Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[NH2:25][C:26]1[C:34]2[O:33][CH:32]=[CH:31][C:30]=2[CH:29]=[CH:28][CH:27]=1.Cl>C(O)(C)C>[O:33]1[C:34]2[C:26]([NH:25][C:2]3[C:11]4[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]5[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]5)=[C:9]([O:12][CH3:13])[CH:10]=4)[N:5]=[CH:4][N:3]=3)=[CH:27][CH:28]=[CH:29][C:30]=2[CH:31]=[CH:32]1
Reactant: Nc1cccc2ccoc12
Reactant: COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1
Agent: Cl
Solvent: CC(C)O
Product: COc1cc2c(Nc3cccc4ccoc34)ncnc2cc1OCCCN1CCN(C)CC1
Temperature: 85 °C
Yield: 70.6 %

Procedure:
A mixture of 4-chloro-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazoline (0.1 g), 7-aminobenzofuran (0.057 g), isopropanol (4 ml) and a solution of hydrogen chloride in isopropanol (6M, 0.06 ml) was stirred and heated to 85° C. for 3 hours. The resultant mixture was cooled to ambient temperature and the precipitate was isolated by filtration, washed in turn with a 1:1 mixture of diethyl ether and isopropanol and with diethyl ether and dried under vacuum. There was thus obtained the title compound (0.09 g) as a dihydrochloride salt; NMR Spectrum: (DMSOd6 and CF3COOD) 2.35 (m, 2H), 2.9 (s, 3H), 3.45 (br m, 5H), 3.8 (br m, 5H), 4.05 (s, 3H), 4.35 (t, 2H), 7.1 (d, 1H), 7.45 (m, 3H), 7.75 (d, 1H), 8.05 (s, 1H), 8.25 (s, 1H), 8.8 (s, 1H); Mass Spectrum: M+H+ 448.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:13]=[C:14]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:15]=[CH:16][CH:17]=2)[C@@H:8]([OH:24])[CH2:7]1)=[O:5])[CH3:2].[H-].[Na+].Br[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][C:30]=1[O:36][CH2:37][CH2:38][CH2:39][O:40][CH3:41].O>CN(C=O)C>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:13]=[C:14]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:15]=[CH:16][CH:17]=2)[C@@H:8]([O:24][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][C:30]=2[O:36][CH2:37][CH2:38][CH2:39][O:40][CH3:41])[CH2:7]1)=[O:5])[CH3:2]
Reactant: COCCCOc1cc(C)ccc1CBr
Reactant: CCOC(=O)N1CC[C@H](c2cccc(-c3ccccc3)c2)[C@@H](O)C1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)N1CC[C@H](c2cccc(-c3ccccc3)c2)[C@@H](OCc2ccc(C)cc2OCCCOC)C1
Temperature: 60 °C
Reaction time: 0.17 h

Procedure:
A suspension of the title C compound, (3R,4R)-4-biphenyl-3-yl-3-hydroxy-piperidine-1-carboxylic acid ethyl ester (150 mg, 0.45 mmol) and sodium hydride (60% dispersion in mineral oil, 30 mg, 0.68 mmol) in 10 mL of dry DMF is stirred for 10 min at 60° C. under argon. After cooling to room temperature, 1-bromomethyl-2-(3-methoxy-propoxy)-4-methyl-benzene (252 mg, 0.9 mmol) is added and the mixture further stirred for 3 h at 60° C. After addition of H2O, the aqueous layer is extracted twice with ethyl acetate and the combined organic extracts are dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is purified by preparative HPLC (Macherey-Nagel 250/4 nucleosil 100-10 C18 column, 20:80 CH3CN+0.1% TFA over 11 min, then 100% CH3CN+0.1% TFA for 5.5 min, 40 mL/min). To the combined fractions containing the desired product is added 1M aqueous sodium carbonate solution and the acetonitrile is removed under reduced pressure. The resulting aqueous suspension is extracted twice with ethyl acetate. The combined organic layers are dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford the title compound. MS 535.2 [M+18]; Rt (HPLC, Nucleosil C18, 10:90-100:0 CH3CN/H2O+0.1% TFA within 5 min, then 100% CH3CN+0.1% TFA): 7.29 min.
Reaction SMILES: C([O:4][C@@H:5]1[CH2:24][CH2:23][C@@:22]2([CH3:25])[C@@H:7]([CH2:8][CH2:9][C@@H:10]3[C@@H:21]2[CH2:20][CH2:19][C@@:18]2([CH3:26])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[C:15](=[O:17])[CH3:16])[CH2:6]1)(=O)C.[CH3:27][Mg]Br.[Cl-].[NH4+].O>C1C=CC=CC=1>[OH:4][C@@H:5]1[CH2:24][CH2:23][C@@:22]2([CH3:25])[C@@H:7]([CH2:8][CH2:9][C@@H:10]3[C@@H:21]2[CH2:20][CH2:19][C@@:18]2([CH3:26])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[C:15]([OH:17])([CH3:16])[CH3:27])[CH2:6]1
Reactant: C[Mg]Br
Reactant: CC(=O)O[C@@H]1CC[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@@H](C(C)=O)CC[C@@H]32)C1
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: c1ccccc1
Product: CC(C)(O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a stirred mixture of 3α-acetoxy-5α-pregnan-20-one (120 mg, 360.5 g/m, 0.32 mmol) in 25 mL of dry benzene, was added 4.6 mL of 3M methylmagnesium bromide dropwise. After the addition of methylmagnesium bromide was completed, the reaction mixture was allowed to stir at room temperature for 18 h and then refluxed for 2 h. The excess methylmagnesium bromide was decomposed by dropwise addition of 30 mL of saturated ammonium chloride solution in an ice bath. The solution product was poured into water and extracted with chloroform twice. The extracts were dried over magnesium sulfate and evaporated to give 110 mg of crude product. The product was recrystallized in methanol to give 83 mg of 3α,20-dihydroxy-20-methyl-5α-pregnane.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:11][C:10](=[O:12])[C:9]([F:14])([F:13])[CH2:8][N:7]([CH:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[C:6]=2[N:20]=1.[C:21](=O)([O-])[O-].[Cs+].[Cs+].IC>CN(C)C=O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:21])[C:10](=[O:12])[C:9]([F:14])([F:13])[CH2:8][N:7]([CH:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[C:6]=2[N:20]=1
Reactant: O=C1Nc2cnc(Cl)nc2N(C2CCCC2)CC1(F)F
Reactant: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CI
Product: CN1C(=O)C(F)(F)CN(C2CCCC2)c2nc(Cl)ncc21
Reaction time: 4 h
Yield: 94 %

Procedure:
To a solution of 1.4 g (0.0046 mole) of 2-chloro-9-cyclopentyl-7,7-difluoro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-20) in 30 mL of dimethylformamide was added 2.27 g (0.0069 mole) of cesium carbonate, followed by 0.87 mL (0.014 mole) of iodomethane. After stirring four hours, the mixture filtered and then concentrated under reduced pressure. Ice water was added to the residue to give a precipitate. The solid was collected by filtration, washed with water and dried under vacuum to give 1.37 g of 2-chloro-9-cyclopentyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-20) as a white solid.
Reaction SMILES: C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:13][N:14]1[C:18]([CH2:23][CH:24]([CH3:26])[CH3:25])([CH2:19][C:20](O)=[O:21])[C:17](=[O:27])[N:16]([CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:15]1=[O:36].Cl.[CH2:38]([O:45][NH2:46])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.CN1CCOCC1>C(Cl)Cl>[CH2:38]([O:45][NH:46][C:20](=[O:21])[CH2:19][C:18]1([CH2:23][CH:24]([CH3:25])[CH3:26])[C:17](=[O:27])[N:16]([CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:15](=[O:36])[N:14]1[CH3:13])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1
Reactant: CC(C)CC1(CC(=O)O)C(=O)N(CCc2ccccc2)C(=O)N1C
Reactant: NOCc1ccccc1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: CC(C)CC1(CC(=O)NOCc2ccccc2)C(=O)N(CCc2ccccc2)C(=O)N1C
Temperature: 25 °C
Reaction time: 1 h
Yield: 63.7 %

Procedure:
CDI (57.0 mg, 0.352 mmol) is added to a solution of 3-methyl-4-(2-methylpropyl)-2,5-dioxo-1-(2-phenylethyl)-4-imidazolidineacetic acid (113 mg, 0.340 mmol) and CH2Cl2 (2.5 mL). The solution is stirred for 1 hour at room temperature and then O-benzyl hydroxylaminehydrochloride (67.0 mg, 0.420 mmol) and N-methylmorpholine (46 μL, 0.42 mmol) are added. The solution is stirred for 60 hours at room temperature. Basic workup (CH2Cl2, NaHCO3, MgSO4) and purification by flash chromatography (1:1 hexane:EtOAc) provides 94.8 mg (64%) of the title compound as a white solid.
Reaction SMILES: F[C:2]1[C:10]2[S:9][C:8]([C:11]3[C:12]([NH2:28])=[N:13][CH:14]=[C:15]([C:17]4[CH:18]=[N:19][N:20]([CH:22]5[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]5)[CH:21]=4)[CH:16]=3)=[N:7][C:6]=2[C:5](C(F)(F)F)=[CH:4][CH:3]=1.I[C:34]1SC2C=CC(C)=CC=2N=1>>[CH3:34][C:4]1[CH:3]=[CH:2][C:10]2[S:9][C:8]([C:11]3[C:12]([NH2:28])=[N:13][CH:14]=[C:15]([C:17]4[CH:18]=[N:19][N:20]([CH:22]5[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]5)[CH:21]=4)[CH:16]=3)=[N:7][C:6]=2[CH:5]=1
Reactant: Cc1ccc2sc(I)nc2c1
Reactant: Nc1ncc(-c2cnn(C3CCNCC3)c2)cc1-c1nc2c(C(F)(F)F)ccc(F)c2s1
Product: Cc1ccc2sc(-c3cc(-c4cnn(C5CCNCC5)c4)cnc3N)nc2c1

Procedure:
Following the procedure for 3-(7-fluoro-4-trifluoromethylbenzothiazol-2-yl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine, using 2-iodo-5-methyl-1,3-benzothiazole and conducting the Suzuki coupling at 80° C. for 3 h, the title compound was obtained as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ=8.96-8.87 (brm, 1H), 8.75-8.65 (brm, 1H), 8.51 (d, J=2.0 Hz, 1H), 8.40 (s, 1H), 8.37 (brs, 1H), 8.35 (very brs, 1H), 8.06 (d, J=8.0 Hz, 1H), 8.06 (s, 1H), 7.36 (dd, J=8.0, 1.0 Hz, 1H), 4.56-4.48 (mc, 1H), 3.11 (brq, J=11.0 Hz, 2H), 2.30-2.10 (m, 4H); CH3 and additional 2H hidden under water peak. MS(ES+): m/z=391.14 (72) [MH+], 308.09 (100) [MH+-piperidine]. HPLC: tR=2.10 min (polar—5 min, ZQ2).
Reaction SMILES: [NH2:1][CH:2]1[CH2:14][O:13][C:12]2[CH:11]=[CH:10][C:9]3[CH2:8][NH:7][C:6](=[O:15])[C:5]=3[C:4]=2[CH2:3]1.[F:16][C:17]1[CH:18]=[C:19]2[C:23](=[C:24]([F:26])[CH:25]=1)[NH:22][CH:21]=[C:20]2[CH2:27][CH2:28][CH:29]=O.C(O)(=O)C.[BH3-]C#N.[Na+]>CO>[F:16][C:17]1[CH:18]=[C:19]2[C:23](=[C:24]([F:26])[CH:25]=1)[NH:22][CH:21]=[C:20]2[CH2:27][CH2:28][CH2:29][NH:1][CH:2]1[CH2:14][O:13][C:12]2[CH:11]=[CH:10][C:9]3[CH2:8][NH:7][C:6](=[O:15])[C:5]=3[C:4]=2[CH2:3]1
Reactant: O=CCCc1c[nH]c2c(F)cc(F)cc12
Reactant: NC1COc2ccc3c(c2C1)C(=O)NC3
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: O=C1NCc2ccc3c(c21)CC(NCCCc1c[nH]c2c(F)cc(F)cc12)CO3
Reaction time: 2 h

Procedure:
To a mixture of (1) (202 mg, 0.99 mmol), 3-(5,7-difluoro-1H-indol-3-yl)propanal ((41), 247 mg, 1.09 mmol) in acetic acid (145 μl, 2.36 mmol) and methanol (10 ml) was added NaBH3CN (126 mg, 2.00 mmol) in portions. Resulting mixture was stirred for 2.0 hr. The solvent was removed in vacuo and the residue was dissolved in CH2Cl2 and washed with 1 N NaOH and saturated NaCl. The organic solution was dried over Na2SO4 and concentrated in vacuo. The compound was purified on silica gel eluting with 70% EtOAc/Hexane to give (18), which was treated with 1 equivalent of etherate HCl to form HCl salt. MS (ES) m/z 412.2.
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[C:9]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[C:10]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)=[C:6]2[N:5]=[C:4]([CH3:25])[N:3]=1.[H-].[Na+].[CH2:28]([OH:30])[CH3:29]>>[Cl:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:9]1[C:10]([C:11]2[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=2)=[C:6]2[N:5]=[C:4]([CH3:25])[N:3]=[C:2]([O:30][CH2:28][CH3:29])[N:7]2[N:8]=1
Reactant: Cc1nc(Cl)n2nc(-c3ccccc3Cl)c(-c3ccc(Cl)cc3)c2n1
Reactant: CCO
Agent: [H-]
Agent: [Na+]
Product: CCOc1nc(C)nc2c(-c3ccc(Cl)cc3)c(-c3ccccc3Cl)nn12
Reaction time: 6 h

Procedure:
To a solution of 4-chloro-7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazine (I-2A-1b; 20 mg, 0.051 mmol) in ethanol (1 ml) was added NaH (60% dispersion in oil, 2 mg, 0.05 mmol), portionwise. After stirring for 6 hours, the reaction was concentrated, in vacuo. The residue was redisolved in methylene chloride, filtered through a 0.45 μm disk, and then concentrated to afford 12A-1 (18 mg, 88%) as a solid: +APcI MS (M+1) 399.1; 1H NMR (400 MHz, CD2Cl2) δ 7.50-7.37 (m, 6H), 7.24 (d, J=8.7 Hz, 2H), 4.80 (q, J=7.2 Hz, 2H), 2.63 (s, 3H), 1.57 (t, J=7.1 Hz, 3H).
Reaction SMILES: FC(F)(F)C(O)=O.[CH:8]1([CH2:11][CH2:12][O:13][C:14]2[NH:15][C:16]([NH2:25])=[C:17]3[C:21]([N:22]=2)=[N:20][C:19]([O:23][CH3:24])=[N:18]3)[CH2:10][CH2:9]1.Br[CH2:27][CH2:28][CH:29]1[CH2:33][CH2:32][CH2:31][O:30]1>>[CH:8]1([CH2:11][CH2:12][O:13][C:14]2[N:22]=[C:21]3[C:17]([N:18]=[C:19]([O:23][CH3:24])[N:20]3[CH2:27][CH2:28][CH:29]3[CH2:33][CH2:32][CH2:31][O:30]3)=[C:16]([NH2:25])[N:15]=2)[CH2:10][CH2:9]1
Reactant: BrCCC1CCCO1
Reactant: COc1nc2nc(OCCC3CC3)[nH]c(N)c-2n1
Solvent: O=C(O)C(F)(F)F
Product: COc1nc2c(N)nc(OCCC3CC3)nc2n1CCC1CCCO1

Procedure:
Prepared similarly to Intermediate 213 from 2-[(2-cyclopropylethyl)oxy]-8-(methyloxy)-1H-purin-6-amine trifluoroacetate and 2-(2-bromoethyl)tetrahydrofuran.
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[OH:12])=O.[I-].[Na+].[N-:15]=[N+:16]=[N-:17].[Na+]>CS(C)=O>[N:15]([CH2:2][C:3]1[O:12][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=1)=[N+:16]=[N-:17]
Reactant: O=C(CCl)Nc1ccccc1O
Reactant: [N-]=[N+]=[N-]
Agent: [I-]
Agent: [Na+]
Solvent: CS(C)=O
Product: [N-]=[N+]=NCc1nc2ccccc2o1
Reaction time: 0.5 h

Procedure:
To a mixture of 8.34 g (49.8 mmol) of 2-chloro-N-(2-hydroxyphenyl)acetamide (PREPARATION 4) and 0.75 g (5 mmol) of sodium iodide in 25 ml of DMSO were added 3.56 g (5.47 mmol) of sodium azide. A moderate exotherm ensued. After stirring for 30 min the reaction was partitioned between ethyl ether and saline. The organic layers were dried over magnesium sulfate and concentrated. The crude product was chromatographed on silica gel (700 ml) eluting with ethyl acetate/hexane (5/95), the appropriate fractions are pooled and concentrated to give the title compound, NMR (CDCl3) 4.60, 7.39, 7.56, 7.76 δ.
Reaction SMILES: [O:1]1[C:5]2=[CH:6][N:7]=[CH:8][CH:9]=[C:4]2[C:3]([NH2:10])=[N:2]1.Cl[C:12]([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:13]>CC#N.O.C([O-])(O)=O.[Na+]>[C:15]1([O:14][C:12](=[O:13])[NH:10][C:3]2[C:4]3[C:5](=[CH:6][N:7]=[CH:8][CH:9]=3)[O:1][N:2]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: Nc1noc2cnccc12
Reactant: O=C(Cl)Oc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: O=C(Nc1noc2cnccc12)Oc1ccccc1
Temperature: 70 °C
Yield: 78.3 %

Procedure:
To a suspension of isoxazolo[5,4-c]pyridin-3-ylamine (1.49 g, 11.0 mmol) in CH3CN (50 mL) was added phenyl chloroformate (0.696 mL, 5.50 mmol). The reaction mixture was heated at 70° C. overnight, then cooled to rt, diluted with H2O (100 mL) and saturated aqueous NaHCO3 (10 mL). The resulting yellow precipitate was filtered and dried under vacuum to give isoxazolo[5,4-c]pyridin-3-yl-carbamic acid phenyl ester (1.099 g, 39%). MS (ESI+): calcd for C13H9N3O3 m/z 255.06, found 256.1 (M+H)+.
Reaction SMILES: [C:1]([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[CH3:15])[O:11][C:10]([CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH:26](Cl)[C:27](OCC)=[O:28])=[CH:21][CH:20]=1)([CH3:16])[CH2:9][CH2:8]2)(=[O:3])[CH3:2].[NH2:33][C:34](N)=[S:35].S1(CCCC1)(=O)=[O:38]>>[C:1]([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[CH3:15])[O:11][C:10]([CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH:26]3[S:35][C:34](=[O:38])[NH:33][C:27]3=[O:28])=[CH:21][CH:20]=1)([CH3:16])[CH2:9][CH2:8]2)(=[O:3])[CH3:2]
Reactant: CCOC(=O)C(Cl)Cc1ccc(OCC2(C)CCc3cc(OC(C)=O)c(C)cc3O2)cc1
Reactant: O=S1(=O)CCCC1
Reactant: NC(N)=S
Product: CC(=O)Oc1cc2c(cc1C)OC(C)(COc1ccc(CC3SC(=O)NC3=O)cc1)CC2
Temperature: 120 °C

Procedure:
The reactions described in Example 1(a) were repeated, except that 1.5 g of ethyl 3-[4-(6-acetoxy-2,7-dimethylchroman-2-ylmethoxy)phenyl]-2-chloropropionate, 300 mg of thiourea and 2 ml of sulfolane were heated at 120° C. for 2 hours. The reaction mixture was then purified by adding diethyl ether to the reaction mixture, and distilling off the solvent to leave a residue. This residue was purified by column chromatography through silica gel eluted first with a 9:1 by volume mixture of benzene and ethyl acetate, to give the title compound.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]=[CH:12][O:13][CH:14]=2)=[CH:6][CH:5]=1)([O-])=O.[H][H]>[C].[Pd].C(O)C.O1CCCC1>[O:13]1[CH:14]=[C:10]([C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=2)[N:11]=[CH:12]1
Reactant: [H][H]
Reactant: O=[N+]([O-])c1ccc(-c2cocn2)cc1
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: Nc1ccc(-c2cocn2)cc1

Procedure:
5% Palladium-carbon powder was added to an ethanol-tetrahydrofuran mixed suspension of 4-(4-nitrophenyl)-1,3-oxazol and stirred for 12 hours at room temperature in a hydrogen atmosphere. The reaction solution was filtered through Celite and the filtrate was evaporated under reduced pressure. The resulting crude product is purified with a silica gel column chromatography to obtain [4-(1,3-oxazol-4-yl)phenyl]amine (pale yellow solid). Electron Impact-MS(M)+: 160.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[N:11]=[C:10]([C:12]([OH:14])=O)[CH:9]=[CH:8][C:7]=2[CH:15]2[CH2:19][CH2:18][O:17][CH2:16]2)[CH2:3][CH2:2]1.C1(COC2N=C(C(O)=O)C=CC=2C2CCCO2)CC1.[NH2:39][C@@H:40]([CH2:44][CH:45]([CH3:47])[CH3:46])[C:41]([NH2:43])=[O:42]>>[C:41]([C@@H:40]([NH:39][C:12]([C:10]1[CH:9]=[CH:8][C:7]([CH:15]2[CH2:19][CH2:18][O:17][CH2:16]2)=[C:6]([O:5][CH2:4][CH:1]2[CH2:2][CH2:3]2)[N:11]=1)=[O:14])[CH2:44][CH:45]([CH3:47])[CH3:46])(=[O:42])[NH2:43]
Reactant: O=C(O)c1ccc(C2CCOC2)c(OCC2CC2)n1
Reactant: CC(C)C[C@H](N)C(N)=O
Agent: O=C(O)c1ccc(C2CCCO2)c(OCC2CC2)n1
Product: CC(C)C[C@H](NC(=O)c1ccc(C2CCOC2)c(OCC2CC2)n1)C(N)=O

Procedure:
The title compound was synthesized in analogy to Example 1, using the mixture of 6-(cyclopropylmethoxy)-5-(tetrahydrofuran-3-yl)-pyridine-2-carboxylic acid and 6-(cyclopropylmethoxy)-5-(tetrahydrofuran-2-yl)-pyridine-2-carboxylic acid (mixture from Example 114 d), and (2S)-2-amino-4-methyl-pentanamide (CAN 687-51-4) as starting materials, MS (EI): m/e=376.2 [M+H]+.