Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[Cl:12][C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1>>[CH3:8][O:7][C:5](=[O:6])[C:4]1[CH:9]=[CH:10][CH:11]=[C:2]([NH:17][C:16]2[CH:18]=[CH:19][C:13]([Cl:12])=[CH:14][CH:15]=2)[CH:3]=1
Reactant: COC(=O)c1cccc(Br)c1
Reactant: Nc1ccc(Cl)cc1
Product: COC(=O)c1cccc(Nc2ccc(Cl)cc2)c1

Procedure:
Reaction of methyl 3-bromobenzoate with 4-chloroaniline according to general procedure A provided methyl ester of Compound 8 as a yellow oil (52% yield). 1H NMR (CDCl3, 500 MHz): δ=7.70 (s, 1H), 7.61 (d, J=7.6 Hz, 1H), 7.33 (t, J=7.9 Hz, 1H), 7.21-7.27 (m, 3H), 7.01 (d, J=8.8 Hz, 2H), 5.78 (s, 1H), 3.91 (s, 3H). 13C NMR (CDCl3, 125 MHz): δ=167.2, 143.4, 141.4, 131.7, 129.7, 126.7, 122.5, 122.0, 119.8, 118.7, 52.4.
Reaction SMILES: [CH2:1]([N:8]1[C:12]2[CH:13]=[CH:14][C:15]3[N:16]([C:17]([CH3:20])=[N:18][N:19]=3)[C:11]=2[CH:10]=[C:9]1[C:21]1[CH:22]=[N:23][NH:24][CH:25]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C=O)C.[H-].[Na+].Cl[CH2:34][C:35]#[N:36]>>[CH2:1]([N:8]1[C:12]2[CH:13]=[CH:14][C:15]3[N:16]([C:17]([CH3:20])=[N:18][N:19]=3)[C:11]=2[CH:10]=[C:9]1[C:21]1[CH:22]=[N:23][N:24]([CH2:34][C:35]#[N:36])[CH:25]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N#CCCl
Reactant: Cc1nnc2ccc3c(cc(-c4cn[nH]c4)n3Cc3ccccc3)n12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1nnc2ccc3c(cc(-c4cnn(CC#N)c4)n3Cc3ccccc3)n12
Reaction time: 0.17 h

Procedure:
A solution of 6-benzyl-1-methyl-7-(1H-pyrazol-4-yl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine (14 mg, 0.043 mmol, from Example 63) in DMF (0.56 mL, 7.2 mmol) was treated with NaH (5.1 mg, 0.21 mmol). After 10 minutes, the mixture was treated with chloroacetonitrile (8.1 μL, 0.13 mmol, Fluka). After 10 minutes, the reaction was quenched by the addition of water. The product was purified via preparative HPLC-MS (C18 eluting with a gradient of MeCN and H2O containing 0.15% NH4OH). Yield: (7.0 mg, 45%).
Reaction SMILES: [F:1][C:2]1[CH:36]=[CH:35][C:5]([CH2:6][C:7]2[CH:16]=[C:15]3[C:10]([C:11]([OH:34])=[C:12]([C:29]([O:31]CC)=O)[C:13](=[O:28])[N:14]3[CH2:17][C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)=[N:9][CH:8]=2)=[CH:4][CH:3]=1.[NH2:37][CH2:38][C:39]1[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=1>>[F:1][C:2]1[CH:36]=[CH:35][C:5]([CH2:6][C:7]2[CH:16]=[C:15]3[C:10]([C:11]([OH:34])=[C:12]([C:29]([NH:37][CH2:38][C:39]4[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=4)=[O:31])[C:13](=[O:28])[N:14]3[CH2:17][C:18]3[CH:19]=[CH:20][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:22][CH:23]=3)=[N:9][CH:8]=2)=[CH:4][CH:3]=1
Reactant: NCc1ccncc1
Reactant: CCOC(=O)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2n(Cc2ccc(S(C)(=O)=O)cc2)c1=O
Product: CS(=O)(=O)c1ccc(Cn2c(=O)c(C(=O)NCc3ccncc3)c(O)c3ncc(Cc4ccc(F)cc4)cc32)cc1

Procedure:
This compound was prepared from ethyl 7-(4-fluorobenzyl)-4-hydroxy-1-[4-(methylsulfonyl)benzyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate and 4-(aminomethyl)pyridine employing methods similar to those described in Example 5 and was obtained as a white solid; 1H NMR (CDCl3) δ 10.59 (1H, t, J˜6 Hz), 8.64 (2H, d, J=6 Hz), 8.62 (1H, d, J=1.2 Hz), 7.86 (2H, d, J=8 Hz), 7.55 (2H, d, J=6 Hz), 7.22 (2H, d, J=8 Hz), 7.06 (1H, s), 7.00 (4H, m), 5.43 (2H, br), 4.78 (2H, d, J=6 Hz), 4.05 (2H, s), 3.04 (3H, s); ES+ MS: 573 (M+H+, 100).
Reaction SMILES: [CH3:1][C:2]1[C:6]2[N:7]=[CH:8][N:9]=[C:10](O)[C:5]=2[NH:4][N:3]=1.C(N(CC)C1C=CC=CC=1)C.P(Cl)(Cl)([Cl:25])=O>>[Cl:25][C:10]1[C:5]2[NH:4][N:3]=[C:2]([CH3:1])[C:6]=2[N:7]=[CH:8][N:9]=1
Reactant: Cc1n[nH]c2c(O)ncnc12
Reactant: O=P(Cl)(Cl)Cl
Solvent: CCN(CC)c1ccccc1
Product: Cc1n[nH]c2c(Cl)ncnc12
Reaction time: 0.25 h

Procedure:
A mixture of 3-methyl-7-hydroxypyrazolo[4,3-d]pyrimidine (1.0 g, 6.6 mmol), N,N-diethylaniline (2.0 g) and phosphorous oxychloride (16.5 g) was heated with magnetic stirring in an oil bath. The temperature was raised from 55° to 78° over the course of 40 min. At this point, all of the starting material had dissolved and the solution had turned red. The excess POCl3 was distilled off in vacuo (this procedure took 15 min.) and ice-water (50 ml) was added to the residue. The resulting red solution was saturated with sodium chloride (12 g) whereupon it turned yellow. The solution was extracted with ethyl acetate (4×40 ml) and the combined extract was filtered through alumina (5 g; 80-325 mesh), washed with brine (40 ml), dried (Na2SO4) and evaporated, yielding 0.83 g (74%) of eggshell colored crystals.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:18])[CH:5]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].[C:19]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])(=[O:22])[CH:20]=[CH2:21].C1CCN2C(=NCCC2)CC1.Cl>C(#N)C>[C:12]1([CH2:11][C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:18])([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:21][CH2:20][C:19]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: CCOC(=O)C(Cc1ccccc1)C(=O)OCC
Reactant: C=CC(=O)OC(C)(C)C
Agent: Cl
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Product: CCOC(=O)C(CCC(=O)OC(C)(C)C)(Cc1ccccc1)C(=O)OCC
Temperature: 25 °C
Reaction time: 6 h
Yield: 97.8 %

Procedure:
2.5 g (10 mmol) of benzylmalonic acid diethyl ester and 1.45 ml (10 mmol) of t-butyl acrylate in 5 ml of acetonitrile were treated with 1.49 ml of DBU and stirred at room temperature for 6 hours. Thereafter, the mixture was poured into dilute hydrochloric acid (pH 2), extracted with ether, the organic phase was washed with a small amount of water, dried over sodium sulfate and the solvent was removed under reduced pressure. There were obtained 3.7 g (97%) of 4-t-butyl 2,2-diethyl 1-phenyl-2,2,4-butanetricarboxylate as a pale yellow oil which was used directly in the next step.
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:27])=[N:4][C:5]([O:21][CH2:22][C:23]([O:25]C)=[O:24])=[C:6]([Cl:20])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15]C)=[C:11]([CH:17]([CH3:19])[CH3:18])[CH:10]=1.B(Br)(Br)Br.O>C(Cl)Cl>[Cl:1][C:2]1[C:3]([F:27])=[N:4][C:5]([O:21][CH2:22][C:23]([OH:25])=[O:24])=[C:6]([Cl:20])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[C:11]([CH:17]([CH3:19])[CH3:18])[CH:10]=1
Reactant: COC(=O)COc1nc(F)c(Cl)c(Oc2ccc(OC)c(C(C)C)c2)c1Cl
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: O
Product: CC(C)c1cc(Oc2c(Cl)c(F)nc(OCC(=O)O)c2Cl)ccc1O
Reaction time: 2 h
Yield: 71.5 %

Procedure:
To a solution of 3,5-dichloro-2-fluoro-4-(3-isopropyl-4-methoxyphenoxy)-6-methoxycarbonylmethoxy-pyridine (120 mg) in CH2Cl2 (3.0 mL) was added a solution of BBr3 in CH2Cl2 (1 mL, 1.0 M) at ambient temperature. The resulting mixture was stirred for 2 h, poured to stirring water (50 mL), extracted with CH2Cl2 (20 mL×3) from water, dried (Na2SO4) and concentrated to dryness under reduced pressure. The residue was dissolved in THF:MeOH:H2O=3:1:1 (5 mL), treated with a solution of LiOH in water (1 mL, 1.0 M) and stirred at ambient temperature for 30 min. The reaction mixture was diluted with a 1.0 M solution of HCl (50 mL), extracted with ethyl acetate(50 mL×3), dried (Na2SO4) and concentrated under reduced pressure. Purification by HPLC afforded the title compound as a colorless oil (80 mg).
Reaction SMILES: [Li].[C:2]([C:4]1[CH:5]=[C:6]([C:15]([O-])=[CH:16][C:17](=O)[C:18]([O:20]CC)=[O:19])[CH:7]=[C:8]([O:10][C:11]([F:14])([F:13])[F:12])[CH:9]=1)#[N:3].ClC1C=C(C2N(C3C=CC=CN=3)N=C(C(O)=O)C=2)C=C(F)C=1.Cl.[N:48]1[CH:53]=[CH:52][CH:51]=[C:50]([NH:54][NH2:55])[CH:49]=1>>[C:2]([C:4]1[CH:5]=[C:6]([C:15]2[N:54]([C:50]3[CH:49]=[N:48][CH:53]=[CH:52][CH:51]=3)[N:55]=[C:17]([C:18]([OH:20])=[O:19])[CH:16]=2)[CH:7]=[C:8]([O:10][C:11]([F:12])([F:13])[F:14])[CH:9]=1)#[N:3]
Reactant: CCOC(=O)C(=O)C=C([O-])c1cc(C#N)cc(OC(F)(F)F)c1
Reactant: NNc1cccnc1
Agent: Cl
Agent: O=C(O)c1cc(-c2cc(F)cc(Cl)c2)n(-c2ccccn2)n1
Agent: [Li]
Product: N#Cc1cc(OC(F)(F)F)cc(-c2cc(C(=O)O)nn2-c2cccnc2)c1

Procedure:
300 mg (0.81 mmol) of the compound of Example 11A is reacted analogously to the synthesis of the compound of Example 20A with 175 mg (1.21 mmol) of 3-pyridylhydrazine hydrochloride. After hydrolysis, 148 mg (49% of theory) of the title compound is obtained.
Reaction SMILES: C([O:3][C:4](=[O:21])[CH2:5][N:6]1[C:10]2[C:11]3[CH:12]=[C:13]([CH3:20])[CH:14]=[CH:15][C:16]=3[O:17][C:18](=[O:19])[C:9]=2[CH:8]=[N:7]1)C.[Li+].[OH-:23].Cl>C1COCC1>[C:4]([CH2:5][N:6]1[C:10]([C:11]2[CH:12]=[C:13]([CH3:20])[CH:14]=[CH:15][C:16]=2[OH:23])=[C:9]([C:18]([OH:17])=[O:19])[CH:8]=[N:7]1)([OH:3])=[O:21]
Reactant: [OH-]
Reactant: CCOC(=O)Cn1ncc2c(=O)oc3ccc(C)cc3c21
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Product: Cc1ccc(O)c(-c2c(C(=O)O)cnn2CC(=O)O)c1

Procedure:
To a solution of (8-Methyl-4-oxo-4H-chromeno[4,3-C]pyrazol-1-yl)-acetic acid ethyl ester g (1 mmol, 286 mg) in THF (4 mL) was added 1M aq. LiOH (2 mL, 2 mmol) was added and the resultant mixture was stirred for 2 h at rt. The reaction mixture was neutralized with 1N HCl, and concentrated in vacuo to remove THF. The crude residue was extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried over Na2SO4, and concentrated to provide the desired product h that is used without further purification.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])[CH2:16][NH:17][C:18]([CH3:31])([CH3:30])[CH2:19][C:20]2[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=2)[C:23]([O:25][CH3:26])=[O:24])=[CH:11][C:10]=1CO[Si](C(C)(C)C)(C)C)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC1C=CC([C@@H](O[Si](C(C)(C)C)(C)C)CBr)=C2C=1[NH:65][C:64](=[O:67])[CH:63]=[CH:62]2)C1C=CC=CC=1>>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([O:32][Si:33]([C:36]([CH3:37])([CH3:38])[CH3:39])([CH3:35])[CH3:34])[CH2:16][NH:17][C:18]([CH3:31])([CH3:30])[CH2:19][C:20]2[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=2)[C:23]([O:25][CH3:26])=[O:24])=[C:11]2[C:10]=1[NH:65][C:64](=[O:67])[CH:63]=[CH:62]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)[Si](C)(C)O[C@@H](CBr)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Reactant: COC(=O)c1cccc(CC(C)(C)NC[C@H](O[Si](C)(C)C(C)(C)C)c2ccc(OCc3ccccc3)c(CO[Si](C)(C)C(C)(C)C)c2)c1
Product: COC(=O)c1cccc(CC(C)(C)NC[C@H](O[Si](C)(C)C(C)(C)C)c2ccc(OCc3ccccc3)c3[nH]c(=O)ccc23)c1

Procedure:
The title compound was synthesized in a manner analogous to that described for Intermediate 47, using (R)-8-(benzyloxy)-5-[2-bromo-1-[(tert-butyldimethylsilyl)oxy]ethyl]quinolin-2(1H)-one in place of Intermediate 6. ES/MS calcd. for C36H47N2O5Si+ 615.3. found m/z=615.3 (M+H)+.
Reaction SMILES: F[C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[CH:12][N:13]=[C:14]([C:17]4[CH:18]=[N:19][N:20]([CH3:22])[CH:21]=4)[CH:15]=3)[N:10](C3CCCCO3)[N:9]=2)[CH:5]=[CH:4][CH:3]=1.[F:29][C:30]([F:45])([F:44])[C:31]1([NH:36]C(=O)OC(C)(C)C)[CH2:35][CH2:34][NH:33][CH2:32]1>>[CH3:22][N:20]1[CH:21]=[C:17]([C:14]2[CH:15]=[C:16]3[C:8]([C:6]4[N:7]=[C:2]([N:33]5[CH2:34][CH2:35][C:31]([C:30]([F:45])([F:44])[F:29])([NH2:36])[CH2:32]5)[CH:3]=[CH:4][CH:5]=4)=[N:9][NH:10][C:11]3=[CH:12][N:13]=2)[CH:18]=[N:19]1
Reactant: CC(C)(C)OC(=O)NC1(C(F)(F)F)CCNC1
Reactant: Cn1cc(-c2cc3c(-c4cccc(F)n4)nn(C4CCCCO4)c3cn2)cn1
Product: Cn1cc(-c2cc3c(-c4cccc(N5CCC(N)(C(F)(F)F)C5)n4)n[nH]c3cn2)cn1
Yield: 47.3 %

Procedure:
Following the procedures as described in Example 189, 3-(6-fluoropyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine and tert-butyl 3-(trifluoromethyl)pyrrolidin-3-ylcarbamate were reacted. The product was deprotected and purified to give 286 as a white solid (47.3% over two steps). 1H NMR (400 MHz, DMSO) δ 9.02 (s, 1H), 8.65 (s, 1H), 8.09 (s, 1H), 7.86 (s, 1H), 7.65 (t, J=7.9 Hz, 1H), 7.44 (d, J=7.4 Hz, 1H), 6.51 (d, J=8.3 Hz, 1H), 3.91-3.86 (m, 4H), 3.84-3.65 (m, 3H), 2.47 (s, 2H), 2.38-2.27 (m, 1H), 2.05 (dd, J=12.3, 6.1 Hz, 1H); 1 proton not seen. LC/MS: m/z 429.2 [M+1]
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([CH3:10])=[C:5]([CH:7]=[CH:8][CH:9]=1)[NH2:6].NC1C=[C:16]([O:18]C)[CH:15]=CC=1C(=O)C>>[NH2:6][C:5]1[C:4]([CH3:10])=[C:3]([O:2][CH3:1])[CH:9]=[CH:8][C:7]=1[C:16](=[O:18])[CH3:15]
Reactant: COc1ccc(C(C)=O)c(N)c1
Reactant: COc1cccc(N)c1C
Product: COc1ccc(C(C)=O)c(N)c1C
Yield: 23 %

Procedure:
Compound 40b was synthesized from 3-methoxy-2-methylaniline 39b as a yellow solid in 23% yield, according to the procedure as described for compound 40a.
Reaction SMILES: [N+:1]([C:4]1[CH:19]=[CH:18][C:7]2[S:8][C:9]3[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=3[C:11](=O)[CH2:12][C:6]=2[CH:5]=1)([O-:3])=[O:2].[CH2:20]([N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)[C:21]1[CH:29]=[CH:28][C:27]2[O:26][CH2:25][O:24][C:23]=2[CH:22]=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.[Ti](Cl)(Cl)(Cl)Cl>[N+:1]([C:4]1[CH:19]=[CH:18][C:7]2[S:8][C:9]3[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=3[C:11]([N:33]3[CH2:34][CH2:35][N:30]([CH2:20][C:21]4[CH:29]=[CH:28][C:27]5[O:26][CH2:25][O:24][C:23]=5[CH:22]=4)[CH2:31][CH2:32]3)=[CH:12][C:6]=2[CH:5]=1)([O-:3])=[O:2]
Reactant: c1cc2c(cc1CN1CCNCC1)OCO2
Reactant: O=C1Cc2cc([N+](=O)[O-])ccc2Sc2ccccc21
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Product: O=[N+]([O-])c1ccc2c(c1)C=C(N1CCN(Cc3ccc4c(c3)OCO4)CC1)c1ccccc1S2
Temperature: 25 °C
Yield: 17 %

Procedure:
To a stirred solution of 2-nitro-10-oxo-dibenzo[b,f]thiepine (0.54 g, 2.00 mmol) and 1-piperonylpiperazine (2.04 g, 9.26 mmol) in toluene (15 mL) was added titanium tetrachloride (0.24 mL, 2.2 mmol) at room temperature under argon. The resulted mixture was heated at reflux for 3.5 h and then cooled down to room temperature. The whole mixture was poured into a saturated sodium bicarbonate solution (50 mL). After separation, the aqueous phase was extracted with dichloromethane (2×50 mL). The combined organic solution was dried (MgSO4), filtered and concentrated in vacuo to dryness. The residue was subjected to column chromatography using ethyl acetate/hexanes (1/2) as eluent. Thus 0.161 g (17%) of the title compound was obtained as a yellow solid; m.p. 188°-190° C.; MS 474 (M+ 1).
Reaction SMILES: Cl.[O:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]1[CH:16]=[C:15]([C:17]([OH:19])=[O:18])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]=1.[C:20]1(C)C=CC=C[CH:21]=1>C(O)C>[CH2:20]([O:18][C:17]([C:15]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]=[C:7]([C:3]2[O:2][CH:6]=[CH:5][CH:4]=2)[CH:16]=1)=[O:19])[CH3:21]
Reactant: Cc1ccccc1
Reactant: O=C(O)c1cc(-c2ccco2)nc2ccccc12
Agent: Cl
Solvent: CCO
Product: CCOC(=O)c1cc(-c2ccco2)nc2ccccc12
Temperature: 25 °C

Procedure:
To 40 ml of a saturated solution of hydrochloric acid in ethanol 2 g of 2-Furan-2-yl-quinoline-4-carboxylic acid was added and the mixture was heated to reflux for 3 h. Then, after cooling to RT, 30 ml of toluene was added and the solvents were removed under reduced pressure. The obtained crude product was pure enough for the next reaction step. Yield: 2.5 g.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:15]3[N:22]=[CH:23][C:24]([C:25](O)=[O:26])=[C:14]3[N:13]=2)[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].[S:28]([C:32]1[CH:33]=[C:34]([NH2:38])[CH:35]=[CH:36][CH:37]=1)(=[O:31])(=[O:30])[NH2:29]>>[S:28]([C:32]1[CH:33]=[C:34]([NH:38][C:25]([C:24]2[CH:23]=[N:22][N:15]3[C:16]([C:18]([F:19])([F:20])[F:21])=[CH:17][C:12]([C:4]4[CH:5]=[CH:6][C:7]([C:8]([F:10])([F:9])[F:11])=[C:2]([Cl:1])[CH:3]=4)=[N:13][C:14]=23)=[O:26])[CH:35]=[CH:36][CH:37]=1)(=[O:30])(=[O:31])[NH2:29]
Reactant: O=C(O)c1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)c(Cl)c3)nc12
Reactant: Nc1cccc(S(N)(=O)=O)c1
Product: NS(=O)(=O)c1cccc(NC(=O)c2cnn3c(C(F)(F)F)cc(-c4ccc(C(F)(F)F)c(Cl)c4)nc23)c1

Procedure:
The title compound was prepared from 5-(3-chloro-4-trifluoromethyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.17) and 3-sulfamoyl-phenylamine [commercially available] according to general procedure II. Yellow solid. MS (ISP) 562.1 [(M+H)+]; mp 287° C.
Reaction SMILES: [F:1][C:2]1[N:7]=[C:6](I)[C:5]([O:9][CH3:10])=[CH:4][CH:3]=1.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13](B(O)O)[CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[F:1][C:2]1[N:7]=[C:6]([C:13]2[CH:12]=[N:11][CH:16]=[CH:15][CH:14]=2)[C:5]([O:9][CH3:10])=[CH:4][CH:3]=1
Reactant: COc1ccc(F)nc1I
Reactant: OB(O)c1cccnc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc(F)nc1-c1cccnc1
Temperature: 25 °C
Yield: 73.9 %

Procedure:
6-Fluoro-2-iodo-3-methoxypyridine (52 mg), tetrakistriphenylphosphine palladium(0) (24 mg), and 3-pyridineboronic acid (76 mg) were suspended in a mixed solvent composed of N,N-dimethylformamide (0.75 ml) and a 2 N aqueous potassium carbonate solution (0.75 ml), and the suspension was stirred at 80° C. for 4 hr. The reaction solution was cooled to room temperature, the reaction solution was then filtered, and the solvent was removed from the filtrate by distillation under the reduced pressure. Water was then added to the residue, and the mixture was extracted with dichloromethane. The dichloromethane layer was washed with water and saturated brine and was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using acetone-chloroform to give 6-fluoro-3-methoxy-[2,3′]bipyridine (31 mg, yield 72%).
Reaction SMILES: O.OO.[Br:4][C:5]1[C:6]([F:17])=[CH:7][CH:8]=[C:9]2[C:14]=1[NH:13][C:12](=[O:15])[CH:11]([CH3:16])[NH:10]2.[OH-].[Na+]>CO>[Br:4][C:5]1[C:6]([F:17])=[CH:7][CH:8]=[C:9]2[C:14]=1[NH:13][C:12](=[O:15])[C:11]([CH3:16])=[N:10]2
Reactant: CC1Nc2ccc(F)c(Br)c2NC1=O
Agent: OO
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: Cc1nc2ccc(F)c(Br)c2[nH]c1=O
Temperature: 85 °C

Procedure:
A mixture of water (14 mL) and 30% H2O2 (30.0 mL, 294 mmol) was added slowly dropwise to a solution of 8-bromo-7-fluoro-3-methyl-3,4-dihydroquinoxalin-2(1H)-one (600e) (21.7 g, 84 mmol) in 1 N NaOH (168 mL, 168 mmol) and MeOH (140 mL). The flask was fitted with a reflux condenser and heated at 85° C. for 3 h. LC-MS indicated ca. 87% conversion to the desired product (M+1=257.0/259.0). The reaction mixture was cooled to RT and acidified with 2 N HCl to ca. pH 6 and was diluted with CHCl3/IPA(4:1) (100 mL), added to a separatory funnel. The resulting suspension was filtered through a sintered glass frit, washing with water and dried affording 8-bromo-7-fluoro-3-methylquinoxalin-2(1H)-one (5.83 g, 22 mmol, 22% yield) as a light brown solid. m/z (ESI, +ve ion) 257.0/259.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.83 (1H, br. s.), 7.67-7.88 (1H, m), 7.34 (1H, t, J=8.4 Hz), 2.43 (3H, s). 19F NMR (377 MHz, DMSO-d6) δ ppm −104.13 (1F, s). The aq. solution was extracted with CHCl3:i-PrOH 9:1 (6×100 mL), dried over MgSO4, filtered and concentrated affording additional 8-bromo-7-fluoro-3-methylquinoxalin-2(1H)-one (12.51 g, 49 mmol, 58% yield) as a dark brown amorphous solid (ca. 80% purity). The material was used in the subsequent step without further purification.
Reaction SMILES: CC(N)[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O[C@H]3OC[C@@](O)(C)[C@H](NC)[C@H]3O)[C@H](N)C[C@@H]2N)[C@H](N)CC1.[CH3:33][CH:34]([NH:64][CH3:65])[C@H:35]1[O:40][C@H:39]([O:41][C@H:42]2[C@H:47]([OH:48])[C@@H:46]([O:49][C@H:50]3[O:55][CH2:54][C@@:53]([OH:57])([CH3:56])[C@H:52]([NH:58][CH3:59])[C@H:51]3[OH:60])[C@H:45]([NH2:61])[CH2:44][C@@H:43]2[NH2:62])[C@H:38]([NH2:63])[CH2:37][CH2:36]1.C[C@@]1(O)[C@H](NC)[C@@H](O)[C@@H](O[C@@H]2[C@@H](O)[C@H](O[C@H]3O[C@H](CN)CC[C@H]3N)[C@@H](N)C[C@H]2N)OC1.OS(O)(=O)=O>O>[CH3:33][C@@H:34]([NH:64][CH3:65])[C@H:35]1[O:40][C@H:39]([O:41][C@H:42]2[C@H:47]([OH:48])[C@@H:46]([O:49][C@H:50]3[O:55][CH2:54][C@@:53]([OH:57])([CH3:56])[C@H:52]([NH:58][CH3:59])[C@H:51]3[OH:60])[C@H:45]([NH2:61])[CH2:44][C@@H:43]2[NH2:62])[C@H:38]([NH2:63])[CH2:37][CH2:36]1
Reactant: CNC(C)[C@@H]1CC[C@@H](N)[C@@H](O[C@H]2[C@H](O)[C@@H](O[C@H]3OC[C@](C)(O)[C@H](NC)[C@H]3O)[C@H](N)C[C@@H]2N)O1
Agent: CN[C@@H]1[C@@H](O)[C@@H](O[C@@H]2[C@@H](O)[C@H](O[C@H]3O[C@H](C(C)N)CC[C@H]3N)[C@@H](N)C[C@H]2N)OC[C@]1(C)O
Agent: CN[C@@H]1[C@@H](O)[C@@H](O[C@@H]2[C@@H](O)[C@H](O[C@H]3O[C@H](CN)CC[C@H]3N)[C@@H](N)C[C@H]2N)OC[C@]1(C)O
Agent: O=S(=O)(O)O
Solvent: O
Product: CN[C@@H]1[C@@H](O)[C@@H](O[C@@H]2[C@@H](O)[C@H](O[C@H]3O[C@H]([C@@H](C)NC)CC[C@H]3N)[C@@H](N)C[C@H]2N)OC[C@]1(C)O
Temperature: 25 °C
Reaction time: 216 h

Procedure:
Foam wound materials containing gentamicin sulfate were prepared as shown in Example 1. Once materials were prepared they were placed onto grid supports and maintained at room temperature. All were covered with a foil wrap. Every 12 hours for nine days, 5 ml of water was applied onto the foam bandage materials and eluent was collected. Two ml samples containing SDMC entrapped gentamicin were assayed for gentamicin antibiotic activity using standard antimicrobial assays. The results are shown in Table X.
Reaction SMILES: C(N(CC)CC)C.[CH3:8][O:9][C:10]1[CH:11]=[C:12]([CH:14]=[CH:15][CH:16]=1)[NH2:13].[C:17]1([O:23][C:24](Cl)=[S:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>ClCCl>[CH3:8][O:9][C:10]1[CH:11]=[C:12]([NH:13][C:24](=[S:25])[O:23][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:14]=[CH:15][CH:16]=1
Reactant: S=C(Cl)Oc1ccccc1
Reactant: COc1cccc(N)c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1cccc(NC(=S)Oc2ccccc2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 77.4 %

Procedure:
Triethylamine (0.87 g, 8.63 mmol) was added to a solution of 3-methoxyaniline (1 g, 8.63 mmol) dissolved in dichloromethane (20 ml), and thereto phenylchlorothioformate (1.49 g, 8.63 mmol) was added by dropping. The resulting solution was stirred for 2 hours at the room temperature, washed with distilled water, concentrated and purified by column chromatography to give the titled compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([O:11][Si](CC)(CC)CC)[CH2:9]I)=[CH:4][C:3]=1[NH:19][S:20]([CH3:23])(=[O:22])=[O:21].CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:9][O:11]2)=[CH:4][C:3]=1[NH:19][S:20]([CH3:23])(=[O:22])=[O:21]
Reactant: CC[Si](CC)(CC)O[C@@H](CI)c1ccc(Cl)c(NS(C)(=O)=O)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CS(=O)(=O)Nc1cc([C@@H]2CO2)ccc1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 50 %

Procedure:
(R)-N-(2-chloro-5-(2-iodo-1-(triethylsilyloxy)ethyl)phenyl)methanesulfonamide (2.2308 g) was dissolved in dehydrated THF (40 mL), and a 1 mol/L TBAF-THF solution (10 mL; manufactured by Sigma-Aldrich Co.) was added thereto. The mixture was purged with nitrogen, and then was stirred for one hour at room temperature. The reaction solution was poured into brine, and the mixture was extracted with once with ethyl acetate. The organic layer was washed once with water, and then was dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The resulting residue was purified by column chromatography (“COLUMN-B”; n-hexane:ethyl acetate 71:29→50:50), and thus the title compound (0.564 g) was obtained.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([C:18]3[CH:19]=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=3)[N:9]=2)[CH:5]=[CH:4][N:3]=1.[C:28]([NH:32][S:33]([C:36]1[S:37][C:38](B2OC(C)(C)C(C)(C)O2)=[CH:39][CH:40]=1)(=[O:35])=[O:34])([CH3:31])([CH3:30])[CH3:29]>>[C:28]([NH:32][S:33]([C:36]1[S:37][C:38]([C:2]2[CH:7]=[C:6]([C:8]3[N:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([C:18]4[CH:19]=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=4)[N:9]=3)[CH:5]=[CH:4][N:3]=2)=[CH:39][CH:40]=1)(=[O:34])=[O:35])([CH3:31])([CH3:29])[CH3:30]
Reactant: CC(C)(C)NS(=O)(=O)c1ccc(B2OC(C)(C)C(C)(C)O2)s1
Reactant: FC(F)(F)c1ccc(-c2cc(C(F)(F)F)nc(-c3ccnc(Cl)c3)n2)cn1
Product: CC(C)(C)NS(=O)(=O)c1ccc(-c2cc(-c3nc(-c4ccc(C(F)(F)F)nc4)cc(C(F)(F)F)n3)ccn2)s1

Procedure:
5-{4-[4-Trifluoromethyl-6-(6-trifluoromethyl-pyridin-3-yl)-pyrimidin-2-yl]-pyridin-2-yl}-thiophene-2-sulfonic-acid tert-butylamide was prepared from 2-(2-chloro-pyridin-4-yl)-4-trifluoromethyl-6-(6-trifluoromethyl-pyridin-3-yl)-pyrimidine (example B.4) (0.405 g, 1.0 mmol) and N-tert-butyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-thiophene-2-sulfonamide (example C.1) (0.414 g, 1.2 mmol) according to the general procedure III. Obtained as an off-white solid (0.44 g), which was subsequently deprotected.