Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@:13]([CH2:22][CH2:23][CH2:24][OH:25])([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[O:12][C:11]2=[O:26])[CH3:9])=[CH:4][CH:3]=1.[N:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1B(O)O>>[OH:25][CH2:24][CH2:23][CH2:22][C@@:13]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:12][C:11](=[O:26])[N:10]([C@H:8]([C:5]2[CH:6]=[CH:7][C:2]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][N:27]=3)=[CH:3][CH:4]=2)[CH3:9])[CH2:15][CH2:14]1
Reactant: C[C@@H](c1ccc(Br)cc1)N1CC[C@](CCCO)(c2ccccc2)OC1=O
Reactant: OB(O)c1ccccn1
Product: C[C@@H](c1ccc(-c2ccccn2)cc1)N1CC[C@](CCCO)(c2ccccc2)OC1=O

Procedure:
The title compound was prepared from (R)-3-((S)-1-(4-bromophenyl)ethyl)-6-(3-hydroxypropyl)-6-phenyl-1,3-oxazinan-2-one and pyridine-2-boronic acid following procedures analogous to those described in Example 75 Step 1. LC-MS Method 2 tR=1.01 min, m/z=416.21; 1H NMR (CD3OD) 1.30 (m, 1H), 1.55 (d, 3H), 1.62 (m, 1H), 1.94 (m, 2H), 2.20 (m, 1H), 2.32 (m, 1H), 2.48 (m, 1H), 3.09 (m, 1H), 3.44 (m, 2H), 5.57 (m, 1H), 7.03 (d, 2H), 7.29-7.40 (m, 6H), 7.67 (d, 2H), 7.73 (d, 1H), 7.84 (t, 1H), 8.55 (d, 1H).
Reaction SMILES: S(Cl)(Cl)=O.[N+:5]([C:8]1[C:16]([CH3:17])=[CH:15][CH:14]=[CH:13][C:9]=1[C:10]([OH:12])=[O:11])([O-:7])=[O:6].[CH3:18]O>>[N+:5]([C:8]1[C:16]([CH3:17])=[CH:15][CH:14]=[CH:13][C:9]=1[C:10]([O:12][CH3:18])=[O:11])([O-:7])=[O:6]
Reactant: Cc1cccc(C(=O)O)c1[N+](=O)[O-]
Reactant: CO
Solvent: O=S(Cl)Cl
Product: COC(=O)c1cccc(C)c1[N+](=O)[O-]
Temperature: 60 °C

Procedure:
Thionylchloride (253 mL) was added dropwise to 3 1 methanol at 0°-10° C. Toward end of the addition, the temperature was allowed to rise to 20° C. Solid 2-nitro-3-methylbenzoic acid (500 g) was charged in one portion and the reaction mixture was heated to reflux overnight. It was distilled until pot reached 73° C. After cooling to 60° C., 685 mL water was introduced dropwise and the reaction mixture was cooled to 20° C. Upon adding 26 mL water and 125 mL 80% NaOH, the pH was adjusted to 7. The product was collected by filtration and washed with 3×100 mL water and air dried overnight. Yield of methyl 2-nitro-3-methylbenzoate was 503.5 g (93.5%), mp 72° C.
Reaction SMILES: C(N(CC)CC)C.[C:8]1([NH:14][C:15]2[C:16]([NH2:21])=[N:17][CH:18]=[CH:19][CH:20]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[C:22]([O:26][C:27]([NH:29][C@@H:30]([CH3:34])[C:31](O)=[O:32])=[O:28])([CH3:25])([CH3:24])[CH3:23].C1C=NC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:22]([O:26][C:27](=[O:28])[NH:29][C@H:30]([C:31](=[O:32])[NH:21][C:16]1[C:15]([NH:14][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:20][CH:19]=[CH:18][N:17]=1)[CH3:34])([CH3:23])([CH3:24])[CH3:25]
Reactant: Nc1ncccc1Nc1ccccc1
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[C@H](NC(=O)OC(C)(C)C)C(=O)Nc1ncccc1Nc1ccccc1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 119.4 %

Procedure:
Triethylamine (1.5 mL, 11.0 mmol) was added to a mixture of N3-phenylpyridine-2,3-diamine (510 mg, 2.75 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (0.94 g, 4.96 mmol), HOAt (670 mg, 4.96 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.95 g, 4.96 mmol) in anhydrous DCM (30 mL) at 0° C. under a nitrogen atmosphere. The reaction mixture was stirred at 0° C. for 10 min then slowly warmed to RT. Stirring at RT was continued for 18 h. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The aqueous phase was further extracted with DCM (×3) and the combined organic fractions washed with water, dried (Na2SO4) and concentrated in vacuo to afford the title compound as a light brown foam (1.17 g, quantitative). LCMS (Method C): RT 3.04 min [M+H]+ 357.3.
Reaction SMILES: [H-].[Na+].[CH:3]1([N:7]2[CH2:13][CH2:12][C:11]3[CH:14]=[C:15]([OH:18])[CH:16]=[CH:17][C:10]=3[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1.[CH3:19][O:20][C:21]([C:23]1[CH:28]=[N:27][C:26](Cl)=[CH:25][N:24]=1)=[O:22]>CN(C)C=O.ClCCl>[CH3:19][O:20][C:21]([C:23]1[CH:28]=[N:27][C:26]([O:18][C:15]2[CH:16]=[CH:17][C:10]3[CH2:9][CH2:8][N:7]([CH:3]4[CH2:6][CH2:5][CH2:4]4)[CH2:13][CH2:12][C:11]=3[CH:14]=2)=[CH:25][N:24]=1)=[O:22]
Reactant: Oc1ccc2c(c1)CCN(C1CCC1)CC2
Reactant: COC(=O)c1cnc(Cl)cn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COC(=O)c1cnc(Oc2ccc3c(c2)CCN(C2CCC2)CC3)cn1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Sodium hydride (60% disp. in mineral oil, 332 mg, 8.3 mmol) was added to a stirred solution of 3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol (E3) (1.64 g, 7.5 mmol) in dimethyl formamide (4 ml). After 0.5 hours, a solution of 5-chloro-pyrazine-2-carboxylic acid methyl ester (1.95 g, 11.3 mmol) in dimethyl formamide (8 ml) was added and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with dichloromethane and the organic layer was washed with water, brine and dried over magnesium sulfate. The organic layer was filtered, concentrated in vacuo and the resulting residue was purified by column chromatography eluting with a mixture of 0.880 ammonia:ethanol:dichloromethane (1:9:90) to afford the title compound (E122). MS (ES+) m/e 354 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:25])[C:7]=1[NH:8][C:9](=[O:24])[C:10]1[CH:15]=[CH:14][C:13]([S:16][CH3:17])=[C:12]([O:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH:11]=1.C(C1C=C(C)C=C(C(C)(C)C)N=1)(C)(C)C.[Xe](F)[F:42]>ClCCl>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:25])[C:7]=1[NH:8][C:9](=[O:24])[C:10]1[CH:15]=[CH:14][C:13]([S:16][CH2:17][F:42])=[C:12]([O:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH:11]=1
Reactant: CSc1ccc(C(=O)Nc2c(Cl)cncc2Cl)cc1OC1CCCC1
Reactant: F[Xe]F
Agent: Cc1cc(C(C)(C)C)nc(C(C)(C)C)c1
Solvent: ClCCl
Product: O=C(Nc1c(Cl)cncc1Cl)c1ccc(SCF)c(OC2CCCC2)c1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
A solution of N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(methylthio)benzamide (1 g; that is prepared as described in Example 20) in dichloromethane (100 mL), containing molecular sieve 4A, under nitrogen, is treated with 2,6-di-tert-butyl-4-methylpyridine (1.28 g). The resulting mixture is stirred at room temperature for 1.5 hours, and then it is cooled to 0° C. (in an ice/salt bath) and treated with xenon difluoride (0.51 g) in one portion. After stirring for a further 2 hours in the cold, the mixture is filtered, and the filtrate is washed with saturated aqueous ammonium chloride solution. The organic phase is dried over sodium sulfate and evaporated. The resulting residue is subjected to flash chromatography, eluting with a mixture of ethyl acetate and pentane (2:3 v/v), to give impure N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(fluoromethylthio)-benzamide (600 mg). It is further purified by reversed phase HPLC on octadecylsilyl silica gel, eluting with a mixture of methanol and water (7:3 v/v), to give N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(fluoromethylthio)benzamide (519 mg), in the form of a white solid, m.p. 111°-113° C. [Elemental analysis: C,51.50; H,4.12; N,6.74%; calculated: C,52.05; H,4.12; N,6.74%].
Reaction SMILES: C[O:2][C:3]([C:5]1[S:6][C:7]([C:14](=[O:31])[NH:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][Si](C(C)(C)C)(C)C)[CH:18]=2)=[CH:8][C:9]=1[C:10]([F:13])([F:12])[F:11])=[O:4].O.[OH-].[Li+].C1COCC1.Cl>O>[OH:23][C:19]1[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=1)[CH2:16][NH:15][C:14]([C:7]1[S:6][C:5]([C:3]([OH:4])=[O:2])=[C:9]([C:10]([F:13])([F:11])[F:12])[CH:8]=1)=[O:31]
Reactant: COC(=O)c1sc(C(=O)NCc2cccc(O[Si](C)(C)C(C)(C)C)c2)cc1C(F)(F)F
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(NCc1cccc(O)c1)c1cc(C(F)(F)F)c(C(=O)O)s1

Procedure:
A mixture of 5-[3-(tert-Butyl-dimethyl-silanyloxy)-benzylcarbamoyl]-3-trifluoromethyl-thiophene-2-carboxylic acid methyl ester (210 mg, 0.44 mmol), lithium hydroxide monohydrate (370, mg, 8.87 mmol), THF (4 mL) and water (4 mL) was stirred over weekend, acidified with 1N HCl and extracted with EtOAc (×3). The organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and evaporated to give the title compound, 120 mg (79%). MS m/e 346.0 (M+H+).
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[Br:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]Br>CC(C)=O>[Br:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:10][CH:11]=1
Reactant: COC(=O)c1ccc(O)cc1
Reactant: BrCCCCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)c1ccc(OCCCCCCCBr)cc1
Yield: 69.9 %

Procedure:
To a mixture of methyl 4-hydroxybenzoate (1.52 g) and potassium carbonate (0.76 g) in acetone (30 ml) was added dropwise a solution of 1,7-dibromoheptane (3.1 g) in acetone (10 ml) at room temperature with stirring. The mixture was stirred at room temperature for 2.5 hours, and then refluxed for overnight with stirring. The reaction mixture was filtered under reduced pressure and the filtrate was concentrated under reduced pressure to give an oily solid. The oily solid was subjected to column chromatography on silica gel (silica gel 60 F254, Merck: 200 g) and eluted with a mixture of ethyl acetate and n-hexane (1:3). The fractions containing the objective compound were combined and concentrated under reduced pressure to give methyl 4-(7-bromo-n-heptyloxy]benzoate (2.3 g).
Reaction SMILES: I[CH2:2][C:3]([F:6])([F:5])[F:4].[CH2:7]([N:10]1[C:18]2[C:13](=[N:14][C:15]([C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH:30]=[C:29]5[CH2:31][NH:32][CH2:33][C:28]5=[N:27]4)=[CH:22][CH:21]=3)=[C:16]([Cl:19])[CH:17]=2)[N:12]=[C:11]1[O:34][C@H:35]1[C@H:39]2[O:40][CH2:41][C@@H:42]([OH:43])[C@H:38]2[O:37][CH2:36]1)[CH:8]=[CH2:9].C(N(CC)C(C)C)(C)C.FC(F)(F)S(OCC(F)(F)F)(=O)=O>O1CCOCC1>[CH2:7]([N:10]1[C:18]2[C:13](=[N:14][C:15]([C:20]3[CH:21]=[CH:22][C:23]([N:26]4[CH:30]=[C:29]5[CH2:31][N:32]([CH2:2][C:3]([F:6])([F:5])[F:4])[CH2:33][C:28]5=[N:27]4)=[CH:24][CH:25]=3)=[C:16]([Cl:19])[CH:17]=2)[N:12]=[C:11]1[O:34][C@H:35]1[C@H:39]2[O:40][CH2:41][C@@H:42]([OH:43])[C@H:38]2[O:37][CH2:36]1)[CH:8]=[CH2:9]
Reactant: FC(F)(F)CI
Reactant: C=CCn1c(O[C@@H]2CO[C@H]3[C@@H]2OC[C@H]3O)nc2nc(-c3ccc(-n4cc5c(n4)CNC5)cc3)c(Cl)cc21
Agent: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Product: C=CCn1c(O[C@@H]2CO[C@H]3[C@@H]2OC[C@H]3O)nc2nc(-c3ccc(-n4cc5c(n4)CN(CC(F)(F)F)C5)cc3)c(Cl)cc21
Temperature: 80 °C
Reaction time: 48 h

Procedure:
2-iodo-1,1,1-trifluoroethane (12.5 μl, 0.127 mmol) was added to a stirred solution of (3R,3aR,6R,6aR)-6-[1-allyl-6-chloro-5-[4-(5,6-dihydro-4H-pyrrolo[3,4-c]pyrazol-2-yl)phenyl]imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol (59.9 mg, 0.115 mmol) in dioxane (0.46 ml). The reaction mixture was a pale yellow solution that was heated to 80° C. After 2 days, N,N-diisopropylethylamine (40 μl, 0.229 mmol), 2,2,2-trifluoroethyl trifluoromethane-sulfonate (34 μl, 0.236 mmol), and additional dioxane (0.2 ml) were added to the reaction mixture. After stirring an additional 18 hours, the reaction mixture was cooled to room temperature. The reaction mixture was evaporated under reduced pressure to give a dark amber residue. The residue was purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-80% acetonitrile/water+0.05% TFA gradient followed by a 80% acetonitrile/water+0.05% TFA flush. The product fractions were combined and evaporated under reduced pressure to give the desired product as an amber residue. LC-MS: calculated for C28H26ClF3N6O4 602.17 observed m/e: 603.19 (M+H)+ (Rt 1.20/2 min)
Reaction SMILES: CN(C)C1C=CC=CC=1.[C:10]([O:13][CH2:14][C:15]1[N:29]=[C:18]2[N:19]=[C:20]([CH2:24][O:25][C:26](=[O:28])[CH3:27])[CH:21]=[C:22](O)[N:17]2[N:16]=1)(=[O:12])[CH3:11].C(Cl)(Cl)[Cl:31]>P(Cl)(Cl)(Cl)=O>[Cl:31][C:22]1[N:17]2[N:16]=[C:15]([CH2:14][O:13][C:10](=[O:12])[CH3:11])[N:29]=[C:18]2[N:19]=[C:20]([CH2:24][O:25][C:26](=[O:28])[CH3:27])[CH:21]=1
Reactant: ClC(Cl)Cl
Reactant: CC(=O)OCc1cc(O)n2nc(COC(C)=O)nc2n1
Solvent: CN(C)c1ccccc1
Solvent: O=P(Cl)(Cl)Cl
Product: CC(=O)OCc1cc(Cl)n2nc(COC(C)=O)nc2n1
Temperature: 50 °C
Reaction time: 1.5 h

Procedure:
In 300 ml of phosphorus oxychloride was added dropwise 28 ml of N,N-dimethylaniline, and 30.5 g of 2,5-bis(acetoxymethyl)-7-hydroxy-s-triazolo[1,5-a]pyrimidine was added to the mixture and the mixture was stirred at 50° C. for 1.5 hours. An oily residue obtained by removing phosphorus oxychloride was dissolved in 500 ml of chloroform and ice-cooled. After addition of crushed ice and water to the mixture and stirring thereof, a chloroform layer was separated, washed with water and dried over anhydrous magnesium sulfate. Then, the mixture was condensed. This was applied to a silica gel column chromatography (eluent: chloroform) and fractions containing the title compound were condensed to obtain 14 g of the title compound as an oily product.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13]([OH:40])=[C:14]([C:35](OCC)=[O:36])[C:15](=[O:34])[N:16]3[CH2:19][CH2:20][CH2:21][N:22]([CH3:33])[C:23]([O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[O:24])=[N:11][CH:10]=2)=[CH:4][CH:3]=1.[O:41]1[CH2:45][CH2:44][CH2:43][CH:42]1[CH2:46][NH2:47]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13]([OH:40])=[C:14]([C:35]([NH:47][CH2:46][CH:42]4[CH2:43][CH2:44][CH2:45][O:41]4)=[O:36])[C:15](=[O:34])[N:16]3[CH2:19][CH2:20][CH2:21][N:22]([CH3:33])[C:23](=[O:24])[O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[N:11][CH:10]=2)=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2n(CCCN(C)C(=O)OCc2ccccc2)c1=O
Reactant: NCC1CCCO1
Product: CN(CCCn1c(=O)c(C(=O)NCC2CCCO2)c(O)c2ncc(Cc3ccc(F)cc3)cc21)C(=O)OCc1ccccc1

Procedure:
This compound was prepared from ethyl 7-[(4-fluorophenyl)methyl]-4-hydroxy-1-[3-(methyl{[(phenylmethyl)oxy]carbonyl}amino)propyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate and (tetrahydro-2-furanylmethyl)amine using conditions similar to Example 497: ES+ MS: 603 (M+H+).
Reaction SMILES: N[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5](SC2C=CC(S(O)(=O)=O)=CC=2)=[CH:4][C:3]=1OC1C=CC(S(O)(=O)=O)=C(N)C=1.N1C(Cl)=NC(Cl)=NC=1Cl>>[CH:9]1[C:8]2[C:7](=[O:17])[C:6]3[C:15](=[CH:2][CH:3]=[CH:4][CH:5]=3)[C:14](=[O:16])[C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: Nc1cc(Oc2cc(Sc3ccc(S(=O)(=O)O)cc3)c3c(c2N)C(=O)c2ccccc2C3=O)ccc1S(=O)(=O)O
Agent: Clc1nc(Cl)nc(Cl)n1
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
Example 1 was repeated, provided that the compounds shown in 1st, 2nd and 3rd column of the following table were used in place of 1-amino-2-(3'-amino-4'-sulfophenoxy)-4-(4'-sulfophenylthio)anthraquinone, cyanuric chloride and 1-aminobenzene-3-β-sulfatoethylsulfone, respectively, thereby obtaining a corresponding anthraquinone compound. A color shade obtained by dyeing cotton with the compound is as shown in a 4th column of the table.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N+:13]([O-:15])=[O:14])[CH:5]=[C:6]2[C:11]=1[NH:10][C:9](=[O:12])[CH2:8][CH2:7]2.I[CH3:17]>CN(C=O)C.O>[F:1][C:2]1[CH:3]=[C:4]([N+:13]([O-:15])=[O:14])[CH:5]=[C:6]2[C:11]=1[N:10]([CH3:17])[C:9](=[O:12])[CH2:8][CH2:7]2
Reactant: CI
Reactant: O=C1CCc2cc([N+](=O)[O-])cc(F)c2N1
Solvent: O
Solvent: CN(C)C=O
Product: CN1C(=O)CCc2cc([N+](=O)[O-])cc(F)c21
Yield: 88.9 %

Procedure:
8-Fluoro-6-nitro-3,4-dihydro-1H-quinolin-2-one (Step 1, 3.13 g, 0.0149 mol) and iodomethane (1.39 ml, 0.0223 mol) in DMF (25 ml) are stirred at room temperature overnight. The reaction is diluted with water and the resulting precipitate collected by filtration, washed well with water, and dried under vacuum to give the title compound as an orange solid (2.97 g, 89%); 1H NMR (300 MHz, CDCl3) δ 2.56–2.61 (m, 2H), 2.99–3.04 (m, 2H), 3.32 (s, 3H), overlapping 8.06 (s, 1H) and 8.08 (dd, 1H); [M+H]+=225.
Reaction SMILES: C(N(CC)CC)C.Cl.Cl[C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]=[CH:12][C:11]=1[N+:20]([O-:22])=[O:21].[NH2:23][CH2:24][CH2:25][CH2:26][NH:27][C:28](=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>ClCCl>[N+:20]([C:11]1[CH:12]=[N:13][C:14]2[C:19]([C:10]=1[NH:23][CH2:24][CH2:25][CH2:26][NH:27][C:28](=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[CH:18][CH:17]=[CH:16][CH:15]=2)([O-:22])=[O:21]
Reactant: O=[N+]([O-])c1cnc2ccccc2c1Cl
Reactant: NCCCNC(=O)c1ccccc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(NCCCNc1c([N+](=O)[O-])cnc2ccccc12)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 25.6 %

Procedure:
Triethylamine (9.3 mL, 67 mmol) was added to a mixture of 4-chloro-3-nitroquinoline hydrochloride (16.4 g, 67 mmol) and dichloromethane (400 mL). A solution of N-(3-aminopropyl)benzamide (11.9 g, 67 mmol) in dichloromethane (100 mL) was added all a once. The reaction mixture was stirred at ambient temperature for 1 hour and then heated on a steam bath for 1 hour. The resulting precipitate was isolated by filtration to provide 6 g of N1-{3-[(3-nitroquinolin-4-yl)amino]propyl}benzamide as a yellow solid, m.p. 209-211° C. 1H NMR (500 MHz, DMSO-d6) δ 9.07 (broad s, I—H), 9.05 (s, 1H), 8.54 (t, J=6.0 Hz, 1H), 8.51 (d, J=8.0 Hz, 1H), 7.89 (d, J=8.0 Hz, 1H), 7.82 (t, J=8.0 Hz, 1H), 7.76 (d, J=8.0 Hz, 2H), 7.55 (t, J=8.0 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 7.43 (t, J=8.0 Hz, 2H), 3.69 (q, J=6.0 Hz, 2H), 3.35 (q, J=6.0 Hz, 2H), 2.00 (quintet, J=7.0 Hz, 2H).
Reaction SMILES: [C:1]([C:4]1[CH:28]=[CH:27][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16](O)[C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=3)[C:20]([OH:22])=[O:21])=[CH:12][CH:11]=2)=[C:6]([CH3:29])[C:5]=1[OH:30])(=[O:3])[CH3:2].ClCCl.CN(S(F)(F)[F:38])C.Cl>[OH-].[Na+].O1CCCC1>[C:1]([C:4]1[CH:28]=[CH:27][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16]([F:38])[C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=3)[C:20]([OH:22])=[O:21])=[CH:12][CH:11]=2)=[C:6]([CH3:29])[C:5]=1[OH:30])(=[O:3])[CH3:2]
Reactant: CC(=O)c1ccc(OCc2ccc(C(O)c3cccc(C(=O)O)c3)cc2)c(C)c1O
Reactant: CN(C)S(F)(F)F
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: C1CCOC1
Product: CC(=O)c1ccc(OCc2ccc(C(F)c3cccc(C(=O)O)c3)cc2)c(C)c1O
Temperature: -78 °C
Yield: 69.7 %

Procedure:
A suspension of 3-{[4-(4-acetyl-3-hydroxy-2-methyl-phenoxymethyl)-phenyl]-hydroxy-methyl}-benzoic acid (100 mg, 0.246 mmol) and dichloromethane (5 mL) is stirred at −78° C. Dimethylamino sulfur trifluoride (35 μL, 0.271 mmol) is added and the mixture is warmed to room temperature. An additional portion of dimethylamino sulfur trifluoride (35 μL, 0.271 mmol) is added and suspension becomes a solution. The reaction mixture is diluted with aqueous 2N sodium hydroxide (5 mL) and tetrahydrofuran (2 mL) and stirred 10 min. The pH is adjusted to 2 with aqueous 5N hydrochloric acid and extracted with ethyl acetate (2×20 mL). The combined extracts are concentrated and the resulting residue is purified via silica chromatography eluting with hexanes to 1:1 hexanes:ethyl acetate to give the title compound (70 mg, 70%) as a white solid. 1H NMR (DMSO-d6) δ 13.12 (s, 1H), 12.86 (s, 1H), 7.93-7.95 (m, 2H), 7.82 (d, 1H), 7.68 (d, 1H), 7.44-7.59 (m, 5H), 6.75-6.90 (d, 1H), 6.72 (d, 1H), 5.29 (s, 2H), 2.59 (s, 3H), 2.06 (s, 3H). LCMS M−1 407.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1([C:16]([F:19])([F:18])[F:17])[CH2:14][CH2:13][O:12][CH2:11][C:10](=O)[NH:9]1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:29])=CC=1>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1([C:16]([F:19])([F:18])[F:17])[CH2:14][CH2:13][O:12][CH2:11][C:10](=[S:29])[NH:9]1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: O=C1COCCC(c2ccccc2F)(C(F)(F)F)N1
Solvent: C1CCOC1
Product: Fc1ccccc1C1(C(F)(F)F)CCOCC(=S)N1
Temperature: 25 °C
Yield: 180.6 %

Procedure:
To a solution of 5-(2-fluoro-phenyl)-5-trifluoromethyl-[1,4]oxazepan-3-one (1.19 g, 4.29 mmol) in 15 mL THF was added Lawesson's reagent (955 mg, 2.36 mmol). The reaction mixture was stirred at room temperature over night. The mixture was then partitioned between aqueous Na2CO3 solution (2 mol/L) and TBME. The layers were separated, washed with aqueous Na2CO3 solution (2 mol/L), brine and TBME. The combined organic layers were dried over MgSO4.H2O and evaporated. The crude product was purified on a silica gel column by eluting with hexane/EtOAc 95/5->90/10 to give 1.25 g of the title compound as a yellow resin.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:20]=[CH:19][CH:18]=[CH:17][C:12]=2[C:13]([O:15][CH3:16])=[O:14])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1/[CH:29]=[CH:30]/B(O)O>>[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1/[CH:29]=[CH:30]/[C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:20]=[CH:19][CH:18]=[CH:17][C:12]=2[C:13]([O:15][CH3:16])=[O:14])(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: COC(=O)c1ccccc1S(=O)(=O)c1ccc(Br)cc1
Reactant: OB(O)/C=C/c1ccc(F)cc1F
Product: COC(=O)c1ccccc1S(=O)(=O)c1ccc(/C=C/c2ccc(F)cc2F)cc1

Procedure:
The title compound was prepared according to the method described in Example 138, Step 3 using methyl 2-[(4-bromophenyl)sulfonyl]benzoate (Step 1) in place of (1S)-1-[2-({4-bromo-3-methylphenyl}sulfonyl)phenyl]ethanol and [(E)-2-(2,4-difluorophenyl)vinyl]boronic acid (Step 2) in place of [(E)-2-(4-fluorophenyl)vinyl]boronic acid. δH (500 MHz, d6 DMSO): 8.22-8.20 (1H, m), 7.94-7.80 (7H, m), 7.69-7.63 (1H, m), 7.44 (1H, d, J 16.4), 7.39 (1H, d, J 16.4), 7.35-7.30 (1H, m), 7.19-7.15 (1H, m), 3.87 (3H, s). m/z (ES+) 383 [(M-MeO)+].
Reaction SMILES: Br[C:2]1[N:3]=[C:4]([CH3:7])[S:5][CH:6]=1.[CH2:8]([N:12]1[N:16]=[C:15]2[CH:17]=[CH:18][CH:19]=[CH:20][C:14]2=[N:13]1)[CH2:9][C:10]#[CH:11]>>[CH3:7][C:4]1[S:5][CH:6]=[C:2]([C:11]#[C:10][CH2:9][CH2:8][N:12]2[N:13]=[C:14]3[CH:20]=[CH:19][CH:18]=[CH:17][C:15]3=[N:16]2)[N:3]=1
Reactant: C#CCCn1nc2ccccc2n1
Reactant: Cc1nc(Br)cs1
Product: Cc1nc(C#CCCn2nc3ccccc3n2)cs1
Yield: 50.8 %

Procedure:
The title compound was prepared in accordance with the general method of Example 1, from 4-bromo-2-methylthiazole (30 mg, 0.13 mmol) and 2-(but-3-ynyl)-2H-benzo[d][1,2,3]triazole (30 mg, 0.17 mmol, Example 109(D)). Reaction time: 13 hours. The crude residue was purified by flash chromatography (DCM/MeOH 98:2) to yield 18 mg (66 μmol, 50%) of 2-(4-(2-methylthiazol-4-yl)but-3-ynyl)-2H-benzo[d][1,2,3]triazole as a yellow solid.
Reaction SMILES: [C:1]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH:12]1[CH2:16][CH2:15][CH2:14][C:13]1=[O:17])([O:3][CH2:4][CH3:5])=[O:2].[CH3:18][C:19](OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=[O:20].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)(=O)C>[C:19]([O:17][C:13]1[CH2:14][CH2:15][CH2:16][C:12]=1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][C:1]([O:3][CH2:4][CH3:5])=[O:2])(=[O:20])[CH3:18]
Reactant: CCOC(=O)CCCCCCC1CCCC1=O
Reactant: CC(=O)OCc1c2ccccc2c(COC(C)=O)c2ccccc12
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC(=O)O
Solvent: O
Product: CCOC(=O)CCCCCCC1=C(OC(C)=O)CCC1
Reaction time: 16 h

Procedure:
A stirred solution of 100 g. of 2-(6-carbethoxyhexyl)cyclopentan-1-one (Example 9) in 250 ml. of acetic anyhydride containing 0.940 g. of p-toluenesulfonic acid monohydrate is heated to boiling under partial reflux allowing distillate at 118° C. or less (i.e., acetic acid) to escape through a Vigreaux column equipped with a condenser to collect the distillate. After 16 hours, during which period acetic anhydride is added in portions in order to keep the solvent level at at least 100 ml., the solution is cooled and poured cautiously into a stirred cold mixture of saturated sodium bicarbonate solution (400 ml.) and hexane (250 ml.). The resulting mixture is stirred for an additional 30 minutes during which period solid sodium bicarbonate is added periodically to insure a basic solution. The hexane layer is separated and washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness. Distillation of the residual oil gives 102 g. (87%) of pale yellow oil, b.p. 118° C. (0.07 mm).