Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][CH2:2][C:3]1[S:7][C:6]([CH2:8][C:9]([OH:11])=O)=[CH:5][CH:4]=1.[Cl:12]CC1C=CC(CC(O)=O)=CC=1>>[Cl:1][CH2:2][C:3]1[S:7][C:6]([CH2:8][C:9]([Cl:12])=[O:11])=[CH:5][CH:4]=1
Reactant: O=C(O)Cc1ccc(CCl)cc1
Reactant: O=C(O)Cc1ccc(CCl)s1
Product: O=C(Cl)Cc1ccc(CCl)s1

Procedure:
When in the procedure of Example 1 (B) 5-chloromethyl-2-thienylacetic acid, is substituted for p-chloromethylphenyl acetic acid, 5-chloromethyl-2-thienylacetyl chloride is obtained.
Reaction SMILES: [CH:1](OC)([O:4][CH3:5])[O:2][CH3:3].O.[O-2].[O-2].[O-2].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.[Al+3].[Al+3].[Cl:26][C:27]1[C:28]([C:37]2[CH:42]=[CH:41][C:40]([Cl:43])=[C:39](C=O)[CH:38]=2)=[N:29][CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1>ClCCl>[Cl:26][C:27]1[C:28]([C:37]2[CH:42]=[CH:41][C:40]([Cl:43])=[C:39]([CH:1]([O:4][CH3:5])[O:2][CH3:3])[CH:38]=2)=[N:29][CH:30]=[C:31]([C:33]([F:35])([F:36])[F:34])[CH:32]=1
Reactant: COC(OC)OC
Reactant: O=Cc1cc(-c2ncc(C(F)(F)F)cc2Cl)ccc1Cl
Agent: O=[Si]=O
Agent: [Al+3]
Agent: [O-2]
Solvent: O
Solvent: ClCCl
Product: COC(OC)c1cc(-c2ncc(C(F)(F)F)cc2Cl)ccc1Cl

Procedure:
50 ml of trimethyl orthoformate were added to 40.0 g of montmorillonite K-10 in 250 ml of anhydrous dichloromethane, after which a solution of 20.0 g of 3-chloro-2-(4-chloro-3-formylphenyl)-5-trifluoromethylpyridine in 50 ml of dichloromethane was added dropwise while stirring and cooling in ice. After stirring at 23° C. for 20 hours, the clay was removed and thoroughly washed with dichloromethane. The dichloromethane phase was concentrated. The residue was purified by chromatography on silica gel with cyclohexane/ethyl acetate (10:1). Yield: 22.1 g (96%) of a colorless oil.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[C:7](=[O:33])[N:8]([CH:15]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]([F:29])[F:28])=[C:22]([O:30][CH2:31][CH3:32])[CH:21]=1)[CH2:16][C:17](O)=[O:18])[C:9]2=[O:14])(=[O:3])[CH3:2].C1N=C[N:36](C(N2C=NC=C2)=O)C=1.[NH4+].[OH-]>C1COCC1>[C:1]([NH:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[C:7](=[O:33])[N:8]([CH:15]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]([F:28])[F:29])=[C:22]([O:30][CH2:31][CH3:32])[CH:21]=1)[CH2:16][C:17]([NH2:36])=[O:18])[C:9]2=[O:14])(=[O:3])[CH3:2]
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CCOc1cc(C(CC(=O)O)N2C(=O)c3cccc(NC(C)=O)c3C2=O)ccc1OC(F)F
Agent: [NH4+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CCOc1cc(C(CC(N)=O)N2C(=O)c3cccc(NC(C)=O)c3C2=O)ccc1OC(F)F
Yield: 78.8 %

Procedure:
3-(4-Acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionamide was prepared by the procedure of Example 6 from 3-(4-acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid (0.5 g, 1.1 mmol), CDI (0.19 g, 1.2 mmol) and NH4OH (0.1 ml, 1.2 mmol) in THF (30 ml) to give 3-(4-acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionamide as white solid (0.40 g, 80%): mp 178-180° C.; 1HNMR (CDCl3): δ1.44 (t, J=7.0 Hz, 3H, OCH2CH3), 2.26 (s, 3H, CH3CO), 3.03 (dd, J=5, 15 Hz, 1H, CH2), 3.70 (dd, J=10, 15 Hz, 1H, CH2), 4.09 (q, J=7.0 Hz, 2H, OCH2CH3), 5.38 (broad, 1H, NH2), 5.61 (broad, 1H, NH2), 5.76-5.83 (m, 1H, CHN), 6.83 (t, JH-F=75 Hz, 1H, CF2H), 7.06-7.14 (m, 3H, Ar), 7.46 (d, J=7.5 Hz, 1H, Ar), 7.65 (t, J=7.5 Hz, 1H, Ar), 7.74 (d, J=7.5 Hz, 1H, Ar), 9.45 (s, 1H, NHCO). 13CNMR (DMSO-d6): 14.4, 24.2, 36.7, 50.0, 64.2, 93.9, 112.5, 113.2, 116.7, 116.7, 118.0, 119.4, 121.2, 125.9, 131.4, 135.8, 136.4, 137.6, 139.0, 149.7, 167.2, 168.2, 169.2, 171.0; Anal Calcd for C22H21F2N3O6: C, 57.27; H, 4.59; N, 9.11. Found: C, 57.04; H, 4.41; N, 8.93.
Reaction SMILES: [NH2:1][C:2]1[N:7]([CH2:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[C:6](=[O:15])[N:5]([CH2:16][CH2:17][CH3:18])[C:4](=[O:19])[C:3]=1[N:20]=O.C1(CN2C(N)=C(N)C(=O)N(CCC)C2=O)CCCCC1.[CH:42]([C:44]1[CH:45]=[C:46]([CH:52]=[CH:53][CH:54]=1)[CH:47]=[CH:48][C:49]([OH:51])=[O:50])=O>>[CH:9]1([CH2:8][N:7]2[C:2]3[NH:1][C:42]([C:44]4[CH:45]=[C:46]([CH:52]=[CH:53][CH:54]=4)/[CH:47]=[CH:48]/[C:49]([OH:51])=[O:50])=[N:20][C:3]=3[C:4](=[O:19])[N:5]([CH2:16][CH2:17][CH3:18])[C:6]2=[O:15])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: CCCn1c(=O)c(N=O)c(N)n(CC2CCCCC2)c1=O
Reactant: O=Cc1cccc(C=CC(=O)O)c1
Agent: CCCn1c(=O)c(N)c(N)n(CC2CCCCC2)c1=O
Product: CCCn1c(=O)c2nc(-c3cccc(/C=C/C(=O)O)c3)[nH]c2n(CC2CCCCC2)c1=O
Yield: 75 %

Procedure:
In the manner of step (d) of Example 1, 6amino-1-(cyclohexylmethyl)-3-propyl-5-nitrosouracil (step (c) example 12, 2.355 g, 8.00 mmol) was reduced to 1-(cyclohexylmethyl)-5,6-diamino-3-propyluracil, which was condensed with 3-formylcinnamic acid (T. Higa, A. J. Krubsack, J. Org. Chem. 1975, 40: 3037-3045, 1.424 g, 8.00 mmol) to give (E)-3-[3-(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6dioxo-1-propyl-9H-purin-8-yl]cinnamic acid as a pale yellow solid (2.632 g, 75%), m.p. >350° C.; 1H-NMR (DMSO-d6) consistent with structure.
Reaction SMILES: [Br:1][C:2]1[N:6]2[N:7]=[C:8]([O:11][CH3:12])[CH:9]=[CH:10][C:5]2=[N:4][C:3]=1[C:13]1[CH:14]=[CH:15][C:16]([CH3:20])=[C:17]([CH:19]=1)[NH2:18].N1C=CC=CC=1.[CH3:27][C:28]([CH3:33])([CH3:32])[C:29](Cl)=[O:30]>C(#N)C>[Br:1][C:2]1[N:6]2[N:7]=[C:8]([O:11][CH3:12])[CH:9]=[CH:10][C:5]2=[N:4][C:3]=1[C:13]1[CH:14]=[CH:15][C:16]([CH3:20])=[C:17]([NH:18][C:29](=[O:30])[C:28]([CH3:33])([CH3:32])[CH3:27])[CH:19]=1
Reactant: COc1ccc2nc(-c3ccc(C)c(N)c3)c(Br)n2n1
Reactant: CC(C)(C)C(=O)Cl
Solvent: c1ccncc1
Solvent: CC#N
Product: COc1ccc2nc(-c3ccc(C)c(NC(=O)C(C)(C)C)c3)c(Br)n2n1
Temperature: 25 °C
Reaction time: 4 h
Yield: 96.8 %

Procedure:
A solution of 5-(3-bromo-6-methoxyimidazo[1,2-b]pyridazin-2-yl)-2-methylaniline (0.165 g, 0.495 mmol) in acetonitrile (25 mL) containing pyridine (1.48 mmol) is added trimethylacetylchloride (0.495 mmol). The mixture is stirred at room temperature for 4 hours, then concentrated to dryness and purified via chromatography (hexanes to EtOAc) to afford 0.200 g (97%) of the title compound as a white solid: Rf 0.41 (1:1 EtOAc:hexanes); LCMS (m/z)=417.3, 419.3 [M+H]+, tR=2.76 min.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:12]([O:14]CC)=O)=[CH:4][C:5]2[O:10][CH2:9][CH2:8][O:7][C:6]=2[CH:11]=1.Cl.[CH:18](N)=[NH:19]>C(N)=O>[N:1]1[C:2]2[C:3](=[CH:4][C:5]3[O:10][CH2:9][CH2:8][O:7][C:6]=3[CH:11]=2)[C:12](=[O:14])[NH:19][CH:18]=1
Reactant: N=CN
Reactant: CCOC(=O)c1cc2c(cc1N)OCCO2
Agent: Cl
Solvent: NC=O
Product: O=c1[nH]cnc2cc3c(cc12)OCCO3
Temperature: 130 °C
Yield: 83.9 %

Procedure:
According to the procedure described in Example 6A Step 4, a mixture of ethyl 7-amino-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxylate (1.45 g, 6.5 mmol) and formamidine hydrochloride (1.208 g, 15 mmol) in formamide (20 mL) was heated at 130° C. for 8 hours, to afford 7,8-dihydro-[1,4]dioxino[2,3-g]quinazolin-4(3H)-one as a solid (1.114 g, 84%). 1H NMR (300 MHz, CDCl3 and drops DMSO-d6) δ 11.80 (br, 1H), 7.88 (s, 1H), 7.63 (s, 1H), 7.13 (s, 1H), 4.36 (m, 4H); LC-MS (ESI) m/z 205 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:14])[C:5]1[CH:10]=[C:9]([OH:11])[C:8]([OH:12])=[C:7]([OH:13])[CH:6]=1)[CH3:2].[C:15](=O)([O-])[O-].[K+].[K+].BrCBr>CN(C=O)C>[CH2:1]([O:3][C:4]([C:5]1[CH:10]=[C:9]([OH:11])[C:8]2[O:12][CH2:15][O:13][C:7]=2[CH:6]=1)=[O:14])[CH3:2]
Reactant: O=C([O-])[O-]
Reactant: CCOC(=O)c1cc(O)c(O)c(O)c1
Agent: [K+]
Solvent: BrCBr
Solvent: CN(C)C=O
Product: CCOC(=O)c1cc(O)c2c(c1)OCO2
Temperature: 60 °C

Procedure:
5 g (25.2 mmol) of 3,4,5-Trihydroxy-benzoic acid ethyl ester was dissolved in 50 ml of DMF and treated at 0° C. with 13.95 g (101 mmol) of potassium carbonate and 4.39 g (25.2 mmol) of dibromomethane. The reaction solution was heated at 60° C. for 3 h. The solvent was removed under reduced pressure, the residue was taken-up in ethyl acetate and the solution was washed three times with water and twice with saturated aqueous sodium chloride. The organic phase was dried with magnesium sulphate, filtered and the solvent was removed under reduced pressure. The residue was chromatographed on silica gel eluting with n-heptane/ethyl acetate (3/1).
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:12][N:7]2[CH2:8][CH2:9][NH:10][CH2:11][CH:6]2[CH2:5][CH2:4]1.Br[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)CC(C)C>[OH:1][CH2:2][CH:3]1[CH2:12][N:7]2[CH2:8][CH2:9][N:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[CH2:11][CH:6]2[CH2:5][CH2:4]1
Reactant: OCC1CCC2CNCCN2C1
Reactant: Brc1ccccn1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(C)CCO
Product: OCC1CCC2CN(c3ccccn3)CCN2C1
Temperature: 25 °C
Yield: 42 %

Procedure:
A mixture of 1.0 g (5.9 mmol) of (7RS,9aSR)-7-hydroxymethyl-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine (U.S. Pat. No. 5,326,874); 4.6 9 (29 mmol) of 2-bromopyridine, 1.5 g (14 mmol) of sodium carbonate and 50 mL of isoamyl alcohol were refluxed for 18 h. The mixture was cooled to room temperature, filtered, and concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with saturated sodium carbonate. The organic layer was dried (magnesium sulfate), filtered and evaporated, and the crude product was purified by flash chromatography on silica gel eluting first with chloroform followed by 95:5 chloroform:methanol to give 0.61 g (42%) of the title compound. 13C NMR (base, CDCl3): δ 26.8, 29.0, 39.0, 45.1, 50.7, 54.8, 58.7, 60.8, 66.0, 107.1, 113.3, 137.5, 147.9, 159.3.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]([NH2:16])[CH2:12][CH2:13][CH2:14][CH3:15])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C(=O)([O-])[O-].[Na+].[Na+].C(N1[C:32](=[O:33])[C:31]2=[CH:34][CH:35]=[CH:36][CH:37]=[C:30]2[C:29]1=[O:38])(OCC)=O>O.C(#N)C>[C:29]1(=[O:38])[N:16]([CH:11]([C:5]2[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:12][CH2:13][CH2:14][CH3:15])[C:32](=[O:33])[C:31]2=[CH:34][CH:35]=[CH:36][CH:37]=[C:30]12
Reactant: CCOC(=O)N1C(=O)c2ccccc2C1=O
Reactant: CCCCC(N)c1ccc(OC)c(OC)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: CCCCC(c1ccc(OC)c(OC)c1)N1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 38 %

Procedure:
To a stirred solution of 1-(3′,4′-dimethoxyphenyl)pentylamine (0.3 grams, 1.34 mmol) and sodium carbonate (0.15 grams, 1.45 mmol) in a mixture of water (10 milliliters) and acetonitrile (10 milliliters) was added N-carbethoxyphthalimide (0.29 grams, 1.34 mmol). The resulting solution was stirred for 3 hours at room temperature, the acetonitrile was evaporated and a two phase mixture resulted. The organic phase was extracted into methylene chloride, dried over magnesium sulfate and concentrated to afford 0.41 grams of crude product as an oil. The crude product was purified by flash chromatography (silica gel, 30% ethyl acetate/hexane) to afford 0.18 grams (38%) of the product as an oil: 1H NMR (CDCl3) δ7.88-7.63(m, 4H), 7.20-7.07(m, 2H),6.82-6.76(m, 1H), 5.34-5.18(m, 1H), 3.89(s, 3H), 3.85(s, 3H),2.66-2.43(m, 1H),2.40-2.17(m, 1H), 1.50-1.20(m, 2H), 0.96-0.81(m, 3H). 13C NMR (CDCl3) δ1.68.5, 148.8, 148.5, 133.8, 132.5, 131.9, 123.1, 120.6, 111.6, 110.8, 55.9, 55.8, 55.0, 30.9, 29.2, 22.3, 13.9.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].F[C:14]1[CH:21]=[CH:20][C:19]([CH:22]=[O:23])=[CH:18][C:15]=1[C:16]#[N:17].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CC(=O)OCC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:14]2[CH:21]=[CH:20][C:19]([CH:22]=[O:23])=[CH:18][C:15]=2[C:16]#[N:17])=[CH:4][C:3]=1[C:9]([F:10])([F:11])[F:12]
Reactant: N#Cc1cc(C=O)ccc1F
Reactant: Oc1ccc(Cl)c(C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: N#Cc1cc(C=O)ccc1Oc1ccc(Cl)c(C(F)(F)F)c1
Temperature: 130 °C
Yield: 95.9 %

Procedure:
A mixture of 4-chloro-3-(trifluoromethyl)phenol (1 g, 5.09 mmol), 2-fluoro-5-formylbenzonitrile (0.759 g, 5.09 mmol) and K2CO3 (0.844 g, 6.11 mmol) in DMF (10 mL) was heated with a microwave condition at 130° C. for 4 h. The solution was diluted with EA and washed with water twice, dried over Na2SO4 and concentrated in vacuo to afford the title compound (1.59 g, 96% yield) as a yellow solid. LCMS: rt=3.54 min, [M+H+]=326
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][OH:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH3:19][S:20](Cl)(=[O:22])=[O:21]>ClCCl>[CH3:19][S:20]([O:11][CH2:10][CH2:9][CH2:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)(=[O:22])=[O:21]
Reactant: OCCCCc1ccccc1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCCCc1ccccc1
Temperature: 10 °C
Reaction time: 1 h

Procedure:
To an ice cooled solution of 4-phenyl-1-butanol (20 g) and triethyl amine (15 g) in 200 ml of dichloromethane, a solution of methanesulfonyl chloride (12 ml) in 50 ml of dichloromethane was added dropwise. After stirring for 1 h at 10° C. the reaction mixture was washed with water. Extraction of the water phase with dichloromethane, drying of the combined organic phases over MgSO4 followed by removal of the volatile components in vacuo, gave 29 g of a slightly yellow oil, 4-phenyl-1-butyl methanesulfonate, which was sufficiently pure for use in the next step. A mixture of spiro[isobenzofuran-1(3H),4'-piperidine] (2 g), 4-phenyl-1-butyl methanesulfonate (6 g) and potassium carbonate (14 g) in 75 ml of 4-methyl-2-pentanone was refluxed for 20 h. After cooling the reaction mixture was filtered and concentrated in vacuo. The remaining viscous oil was applied to a silica gel column (eluent:ether/methanol/triethyl amine=93:5:2) giving a colorless oil which crystallized as the fumarate salt, 2a, from acetone by addition of fumaric acid. Yield: 0.7 g, mp: 197°-99° C.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH:13]([CH2:16]O)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([N:21](C(C)C)CC)(C)C.CS(Cl)(=O)=O>C(Cl)Cl>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH:13]([CH2:16][NH2:21])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCN(C(C)C)C(C)C
Reactant: O=C(OCc1ccccc1)N1CCC(CO)C1
Agent: CS(=O)(=O)Cl
Solvent: ClCCl
Product: NCC1CCN(C(=O)OCc2ccccc2)C1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 78.3 %

Procedure:
To a 0° C. solution of 350 mg of 1-benzyloxycarbonyl-3-hydroxymethylpyrrolidine in 10 mL of CH2Cl2 was added 288 mg of diisopropylethylamine, then 204 mg of methanesulfonyl chloride. After 10 min, the cooling bath was removed and the mixture was stirred for 30 min at room temperature. The mixture was diluted with 25 mL of EtOAc and washed with 10 mL of saturated NaHCO3, 2×10 mL of 1 N HCl and 10 mL of brine. The organic phase was dried over MgSO4 and concentrated. The residue was dissolved in 10 mL of DMF and 145 mg of sodium azide was added. The mixture was heated to 100° C. and stirred overnight at this temperature, then cooled, diluted with 25 mL of EtOAc, and washed with 2×10 mL of water and 10 ml of brine. The organic phase was dried over MgSO4 and concentrated. The residue was dissolved in 10 mL of 9:1 THF-water and 586 mg of triphenylphosphine was added. The mixture was heated to 50° C. and stirred at this temperature for 3 h, then cooled, poured into 20 mL of 1 N HCl, and extracted with 2×10 mL of EtOAc. The aqueous phase was made very basic (pH>12) by addition of 5 N NaOH, then extracted with 4×10 mL of EtOAc. The combined organic extracts were washed with 10 mL of brine, dried over MgSO4, and concentrated. The residue was purified by flash chromatography, eluting with 20:1 CH2Cl2-2M NH3 in MeOH, to yield 273 mg of the title compound as a colorless oil. 1H NMR (500 MHz, CDCl3): δ 7.28-7.40 (m, 5H), 5.13 (m, 2H), 3.47-3.67 (m, 2H), 3.38 (dt J=9.8, 16.7 Hz, 1H), 3.09 (ddd, J=7.6, 10.5, 15.1 Hz, 1H), 2.64-2.78 (m, 2H), 2.23 (dt, J=7.8, 15.3 Hz, 1H), 1.96-2.08 (m, 1H), 1.52-1.67 (m, 1H), 1.25 (br s, 2H).
Reaction SMILES: [C:1]([O:4][C:5]1[CH:12]=[C:11]([N:13]([CH2:16][CH3:17])[CH2:14][CH3:15])[CH:10]=[CH:9][C:6]=1[CH:7]=O)(=[O:3])[CH3:2].C([O-])(=O)C.[NH4+].[N+:23]([CH3:26])([O-:25])=[O:24]>>[CH2:14]([N:13]([C:11]1[CH:10]=[CH:9][C:6]([CH:7]=[CH:26][N+:23]([O-:25])=[O:24])=[C:5]([O:4][C:1](=[O:3])[CH3:2])[CH:12]=1)[CH2:16][CH3:17])[CH3:15]
Reactant: CCN(CC)c1ccc(C=O)c(OC(C)=O)c1
Reactant: C[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: [NH4+]
Product: CCN(CC)c1ccc(C=C[N+](=O)[O-])c(OC(C)=O)c1
Temperature: 100 °C
Yield: 36 %

Procedure:
A solution was prepared by dissolving 23.5 grams (0.10 mol) of 2-acetyloxy-4-(N,N-diethylamino)benzaldehyde in 100 ml of nitromethane, and added with 3 grams of ammonium acetate. The mixture was heated at 100° C. for 5 hours under agitation. The reaction solution was then cooled on a dry ice-acetone bath until crystallization had been completed. The separated solid (crystal) was filtered off and dried in vacuum. The obtained product was recrystallized from acetonitrile for two times. An amount of 10 grams of red crystals was obtained. The yield was 36%.
Reaction SMILES: [C:1]([N:5]1[CH2:8][CH:7]([OH:9])[CH2:6]1)([CH3:4])([CH3:3])[CH3:2].N12CCN(CC1)CC2.C(N(C(C)C)CC)(C)C.Cl[C:28]1[N:33]2[N:34]=[C:35]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=3[Cl:50])[C:36]([C:37]3[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=3)=[C:32]2[N:31]=[C:30]([CH3:51])[N:29]=1>O1CCCC1>[C:1]([N:5]1[CH2:8][CH:7]([O:9][C:28]2[N:33]3[N:34]=[C:35]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=4[Cl:50])[C:36]([C:37]4[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=4)=[C:32]3[N:31]=[C:30]([CH3:51])[N:29]=2)[CH2:6]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1nc(Cl)n2nc(-c3ccccc3Cl)c(-c3ccc(Cl)cc3)c2n1
Reactant: CC(C)(C)N1CC(O)C1
Agent: C1CN2CCN1CC2
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nc(OC2CN(C(C)(C)C)C2)n2nc(-c3ccccc3Cl)c(-c3ccc(Cl)cc3)c2n1
Reaction time: 48 h

Procedure:
To a solution of 1-tert-butylazetidin-3-ol (19 mg, 0.15 mmol), 1,4-diazabicyclo[2.2.2]octane (11 mg, 0.10 mmol), and diisopropylethylamine (0.026 ml, 0.15 mmol) in tetrahydrofuran (1 ml) was added 4-chloro-7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazine (I-2A-1b; 39 mg, 0.10 mmol), portionwise. After stirring for 2 days, the reaction was concentrated, in vacuo, and the residue purified on a Biotage™ Flash 12S column using 20-40% ethyl acetate in hexanes to afford 11A-1 (25 mg, 52%) as a solid: +APcI MS (M+1) 482.3; 1H NMR (400 MHz, CD3OD) δ 7.52-7.42 (m, 4H), 7.39 (d, J=8.3 Hz, 2H), 7.24 (d, J=8.3 Hz, 2H), 5.58 (quintet, J=6.2 Hz, 1H), 3.80-3.75 (m, 2H), 3.63-3.58 (m, 2H), 2.60 (s, 3H), 1.04 (s, 9H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:20]2[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][CH:21]=2)[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])[C:9]1=[O:19].[C:28](Cl)(=[O:30])[CH3:29].C(N(C(C)C)C(C)C)C>C(Cl)Cl>[NH:1]([C:2]1[CH:3]=[C:4]([C:20]2[CH:21]=[CH:22][C:23]([C:26]#[N:27])=[CH:24][CH:25]=2)[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])[C:9]1=[O:19])[C:28]([CH3:29])=[O:30]
Reactant: COC(=O)CCN1CCN(c2ccc(-c3ccc(C#N)cc3)cc2N)C1=O
Reactant: CC(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COC(=O)CCN1CCN(c2ccc(-c3ccc(C#N)cc3)cc2NC(C)=O)C1=O

Procedure:
Prepared from 1-(3-amino-4'-cyano-4-biphenylyl)-3-(2-methoxycarbonyl-ethyl)-imidazolidin-2-one and acetylchloride in methylene chloride at ambient temperature using ethyl-diisopropylamine.
Reaction SMILES: C(O[CH:4]([O:6][C:7]1[CH:14]=[CH:13][C:10]([CH:11]=[CH2:12])=[CH:9][CH:8]=1)[CH3:5])C.[OH:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=[CH2:21])=[CH:18][CH:17]=1>>[CH2:16]([O:15][CH2:5][CH2:4][O:6][C:7]1[CH:8]=[CH:9][C:10]([CH:11]=[CH2:12])=[CH:13][CH:14]=1)[CH3:17].[OH:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=[CH2:21])=[CH:18][CH:17]=1
Reactant: C=Cc1ccc(OC(C)OCC)cc1
Agent: C=Cc1ccc(O)cc1
Product: C=Cc1ccc(OCCOCC)cc1

Procedure:
To a solution of poly(p-hydroxystyrene) (4.0 g) obtained in above (2) and ethyl vinyl ether (1.2 g) in a mixed solvent (35 ml) of 1,4-dioxane and pyridine, a catalytic amount of p-toluenesulfonic acid was added and reacted with stirring at room temperature for 24 hours. The reaction mixture was poured into H2O (1 l) and a white solid was precipitated. The polymer was filtered, washed with h2O and dried under reduced pressure to afford 5.0 g of poly[p-(1-ethoxyethoxy)styrene/p-hydroxystyrene] as white powder having Mw 10000 (GPC with polystyrene calibration). The polymer was found to have p-(1-ethoxyethoxy)styrene unit and p-hydroxystyrene unit in a molar ratio of ca. 4:6 based on 1HNMR.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:12][C@H:13]3[CH2:18][CH2:17][C@H:16]([C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:15][CH2:14]3)[CH:8]=2)[CH:3]=1.[I:23]N1C(=O)CCC1=O>C(Cl)Cl.[Cl-].[Cl-].[Cl-].[Cl-].[Zr+4]>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([I:23])=[C:7]([O:12][C@H:13]1[CH2:18][CH2:17][C@H:16]([C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:15][CH2:14]1)[CH:6]=[CH:5]2
Reactant: CC(C)(C)[C@H]1CC[C@H](Oc2ccc3cc(Br)ccc3c2)CC1
Reactant: O=C1CCC(=O)N1I
Agent: [Zr+4]
Agent: [Cl-]
Solvent: ClCCl
Product: CC(C)(C)[C@H]1CC[C@H](Oc2ccc3cc(Br)ccc3c2I)CC1
Temperature: 23 °C
Reaction time: 0.08 h

Procedure:
To a solution of 2-Bromo-6-(trans-4-tert-butyl-cyclohexyloxy)-naphthalene (500 mg, 0.001 mol) in Methylene chloride (2 mL, 0.03 mol), N-iodosuccinimide (600 mg, 0.003 mol) was added, followed by zirconium tetrachloride (60 mg, 0.0003 mol) at 23° C. The reaction mixture was then sonicated and stirred for 5 minutes at 23° C. Reaction was then diluted with DCM and the solids were removed via filtration through a 4 micron filter. 1 g of SiO2 was added directly to the solution and the solvent was then removed under reduced pressure. The SiO2 was then loaded onto a column (SiO2, 24 g, 0-10% ethyl acetate/hexanes (ran neat hexanes for first 9 minutes of a 30 min gradient)) to give the DP as a tan amorphous solid with 20% impurity (SM) by HNMR. Material was then triturated with methanol, filtered, and dried on filter to give 386 mg of the desired product as a white solid in (60%). ESI-MS: 488 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[C:3]([N:9]=[CH:10][N:11](C)C)=[N:4][C:5]([Br:8])=[CH:6][N:7]=1.Cl.N[OH:16]>CO>[Br:1][C:2]1[C:3]([NH:9][CH:10]=[N:11][OH:16])=[N:4][C:5]([Br:8])=[CH:6][N:7]=1
Reactant: NO
Reactant: CN(C)C=Nc1nc(Br)cnc1Br
Agent: Cl
Solvent: CO
Product: ON=CNc1nc(Br)cnc1Br
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of N′-(3,6-dibromo-pyrazin-2-yl)-N,N-dimethylformamidine (18.6 g, 60.80 mmol) in methanol (200 mL) is added hydroxylamine hydrochloride (5.91 g, 85.12 mmol) in one portion. The reaction is stirred at room temperature for 16 hours. The solvent is evaporated and the solid residue is treated with cold (ice cooling) water and collected by filtration. The precipitate is washed twice with water and petroleum ether and dried in vacuo yielding the title compound. 1H -NMR (400 MHz, d6-DMSO) δ(ppm) 7.82 (br s, 1H), 8.21 (s, 1H), 8.34 (m, 1H), 11.17 (br s, 1H). LCMS: Rt 3.17 min (98.7%), m/z (APCI) 295 (M+H)+.