved in EtOAc, washed with aqueous NaHCO3 and then brine. After drying (MgSO4), the organic layer was concentrated and the crude oxime purified by chromatography (SiO2, 10-25% EtOAc in hexane) to give 1.4 g (90%) of the title compound as a white solid. m.p: 127-129° C.
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][C:12]=1[F:18]>>[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][C:2]2[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=2)=[CH:13][C:12]=1[F:18]
Reactant: Oc1ccc(Cl)c(F)c1
Reactant: O=Cc1ccc(F)cc1
Product: O=Cc1ccc(Oc2ccc(Cl)c(F)c2)cc1

Procedure:
The title compound was prepared by a procedure similar to that described for D4 starting from 4-fluorobenzaldehyde and 4-chloro-3-fluorophenol.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][CH:11]=2)[C:5]([N+:20]([O-:22])=[O:21])=[CH:4][CH:3]=1.[NH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[O:26]1[CH2:27][CH2:28][N:23]([C:2]2[N:7]=[C:6]([NH:8][CH2:9][C:10]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH:13]=[CH:12][CH:11]=3)[C:5]([N+:20]([O-:22])=[O:21])=[CH:4][CH:3]=2)[CH2:24][CH2:25]1
Reactant: O=[N+]([O-])c1ccc(Cl)nc1NCc1cccc2ccccc12
Reactant: C1COCCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccc(N2CCOCC2)nc1NCc1cccc2ccccc12
Temperature: 80 °C
Reaction time: 1 h
Yield: 95.8 %

Procedure:
A mixture of 6-chloro-N-(naphthalen-1-ylmethyl)-3-nitropyridin-2-amine (3.21 g, 10.2 mmol), morpholine (2.66 g, 30.6 mmol) and K2CO3 (2.11 g, 15.3 mmol) in DMF (50 mL) was stirred at 80° C. for 1 h. It was cooled to room temperature and poured into water (300 mL). It was extracted with EA (300 mL×2). The combined organic layers were washed with brine (300 mL×3), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel eluted with EtOAc/Pet ether=1/1 to afford the desired product as a yellow solid (3.56 g, 96%); LC/MS: MS (ES+) m/e 365 (MH+); 1H NMR (300 MHz, DMSO-d6) δ ppm 3.53 (t, J=4.2 Hz, 4H), 3.60 (t, J=4.2 Hz, 4H), 5.19 (d, J=5.7 Hz, 2H), 6.33 (d, J=9.6 Hz, 1H), 7.44-7.61 (m, 4H), 7.85 (d, J=7.5 Hz, 1H), 7.97 (d, J=7.5 Hz, 1H), 8.12 (d, J=9.6 Hz, 1H), 8.21 (d, J=7.5 Hz, 1H), 9.25 (t, J=5.7 Hz, 1H).
Reaction SMILES: [CH3:1][C:2]1[N:3]([C:8]2[CH:9]=[C:10]([C:14]([OH:20])([CH3:19])[C:15]([F:18])([F:17])[F:16])[N:11]([CH3:13])[N:12]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.[H-].[Na+].[CH3:23]I>C1COCC1>[CH3:7][C:4]1[N:3]([C:8]2[CH:9]=[C:10]([C:14]([O:20][CH3:23])([CH3:19])[C:15]([F:18])([F:17])[F:16])[N:11]([CH3:13])[N:12]=2)[C:2]([CH3:1])=[CH:6][CH:5]=1
Reactant: CI
Reactant: Cc1ccc(C)n1-c1cc(C(C)(O)C(F)(F)F)n(C)n1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(C)(c1cc(-n2c(C)ccc2C)nn1C)C(F)(F)F
Reaction time: 0.17 h

Procedure:
To a solution of 2-[5-(2,5-dimethyl-pyrrol-1-yl)-2-methyl-2H-pyrazol-3-yl]-1,1,1-trifluoro-propan-2-ol (0.5 g, 1.7 mmol) in THF (10 mL) at 0° C., sodium hydride (0.21 g, 60%, 5.2 mmol) is added, and the mixture is stirred for 10 min followed by the addition of methyl iodide (0.22 mL, 3.5 mmol). The ice bath is removed and the reaction mixture is stirred at room temperature for 5 hour, poured into water, separated, and the water layer is extracted with DCM. The organic layers are combined and concentrated. The residue is purified by FCC to give the title compound. MS (ESI) m/z 302.0 (M+1).
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[C:7]2[CH:8]=[C:9](B(O)O)[CH:10]=[CH:11][C:6]=2[NH:5][C:4](=[O:15])[O:3]1.[Br:17][C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[C:20](Br)[CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:17][C:18]1[CH:19]=[C:20]([C:9]2[CH:10]=[CH:11][C:6]3[NH:5][C:4](=[O:15])[O:3][C:2]([CH3:16])([CH3:1])[C:7]=3[CH:8]=2)[CH:21]=[C:22]([F:24])[CH:23]=1
Reactant: Fc1cc(Br)cc(Br)c1
Reactant: CC1(C)OC(=O)Nc2ccc(B(O)O)cc21
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: CC1(C)OC(=O)Nc2ccc(-c3cc(F)cc(Br)c3)cc21
Temperature: 85 °C
Yield: 40 %

Procedure:
A mixture of (1,4-dihydro-4,4-dimethyl-2-oxo-2H-3,1-benzoxazin-6-yl)boronic acid (2.22 g, 10 mmol), 1,3-dibromo-5-fluorobenzene (3.05 g, 12 mmol), tetrakis(triphenylphosphine)palladium (0) (0.6 g, 0.52 mmol), and sodium carbonate (2.2 g, 21 mmol) in a mixture of DME and water (70 mL/15 mL) was degassed to remove the oxygen and then heated at 85° C. under a blanket of nitrogen for 3 hours. The reaction mixture was cooled to ambient temperature and quenched with a saturated aqueous ammonium chloride solution (20 mL). Ethyl acetate (100 mL) was added and organic layer was separated. The aqueous layer was extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with brine and dried with MgSO4. The solvent was removed in vacuo and the residue was purified by a silica gel flash chromatography (hexane:ethyl acetate/1:1) to give 6-(3-bromo-5-fluorophenyl)-4,4-dimethyl-1,4-dihydrobenzo[d][1,3]oxazin-2-one as a white solid (1.4 g, 40%): mp 182-183° C.; 1H-NMR (DMSO-d6) δ 10.36 (s, 1H, D2O exchangeable), 7.78 (s, 1H), 7.58-7.65 (m, 3H), 7.49 (dd, 1H, J=8.3, 1.8 Hz), 6.96 (d, 1H, J=8.5 Hz), 1.69 (s, 6H); 19F-NMR (DMSO-d6) δ −112.46 (m, 1F); MS (CI) m/z 352 ([M+H]+, 78%), 350 ([M+H]+, 75%). Anal. Calcd. For C16H13BrFNO2: C, 54.88; H, 3.74; N, 4.00. Found: C, 54.83; H, 3.82; N, 3.95.
Reaction SMILES: [N:1]([CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][OH:27])=[N+]=[N-].[C:28]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:33]=CC=C[CH:29]=1.O>C1COCC1>[CH2:4]([NH2:1])[CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:33][C:28]#[CH:29]
Reactant: [N-]=[N+]=NCCOCCOCCOCCOCCOCCOCCOCCO
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: C#CCOCCOCCOCCOCCOCCOCCOCCOCCN
Reaction time: 12 h
Yield: 79.4 %

Procedure:
23-Azido-3,6,9,12,15,18,21-heptaoxatricosan-1-ol (azido-PEG8-yne) (960 mg, 2.52 mmol, 1 equiv.), triphenylphosphine (992 mg, 3.78 mmol, 1.5 equiv.), and water (68 μL, 3.78 mmol, 1.5 equiv.) were dissolved in THF (10 mL) and stirred for 12 h. Reaction was concentrated and chromatographed (3 cm×20 cm Silica, CH2Cl2 then ramp to 80:20:1 CH2Cl2:MeOH:Et3N) and concentrated to yield 3,6,9,12,15,18,21,24-octaoxaheptacos-26-yn-1-amine (9) as a clear oil (815 mg, 91% yield). IR (thin film, NaCl) 3105 (br), 2914 (m), 1781 (m), 1638 (m), 1169 (s) cm−1. 1H-NMR (500 MHz, CDCl3) δ 4.17 (d, 2H, J=2.4), 3.66-3.57 (m, 28H), 3.54 (t, 2H, J=5.3 Hz), 2.88 (t, 2H, J=5.0 Hz), 2.41 (t, 1H, J=2.4 Hz), 2.18 (br s, 2H). 13C NMR (125 MHz, CDCl3) δ 79.52, 74.59, 72.54, 70.41, 70.38, 70.38, 70.35, 70.31, 70.20, 70.06, 68.90, 58.20, 41.44. HRMS (ES+) calc'd for C19H37NO8 (M+H) m/z 408.259194. Found 408.25712.
Reaction SMILES: [OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([SH:8])[CH2:4][CH2:3]1.[H-].[Na+].CN(C)C=[N:14][S:15]([C:18]1[S:19][C:20](Br)=[CH:21][CH:22]=1)(=[O:17])=[O:16]>CN(C=O)C>[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([S:8][C:20]2[S:19][C:18]([S:15]([NH2:14])(=[O:17])=[O:16])=[CH:22][CH:21]=2)[CH2:4][CH2:3]1
Reactant: CN(C)C=NS(=O)(=O)c1ccc(Br)s1
Reactant: O[C@H]1CC[C@H](S)CC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: NS(=O)(=O)c1ccc(S[C@H]2CC[C@H](O)CC2)s1
Reaction time: 8 h

Procedure:
Trans-4-Hydroxycyclohexylmercaptan (9.92 g, 0.075 mol) in DMF (10 ml) was added dropwise to a stirred mixture of NaH (3.45 g, 50 % oil, 0.075 mol) and DMF (40 ml). When gas evolution was complete, N,N-dimethyl-N'-(5-bromothiophene-2-sulfonyl)formamidine (14.85 g, 0.05 mol) was added in one portion, rinsed in with DMF (10 ml) and the resulting mixture was heated on the steam bath for 1 hour. The DMF was removed under reduced pressure and the residue was stirred with methanol (50 ml) and 10% sodium hydroxide solution (50 ml) overnight. The methanol was evaporated and the resulting aqueous solution was added to 10% HCl (400 ml) and chilled. The solid that separated was collected and washed with water. The residue was triturated with 1-chlorobutane to give a solid, (12.0 g) after drying. Recrystallization from water followed by dichloroethane gave material with m.p. 145°-147° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[N:7]([CH2:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([CH:16]=[C:17](Br)Br)[CH2:12][CH2:11]1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[CH2:26]=[O:27]>O1CCCC1>[C:1]([O:5][C:6](=[O:20])[N:7]([CH2:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([C:16]#[C:17][CH2:26][OH:27])[CH2:12][CH2:11]1)[CH3:8])([CH3:4])([CH3:3])[CH3:2]
Reactant: C=O
Reactant: CN(C[C@H]1CC[C@H](C=C(Br)Br)CC1)C(=O)OC(C)(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CN(C[C@H]1CC[C@H](C#CCO)CC1)C(=O)OC(C)(C)C
Temperature: 25 °C

Procedure:
A solution of 32.9 g (80 mmol) of trans-[4-(2,2-dibromo-vinyl)-cyclohexylmethyl]-methyl-carbamic acid tert-butyl ester in 640 ml tetrahydrofuran was treated at −78° C. with 105 ml (168 mmol) of n-butyl-lithium (ca 1.6 M in hexane). After 2 hours at this temperature, 24 g (800 mmol) of paraformaldehyde were added. The reaction mixture was warmed up to room temperature for 3 hours and after 0.5 hours at this temperature extracted with water/ether (3×). The organic phases were washed with aqueous 10% NaCl, dried over sodium sulfate and evaporated. Purification by flash-chromatography on silica gel (hexane/EtOAc 9:1 to 2:1) yielded 12.1 g (54%) of trans-[4-(3-hydroxy-prop-1-ynyl)-cyclohexylmethyl]-methyl-carbamic acid tert-butyl ester as orange viscous oil, MS: 282 (MH+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:20])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14](Cl)=[O:15])=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18].[F:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26][NH2:27])=[CH:24][CH:23]=1>>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:20])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([NH:27][CH2:26][C:25]2[CH:28]=[CH:29][C:22]([F:21])=[CH:23][CH:24]=2)=[O:15])=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18]
Reactant: NCc1ccc(F)cc1
Reactant: O=C(Cl)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1
Product: O=C(NCc1ccc(F)cc1)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1

Procedure:
Prepared according to the procedure described for example 50 from 5-[(3,5-dichloro-4-pyridyl)sulfanyl]-4-nitro-thiophene-2-carbonyl chloride (100 mg, 0.27 mmol) and 4-fluorobenzylamine (40 mg, 0.32 mmol). The title compound was obtained as a solid (60 mg, 48% yield). 1H NMR (400 MHz, d6-DMSO) δ: 9.37 (1H, m), 9.03 (2H, s), 8.46 (1H, s), 7.32 (2H, dd), 7.20 (2H, dd), 4.43 (2H, m). MS m/z: 456.04, 458.00 [M+H]+.
Reaction SMILES: [N:1]1[C:9]([NH2:10])=[C:8]2[C:4]([N:5]=[CH:6][NH:7]2)=[N:3][CH:2]=1.[F-].[CH2:12]([N+](CCCC)(CCCC)CCCC)CCC.CI>O1CCCC1>[CH3:12][N:5]1[CH:6]=[N:7][C:8]2[C:4]1=[N:3][CH:2]=[N:1][C:9]=2[NH2:10]
Reactant: CCCC[N+](CCCC)(CCCC)CCCC
Reactant: Nc1ncnc2nc[nH]c12
Agent: [F-]
Solvent: C1CCOC1
Solvent: CI
Product: Cn1cnc2c(N)ncnc21

Procedure:
Adenine (2.0 g, 14.8 mmol), tetrahydrofuran (100 mL) and tetrabutyl-ammonium-fluoride solution in 1.0 M tetrahydrofuran (37 mL, 37 mmol) were added in 300 mL mad apple-type flask with a magnetic stirrer. Methyl-iodide (2.72 mL) added drop wise to the solution in 10 minutes during stirring and allowed to stir for 2.5 hr. The reaction solution was evaporated under reduced pressure. The residues were dissolved in methanol and filtered. The filtrate was added ethanol-water mixture. The object was recrystallized in ethanol-water mixture to give white solids (1.0 g, yield, 45%). 1H NMR (400 MHz, DMSO-d6): δ 3.70 (s, 3H), 7.15 (br, 2H), 8.07 (s, 1H), 8.13 (s, 1H), 13C NMR (100 MHz, DMSO-d6): δ 29.3, 118.6, 141.3, 149.8, 152.4, 155.9; MS (ESI+)calcd for C6H7N5+(M+H+) 150.0774, found 150.0914.
Reaction SMILES: [CH2:1]1[O:17][C:16]2[CH:15]=[CH:14][C:5]([CH:6]=[N:7][CH2:8][CH:9]([O:12][CH3:13])[O:10][CH3:11])=[CH:4][C:3]=2[O:2]1.[BH4-].[Na+]>CO>[CH2:1]1[O:17][C:16]2[CH:15]=[CH:14][C:5]([CH2:6][NH:7][CH2:8][CH:9]([O:12][CH3:13])[O:10][CH3:11])=[CH:4][C:3]=2[O:2]1
Reactant: COC(CN=Cc1ccc2c(c1)OCO2)OC
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COC(CNCc1ccc2c(c1)OCO2)OC
Temperature: 25 °C
Yield: 45.5 %

Procedure:
Imine 11b (10.74 g, 0.045 mol) was dissolved in methanol (100 mL) and NaBH4 (2×3 g) was added over 1 h while stirring the reaction mixture at room temperature. The reaction was quenched with methanol and the reaction mixture was concentrated and then diluted with diethyl ether (400 mL). The precipitate formed was removed by filtration. The filtrate was washed with water (2×200 mL), brine (200 mL), dried (Na2SO4) and concentrated to provide a yellow liquid (4.90 g, 46%). 1H NMR (300 MHz CDCl3) 6.79-6.69 (m, 3H), 5.86 (s, 2H), 4.41 (t, J=5.4 Hz, 1H), 3.64 (s, 2H), 3.30 (s, 6H), 2.65 (d, J=5.4 Hz, 2H).
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:6]=[CH:7][CH:8]=1>Br>[NH:12]1[CH2:13][CH2:14][CH:9]([C:5]2[CH:4]=[C:3]([OH:2])[CH:8]=[CH:7][CH:6]=2)[CH2:10][CH2:11]1
Reactant: COc1cccc(C2CCNCC2)c1
Agent: Br
Product: Oc1cccc(C2CCNCC2)c1
Temperature: 120 °C
Reaction time: 3 h

Procedure:
4-(3-Methoxy-phenyl)-piperidine (1.7 g) was dissolved in 48-% HBr (60 ml) and stirred at 120° C. under an Argon-atmosphere for 3 h. The excess of HBr was then evaporated and absolute ethanol added and evaporated. This procedure was repeated several times to yield dry crystals of 3-piperidin-4-yl-phenol×HBr (2.3 g). MS m/z (relative intensity, 70 eV) 177 (M+, bp), 176 (23), 91 (14), 57 (44), 56 (60).
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.[C:11]1([C:17]2([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:19][CH:18]2[C:20]#N)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.S(=O)(=O)(O)[OH:29]>CCCCCC.C1(C)C=CC=CC=1>[C:11]1([C:17]2([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:19][CH:18]2[CH:20]=[O:29])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=S(=O)(O)O
Reactant: N#CC1CC1(c1ccccc1)c1ccccc1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: O=CC1CC1(c1ccccc1)c1ccccc1
Temperature: -40 °C
Reaction time: 1 h

Procedure:
A solution of diisobutylaluminum hydride in hexane (25%; 212 mL) was added over 30 minutes to a solution of 2,2-diphenylcyclopropanecarbonitrile (45.4 g) in dry toluene (400 mL) maintained at -40° C. during the addition. After the reaction had been stirred at room temperature for 1 hour, it was rechilled to 0°-5° C. and 2N sulfuric acid (400 mL) was added dropwise. The two phase system was stirred at ambient temperature for 1 hours then the layers were separated and the aqueous phase was extracted with ethyl acetate (2×300 mL). The organic layers were washed with Rochelle salt solution (5%; 2×200 mL), then were dried (Na2SO4) and evaporated to give 2,2-diphenylcyclopropanecarboxaldehyde as a solid, mp 71°-73° C. A sample was crystallized from benzene-hexane to provide the purified aldehyde, mp 75°-76° C.