Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[C:11]([O:16][CH3:17])(=[O:15])[C@H:12]([CH3:14])O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(OCC)(=O)C>[CH3:17][O:16][C:11](=[O:15])[C@H:12]([O:10][C:8]1[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([F:1])[CH:9]=1)[CH3:14]
Reactant: COC(=O)[C@H](C)O
Reactant: N#Cc1ccc(O)cc1F
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Product: COC(=O)[C@@H](C)Oc1ccc(C#N)c(F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 35.8 %

Procedure:
To a stirred solution of 2-fluoro-4-hydroxybenzonitrile (0.2 g, 1.5 mmol), methyl (S)-(−)-lactate (0.14 mL, 1.5 mmol) and triphenylphosphine (1.15 g, 4.4 mmol) at room temperature, diethyl azodicarboxylate (0.67 mL, 4.4 mmol) was added dropwise. The mixture was stirred at room temperature overnight, diluted with ethyl acetate and washed successively with dilute aqueous sodium hydroxide, dilute aqueous hydrochloric acid, brine, and dried (Na2SO4). Solvents were stripped in vacuo. The resulting oil was washed with diethyl ether and the precipitate was filtered off. The mother liquor was adsorbed onto silica gel and the product purified by flash column chromatography (20% dichloromethane/hexane), affording 0.12 g of a pink oil (36% yield).
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:7][C:8]1[C:16]2[C:11](=[N:12][CH:13]=[N:14][C:15]=2[NH2:17])[NH:10][N:9]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:38](Cl)[CH3:39])[C:22]2[O:28][CH2:27][CH2:26][N:25]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:24][C:23]=2[C:36]=1[CH3:37]>CN(C)C=O.C(OCC)(=O)C>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([CH:38]([C:21]3[C:22]4[O:28][CH2:27][CH2:26][N:25]([C:29]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:30])[CH2:24][C:23]=4[C:36]([CH3:37])=[C:19]([Cl:18])[CH:20]=3)[CH3:39])[N:9]=[C:8]([CH3:7])[C:16]=12
Reactant: Cc1c(Cl)cc(C(C)Cl)c2c1CN(C(=O)OC(C)(C)C)CCO2
Reactant: Cc1n[nH]c2ncnc(N)c12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1c(Cl)cc(C(C)n2nc(C)c3c(N)ncnc32)c2c1CN(C(=O)OC(C)(C)C)CCO2
Reaction time: 0.17 h
Yield: 61.9 %

Procedure:
Cesium carbonate (500 mg, 2 mmol) was added to a mixture of 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (150 mg, 0.98 mmol) in N,N-dimethylformamide (30 mL) and stirred for 10 minutes. To this was added tert-butyl 7-chloro-9-(1-chloroethyl)-6-methyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (290 mg, 0.82 mmol) in N,N-dimethylformamide (1 mL) and the reaction was stirred at 80° C. for 1 hour. The mixture was diluted with ethyl acetate and washed with water and brine. The extracts were dried over sodium sulfate, filtered and evaporated. The crude was dissolved in methylene chloride and filtered to remove insoluble material (unwanted regioisomer). Purification on silica gel using ethyl acetate in hexanes (0-100%) followed by methanol in ethyl acetate (0-15%) gave the desired compound (240 mg, 62%). LCMS calculated for C23H30ClN6O3(M+H)+: m/z=473.2; found: 473.2. 1H NMR (300 MHz, CD3OD): δ 8.14 (s, 1 H), 7.29 (m, 1 H), 6.32 (m, 1 H), 4.70 (m, 1 H), 4.40 (m, 1 H), 3.83 (m, 2 H), 3.57 (m, 2 H), 2.58 (s, 3 H), 2.48 (m, 3 H), 1.78 (m, 3 H), 1.39 (, 9H).
Reaction SMILES: C[O:2][C:3](=[O:25])[CH2:4][CH2:5][O:6][CH2:7][C:8]([C:20](=[O:24])[NH:21][CH2:22][CH3:23])([C:15](=[O:19])[NH:16][CH2:17][CH3:18])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[OH-].[Na+]>C1COCC1.CO>[CH2:17]([NH:16][C:15]([C:8]([C:20](=[O:24])[NH:21][CH2:22][CH3:23])([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:7][O:6][CH2:5][CH2:4][C:3]([OH:25])=[O:2])=[O:19])[CH3:18]
Reactant: CCNC(=O)C(COCCC(=O)OC)(C(=O)NCC)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CCNC(=O)C(COCCC(=O)O)(C(=O)NCC)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.8 %

Procedure:
3-(2,2′-Bisethylcarbamoyl-2-phenylethoxy)propionic acid methyl ester (125 mg) was dissolved in THF (0.5 mL) and MeOH (0.5 mL), and 1N sodium hydroxide (0.5 mL) was added thereto. The solution was stirred at room temperature for 1 hour and then concentrated. The residue was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with water and concentrated to give 3-(2,2′-bisethylcarbamoyl-2-phenylethoxy)propionic acid (115 mg).
Reaction SMILES: Cl[CH2:2][C:3](=O)[CH:4]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:8]([F:18])[CH:7]=1)[CH3:5].C(Cl)(Cl)Cl.[CH3:24][NH:25][C:26]([NH2:28])=[S:27].C(=O)(O)[O-].[Na+]>CO.[Na+].[Cl-]>[CH3:24][NH:25][C:26]1[S:27][CH:2]=[C:3]([CH:4]([C:6]2[CH:11]=[CH:10][C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:8]([F:18])[CH:7]=2)[CH3:5])[N:28]=1
Reactant: CNC(N)=S
Reactant: CC(C(=O)CCl)c1ccc(-c2ccccc2)c(F)c1
Agent: O=C([O-])O
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Solvent: ClC(Cl)Cl
Product: CNc1nc(C(C)c2ccc(-c3ccccc3)c(F)c2)cs1
Yield: 70 %

Procedure:
A mixture of (+)-1-chloro-3-(2-fluoro-4-biphenylyl)-2-butanone (27.7 mg, 0.1 mmol; [α]D25°C. +180° (c=0.744, CHCl3), N-methylthiourea (9 mg, 0.1 mmol) and sodium bicarbonate (9.2 mg, 0.11 mmol) in methanol (1 ml) was stirred at room temperature for 28 hr and the mixture was diluted with NaCl aq., then extracted with ethyl acetate. The extracts were dried with magnesium sulfate and evaporated under reduced pressure to a residue, which was chromatographed to afford (+)-2-methylamino-4-(1-(2-fluoro-4-biphenylyl)ethyl)thiazole (21.9 mg, 70% yield): [α]D25°C. +10.7° (c=0.15, CHCl3); 70%ee.
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:12][C@@H:13]1[C:41](=[O:42])[N:15]2[C:16]([C:25]([O:27]C(C3C=CC=CC=3)C3C=CC=CC=3)=[O:26])=[C:17]([CH2:20][O:21][C:22](=[O:24])[NH2:23])[CH2:18][S:19][C@H:14]12.C(Cl)(Cl)Cl.FC(F)(F)C(O)=O.C1(OC)C=CC=CC=1.N>O.C(OCC)(=O)C>[NH2:12][C@@H:13]1[C:41](=[O:42])[N:15]2[C:16]([C:25]([OH:27])=[O:26])=[C:17]([CH2:20][O:21][C:22](=[O:24])[NH2:23])[CH2:18][S:19][C@H:14]12
Reactant: NC(=O)OCC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)[C@@H](N)[C@H]2SC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: N
Solvent: ClC(Cl)Cl
Solvent: CCOC(C)=O
Solvent: COc1ccccc1
Product: NC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](N)[C@H]2SC1
Reaction time: 1 h
Yield: 96.1 %

Procedure:
Diphenylmethyl (6R,7R)-7-amino-3-carbamoyloxymethylceph-3-em-4-carboxylate toluene-p-sulphonic acid salt (300.0 g, 0.44 mole), solvated with ca. 0.6 mole of chloroform, was added in portions over 30 minutes to a stirred mixture of trifluoroacetic acid (300 ml) and anisole (300 ml) immersed in a water-bath at 20°. The temperature of the mixture rose from 23° to 28° over the first 20 minutes but fell back to 26° by the end of the addition. The golden yellow solution was stirred for 1 hour, the temperature falling to 21°, and was then added to a stirred mixture of ethyl acetate (1.5 liters) and water (1.5 liters) immersed in an ice-bath. The pH of the stirred mixture was adjusted to 3.8 over 10 minutes with ammonia solution (S.G. 0.880), the temperature rising to 38°. The suspension was stirred and cooled to 10° over 1.25 hours and filtered. The cream solid was washed with water (750 ml) and ethyl acetate (4 × 200 ml) and dried in vacuo to give the title compound (115.6 g, 96.2%); λmax (pH6 phosphate) 265nm (ε7,750); purity by HPLC (high pressure liquid chromatography) 99.7%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:46]2[CH:51]=[CH:50][C:49]([C:52]([F:55])([F:54])[F:53])=[CH:48][CH:47]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][CH2:17][N:18]([CH2:34][CH2:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]([O:44]C)=[O:43])=[CH:38][CH:37]=1)[CH:19]1[CH2:28][CH2:27][CH2:26][C:25]2[N:24]=[C:23]([C:29]([O:31]CC)=[O:30])[CH:22]=[CH:21][C:20]1=2.[OH-].[Na+]>O1CCOCC1>[C:42]([C:39]1[CH:38]=[CH:37][C:36]([CH2:35][CH2:34][N:18]([CH2:17][CH2:16][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[O:9][CH2:8][C:7]2[CH:6]=[CH:5][C:4]([C:46]3[CH:47]=[CH:48][C:49]([C:52]([F:54])([F:55])[F:53])=[CH:50][CH:51]=3)=[CH:3][C:2]=2[Cl:1])[CH:19]2[CH2:28][CH2:27][CH2:26][C:25]3[N:24]=[C:23]([C:29]([OH:31])=[O:30])[CH:22]=[CH:21][C:20]2=3)=[CH:41][CH:40]=1)([OH:44])=[O:43]
Reactant: CCOC(=O)c1ccc2c(n1)CCCC2N(CCc1ccc(C(=O)OC)cc1)CCc1ccccc1OCc1ccc(-c2ccc(C(F)(F)F)cc2)cc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: O=C(O)c1ccc(CCN(CCc2ccccc2OCc2ccc(-c3ccc(C(F)(F)F)cc3)cc2Cl)C2CCCc3nc(C(=O)O)ccc32)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
42 g (54.46 mmol) of ethyl 5-([2-(2-{[3-chloro-4′-(trifluoromethyl)biphenyl-4-yl]methoxy}-phenyl)ethyl]{2-[4-(methoxycarbonyl)phenyl]ethyl}amino)-5,6,7,8-tetrahydroquinoline-2-carboxylate (Enantiomer 2, Example 92A) were dissolved in 429 ml of dioxane, 163 ml of 1 N aqueous sodium hydroxide solution were added and the mixture was then stirred at room temperature overnight. After the reaction had gone to completion, the dioxane was removed on a rotary evaporator and the mixture that remained was diluted with about 750 ml of water. The mixture was then acidified to pH 4-5 using acetic acid. The precipitated solid was filtered off with suction and washed repeatedly with water (about 250 ml of water in total). The solid was then taken up in 750 ml of water and stirred at room temperature overnight. After another filtration with suction, the solid was again washed with water and then dried under high vacuum overnight using the drying agent phosphorus pentoxide. The drying agent was then removed and the solid was dried at 40° C. for a further 24 h. In this manner, 35 g (48 mmol, 88% of theory) of the title compound were obtained.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[S:9]([NH:12][C:13]1[CH:14]=[C:15]([CH:21]=[CH:22][C:23]=1[F:24])[C:16](OCC)=[O:17])(=[O:11])=[O:10].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:35][C:36]1[N:41]=[C:40]([CH3:42])[CH:39]=[CH:38][N:37]=1>C1COCC1>[Cl:35][C:36]1[N:41]=[C:40]([CH2:42][C:16]([C:15]2[CH:21]=[CH:22][C:23]([F:24])=[C:13]([NH:12][S:9]([C:3]3[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=3[F:8])(=[O:11])=[O:10])[CH:14]=2)=[O:17])[CH:39]=[CH:38][N:37]=1
Reactant: Cc1ccnc(Cl)n1
Reactant: CCOC(=O)c1ccc(F)c(NS(=O)(=O)c2c(F)cccc2F)c1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: O=C(Cc1ccnc(Cl)n1)c1ccc(F)c(NS(=O)(=O)c2c(F)cccc2F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 50 %

Procedure:
To a solution of ethyl 3-{[(2,6-difluorophenyl)sulfonyl]amino}-4-fluorobenzoate (5.0 g, 13.9 mmol) in THF (100 mL) was added 1.0 M LiHMDS in THF (34.8 mL, 34.8 mmol). A solution of 2-chloro-4-methylpyrimidine (2.7 g, 20.9 mmol) in THF (100 mL) was added dropwise over 30 min, and the reaction was stirred overnight at rt. The reaction was quenched with 10 mL of MeOH and concentrated, and the residue was partitioned between EtOAc and saturated aqueous NaHCO3. The aqueous layer was extracted with 2×50 mL EtOAc, and the combined organic layers were passed through a pad of silica gel, concentrated, and adsorbed onto silica gel. The crude product was purified via flash chromatography with 0-100% EtOAc/DCM to generate 3.07 g (50% yield) of the title compound as a white powder. MS (ESI): 443 (M+H).
Reaction SMILES: BrCC1C=C(Cl)SC=1Cl.[Cl:10][C:11]1[S:12][C:13]([Cl:19])=[CH:14][C:15]=1[C:16](O)=[O:17]>C1COCC1>[Cl:10][C:11]1[S:12][C:13]([Cl:19])=[CH:14][C:15]=1[CH2:16][OH:17]
Reactant: O=C(O)c1cc(Cl)sc1Cl
Agent: Clc1cc(CBr)c(Cl)s1
Solvent: C1CCOC1
Product: OCc1cc(Cl)sc1Cl
Temperature: 25 °C
Reaction time: 1 h

Procedure:
3-bromomethyl-2,5-dichloro-thiophene: Borane-THF complex (6.009 mL, 6.01 mmol) was added dropwise into a THF (5 mL) solution of 2,5-dichlorothiophene-3-carboxylic acid (296 mg, 1.502 mmol). The resultant solution was stirred at rt under argon overnight. The reaction was quenched with dilute HCl (12 mL) and stirred at rt for 1 h. The reaction was diluted with water and extracted with EtOAc (2×20 mL), washed with NaOH solution and brine, dried (Na2SO4), filtered and evaporated to provide (2,5-dichloro-thiophen-3-yl)-methanol, which was purified by flash chromatography. LCMS m/z 183.2 (M+H)+. To a solution of this intermediate (215 mg, 1.175 mmol) in DCM (7 mL) was added PBr3 (0.144 mL, 1.527 mmol) via syringe. The reaction mixture was stirred at rt under argon for 15 min, then quenched with water (18 mL) and stirred at rt for 1 h. The aqueous layer was extracted with DCM (2×10 ml) and the combined organic layers were dried (Na2SO4), filtered and concentrated yielding 103A (250 mg). 1HNMR (400 MHz, CD3OD) δ: 4.47 (s, 2H), 7.02 (s, 1H).
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.CO[C:13]([CH2:15][CH2:16][C:17]1[CH:18]=[CH:19][C:20]2[CH:21]3[CH2:30][CH2:29][CH2:28][CH:22]3[C:23](=[O:27])[NH:24][C:25]=2[CH:26]=1)=O.[Cl:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=1)[CH2:35][NH2:36].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>C1(C)C=CC=CC=1.C(OCC)(=O)C.O.C(O)(C)C>[Cl:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=1)[CH2:35][NH:36][CH:16]([C:17]1[CH:18]=[CH:19][C:20]2[CH:21]3[CH2:30][CH2:29][CH2:28][CH:22]3[C:23](=[O:27])[NH:24][C:25]=2[CH:26]=1)[CH2:15][CH3:13]
Reactant: COC(=O)CCc1ccc2c(c1)NC(=O)C1CCCC21
Reactant: NCc1cccc(Cl)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: CC(C)O
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: CCC(NCc1cccc(Cl)c1)c1ccc2c(c1)NC(=O)C1CCCC21
Reaction time: 2 h
Yield: 41.4 %

Procedure:
1.6 ml (1.9 mmol) of 1.2 M diisobutylaluminum hydride (DIBAH) in toluene is added in drops to a solution of 510 mg (1.9 mmol) of 7-(methoxycarbonylethyl)-1,2,3,3a,5,9b-hexahydrocyclopenta[c]quinolin-4-one in 50 ml of toluene at −70° C. After 2 hours at −70° C., the batch is mixed with 0.75 ml (0.9 mmol) of DIBAH solution, stirred for 15 minutes, treated with 3 ml of isopropanol and 1 ml of water and stirred for 2 hours at room temperature. The reaction solution is filtered and concentrated by evaporation in a vacuum. The residue is dissolved in 50 ml of 1,2-dichloroethane, mixed with 0.38 ml (3.1 mmol) of 3-chlorobenzylamine, 0.91 g (4.3 mmol) of sodium (triacetoxy)-borohydride and 0.017 ml (0.29 mmol) of acetic acid and stirred for 24 hours at room temperature. The batch is diluted with ethyl acetate, washed with water, dried (Na2SO4) and concentrated by evaporation in a vacuum. Column chromatography on silica gel with ethyl acetate-methanol yields 290 mg of product.
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2[C:22]3[C:17](=[CH:18][C:19]([O:23][CH3:24])=[CH:20][CH:21]=3)[O:16][C:15](=[O:25])[CH:14]=2)[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:26]1([CH2:32][O:33][CH2:34][CH2:35][CH2:36][Mg]Br)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2([CH2:36][CH2:35][CH2:34][O:33][CH2:32][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:22]3[C:17](=[CH:18][C:19]([O:23][CH3:24])=[CH:20][CH:21]=3)[O:16][C:15](=[O:25])[CH2:14]2)[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Br[Mg]CCCOCc1ccccc1
Reactant: COc1ccc2c(-c3cn(Cc4ccccc4)cn3)cc(=O)oc2c1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: COc1ccc2c(c1)OC(=O)CC2(CCCOCc1ccccc1)c1cn(Cc2ccccc2)cn1
Reaction time: 1 h

Procedure:
A solution of 1 mmol of 4-(1-benzyl-1H-imidazol-4-yl)-7-methoxychromen-2-one in 5 ml of tetrahydrofuran is added to a solution of 3 mmol of 3-(phenylmethoxy)propylmagnesium bromide [183312-54-1] in 5 ml of tetrahydrofuran. The mixture is subsequently stirred for 1 hour and then poured into saturated aqueous ammonium chloride solution. It is extracted with diethyl ether (3×). The combined organic phases are dried over sodium sulphate and evaporated. From the residue the title compound is identified by means of flash chromatography (SiO2 60F) on the basis of the Rf value.
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:33]=[CH:32][C:16]([CH2:17][NH:18][C:19]3[CH:31]=[CH:30][C:22]4[O:23][C:24]([CH3:29])([CH3:28])[O:25][C:26](=[O:27])[C:21]=4[CH:20]=3)=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[C:34]1([CH2:40][CH2:41][CH:42]=O)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]#[C:12][C:13]2[CH:33]=[CH:32][C:16]([CH2:17][N:18]([CH2:42][CH2:41][CH2:40][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:19]3[CH:31]=[CH:30][C:22]4[O:23][C:24]([CH3:29])([CH3:28])[O:25][C:26](=[O:27])[C:21]=4[CH:20]=3)=[CH:15][CH:14]=2)=[CH:9][CH:10]=1)[CH2:2][CH2:3][CH3:4]
Reactant: O=CCCc1ccccc1
Reactant: CCCCc1ccc(C#Cc2ccc(CNc3ccc4c(c3)C(=O)OC(C)(C)O4)cc2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Product: CCCCc1ccc(C#Cc2ccc(CN(CCCc3ccccc3)c3ccc4c(c3)C(=O)OC(C)(C)O4)cc2)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 77.5 %

Procedure:
To a solution of 6-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2,2-dimethyl-4H-1,3-benzodioxin-4-one (150 mg, 0.34 mmol) in anhydrous DCE (3 mL) were added 3-phenylpropionaldehyde (Aldrich, 75 μL, 0.51 mmol) and sodium triacetoxyborohydride (110 mg, 0.51 mmol). The reaction mixture was stirred at rt for 24 hrs. The solvent was removed under reduced pressure. The residue was taken up with an aqueous solution of NaOH (2 mL) and extracted with Et2O (6 ml). The organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure. Purification by flash chromatography on silicagel (pentane/DCM (2/3)) gave 147 mg (77%) of the title compound as a yellow oil. HPLC, Rt: 6.3 min (purity: 99.1%). 1H NMR (CDCl3) δ: 7.45 (m, 4H), 7.32-7.15 (m, 10H), 6.91 (m, 1H), 6.80 (m, 1H), 4.49 (s, 2H), 3.42 (t, J=7.4 Hz, 2H), 2.65 (m, 4H), 1.71 (s, 6H), 1.61 (m, 2H), 1.37 (m, 2H), 0.94 (t, J=7.2 Hz, 3H)
Reaction SMILES: [CH2:1]([C:5]1[N:9]([C:10]2[N:15]=[C:14]([C:16]3[S:17][CH:18]=[CH:19][CH:20]=3)[C:13]([CH3:21])=[CH:12][N:11]=2)[N:8]=[CH:7][C:6]=1[CH2:22][NH2:23])[CH2:2][CH2:3][CH3:4].[CH3:24][N:25]1[C:29]([S:30](Cl)(=[O:32])=[O:31])=[CH:28][N:27]=[C:26]1[CH3:34].C(N(C(C)C)CC)(C)C>ClCCl>[CH2:1]([C:5]1[N:9]([C:10]2[N:15]=[C:14]([C:16]3[S:17][CH:18]=[CH:19][CH:20]=3)[C:13]([CH3:21])=[CH:12][N:11]=2)[N:8]=[CH:7][C:6]=1[CH2:22][NH:23][S:30]([C:29]1[N:25]([CH3:24])[C:26]([CH3:34])=[N:27][CH:28]=1)(=[O:32])=[O:31])[CH2:2][CH2:3][CH3:4]
Reactant: Cc1ncc(S(=O)(=O)Cl)n1C
Reactant: CCCCc1c(CN)cnn1-c1ncc(C)c(-c2cccs2)n1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCCCc1c(CNS(=O)(=O)c2cnc(C)n2C)cnn1-c1ncc(C)c(-c2cccs2)n1

Procedure:
The title compound was prepared by mixing a sample of (5-butyl-1-(5-methyl-4-(thiophen-2-yl)pyrimidin-2-yl)-1H-pyrazol-4-yl)methanamine, (from Step 3 of Example 36), 1,2-dimethyl-1H-imidazole-5-sulfonyl chloride and diisopropylethylamine in dichloromethane. 1H NMR (400 MHz, CD3OD) δ 8.68 (s 1H), 7.94 (m, 1H), 7.78 (m, 1H), 7.56 (m, 1H), 7.37 (m, 1H), 7.29 (m, 1H), 4.09 (s 2H), 3.70 (s 3H), 3.18 (br t, 2H), 2.64 (s, 3H), 2.35 (s, 3H), 1.49 (m, 2H), 1.32 (m, 2H), 0.84 (m 3H). LCMS (ES+) m/z 486 (M+1).
Reaction SMILES: C1(S([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([S:19]([CH2:21][CH3:22])=[O:20])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:23]([C:30]2[CH:35]=[CH:34][C:33]([S:36]([CH3:39])(=[O:38])=[O:37])=[CH:32][CH:31]=2)=[CH:24][CH:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)(=O)=O)C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>[Cl-].[Na+].O>[CH:25]1([CH:24]=[C:23]([C:11]2[NH:10][C:14]3=[N:15][CH:16]=[C:17]([S:19]([CH2:21][CH3:22])=[O:20])[CH:18]=[C:13]3[CH:12]=2)[C:30]2[CH:35]=[CH:34][C:33]([S:36]([CH3:39])(=[O:38])=[O:37])=[CH:32][CH:31]=2)[CH2:29][CH2:28][CH2:27][CH2:26]1
Reactant: CCS(=O)c1cnc2c(c1)cc(C(=CC1CCCC1)c1ccc(S(C)(=O)=O)cc1)n2S(=O)(=O)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: CCS(=O)c1cnc2[nH]c(C(=CC3CCCC3)c3ccc(S(C)(=O)=O)cc3)cc2c1
Yield: 87.1 %

Procedure:
A mixture of 1-benzenesulfonyl-2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-vinyl]-5-ethanesulfinyl-1H-pyrrolo[2,3-b]pyridine (56 mg, 0.096 mmol) and a solution of tetrabutylammonium fluoride in tetrahydrofuran (1 M, 3.85 mL, 3.85 mmol) was stirred for 12 h at room temperature. The mixture was poured into brine (5 mL), extracted with ethyl acetate (2×20 mL), washed with a saturated aqueous ammonium chloride solution (3×10 mL), dried over anhydrous sodium sulfate and then concentrated in vacuo to give 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-vinyl]-5-ethanesulfinyl-1H-pyrrolo[2,3-b]pyridine (37 mg, 88%) as a solid which was used in the next step without purification: LC/MS m/e calcd for C23H26N2O3S2 [M+H]+ 443.6, observed 443.1.
Reaction SMILES: [C:1](Cl)(=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[NH2:17][C@H:18]([C:41]([O:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51]/[CH:52]=[CH:53]\[CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH3:61])=[O:42])[CH2:19][C:20]([O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]/[CH:31]=[CH:32]\[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])=[O:21]>>[C:1]([NH:17][C@H:18]([C:41]([O:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51]/[CH:52]=[CH:53]\[CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH3:61])=[O:42])[CH2:19][C:20]([O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]/[CH:31]=[CH:32]\[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])=[O:21])(=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCCCCCCC(=O)Cl
Reactant: CCCCCCCC/C=C\CCCCCCCCOC(=O)C[C@H](N)C(=O)OCCCCCCCC/C=C\CCCCCCCC
Product: CCCCCCCC/C=C\CCCCCCCCOC(=O)C[C@H](NC(=O)CCCCCCCCCCCCC)C(=O)OCCCCCCCC/C=C\CCCCCCCC

Procedure:
Following the procedure for preparation of a final product in Example 1, a 10% excess of myristoyl chloride is stirred for 30 minutes at room temperature with dioleyl aspartate. Dioleyl N-myristoyl-L-aspartate, another fat mimetic of this invention, is obtained and further purified by silica gel chromatography.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:29](O)=[O:30])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17]([N:22]1[CH2:27][CH2:26][CH2:25][CH2:24][C:23]1=[O:28])[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:32][C:33]1[CH:34]=[N:35][CH:36]=[CH:37][C:38]=1[N:39]1[CH2:44][C@H:43]([CH3:45])[CH2:42][C@H:41]([NH:46][C:47](=[O:53])[O:48][C:49]([CH3:52])([CH3:51])[CH3:50])[CH2:40]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:49]([O:48][C:47]([NH:46][C@H:41]1[CH2:42][C@@H:43]([CH3:45])[CH2:44][N:39]([C:38]2[CH:37]=[CH:36][N:35]=[CH:34][C:33]=2[NH:32][C:29]([C:13]2[C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:21][C:20]3[C:15](=[CH:16][C:17]([N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][C:23]4=[O:28])=[CH:18][CH:19]=3)[N:14]=2)=[O:30])[CH2:40]1)=[O:53])([CH3:50])([CH3:51])[CH3:52]
Reactant: C[C@@H]1C[C@H](NC(=O)OC(C)(C)C)CN(c2ccncc2N)C1
Reactant: O=C(Nc1cc2ccc(N3CCCCC3=O)cc2nc1C(=O)O)OCc1ccccc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: C[C@@H]1C[C@H](NC(=O)OC(C)(C)C)CN(c2ccncc2NC(=O)c2nc3cc(N4CCCCC4=O)ccc3cc2NC(=O)OCc2ccccc2)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 19.6 %

Procedure:
To a mixture of 3-{[(benzyloxy)carbonyl]amino}-7-(2-oxopiperidin-1-yl)quinoline-2-carboxylic acid (0.015 g, 0.036 mmol), tert-butyl [(3S,5R)-1-(3-aminopyridin-4-yl)-5-methylpiperidin-3-yl]carbamate (0.013 g, 0.043 mmol) and HATU (0.034 g, 0.089 mmol) in DMF (0.3 mL), DIPEA (0.019 mL, 0.11 mmol) was added. The mixture was stirred at room temperature for 2 h, then quenched with 5 mL of EtOAc and 3 mL of 1 M NaOH. The resulting layers were separated and the aqueous phase was extracted with EtOAc. The combined organic extracts were concentrated under reduced pressure, then purified by preparative HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 60 mL/min.) to afford the sub-title compound (0.005 g, 20%). LCMS calc. for C39H46N7O6 [M+H]: m/z=708.3. found: 708.4.