Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]([C:16]3[CH:27]=[CH:26][C:19]([O:20][CH2:21][C:22](OC)=[O:23])=[CH:18][CH:17]=3)=[O:15])[CH2:9][CH2:8]2)=[CH:3][CH:2]=1.[CH3:28][O:29][CH2:30][CH2:31][NH2:32]>>[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]([C:16]3[CH:27]=[CH:26][C:19]([O:20][CH2:21][C:22]([NH:32][CH2:31][CH2:30][O:29][CH3:28])=[O:23])=[CH:18][CH:17]=3)=[O:15])[CH2:9][CH2:8]2)=[CH:3][CH:2]=1
Reactant: COC(=O)COc1ccc(C(=O)CN2CCN(c3ccncc3)CC2)cc1
Reactant: COCCN
Product: COCCNC(=O)COc1ccc(C(=O)CN2CCN(c3ccncc3)CC2)cc1
Reaction time: 18 h

Procedure:
A suspension of the product of Example 1, (100 mg) in 2-methoxyethylamine (1 ml) was stirred for 18 hours. Filtration of the solid and washing with ethyl acetate gave the title compound, 70 mg, as a white crystalline solid: m.p. 142°-145° C.; NMR (d6DMSO+d4 acetic acid) δ8.20 (2H, d), 8.00 (2H, d), 7.14 (2H, d), 7.06 (2H, d), 4.62 (2H, s), 3.72 (4H, t), 3.38 (4H, m), 3.26 (3H, s), 2.78 (4H, t); m/e 413 (M+H)+ ; calculated for C22H28N4O4 : C, 64.1; H, 6.8; N, 13.6. found: C, 63.9; H, 6.8; N, 13.3%.
Reaction SMILES: [Br:1][C:2]1[O:3][C:4]2[CH:23]=[CH:22][CH:21]=[CH:20][C:5]=2[C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)=[CH:9][CH:8]=1.C[O:25][C:26](=[O:36])[CH:27]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)O>>[Br:1][C:2]1[O:3][C:4]2[CH:23]=[CH:22][CH:21]=[CH:20][C:5]=2[C:6]=1[C:7]1[CH:8]=[CH:9][C:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH:27]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:26]([OH:36])=[O:25])=[CH:15][CH:14]=2)=[CH:11][CH:12]=1
Reactant: COC(=O)C(O)Cc1ccccc1
Reactant: Oc1ccc(-c2ccc(-c3c(Br)oc4ccccc34)cc2)cc1
Product: O=C(O)C(Cc1ccccc1)Oc1ccc(-c2ccc(-c3c(Br)oc4ccccc34)cc2)cc1

Procedure:
The title compound was prepared from 4′-(2-bromo-benzofuran-3-yl)-biphenyl-4-ol and 3-phenyllactic acid methyl ester, in substantially the same manner, as described in Example 1, steps g-h, and was obtained as a white solid, mp 148-149° C.; MS m/e 512 (M+);
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[N:10][N:11]([CH3:27])[C:12]=1[C:13]1[N:14]=[CH:15][N:16]([C:18]2[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][N:19]=2)[CH:17]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:59][CH:60]1[CH2:65][CH2:64][O:63][CH2:62][CH2:61]1>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[N:10][N:11]([CH3:27])[C:12]=1[C:13]1[N:14]=[CH:15][N:16]([C:18]2[CH:26]=[CH:25][C:21]([C:22]([NH:59][CH:60]3[CH2:65][CH2:64][O:63][CH2:62][CH2:61]3)=[O:24])=[CH:20][N:19]=2)[CH:17]=1
Reactant: NC1CCOCC1
Reactant: Cn1nnc(-c2ccccc2F)c1-c1cn(-c2ccc(C(=O)O)cn2)cn1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cn1nnc(-c2ccccc2F)c1-c1cn(-c2ccc(C(=O)NC3CCOCC3)cn2)cn1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 81.8 %

Procedure:
To a solution of 6-(4-(4-(2-fluorophenyl)-1-methyl-1H-1,2,3-triazol-5-yl)-1H-imidazol-1-yl)nicotinic acid (75 mg, 0.194 mmol) and TBTU (73 mg, 0.226 mmol) in DMF (2.0 mL) was added DIPEA (180 μL, 1.03 mmol). Then 4-aminotetrahydropyran (24 μL, 0.226 mmol) was added and the mixture was stirred at room temperature under Ar for 30 min. The mixture was then evaporated and purification by chromatography (reverse phase HPLC) afforded the title compound (71 mg, 77%) as a white solid. MS: m/e=448.2 [M+H]+.
Reaction SMILES: [CH2:1]([NH:8][C:9](=[O:27])[N:10]([CH3:26])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13](B2OC(C)(C)C(C)(C)O2)[CH:12]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].Br[C:29]1[CH:41]=[CH:40][C:32]([CH:33]=[CH:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:31][CH:30]=1.CN(C)C=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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.O>[CH2:1]([NH:8][C:9](=[O:27])[N:10]([C:11]1[CH:12]=[C:13]([C:29]2[CH:41]=[CH:40][C:32]([CH:33]=[CH:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:31][CH:30]=2)[CH:14]=[CH:15][CH:16]=1)[CH3:26])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCCCCNC(=O)N(C)c1cccc(B2OC(C)(C)C(C)(C)O2)c1
Reactant: CCOC(=O)C=Cc1ccc(Br)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCCNC(=O)N(C)c1cccc(-c2ccc(C=CC(=O)OCC)cc2)c1
Temperature: 90 °C
Reaction time: 3 h
Yield: 74.9 %

Procedure:
308 mg (0.26 mmol, 5 mol %) of tetrakis(triphenylphosphine)palladium are added to a solution of 2 g (5.34 mmol, 1.0 eq) of 3-heptyl-1-methyl-1-[3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]urea and 1.6 g (6.4 mmol, 1.2 eq) of ethyl 4-bromocinnamate in 20 mL of an 8/2 mixture of dimethylformamide and of 2M potassium phosphate solution. The reaction mixture is stirred for 3 hours at 90° C. The reaction is stopped by addition of 50 mL of water and then extracted with ethyl acetate. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated off and the residue is then chromatographed on silica gel (70/30 heptane/ethyl acetate). 1.69 g of ethyl 3-[3′-(3-heptyl-1-methylureido)biphenyl-4-yl]acrylate in oil form are obtained. Yield=75%
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([Cl:9])[CH:3]=1.[C:10]([O:14][CH2:15][CH2:16][CH2:17][CH3:18])(=[O:13])[CH:11]=[CH2:12].CN(C1CCCCC1)C1CCCCC1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>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].O1CCOCC1>[Cl:9][C:4]1[CH:3]=[C:2](/[CH:12]=[CH:11]/[C:10]([O:14][CH2:15][CH2:16][CH2:17][CH3:18])=[O:13])[CH:7]=[CH:6][C:5]=1[OH:8]
Reactant: Oc1ccc(Br)cc1Cl
Reactant: C=CC(=O)OCCCC
Agent: [Pd]
Agent: CC(C)(C)[PH+](C(C)(C)C)C(C)(C)C
Agent: CN(C1CCCCC1)C1CCCCC1
Solvent: C1COCCO1
Product: CCCCOC(=O)/C=C/c1ccc(O)c(Cl)c1

Procedure:
To a dioxane (10 mL) solution of 4-bromo-2-chlorophenol (207 mg) were added n-butyl acrylate (0.158 mL), N-methyldicyclohexylamine (0.236 mL), tri-tert-butylphosphonium tetrafluoroborate (12 mg), and tris(dibenzylideneacetone)dipalladium (0) (18 mg) under a N2 atmosphere. The resultant mixture was refluxed over night. After cooling, the reaction mixture was filtered off on Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=4/1 to 2/1) to afford butyl (E)-3-(3-chloro-4-hydroxyphenyl)prop-2-enoate (244 mg) as a colorless oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][C:15]=1[C:16]1[S:17][C:18]2[C:23]([N:24]=1)=[CH:22][CH:21]=[C:20]([C:25]1([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:27][CH2:26]1)[N:19]=2)[CH2:5][NH:6][CH2:7][C:8]([O:10]CC)=[O:9].O.O.[OH-].[Li+]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][C:15]=1[C:16]1[S:17][C:18]2[C:23]([N:24]=1)=[CH:22][CH:21]=[C:20]([C:25]1([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH2:26][CH2:27]1)[N:19]=2)[CH2:5][NH:6][CH2:7][C:8]([OH:10])=[O:9]
Reactant: CCOC(=O)CNCc1ccc(-c2nc3ccc(C4(c5ccccc5)CC4)nc3s2)c(F)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)CNCc1ccc(-c2nc3ccc(C4(c5ccccc5)CC4)nc3s2)c(F)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Ethyl 2-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)-benzylamino)acetate (80 mg, 0.173 mmol) was dissolved in THF (1.4 mL) and water (347 μL) before lithium hydroxide monohydrate (21.82 mg, 0.520 mmol) was added and stirred at ambient temperature for 16 h. The reaction mixture was concentrated, acidified to pH 7 with 1 N HCl, filtered, and washed with water, DMSO, then water, and dried in a vacuum oven to give the title compound. MS (ESI) m/z: Calculated: 433.1; Observed: 433.8 (M++H).
Reaction SMILES: Br[C:2]([CH3:19])([CH3:18])[C:3]([NH:5][C:6]1[CH:15]=[C:14]([Cl:16])[CH:13]=[C:8]([C:9]([O:11][CH3:12])=[O:10])[C:7]=1[OH:17])=[O:4].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[Cl:16][C:14]1[CH:13]=[C:8]([C:9]([O:11][CH3:12])=[O:10])[C:7]2[O:17][C:2]([CH3:19])([CH3:18])[C:3](=[O:4])[NH:5][C:6]=2[CH:15]=1
Reactant: COC(=O)c1cc(Cl)cc(NC(=O)C(C)(C)Br)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1cc(Cl)cc2c1OC(C)(C)C(=O)N2
Temperature: 80 °C
Reaction time: 4 h
Yield: 78 %

Procedure:
A mixture of 7.0 g of methyl 3-(2-bromo-2-methylpropionylamino)-5-chlorosalicylate, 3.6 g of potassium carbonate and 70 ml of dimethylformamide is stirred at 80° C. for 4 hours. After cooling, the resultant solution is poured into water and extracted with chloroform. The extract is washed with water and dried over magnesium sulfate followed by distillation of the solvent under reduced pressure to give 4.2 g of methyl 6-chloro-3,4-dihydro-2,2-dimethyl-3-oxo-2H-1,4-benzoxazine-8-carboxylate, melting at 178°-179° C.
Reaction SMILES: [Br:1][C:2]1[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[CH:10][C:3]=1[C:4](N(OC)C)=[O:5].[CH3:16][Mg]Br.C(OCC)(=O)C.Cl>O1CCCC1>[Br:1][C:2]1[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[CH:10][C:3]=1[C:4](=[O:5])[CH3:16]
Reactant: C[Mg]Br
Reactant: COc1cccc(C(=O)N(C)OC)c1Br
Agent: Cl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COc1cccc(C(C)=O)c1Br
Temperature: 25 °C
Reaction time: 15 h
Yield: 90 %

Procedure:
Under a nitrogen atmosphere, 2-bromo-N, 3-dimethoxy-N-methylbenzamide (16.8 g, 61.5 mmol) which had been obtained in Reference example 3 (3a) was dissolved in tetrahydrofuran (300 mL), and added dropwise with a 1.0 M solution of methyl magnesium bromide in tetrahydrofuran (123 mL, 123 mmol) at 0° C. Upon the completion of the dropwise addition, the temperature of the reaction solution was raised to room temperature and stirred for 15 hours. The reaction solution was added with ethyl acetate and 1 N hydrochloric acid for fractionation, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with saturated sodium hydrogen carbonate, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate, 100:0-60:40, V/V) to give the title compound as a colorless oily substance (12.7 g, yield 90%).
Reaction SMILES: [C:1]([Mg]Br)#[CH:2].C1COCC1.[C:10]([O:14][C:15]([N:17]1[CH2:21][CH2:20][C@H:19]([CH:22]=[O:23])[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]>>[C:10]([O:14][C:15]([N:17]1[CH2:21][CH2:20][C@H:19]([CH:22]([OH:23])[C:1]#[CH:2])[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]
Reactant: CC(C)(C)OC(=O)N1CC[C@H](C=O)C1
Reactant: C#C[Mg]Br
Solvent: C1CCOC1
Product: C#CC(O)[C@H]1CCN(C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
0.5 M Ethynylmagnesium bromide in THF (6.3 mL, 3140 μmol) was added dropwise over 5 minutes to a stirred solution of (S)-3-formylpyrrolidine-1-carboxylic acid t-butyl ester (0.5 g, 2 mmol) in THF (5 mL, 60 mmol) at 0° C. The mixture was allowed to warm to room temperature. After 4 hours, the reaction was quenched with the addition of saturated aqueous NH4Cl (10 mL) and extracted with EtOAc (2×10 mL). The organic layers were combined, dried over MgSO4, filtered, and concentrated in vacuo.
Reaction SMILES: [NH:1]([CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[C:17](Cl)(=[O:26])[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1>N1C=CC=CC=1.CC(OC)(C)C>[CH3:25][O:24][C:21]1[CH:22]=[CH:23][C:18]([C:17]([N:1]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)=[O:26])=[CH:19][CH:20]=1
Reactant: c1ccc(NCCc2ccccn2)cc1
Reactant: COc1ccc(C(=O)Cl)cc1
Solvent: O
Solvent: COC(C)(C)C
Solvent: c1ccncc1
Product: COc1ccc(C(=O)N(CCc2ccccn2)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
In a 25 ml round-bottom flask 0.085 p-anisoyl chloride and 0.04 mL of pyridine are dissolved in 3 ml of MTBE. To this solution was added 0.10 g of 2-(2-anilinoethyl)pyridine. The solution is stirred at room temperature for 24 h. To the solution was added 5 mL of water. The organic layer was separated and washed with 5 mL of water. The organic layer was dried over MgSO4. The solvent was evaporated to yield a brown oil. The oil was purified on silica gel to afford 0.15 g of an off-white solid with the following spectroscopic properties:
Reaction SMILES: [C:1]([C@:3]1([OH:24])[CH2:8][CH2:7][C@H:6]2[C@H:9]3[C:19](=[CH:20][CH2:21][C@:4]12[CH3:5])[C@:17]1([CH3:18])[C:12]([CH2:13][C:14](=[O:22])[CH2:15][CH2:16]1)=[C:11]([F:23])[CH2:10]3)#[CH:2]>C1COCC1>[C:1]([C@:3]1([OH:24])[CH2:8][CH2:7][C@H:6]2[C@H:9]3[C:19](=[CH:20][CH2:21][C@:4]12[CH3:5])[C@:17]1([CH3:18])[C:12](=[CH:13][C:14](=[O:22])[CH2:15][CH2:16]1)[C@@H:11]([F:23])[CH2:10]3)#[CH:2]
Reactant: C#C[C@]1(O)CC[C@H]2[C@@H]3CC(F)=C4CC(=O)CC[C@]4(C)C3=CC[C@@]21C
Solvent: C1CCOC1
Product: C#C[C@]1(O)CC[C@H]2[C@@H]3C[C@H](F)C4=CC(=O)CC[C@]4(C)C3=CC[C@@]21C
Reaction time: 3 h

Procedure:
17α-Ethynyl-6-fluoro-17β-hydroxyandrost-5,9(11)diene-3-one (VI, Example 11) is dissolved in THF (200 ml) and the mixture dried over sodium sulfate. The dried solution is filtered and cooled in an ice bath to which concentrated hydrochloric acid (20 ml) is added slowly. After stirring at 20°-25° for 3 hr the solution is cooled in an ice bath and water (140 ml) is added followed by sodium hydroxide (50%) to neutralize the solution. The pH is checked by pH meter. The THF is removed under reduced pressure with heat to give a solid which is collected by suction filtration. The solid is washed with water and dried under reduced pressure at 50°. The solid is suspended in ethyl acetate (30 ml) and heated to boiling on a steambath. After stirring for 3 hr at 20°-25° and 2 hr on an ice bath the mixture is filtered using suction and the solids dried under reduced pressure with heat to give the title compound.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][C@H:14]3[CH2:18][CH2:17][N:16]([C:19]([CH:21]4[CH2:23][CH2:22]4)=[O:20])[CH2:15]3)=[N:11][NH:10][C:9]2=[O:24])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[CH:35][C:36]3[O:40][CH:39]=[CH:38][C:37]=3[CH:41]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[O:40]1[C:36]2[CH:35]=[CH:34][C:33]([C:2]3[CH:7]=[CH:6][C:5]([N:8]4[C:12]([CH2:13][C@H:14]5[CH2:18][CH2:17][N:16]([C:19]([CH:21]6[CH2:23][CH2:22]6)=[O:20])[CH2:15]5)=[N:11][NH:10][C:9]4=[O:24])=[CH:4][CH:3]=3)=[CH:41][C:37]=2[CH:38]=[CH:39]1
Reactant: O=C(C1CC1)N1CC[C@H](Cc2n[nH]c(=O)n2-c2ccc(Br)cc2)C1
Reactant: CC1(C)OB(c2ccc3occc3c2)OC1(C)C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: C1COCCO1
Product: O=C(C1CC1)N1CC[C@H](Cc2n[nH]c(=O)n2-c2ccc(-c3ccc4occc4c3)cc2)C1
Temperature: 25 °C
Yield: 35 %

Procedure:
A solution of 4-(4-bromophenyl)-5-{[(3R)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (0.256 mmol) in dioxane (1.5 mL) was treated with 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (0.281 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (10 mg), and 2M aq potassium carbonate (0.767 mmol). The reaction mixture was purged with nitrogen, sealed, and irradiated in a microwave (Biotage Initiator) at 150° C. for 15 min. The reaction mixture was cooled to room temperature and was diluted with water (50 mL). The aqueous layer was acidified to pH˜4 using 1N aq HCl and was extracted with dichloromethane. The resulting organic phase was treated with Si-Thiol (Silicycle, 20 mg), dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by reverse phase HPLC (20-50% acetonitrile/water+0.1% NH4OH) to afford the title compound as an amorphous white solid (35%). MS(ES)+ m/e 429.0 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[C:14](=[O:18])[CH2:15][CH2:16][CH2:17][C:12]=3[N:11]=[C:10]2[CH:19]([CH3:21])[CH3:20])=[CH:4][CH:3]=1.[BH4-].[Na+]>CO.ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[C:13]3[CH:14]([OH:18])[CH2:15][CH2:16][CH2:17][C:12]=3[N:11]=[C:10]2[CH:19]([CH3:21])[CH3:20])=[CH:6][CH:7]=1
Reactant: CC(C)c1nc2c(n1Cc1ccc(Cl)cc1)C(=O)CCC2
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: CC(C)c1nc2c(n1Cc1ccc(Cl)cc1)C(O)CCC2
Temperature: 25 °C
Reaction time: 1 h
Yield: 55 %

Procedure:
To a stirred solution of Intermediate 57 (300 mg) in a mixture of methanol (2.5 mL) and dichloromethane (2.5 mL) at ambient temperature was added sodium borohydride (75.0 mg) in one charge. The reaction was stirred at ambient temperature under an atmosphere of nitrogen for 1 hr (incomplete). Stirring continued for 16 hr. The reaction was partitioned between ethyl acetate (40 mL) and water (40 mL). The organic was dried (hydrophobic frit) and concentrated in vacuo to give the title compound (166 mg). LC/MS MH+ 305, 307, Rt 1.38 min (5 min run).
Reaction SMILES: [NH2:1][CH2:2][C:3]1(O)[C:12]2[C:7](=[C:8]([O:13][CH3:14])[CH:9]=[CH:10][CH:11]=2)[CH2:6][CH:5]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:4]1.[ClH:22]>C(O)(C)C>[ClH:22].[NH2:1][CH2:2][C:3]1[C:12]2[C:7](=[C:8]([O:13][CH3:14])[CH:9]=[CH:10][CH:11]=2)[CH2:6][CH:5]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:4]=1
Reactant: COc1cccc2c1CC(c1ccccc1)CC2(O)CN
Agent: Cl
Solvent: CC(C)O
Product: COc1cccc2c1CC(c1ccccc1)C=C2CN
Yield: 33 %

Procedure:
1-Aminomethyl-1-hydroxy-5-methoxy-3-phenyl-1,2,3,4-tetrahydronaphthalene (2.0 g, 7.2 mmol), from Step 1, was heated at reflux temperature for 2 h in 75 mL of isopropyl alcohol saturated with hydrogen chloride. The resultant solution was concentrated and the solid residue was triturated with hot toluene to give 0.72 g (33% yield) of 1-aminomethyl-5-methoxy-3-phenyl-3,4-dihydronaphthalene hydrochloride, m.p. 193°-196° C.; 1H NMR (d6-DMSO) δ 2.78 (dd, 1H), 3.14 (dd, 1H), 3.2-3.5 (m, 2H+H2O), 3.84 (s, 3H), 3.93 (d, 1H), 6.2 (m, 1H), 6.54 (d, 1H), 6.60 (d, 1H), 6.75 (d, 1H), 7.2-7.5 (m, 5H).
Reaction SMILES: [F:1][C:2]1[CH:23]=[C:22]([N+:24]([O-])=O)[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]=1[C:12]#[C:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1.C1COCC1.[NH4+].[Cl-]>[Zn].CO>[NH2:24][C:22]1[CH:21]=[CH:20][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]=2[C:12]#[C:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[C:2]([F:1])[CH:23]=1
Reactant: Nc1nccc(Oc2ccc([N+](=O)[O-])cc2F)c1C#Cc1ccccn1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CO
Solvent: C1CCOC1
Product: Nc1ccc(Oc2ccnc(N)c2C#Cc2ccccn2)c(F)c1
Temperature: 60 °C
Yield: 78 %

Procedure:
A mixture of 4-(2-fluoro-4-nitrophenoxy)-3-(2-(pyridin-2-yl)ethynyl)pyridin-2-amine (35 mg, 0.1 mmol), THF (1.5 mL) and MeOH (1.5 ml) was treated with zinc dust (65 mg, 1.0 mmol) and NH4Cl (53 mg, 1.0 mmol) and heated at 60° C. for 45 min. The reaction mixture was cooled, filtered and concentrated under vacuum. The residue was partitioned between EtOAc and saturated aq. NaHCO3 solution. The organic phase was separated, washed with brine, dried (MgSO4) and concentrated to give the title compound (25 mg, 78%) as a brown solid. MS (ESI+): m/z 321.2 (M+H)+.
Reaction SMILES: C([O:8][C:9]1[C:10]2[CH2:23][C@:22]3([CH3:36])[C@@H:24]([CH3:35])[CH2:25][CH2:26][C@H:27]4[C:28]([CH3:34])([CH3:33])[C@@H:29]([OH:32])[CH2:30][CH2:31][C@@:21]34[O:20][C:11]=2[C:12]2[CH:13]([OH:19])[NH:14][C:15](=[O:18])[C:16]=2[CH:17]=1)C1C=CC=CC=1.C(OCC)(=O)C>C1COCC1.[C].[Pd]>[OH:19][CH:13]1[C:12]2[C:11]3[O:20][C@@:21]45[CH2:31][CH2:30][C@H:29]([OH:32])[C:28]([CH3:34])([CH3:33])[C@@H:27]4[CH2:26][CH2:25][C@H:24]([CH3:35])[C@@:22]5([CH3:36])[CH2:23][C:10]=3[C:9]([OH:8])=[CH:17][C:16]=2[C:15](=[O:18])[NH:14]1
Reactant: C[C@H]1CC[C@H]2C(C)(C)[C@@H](O)CC[C@]23Oc2c(c(OCc4ccccc4)cc4c2C(O)NC4=O)C[C@]13C
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: C[C@H]1CC[C@H]2C(C)(C)[C@@H](O)CC[C@]23Oc2c(c(O)cc4c2C(O)NC4=O)C[C@]13C
Temperature: 25 °C
Reaction time: 3 h
Yield: 97.1 %

Procedure:
To the above Compound (29a) (100 mg, 0.20 mmol) dissolved in 5.0 ml of THF and 2.0 ml of ethyl acetate was added 45 mg of 10% palladium-carbon, and the mixture stirred at room temperature for 3 hours under hydrogen atmosphere. The palladium-carbon was filtered off, and the filtrate concentrated under reduced pressure. The residue was then purified by a silica gel column chromatography (silica gel 5.2 g; ethyl acetate) to give 78 mg (96%) of Compound (30a).
Reaction SMILES: [O:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=O.[NH2:16][OH:17]>>[O:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13](=[N:16][OH:17])[OH:15]
Reactant: O=CCCCCCCCCCCC(=O)O
Reactant: NO
Product: O=CCCCCCCCCCCC(O)=NO

Procedure:
Vernolia oil undergoes saponification and acification followed by cold temperature (-20° C.) crystallization to yield a methylated product comprised of vernolic, palmitic, oleic, linoleic and stearic acid. The vernolic acid is isolated and further purified through a series of low temperature recrystalizations. The purified vernolic acid, ##STR1## is then hydrogenated to yield 12,13-epoxystearic acid, having the formula: ##STR2## The 12,13-epoxystearic acid is then oxidized to yield 12-oxododecanoic acid, ##STR3## By reacting the 12-oxododecanoic acid with hydroxylamine, 12-oxododecanoic acid oxime ##STR4## is formed. The Nylon-12 monomer, 12-aminododecanoic acid:
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[C:7]([NH:11][C:12]2[N:17]=[C:16]([NH:18][CH2:19][CH:20]3[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21]3)[C:15]([C:32](=[O:34])N)=[CH:14][N:13]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2].C(O)(C(F)(F)F)=[O:36]>C(Cl)Cl>[C:1]([NH:4][C:5]1[CH:6]=[C:7]([NH:11][C:12]2[N:17]=[C:16]([NH:18][CH2:19][CH:20]3[CH2:24][CH2:23][NH:22][CH2:21]3)[C:15]([C:32]([OH:34])=[O:36])=[CH:14][N:13]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2]
Reactant: O=C(O)C(F)(F)F
Reactant: CC(=O)Nc1cccc(Nc2ncc(C(N)=O)c(NCC3CCN(C(=O)OC(C)(C)C)C3)n2)c1
Solvent: ClCCl
Product: CC(=O)Nc1cccc(Nc2ncc(C(=O)O)c(NCC3CCNC3)n2)c1

Procedure:
A solution of tert-butyl 3-((2-(3-acetamidophenylamino)-5-carbamoylpyrimidin-4-ylamino)methyl)pyrrolidine-1-carboxylate (65 mg, 0.138 mmol) in TFA (1 mL) and CH2Cl2 mL) was stirred at room temperature for 2 h. TFA and CH2Cl2 were removed in vacuo. The residue was purified by HPLC to give the titled compound (25 mg). MS 370.3 (M+H); UV 206.4, 244.2 nm.
Reaction SMILES: [O:1]=[C:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[NH:18][S:19]([C:22]2[CH:31]=[CH:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:23]=2)(=[O:21])=[O:20])[O:3]1.[OH-].[Na+].Cl.[CH2:35]([OH:37])[CH3:36]>>[CH2:35]([O:37][C:2](=[O:1])[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[NH:5][C:4](=[O:3])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[NH:18][S:19]([C:22]1[CH:31]=[CH:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=1)(=[O:21])=[O:20])[CH3:36]
Reactant: O=c1oc(-c2ccccc2NS(=O)(=O)c2ccc3ccccc3c2)nc2ccccc12
Reactant: CCO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: CCOC(=O)c1ccccc1NC(=O)c1ccccc1NS(=O)(=O)c1ccc2ccccc2c1
Temperature: 20 °C
Reaction time: 0.25 h

Procedure:
A 1 L three-necked flask was charged with 67.7 g (0.158 mol) N-[2-(4-oxo-4H-3,1-benzoxazin-2-yl)phenyl]-2-naphthalenesulfonamide) and 200 g ethanol. Under stirring, 0.33 g sodium hydroxide (0.0083 mol, correlates to 5.2% of applied raw material) was added. After 15 minutes, the reaction mixture was heated until reflux for 5 hours. Completion of the reaction was monitored by thin layer chromatography. After the 5 hours, the intermediate mixture was cooled to 20° C., and within 20 minutes 4.5 g of 10% hydrochloric acid solution (0.012 mol) was added drop wise. The precipitate consisted of tiny white crystals, and was stirred for 1 hour at room temperature, then filtered by suction, washed with first 150 ml ethanol, then 300 ml water and dried at 85° C. in a circulating air oven.