Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[OH:11])([CH2:3][CH3:4])[CH3:2].CCN(CC)CC.[CH3:19][NH:20][C:21](=S)[OH:22]>C(#N)C>[CH3:19][NH:20][C:21](=[O:22])[O:11][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=1[CH:1]([CH2:3][CH3:4])[CH3:2]
Reactant: CNC(O)=S
Reactant: CCC(C)c1ccccc1O
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCC(C)c1ccccc1OC(=O)NC
Reaction time: 30 h

Procedure:
To a solution of 2-Sec. butylphenol (1.5 g, 0.01 mole) 0.2 ml of Et3N was added under stirring. S-methyl ester of N-methylcarbamothioic acid (1.05 g, 0.01 mole) in acetonitrile (10 ml) was added dropwise over a period of 4 hrs, keeping reflux temperature. After 30 hr, acetonitrile was evaporated under vacuum. The residue was taken in dichloromethane (25 ml), washed with water and a 5% cold NaOH solution, followed by water and brine and dried over sodium sulphate. After removal of the solvent, the liquid residue obtained was further purified by distillation to give 2-Sec. butylphenyl N-methylcarbamate of the formula VI; IR: 3329 (N-H), 1730 (-COO), 1535, 1490 and 750 (aromatic); PMR (CdCl3, 90 MHz): 0.81 (3H, 1, primary methyl of side chain), 1.18 (3H, d, J=7Hz, secondary/methyl of side chain), 1.58 (2H, m, methylene protons of side chain), 2.88 (4H, doublet overlapping a multiplet, NH- CH3 and benzylic proton), 4.97 (1H, br s, N H) and 6.95 to 7.25 (4H, m, aromatic).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:9])[CH2:5][C:6]([OH:8])=O)[CH3:2].C([Li])CCC.[CH3:15][N:16]([CH3:30])[C:17]1[C:25]([F:26])=[C:24]([F:27])[C:23]([F:28])=[C:22]([F:29])[C:18]=1C(Cl)=O.C(O[Li])(=O)CC(O[Li])=O.Cl>C1COCC1.O>[CH3:15][N:16]([CH3:30])[C:17]1[C:25]([F:26])=[C:24]([F:27])[C:23]([F:28])=[C:22]([F:29])[C:18]=1[C:6](=[O:8])[CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:9]
Reactant: CN(C)c1c(F)c(F)c(F)c(F)c1C(=O)Cl
Reactant: CCOC(=O)CC(=O)O
Agent: Cl
Agent: [Li]CCCC
Agent: [Li]OC(=O)CC(=O)O[Li]
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)CC(=O)c1c(F)c(F)c(F)c(F)c1N(C)C
Temperature: -78 °C
Reaction time: 1.75 h

Procedure:
To a solution of 4.76 g (36 mmol) of malonic acid monoethyl ester and 75 ml of THF at -35° C. was added 25 ml (40 mmol) of 1.5N n-butyl lithium solution. The remaining 25 ml (40 mmol) of 1.5N butyllithium solution was added at 0° . After cooling to -78° C., a solution of the 4.8 g of 2-(dimethyl- amino)-3,4,5,6-tetrafluorobenzoyl chloride in 50 ml of THF was added to the dilithio malonate over a 15 minute period. The reaction mixture was stirred for 1.75 hours while the temperature came up to -30° C. The reaction mixture was poured into ice, water, and 50 ml of 1N HCl. The mixture was extracted with ether and the ether extract was washed with H2O, 5% NaHCO3, and HCl. After drying over MgSO4 the ether solution was concentrated to 4.4 g of oil product. NMR spectra indicated the desired product.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[Cl:26])[N:18]=[C:17]([C:27]([F:30])([F:29])[F:28])[CH:16]=2)[CH:12]=[CH:13][CH:14]=1)C1C=CC=CC=1.[H][H]>CO.[Pd]>[Cl:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[N:19]1[C:15]([C:11]2[CH:10]=[C:9]([OH:8])[CH:14]=[CH:13][CH:12]=2)=[CH:16][C:17]([C:27]([F:30])([F:28])[F:29])=[N:18]1
Reactant: [H][H]
Reactant: FC(F)(F)c1cc(-c2cccc(OCc3ccccc3)c2)n(-c2ccccc2Cl)n1
Agent: [Pd]
Solvent: CO
Product: Oc1cccc(-c2cc(C(F)(F)F)nn2-c2ccccc2Cl)c1

Procedure:
To a solution of 5-(3-(benzyloxy)phenyl)-1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole in MeOH (100 mL) was added 10% palladium on carbon (1.04 g). The black suspension was shaken on the Pair hydrogenator at 40-50 psi hydrogen pressure for 5 hours. At this time the reaction was incomplete as evidenced by HPLC analysis. The reaction suspension was treated with additional Pd/C and shaken under 60 psi hydrogen pressure for an additional 16 hours. At this time HPLC showed no remaining starting 5-(3-(benzyloxy)phenyl)-1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole. The reaction mixture was filtered through a pad of Celite that was then washed thoroughly with MeOH. The filtrate was concentrated under reduced pressure to afford 3-(1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)phenol as a brittle foam. This material was pure enough for use in subsequent transformations. MS(ES): 339 [M+H]+.
Reaction SMILES: C(C1C(O)=C(NC(C2C=CC3OC(COCC4C=CC=CC=4)=CC=3C=2)=O)C=CC=1)(=O)C.C(OCC)(=O)C(OCC)=O.[CH2:42]([O:49][CH2:50][C:51]1[O:52][C:53]2[CH:59]=[CH:58][C:57]([C:60]([NH:62][C:63]3[C:72]4[O:71][C:70]([C:73]([O:75]CC)=[O:74])=[CH:69][C:68](=[O:78])[C:67]=4[CH:66]=[CH:65][CH:64]=3)=[O:61])=[CH:56][C:54]=2[CH:55]=1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>>[CH2:42]([O:49][CH2:50][C:51]1[O:52][C:53]2[CH:59]=[CH:58][C:57]([C:60]([NH:62][C:63]3[C:72]4[O:71][C:70]([C:73]([OH:75])=[O:74])=[CH:69][C:68](=[O:78])[C:67]=4[CH:66]=[CH:65][CH:64]=3)=[O:61])=[CH:56][C:54]=2[CH:55]=1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1
Reactant: CCOC(=O)c1cc(=O)c2cccc(NC(=O)c3ccc4oc(COCc5ccccc5)cc4c3)c2o1
Agent: CC(=O)c1cccc(NC(=O)c2ccc3oc(COCc4ccccc4)cc3c2)c1O
Solvent: CCOC(=O)C(=O)OCC
Product: O=C(Nc1cccc2c(=O)cc(C(=O)O)oc12)c1ccc2oc(COCc3ccccc3)cc2c1

Procedure:
Following the process described in example 1 (point A), starting from N-(3-acetyl-2-hydroxyphenyl)-2-(benzyloxymethyl)benzofuran-5-carboxamide and diethyl oxalate, ethyl 8-[2-(benzyloxymethyl)benzofuran-5-carboxamido]-4-oxo-4H-1-benzopyran-2-carboxylate was prepared which was subsequently hydrolysed according to the process described in example 1 (point M) to yield the title compound as a white solid with melting point 215-218° C. (65% global yield).
Reaction SMILES: [C:1]([CH2:3][C:4]([N:6]([CH:17]([CH3:19])[CH3:18])[C:7]1[CH:16]=[CH:15][C:10]2[N:11]=[C:12]([SH:14])[S:13][C:9]=2[CH:8]=1)=[O:5])#[N:2].[CH2:20]([NH:22][S:23]([C:26]1[CH:31]=[CH:30][C:29]([CH:32]=O)=[CH:28][CH:27]=1)(=[O:25])=[O:24])[CH3:21].N1CCCCC1>C(O)C>[C:1]([C:3](=[CH:32][C:29]1[CH:28]=[CH:27][C:26]([S:23](=[O:25])(=[O:24])[NH:22][CH2:20][CH3:21])=[CH:31][CH:30]=1)[C:4]([N:6]([CH:17]([CH3:19])[CH3:18])[C:7]1[CH:16]=[CH:15][C:10]2[N:11]=[C:12]([SH:14])[S:13][C:9]=2[CH:8]=1)=[O:5])#[N:2]
Reactant: CC(C)N(C(=O)CC#N)c1ccc2nc(S)sc2c1
Reactant: CCNS(=O)(=O)c1ccc(C=O)cc1
Solvent: CCO
Solvent: C1CCNCC1
Product: CCNS(=O)(=O)c1ccc(C=C(C#N)C(=O)N(c2ccc3nc(S)sc3c2)C(C)C)cc1
Temperature: 80 °C
Reaction time: 1.5 h

Procedure:
α-cyano-N-isopropyl-N-(2-mercaptobenzothiazol-6-yl)acetamide (71 mg, 0.244 mmol) and N-ethyl-4-formylbenzenesulfonamide (52 mg, 0.244 mmol) were combined in absolute ethanol (1 ml). The mixture was stirred 15 minutes with activated 4A molecular sieves in a sealed vessel. Piperidine (27 μL, 0.268 mmol) was added and the mixture was heated to 80° C. After 1.5 hours, the solution was concentrated in vacuo and purified by preparative TLC (50% ethyl acetate, 50% hexanes) to yield 19 mg (16%). 1H NMR(CDCl3) δ=1.08 (t, 3H), 1.20 (m, 6H), 2.99 (t, 2H), 4.98 (m, 1H), 5.41 (m, 1H), 7.17 (d, 1H), 7.32 (m, 3H), 7.81 (d, 2H), 7.88 (d, 2H), 7.96 (s, 1H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:7]2[CH2:16][CH2:17][CH2:18]O.[I:20]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CN=C1.C([O-])(O)=O.[Na+]>ClCCl>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:7]2[CH2:16][CH2:17][CH2:18][I:20]
Reactant: II
Reactant: CCOC(=O)c1[nH]c2c(Br)cccc2c1CCCO
Agent: O=C([O-])O
Agent: [Na+]
Agent: c1c[nH]cn1
Solvent: ClCCl
Product: CCOC(=O)c1[nH]c2c(Br)cccc2c1CCCI
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a mixture of EXAMPLE 1B (1.116 g) in dichloromethane (30 mL) at 0° C. was added iodine (1.01 g), triphenyl phosphine (1.03 g) and imidazole (0.535 g). The mixture was stirred at 0° C. for 1 hour and treated with saturated NaHCO3 (50 mL). Stirring was continued for 30 minutes, and the organic layer was washed with a saturated aqueous Na2S2O3 (50 mL), water (20 mL), and brine (50 mL) and dried (Na2SO4), filtered and concentrated. The concentrate was purified by column chromatography on silica gel (with 0-20% ethyl acetate in hexanes.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][C:11]2=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH2:15]([NH2:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C([BH3-])#N.[Na+]>C(O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][CH:11]2[NH:22][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: NCc1ccccc1
Reactant: O=C1CCCc2ccc([N+](=O)[O-])cc21
Agent: [Ti+4]
Agent: CC(C)[O-]
Agent: [BH3-]C#N
Solvent: CCO
Product: O=[N+]([O-])c1ccc2c(c1)C(NCc1ccccc1)CCC2
Reaction time: 1 h

Procedure:
7-Nitro-1-tetralone (2.0 g, 10.5 mmol), benzylamine (1.2 ml, 10.5 mmol) and titanium isopropoxide (3.9 ml, 13.1 mmol) were combined and stirred for 1 hr. The mixture was diluted with absolute ethanol (12 ml), treated with sodium cyanoborohydride (0.44 g, 7.0 mmol) and allowed to stir for 20 hr. The solids were filtered and washed with ethanol. The ethanol was concentrated and the remaining oil used immediately in the next reaction: M.S. (M+H)+ =283.
Reaction SMILES: C[O:2][CH:3]=[CH:4][CH:5]1[CH2:10][CH2:9][CH2:8][O:7][CH2:6]1.Cl>C1COCC1.O>[O:7]1[CH2:8][CH2:9][CH2:10][CH:5]([CH2:4][CH:3]=[O:2])[CH2:6]1
Reactant: COC=CC1CCCOC1
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Product: O=CCC1CCCOC1

Procedure:
To a stirring solution of 3-[2-(methoxy)ethenyl]tetrahydro-2H-pyran (2.22 gm) in THF (15 ml) was added 2N hydrochloric acid (15 ml). After 1 h the mixture was diluted with water and extracted three times with ether. The combined extracts were washed with brine, dried (Na2SO4) and evaporated to give the title product as a pale yellow oil, yield 1.79 g.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].CSSC.[Cl:9][C:10]1[N:11]=[C:12]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:13]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26]C)=[C:22]([CH3:28])[CH:21]=2)[C:14]=1[CH2:15][C:16]([OH:18])=[O:17]>ClCCl>[Cl:9][C:10]1[N:11]=[C:12]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:13]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([OH:26])=[C:22]([CH3:28])[CH:21]=2)[C:14]=1[CH2:15][C:16]([OH:18])=[O:17]
Reactant: COc1ccc(Cn2c(-c3ccccc3)nc(Cl)c2CC(=O)O)cc1C
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: CSSC
Product: Cc1cc(Cn2c(-c3ccccc3)nc(Cl)c2CC(=O)O)ccc1O
Temperature: 25 °C
Reaction time: 3 h
Yield: 75.6 %

Procedure:
Aluminum chloride (1.2 g) and 0.8 ml of dimethyl disulfide were dissolved in 20 ml of dichloromethane, then 1.1 g of 4-chloro-1-(4-methoxy-3-methylbenzyl)-2-phenylimidazole-5-acetic acid was added, and the mixture was stirred at room temperature. During this procedure, the material dissolved once and then a precipitate separated out. After the mixture was allowed to stand at room temperature for 3 hours, the supernatant was discarded and the precipitate was further treated in accordance with the procedure of Example 8 to give 0.8 g of 4-chloro-1-(4-hydroxy-3-methylbenzyl)-2-phenylimidazole-5-acetic acid as colorless scales, m.p. 190°-192° C. (decompn.).
Reaction SMILES: [CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]>Cl[Ru](=CC1C=CC=CC=1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)Cl.CCCCCC>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH:7]=[CH:8][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: C=CCCCCCC
Agent: Cl[Ru](Cl)(=Cc1ccccc1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1
Solvent: CCCCCC
Product: CCCCCCC=CCCCCCC
Reaction time: 15 h
Yield: 79.3 %

Procedure:
A mixture of 1-octene (7.15 g, 64 mmol) and Grubbs' catalyst (0.030 g, 0.04 mmol, 0.0006 equ) was stirred under a static vacuum for 15 hours, then passed through a plug of silica eluting with hexane. Concentration gave tetradec-7-ene (4.982 g, 80%) as a colourless liquid.
Reaction SMILES: [SH2:1].[Na].[CH2:3]([C:8]([C:10]1[CH:15]=[CH:14][C:13](Cl)=[CH:12][CH:11]=1)=[O:9])[C:4]([CH3:7])([CH3:6])[CH3:5]>CN1CCCC1=O>[CH2:3]([C:8]([C:10]1[CH:15]=[CH:14][C:13]([SH:1])=[CH:12][CH:11]=1)=[O:9])[C:4]([CH3:7])([CH3:6])[CH3:5]
Reactant: S
Reactant: CC(C)(C)CC(=O)c1ccc(Cl)cc1
Agent: [Na]
Solvent: CN1CCCC1=O
Product: CC(C)(C)CC(=O)c1ccc(S)cc1
Temperature: 140 °C

Procedure:
18.5 g (0.2 mol) of sodium hydrogen sulphide (NaSH·H2O) in 100 ml of N-methylpyrrolidone are introduced and the water is removed by partial distillation with xylene. The mixture is cooled to 140° C., 21.05 g (0.1 mol) of 4-(neopentylcarbonyl)-chlorobenzene are added, and the mixture is further reacted at 160° C. for 3 hours and worked up as described in Example I-1 to give 14 g (70% of theory) of the desired product of boiling point: 110°-115° C./0.1 mbar.
Reaction SMILES: C([O:3][C:4](=[O:43])[CH2:5][N:6]([C:16]([C:18]1[N:19]([CH2:31][C:32]2[CH:36]=[C:35]([C:37]3[S:38][C:39]([Cl:42])=[CH:40][CH:41]=3)[O:34][N:33]=2)[C:20]2[C:25]([CH:26]=1)=[C:24]([C:27]([F:30])([F:29])[F:28])[CH:23]=[CH:22][CH:21]=2)=[O:17])[CH:7]1[CH2:12][CH2:11][N:10]([CH:13]([CH3:15])[CH3:14])[CH2:9][CH2:8]1)C.C(OC(=O)CN(C(C1N(CC2C=C(C3SC(Cl)=CC=3)ON=2)C2C(C=1)=CC=CC=2C)=O)C1CCN(C(C)C)CC1)C>>[Cl:42][C:39]1[S:38][C:37]([C:35]2[O:34][N:33]=[C:32]([CH2:31][N:19]3[C:20]4[C:25](=[C:24]([C:27]([F:30])([F:28])[F:29])[CH:23]=[CH:22][CH:21]=4)[CH:26]=[C:18]3[C:16]([N:6]([CH2:5][C:4]([OH:43])=[O:3])[CH:7]3[CH2:8][CH2:9][N:10]([CH:13]([CH3:15])[CH3:14])[CH2:11][CH2:12]3)=[O:17])[CH:36]=2)=[CH:41][CH:40]=1
Reactant: CCOC(=O)CN(C(=O)c1cc2c(C(F)(F)F)cccc2n1Cc1cc(-c2ccc(Cl)s2)on1)C1CCN(C(C)C)CC1
Agent: CCOC(=O)CN(C(=O)c1cc2cccc(C)c2n1Cc1cc(-c2ccc(Cl)s2)on1)C1CCN(C(C)C)CC1
Product: CC(C)N1CCC(N(CC(=O)O)C(=O)c2cc3c(C(F)(F)F)cccc3n2Cc2cc(-c3ccc(Cl)s3)on2)CC1

Procedure:
The title compound was prepared analogously to example 185 with the difference that [{1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-trifluoromethyl-1H-indole-2-carbonyl}-(1-isopropyl-piperidin-4-yl)-amino]-acetic acid ethyl ester was used instead [{1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-7-methyl-1H-indole-2-carbonyl}-(1-isopropyl-piperidin-4-yl)-amino]-acetic acid ethyl ester. MS (ESI+): m/e=609, chloro pattern.
Reaction SMILES: [BH4-].[Na+].C[O:4][C:5]([CH2:7][C:8]1[O:12][N:11]=[C:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[C:9]=1[C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1)=O.Cl>CO>[OH:4][CH2:5][CH2:7][C:8]1[O:12][N:11]=[C:10]([C:13]2[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)[C:9]=1[C:21]1[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=1
Reactant: COC(=O)Cc1onc(-c2ccc(OC)cc2)c1-c1ccc(OC)cc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COc1ccc(-c2noc(CCO)c2-c2ccc(OC)cc2)cc1
Reaction time: 1 h
Yield: 97.7 %

Procedure:
A 5.9 g of sodium borohydride was added to a suspension of 5 g of 5-methoxycarbonylmethyl-3,4-bis(4-methoxyphenyl)isoxazole in 20 ml of methanol, and the resulting mixture was stirred for 1 hour with ice cooling. The reaction mixture was made acidic by portionwise addition of 1N hydrochloric acid and then extracted with 80 ml of ethyl acetate. The organic layer was washed with 20 ml of 1N hydrochloric acid and 20 ml of water in that order, subsequently dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 4.5 g (yield 98%) of 5-(2-hydroxyethyl)-3,4-bis(4-methoxyphenyl)isoxazole.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]2[CH:17]=[N:16][CH:15]=[CH:14][N:13]=2)[N:3]=1.[C:18]([C:21]1[CH:22]=[CH:23][C:24]([O:28][CH3:29])=[C:25]([CH:27]=1)[NH2:26])([OH:20])=[O:19]>>[C:18]([C:21]1[CH:22]=[CH:23][C:24]([O:28][CH3:29])=[C:25]([CH:27]=1)[NH:26][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]2[CH:17]=[N:16][CH:15]=[CH:14][N:13]=2)[N:3]=1)([OH:20])=[O:19]
Reactant: COc1ccc(C(=O)O)cc1N
Reactant: FC(F)(F)c1cc(Cl)nc(-c2cnccn2)n1
Product: COc1ccc(C(=O)O)cc1Nc1cc(C(F)(F)F)nc(-c2cnccn2)n1

Procedure:
The title compound was prepared from 4-chloro-2-(2-pyrazinyl)-6-trifluoromethylpyrimidine (40 mg, 0.154 mmol) and 5-carboxy-2-methoxyaniline (38 mg, 0.231 mmol), similar to Example 180 and was isolated as an off white solid (20 mg, 33%). 1H NMR (CDCl3): 9.99 (brs, 1H), 9.660 (d, J=1.5 Hz, 1H), 8.86 (m, 3H), 7.80 (d, 2H), 7.2 (m, 2H), 3.94 (s, 3H).
Reaction SMILES: [CH2:1]([O:19][C:20]1[O:24][C:23]([C:25]([OH:27])=O)=[CH:22][CH:21]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH2:28](OC1OC(C(O)=O)=CC=1)CCCCCCCCCCCCC>>[CH2:1]([O:19][C:20]1[O:24][C:23]([C:25]([CH3:28])=[O:27])=[CH:22][CH:21]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCC/C=C\CCCCCCCCOc1ccc(C(=O)O)o1
Reactant: CCCCCCCCCCCCCCOc1ccc(C(=O)O)o1
Product: CCCCCCCC/C=C\CCCCCCCCOc1ccc(C(C)=O)o1

Procedure:
When in the procedure of Example 1(B) an appropriate amount of 5-(cis-9-octadecen-1-yloxy)-2-furoic acid is substituted for 5-(tetradecyloxy)-2-furoic acid, methyl 5-(cis-9-octadecen-1-yloxy)-2-furyl ketone is obtained.
Reaction SMILES: Br[CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][C@@H:21]([CH3:35])[C@@H:22]([CH3:34])[CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH3:33])[CH:25]=2)=[CH:16][C:15]=1[O:36][CH3:37].C(=O)([O-])[O-].[K+].[K+].[N+:44]([C:47]1[NH:48][CH:49]=[CH:50][N:51]=1)([O-:46])=[O:45]>>[CH3:33][O:32][C:26]1[CH:25]=[C:24]([CH2:23][C@H:22]([CH3:34])[C@H:21]([CH3:35])[CH2:20][C:17]2[CH:18]=[CH:19][C:14]([O:13][CH2:12][CH2:11][O:10][CH2:9][CH2:8][O:7][CH2:6][CH2:5][O:4][CH2:3][CH2:2][N:48]3[CH:49]=[CH:50][N:51]=[C:47]3[N+:44]([O-:46])=[O:45])=[C:15]([O:36][CH3:37])[CH:16]=2)[CH:29]=[CH:28][C:27]=1[O:30][CH3:31]
Reactant: COc1ccc(C[C@H](C)[C@H](C)Cc2ccc(OCCOCCOCCOCCBr)c(OC)c2)cc1OC
Reactant: O=[N+]([O-])c1ncc[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COc1ccc(C[C@H](C)[C@H](C)Cc2ccc(OCCOCCOCCOCCn3ccnc3[N+](=O)[O-])c(OC)c2)cc1OC
Yield: 83.3 %

Procedure:
The Standard Procedure 2 was followed by use of 9b (36.6 mg, 0.0627 mmol, 1.0 equiv), potassium carbonate (18.0 mg, 0.130 mmol, 2.1 equiv), and 2-nitroimidazole (6b, 14.4 mg, 0.126 mmol, 2.0 equiv). After workup and purification with column chromatography (80% EtOAc in hexanes as eluant), 10d (32.1 mg, 0.0522 mmol) was obtained in 83% yield as a yellow gummy oil: 1H NMR (CDCl3, 400 MHz) δ 0.81 (d, J=6.4 Hz, 3H, CH3), 0.82 (d, J=6.4 Hz, 3H, CH3), 1.73 (m, 2H, 2×CH), 2.25-2.31 (m, 2H, 2×ArCH), 2.73-2.75 (m, 2H, 2×ArCH), 3.57-3.86 (m, 21H, 3×OCH3+6×OCH2), 4.12 (t, J=5.0 Hz, 2H, CH2N), 4.56 (t, J=4.8 Hz, 2H, CH2O), 6.62-6.68 (m, 4H, 4×ArH), 6.75-6.79 (m, 2H, 2×ArH), 7.08 (s, 1H, nitroimidazole C5-H), 7.23 (s, 1H, nitroimidazole C4-H); 13C NMR (CDCl3, 100 MHz) δ 16.08, 16.14, 38.71, 38.80, 39.06, 39.16, 49.77, 55.73, 55.76, 55.83, 68.56, 69.28, 69.67, 70.43 70.54, 70.65, 110.96, 112.20, 112.77, 113.64, 120.85, 120.95, 127.31, 127.91, 134.37, 135.23, 144.62, 146.12, 146.96, 148.61, 149.23; IR (neat) 2925 (s), 2868 (s), 1655 (w), 1590 (w), 1515 (s), 1488 (w), 1459 (m), 1362 (s), 1260 (s), 1030 (s) cm−1; HRMS (FAB) m/z calcd for C32H46N3O9 (M+H)+: 616.3234. found: 616.3234.
Reaction SMILES: ClC1C2C(=CC=CC=2)C(C)=NN=1.[NH2:13][C:14]1[CH:34]=[CH:33][C:17]2[N:18]([C:21]3[CH:26]=[CH:25][C:24](C4C=CC=CC=4)=[CH:23][CH:22]=3)[CH:19]=[N:20][C:16]=2[CH:15]=1>CC(O)C>[NH2:13][C:14]1[CH:34]=[CH:33][C:17]2[N:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:19]=[N:20][C:16]=2[CH:15]=1
Reactant: Nc1ccc2c(c1)ncn2-c1ccc(-c2ccccc2)cc1
Agent: Cc1nnc(Cl)c2ccccc12
Solvent: CC(C)O
Product: Nc1ccc2c(c1)ncn2-c1ccccc1
Temperature: 25 °C
Yield: 181.6 %

Procedure:
A solution of 1-chloro-4-methylphthalazine (25 mg, 0.14 mmol) and 5-amino-1-(biphen-4-yl)benzimidazole (3) (28.5 mg, 0.10 mmol) in i-PrOH (2 mL) is stirred at 95° C. under argon for 2.5 h, cooled to room temperature, and concentrated at reduced pressure. The residue is diluted with sat. NaHCO3 (15 mL) and extracted with CHCl3 (60 mL). The extract is washed (brine) and dried. After solvent removal at reduced pressure, the residue is purified on silica gel (3.2% to 4.8% methanol/ethyl acetate) to give 38 mg (88%) of 4 (BI-3039) as a light-brown solid, mp 272-274° C. IR 3339, 2979, 1522, 1412 cm−1; 1H NMR (CD3OD/CDCl3) δ 2.82 (s, 3H, CH3), 7.36-7.53 (m, 3H, PhH), 7.62 (d, J=9.00 Hz, 1H, 7-BenzimidH), 7.69 (m, 2H, Aril, 2H PhH), 7.79 (d, J=8.7 Hz, 1H, 6-BenzimidH), 7.86 (d, J=8.1 Hz, 2H, ArH), 7.91-7.98 (m, 2H, 6,7-PhthH), 8.07 (m, 1H, 5-PhthH), 8.10 (s, 1H, 4-BenzimidH), 8.32 (s, 1H, 2-BenzimidH), 8.45 ppm (m, 1H, 8-PhthH).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12](=O)[CH2:13][C:14]([O:16]CC)=[O:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:20]([C:23]1[CH:33]=[CH:32][C:26]([C:27]([NH:29][CH2:30][CH3:31])=[O:28])=[CH:25][CH:24]=1)=[N+:21]=[N-:22].[O-]CC.[Na+].O>C(O)C>[CH2:30]([NH:29][C:27]([C:26]1[CH:32]=[CH:33][C:23]([N:20]2[C:12]([CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[C:13]([C:14]([OH:16])=[O:15])[N:22]=[N:21]2)=[CH:24][CH:25]=1)=[O:28])[CH3:31]
Reactant: CCOC(=O)CC(=O)CCCCCc1ccccc1
Reactant: CCNC(=O)c1ccc(N=[N+]=[N-])cc1
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CCNC(=O)c1ccc(-n2nnc(C(=O)O)c2CCCCCc2ccccc2)cc1
Temperature: 60 °C
Reaction time: 14 h
Yield: 99.4 %

Procedure:
Ethyl 8-phenyl-3-oxooctanoate (1.01 g, 3.84 mmol, 1.23 eq.) obtained in Example 101a) and 4-azido-N-ethylbenzamide (purity 95%, 0.624 g, 3.12 mmol) were dissolved in ethanol (20 ml), sodium ethoxide (290 mg, 3.84 mmol, 1.23 eq.) was added, and the mixture was stirred at room temperature for 30 min and at 60° C. for 14 hr. Water (20 ml) was added to the reaction mixture, ethanol was evaporated, and the residue was diluted with 2% aqueous sodium carbonate solution (20 ml) and washed with ethyl acetate-hexane (2:1, 50 ml). The organic layer was extracted with 2% aqueous sodium carbonate solution (20 ml). The aqueous layers were combined, acidified (pH<3) with 6N hydrochloric acid and stood still at 0° C. The precipitate was collected by filtration, washed with ice-cold water and dried to give the title compound as a pale-yellow powder (1.26 g, 3.10 mmol, 99.5%).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][N:14]([C:17]([C:19]2[N:20]=[CH:21][O:22][C:23]=2[CH2:24][CH2:25][C:26]([O:28]C(C)(C)C)=[O:27])=[O:18])[CH2:13][CH2:12]1)([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O>>[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][N:14]([C:17]([C:19]2[N:20]=[CH:21][O:22][C:23]=2[CH2:24][CH2:25][C:26]([OH:28])=[O:27])=[O:18])[CH2:13][CH2:12]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)CCc1ocnc1C(=O)N1CCN(c2ccccc2C(C)(C)C)CC1
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)c1ccccc1N1CCN(C(=O)c2ncoc2CCC(=O)O)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 76.3 %

Procedure:
A mixture of tert-butyl 3-(4-{[4-(2-tert-butylphenyl)piperazin-1-yl]carbonyl}-1,3-oxazol-5-yl)propanoate (Example 177, 0.60 g, 1.36 mmol) and trifluoroacetic acid (5.0 mL) was stirred at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure and the resulting residue was suspended in water. The mixture was adjusted to pH 4 with 10% NaHCO3 and then extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting white solid was triturated with hexane and ethyl acetate successively to give the title compound (0.40 g) as a white solid: mp 180-181° C.