Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[N+:21]([O-])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[NH2:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H](Nc2ccccc2[N+](=O)[O-])C1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC[C@@H](Nc2ccccc2N)C1
Yield: 79.7 %

Procedure:
The solution of 3(R)-(2-Nitro-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (134 mg) and Pd-C (10%, 150 mg) in MeOH (30 ml) was stirred under H2 (1 atm) for 24 hrs. After filtration through Celite, the filtrate was concentrated to give colorless oil (96.8 mg, 80%). 1H-NMR (300 MHz, CDCl3) δ 6.80 (m, 5H), 4.10 (m, 1H), 3.78 (m, 1H), 3.39 (m, 3H), 3.15 (m, 1H), 2.95 (m, 1H), 2.08 (m, 1H), 1.80 (m, 1H), 1.60 (m 3H), 1.50 (s, 9H) ppm; LRMS (calculated for C16H21N3O2-BOC)+ 191, found (M-BOC)+ 191.
Reaction SMILES: [ClH:1].O1CCOCC1.[CH2:8]([NH:15][C:16]1[CH:21]=[C:20]([O:22][C:23]2[CH:28]=[CH:27][C:26]([NH:29]C(=O)OC(C)(C)C)=[CH:25][C:24]=2[F:37])[CH:19]=[CH:18][N:17]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>>[ClH:1].[NH2:29][C:26]1[CH:27]=[CH:28][C:23]([O:22][C:20]2[CH:19]=[CH:18][N:17]=[C:16]([NH:15][CH2:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:21]=2)=[C:24]([F:37])[CH:25]=1
Reactant: CC(C)(C)OC(=O)Nc1ccc(Oc2ccnc(NCc3ccccc3)c2)c(F)c1
Agent: Cl
Solvent: C1COCCO1
Product: Nc1ccc(Oc2ccnc(NCc3ccccc3)c2)c(F)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 100 %

Procedure:
Anhydrous HCl in dioxane (4N, 2.00 mL, 8.00 mmol, 165 eq) was added to tert-butyl 4-(2-(benzylamino)pyridin-4-yloxy)-3-fluorophenylcarbamate (0.020 g, 0.0489 mmol, 1.0 eq) and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo to afford the title compound (0.017 g, 100%) a solid that was used without further purification. MS(ESI+) m/z 310 (M+H)+; HRMS(ESI+) calcd.: 310.1356, found: 310.1364.
Reaction SMILES: [NH2:1][C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[CH:14](N)=[O:15]>>[CH:14]([NH:1][C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=1)=[O:15]
Reactant: N[C@@H](Cc1ccc(O)cc1)C(=O)O
Reactant: NC=O
Product: O=CN[C@@H](Cc1ccc(O)cc1)C(=O)O

Procedure:
Under a nitrogen atmosphere, a slurry of 1.81 gm (10 mmol) tyrosine in 4.0 ml (100 mmol) formamide was heated at 90° C. for 19 hours and 10 minutes. Examination of the resulting homogeneous solution by proton NMR showed an 84% conversion of the tyrosine to its N-formyl derivative.
Reaction SMILES: [Cl:1][C:2]1[C:6]([NH2:7])=[CH:5][N:4]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[N:3]=1.C(OCC)(=O)C.C(=O)(O)[O-].[Na+].[Cl:25][CH2:26][CH2:27][C:28](Cl)=[O:29]>O>[Cl:25][CH2:26][CH2:27][C:28]([NH:7][C:6]1[C:2]([Cl:1])=[N:3][N:4]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:5]=1)=[O:29]
Reactant: Nc1cn(-c2cccnc2)nc1Cl
Reactant: O=C(Cl)CCCl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Product: O=C(CCCl)Nc1cn(-c2cccnc2)nc1Cl
Temperature: 5 °C
Yield: 95.5 %

Procedure:
A 100 mL, three-neck round bottom flask was charged with 3-chloro-1-(pyridine-3-yl)-1H-pyrazol-4-amine (1.00 g, 5.14 mmol) and ethyl acetate (10 mL). Sodium bicarbonate (1.08 g, 6.17 mmol) was added and the reaction mixture was cooled to 5° C. 3-Chloropropanoyl chloride (0.783 g, 6.17 mmol) was added dropwise at <20° C. The reaction was allowed to warm up to 20° C. and stirred for 2 hours, at which point thin layer chromatography analysis (Eluent: ethyl acetate) indicated that the reaction was complete. The reaction was diluted with water (50 mL) and the layers separated. The aqueous layer was extracted with ethyl acetate (20 mL) and the combined organic layers were concentrated to dryness to afford a white solid (1.40 g, 96%): mp 152-154° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.04 (s, 1H), 9.07 (d, J=2.7 Hz, 1H), 8.89 (s, 1H), 8.54 (dd, J=4.7, 1.4 Hz, 1H), 8.23 (ddd, J=8.4, 2.7, 1.4 Hz, 1H), 7.54 (dd, J=8.4, 4.7, Hz, 1H), 3.90 (t, J=6.2 Hz, 2H), 2.94 (t, J=6.2 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) δ 167.90, 147.50, 139.47, 135.46, 133.47, 125.51, 124.20, 122.47, 119.87, 40.63, 37.91; ESIMS m/z 285 ([M+H]+).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C@@H:9]2[CH2:13][N:12]([C@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[C:11](=O)[CH2:10]2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:32])=CC=1>>[CH2:1]([O:3][C:4]([C:6]1([C@H:9]2[CH2:13][N:12]([C@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[C:11](=[S:32])[CH2:10]2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)C1([C@H]2CC(=O)N([C@@H](C)c3ccccc3)C2)CC1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Product: CCOC(=O)C1([C@@H]2CC(=S)N([C@@H](C)c3ccccc3)C2)CC1

Procedure:
The thus separated (4R)-4-(1-ethoxycarbonylcyclopropyl)-1-[(S)-1-phenylethyl]-2-pyrrolidone is allowed to react with Lawesson reagent to give (4S)-4-(1-ethoxycarbonylcyclopropyl)-1-[(S)-1-phenylethyl]-2-pyrrolidinethione. This reaction can also be effected using phosphorus pentasulfide.
Reaction SMILES: C1(O[C:8]([N:10]2[CH2:14][CH2:13][CH:12]([CH2:15][C:16]([N:18]3[CH2:23][CH2:22][CH:21]([CH:24]4[C:30]5=[N:31][CH:32]=[C:33]([Br:35])[CH:34]=[C:29]5[CH2:28][CH2:27][C:26]5[CH:36]=[C:37]([Cl:41])[CH:38]=[C:39]([Cl:40])[C:25]4=5)[CH2:20][CH2:19]3)=[O:17])[CH2:11]2)=[NH:9])C=CC=CC=1.[NH2:42][OH:43].Cl.NO.[OH-].[Na+]>CO>[Br:35][C:33]1[CH:34]=[C:29]2[CH2:28][CH2:27][C:26]3[CH:36]=[C:37]([Cl:41])[CH:38]=[C:39]([Cl:40])[C:25]=3[CH:24]([CH:21]3[CH2:20][CH2:19][N:18]([C:16](=[O:17])[CH2:15][CH:12]4[CH2:13][CH2:14][N:10]([C:8](=[NH:9])[NH:42][OH:43])[CH2:11]4)[CH2:23][CH2:22]3)[C:30]2=[N:31][CH:32]=1
Reactant: N=C(Oc1ccccc1)N1CCC(CC(=O)N2CCC(C3c4ncc(Br)cc4CCc4cc(Cl)cc(Cl)c43)CC2)C1
Reactant: NO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: N=C(NO)N1CCC(CC(=O)N2CCC(C3c4ncc(Br)cc4CCc4cc(Cl)cc(Cl)c43)CC2)C1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Dissolve the product of Example 9 (1 equivalent) in CH3OH. Prepare an aqueous solution of hydroxylamine by dissolving hydroxylamine hydrochloride (1 equivalent) in 50% (w/v) NaOH (1 equivalent) and add to the mixture; stir at 25° C. for 18 h. Evaporate the solution to dryness and triturate with water. Filter off the solid and purify on silica gel to give the title compound.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]([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][CH2:39][CH2:40][CH2:41][CH3:42])=[O:25]>O1CCCC1>[OH:25][CH:24]([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][CH2:39][CH2:40][CH2:41][CH3:42])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH3:7]
Reactant: CCCCCCCCCCCCCCCCCC(=O)CCCCCCCCCCCCCCCCC
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CCCCCCCCCCCCCCCCCC(O)CCCCCCCCCCCCCCCCC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
18-Hydroxypentatriacontane (2-1) was prepared as follows and used without further purification. In a dry flask charged with argon was prepared a solution of lithium aluminum hydride (0.75 g, (19.8 mmol)) in freshly distilled tetrahydrofuran (400 mL). To this solution was added stearone (5.0 g, (9.9 mmol)). The reaction mixture was slowly brought to reflux (and allowed to stir at reflux overnight). After cooling to room temperature, the remaining lithium aluminum hydride was quenched by the dropwise addition of water (0.76 mL), followed by 15% NaOH (0.76 mL), and water again (2.2 mL). The reaction mixture was allowed to stir for 1 hour. The solvent was evaporated, and the resulting solids were triturated with hot toluene (300 mL). The toluene was evaporated to yield the desired alcohol (4.9 g. 97% yield) 1H NMR (300 MHz, CDCl3, TMS=0), δ3.58 (m, 1H), 1.38 (m, 4H), 1.25 (bs, 60H), 0.88 (t, 6H, J=6.5).
Reaction SMILES: [CH:1]([C:4]1[NH:8][N:7]=[CH:6][CH:5]=1)([CH3:3])[CH3:2].Br[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12]>>[CH2:14]([O:13][C:11](=[O:12])[CH2:10][N:8]1[C:4]([CH:1]([CH3:3])[CH3:2])=[CH:5][CH:6]=[N:7]1)[CH3:15]
Reactant: CCOC(=O)CBr
Reactant: CC(C)c1ccn[nH]1
Product: CCOC(=O)Cn1nccc1C(C)C
Yield: 6 %

Procedure:
Prepared according to the method described for Preparation 75 using 5-isopropyl-1H-pyrazole and ethyl bromoacetate. The residue was purified using silica gel column chromatography eluting with 4:1 hexane:EtOAc. The title compound was isolated as the lower running minor product in 6% yield, and taken directly on to the next step.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([N+:15]([O-:17])=[O:16])[C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]1.ClCCl.C(=O)([O-])[O-].[K+].[K+].[CH:27]1(B(O)O)[CH2:29][CH2:28]1>O1CCOCC1.Cl[Pd-2](Cl)([P+](C1C=CCC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CCC=1>[CH:27]1([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([N+:15]([O-:17])=[O:16])[C:7]=2[N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[CH2:29][CH2:28]1
Reactant: OB(O)C1CC1
Reactant: CN1CCN(c2c(Br)cncc2[N+](=O)[O-])CC1
Agent: Cl[Pd-2](Cl)([P+](C1=CCC=C1)(c1ccccc1)c1ccccc1)[P+](C1=CCC=C1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: C1COCCO1
Product: CN1CCN(c2c(C3CC3)cncc2[N+](=O)[O-])CC1
Temperature: 100 °C

Procedure:
A mixture of 1-(3-bromo-5-nitro-4-pyridyl)-4-methyl-piperazine (synthesized from 1-methylpiperazine and 3-bromo-4-chloro-5-nitropyridine using procedure Step 1 of Preparation N-1) (467.4 mg, 1.552 mmol), ferrous; dichloro-bis[cyclopenta-1,4-dien-1-yl(diphenyl)phosphaniumyl]palladium(2-); dichloromethane (63.37 mg, 0.07760 mmol), potassium carbonate (429.0 mg, 3.104 mmol) and cyclopropylboronic acid (200.0 mg, 2.328 mmol) in dioxane (5 mL) was degassed and flushed with nitrogen (×2). The reaction was heated at 100° C. in a sealed tube for 18 h. At room temperature the reaction mixture was filtered through Celite and evaporated to dryness, yielding 1-(3-cyclopropyl-5-nitropyridin-4-yl)-4-methylpiperazine as a dark orange solid that was used directly in the next reaction without further purification (288 mg, 66%). MS (ES+) 263.2
Reaction SMILES: [BrH:1].[C:2]([C:4]([S:10][C:11]([F:14])([F:13])[F:12])=[CH:5][CH:6]=[CH:7]OC)#[N:3].C([O-])([O-])=O.[Na+].[Na+]>CC(O)=O>[Br:1][C:2]1[C:4]([S:10][C:11]([F:14])([F:13])[F:12])=[CH:5][CH:6]=[CH:7][N:3]=1
Reactant: COC=CC=C(C#N)SC(F)(F)F
Reactant: Br
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: FC(F)(F)Sc1cccnc1Br
Temperature: 55 °C

Procedure:
A solution of 30% HBr, AcOH (70 mL) was added dropwise with stirring at 40° C. to a solution of 4-cyano-4-trifluoromethylthio-3-butenealdehydedimethylacetal and 1-cyano-1-trifluoromethylthio-4-methoxy-1,3-butadiene (8.8 g) in AcOH (40 mL). After the addition, the solution was heated at 55° C. for 2 hours, poured onto ice and neutralized with solid Na2CO3. The solution was extracted with CH2Cl2 (3-) and the CH2Cl2 extracts dried, filtered and concentrated to dryness. The residual oil was distilled at 68°-71° C. at 0.3 mm of yield 4.0 g (16%) of 2-bromo-3-trifluoromethylthiopyridine 1H NMR (CDCL3) δ 7.35 (1H, dd, J=4 and 8), 8.05 (1H, dd, J=2 and 8), 8.45 (1H, dd, J=3 and 4); 19F NFR (CDCl3) +40.7 (s).
Reaction SMILES: Br[C:2]1[C:7]([SiH:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:6][C:5]([CH3:21])=[CH:4][N:3]=1.[Br-].[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[Zn+].N>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.O1CCCC1>[CH3:21][C:5]1[CH:6]=[C:7]([SiH:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:2]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=2)=[N:3][CH:4]=1
Reactant: Cc1cnc(Br)c([SiH](c2ccccc2)c2ccccc2)c1
Reactant: [Zn+]c1ccccn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: N
Agent: [Br-]
Solvent: C1CCOC1
Product: Cc1cnc(-c2ccccn2)c([SiH](c2ccccc2)c2ccccc2)c1
Temperature: 25 °C

Procedure:
To a reaction container equipped with a cooling apparatus, 2.28 g of tetrakis(triphenylphosphine)palladium, 7 g of 2-bromo-5-methyldiphenylsilylpyridine obtained in the above-mentioned Example 5-2 and 125 mL of tetrahydrofuran were added. To the obtained mixture, 39.51 mL of 2-pyridyl zinc bromide (0.5 M/tetrahydrofuran solution) was added with stirring at room temperature. The obtained mixture was stirred at 50° C. for 7 hours and 25 minutes to effect reaction. The reaction mixture was cooled until room temperature and then, 170 mL of 28% aqueous ammonia solution was added thereto. The obtained mixture was extracted three times with 200 mL of chloroform. The obtained organic layers were mixed and dried with magnesium sulfate. After removing magnesium sulfate by filtration, the filtrate was concentrated to obtain a crude product. The crude product was purified with silica gel column chromatography followed by further recrystallization with hexane to obtain 2.56 g of 5-methyldiphenylsilyl-2,2′-bipyridine.
Reaction SMILES: N[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5](SC2C=CC=C(S(CCO)(=O)=O)C=2)=[CH:4][C:3]=1Br.C1(O)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].CO>CN(C)C=O.OS(O)(=O)=O.O=S(=O)=O>[CH:9]1[C:8]2[C:7](=[O:17])[C:6]3[C:15](=[CH:2][CH:3]=[CH:4][CH:5]=3)[C:14](=[O:16])[C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: Nc1c(Br)cc(Sc2cccc(S(=O)(=O)CCO)c2)c2c1C(=O)c1ccccc1C2=O
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: O=S(=O)=O
Solvent: CO
Solvent: CN(C)C=O
Solvent: Oc1ccccc1
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
1-Amino-2-bromo-4-(3'-β-hydroxyethylsulfonylphenylthio)anthraquinone (5.2 parts) and phenol (9.5 parts) were allowed to react with each other at 100° to 120° C. in dimethylformamide in the presence of potassium carbonate. After completion of the reaction methanol was added thereto to deposit crystals, which were collected on a filter, well washed with water and then dried at 80° C. The product obtained was subjected to both sulfonation and esterification at 20° to 40° C. in 10% oleum. Thereafter, ice was added to the reaction mixture to deposit crystals, which were collected on a filter to obtain an anthraquinone compound of the following formula (free acid form). ##STR197##
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:10]([O:12][CH3:13])=[O:11])=[N:4][C:5](Br)=[C:6]([F:8])[CH:7]=1.[F:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=1B1OC(C)(C)C(C)(C)O1.CCN(C(C)C)C(C)C>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[NH2:1][C:2]1[C:3]([C:10]([O:12][CH3:13])=[O:11])=[N:4][C:5]([C:16]2[C:15]([F:14])=[CH:20][CH:19]=[CH:18][C:17]=2[F:21])=[C:6]([F:8])[CH:7]=1
Reactant: CC1(C)OB(c2c(F)cccc2F)OC1(C)C
Reactant: COC(=O)c1nc(Br)c(F)cc1N
Agent: CC(C)(C)[P]([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1nc(-c2c(F)cccc2F)c(F)cc1N
Temperature: 100 °C
Yield: 74.4 %

Procedure:
To a screw-cap vial equipped with a magnetic stir bar, methyl 3-amino-6-bromo-5-fluoropyridine-2-carboxylate (99.6 mg, 0.400 mmol) was added, followed by 2-(2,6-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Combi-Blocks, 190 mg, 0.80 mmol), and bis(tri-tert-butylphosphine)palladium (40.9 mg, 0.080 mmol). The vial was sealed with a PTFE-lined septum, evacuated and backfilled with nitrogen three times. 1,4-Dioxane (2.0 mL) was added via a syringe, followed by DIPEA (0.14 mL, 0.80 mmol) and deoxygenated water (0.05 mL). The mixture was heated at 100° C. for 2 h. After cooling to room temperature, the mixture was diluted with EtOAc (40 mL) and washed with water (40 mL) and brine (40 mL), then dried over Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by chromatography on silica gel (0-50% EtOAc in hexanes) to give the sub-title compound as a white solid (84.0 mg, 74%). LCMS calc. for C13H10F3N2O2(M+H)+: m/z=283.1. found 283.1.
Reaction SMILES: [C:1]([O:14][CH:15]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH2:16][C:17]([O:19]C(C)(C)C)=O)(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[NH2:35][CH2:36][C:37]([NH:39][C@H:40]([C:43]([OH:45])=[O:44])[CH2:41][OH:42])=[O:38]>>[C:1]([O:14][CH:15]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH2:16][C:17]([NH:35][CH2:36][C:37]([NH:39][C@H:40]([C:43]([OH:45])=[O:44])[CH2:41][OH:42])=[O:38])=[O:19])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: NCC(=O)N[C@@H](CO)C(=O)O
Reactant: CCCCCCCCCCCC(=O)OC(CCCCCCCCCCC)CC(=O)OC(C)(C)C
Product: CCCCCCCCCCCC(=O)OC(CCCCCCCCCCC)CC(=O)NCC(=O)N[C@@H](CO)C(=O)O
Yield: 61.5 %

Procedure:
Starting from tert-butyl 3-dodecanoyloxytetradecanoate (165 mg) prepared by the method described in Preparation 3-(2) and N-glycyl-L-serine (162 mg), N-[N-(3-dodecanoyloxytetradecanoyl)glycyl]-L-serine (120 mg) was obtained as an amorphous powder according to similar manner to that of Example 1.
Reaction SMILES: [S:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[CH:3]=[C:2]1[C:10](OC)=[O:11].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[S:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[CH:3]=[C:2]1[CH2:10][OH:11]
Reactant: COC(=O)c1cc2cnccc2s1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCc1cc2cnccc2s1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of methyl thieno[3,2-c]pyridine-2-carboxylate (D-2) (15 g, 77.6 mmol) in anhydrous THF (250 mL) was added LiAlH4 (4.42 g, 116.4 mmol) in portions at 0° C. The suspension was stirred at 0° C. for 1 h and then quenched by adding saturated aqueous NH4Cl and filtered. The filtrate was washed with brine and concentrated. The residue was used in the next step without any further purification (10.3 g).
Reaction SMILES: [CH3:1][C:2]1[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][C:3]=1[O:4][C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1.C(O)=O>CO.[Pd]>[CH3:1][C:2]1[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][C:3]=1[O:4][C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1
Reactant: Cc1ccc([N+](=O)[O-])cc1Oc1cccnc1
Agent: [Pd]
Solvent: CO
Solvent: O=CO
Product: Cc1ccc(N)cc1Oc1cccnc1
Reaction time: 1 h
Yield: 82.8 %

Procedure:
A solution of 3-(2-methyl-5-nitrophenoxy)pyridine (80 mg, 0.35 mmol) and 10% Pd/C (50% wet, 165 mg, 0.08 mmol) in methanol (4 mL) was treated with formic acid (89%, 1 mL, 35 mmol) and the resultant solution was stirred at RT. After 1 h, the reaction mixture was filtered through Celite®, and the filter cake was washed with methanol. The filtrates were concentrated in vacuo, diluted with 40 mL of a pH 12 aqueous solution and extracted with ethyl acetate (3×25 mL). The extracts were dried (Na2SO4) and concentrated in vacuo to provide 4-methyl-3-(pyridin-3-yloxy)benzenamine (58 mg, 83% yield). 1H NMR (400 MHz, CDCl3) δ 8.36 (m, 2H), 8.32 (dd, J=4.6, 1.4 Hz, 1H), 7.26-7.18 (m, 3H), 7.05 (d, J=8.0 Hz, 1H), 6.49 (dd, J=8.8, 2.4 Hz, 1H), 6.29 (d, J=2.4 Hz, 1H), 2.11 (s, 3H); MS (ESI) m/z: 201.0 (M+H+).
Reaction SMILES: [N:1]1([C:6]([C:8]2[CH:9]=[C:10]([CH:12]=[CH:13][CH:14]=2)[NH2:11])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>O1CCCC1>[N:1]1([CH2:6][C:8]2[CH:9]=[C:10]([CH:12]=[CH:13][CH:14]=2)[NH2:11])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Nc1cccc(C(=O)N2CCCC2)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: Nc1cccc(CN2CCCC2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 98.3 %

Procedure:
To a solution of 1.12 g of 3-(pyrrolidin-1-ylcarbonyl)aniline obtained in stage b) below in 100 mL of tetrahydrofuran are added, under argon, 0.89 g of lithium aluminium hydride. The reaction mixture is stirred for one hour at room temperature and then cooled to 0° C. and treated successively with 0.89 mL of water, 0.89 mL of 15% (by weight) sodium hydroxide solution and 2.67 mL of water. The solid formed is filtered off and washed with ethyl acetate, and the filtrate is concentrated under reduced pressure to give 1.02 g of 3-(pyrrolidin-1-ylmethyl)aniline, the characteristics of which are as follows:
Reaction SMILES: [CH3:1][CH:2]([CH2:7][C:8]([CH3:11])([CH3:10])[CH3:9])[CH2:3][PH:4](=[O:6])[OH:5].[CH3:12][CH2:13][C:14]([CH2:22][O:23][CH2:24][CH:25]=[CH2:26])([CH2:17][O:18][CH2:19][CH:20]=[CH2:21])[CH2:15][OH:16]>C(OOC(CC)(C)C)(CC)(C)C>[OH:16][CH2:15][C:14]([CH2:17][O:18][CH2:19][CH2:20][CH2:21][P:4]([OH:6])([CH2:3][CH:2]([CH3:1])[CH2:7][C:8]([CH3:10])([CH3:9])[CH3:11])=[O:5])([CH2:13][CH3:12])[CH2:22][O:23][CH2:24][CH2:25][CH2:26][P:4]([CH2:3][CH:2]([CH3:1])[CH2:7][C:8]([CH3:10])([CH3:9])[CH3:11])(=[O:5])[OH:6]
Reactant: C=CCOCC(CC)(CO)COCC=C
Reactant: CC(C[PH](=O)O)CC(C)(C)C
Agent: CCC(C)(C)OOC(C)(C)CC
Product: CCC(CO)(COCCCP(=O)(O)CC(C)CC(C)(C)C)COCCCP(=O)(O)CC(C)CC(C)(C)C
Temperature: 140 °C
Yield: 100.1 %

Procedure:
10 g (0.056 moles) of 2,4,4-trimethylpentyl phosphinic acid, 6.01 g (0.028 moles) of trimethylolpropane diallyl ether and 0.4 mL (0.0019 moles) of di-tert-amylperoxide are mixed in a 100 mL single neck flask. The mixture is purged with argon to remove oxygen and is heated under argon for 6 hours at 140° C. Tert-amyl alcohol is removed by distillation and 16 g (quantitative yield) of [3-(2-hydroxymethyl-2-{3-[hydroxy-(2,4,4-trimethylpentyl)-phosphinoyl]-propoxymethyl}-butoxy)-propyl]-(2,4,4-trimethylpentyl)-phosphinic acid is obtained as a viscous oil.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].Cl.Cl[CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[N:16]1([CH2:15][CH2:14][O:1][C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=2)[C:5]([O:7][CH3:8])=[O:6])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1
Reactant: COC(=O)c1cccc(O)c1
Reactant: ClCCN1CCOCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: COC(=O)c1cccc(OCCN2CCOCC2)c1
Temperature: 25 °C
Reaction time: 96 h
Yield: 60.6 %

Procedure:
A mixture of methyl 3-hydroxybenzoate (8.0 g, 56 mmol) and 4-(2-chloroethyl)-morpholine hydrochloride (15.7 g, 84 mmol) and potassium carbonate (11.5 g, 83 mmol) in toluene (50 ml) was heated at reflux. After 4 days, the reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic layer was washed with water and then extracted with dilute hydrochloric acid. The acidic layer was separated, basified with 5 N sodium hydroxide and the product was extracted into ethyl acetate. The organics were removed in vacuo and the residue was purified by flash chromatography (elution gradient 3% acetone/methylene chloride) to give methyl 3-(2-morpholin-4-ylethoxy)benzoate (9.0 g) as an oil.