Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[N:17]=[CH:16]3)=[CH:11][CH:10]=2)O1.[CH3:25][O:26][C:27]([C:29]1[N:30]([CH3:35])[C:31](Br)=[N:32][CH:33]=1)=[O:28].C(=O)([O-])[O-].[K+].[K+]>COCCOC.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:25][O:26][C:27]([C:29]1[N:30]([CH3:35])[C:31]([C:9]2[CH:10]=[CH:11][C:12]([N:15]3[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[N:17]=[CH:16]3)=[CH:13][CH:14]=2)=[N:32][CH:33]=1)=[O:28]
Reactant: CC1(C)OB(c2ccc(-n3cnc4ccccc43)cc2)OC1(C)C
Reactant: COC(=O)c1cnc(Br)n1C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: COCCOC
Product: COC(=O)c1cnc(-c2ccc(-n3cnc4ccccc43)cc2)n1C
Temperature: 90 °C
Yield: 36 %

Procedure:
To a solution of 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-benzoimidazole (0.43 g, 1.5 mmol) and 2-bromo-3-methyl-3H-imidazole-4-carboxylic acid methyl ester (0.25 g, 1.15 mmol) in DME (9 mL) was added tetrakis(triphenylphosphine)palladium(0) (0.07 g, 0.057 mmol) and 2 M aqueous potassium carbonate (1.4 mL) and the reaction mixture was heated at 90° C. for 12 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The reaction mixture was filtered and the filtrate washed with water, dried (Na2SO4), and the solvent removed under reduced pressure. Purification by flash column chromatography (silica, petroleum ether:ethyl acetate 7:3→1:1 then dichloromethane:methanol 99:1→97:3) provided the title compound (36%). LCMS (ESI+) 332.2 (MH+).
Reaction SMILES: [F:1][CH:2]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH2:3][OH:4].N1C=CC=CC=1.[C:19]1([CH3:29])[CH:24]=[CH:23][C:22]([S:25](Cl)(=[O:27])=[O:26])=[CH:21][CH:20]=1.Cl>O>[C:19]1([CH3:29])[CH:24]=[CH:23][C:22]([S:25]([O:4][CH2:3][CH:2]([F:1])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])(=[O:27])=[O:26])=[CH:21][CH:20]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CCCCCCCCC(F)CO
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: CCCCCCCCC(F)COS(=O)(=O)c1ccc(C)cc1
Reaction time: 1 h
Yield: 72.2 %

Procedure:
17 g of 2-fluorodecanol and 60 ml of pyridine were charged into a 300 ml three-necked round bottom flask and cooled to 0° C. to which 24 g of p-toluenesulfonyl chloride was added in 15 min. The system was held at 0° C. for 1 hour and then subjected to reaction for 7 hours while being held below 20° C. Then, the mixture was charged into water and acidified with hydrochloric acid, followed by extraction with dichloromethane. The organic layer was washed with water, dried with magnesium sulfate and then purified by silica gel chromatography with the use of dichloromethane as the eluent to obtain 23 g of 2-fluorodecyl p-toluenesulfonate.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[O:11]1[CH2:16][CH2:15][CH:14]([CH:17]([C:20]2[CH:21]=[N:22][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:24][CH:25]=2)[CH2:18][NH2:19])[CH2:13][CH2:12]1>>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:19][CH2:18][CH:17]([CH:14]1[CH2:15][CH2:16][O:11][CH2:12][CH2:13]1)[C:20]1[CH:21]=[N:22][C:23]([C:26]([F:29])([F:27])[F:28])=[CH:24][CH:25]=1)=[O:6]
Reactant: NCC(c1ccc(C(F)(F)F)nc1)C1CCOCC1
Reactant: O=C(O)c1ccccc1Cl
Product: O=C(NCC(c1ccc(C(F)(F)F)nc1)C1CCOCC1)c1ccccc1Cl

Procedure:
From 2-chlorobenzoic acid and 2-(tetrahydro-2H-pyran-4-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)ethanamine. LCMS (MH+): m/z=413.0, tR (minutes, Method E)=0.64
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH3:11])[C:7]([CH3:10])=[CH:8][CH:9]=1)([O-:3])=[O:2].[CH2:12]=[O:13].[C:14]([O-:17])([O-])=O.[K+].[K+].[O-2].[O-2].[O-2].[Al+3].[Al+3]>CS(C)=O>[CH3:11][C:6]1[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:9]=[CH:8][C:7]=1[CH:10]([CH2:14][OH:17])[CH2:12][OH:13]
Reactant: C=O
Reactant: Cc1ccc([N+](=O)[O-])cc1C
Reactant: O=C([O-])[O-]
Agent: [Al+3]
Agent: [K+]
Agent: [O-2]
Solvent: CS(C)=O
Product: Cc1cc([N+](=O)[O-])ccc1C(CO)CO
Temperature: 500 °C

Procedure:
1.2 g (8.0 mmol) 4-Nitro-o-xylene and 0.66 g (22 mmol) paraformaldehyde were added to a mixture of 1.2 g catalyst in 4 ml of dimethylsulphoxide. The catalyst had been prepared by heating for 24 hours at 500° C. a composition containing 20 g K2CO3 per 100 g gamma-alumina, i.e. 2.89 mmol K+ /g Al2O3. The reaction mixture was stirred under nitrogen at 20°-25° C. The conversion of 4-nitro-o-xylene and the selectivity during the reaction were determined by gas-liquid chromatography, whereby the alcohols were analysed via their trimethylsilyl ethers. The results are given in Table I.
Reaction SMILES: C[N:2]([CH3:5])C=O.[CH2:6]([O:8][CH:9]([O:13][CH2:14][CH3:15])[CH2:10]CCl)[CH3:7]>C(O)C.[Pd]>[CH2:6]([O:8][CH:9]([O:13][CH2:14][CH3:15])[CH2:10][CH2:5][NH2:2])[CH3:7]
Reactant: CCOC(CCCl)OCC
Reactant: CN(C)C=O
Agent: [Pd]
Solvent: CCO
Product: CCOC(CCN)OCC
Temperature: 60 °C
Reaction time: 96 h
Yield: 63 %

Procedure:
To 500 mL of dimethylformamide (DMF) containing Nan3 (26.0 g, 400 mmol) was added 3-chloropropionaldehyde diethyl acetal (33.3 g, 200 mmol). The solution was warmed to 60° C., and the reaction was monitored by GC (50° C., 1 min to 250° C. at 15° C./min, DB5-15m). (Retention time (tR) of starting material 5.1 min, product 6.5 min). The reaction mixture was diluted with 1 L of ice water and extracted with ether (3×500 mL). The combined ether extracts were washed with water (2×500 mL) and then dried over MgSO4. Removal of solvent afforded a crude product, which was dissolved in 500 mL of ethanol containing Pd/C (10%, 2.03 g, 2 mmol). The suspension was degassed, saturated with H2, and stirred under an H2 balloon for four days at which time GC analysis of the product amine (tR 5.4 min) indicated a complete reaction. The solution was degassed and filtered through Celite 545, and the solvent was removed under reduced pressure. The residue was diluted with 25 mL of 12 N KOH and extracted with ether (2×50 mL). The ether layer was filtered through glass wool/Na2CO3 and dried over Na The solvent was removed under water aspirator vacuum, and the residue was distilled to yield 3-aminopropanal diethylacetal (18.6 g 126 mmol, 63%): bp17 80°-81.5° C. (bp20 68°-70° C. agreed with b.p. in Becke, F. German Patent 845,348, 1952, Chem. Abstr. 47 (1952) 542); 1H-NMR (200 MHz CDCl3) δ 1.21 (t, 6 H, CH3), 1.58 (s, 2 H, NH2), 1.78 (q. 2 H CH2). 2.81 (t, 2 H, NCH2), 3.53 and 3.66 (m, 4 H, OCH2), 4.62 (t, 1 H, CH). Anal. Calcd for C7H17NO2 : C, 57.1; H, 11.6. Found: C, 57.1; H, 11.5.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][CH:7]=1)[CH2:3][OH:4].C(N(C(C)C)CC)(C)C.Cl[C:23](Cl)([O:25]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[CH3:12][C:9]1[CH:8]=[CH:7][C:6]([CH2:5][C@H:2]2[CH2:3][O:4][C:23](=[O:25])[NH:1]2)=[CH:11][CH:10]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: Cc1ccc(C[C@H](N)CO)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1ccc(C[C@H]2COC(=O)N2)cc1
Temperature: 0 °C
Reaction time: 3 h

Procedure:
A stirred solution of (2S)-2-amino-3-(4-methylphenyl)propan-1-ol (Step A, 460 mg, 2.79 mmol) in CH2Cl2 (20 mL) at 0° C. was treated with diisopropylethylamine (2.92 mL, 16.74 mmol) and triphosgene (414 mg, 1.39 mmol) under an atmosphere of N2. The reaction stirred at 0° C. for 3 h. The reaction was quenched with sat. NaHCO3 (10 mL) and extracted with EtOAc (4×20 mL). The combined organic layers were washed with brine (25 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash silica gel chromatography (0-70% EtOAc/hexanes gradient) to afford (4S)-4-(4-methylbenzyl)-1,3-oxazolidin-2-one as a white solid. LCMS=192.2 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.17 (d, J=8 Hz, 2 H), 7.09 (d, J=7.7 Hz, 2 H), 5.39 (br s, 1 H), 4.48 (t, J=8.4 Hz, 1 H), 4.37 (dd, J=8.6, 5.6 Hz, 1 H), 4.11-4.06 (m, 1 H), 2.86 (d, J=7.1 Hz, 2 H), 2.36 (s, 3 H).
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[O:11]([CH2:18][CH:19]([OH:28])[CH2:20][O:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>ClCCl>[O:11]([CH2:18][C:19]([CH2:20][O:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:28])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: OC(COc1ccccc1)COc1ccccc1
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CS(C)=O
Product: O=C(COc1ccccc1)COc1ccccc1
Reaction time: 0.25 h
Yield: 82.6 %

Procedure:
A solution of 0.44 ml (6.2 mmol) of dimethylsulfoxide in 25 ml of dichloromethane was cooled under inert atmosphere to -63° C., treated with 2.3 ml (4.6 mmol) of oxalyl chloride (2M in dichloromethane), and stirred for 15 min. A solution of 0.75 g (3.1 mmol) of the resultant compound of Example 4 in 10 ml of dichloromethane was subsequently added, the solution was stirred for 30 min, and 1.73 ml (12.4 mmol) of triethylamine was added. After stirring for an additional 15 min, the solution was quenched with 10% aqueous citric acid, poured into a mixture of 1:1 ether:hexane and 10% citric acid, extracted with ether, washed with aqueous brine, dried over MgSO4, and concentrated to a yellow oil. Purification by flash chromatography using 20% ethyl acetate in hexane gave 0.62 g (83%) of the desired compound as a white, crystalline solid, m.p. 55°-57° C. 1H NMR (CDCl3) δ 4.89 (s, 4H), 6.92 (m, 4H), 7.02 (m, 2H), 7.30 (m, 4H). Mass spectrum (M+NH4)+ =260.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][CH3:10])=[CH:4][CH:3]=1.Br[C:12]1[C:13]2[C:14]3[CH:27]=[CH:26][S:25][C:15]=3[C:16](=[O:24])[NH:17][C:18]=2[CH:19]=[CH:20][C:21]=1[O:22][CH3:23]>>[CH3:23][O:22][C:21]1[CH:20]=[CH:19][C:18]2[NH:17][C:16](=[O:24])[C:15]3[S:25][CH:26]=[CH:27][C:14]=3[C:13]=2[C:12]=1[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][CH3:10])=[CH:4][CH:3]=1
Reactant: CNCc1ccc(Br)cc1
Reactant: COc1ccc2[nH]c(=O)c3sccc3c2c1Br
Product: CNCc1ccc(-c2c(OC)ccc3[nH]c(=O)c4sccc4c23)cc1
Yield: 41.4 %

Procedure:
Following General Procedure E, 1-(4-bromophenyl)-N-methylmethanamine (200 mg, 1.0 mmol) was reacted to bis(pinacoato)diboron (280 mg, 1.1 mmol) to afford the crude boronic ester which was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (310 mg, 1.0 mmol) to afford the desired product (145 mg, 42%) as a white solid: 1H NMR (500 MHz, CD3OD) δ 7.65 (d, J=8.1 Hz, 2H), 7.58-7.52 (m, 2H), 7.42-7.35 (m, 3H), 6.02 (d, J=5.4 Hz, 1H), 4.33 (s, 2H), 3.73 (s, 3H), 2.83 (s, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([O:23][CH3:24])=[CH:5][C:6]2[CH2:7][CH:8]3[CH2:22][NH:21][CH2:20][CH2:19][N:9]3[CH:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:11]=2[CH:12]=1.[Cl:25][CH2:26][S:27][CH3:28].C(N(CC)CC)C>C(Cl)Cl.CN(C)C1C=CN=CC=1>[ClH:25].[ClH:25].[CH3:1][O:2][C:3]1[C:4]([O:23][CH3:24])=[CH:5][C:6]2[CH2:7][CH:8]3[CH2:22][N:21]([CH2:26][S:27][CH3:28])[CH2:20][CH2:19][N:9]3[CH:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:11]=2[CH:12]=1
Reactant: CSCCl
Reactant: COc1cc2c(cc1OC)C(c1ccccc1)N1CCNCC1C2
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cc2c(cc1OC)C(c1ccccc1)N1CCN(CSC)CC1C2
Product: Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
8,9-Dimethoxy-6-phenyl-1,3,4,6,11,11a-hexahydro-2H-pyrazino[1,2-b]isoquinoline (the compound obtained in Example 1-(6)) (3.2 g) is dissolved in methylene chloride (20 ml), and thereto are added chloromethyl methylsulfide (8.4 ml), triethylamine (3.5 ml) and 4-(dimethylamino)pyridine (61 mg), and the mixture is stirred at room temperature overnight. The reaction solution is washed with a saturated aqueous sodium hydrogen carbonate solution, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by column chromatography on silica gel (eluent; chloroform:ethyl acetate=9:1). The resulting precipitates (115 mg) are dissolved in chloroform, and thereto is added a 4M hydrochloric acid in ethyl acetate, and the solvent is removed by evaporation under reduced pressure. The residue is recrystallized from ethanol to give 8,9-dimethoxy-2-(methylthiomethyl)-6-phenyl-1,3,4,6,11,11a-hexahydro-2H-pyrazino[1,2-b]isoquinoline dihydrochloride (60 mg).
Reaction SMILES: [OH-:1].[Li+].[CH3:3][C:4]([C:6]1[CH:7]=[CH:8][C:9](O)=[CH:10][C:11]=1[OH:12])=[O:5].[CH:14]1[C:26]2[C:25](=[O:27])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]=2[C:17]([C:28](Cl)=O)=[CH:16][CH:15]=1.Cl>C1COCC1>[CH:14]1[C:26]2[C:25](=[O:27])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]=2[C:17]([C:28]2[O:12][C:11]3[C:6]([C:4](=[O:5])[C:3]=2[OH:1])=[CH:7][CH:8]=[CH:9][CH:10]=3)=[CH:16][CH:15]=1
Reactant: [OH-]
Reactant: O=C(Cl)c1cccc2c1-c1ccccc1C2=O
Reactant: CC(=O)c1ccc(O)cc1O
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Product: O=C1c2ccccc2-c2c1cccc2-c1oc2ccccc2c(=O)c1O
Temperature: -10 °C
Reaction time: 2 h

Procedure:
Dry, pulverulent lithium hydroxide (11.55 mmol, 3.3 equivalents) is added in one portion to a well-stirred solution of 2,4-dihydroxyacetophenone (3.22 mmol) in dry THF (5 ml) under an argon atmosphere at −78° C. The reaction mixture is stirred at −78° C. for one hour and subsequently at −10° C. for two hours. After the mixture has been re-cooled to −78° C., a solution of 9-fluorenone-4-carbonyl chloride (3.3 mmol) in THF (10 ml) is added in one portion. The mixture is stirred at −78° C. for one hour and at room temperature for 4 hours until the starting material has disappeared. The reaction mixture is emptied into a mixture of ice (150 g) and concentrated HCl (5 ml) and extracted with chloroform (3×50 ml). The solvents are removed from the dried extracts, and the residue is dried under reduced pressure for 24 hours. Glacial acetic acid (30 ml) and sulfuric acid (0.2 ml) are added to the residue, and the mixture is heated at 95–100° C. for from 30 minutes to one hour under an argon atmosphere. Approximately one third of the acetic acid is stripped off, and the residue is emptied into water. The precipitated product is filtered, washed and dried and recrystallised in methanol, giving 2-(9-fluorenon-4-yl)hydroxychromone. EI-MS (70 eV) m/e (rel. abund.)=340.
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([C:8](=[O:11])[NH:9][CH3:10])[C:5]([NH:12][C:13]2[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:56]=[CH:55][C:27]([CH2:28][P:29](=[O:54])([O:33][CH2:34][C:35]4([CH2:39][N:40]5[CH:44]=[C:43]([B:45]6[O:49][C:48]([CH3:51])([CH3:50])[C:47]([CH3:53])([CH3:52])[O:46]6)[CH:42]=[N:41]5)[CH2:38][O:37][CH2:36]4)[O:30][CH2:31][CH3:32])=[CH:26][C:25]=3[O:57][CH3:58])[N:14]=2)=[CH:4][CH:3]=1.BrC1N=C(C(=O)NC)C(NC2C(C(F)(F)F)=CN=C(NC3C=CC(CP(=O)(O)OCC)=C([Cl:95])C=3OC)N=2)=CC=1.CC1(C)C(C)(C)OB(C2C=NN(CC3(CO)COC3)C=2)O1>>[Br:1][C:2]1[N:7]=[C:6]([C:8](=[O:11])[NH:9][CH3:10])[C:5]([NH:12][C:13]2[C:18]([C:19]([F:21])([F:20])[F:22])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:56]=[CH:55][C:27]([CH2:28][P:29](=[O:54])([O:33][CH2:34][C:35]4([CH2:39][N:40]5[CH:44]=[C:43]([B:45]6[O:49][C:48]([CH3:50])([CH3:51])[C:47]([CH3:53])([CH3:52])[O:46]6)[CH:42]=[N:41]5)[CH2:38][O:37][CH2:36]4)[O:30][CH2:31][CH3:32])=[C:26]([Cl:95])[C:25]=3[O:57][CH3:58])[N:14]=2)=[CH:4][CH:3]=1
Reactant: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(Br)nc3C(=O)NC)n2)c(OC)c1)OCC1(Cn2cc(B3OC(C)(C)C(C)(C)O3)cn2)COC1
Reactant: CCOP(=O)(O)Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(Br)nc3C(=O)NC)n2)c(OC)c1Cl
Agent: CC1(C)OB(c2cnn(CC3(CO)COC3)c2)OC1(C)C
Product: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(Br)nc3C(=O)NC)n2)c(OC)c1Cl)OCC1(Cn2cc(B3OC(C)(C)C(C)(C)O3)cn2)COC1

Procedure:
Prepared analogously to Compound 44A using ethyl hydrogen (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-2-chloro-3-methoxybenzyl)phosphonate (Compound 54B, 200 mg, 0.306 mmol) and (3-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]methyl}oxetan-3-yl)methanol (Compound 44B, 95 mg, 321 mmol) to afford 264 mg of the title compound as a racemic mixture (93%). MS (ESI): m/z=929.64/931.71 [M+H]+. UPLC: tR=1.67 min (UPLC-TOF: polar—2 min).
Reaction SMILES: [CH2:1]([O:8][CH2:9][C@@:10]1([N:37]2[CH:45]=[C:43]([CH3:44])[C:41](=[O:42])[NH:40][C:38]2=[O:39])[O:33][C@H:13]([CH2:14][O:15][Si:16]([C:29]([CH3:32])([CH3:31])[CH3:30])([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:12]([CH2:34][CH:35]=C)[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[N+]1([O-])CC[O:50]CC1>C(OCC)C.O.O=[Os](=O)(=O)=O>[CH2:1]([O:8][CH2:9][C@@:10]1([N:37]2[CH:45]=[C:43]([CH3:44])[C:41](=[O:42])[NH:40][C:38]2=[O:39])[O:33][C@H:13]([CH2:14][O:15][Si:16]([C:29]([CH3:30])([CH3:32])[CH3:31])([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C@@H:12]([CH2:34][CH:35]=[O:50])[CH2:11]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C=CC[C@H]1C[C@](COCc2ccccc2)(n2cc(C)c(=O)[nH]c2=O)O[C@@H]1CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Reactant: C[N+]1([O-])CCOCC1
Agent: O=[Os](=O)(=O)=O
Solvent: CCOCC
Solvent: O
Product: Cc1cn([C@@]2(COCc3ccccc3)C[C@H](CC=O)[C@@H](CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)O2)c(=O)[nH]c1=O

Procedure:
A solution of 18 (1 mmol), OsO4 (0.1 mmol) and 4-methylmorpholine N-oxide (2 mmol) in diethyl ether and water are stirred overnight. A solution of NaIO4 is added and the solution further stirred. The aqueous layer is extracted with diethyl ether and the combined organic layer is evaporated under vacuum to yield the crude product, compound 55.
Reaction SMILES: [CH2:1]([C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([O:16][C:17]3[S:18][C:19]4[CH:25]=[C:24]([C:26]5[CH2:31][CH2:30][N:29]([S:32]([CH2:35][CH2:36][CH2:37][C:38](O)=[O:39])(=[O:34])=[O:33])[CH2:28][CH:27]=5)[CH:23]=[CH:22][C:20]=4[N:21]=3)[CH2:12][CH2:11]2)=[N:8][CH:9]=1)[CH2:2][CH3:3].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[NH2:55][CH2:56][C:57]([CH3:60])([OH:59])[CH3:58].CCN(CC)CC>C(Cl)Cl>[OH:59][C:57]([CH3:60])([CH3:58])[CH2:56][NH:55][C:38](=[O:39])[CH2:37][CH2:36][CH2:35][S:32]([N:29]1[CH2:30][CH2:31][C:26]([C:24]2[CH:23]=[CH:22][C:20]3[N:21]=[C:17]([O:16][CH:13]4[CH2:12][CH2:11][N:10]([C:7]5[N:6]=[CH:5][C:4]([CH2:1][CH2:2][CH3:3])=[CH:9][N:8]=5)[CH2:15][CH2:14]4)[S:18][C:19]=3[CH:25]=2)=[CH:27][CH2:28]1)(=[O:34])=[O:33]
Reactant: CCCc1cnc(N2CCC(Oc3nc4ccc(C5=CCN(S(=O)(=O)CCCC(=O)O)CC5)cc4s3)CC2)nc1
Reactant: CC(C)(O)CN
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: ClCCCl
Solvent: ClCCl
Product: CCCc1cnc(N2CCC(Oc3nc4ccc(C5=CCN(S(=O)(=O)CCCC(=O)NCC(C)(C)O)CC5)cc4s3)CC2)nc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 68.6 %

Procedure:
To a solution of 4-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butanoic acid (30 mg, 0.051 mmol), HOBT (10.2 mg, 0.067 mmol), and EDC (12.8 mg, 0.067 mmol) in CH2Cl2 (1 mL) was added 1-amino-2-methylpropan-2-ol (6.9 mg, 0.077 mmol) followed by slow addition of Et3N (0.03 mL, 0.205 mmol). The reaction mixture was stirred at rt overnight. The reaction mixture was diluted with CH2Cl2 (2 mL), washed with water (2 mL), then brine. The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was recrystallized from 10% water in CH3CN to afford N-(2-hydroxy-2-methylpropyl)-4-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butanamide (24 mg, 0.035 mmol, 68% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.17 (s, 2H), 7.63 (d, J=2.2 Hz, 1H), 7.62 (d, J=4.1 Hz, 1H), 7.38 (dd, J=8.5, 1.7 Hz, 1H), 6.06 (dt, J=3.2, 1.8 Hz, 1H), 6.04-5.99 (m, 1H), 5.45 (tt, J=7.9, 3.8 Hz, 1H), 4.22 (ddd, J=13.3, 6.9, 4.0 Hz, 2H), 4.02 (q, J=2.6 Hz, 2H), 3.73-3.62 (m, 2H), 3.57 (t, J=5.6 Hz, 2H), 3.28 (d, J=6.1 Hz, 2H), 3.10 (t, J=7.0 Hz, 2H), 2.70-2.64 (m, 2H), 2.49 (t, J=6.7 Hz, 2H), 2.41 (t, J=7.4 Hz, 2H), 2.26-2.14 (m, 5H), 1.94 (dtd, J=12.8, 8.3, 3.9 Hz, 2H), 1.62-1.55 (m, 2H), 1.23 (s, 6H), 0.94 (t, J=7.3 Hz, 3H). LCMS (m/z)=657 (M+H)+.
Reaction SMILES: [CH2:1]([O:19][CH2:20][CH:21]([OH:41])[CH2:22][O:23][C:24](=[O:40])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])[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].C1(N=C=NC2CCCCC2)CCCCC1.CN(C1C=CC=CN=1)C.[CH2:66]([CH2:80][C:81](O)=[S:82])[CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH3:79]>ClCCl>[CH2:1]([O:19][CH:20]([C:81](=[S:82])[CH2:80][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH3:79])[CH:21]([CH2:22][O:23][C:24](=[O:40])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])[OH:41])[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: CCCCCCCCCCCCCCCC(O)=S
Reactant: CCCCCCCC/C=C\CCCCCCCCOCC(O)COC(=O)CCCCCCCCCCCCCCC
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Product: CCCCCCCC/C=C\CCCCCCCCOC(C(=S)CCCCCCCCCCCCCCC)C(O)COC(=O)CCCCCCCCCCCCCCC
Temperature: 25 °C
Reaction time: 24 h
Yield: 49 %

Procedure:
3-oleyl-1-palmitoylglycerol (2 g, 0.003 mol) was dissolved in dichloromethane (150 ml) and dicyclohexylcarbodiimide (1.040 g, 0.005 mol), dimethylaminopyridine (0.616 g, 0.005 mol) and tetradecylthioacetic acid (1.455 g, 0.005 mol) were then added. The mixture was stirred at room temperature for 24 hours. The dicyclohexylurea precipitate was filtered, washed with dichloromethane and the filtrate was concentrated. The residue obtained was purified by silica gel chromatography (eluent:CH2Cl2-cyclohexane 4:6) to give the desired compound as an oil (yield: 49%).
Reaction SMILES: CCN(C(C)C)C(C)C.[O:10]([C:17]1[CH:29]=[CH:28][C:20]([C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH2:51]([N:58]1[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]1)[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1>CN(C=O)C.O>[CH2:51]([N:58]1[CH2:63][CH2:62][N:61]([C:25](=[O:27])[CH2:24][NH:23][C:21](=[O:22])[C:20]2[CH:19]=[CH:18][C:17]([O:10][C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=3)=[CH:29][CH:28]=2)[CH2:60][CH2:59]1)[C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=1
Reactant: c1ccc(CN2CCNCC2)cc1
Reactant: O=C(O)CNC(=O)c1ccc(Oc2ccccc2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: O=C(NCC(=O)N1CCN(Cc2ccccc2)CC1)c1ccc(Oc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 58 %

Procedure:
DIPEA (0.114 mL, 0.66 mmol) was added drop wise to (4-phenoxy-benzoylamino)-acetic acid (60 mg, 0.22 mmol) in DMF (5 mL). EDCI (106 mg, 0.55 mmol) and HOBT (35 mg, 0.27 mmol) were then added, and after 10 mins, 1-Benzyl-piperazine (46 mg, 0.27 mmol) was added. The resulting mixture was stirred at room temperature overnight. Water was added, and the resulting solid was isolated by filtration under reduced pressure to afford N-[2-(4-benzyl-piperazin-1-yl)-2-oxo-ethyl]-4-phenoxy-benzamide in 58% yield. LC-MS purity: 99%, 1H NMR (DMSO-D6): δ 8.5 (t, 1H), 7.9 (d, 2H), 7.5 (t, 2H), 7.3 (m, 7H), 7.1 (m, 4H), 4.1 (d, 2H), 3.6 (s, 2H), 3.5 (m, 4H), 2.4 (m, 4H).