Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:13]1[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][CH:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].Cl.[NH2:23][C:24]1([C:27]#[N:28])[CH2:26][CH2:25]1>>[C:27]([C:24]1([NH:23][C:17](=[O:19])[C:16]2[CH:15]=[CH:14][C:13]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])=[CH:21][CH:20]=2)[CH2:26][CH2:25]1)#[N:28]
Reactant: CCCCCCCCCCCCc1ccc(C(=O)O)cc1
Reactant: N#CC1(N)CC1
Agent: Cl
Product: CCCCCCCCCCCCc1ccc(C(=O)NC2(C#N)CC2)cc1
Yield: 37.5 %

Procedure:
General procedure G was used to convert 4-dodecylbenzoic acid (0.52 mmols) to the corresponding acyl chloride. After standard work up procedures, the intermediate was immediately subjected to conditions described in general procedure F in the presence of 1-amino-1-cyclopropanecarbonitrile hydrochloride (0.4 mmols). After flash chromatography, 0.15 mmols of the title product was recovered. 1H NMR (500 MHz, CDCl3) δ 7.68 (d, J=7.1, 2H), 7.23 (d, J=7.5, 2H), 6.82 (s, 1H), 2.63 (t, J=7.7, 2H), 1.65-1.57 (m, 4H), 1.35 (t, J=7.0, 2H), 1.29-1.25 (m, 17H), 0.88 (t, J=6.5, 3H). 13C NMR (126 MHz, CDCl3) δ 167.81, 148.06, 130.01, 128.75, 127.19, 120.07, 35.85, 31.89, 31.11, 29.61, 29.53, 29.42, 29.32, 29.20, 22.66, 20.88, 16.97, 14.08.
Reaction SMILES: [CH2:1]([N:3]([C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[C:15]2[S:20](Cl)(=[O:22])=[O:21])[C:4](=[O:9])[C:5]([F:8])([F:7])[F:6])[CH3:2].[NH3:24]>O1CCCC1>[CH2:1]([N:3]([C:10]1[C:11]2[C:16](=[C:15]([S:20](=[O:22])(=[O:21])[NH2:24])[CH:14]=[CH:13][CH:12]=2)[CH:17]=[CH:18][CH:19]=1)[C:4](=[O:9])[C:5]([F:8])([F:7])[F:6])[CH3:2]
Reactant: N
Reactant: CCN(C(=O)C(F)(F)F)c1cccc2c(S(=O)(=O)Cl)cccc12
Solvent: C1CCOC1
Product: CCN(C(=O)C(F)(F)F)c1cccc2c(S(N)(=O)=O)cccc12
Temperature: 0 °C
Reaction time: 3 h

Procedure:
5-(N-ethyl-2,2,2-trifluoroacetamido)naphthalene-1-sulfonyl chloride (100 mg) was dissolved in tetrahydrofuran (1.0 mL), cooled to 0° C., then concentrated ammonia (0.11 mL) was added. The reaction was stirred at 0° C. for 3 hours, then concentrated and partitioned between water and ethyl acetate. The organic layer was dried over Na2SO4, filtered, and concentrated to give the title compound.
Reaction SMILES: C[O:2][C:3](=[O:28])[CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]([CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[C:20]3[C:24]=2[N:23]([CH3:25])[C:22]([CH3:26])=[CH:21]3)[C:7]1=[O:27].O.[OH-].[Li+]>C1COCC1.O>[CH3:25][N:23]1[C:24]2[C:20](=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:15][N:8]2[C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:6]([CH2:5][CH2:4][C:3]([OH:28])=[O:2])[C:7]2=[O:27])[CH:21]=[C:22]1[CH3:26]
Reactant: COC(=O)CCn1c(=O)n(Cc2cccc3cc(C)n(C)c23)c2ccccc21
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Cc1cc2cccc(Cn3c(=O)n(CCC(=O)O)c4ccccc43)c2n1C
Reaction time: 0.5 h
Yield: 74.5 %

Procedure:
To a stirred solution of 3-[3-(1,2-dimethyl-1H-indol-7-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-propionic acid methyl ester (90 mg, 0.24 mmol) in THF (3 ml) and water (0.5 ml) was added lithium hydroxide monohydrate (15 mg, 0.36 mmol). The reaction was stirred for 0.5 h and concentrated to low volume. The remaining residue was diluted with water and acetic acid (0.3 ml). The resulting suspension was stirred at ambient temperature over night. The precipitate was collected via filtration, washed with water and then suspended in 1:1 acetonitrile/water. The solid precipitate was isolated via filtration and dried to give 65 mg (87%) of 3-[3-(1,2-dimethyl-1H-indol-7-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-propionic acid. LCMS (ESMS): m/z 364.41 (M+H).
Reaction SMILES: [CH2:1]([O:8][C:9]1(O)[CH:18]=[C:17]2[C:12]([CH:13]=[C:14]([N+:19]([O-])=O)[CH:15]=[N:16]2)=[CH:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:23].CN(C)C=[O:27]>[Pt]>[ClH:23].[NH2:19][C:14]1[CH:15]=[N:16][C:17]2[C:12]([C:13]=1[OH:27])=[CH:11][CH:10]=[C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH:18]=2
Reactant: CN(C)C=O
Reactant: O=[N+]([O-])c1cnc2c(c1)=CCC(O)(OCc1ccccc1)C=2
Agent: [Pt]
Agent: Cl
Product: Nc1cnc2cc(OCc3ccccc3)ccc2c1O
Reaction time: 8 h

Procedure:
A 1 L glass Parr bottle was charged with 7-benzyloxy-3-nitroquinolin-7-ol, anhydrous N,N-dimethylformamide (DMF, 500 mL) and 5% Pt/C catalyst (5.0 g). The vessel was placed on Parr apparatus, evacuated and charged with hydrogen gas (˜45 psi, 3.1×105 Pa). The reaction mixture was shaken overnight. The reaction mixture was filtered through glass fiber filters to remove catalyst. To the resulting dark colored solution was added concentrated hydrochloric acid (12 N HCl, 14 ml, 168.8 mmol). The product precipitated as the hydrochloride salt. The reaction mixture was stirred over the weekend. A solid was collected by vacuum filtration, washed with diethyl ether (100 mL), and air dried overnight to provide 44 g of 3-amino-7-benzyloxyquinolin-4-ol hydrochloride. This material was carried on without further purification.
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[C:7]([C:12]([F:15])([F:14])[F:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C@@H:16]([NH:27][C:28](=O)OC(C)(C)C)[CH2:17][C:18]2C3C(=CC=CC=3)NC=2)[C:3]=1[C:35]([NH:37][C:38]1[S:39][CH:40]=[CH:41][N:42]=1)=[O:36].FC(F)(F)C(O)=O.FC(F)(F)C([O-])=O>C(Cl)Cl>[OH:1][C:2]1[C:11]2[C:6](=[C:7]([C:12]([F:13])([F:15])[F:14])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C@@H:16]2[CH2:17][CH2:18][CH2:28][NH:27]2)[C:3]=1[C:35]([NH:37][C:38]1[S:39][CH:40]=[CH:41][N:42]=1)=[O:36]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1c[nH]c2ccccc12)c1nc2c(C(F)(F)F)cccc2c(O)c1C(=O)Nc1nccs1
Agent: O=C([O-])C(F)(F)F
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(Nc1nccs1)c1c([C@@H]2CCCN2)nc2c(C(F)(F)F)cccc2c1O
Yield: 150.1 %

Procedure:
Using the procedure of Example 14, 7.8 g of the product of Example 11, 80 ml of methylene chloride, and 40 ml of trifluoroacetic acid were reacted to obtain 8.0 g of 4-hydroxy-2-[(2S) 2-pyrrolidinyl]-N-(2-thiazolyl)-8-trifluoromethyl-3-quinoline carboxamide in the form of its trifluoroacetate melting at 210° C.
Reaction SMILES: BrC1C=CC=C2C=1C(C1C(O)=CC3OCOC=3C=1)[C:5](=[O:16])N2CCCCC.[C:27]1([CH:33]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)[N:34]2[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH:36]([C:43]3[CH:48]=[CH:47][C:46]([O:49][C:50]([F:53])([F:52])[F:51])=[CH:45][C:44]=3[OH:54])[C:35]2=[O:55])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>>[C:27]1([CH:33]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)[N:34]2[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[C:36]([CH2:5][OH:16])([C:43]3[CH:48]=[CH:47][C:46]([O:49][C:50]([F:52])([F:53])[F:51])=[CH:45][C:44]=3[OH:54])[C:35]2=[O:55])[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: O=C1C(c2ccc(OC(F)(F)F)cc2O)c2ccccc2N1C(c1ccccc1)c1ccccc1
Reactant: CCCCCN1C(=O)C(c2cc3c(cc2O)OCO3)c2c(Br)cccc21
Product: O=C1N(C(c2ccccc2)c2ccccc2)c2ccccc2C1(CO)c1ccc(OC(F)(F)F)cc1O

Procedure:
Following the procedure as described in PREPARATION 1E, and making non-critical variations to replace 4-bromo-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1-pentyl-1,3-dihydro-2H-indol-2-one with 1-(diphenylmethyl)-3-[2-hydroxy-4-(trifluoromethoxy)phenyl]-1,3-dihydro-2H-indol-2-one, the title compound was obtained: MS (ES+) m/z 488 (M−17), 528 (M+23).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[C:11]1[NH:12][CH:13]=[CH:14][CH:15]=1.C(S(C1[CH:22]=[CH:23][C:24](OC)=[C:25]([C:27]2[NH:28][CH:29]=CC=2)C=1)(=O)=O)C>>[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[C:11]1[NH:12][C:13]([CH2:29][N:28]2[CH2:27][CH2:25][CH2:24][CH2:23][CH2:22]2)=[CH:14][CH:15]=1
Reactant: CCS(=O)(=O)c1ccc(OC)c(-c2ccc[nH]2)c1
Reactant: COc1cccc(-c2ccc[nH]2)c1OC
Product: COc1cccc(-c2ccc(CN3CCCCC3)[nH]2)c1OC

Procedure:
This compound was prepared by a method analogous to that used to prepare example 2, but using 2-(2,3-dimethoxyphenyl)-1H-pyrrole (prepared according to the method of Kruse et al., [Heterocycles, 26, 3141, 1987] from the corresponding acid chloride) in place of 2-(5-ethylsulphonyl-2-methoxyphenyl)-1H-pyrrole.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:12]2[CH:17]=[CH:16][N:15]=[C:14](F)[CH:13]=2)=[C:5]([C:7]2[O:8][CH:9]=[CH:10][CH:11]=2)[N:6]=1.[OH-:19].[Na+]>Cl>[NH2:1][C:2]1[S:3][C:4]([C:12]2[CH:17]=[CH:16][NH:15][C:14](=[O:19])[CH:13]=2)=[C:5]([C:7]2[O:8][CH:9]=[CH:10][CH:11]=2)[N:6]=1
Reactant: Nc1nc(-c2ccco2)c(-c2ccnc(F)c2)s1
Reactant: [OH-]
Agent: Cl
Agent: [Na+]
Product: Nc1nc(-c2ccco2)c(-c2cc[nH]c(=O)c2)s1
Yield: 51 %

Procedure:
2-Amino-5-(2-fluoropyridin-4-yl)-4-(2-furyl)thiazole (2.00 g, 7.65 mmol) obtained in Step 1 was suspended in 6 mol/L hydrochloric acid (20 mL), followed by stirring under heating and reflux for 1 hour. The reaction mixture was neutralized with aqueous 10 mol/L sodium hydroxide solution added thereto, and the precipitated solid was collected by filtration. The resulting solid was purified through silica gel column chromatography (chloroform:methanol=17:3) to afford the entitled Compound p (1.01 g, 51%) as a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([CH2:28][CH3:29])[C:12]([NH:17][C@@H]2C3C(=CC=CC=3)C[C@@H]2O)=[N:13][C:14]=1[CH2:15][CH3:16].BrC1N=C(CC)C(N[C@@H:40]2[C:48]3[C:43](=[CH:44][CH:45]=[C:46]([O:49][CH3:50])[CH:47]=3)[CH2:42][C@@H:41]2[CH2:51][CH3:52])=NC=1CC>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.COCCOC>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([CH2:28][CH3:29])[C:12]([NH:17][C@@H:40]2[C:48]3[C:43](=[CH:44][CH:45]=[C:46]([O:49][CH3:50])[CH:47]=3)[CH2:42][C@@H:41]2[CH2:51][CH3:52])=[N:13][C:14]=1[CH2:15][CH3:16]
Reactant: CCc1nc(N[C@@H]2c3cc(OC)ccc3C[C@@H]2CC)c(CC)nc1Br
Reactant: CCc1nc(-c2ccc(Cl)cc2Cl)c(CC)nc1N[C@@H]1c2ccccc2C[C@@H]1O
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: COCCOC
Product: CCc1nc(-c2ccc(Cl)cc2Cl)c(CC)nc1N[C@@H]1c2cc(OC)ccc2C[C@@H]1CC

Procedure:
Following the procedure for the preparation of (1R,2S)-1-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol but substituting 5-bromo-3,6-diethyl-N-[(cis)-2-ethyl-6-methoxy-2,3-dihydro-1H-inden-1-yl]pyrazin-2-amine, ethylene glycol dimethyl ether and tetrakis(triphenylphosphine) palladium and making non-critical variations provided the title compound as a oil: 1H NMR (CDCl3) δ 0.97, 1.22, 1.28, 2.52, 2.65, 2.75, 3.04, 3.81, 4.57, 5.87, 6.84, 6.98, 7.18, 7.34, 7.50; HRMS (FAB) calcd for C26H29Cl2N3O+H 470.1766, found 470.1747
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:7]=[CH:8][C:9]2[C:10]([CH:14]=1)=[N:11][Se:12][N:13]=2>S(=O)(=O)(O)O>[Cl:5][C:6]1[CH:7]=[CH:8][C:9]2[C:10]([C:14]=1[N+:1]([O-:4])=[O:2])=[N:11][Se:12][N:13]=2
Reactant: O=[N+]([O-])O
Reactant: Clc1ccc2n[se]nc2c1
Agent: O=S(=O)(O)O
Product: O=[N+]([O-])c1c(Cl)ccc2n[se]nc12
Reaction time: 2 h
Yield: 98.9 %

Procedure:
At 0-5° C., a 65% aqueous solution of HNO3 (6.5 g, 103.5 mmol, 3.3 equiv) was added to a solution of 5-chloro-benzo[1,2,5]selenadiazole (6.82 g, 31.35 mmol; 1H NMR (400 MHz, d6-DMSO): δ=7.96 (d, J=1.4 Hz, 1H), 7.82 (d, J=10.2 Hz, 1H), 7.52 (dd, J=10.2/1.4 Hz, 1H)) in sulfuric acid (95-97%, 100 ml). After 2 hours at 5° C., the reaction mixture was poured onto ice water, and the precipitate was filtered off. The solid was washed with water and dried under high vacuum to afford the title compound (8.14 g, 99%). 1H NMR (400 MHz, d6-DMSO): δ=8.13 (d, J=8.5 Hz, 1H), 7.82 (d, J=8.5 Hz, 1H).
Reaction SMILES: [OH:1][N:2]=[C:3]([NH2:10])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][CH:5]=1.[F:11][C:12]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:13]=1[C:14](O)=O.N>>[F:11][C:12]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:13]=1[C:14]1[O:1][N:2]=[C:3]([C:4]2[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=2)[N:10]=1
Reactant: NC(=NO)c1cccnc1
Reactant: O=C(O)c1ccc(F)cc1F
Agent: N
Product: Fc1ccc(-c2nc(-c3cccnc3)no2)c(F)c1

Procedure:
The title compound was prepared according to the procedure of Example 8 using N′-hydroxynicotinimidamide (Aldrich) and 2,4-difluorobenzoic acid (Aldrich). 1H NMR (300 MHz, CD3OD) δ 7.23-7.36 (m, 2 H), 7.64 (ddd, J=8.1, 5.0, 0.8 Hz, 1 H), 8.35 (td, J=8.5, 6.4 Hz, 1 H), 8.56 (dt, J=7.8, 1.9 Hz, 1 H), 8.74 (dd, J=5.1, 1.7 Hz, 1 H), 9.30 (dd, J=2.2, 0.8 Hz, 1 H) ppm; MS (DCI/NH3) m/z 260 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[O:10][C:9]([C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[NH:13][N:12]=2)=[CH:8][CH:7]=1)=[O:5])[CH3:2].CC(C)([O-])C.[K+].[Cl:26][C:27]1[S:28][C:29]([CH2:32]Cl)=[CH:30][CH:31]=1>CN(C=O)C>[Cl:26][C:27]1[S:28][C:29]([CH2:32][N:13]2[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:11]([C:9]3[O:10][C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:7][CH:8]=3)=[N:12]2)=[CH:30][CH:31]=1
Reactant: ClCc1ccc(Cl)s1
Reactant: CCOC(=O)c1ccc(-c2n[nH]c3ccccc23)o1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccc(-c2nn(Cc3ccc(Cl)s3)c3ccccc23)o1
Temperature: 25 °C
Reaction time: 2 h
Yield: 39.3 %

Procedure:
600 mg (2.3 mmol) of 3-(5-ethoxycarbonyl-2-furyl)indazole together with 265 mg (2.4 mmol) of potassium tert-butoxide were initially charged in 10 ml of DMF, 430 mg (2.6 mmol) of 2-chloro-5-(chloromethyl)thiophene in 1 ml of DMF were added dropwise and the mixture was stirred at RT for 2 h. Customary work-up gave 350 mg (41%) of the title compound. m.p.: 124-126° C.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=O.C[O:12][C:13]1[CH:18]=CC=C[C:14]=1C=CC(=O)C>>[Br:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[CH:14][C:13](=[O:12])[CH3:18]
Reactant: COc1ccccc1C=CC(C)=O
Reactant: O=Cc1ccc(F)cc1Br
Product: CC(=O)C=Cc1ccc(F)cc1Br

Procedure:
The title compound was prepared from 2-bromo-4-fluoro-benzaldehyde (30 g, 148 mmol), following the procedure describing the synthesis of 4-(2-methoxy-phenyl)-but-3-en-2-one (example 1/a stage 1).
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]2[C:17]([CH:18]=1)=[N:16][C:15]1[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=1[C:9]=2[CH3:19])=[O:4].[OH-].[Na+]>C1COCC1.O>[CH3:19][C:9]1[C:10]2[CH2:11][CH2:12][CH2:13][CH2:14][C:15]=2[N:16]=[C:17]2[C:8]=1[CH:7]=[CH:6][C:5]([C:3]([OH:4])=[O:2])=[CH:18]2
Reactant: COC(=O)c1ccc2c(C)c3c(nc2c1)CCCC3
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: Cc1c2c(nc3cc(C(=O)O)ccc13)CCCC2
Temperature: 70 °C
Yield: 259 %

Procedure:
A solution 9-methyl-5,6,7,8-tetrahydro-acridine-3-carboxylic acid methyl ester (120 mg, 0.04mmols) in THF:water (6 mL:4 mL) added solid sodium hydroxide (75 mg, 0.16mmols) and heated the reaction mixture at 70° C. for 3 h. Reaction completion was monitored by TLC. Alter completion, the reaction mixture was diluted with water and washed with ethyl acetate. The aqueous layer was acidified to pH 3-4 using 1.5N hydrochloric acid solution. Precipitated product was filtered and dried to get the pure product as off white solid (25 mg, 22%). Compound was purified by preparative HPLC.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][N:16]3[CH:19]=[CH:20][N:21]=[C:15]3[CH:14]=2)=[O:10])=[CH:4][CH:3]=1.[H-].[Na+].[C:24]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:25]([S:30](Cl)(=[O:32])=[O:31])=[CH:26][CH:27]=[CH:28][CH:29]=1>O1CCCC1>[N:21]1[CH:20]=[CH:19][N:16]2[CH:17]=[CH:18][C:13]([CH2:12][NH:11][C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([NH:1][S:30]([C:25]4[C:24]([C:34]5[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=5)=[CH:29][CH:28]=[CH:27][CH:26]=4)(=[O:32])=[O:31])=[CH:3][CH:4]=3)=[O:10])=[CH:14][C:15]=12
Reactant: O=S(=O)(Cl)c1ccccc1-c1ccccc1
Reactant: Nc1ccc(NC(=O)NCc2ccn3ccnc3c2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C(NCc1ccn2ccnc2c1)Nc1ccc(NS(=O)(=O)c2ccccc2-c2ccccc2)cc1
Reaction time: 0.5 h

Procedure:
In a 4 mL vial was mixed 1-(4-aminophenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea (50 mg, 0.178 mmol) in anhydrous tetrahydrofuran (2 mL). To this mixture at room temperature was added 60% sodium hydride (24.88 mg, 0.622 mmol). The reaction was stirred about 30 minutes and biphenyl-2-sulfonyl chloride (53.9 mg, 0.213 mmol) was added. The reaction mixture stirred overnight at room temperature and was quenched with saturated ammonium chloride and water. The aqueous solution was extracted with dichloromethane and 10% methanol/dichloromethane. The organic layers were combined, concentrated and purified by normal phase chromatography to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.74 (bs, 1H), 8.56 (s, 1H), 8.47 (dd, J=6.9, 0.9 Hz, 1H), 7.95 (dd, J=7.8, 1.4 Hz, 1H), 7.87 (dd, J=1.2, 0.6 Hz, 1H), 7.62 (m, 1H), 7.54 (m, 1H), 7.51 (m, 1H), 7.38 (m, 4H), 7.30-7.20 (m, 5H), 6.82 (m, 3H), 6.66 (t, J=6.0 Hz, 1H), 4.30 (d, J=6.0 Hz, 2H); (ESI(+)) m/e 498 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[CH:14]=O)=[CH:4][CH:3]=1.[C:16]1([CH2:22][CH2:23][NH2:24])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[CH2:14][NH:24][CH2:23][CH2:22][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:4][CH:3]=1
Reactant: NCCc1ccccc1
Reactant: Cc1noc(-c2ccc(Br)cc2)c1C=O
Product: Cc1noc(-c2ccc(Br)cc2)c1CNCCc1ccccc1

Procedure:
Prepared according to the procedure described in Example 24, Step 1, using 5-(4-bromo-phenyl)-3-methyl-isoxazole-4-carbaldehyde and 2-phenylethylamine.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.[O:11]=[C:12]([CH2:18][CH3:19])[CH2:13][C:14]([O:16][CH3:17])=[O:15].CC(C)([O-])C.[Na+]>>[CH3:17][O:16][C:14](=[O:15])[CH:13]([C:6](=[O:7])[C:5]1[CH:9]=[CH:10][C:2]([Br:1])=[CH:3][CH:4]=1)[C:12](=[O:11])[CH2:18][CH3:19]
Reactant: CCC(=O)CC(=O)OC
Reactant: O=C(Cl)c1ccc(Br)cc1
Agent: CC(C)(C)[O-]
Agent: [Na+]
Product: CCC(=O)C(C(=O)OC)C(=O)c1ccc(Br)cc1

Procedure:
Prepared according to the procedure described in Example 1, Step 2 using 4-bromobenzoyl chloride and methyl 3-oxovalerate; sodium tert-butoxide was used in place of pyridine.
Reaction SMILES: N1C=CC=CC=1.[CH2:7]([S:10][C:11]1[N:15]=[CH:14][NH:13][N:12]=1)[C:8]#[CH:9].[CH2:16]([N:18]([CH2:22][CH3:23])[C:19](Cl)=[O:20])[CH3:17]>O>[CH2:16]([N:18]([CH2:22][CH3:23])[C:19]([N:13]1[CH:14]=[N:15][C:11]([S:10][CH2:7][C:8]#[CH:9])=[N:12]1)=[O:20])[CH3:17]
Reactant: CCN(CC)C(=O)Cl
Reactant: C#CCSc1nc[nH]n1
Solvent: c1ccncc1
Solvent: O
Product: C#CCSc1ncn(C(=O)N(CC)CC)n1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To 31.5 ml of pyridine was added 5.56 g of 3-(2-propynylthio)-1H-1,2,4-triazole and then 6.3 ml of diethylcarbamyl chloride. The resulting mixture was stirred under nitrogen at ambient temperature for 3 days and was then poured into 350 ml of cold water with agitation. The precipitate was collected by filtration, washed with water air dried and then dried in oven to give 8.1 g of the title compound as a solid. m.p. 67°-69° C. NMR (CDCl3): 1.3 (t, 6H); 2,21 (t. 1H); 3.62 (m, 4H); 3.88 (d, 2H); 8.78 (s, 1H).
Reaction SMILES: C([O:8][C:9]1[C:18]([CH2:19][CH2:20][CH3:21])=[C:17]2[C:12]([C:13]([C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:14][C:15](=[O:22])[O:16]2)=[CH:11][CH:10]=1)C1C=CC=CC=1.[C:27](OCC)(=O)C>[Pd]>[C:23]([C:13]1[C:12]2[C:17](=[C:18]([CH2:19][CH2:20][CH3:21])[C:9]([OH:8])=[CH:10][CH:11]=2)[O:16][C:15](=[O:22])[C:14]=1[CH3:27])([CH3:26])([CH3:24])[CH3:25]
Reactant: CCOC(C)=O
Reactant: CCCc1c(OCc2ccccc2)ccc2c(C(C)(C)C)cc(=O)oc12
Agent: [Pd]
Product: CCCc1c(O)ccc2c(C(C)(C)C)c(C)c(=O)oc12
Reaction time: 6 h

Procedure:
A solution of 7-benzyloxy-4-tert-butyl-8-propylcoumarin (718 mg) in ethyl acetate (25 mL) was treated with 10% palladium (107 mg) on carbon. The mixture was shaken under a hydrogen atmosphere (40 psi) for six hours. The mixture was filtered through Celite and concentrated to get the title compound.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[O:3][C:4]1[CH:17]=[CH:16][C:7]([CH2:8][O:9][CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1.CCN(C(C)C)C(C)C.[Cl:29][C:30]1[N:35]=[C:34](Cl)[N:33]=[CH:32][N:31]=1>C(O)(C)C>[Cl:29][C:30]1[N:35]=[C:34]([N:13]2[CH2:14][CH2:15][CH:10]([O:9][CH2:8][C:7]3[CH:16]=[CH:17][C:4]([O:3][C:2]([F:18])([F:1])[F:19])=[CH:5][CH:6]=3)[CH2:11][CH2:12]2)[N:33]=[CH:32][N:31]=1
Reactant: Clc1ncnc(Cl)n1
Reactant: FC(F)(F)Oc1ccc(COC2CCNCC2)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: FC(F)(F)Oc1ccc(COC2CCN(c3ncnc(Cl)n3)CC2)cc1
Temperature: 80 °C
Yield: 25.7 %

Procedure:
To a solution of 4-(4-(trifluoromethoxy)benzyloxy)piperidine (2.2 g, 8.00 mmol) in isopropanol (25 mL, 3 mL/mmol) was added DIPEA (3.6 mL, 0.02 mol) and 2,4-dichloro-1,3,5-triazine (1.2 g, 8.00 mmol) and the reaction was heated at 80° C. for 2 h. The reaction mixture was concentrated under reduced pressure and extracted with EtOAc (2×40 mL). The organic extracts were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. Purification by silica gel column chromatography provided 2-chloro-4-(4-((4-(trifluoromethoxy)benzyl)oxy)piperidin-1-yl)-1,3,5-triazine (800 mg, 57%) as a solid. Observed mass (M+1): 389.0.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([C:14]([OH:16])=O)[CH:11]=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:17][C:18]([CH2:23][CH3:24])([CH2:21][CH3:22])[CH2:19][OH:20]>>[CH2:21]([C:18]([NH:17][C:14]([C:12]1[CH:11]=[CH:10][CH:9]=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[N:13]=1)=[O:16])([CH2:19][OH:20])[CH2:23][CH3:24])[CH3:22]
Reactant: CCC(N)(CC)CO
Reactant: O=C(O)c1cccc(-c2cccc(Cl)c2)n1
Product: CCC(CC)(CO)NC(=O)c1cccc(-c2cccc(Cl)c2)n1

Procedure:
The title compound was synthesized in analogy to Example 1, using 6-(3-chlorophenyl)-2-pyridinecarboxylic acid (CAN 863704-38-5) and 2-amino-2-ethyl-1-butanol (CAN 19792-52-0) as starting materials, MS (LC/MS): 333.1 (M+H).
Reaction SMILES: [CH3:1][CH:2]([CH2:5][CH:6]([CH3:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH2:3]O.S(Cl)([Cl:16])=O>>[CH3:1][CH:2]([CH2:5][CH:6]([CH3:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH2:3][Cl:16]
Reactant: O=S(Cl)Cl
Reactant: CC(CO)CC(C)c1ccccc1
Product: CC(CCl)CC(C)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 62.1 %

Procedure:
219 g of 2,4-dimethyl-4-phenyl-butan-1-ol are added dropwise to 161 g of thionyl chloride, the mixture is stirred overnight at room temperature and then for 2 hours at 140° C., and the crude product is distilled to give 150 g of 2,4-dimethyl-4-phenylbutyl chloride of boiling point 84°-86° C./0.1 mm.
Reaction SMILES: [C:1]([C:4]([C@@H:6]([C@:8]([C:22](=[O:24])[CH3:23])([C@@:10]([C:19](=[O:21])[CH3:20])([C@@H:12]([CH:14]([C:16](=[O:18])[CH3:17])[OH:15])[OH:13])[OH:11])[OH:9])[OH:7])=[O:5])(=[O:3])[CH3:2].N1C=CC=CC=1.[N:31]([CH2:34][CH2:35][CH2:36][C:37](Cl)=[O:38])=[N+:32]=[N-:33].C([O-])(O)=O.[Na+]>C(Cl)Cl>[N:31]([CH2:34][CH2:35][CH2:36][C:37]([C@:12]([C@:10]([C:19](=[O:21])[CH3:20])([C@@:8]([C:22](=[O:24])[CH3:23])([C@@H:6]([CH:4]([C:1](=[O:3])[CH3:2])[OH:5])[OH:7])[OH:9])[OH:11])([OH:13])[C:14]([C:16](=[O:18])[CH3:17])=[O:15])=[O:38])=[N+:32]=[N-:33]
Reactant: [N-]=[N+]=NCCCC(=O)Cl
Reactant: CC(=O)C(=O)[C@H](O)[C@](O)(C(C)=O)[C@@](O)(C(C)=O)[C@H](O)C(O)C(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(=O)C(=O)[C@@](O)(C(=O)CCCN=[N+]=[N-])[C@](O)(C(C)=O)[C@@](O)(C(C)=O)[C@H](O)C(O)C(C)=O

Procedure:
1,3,4,6 tetraacetyl D-glucose (W. E. Dick, Carbohyd. Res., 21, 255-268 (1972)) is dissolved in CH2Cl2 to make a 0.1M solution. 6 eqivalents of pyridine and 3 equivalents of 4-azidobutyryl chloride (S. Kusumoto et. al., Bull. Chem. Soc. Jpn., 59, 1289-1298 (1986)) are added. After several hours, the reaction is poured into saturated NaHCO3, extracted with CH2Cl2, dried over Na2SO4, and concentrated. The residue is purified by flash chromatography to give the title compound.