Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]=[C:2]1[NH:6][C:5]([CH:7]([S:13]([OH:16])(=[O:15])=[O:14])[C:8]([O:10]CC)=[O:9])=[CH:4][S:3]1.[OH-].[Na+].Cl>>[S:13]([CH:7]([C:5]1[NH:6][C:2](=[NH:1])[S:3][CH:4]=1)[C:8]([OH:10])=[O:9])([OH:16])(=[O:14])=[O:15]
Reactant: CCOC(=O)C(c1csc(=N)[nH]1)S(=O)(=O)O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: N=c1[nH]c(C(C(=O)O)S(=O)(=O)O)cs1
Reaction time: 0.25 h
Yield: 86.8 %

Procedure:
Under cooling with ice and stirring, 798 mg of the above ethyl (2-imino-4-thiazolin-4-yl)-2-sulfoacetate is added to 6.6 ml of 1N-sodium hydroxide and the mixture is allowed to stand for 15 minutes. Then, under cooling with ice and stirring, the mixture is neutralized with 7.0 ml of 1N hydrochloric acid, whereupon white precipitate is obtained. The precipitate is recovered by filtration, rinsed with ethanol and ether and dried. By this procedure is obtained 620 mg of 2-sulfo-2-(2-imino-4-thiazolin-4-yl)acetic acid. IR(cm-1, KBr): 1732, 1628, 1603, 1576, 1230, 1190, 1050 NMR(NaHCO3 in D2Q, δ): 4.93(s,1H), 6.90(s,1H)
Reaction SMILES: [CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:53])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([OH:50])[CH:46]([O:51][CH3:52])[CH2:45]2)[CH:7]([CH3:54])[CH:6]([OH:55])[CH2:5][C:4]1=[O:56])[CH3:2].C(O)(=O)C.C(O)(=O)C.[F:65][C:66]1[CH:71]=[CH:70][C:69]([Bi](C2C=CC(F)=CC=2)C2C=CC(F)=CC=2)=[CH:68][CH:67]=1.C(O)(=O)C.C(=O)(O)O.FC1C=CC([Bi](C2C=CC(F)=CC=2)C2C=CC(F)=CC=2)=CC=1>C(Cl)Cl.C([O-])(O)=O.[Na+].CC([O-])=O.CC([O-])=O.[Cu+2]>[CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:53])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([O:50][C:69]3[CH:70]=[CH:71][C:66]([F:65])=[CH:67][CH:68]=3)[CH:46]([O:51][CH3:52])[CH2:45]2)[CH:7]([CH3:54])[CH:6]([OH:55])[CH2:5][C:4]1=[O:56])[CH3:2]
Reactant: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(O)C(OC)C3)C(C)C(O)CC1=O)C(C)CC2OC
Reactant: Fc1ccc([Bi](c2ccc(F)cc2)c2ccc(F)cc2)cc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: O=C(O)O
Solvent: ClCCl
Solvent: CC(=O)O
Product: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(Oc4ccc(F)cc4)C(OC)C3)C(C)C(O)CC1=O)C(C)CC2OC
Reaction time: 48 h

Procedure:
To a stirred mixture of 17-ethyl-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (100 mg, 0.126 mmol, 1 eq) and Cu(OAc)2 (3 mg, 0.0165 mmol, 0.13 eq) in CH2Cl2 (1 ml) in a 4 mL screw-cap vial equipped with a magnetic stir-bar was added tri(4-fluorophenyl)bismuth diacetate [prepared immediately prior to use by addition of acetic acid (0.030 mL, 0.504 mmol, 4 eq) to a suspension of tri(4-fluorophenyl)bismuth carbonate (100 mg, 0.181 mmol, 1.4 eq) in CH2Cl2 (1 mL)]. The reaction vessel was capped and the mixture stirred for two days. The reaction mixture was diluted with several milliliters of saturated aqueous NaHCO3 and extracted 2 times with CH2Cl2. The organic extracts were combined, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The product was isolated by preparative TLC on silica gel (eluted with 3:1 hexanes/EtOAc) to afford 39 mg of 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(4'"-fluorophenyloxy)-3"-methoxycyclohexyl)-1'-methyl-vinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo-[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone. (1H NMR, 13C NMR and mass spectral analysis were consistent with the desired structure).
Reaction SMILES: [NH2:1][C:2]1[N:10]=[CH:9][C:8]([Br:11])=[CH:7][C:3]=1[C:4](O)=[O:5].C1C=CC2N(O)N=[N:18]C=2C=1.CCN=C=NCCCN(C)C.CCN(CC)CC.[NH4+].[Cl-]>CN(C=O)C>[NH2:1][C:2]1[N:10]=[CH:9][C:8]([Br:11])=[CH:7][C:3]=1[C:4]([NH2:18])=[O:5]
Reactant: Nc1ncc(Br)cc1C(=O)O
Reactant: On1nnc2ccccc21
Agent: CCN=C=NCCCN(C)C
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: NC(=O)c1cc(Br)cnc1N
Temperature: 25 °C
Reaction time: 8 h
Yield: 90.6 %

Procedure:
A mixture of 2-amino-5-bromonicotinic acid (2.0 g, 9.20 mmol), HOBT (1.40 g, 11.2 mmol), EDCI (3.52 g, 18.4 mmol), Et3N (4.68 g, 46.0 mmol) and NH4Cl (2.48 g, 46.0 mmol) in DMF (100 mL) was stirred overnight at room temperature. The reaction mixture was concentrated in vacuo, suspended in water and extracted with CH2Cl2. The organic layer was washed with brine, dried over Na2SO4 and concentrated to give the product of 2-amino-5-bromonicotinamide (1.80 g, yield: 80%), which was used for the next step without further purification. 1H NMR (DMSO-d6, 400 MHz) δ 8.14 (dd, J=4.4 Hz, 2.4 Hz, 2H), 8.04 (s, 1H), 7.46 (s, 1H), 7.37 (s, 2H). MS (M+H)+: 216/218.
Reaction SMILES: Cl[C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[Cl:13][C:14]1[CH:21]=[CH:20][C:17]([NH:18][CH3:19])=[CH:16][CH:15]=1>>[Cl:13][C:14]1[CH:21]=[CH:20][C:17]([N:18]([CH3:19])[C:2]2[N:11]=[C:10]([N:18]([C:17]3[CH:20]=[CH:21][C:14]([Cl:13])=[CH:15][CH:16]=3)[CH3:19])[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)=[CH:16][CH:15]=1
Reactant: CNc1ccc(Cl)cc1
Reactant: Clc1nc(Cl)c2ccccc2n1
Product: CN(c1ccc(Cl)cc1)c1nc(N(C)c2ccc(Cl)cc2)c2ccccc2n1

Procedure:
The title compound was prepared from 2,4-dichloroquinazoline (60 mg, 0.3.02 mmol) and 4-chloro-N-methylaniline (72 mg, 0.513 mmol) by a procedure similar to example 1b and was isolated as white powder (50 mg, 83%). 1H NMR (CDCl3): 8.93 (d, J=8.4 Hz, 1H), 7.56 (t, J=7.5 Hz, 1H), 7.47-7.44 (m, 4H), 7.32-7.27 (m, 2H), 7.18-7.14 (m, 2H), 6.95 (t, J=7.5 Hz, 1H), 6.67 (d, J=8.4 Hz, 1H), 4.02 (s, 3H), 3.25 (s, 3H).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][NH:4][CH:5]([C:9]1[O:10][C:11]2[C:16]([C:17](=[O:26])[C:18]=1[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[CH:15][CH:14]=[C:13]([Cl:27])[CH:12]=2)[CH:6]([CH3:8])[CH3:7].C(N(CC)CC)C.[C:35]1([CH3:44])[CH:40]=[CH:39][C:38]([C:41](Cl)=O)=[CH:37][CH:36]=1>C(Cl)Cl.CCOCC>[CH2:19]([C:18]1[C:17](=[O:26])[C:16]2[C:11](=[CH:12][C:13]([Cl:27])=[CH:14][CH:15]=2)[O:10][C:9]=1[CH:5]([N:4]1[CH2:3][CH2:2][N:1]=[C:44]1[C:35]1[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=1)[CH:6]([CH3:7])[CH3:8])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: CC(C)C(NCCN)c1oc2cc(Cl)ccc2c(=O)c1Cc1ccccc1
Reactant: Cc1ccc(C(=O)Cl)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CCOCC
Product: Cc1ccc(C2=NCCN2C(c2oc3cc(Cl)ccc3c(=O)c2Cc2ccccc2)C(C)C)cc1
Temperature: 0 °C
Yield: 50 %

Procedure:
To a cooled (0° C.) solution of 2-[1-(2-amino-ethylamino)-2-methyl-propyl]-3-benzyl-7-chloro-chromen-4-one (4.1 g, 11 mmol) and triethylamine (2.2 mL. 17 mmol) in methylene chloride (100 mL) was added a solution of p-toluoyl chloride (1.7 mmol) in methylene chloride (20 mL). The reaction was maintained at 0° C. for 2 hours, at which time it was diluted with ether (250 mL). The resultant solution was washed with 1 N hydrogen chloride (2×200 mL), saturated sodium bicarbonate (200 mL) and brine (150 mL), dried over magnesium sulfate, and concentrated. The residue was purified by flash chromatography (0→60% ethyl acetate/hexanes) to give 2.8 g, (50%) of the title compound. MS (ES+) m/e 503 [M+H]+.
Reaction SMILES: [CH:1]([N:14]1[C:22]2[C:17](=[CH:18][C:19]([Cl:23])=[CH:20][CH:21]=2)[C:16]([CH2:24][CH2:25][O:26][C:27]2[CH:35]=[CH:34][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=2)=[C:15]1[CH2:36][CH2:37][NH:38]S(CC1C=CC=CC=1)(=O)=O)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:49][C:50]([F:56])([F:55])[S:51](Cl)(=[O:53])=[O:52]>>[CH:1]([N:14]1[C:22]2[C:17](=[CH:18][C:19]([Cl:23])=[CH:20][CH:21]=2)[C:16]([CH2:24][CH2:25][O:26][C:27]2[CH:35]=[CH:34][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=2)=[C:15]1[CH2:36][CH2:37][NH:38][S:51]([C:50]([F:56])([F:55])[F:49])(=[O:53])=[O:52])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: O=C(O)c1ccc(OCCc2c(CCNS(=O)(=O)Cc3ccccc3)n(C(c3ccccc3)c3ccccc3)c3ccc(Cl)cc23)cc1
Reactant: O=S(=O)(Cl)C(F)(F)F
Product: O=C(O)c1ccc(OCCc2c(CCNS(=O)(=O)C(F)(F)F)n(C(c3ccccc3)c3ccccc3)c3ccc(Cl)cc23)cc1
Yield: 49 %

Procedure:
To the methyl 4-{2-[2-(2-aminoethyl)-1-benzhydryl-5-chloro-1H-indol-3-yl]ethoxy}benzoate (Step6, Example 1) was added trifluoromethylsulfonyl chloride according to the procedure in Example 1 Step 7 to generate the product in 49% yield.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([S:11][CH3:12])[C:9]=1[OH:10])[C:5]#[N:6].Cl[C:14]([C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=1)=O.BrC1C2OC(C3C=CC(C([O-])=O)=CC=3)=NC=2C=C(C#N)C=1>>[C:5]([C:4]1[CH:7]=[C:8]([S:11][CH3:12])[C:9]2[O:10][C:14]([C:16]3[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=3)=[N:1][C:2]=2[CH:3]=1)#[N:6]
Reactant: COC(=O)c1ccc(C(=O)Cl)cc1
Reactant: CSc1cc(C#N)cc(N)c1O
Agent: N#Cc1cc(Br)c2oc(-c3ccc(C(=O)[O-])cc3)nc2c1
Product: COC(=O)c1ccc(-c2nc3cc(C#N)cc(SC)c3o2)cc1

Procedure:
The title compound was prepared from 3-amino-4-hydroxy-5-(methylthio)benzonitrile and methyl 4-(chlorocarbonyl)benzoate by a procedure analogous to that described in INTERMEDIATE 1, Step C. Mass spectrum (ESI) 325.0 (M+1).
Reaction SMILES: Cl[C:2]1[C:7]([C:8](=[O:16])[C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=2)=[CH:6][N:5]=[C:4]2[N:17]([CH2:20][CH3:21])[N:18]=[CH:19][C:3]=12.Cl.[NH2:23]O.C([O-])(=O)C.[Na+]>C(O)(=O)C>[Cl:15][C:11]1[CH:10]=[C:9]([C:8]2[O:16][N:23]=[C:2]3[C:7]=2[CH:6]=[N:5][C:4]2[N:17]([CH2:20][CH3:21])[N:18]=[CH:19][C:3]3=2)[CH:14]=[CH:13][CH:12]=1
Reactant: CCn1ncc2c(Cl)c(C(=O)c3cccc(Cl)c3)cnc21
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CC(=O)O
Product: CCn1ncc2c3noc(-c4cccc(Cl)c4)c3cnc21

Procedure:
4-Chloro-5-(3-chlorobenzoyl)-1-ethyl-1H-pyrazolo[3,4-b]pyridine (2.65 g) was stirred overnight at 90° in 75 ml of glacial acetic acid containing 3.0 g of hydroxylamine hydrochloride. Sodium acetate (3.5 g) was then added, followed by an additional 1.0 g of hydroxylamine hydrochloride. The reaction mixture was then evaporated and the residue distributed between aqueous sodium bicarbonate and dichloromethane. The organic layer was evaporated and the residue was triturated with methanol and then chromatographed (230-400 mesh silica gel, 10% ethyl acetate/dichloromethane) to give 1.20 g of product, mp 207°-209°. It was combined with the products of several other runs and recrystallized from ethyl acetate to give analytically pure material, mp 209°-210° C.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1([C:11]2[CH:16]=[CH:15][C:14]([NH2:17])=[C:13](Br)[CH:12]=2)[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=[O:4].[C:19]1(B2OC(C)(C)C(C)(C)O2)[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]=1>CCOC(C)=O.C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1([C:11]2[CH:16]=[CH:15][C:14]([NH2:17])=[C:13]([C:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]=3)[CH:12]=2)[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=[O:4]
Reactant: CC1(C)OB(C2=CCCCC2)OC1(C)C
Reactant: COC(=O)C1(c2ccc(N)c(Br)c2)CCOCC1
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: COC(=O)C1(c2ccc(N)c(C3=CCCCC3)c2)CCOCC1
Yield: 70 %

Procedure:
The title compound was prepared by the Suzuki coupling procedure of Example 16, step (d) using 4-(4-amino-3-bromo-phenyl)-tetrahydro-pyran-4-carboxylic acid methyl ester (as prepared in the Example 16, step (c), 380 mg, 1.21 mmol), and 2-cyclohex-1-enyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (277 mg, 1.33 mmol). Silica gel chromatography (0-2% EtOAc/DCM) afforded the title compound (268 mg, 70%) as a white solid. Mass spectrum (ESI, m/z): Calcd. for C19H25NO3, 316.2 (M+H). found 316.2.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:30]=[C:29]([F:31])[C:9]([CH2:10][O:11][C:12]([N:14]3[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][C@H:15]3[CH2:27][CH3:28])=[O:13])=[C:8]([F:32])[CH:7]=2)[CH2:3][CH2:2]1.Cl.[OH-].[Na+]>CO.O1CCOCC1>[CH:1]1([CH2:4][O:5][C:6]2[CH:30]=[C:29]([F:31])[C:9]([CH2:10][O:11][C:12]([N:14]3[CH2:19][CH2:18][NH:17][CH2:16][C@H:15]3[CH2:27][CH3:28])=[O:13])=[C:8]([F:32])[CH:7]=2)[CH2:3][CH2:2]1
Reactant: CC[C@@H]1CN(C(=O)OC(C)(C)C)CCN1C(=O)OCc1c(F)cc(OCC2CC2)cc1F
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CO
Product: CC[C@@H]1CNCCN1C(=O)OCc1c(F)cc(OCC2CC2)cc1F
Temperature: 25 °C
Reaction time: 18 h
Yield: 76 %

Procedure:
(R)-2-Ethyl-piperazine-1,4-dicarboxylic acid 4-tert-butyl ester 1-(4-cyclopropylmethoxy-2,6-difluoro-benzyl) ester (400 mg) was dissolved in methanol (5 mL), 1100 μL 4 N HCl in dioxane was added and the mixture was stirred for 18 h at room temperature. The mixture was made alkaline with 2 N NaOH and eluted with ethylacetate over a column containing 10 g ChemElut CE1010. The filtrate was collected, solvent was evaporated to give a yellowish oil (237 mg). This residue was purified by column chromatography (silica gel; dichloromethane/methanol gradient) to yield 186 mg (59%) of the product as a colorless oil. MS (ISP): 355.4 (M+H)+.
Reaction SMILES: [C:1]([O:4][CH2:5][CH2:6][O:7][C:8]1[C:12](I)=[C:11]([N:14]([S:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH2:15][O:16][CH2:17][CH2:18][O:19][CH3:20])[N:10]([CH3:34])[N:9]=1)(=[O:3])[CH3:2].C(O)C.C(=O)([O-])[O-].[Cs+].[Cs+].[F:44][C:45]([F:56])([F:55])[C:46]1[CH:51]=[CH:50][C:49](B(O)O)=[CH:48][CH:47]=1>C1(C)C=CC=CC=1.O>[C:1]([O:4][CH2:5][CH2:6][O:7][C:8]1[C:12]([C:49]2[CH:50]=[CH:51][C:46]([C:45]([F:56])([F:55])[F:44])=[CH:47][CH:48]=2)=[C:11]([N:14]([S:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH2:15][O:16][CH2:17][CH2:18][O:19][CH3:20])[N:10]([CH3:34])[N:9]=1)(=[O:3])[CH3:2]
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Reactant: COCCOCN(c1c(I)c(OCCOC(C)=O)nn1C)S(=O)(=O)c1ccc(C(C)(C)C)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: O
Product: COCCOCN(c1c(-c2ccc(C(F)(F)F)cc2)c(OCCOC(C)=O)nn1C)S(=O)(=O)c1ccc(C(C)(C)C)cc1
Temperature: 25 °C

Procedure:
To 2-[(5-{{[4-(tert-butyl)phenyl]sulfonyl}[(2-methoxyethoxy)methyl]amino)-4-iodo-1-methyl-1H-pyrazol-3-yl)oxy]ethyl acetate (Preparation 14) (300 mg) in solution in toluene (5 ml) were successively added ethanol (1 ml), cesium carbonate (805 mg) in water (2 ml), and 4-(trifluoromethyl)phenylboronic acid (187 mg) at room temperature. The reaction mixture was degassed (vacuum followed by nitrogen atmosphere). This operation was repeated 5 times. The tetrakis(triphenylphosphine)-palladium(0) (15 mg) was then added and the reaction mixture degassed twice. The reaction mixture was refluxed for 1.5 hours and then cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between ethyl acetate (20 ml) and a saturated solution of sodium carbonate (20 ml). The organic layer was separated and washed with a saturated solution of sodium carbonate (10 ml) and then brine (10 ml). The solution was dried on magnesium sulfate, the solution filtered on celite and concentrated under reduced pressure. The crude material was purified by chromatography on a suction column packed with silica eluted with ethyl acetate:hexane (1:2 to 3:1 gradually) to yield the desired product as an off white solid (200 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=O)=[C:4]([O:11][CH3:12])[CH:3]=1.ClC1C=C(Cl)C=CC=1C1[C:26]([C:27]2[NH:28][CH:29]=[CH:30][N:31]=2)=[CH:25][N:24]=[C:23]([NH:32][CH2:33][CH2:34][NH:35][C:36]2[CH:41]=[CH:40][C:39]([N+:42]([O-:44])=[O:43])=[CH:38][N:37]=2)[N:22]=1>>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]2[C:26]([C:27]3[NH:31][CH:30]=[CH:29][N:28]=3)=[CH:25][N:24]=[C:23]([NH:32][CH2:33][CH2:34][NH:35][C:36]3[CH:41]=[CH:40][C:39]([N+:42]([O-:44])=[O:43])=[CH:38][N:37]=3)[N:22]=2)=[C:4]([O:11][CH3:12])[CH:3]=1
Reactant: COc1cc(Cl)ccc1C(=O)Cl
Reactant: O=[N+]([O-])c1ccc(NCCNc2ncc(-c3ncc[nH]3)c(-c3ccc(Cl)cc3Cl)n2)nc1
Product: COc1cc(Cl)ccc1-c1nc(NCCNc2ccc([N+](=O)[O-])cn2)ncc1-c1ncc[nH]1

Procedure:
[4-(4-chloro-2-methoxyphenyl)-5-imidazol-2-ylpyrimidin-2-yl]{2-[(5-nitro(2-pyridyl))amino]ethyl}amine was prepared from 4-chloro-2-methoxybenzoyl chloride using the general method for [4-(2,4-dichlorophenyl)-5-imidazol-2-ylpyrimidin-2-yl]{2-[(5-nitro(2-pyridyl))amino]ethyl}amine.
Reaction SMILES: C[O:2][C:3](=[O:17])[CH:4]([CH2:13][CH:14]([CH3:16])[CH3:15])[CH2:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7]>Cl.CC(C)=O>[C:9]([O:8][C:6](=[O:7])[CH2:5][CH:4]([CH2:13][CH:14]([CH3:15])[CH3:16])[C:3]([OH:17])=[O:2])([CH3:12])([CH3:11])[CH3:10]
Reactant: COC(=O)C(CC(=O)OC(C)(C)C)CC(C)C
Agent: Cl
Solvent: CC(C)=O
Product: CC(C)CC(CC(=O)OC(C)(C)C)C(=O)O
Yield: 58.8 %

Procedure:
Acetal 2 (1.01 g, 5.54 mmol) was stirred in a mixture of 2N hydrochloric acid (10 mL) and acetone (10 mL) for 24 hours. After this time, tlc showed complete consumption of the starting acetal. Saturated sodium carbonate solution (20 mL) was added, and the mixture was extracted with ether (3×25 mL). The combined ether fractions were washed with brine, dried (MgSO4), and the solvent was evaporated under reduced pressure. The residue was chromatographed (SiO2, pentane/ether, 95:5) to give the ketone 3 (0.75 g, 97%) as a colorless oil; Rf (heptane/ethyl acetate, 8:2) 0.42; νmax(film)/cm−1 1743 (C═O); δH (400 MHz; CDCl3): 2.37–2.28 (2H, m), 2.20 (2H, dd, J=18.5, 7.5), 2.12 (2H, dd, J=18.7, 6.3), 1.65–1.24 (10H, m).
Reaction SMILES: [N+:1]([C:4]1[CH:10]=[CH:9][C:7]([NH2:8])=[C:6]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[CH:5]=1)([O-:3])=[O:2].CC([O-])(C)C.[K+]>CN(C=O)C.O>[N+:1]([C:4]1[CH:5]=[C:6]2[C:7](=[CH:9][CH:10]=1)[NH:8][C:12]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1)=[CH:11]2)([O-:3])=[O:2]
Reactant: Nc1ccc([N+](=O)[O-])cc1C#Cc1ccccn1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=[N+]([O-])c1ccc2[nH]c(-c3ccccn3)cc2c1
Temperature: 90 °C
Reaction time: 2 h
Yield: 66.4 %

Procedure:
To the solution of 4-nitro-2-(pyridin-2-ylethynyl)aniline (1.5 g, 6.3 mmol) in DMF (50 mL) was added t-BuOK (1.5 g, 13 mmol). The reaction mixture was stirred at 90° C. for 2 h. The mixture was diluted with water and extracted with dichloromethane (3×50 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuum. The residue was purified by chromatography on silica gel (5-10% ethyl acetate/petroleum ether) to afford 5-nitro-2-(pyridin-2-yl)-1H-indole (1.0 g, 67%yield). 1H NMR (300 MHz, d-DMSO) δ 12.40 (s, 1H), 8.66 (d, J=2.1 Hz, 1 H), 8.58 (d, J=1.8 Hz, 1 H), 8.07-7.91 (m, 3 H), 7.59 (d, J=6.6 Hz, 1 H), 7.42-7.37 (m, 2 H).
Reaction SMILES: [C:1]([C:3]1([CH3:17])[CH2:8][CH2:7][C:6]2[C:9]([CH3:16])=[C:10]([OH:15])[C:11]([CH3:14])=[C:12]([CH3:13])[C:5]=2[O:4]1)#[CH:2].Br[C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1.C(OCC)(=O)C>C(Cl)Cl>[CH3:17][C:3]1([C:1]#[C:2][C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)[CH2:8][CH2:7][C:6]2[C:9]([CH3:16])=[C:10]([OH:15])[C:11]([CH3:14])=[C:12]([CH3:13])[C:5]=2[O:4]1
Reactant: Brc1cccnc1
Reactant: C#CC1(C)CCc2c(C)c(O)c(C)c(C)c2O1
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: Cc1c(C)c2c(c(C)c1O)CCC(C)(C#Cc1cccnc1)O2
Reaction time: 18 h

Procedure:
Rac-3,4-dihydro-2-ethynyl-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol, 4,6 g, was reacted as described in Example 4 with 4.74 g of 3-bromopyridine. The reaction time was extended to 18 hours. The product was isolated by chromatography over 150 g of silica gel using 10% (v/v) of ethyl acetate in methylene chloride for elution. Crystallization of the combined clean fractions from ethyl acetate/hexane gave off-white crystals with m.p. 172°-175° C. The analytical sample was recrystallized from tetrahydrofuran/hexane and had m.p. 175°-178° C.
Reaction SMILES: Br[C:2]1[C:6]2[N:7]=[C:8]([Cl:11])[N:9]=[CH:10][C:5]=2[S:4][CH:3]=1.B([C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=1)[C:18]([OH:20])=[O:19])(O)O>>[Cl:11][C:8]1[N:9]=[CH:10][C:5]2[S:4][CH:3]=[C:2]([C:15]3[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=3)[C:18]([OH:20])=[O:19])[C:6]=2[N:7]=1
Reactant: Clc1ncc2scc(Br)c2n1
Reactant: O=C(O)c1cccc(B(O)O)c1
Product: O=C(O)c1cccc(-c2csc3cnc(Cl)nc23)c1
Yield: 65.4 %

Procedure:
3-(2-Chlorothieno[3,2-d]pyrimidin-7-yl)benzoic acid (380 mg, 65% yield) was prepared in the same manner as Step 6 of Example 1 using 7-bromo-2-chlorothieno[3,2-d]pyrimidine (500 mg, 2.0 mmol) and 3-boronobenzoic acid (332 mg, 2.0 mmol).
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[N:11]3[N:12]=[C:13]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][N:25]5[CH2:29][CH2:28][CH2:27][CH2:26]5)=[CH:18][CH:17]=4)[N:14]=[C:10]3[CH:9]=[CH:8][CH:7]=2)[CH:3]=[N:2]1.C(=O)([O-])[O-].[K+].[K+].Cl[CH:37]([OH:39])[CH3:38]>CN(C)C=O>[N:25]1([CH2:24][CH2:23][O:22][C:19]2[CH:18]=[CH:17][C:16]([NH:15][C:13]3[N:14]=[C:10]4[CH:9]=[CH:8][CH:7]=[C:6]([C:4]5[CH:3]=[N:2][N:1]([CH2:38][CH2:37][OH:39])[CH:5]=5)[N:11]4[N:12]=3)=[CH:21][CH:20]=2)[CH2:29][CH2:28][CH2:27][CH2:26]1
Reactant: CC(O)Cl
Reactant: c1cc(-c2cn[nH]c2)n2nc(Nc3ccc(OCCN4CCCC4)cc3)nc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: OCCn1cc(-c2cccc3nc(Nc4ccc(OCCN5CCCC5)cc4)nn23)cn1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a stirred solution of [5-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amine (0.40 g, 1.03 mmol) in dimethylformamide (10 ml) was added potassium carbonate (2 g) followed by 1-chloroethanol (140 μl, 2.06 mmol). The mixture was stirred for 18 hours at room temperature, then filtered and concentrated in vacuo to provide a yellow solid. No further purification was required. Yield: 0.45 g, 89%; LCMS method: 2, RT: 2.10 min, MI: 434 [M+1].
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH:7]1O[CH2:8]1)[CH:2]1[O:4][CH2:3]1.OC1[CH:16]=[CH:15][C:14]([C:17]([C:20]2[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=2)([CH3:19])[CH3:18])=CC=1>>[CH3:19][C:17]([C:14]1[CH:8]=[CH:7][C:6]([O:5][CH2:1][CH:2]2[O:4][CH2:3]2)=[CH:16][CH:15]=1)([C:20]1[CH:21]=[CH:22][C:23]([O:26][CH2:1][CH:2]2[O:4][CH2:3]2)=[CH:24][CH:25]=1)[CH3:18]
Reactant: C(OCC1CO1)C1CO1
Reactant: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Product: CC(C)(c1ccc(OCC2CO2)cc1)c1ccc(OCC2CO2)cc1

Procedure:
By use of the Dienoxy A copolymer described above, a 1,2-polybutadiene epoxy copolymer composition of approximately 33/67 composition was prepared and both the epoxy constituent and the polybutadiene constituent were cured. It should be noted that the blend of Dienoxy A copolymer with the additional diglycidylether of bisphenol A (DGEBA) and the anhydride curative system formed a stable dispersion while a blend of 1,2-polybutadiene with DGEBA and the anhydride curative system rapidly separated into two phases.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:16][CH3:17])[CH:14]=2)[NH:9][CH:8]=1.Br[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:22][CH:21]=1>>[CH2:29]([O:28][C:26]([C:23]1[CH:22]=[CH:21][C:20]([CH2:19][N:9]2[C:10]3[C:15](=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=3)[C:7]([CH2:6][C:2]3[NH:3][CH:4]=[CH:5][N:1]=3)=[CH:8]2)=[CH:25][CH:24]=1)=[O:27])[CH3:30]
Reactant: CCOC(=O)c1ccc(CBr)cc1
Reactant: COc1ccc2[nH]cc(Cc3ncc[nH]3)c2c1
Product: CCOC(=O)c1ccc(Cn2cc(Cc3ncc[nH]3)c3cc(OC)ccc32)cc1

Procedure:
This compound was prepared as described in Example 4 using 3-(1-imidazolylmethyl)-5-methoxyindole and ethyl (α-bromo-p-toluate) as starting materials. The fumarate salt hemihydrate had m.p. 113°-114° C. Found: C, 63.10; H, 5.29; N, 7.82. C23H23N3O3.C4H4O4.1/2H2O requires: C, 63.02; H, 5.48; N, 8.16%.