Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]1[N:11]2[CH2:12][CH2:13][N:14](C(OC(C)(C)C)=O)[CH2:15][C:10]2=[N:9][N:8]=1.Cl.CCO>C(Cl)Cl>[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]1[N:11]2[CH2:12][CH2:13][NH:14][CH2:15][C:10]2=[N:9][N:8]=1
Reactant: CC(C)(C)OC(=O)N1CCn2c(nnc2-c2cnccn2)C1
Agent: Cl
Solvent: ClCCl
Solvent: CCO
Product: c1cnc(-c2nnc3n2CCNC3)cn1
Reaction time: 3 h
Yield: 61 %

Procedure:
To a solution of tert-butyl 3-(pyrazin-2-yl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxylate (9.3 g, 30 mmol) in DCM (100 mL) was added 1.25M HCl in EtOH (30 mL, 37.5 mmol). After 3 h, the reaction mixture was concentrated, and the resulting solid was purified by chromatography (SiO2; 10% MeOH in DCM) to provide the desired product as a white solid (3.7 g, 61%). MS (ESI): mass calcd. for C9H10N6, 202.1; m/z found, 203.1 [M+H]+. 1H NMR (400 MHz, CD3OD) δ 9.35 (d, J=1.4 Hz, 1H), 8.72 (dd, J=2.5, 1.6 Hz, 1H), 8.66 (d, J=2.6 Hz, 1H), 4.50 (t, J=5.6 Hz, 2H), 4.22 (s, 2H), 3.24 (t, J=5.6 Hz, 2H).
Reaction SMILES: [Si]([O:8][C@@H:9]1[C@H:13]([CH2:14][CH3:15])[NH:12][C:11](=[O:16])[CH2:10]1)(C(C)(C)C)(C)C.[Cl:17][C:18]1[C:25]([F:26])=[C:24](I)[CH:23]=[CH:22][C:19]=1[C:20]#[N:21].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[Cl:17][C:18]1[C:25]([F:26])=[C:24]([N:12]2[C:11](=[O:16])[CH2:10][C@H:9]([OH:8])[C@@H:13]2[CH2:14][CH3:15])[CH:23]=[CH:22][C:19]=1[C:20]#[N:21]
Reactant: CC[C@@H]1NC(=O)C[C@@H]1O[Si](C)(C)C(C)(C)C
Reactant: N#Cc1ccc(I)c(F)c1Cl
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Solvent: O
Product: CC[C@H]1[C@@H](O)CC(=O)N1c1ccc(C#N)c(Cl)c1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 24.7 %

Procedure:
A solution of (4S,5S)-4-(tert-butyldimethylsilyloxy)-5-ethylpyrrolidin-2-one (300 mg), 2-chloro-3-fluoro-4-iodobenzonitrile (416 mg), cesium carbonate (602 mg), tris(dibenzylideneacetone)dipalladium(0) (56.4 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (107 mg) in dioxane (10 mL) was stirred at 80° C. overnight under an argon atmosphere. After allowing to room temperature, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent: hexane→hexane-ethyl acetate=2:1). The obtained residue was dissolved in ethanol (10 mL)-tetrahydrofuran (10 mL), concentrated hydrochloric acid (2.06 mL) was added, and the mixture was stirred overnight at room temperature. The mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution under ice-cooling, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: hexane→ethyl acetate), and recrystallized from hexane-ethyl acetate to give the title compound as colorless crystals (yield: 86 mg, 25%).
Reaction SMILES: [CH2:1]([O:8][CH2:9][C@@H:10]([F:13])[CH2:11][OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CN=C1.[C:19]([Si:23]([CH3:26])([CH3:25])Cl)([CH3:22])([CH3:21])[CH3:20].O>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([O:8][CH2:9][C@@H:10]([F:13])[CH2:11][O:12][Si:23]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:26])[CH3:25])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OC[C@H](F)COCc1ccccc1
Agent: c1c[nH]cn1
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OC[C@H](F)COCc1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 97.5 %

Procedure:
After dissolving (S)-3-benzyloxy-2-fluoropropan-1-ol (CAS 197389-28-9) (6.00 g) and imidazole (2.44 g) in N,N-dimethylformamide (60 ml), the mixture was cooled on ice. Next, tert-butyldimethylchlorosilane (5.57 g) was added and the mixture was stirred at room temperature for 16 hours. Water was added to the reaction mixture, and extraction was performed with ethyl acetate. The organic layer was washed with water, a saturated aqueous solution of ammonium chloride, water and brine in that order and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography. The title compound (9.48 g) was thus obtained.
Reaction SMILES: F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[O:25]1[C:30]2([CH2:35][CH2:34][N:33]([CH2:36][C:37]3[C:38]([F:46])=[C:39]([CH2:43][CH2:44][OH:45])[CH:40]=[CH:41][CH:42]=3)[CH2:32][CH2:31]2)[CH2:29][NH:28][CH2:27][CH2:26]1.[CH3:47][CH2:48][CH:49]([C:52]1[S:53][CH:54]=[C:55]([C:57](O)=[O:58])[N:56]=1)[CH2:50][CH3:51].C(N(CC)CC)C>CN(C=O)C>[F:46][C:38]1[C:39]([CH2:43][CH2:44][OH:45])=[CH:40][CH:41]=[CH:42][C:37]=1[CH2:36][N:33]1[CH2:34][CH2:35][C:30]2([O:25][CH2:26][CH2:27][N:28]([C:57]([C:55]3[N:56]=[C:52]([CH:49]([CH2:50][CH3:51])[CH2:48][CH3:47])[S:53][CH:54]=3)=[O:58])[CH2:29]2)[CH2:31][CH2:32]1
Reactant: CCC(CC)c1nc(C(=O)O)cs1
Reactant: OCCc1cccc(CN2CCC3(CC2)CNCCO3)c1F
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCC(CC)c1nc(C(=O)N2CCOC3(CCN(Cc4cccc(CCO)c4F)CC3)C2)cs1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.2 g) was added to a solution of 2-(3-(1-oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-2-fluorophenyl)ethanol (example 67, step f) (0.13 g), 2-(pentan-3-yl)thiazole-4-carboxylic acid (example 71, step d) (0.081 g) and triethylamine (0.23 mL) in DMF (7 mL) at 0° C. The resulting yellow solution was allowed to warm to RT and was stirred for 2 h. The mixture was partitioned between ethyl acetate and brine (100 mL), the organic phase was washed with brine (2×100 mL), dried over sodium sulphate, filtered and then evaporated. The resulting gum was purified by silica gel chromatography eluting with 47.5:47.5:5 isohexane:ethyl acetate:triethylamine to 95:5 ethyl acetate:triethylamine gradient. The fractions containing product were combined, toluene (200 mL) was added, and the solvent evaporated under reduced pressure to give the subtitled compound a as clear gum. Yield 0.25 g.
Reaction SMILES: [Br:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([N+:10]([O-])=O)[CH:5]=[C:4]([CH3:13])[N+:3]=1[O-].[Cl-].[NH4+]>CCO.O.O.[Fe]>[Br:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([NH2:10])[CH:5]=[C:4]([CH3:13])[N:3]=1
Reactant: COc1c([N+](=O)[O-])cc(C)[n+]([O-])c1Br
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: COc1c(N)cc(C)nc1Br
Temperature: 90 °C

Procedure:
A mixture of 124D (0.75 g, 2.9 mmol), iron (0.48 g, 8.6 mmol) and ammonium chloride (0.46 g, 8.6 mmol) in EtOH/H2O (10 mL/3 mL) was refluxed (bath temperature 90° C.) for 4 h. After cooling to room temperature, the reaction mixture was diluted with water, extracted with dichloromethane three times. The combined organic phases were dried over Na2SO4, filtered and concentrated to give 124E as a oil.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][C:9]=1[NH:18][C:19](=[O:40])[CH2:20][C:21](=O)[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]2[CH:33]=[CH:32][N:31]=[C:30]([N:34]3[CH2:38][CH2:37][CH2:36][CH2:35]3)[CH:29]=2)[CH:23]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[N:34]1([C:30]2[CH:29]=[C:28]([C:24]3[CH:23]=[C:22]([C:21]4[CH2:20][C:19](=[O:40])[NH:18][C:9]5[CH:10]=[C:11]([C:14]([F:17])([F:15])[F:16])[CH:12]=[CH:13][C:8]=5[N:7]=4)[CH:27]=[CH:26][CH:25]=3)[CH:33]=[CH:32][N:31]=2)[CH2:35][CH2:36][CH2:37][CH2:38]1
Reactant: CC(C)(C)OC(=O)Nc1ccc(C(F)(F)F)cc1NC(=O)CC(=O)c1cccc(-c2ccnc(N3CCCC3)c2)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1CC(c2cccc(-c3ccnc(N4CCCC4)c3)c2)=Nc2ccc(C(F)(F)F)cc2N1

Procedure:
The title compound was prepared from (2-{3-oxo-3-[3-(2-pyrrolidin-1-yl-pyridin-4-yl)-phenyl]-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example M290) (294 mg, 0.52 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (191 mg, 82%).
Reaction SMILES: [Cl-].[Li+].[BH4-].[Na+].[CH2:5]([O:12][C:13]([NH:15][CH2:16][CH2:17][CH2:18][CH2:19][C@@H:20]([NH:26][C:27]([NH:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[S:28])[C:21](OCC)=[O:22])=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[BH4-]>C(O)C.O1CCCC1.ClCCl.C(OCC)(=O)C>[C:30]([NH:29][C:27]([NH:26][C@@H:20]([CH2:21][OH:22])[CH2:19][CH2:18][CH2:17][CH2:16][NH:15][C:13](=[O:14])[O:12][CH2:5][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)=[S:28])([CH3:33])([CH3:32])[CH3:31]
Reactant: CCOC(=O)[C@@H](CCCCNC(=O)OCc1ccccc1)NC(=S)NC(C)(C)C
Agent: [BH4-]
Agent: [Cl-]
Agent: [Li+]
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: CCO
Product: CC(C)(C)NC(=S)N[C@@H](CO)CCCCNC(=O)OCc1ccccc1
Temperature: 20 °C
Reaction time: 16 h
Yield: 60.3 %

Procedure:
1.78 g of lithium chloride and then 1.6 g of sodium borohydride are added, under an inert atmosphere, to a stirred solution of 12.7 g of ethyl (2R)-6-{[(benzyloxy)-carbonyl]amino}-2-{[(tert-butylamino)carbothioyl]-amino}hexanoate in 130 cm3 of ethanol and 65 cm3 of tetrahydrofuran, cooled to between 0° C. and 5° C. After stirring for 16 hours at a temperature in the region of 20° C., a further 0.4 g of borohydride is added and the mixture is maintained at about 80° C. for 4 hours. The reaction medium is filtered and the filter cake is washed with ethanol. The filtrate is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. and the residue obtained is taken up in a dichloromethane/ethyl acetate mixture (85/15 by volume) and left under cold conditions at about 5° C. The crystalline product is spin-filtered and purified by chromatography at atmospheric pressure on a column of silica gel (particle size 40-63μ; mass of silica: 600 g), eluting with a dichloromethane/ethyl acetate mixture (85/15 by volume). The fractions containing the expected product are collected. These fractions are combined and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. 6.9 g of benzyl (5R)-5-{[(tert-butylamino)carbothioyl]amino}-6-hydroxyhexylcarbamate are obtained in the form of a colorless oil. (αD20=+24.0±0.8 at a concentration of 0.5% in methanol).
Reaction SMILES: Cl[C:2]1[N:3]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[Cl:21])[C:4](=[O:14])[C:5]2[C:6]([N:13]=1)=[N:7][C:8]([S:11][CH3:12])=[N:9][CH:10]=2.[C:22]([NH:25][NH2:26])(=O)[CH3:23]>C(#N)C>[Cl:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[N:3]1[C:4](=[O:14])[C:5]2[C:6](=[N:7][C:8]([S:11][CH3:12])=[N:9][CH:10]=2)[N:13]2[C:22]([CH3:23])=[N:25][N:26]=[C:2]12
Reactant: CC(=O)NN
Reactant: CSc1ncc2c(=O)n(-c3ccccc3Cl)c(Cl)nc2n1
Solvent: CC#N
Product: CSc1ncc2c(=O)n(-c3ccccc3Cl)c3nnc(C)n3c2n1

Procedure:
A mixture of Example 1B (0.150 g, 0.442 mmol) and acetohydrazide (0.072 g, 0.973 mmol) in acetonitrile (5 mL) was heated at 150° C. for 15 minutes in a Biotage microwave reactor. The solid was filtered. The filtrate was concentrated, treated with saturated aqueous NaHCO3 and extracted with ethyl acetate (2×). The combined organic layers were dried over MgSO4, filtered, concentrated, and purified on a 12 g column using the ISCO Companion flash system eluting with CH2Cl2/ethyl acetate (3:7 to 2:8) to provide the title compound.
Reaction SMILES: C(C1CCC2C(=C(C(=O)C)C=CC=2[Cl:14])C1=O)(=O)C.[C:19]([NH:22][CH:23]1[CH2:32][CH2:31][C:30]2[C:25](=[C:26]([NH:33]C(=O)C)[CH:27]=[CH:28][CH:29]=2)[C:24]1=[O:37])(=[O:21])[CH3:20]>>[C:19]([NH:22][CH:23]1[CH2:32][CH2:31][C:30]2[C:25](=[C:26]([NH2:33])[CH:27]=[CH:28][C:29]=2[Cl:14])[C:24]1=[O:37])(=[O:21])[CH3:20]
Reactant: CC(=O)Nc1cccc2c1C(=O)C(NC(C)=O)CC2
Reactant: CC(=O)c1ccc(Cl)c2c1C(=O)C(C(C)=O)CC2
Product: CC(=O)NC1CCc2c(Cl)ccc(N)c2C1=O

Procedure:
The reaction was carried out in the same manner as in Example 1-(4), except that 270 mg of the compound prepared in (1) above was used instead of 2,8-diacetylamino-1-tetralone of Example 1-(4), and post-treated to produce 160 mg of the title compound.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12])=[CH:4][CH:3]=1.[CH3:14][C:15](=[CH2:17])[CH3:16]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][CH2:10][C:11]([O:13][C:15]([CH3:17])([CH3:16])[CH3:14])=[O:12])=[CH:6][CH:7]=1
Reactant: O=C(O)CCCc1ccc(F)cc1
Reactant: C=C(C)C
Product: CC(C)(C)OC(=O)CCCc1ccc(F)cc1

Procedure:
In Scheme A, step 1, 4-(p-fluorophenyl)butyric acid is contacted with isobutylene to give t-butyl 4-(p-fluorophenyl)butyrate.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:18])[C:11]=1[N:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)[N:8]([C:19]1[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=1)[CH:7]=[C:6]([C:26]([OH:28])=[O:27])[C:5]2=[O:29].[CH3:30]I>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:18])[C:11]=1[N:12]1[CH2:17][CH2:16][N:15]([CH3:30])[CH2:14][CH2:13]1)[N:8]([C:19]1[CH:20]=[CH:21][C:22]([OH:25])=[CH:23][CH:24]=1)[CH:7]=[C:6]([C:26]([OH:28])=[O:27])[C:5]2=[O:29]
Reactant: CI
Reactant: O=C(O)c1cn(-c2ccc(O)cc2)c2c(F)c(N3CCNCC3)c(F)cc2c1=O
Solvent: CN(C)C=O
Product: CN1CCN(c2c(F)cc3c(=O)c(C(=O)O)cn(-c4ccc(O)cc4)c3c2F)CC1
Yield: 39.3 %

Procedure:
To a solution of 6,8-Difluoro-1-(4-hydroxyphenyl)-7-(1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (4.18 g) in DMF (29 ml) is added a solution of methyl iodide (7.7 g) in DMF (20 ml). The mixture is heated in a stainless steel autoclave on an oil bath at 110°-120° C. for 5 hours. DMF is distilled off under reduced pressure, and to the residue is added 10% aqueous sodium hydroxide to regulate pH 13. The insoluble substance is filtered off, and the remaining mixture is regulated to pH 8 with acetic acid. The precipitated crystals are separated by filtration, washed with water, dried, and then recrystallized from DMF to give 6,8-difluoro-1-(4-hydroxyphenyl)-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (1.7 g) as pale yellowish white crystals, m.p. >300° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH:15]([OH:17])[CH3:16])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:15](=[O:17])[CH3:16])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CC(O)C1(c2ccc(Cl)c(Cl)c2)CCCCC1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: CC(=O)C1(c2ccc(Cl)c(Cl)c2)CCCCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 63.6 %

Procedure:
To a solution of crude 1-(1-(3,4-dichlorophenyl)cyclohexyl)ethanol (494 mg, 1.81 mmol) in CH2Cl2 (18 mL) was added Dess-Martin periodinane (997 mg, 2.35 mmol). The resulting suspension was stirred at RT for 2 h and was then concentrated. The crude ketone was purified by silica gel column chromatography with an EtOAc/hexane gradient (product Rf=0.6 in 10% EtOAc/hexanes) to give 1-(1-(3,4-dichlorophenyl)cyclohexyl)ethanone (312 mg, 67%) as an orange oil. HPLC Rt=11.61 min; 1H NMR (400 mHz, CDCl3) 7.42-7.40 (m, 2H), 7.15 (dd, J=2.2, 8.4 Hz, 1H), 2.32-2.29 (m, 2H), 1.92 (s, 3H), 1.80-1.74 (m, 2H), 1.65-1.43 (m, 5H), 1.35-1.30 (m, 1H); 13C NMR (100 mHz, CDCl3) 209.5, 143.3, 133.2, 131.3, 130.9, 128.9, 126.3, 56.2, 33.7, 25.8 (2 overlapping peaks), 23.2.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([F:14])([F:13])[F:12])[CH:6]=1)=O.[NH2:15][C:16]([NH2:18])=[S:17]>CO>[F:12][C:11]([F:14])([F:13])[C:7]1[CH:6]=[C:5]([C:3]2[S:17][C:16]([NH2:18])=[N:15][CH:2]=2)[CH:10]=[CH:9][CH:8]=1
Reactant: NC(N)=S
Reactant: O=C(CBr)c1cccc(C(F)(F)F)c1
Solvent: CO
Product: Nc1ncc(-c2cccc(C(F)(F)F)c2)s1
Temperature: 75 °C
Reaction time: 8 h

Procedure:
Into a 100-mL round bottom flask, was placed a solution of 2-bromo-1-(3-(trifluoromethyl)phenyl)ethanone (2.5 g, 9.40 mmol, 1.00 equiv) in methanol (50 mL), and thiourea (710 mg, 9.33 mmol, 1.00 equiv). The resulting solution was stirred overnight at 75° C. in an oil bath. The reaction mixture was cooled with a water/ice bath. The solids were collected by filtration. The residue was dissolved in 200 mL of ethyl acetate. The resulting mixture was washed with 1×50 mL of sodium hydroxide (1 N) and 2×50 mL of brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. This resulted in 2.2 g (96%) of 5-(3-(trifluoromethyl)phenyl)thiazol-2-amine as a white solid.
Reaction SMILES: [C:1]([OH:20])(=[O:19])[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].C[O-].[Na+].[CH3:24][C:25](C)=O>>[C:1]([OH:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:24][CH3:25]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Reactant: CC(C)=O
Agent: C[O-]
Agent: [Na+]
Product: CCCCCCCCCCCCCCCCCCCC(=O)O
Yield: 29 %

Procedure:
High-oleic sunflower oil having 86% of oleic acid content relative to the constituent fatty acid and fully hydrogenated rapeseed oil were mixed and the mixture was subjected to random interesterification using sodium methylate to obtain a reaction oil. The reaction oil was subjected to solvent fractionation with acetone to remove high melting point fraction and low melting point fraction, and to obtain mid fraction at a yield of 29%. The obtained mid fraction was purified by conventional methods to obtain StStO fat (StOSt=22.4%, StLSt=2.5%, StOO=1.6%, arachidic acid content=0.5%).
Reaction SMILES: I[CH2:2][CH2:3][CH3:4].[CH2:5]1[O:9][C:8]2[CH:10]=[C:11]([OH:14])[CH:12]=[CH:13][C:7]=2[O:6]1>>[CH2:2]([O:14][C:11]1[CH:12]=[CH:13][C:7]2[O:6][CH2:5][O:9][C:8]=2[CH:10]=1)[CH2:3][CH3:4]
Reactant: Oc1ccc2c(c1)OCO2
Reactant: CCCI
Product: CCCOc1ccc2c(c1)OCO2

Procedure:
Starting from commercially available iodopropane and sesamol the title compound is obtained as colorless oil.
Reaction SMILES: [C:1](C1C=CC=CC=1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.BrC1C=CC(C)=CC=1.[Br:23][C:24]1[CH:31]=[CH:30][C:27]([CH:28]=[O:29])=[CH:26][CH:25]=1>>[Br:23][C:24]1[CH:31]=[CH:30][C:27]([CH:28]([C:5]2[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=2)[OH:29])=[CH:26][CH:25]=1
Reactant: O=Cc1ccc(Br)cc1
Reactant: O=C(c1ccccc1)c1ccccc1
Agent: Cc1ccc(Br)cc1
Product: Cc1ccc(C(O)c2ccc(Br)cc2)cc1

Procedure:
The procedure below details the synthesis of a benzophenone dimer comprising a metal carboxylate and linked by a diamine terminated bridging moiety via the scheme set forth in FIG. 1. As shown in FIG. 1, synthesis of the benzophenone crosslinker (8) starts with a reaction between a Grignard reagent derived from commercially available 4-bromotoluene (1) and 4-bromobenzaldehyde (2), yielding (4′-bromophenyl)-4-methylphenyl methanol (3). Alcohol (3) was then oxidized with potassium permanganate (KMnO4) to provide 4-bromophenyl-p-toylmethanone (4), followed by oxidation of the methyl group with CrO3 to yield 4-(p-bromobenzoyl) benzoic acid (5). Esterification of acid (5) provided 4-(p-bromobenzoyl) benzoate (6). The bifunctional coupling between pentane diamine (NH2(CH2)5NH2)and methyl 4-(p-bromobenzoyl) benzoate (6) to yield the benzophenone dimer (7) was achieved using 1,1-bis(diphenyphosphino)ferrocene (DPPF) as the catalyst. The benzophenone dimer (7) was then hydrolyzed to provide the dipotassium salt (8). Details of each step are set forth below.
Reaction SMILES: [NH:1]1[CH2:9][CH2:8][CH:4]([C:5]([OH:7])=[O:6])[CH2:3][CH2:2]1.[C:10](OC(=O)C)(=[O:12])[CH3:11]>>[C:10]([N:1]1[CH2:9][CH2:8][CH:4]([C:5]([OH:7])=[O:6])[CH2:3][CH2:2]1)(=[O:12])[CH3:11]
Reactant: O=C(O)C1CCNCC1
Reactant: CC(=O)OC(C)=O
Product: CC(=O)N1CCC(C(=O)O)CC1
Yield: 74 %

Procedure:
Isonipecotic acid (25.0 g, 0.19 mol) was dissolved in acetic anhydride (100 mL) and the solution stirred at reflux for 8 h, then the solvent was removed under reduced pressure and the crude compound crystallized from MeOH/ether to afford the title compound as a white solid (24.4 g, 74%). m.p. 171° C. 1H NMR (DMSO): 1.2-1.5 (m, 2H), 1.65-1.85 (m, 2H), 1.942 (s, 3H), 2.35-2.5 (m, 1H), 2.641 (t, J=11.7Hz, 1H), 3.038 (t, J=11.7Hz, 1H), 3.69 (d, J=13.5Hz, 1H), 4.15 (d, J=13.2Hz, 1H), 12.22 (bs, 1H). IR (KBr): 1721, 1613, 1316, 1202 (cm−1). MS (m/z): 171, 128, 82.
Reaction SMILES: [CH2:1]([NH:3][C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[CH:12]1[CH2:21][CH2:20][C:19]2[CH:18]=[C:17]([O:22][C:23](=[O:28])[C:24]([CH3:27])([CH3:26])[CH3:25])[CH:16]=[CH:15][C:14]=2[CH2:13]1)[CH3:2].C([O:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](O)=[O:38])=[CH:35][CH:34]=1)(=O)C.C(OC1C=CC(C(CCNC2C=C(OC)C=CC=2C2CCC3C=C(OC(=O)C(C)(C)C)C=CC=3C2)=O)=CC=1)(=O)C>>[CH2:1]([N:3]([C:37](=[O:38])[C:36]1[CH:40]=[CH:41][C:33]([OH:32])=[CH:34][CH:35]=1)[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[CH:12]1[CH2:21][CH2:20][C:19]2[CH:18]=[C:17]([O:22][C:23](=[O:28])[C:24]([CH3:27])([CH3:26])[CH3:25])[CH:16]=[CH:15][C:14]=2[CH2:13]1)[CH3:2]
Reactant: CCNc1cc(OC)ccc1C1CCc2cc(OC(=O)C(C)(C)C)ccc2C1
Reactant: CC(=O)Oc1ccc(C(=O)O)cc1
Agent: COc1ccc(C2CCc3cc(OC(=O)C(C)(C)C)ccc3C2)c(NCCC(=O)c2ccc(OC(C)=O)cc2)c1
Product: CCN(C(=O)c1ccc(O)cc1)c1cc(OC)ccc1C1CCc2cc(OC(=O)C(C)(C)C)ccc2C1

Procedure:
Synthesized from pivalic acid 6-(2-ethylamino-4-methoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-yl ester and 4-acetoxybenzoic acid according to an analogous synthetic method to Preparation Example 154, pivalic acid 6-{2-[(4-acetoxybenzoyl)ethylamino]-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester (3.2 g) was used according to an analogous synthetic method to Preparation Example 155 to provide the title compound (2.1 g).
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12][CH2:11][NH:10]2)=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.[N:30]1[O:31][N:32]=[C:33]2[CH:38]=[C:37]([C:39](Cl)=[O:40])[CH:36]=[CH:35][C:34]=12>C(Cl)Cl>[N:30]1[O:31][N:32]=[C:33]2[CH:38]=[C:37]([C:39]([N:10]3[CH2:11][CH2:12][C:13]4[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=4)[C@H:9]3[C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:19])[F:20])=[CH:8][CH:7]=3)=[O:40])[CH:36]=[CH:35][C:34]=12
Reactant: O=C(Cl)c1ccc2nonc2c1
Reactant: FC(F)(F)c1ccc([C@H]2NCCc3ccccc32)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(c1ccc2nonc2c1)N1CCc2ccccc2[C@H]1c1ccc(C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of (R)-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (50 mg, 180 μmol) and diea (31 μL, 180 μmol) in DCM (1 mL) was added benzo[c][1,2,5]oxadiazole-5-carbonyl chloride (43 mg, 234 μmol). The resulting mixture was then stirred at RT for overnight. Then, the mixture was concentrated and the residue was dissolved in MeOH (1 mL). The solution mixture was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA) to give a desired product, which was then dissolved in MeOH (1 mL). The solution was then washed through PL-HCO3 resin and the resin was then washed with MeOH (1 mL). The combined washings were concentrated and dried under vacuum to give the title compound as a white solid. MS (ESI, positive ion) m/z: 424 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:13]=[C:14]2C(=O)OC(C)(C)[O:16][C:15]2=[O:23])[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].C(O)=O>C(N(CC)CC)C>[CH3:12][O:11][C:7]1[CH:6]=[C:5]([CH2:13][CH2:14][C:15]([OH:23])=[O:16])[CH:4]=[C:3]([O:2][CH3:1])[C:8]=1[O:9][CH3:10]
Reactant: COc1cc(C=C2C(=O)OC(C)(C)OC2=O)cc(OC)c1OC
Solvent: CCN(CC)CC
Solvent: O=CO
Product: COc1cc(CCC(=O)O)cc(OC)c1OC

Procedure:
16.1 g (0.05 mol) of 5-(3,4,5-trimethoxyphenylmethylene)- 2,2-dimethyl-1,3-dioxane-4,6-dione (m.p.: 159°-160° C.) were added to 50 ml of the mixture of formic acid and triethylamine prepared as described in Example 1, then the procedure described in Example 2 was followed.