Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[C:5]([N:10]2[CH2:15][CH:14]=[C:13]([C:16]([OH:18])=O)[CH2:12][CH2:11]2)=[N:6][CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].C[N+]1(C2N=C(OC)N=C(OC)N=2)CCOCC1.[Cl-].CN1CCOCC1.Cl.[CH3:45][NH:46][O:47][CH3:48]>CO>[CH3:48][O:47][N:46]([CH3:45])[C:16]([C:13]1[CH2:12][CH2:11][N:10]([C:5]2[C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=[CH:7][N:6]=2)[CH2:15][CH:14]=1)=[O:18]
Reactant: O=C(O)C1=CCN(c2ncccc2[N+](=O)[O-])CC1
Reactant: CNOC
Agent: COc1nc(OC)nc([N+]2(C)CCOCC2)n1
Agent: Cl
Agent: [Cl-]
Solvent: CO
Solvent: CN1CCOCC1
Product: CON(C)C(=O)C1=CCN(c2ncccc2[N+](=O)[O-])CC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 77 %

Procedure:
To a solution of Compound 260a (100 mg, 0.40 mmol) in methanol (10 mL) stirred at r.t., was added DMT-MM (4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, 142 mg, 0.52 mmol), N-methylmorpholine (88.4 μL, 0.81 mmol) and N,O-dimethylhydroxylamine hydrochloride (60 mg, 0.615 mmol). The reaction mixture was stirred at r.t. for 3 h. The solvent was evaporated to dryness in vacuo. The residue was diluted with aq. 1N NaOH and dichloromethane. The combined organic layers were washed with brine, dried on Na2SO4 and evaporated to dryness in vacuo to afford a residue, which was purified by flash chromatography (EtOAc—Petroleum Ether 60:40) affording the title product (90 mg).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=1.ClC(Cl)(O[C:27](=[O:33])OC(Cl)(Cl)Cl)Cl.[F:35][C:36]1[C:42]([F:43])=[CH:41][CH:40]=[C:39]([F:44])[C:37]=1[NH2:38].C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.C(N(CC)CC)C>[F:35][C:36]1[C:42]([F:43])=[CH:41][CH:40]=[C:39]([F:44])[C:37]=1[NH:38][C:27]([NH:22][C:19]1[CH:18]=[CH:17][C:16]([O:15][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[N:9]=[CH:8][CH:7]=2)=[CH:21][CH:20]=1)=[O:33]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Reactant: Nc1c(F)ccc(F)c1F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=O)Nc4c(F)ccc(F)c4F)cc3)c2cc1OC
Yield: 37.9 %

Procedure:
6,7-Dimethoxy-4-(4-aminophenoxy)quinoline (50 mg) was dissolved in toluene (5 ml) with heat, after the addition of triethylamine (1 ml), triphosgene (55 mg) was added, and the admixture was refluxed with heat for 3 minutes. 2,3,6-trifluoroaniline (53 mg) was added to the reaction mixture, and the admixture was refluxed with heat for 20 minutes. After the addition of aqueous sodium hydrogen carbonate, the reaction mixture was extracted 2 times with ethyl acetate, and the organic layer was then washed with brine and dried with anhydrous sodium sulfate. The solvent was removed by reduced-pressure distillation, and the resulting residue was purified by column chromatography on silica gel eluting with chloroform/acetone (10/1) to obtain 30 mg of the title compound (yield: 38%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[C:6]([NH:9][C@@H:10]2[C@@H:15]3[CH2:16][C@@H:12]([CH:13]=[CH:14]3)[C@@H:11]2[C:17]([NH2:19])=[O:18])[C:5]([Cl:20])=[CH:4][N:3]=1.[OH:21][C@H:22]([CH2:40][O:41][CH3:42])[CH2:23][N:24]1[CH2:29][CH2:28][CH:27]([C:30]2[CH:37]=[CH:36][C:33]([CH:34]=O)=[C:32]([O:38][CH3:39])[CH:31]=2)[CH2:26][CH2:25]1>>[Cl:20][C:5]1[C:6]([NH:9][C@@H:10]2[C@@H:15]3[CH2:16][C@@H:12]([CH:13]=[CH:14]3)[C@@H:11]2[C:17]([NH2:19])=[O:18])=[C:7]2[N:8]=[C:34]([C:33]3[CH:36]=[CH:37][C:30]([CH:27]4[CH2:26][CH2:25][N:24]([CH2:23][C@H:22]([OH:21])[CH2:40][O:41][CH3:42])[CH2:29][CH2:28]4)=[CH:31][C:32]=3[O:38][CH3:39])[NH:1][C:2]2=[N:3][CH:4]=1
Reactant: NC(=O)[C@@H]1[C@H](Nc2c(Cl)cnc(N)c2N)[C@H]2C=C[C@@H]1C2
Reactant: COC[C@@H](O)CN1CCC(c2ccc(C=O)c(OC)c2)CC1
Product: COC[C@@H](O)CN1CCC(c2ccc(-c3nc4c(N[C@H]5[C@@H](C(N)=O)[C@@H]6C=C[C@H]5C6)c(Cl)cnc4[nH]3)c(OC)c2)CC1
Yield: 47.1 %

Procedure:
In a similar fashion to Compound LXXXVII, (1S,2S,3R,4R)-3-(2,3-Diamino-5-chloro-pyridin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (109 mg, 0.373 mmol) and 4-[1-((S)-2-Hydroxy-3-methoxy-propyl)-piperidin-4-yl]-2-methoxy-benzaldehyde (126 mg, 0.410 mmol) were reacted to produce 102 mg (47%) of the title compound. mp: 189-191° C., 1H NMR (300 MHz, CDCl3): 10.67 (s, 1H), 8.35 (d, J=8 Hz, 1H), 8.04 (s, 1H), 7.04 (d, J=8 Hz, 1H), 6.94 (s, 1H), 6.39-6.35 (m, 3H), 5.51 (d, J=8 Hz, 1H), 5.19 (t, J=8 Hz, 1H), 5.07 (s, 1H), 4.08 (s, 3H), 3.89 (m, 1H), 3.19 (s, 2H), 2.98 (d, 1H), 2.91 (s, 1H), 2.88 (d, J=8 Hz, 1H), 2.62 (m, 1H), 2.46-2.22 (m, 5H). MS: 581 (M+H), HPLC: 1.90 min (G method).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4](F)[CH:3]=1.O[C:12]1[C:13]([O:20][CH3:21])=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH:15]=[O:16].C(=O)([O-])[O-:23].[Cs+].[Cs+].O>CN(C=O)C>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:23][C:18]2[CH:19]=[CH:12][C:13]([O:20][CH3:21])=[C:14]([CH:15]=[O:16])[CH:17]=2)[CH:3]=1
Reactant: N#Cc1ccc(Cl)cc1F
Reactant: O=C([O-])[O-]
Reactant: COc1c(O)cccc1C=O
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(Oc2cc(Cl)ccc2C#N)cc1C=O
Yield: 90.2 %

Procedure:
4-Chloro-2-fluorobenzonitrile (0.65 g, 4.2 mmol), 3-hydroxy-2-methoxybenzaldehyde (0.64 g, 4.2 mmol) and cesium carbonate (1.37 g, 4.2 mmol) were heated with stirring in dry DMF (4 ml) at 50° C. for 18 h. The reaction mixture was cooled, poured into water and extracted with ethyl acetate. The ethyl acetate layer was separated, washed with water (2×), 10% aqueous sodium carbonate (2×), water and brine and dried over MgSO4. After filtration, the solvent was removed in vacuo to yield 4-chloro-2-(3-formyl-4-methoxy-phenoxy)-benzonitrile (1.09 g, 90%) as a yellow-orange solid.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]#[CH:11])[CH:5]=[CH:4][C:3]=1[C:12](=[O:15])[CH2:13][CH3:14]>C(N(CC)C1C=CC=CC=1)C>[OH:1][C:2]1[C:3]([C:12](=[O:15])[CH2:13][CH3:14])=[CH:4][CH:5]=[C:6]2[C:7]=1[CH:11]=[CH:10][CH2:9][O:8]2
Reactant: C#CCOc1ccc(C(=O)CC)c(O)c1
Solvent: CCN(CC)c1ccccc1
Product: CCC(=O)c1ccc2c(c1O)C=CCO2
Yield: 45 %

Procedure:
A mixture of 1-(2-hydroxy-4-prop-2-ynyloxy-phenyl)-propan-1-one (19.8 g, 97 mmol) and N,N-diethylaniline (100 mL) was heated to reflux for 3 h. The reaction mixture was concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 5→10% EtOAc in Hexane) and thereafter recrystallized from EtOAc/Hexane, to give 8.91 g (45%) of 1-(5-hydroxy-2H-chromen-6-yl)-propan-1-one.
Reaction SMILES: [ClH:1].[N:2]1([C:16]([C@H:18]([NH:26][C:27](=[O:32])[C:28]([NH2:31])([CH3:30])[CH3:29])[CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:7][CH2:6][C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[CH:8]2)[CH2:4][CH2:3]1>[Pd]>[ClH:1].[N:2]1([C:16]([C@H:18]([NH:26][C:27](=[O:32])[C:28]([NH2:31])([CH3:30])[CH3:29])[CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:7][CH2:6][C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:9][CH2:8]2)[CH2:4][CH2:3]1
Reactant: CC(C)(N)C(=O)N[C@H](Cc1ccccc1)C(=O)N1CCC2(C=Cc3ccccc32)CC1
Agent: [Pd]
Agent: Cl
Product: CC(C)(N)C(=O)N[C@H](Cc1ccccc1)C(=O)N1CCC2(CCc3ccccc32)CC1
Yield: 96.7 %

Procedure:
Prepared from the intermediate obtained from Example 26, Step C (31 mg, 0.068 mmole) by the procedure described in Example 20, Step B (use 10% Pd on carbon instead of Pd(OH)2 to give 30 mg (97%) of the title compound.
Reaction SMILES: [NH2:1][C:2]1[NH:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:9][CH:8]=2)[C:3]=1[C:20]([NH2:22])=[O:21].C([O:25][C:26](=O)[CH2:27][C:28]([CH:30]1[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]1)=O)C>CC(O)=O>[O:25]=[C:26]1[CH:27]=[C:28]([CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[N:6]2[N:5]=[C:4]([C:7]3[CH:8]=[CH:9][C:10]([O:13][C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)=[CH:11][CH:12]=3)[C:3]([C:20]([NH2:22])=[O:21])=[C:2]2[NH:1]1
Reactant: NC(=O)c1c(-c2ccc(Oc3ccccc3)cc2)n[nH]c1N
Reactant: CCOC(=O)CC(=O)C1CCN(C(=O)OC(C)(C)C)CC1
Solvent: CC(=O)O
Product: NC(=O)c1c(-c2ccc(Oc3ccccc3)cc2)nn2c(C3CCNCC3)cc(=O)[nH]c12
Temperature: 90 °C
Reaction time: 16 h
Yield: 49.9 %

Procedure:
A mixture of 5-amino-3-(4-phenoxyphenyl)-1H-pyrazole-4-carboxamide (412 mg, 1.4 mmol) and tert-butyl 4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (420 mg, 1.4 mmol) in HOAc (20 mL) was stirred at 90° C. for 16 hr. The solvent was removed under vacuum, and the residue was partitioned between aq. NaHCO3 and ethyl acetate. The organic layer was washed with brine, dried over Na2SO4 and concentrated under vacuum. The residue was purified by Pre-HPLC eluting from 25% to 90% CH3CN in 0.1% TFA in H2O. Fractions containing the desired product were combined and lyophilized overnight to afford 5-oxo-2-(4-phenoxyphenyl)-7-(piperidin-4-yl)-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carboxamide (0.3 g, 50%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.71 (br s, 1H), 8.68-8.65 (m, 1H), 8.42-8.39 (m, 1H), 7.74 (d, J=8.4 Hz, 2H), 7.47-7.41 (m, 2H), 7.22-7.18 (m, 1H), 7.14-7.09 (m, 4H), 5.72 (s, 1H), 3.50-3.35 (m, 2H), 3.17-3.06 (m, 1H), 3.01-2.87 (m, 2H), 2.15-2.05 (m, 2H), 1.83-1.72 (m, 2H). MS (ESI) m/e [M+1]+ 430.1.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[S:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7](=[O:19])[CH2:6][CH2:5]2.[O:20]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[CH:22]=[C:21]1[S:29](Cl)(=[O:31])=[O:30]>N1C=CC=CC=1>[CH2:12]([S:11][C:10]1[CH:9]=[C:8]2[C:4]([CH2:5][CH2:6][C:7]2=[O:19])=[CH:3][C:2]=1[NH:1][S:29]([C:21]1[O:20][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[CH:22]=1)(=[O:30])=[O:31])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: O=S(=O)(Cl)c1cc2ccccc2o1
Reactant: Nc1cc2c(cc1SCc1ccccc1)C(=O)CC2
Solvent: c1ccncc1
Product: O=C1CCc2cc(NS(=O)(=O)c3cc4ccccc4o3)c(SCc3ccccc3)cc21
Yield: 97.3 %

Procedure:
Following General Procedure B, the title compound (752 mg, 47%) was prepared from 5-Amino-6-(benzylthio)-2,3-dihydro-1H-inden-1-one (463 mg, 1.72 mmol) and benzofuran-2-sulfonyl chloride (371 mg, 1.72 mmol) in pyridine (3 ml).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14].[NH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1>C(#N)C>[N:15]1([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1
Reactant: C1COCCN1
Reactant: OCCCCCCCCCCCCBr
Solvent: CC#N
Product: OCCCCCCCCCCCCN1CCOCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 77.4 %

Procedure:
To a solution of 5.30 g (20 mmol) of 12-bromo-1-dodecanol in 100 ml of acetonitrile is added dropwise 6 ml (68.6 mmol) of morpholine at 0° C. The solution is then stirred at room temperature overnight and filtered. After removal of the acetonitrile, the residue is dissolved in 250 ml of dichloromethane. The dichloromethane solution is washed with water, dried over magnesium sulfate and filtered. The dichloromethane is removed under reduced pressure and the residue is purified by silica gel column chromatography to give 4.2 g (79.2%) of 12-(4-morpholinyl)-1-dodecanol.
Reaction SMILES: [CH3:1][C:2]1([CH3:18])[CH2:7][CH:6]([N:8]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][C:9]2=[O:15])[CH2:5][C:4]([CH3:17])([CH3:16])[NH:3]1.C(=O)([O-])[O-].[Na+].[Na+].[CH2:25](Br)[CH:26]=[CH2:27]>CN(C)C=O>[CH2:27]([N:3]1[C:4]([CH3:17])([CH3:16])[CH2:5][CH:6]([N:8]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][C:9]2=[O:15])[CH2:7][C:2]1([CH3:18])[CH3:1])[CH:26]=[CH2:25]
Reactant: C=CCBr
Reactant: CC1(C)CC(N2CCCCCC2=O)CC(C)(C)N1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=CCN1C(C)(C)CC(N2CCCCCC2=O)CC1(C)C
Temperature: 80 °C

Procedure:
Following the general procedure of Example 3, 12.1 g (0.05 mole) of the compound prepared in Example 1 is dissolved in 75 ml of N,N-dimethylformamide containing a suspension of 10.6 g (0.1 mole) of sodium carbonate. To this mixture is then added 14.6 g (0.05 mole) of allyl bromide and the reaction mixture is then heated at 80° C. for two hours. The solvent is then removed in vacuo and the residue is vacuum distilled at 171°-176° C./0.7 mm to give 7.6 g of the above named product.
Reaction SMILES: Cl.[NH2:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[SH:13].[F:14][C:15]1[CH:22]=[N:21][CH:20]=[CH:19][C:16]=1[CH:17]=O.C(N(C(C)C)C(C)C)C.CS(C)=O>O>[F:14][C:15]1[CH:22]=[N:21][CH:20]=[CH:19][C:16]=1[C:17]1[S:13][C:4]2[CH:5]=[CH:6][C:7]([C:9]([F:10])([F:11])[F:12])=[CH:8][C:3]=2[N:2]=1
Reactant: Nc1cc(C(F)(F)F)ccc1S
Reactant: O=Cc1ccncc1F
Agent: Cl
Solvent: O
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: Fc1cnccc1-c1nc2cc(C(F)(F)F)ccc2s1
Temperature: 170 °C
Reaction time: 5 h
Yield: 60.1 %

Procedure:
A mixture of 2.3 g of 2-amino-4-(trifluoromethyl)-benzenethiol hydrochloride, 1.25 g of 3-fluoroisonicotinaldehyde, 1.29 g of N-ethyldiisopropylamine and 10 ml of DMSO was stirred for 5 hours at 170° C. The reaction mixture was cooled down to room temperature. To the reaction mixture was added water, and the resultant mixture was extracted with ethyl acetate twice. The combined organic layers were washed with water and saturated saline, dried over magnesium sulfate, then, concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, to obtain 1.79 g of 2-(3-fluoropyridin-4-yl)-5-(trifluoromethyl)benzothiazole (hereinafter, referred to as the present compound 1).
Reaction SMILES: [F:1][C:2]1[CH:13]=[CH:12][C:5]([C:6]([NH:8][CH2:9][CH2:10]O)=[O:7])=[C:4]([N+:14]([O-:16])=[O:15])[CH:3]=1.S(Cl)([Cl:19])=O>ClC(Cl)Cl>[Cl:19][CH2:10][CH2:9][NH:8][C:6](=[O:7])[C:5]1[CH:12]=[CH:13][C:2]([F:1])=[CH:3][C:4]=1[N+:14]([O-:16])=[O:15]
Reactant: O=S(Cl)Cl
Reactant: O=C(NCCO)c1ccc(F)cc1[N+](=O)[O-]
Solvent: ClC(Cl)Cl
Product: O=C(NCCCl)c1ccc(F)cc1[N+](=O)[O-]
Yield: 83 %

Procedure:
A mixture of 28 parts of 4-fluoro-N-(2-hydroxyethyl)-2-nitrobenzamide, 40 parts of thionyl chloride and 150 parts of trichloromethane is stirred and refluxed for 2 hours. After cooling, the precipitated product is filtered off and dried, yielding 24.5 parts (83%) of N-(2-chloroethyl)-4-fluoro-2-nitrobenzamide.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:11][CH2:12][CH2:13][NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[NH:8]2)=[C:4]([O:22][CH2:23][C:24]2[CH:37]=[CH:36][C:27]([CH2:28][NH:29]C(=O)C(F)(F)F)=[CH:26][CH:25]=2)[N:3]=1.CN>CO>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:11][CH2:12][CH2:13][NH:14][C:15]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:16])[NH:8]2)=[C:4]([O:22][CH2:23][C:24]2[CH:37]=[CH:36][C:27]([CH2:28][NH2:29])=[CH:26][CH:25]=2)[N:3]=1
Reactant: CC(C)(C)OC(=O)NCCCc1nc2c(OCc3ccc(CNC(=O)C(F)(F)F)cc3)nc(N)nc2[nH]1
Agent: CN
Solvent: CO
Product: CC(C)(C)OC(=O)NCCCc1nc2c(OCc3ccc(CN)cc3)nc(N)nc2[nH]1
Temperature: 50 °C
Yield: 8.9 %

Procedure:
Trifluoroacetamide 11 (Example 23, 100 mg, 0.19 mmol) is dissolved in 2 mL methanol, and 2 mL methylamine (33% in ethanol) are added. The reaction mixture is stirred at 50° C. over night and all volatiles are removed in vacuo. The product is purified by flash column chromatography (CH2Cl2/MeOH 95:5 to 10:1) yielding 77 mg (0.017 mmol, 94%) of the title compound.
Reaction SMILES: CO[C:3](=[O:10])[CH:4](Br)[CH2:5][CH:6]([CH3:8])[CH3:7].[CH2:11]([NH2:14])[CH2:12][NH2:13].C>C(O)C.CN(C=O)C.C(OCC)(=O)C>[CH3:8][CH:6]([CH3:7])[CH2:5][CH:4]1[NH:14][CH2:11][CH2:12][NH:13][C:3]1=[O:10]
Reactant: NCCN
Reactant: COC(=O)C(Br)CC(C)C
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: CN(C)C=O
Product: CC(C)CC1NCCNC1=O
Reaction time: 20 h

Procedure:
A mixture of methyl 2-bromo-4-methylpentanoate (V, Example 3, 14.6 g.) and ethylenediamine (VI, 12.5 g.) in ethanol (250 ml.) is stirred at 20°-25° for 20 hours. The ethanol is removed under reduced pressure and the residual oil is partitioned between chloroform and aqueous sodium bicarbonate. The chloroform layer is separated and the chloroform is removed under reduced pressure to give an oil which is refluxed in DMF (20 ml.) for one hour. After removal of the DMF the residue is column chromatographed on silica gel eluting with chloroform-methanol (99/5). Appropriate fractions are pooled and concentrated to give a residue which is dissolved in ethyl acetate (150 ml.) and decolorized with charcoal. Crystallization from ethyl acetate-SSB gives an oily solid which upon crystallization from ethyl acetate-SSB gives the title compound, m.p. 75°-77°.
Reaction SMILES: Cl.[CH2:2]([O:9][C:10](=[O:23])[C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:22])[C@@H:17]1[CH2:21][CH2:20][CH2:19][NH:18]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.[C:31]1([S:37](Cl)(=[O:39])=[O:38])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(Cl)Cl>[CH2:2]([O:9][C:10](=[O:23])[C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:22])[C@@H:17]1[CH2:21][CH2:20][CH2:19][N:18]1[S:37]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)(=[O:39])=[O:38])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: O=C(OCc1ccccc1)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(OCc1ccccc1)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1S(=O)(=O)c1ccccc1
Reaction time: 1 h
Yield: 98.1 %

Procedure:
L-prolyl-L-proline benzylester hydrochloride (1.69 g, 5 mmole) was dissolved in methylene chloride (30 ml), and triethylamine (1.11 g, 11 mmole) was added thereto at -30° C. Methylene chloride (10 ml) solution of benzene sulfonyl chloride (0.86 g, 5 mmole) was added dropwise to the solution. The mixture was stirred for 1 hour at less than 0° C., and next for 5 hours at room temperature, and methylene chloride (60 ml) was added thereto. The solution was washed with 5% aqueous sodium bicarbonate (100 ml, twice), 1N aqueous hydrochloric acid (100 ml, twice) and water (100 ml) in the order given, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain N-benzenesulfonyl-L-prolyl-L-proline benzylester(yield: 2.17 g, 98.1%)
Reaction SMILES: CC([Si](C)(C)[O:6][CH2:7][CH2:8][N:9]1[C:13]([CH2:14][O:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]3=[N:26][N:27]=[C:28]([C:29]4[CH:33]=[C:32]([CH3:34])[O:31][N:30]=4)[N:18]3[N:17]=2)=[CH:12][N:11]=[N:10]1)(C)C.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>CCO>[CH3:34][C:32]1[O:31][N:30]=[C:29]([C:28]2[N:18]3[N:17]=[C:16]([O:15][CH2:14][C:13]4[N:9]([CH2:8][CH2:7][OH:6])[N:10]=[N:11][CH:12]=4)[C:25]4[C:20]([C:19]3=[N:26][N:27]=2)=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH:33]=1
Reactant: Cc1cc(-c2nnc3c4ccccc4c(OCc4cnnn4CCO[Si](C)(C)C(C)(C)C)nn23)no1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: CCO
Product: Cc1cc(-c2nnc3c4ccccc4c(OCc4cnnn4CCO)nn23)no1
Temperature: 25 °C
Yield: 91.1 %

Procedure:
A solution of 6-({[1-(2-{[(dimethylethyl)(dimethyl)silyl]oxy}ethyl)-1H-[1,2,3]triazol-5-yl]methyl}oxy)-3-(5-methylisoxazol-3-yl)-[1,2,4]triazolo[3,4-α]phthalazine (606 mg, 1.2 mmol) and pyridinium para-toluenesulfonate (602 mg, 2.4 mmol) in EtOH (100 ml) was heated at 70° C. for 36 h. The reaction was cooled to room temperature and concentrated to approximately 25 ml, the resulting solid was filtered off and dried to yield the desired phthalazine (429 mg, 91%). 1H NMR (360 MHz, d6-DMSO) δ 8.55 (1H, d, J=8.0 Hz), 8.22 (1H, d, J=8.0 Hz), 8.12-8.00 (2H, m), 7.93 (1H, t, J=8.0 Hz), 7.11 (1H, s), 5.83 (2H, s), 4.58 (2H, t, J=5.3 Hz), 3.84 (2H, t, J=5.3 Hz), 2.59 (3H, s).
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][OH:12])=[CH:7][CH:6]=1.[Br:13][C:14]1[C:15](Cl)=[N:16][CH:17]=[CH:18][C:19]=1[CH3:20].O>C1COCC1.CCOC(C)=O>[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][O:12][C:15]2[C:14]([Br:13])=[C:19]([CH3:20])[CH:18]=[CH:17][N:16]=2)=[CH:7][CH:6]=1
Reactant: Cc1ccnc(Cl)c1Br
Reactant: COc1ccc(CO)cc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COc1ccc(COc2nccc(C)c2Br)cc1
Temperature: 75 °C
Reaction time: 0.08 h

Procedure:
To a mixture of 60% NaH in mineral oil (0.290 g, 7.27 mmol) in THF (15 mL) at RT in a resealable pressure vessel was added (4-methoxyphenyl)methanol (0.906 ml, 7.27 mmol). After 5 minutes, 3-bromo-2-chloro-4-picoline (1.00 g, 4.84 mmol) was added and the mixture was heated to 75° C. After 1 hr, water was added and the mixture was diluted with EtOAc. After washing with water and brine, the organic fraction was dried with sodium sulfate and purified by silica gel chromatography using 0-30% EtOAc:hexanes to afford 2-(4-methoxybenzyloxy)-3-bromo-4-methylpyridine as a colorless oil. M+H+=308.0.
Reaction SMILES: [CH3:1][C@@H:2]([C@@H:10]1[C@@:14]2([CH3:29])[CH2:15][CH2:16][C@@H:17]3[C@@:22]4([CH3:28])[CH2:23][CH2:24][C@H:25]([OH:27])[CH2:26][C:21]4=[CH:20][CH2:19][C@H:18]3[C@@H:13]2[CH2:12][CH2:11]1)[CH2:3][CH2:4][C@H:5]([CH:7]([CH3:9])[CH3:8])[CH3:6].[C:30](OC(=O)C)(=[O:32])[CH3:31].O>N1C=CC=CC=1>[CH3:1][C@@H:2]([C@@H:10]1[C@@:14]2([CH3:29])[CH2:15][CH2:16][C@@H:17]3[C@@:22]4([CH3:28])[CH2:23][CH2:24][C@H:25]([O:27][C:30]([CH3:31])=[O:32])[CH2:26][C:21]4=[CH:20][CH2:19][C@H:18]3[C@@H:13]2[CH2:12][CH2:11]1)[CH2:3][CH2:4][C@H:5]([CH:7]([CH3:8])[CH3:9])[CH3:6]
Reactant: CC(C)[C@H](C)CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Reactant: CC(=O)OC(C)=O
Solvent: O
Solvent: c1ccncc1
Product: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC[C@H]3[C@@H]4CC[C@H]([C@H](C)CC[C@@H](C)C(C)C)[C@@]4(C)CC[C@@H]32)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 75.3 %

Procedure:
To a solution of 24.0 g (0.06 mol) of campesterol (1) in 180 ml of anhydrous pyridine was added 18.5 ml (0.196 mol) of acetic anhydride. The mixture was stirred at room temperature overnight and then 600 ml of water was added. The precipitate was filtered and washed three times with 200 ml portions of acetonitrile, and then air dried to yield 20.0 g (75%) of (2).
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][Si:13](Cl)(Cl)Cl.C1(C)C=CC=CC=1>CCCCCCCCCCCCCCCC>[Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][SiH3:13]
Reactant: Cl[Si](Cl)(Cl)CCCCCCCCCCCBr
Solvent: CCCCCCCCCCCCCCCC
Solvent: Cc1ccccc1
Product: [SiH3]CCCCCCCCCCCBr
Temperature: 60 °C

Procedure:
Freshly cleaned slides were immersed in a solution of bromoundecyl-trichlorosilane (3% v/v) in hexadecane or toluene. The reaction was heated to 60° C. for 4-6 hours then allowed to cool to room temperature. The slides were washed with CH2Cl2 and ethanol then blown dry under a stream of argon, producing a film with an advancing water contact angle of 82±2 degrees above horizontal.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.Br[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]>>[CH2:11]([O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: O=Cc1ccc(O)cc1
Reactant: CCCCCCCCCBr
Product: CCCCCCCCCOc1ccc(C=O)cc1
Yield: 79.3 %

Procedure:
General procedure K was used to convert 4-hydroxybenzaldehyde (8.2 mmols) and 1-bromononane (12.3 mmols) to 6.5 mmols (79%) of the title product was recovered. 1H NMR (300 MHz, CDCl3) δ 9.88 (s, 1H), 7.83 (d, J=8.9 Hz, 2H), 6.99 (d, J=8.7 Hz, 2H), 4.04 (t, J=6.6 Hz, 2H), 1.76-1.85 (m, 2H), 1.14-1.53 (m, 12H), 0.88 (t, J=6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 164.40, 132.11, 114.86, 68.55, 31.98, 29.47, 29.37, 29.18, 28.90, 28.31, 26.08, 22.79, 14.23.