Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].Cl.[C:6]([C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=1)[CH2:12][NH2:13])(=[O:8])[CH3:7].C(N(CC)CC)C>ClCCl>[C:1]([NH:13][CH2:12][C:11]1[CH:10]=[C:9]([C:6](=[O:8])[CH3:7])[CH:16]=[CH:15][CH:14]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Cl
Reactant: CC(=O)c1cccc(CN)c1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)NCc1cccc(C(C)=O)c1
Temperature: 25 °C
Reaction time: 10 h
Yield: 62.1 %

Procedure:
Acetyl chloride (2.5 g) was added slowly to a suspension of 3-acetylbenzylamine hydrochloride (5.0 g) and triethylamine (6.0 g) in dichloromethane (50 ml) with cooling on an ice-water bath. The mixture was stirred at room temperature for 10 hours. The solvent was removed under reduced pressure. The residue was dissolved in water (100 ml). The solution was alkalified with an aqueous potassium carbonate solution. The mixture was extracted with ethyl acetate (150 ml). The solution was dried with magnesium sulfate. The solvent was removed under reduced pressure to afford 3'-acetylaminomethylacetophenone (3.2 g) (oil).
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH2:10])=[C:5]([N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:4]=1.ClC(Cl)(O[C:22](=[O:28])[O:23][C:24](Cl)(Cl)Cl)Cl.[N-:30]=[C:31]=[O:32]>CCOC(C)=O.CN(C=O)C>[F:17][C:2]([F:1])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH:10][C:31]([NH:30][C:6]2[C:9]3[NH:10][C:22](=[O:28])[O:23][C:24]=3[CH:3]=[CH:4][CH:5]=2)=[O:32])=[C:5]([N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:4]=1
Reactant: [N-]=C=O
Reactant: NCc1ccc(C(F)(F)F)cc1N1CCCC1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C(NCc1ccc(C(F)(F)F)cc1N1CCCC1)Nc1cccc2oc(=O)[nH]c12
Temperature: 80 °C
Yield: 20 %

Procedure:
Amine 2b (289 mg, 1.2 mmol) (Scheme 7) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (356 mg, 1.2 mmol) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and the residue was dissolved in 5 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1b (180 mg, 1.2 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1×20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 100 mg of a white solid. Yield=20% 1HNMR (DMSO, 200 MHz) δ 1.94 (4H, m), 3.23 (4H, m), 4.67 (2H, d, J=5.6 Hz), 6.55 (2H, dd, J=8.8 Hz, J′=1.2 Hz), 7.05 (1H, t, J=8.2 Hz), 7.17 (2H, d, J=7.2 Hz), 7.46 (1H, d), 9.98 (1H, t), 11.53 (1H, bs), 11.80 (1H, bs); [M+1] 421.2 (C20H19F3N4O3 requires 420.39).
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:12]([CH2:31][O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[S:11][C:10]1([C:41]1[CH:46]=[CH:45][C:44]([Cl:47])=[C:43]([CH2:48][C:49]2[CH:58]=[CH:57][C:52]3[O:53][CH2:54][CH2:55][O:56][C:51]=3[CH:50]=2)[CH:42]=1)O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([SiH](CC)CC)C.B(F)(F)F.CCOCC>ClCCl.C(#N)C>[Cl:47][C:44]1[CH:45]=[CH:46][C:41]([C@H:10]2[C@H:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C@@H:14]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C@H:13]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C@@H:12]([CH2:31][O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[S:11]2)=[CH:42][C:43]=1[CH2:48][C:49]1[CH:58]=[CH:57][C:52]2[O:53][CH2:54][CH2:55][O:56][C:51]=2[CH:50]=1
Reactant: OC1(c2ccc(Cl)c(Cc3ccc4c(c3)OCCO4)c2)S[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Agent: CC[SiH](CC)CC
Agent: FB(F)F
Solvent: ClCCl
Solvent: CCOCC
Solvent: CC#N
Product: Clc1ccc([C@@H]2S[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)cc1Cc1ccc2c(c1)OCCO2
Temperature: 0 °C
Yield: 54 %

Procedure:
To a stirred −15° C. solution of lactol (125, 410 mg, 0.50 mmol) in dichloromethane/acetonitrile (4 mL/4 mL) was added triethylsilane (0.49 mL, 3.02 mmol) followed by boron trifluoride diethyl etherate (0.26 mL, 2.01 mmol) at a rate such that the reaction temperature was maintained between −15 and 0° C. The solution was allowed to warm to 0° C. over 0.5 h prior to quenching with saturated sodium bicarbonate solution. After removal of organic volatiles under a reduced pressure, the residue was partitioned between ethyl acetate and water. Following extraction of the aqueous layer with ethyl acetate, the combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography (silica gel, 3 to 25% ethyl acetate in hexane) to yield the title compound (126, 215 mg, 0.27 mmol, 53%) as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([S:9][C:10]2[CH:15]=[CH:14][C:13](NC(=O)CC(F)(F)F)=[CH:12][CH:11]=2)[N:3]=1.ClC1C=C(NC2C=CC=CN=2)N=C(SC2C=CC(NC(=O)CC(F)(F)F)=CC=2)N=1.ClCS(C1C=C(S(CCl)(=O)=O)N=CN=1)(=O)=O.SC1C=CC([C:74]([NH:76][CH2:77][C:78]([F:81])([F:80])[F:79])=[O:75])=CC=1.C(N(CC)CC)C>C(#N)C>[Cl:8][C:6]1[CH:7]=[C:2]([Cl:1])[N:3]=[C:4]([S:9][C:10]2[CH:11]=[CH:12][C:13]([C:74]([NH:76][CH2:77][C:78]([F:81])([F:80])[F:79])=[O:75])=[CH:14][CH:15]=2)[N:5]=1
Reactant: O=C(NCC(F)(F)F)c1ccc(S)cc1
Reactant: O=C(CC(F)(F)F)Nc1ccc(Sc2nc(Cl)cc(Cl)n2)cc1
Agent: O=C(CC(F)(F)F)Nc1ccc(Sc2nc(Cl)cc(Nc3ccccn3)n2)cc1
Agent: O=S(=O)(CCl)c1cc(S(=O)(=O)CCl)ncn1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: O=C(NCC(F)(F)F)c1ccc(Sc2nc(Cl)cc(Cl)n2)cc1

Procedure:
4-(4,6-Dichloropyrimidin-2-ylthio)-N-(2,2,2-trifluoroethyl)benzamide was prepared according the procedure of 1a in Scheme 2 from 4,6-dichloromethylsulfonylpyrimidine (1.0 g, 4.4 mmol), 4-mercapto-N-(2,2,2-trifluoroethyl)benzamide (1.1 g, 4.7 mmol), and triethylamine (0.7 mL, 4.9 mmol) in acetonitrile (30 mL). Desired compound was purified by column chromatography (SiO2, ethyl acetate/heptanes=1:1-1:0, TLC: SiO2) to yield 210 mg (12%) (HPLC method A: Rf=8.508 minutes).
Reaction SMILES: [C:1]([C:5]1[S:9][C:8]([NH2:10])=[C:7]([C:11]([O:13][CH3:14])=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C[OH:16].[OH-].[K+]>O>[C:1]([C:5]1[S:9][C:8]2[NH:10][C:14](=[O:16])[O:13][C:11](=[O:12])[C:7]=2[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CO
Reactant: COC(=O)c1cc(C(C)(C)C)sc1N
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: CC(C)(C)c1cc2c(=O)oc(=O)[nH]c2s1
Temperature: 80 °C
Reaction time: 6 h
Yield: 96 %

Procedure:
To a vial containing methyl 5-tert-butyl-2-aminothiophene-3-carboxylate (0.643 g) in 1:1 methanol: H2O (6 mL) was added KOH (0.5069 g). The vial was capped and the mixture was stirred at 80° C. for 6 h. The solvent was removed under vacuum and the crude product was dissolved in water (50 mL) and transferred to a 100 mL round bottom flask. To the vigorously stirred aqueous solution was added at room temperature drop wise phosgene (2M toluene, 6 mL) over a 15 minute period. The resulting mixture was stirred at room temperature overnight. The crude reaction mixture was filtered; the precipitate was washed with water, dried and dissolved in ethyl acetate (10 mL). The organic solution was dried over anhydrous sodium sulfate, filtered and the solvent was removed under vacuum to give 654.9 mg (96%) of the expected 6-tert-butyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[O:11][C:12]1[C:13]([NH:27][C:28]2[S:29][CH:30]=[C:31]([CH3:33])[N:32]=2)=[N:14][CH:15]=[C:16]([S:18][CH:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)[CH3:20])[CH:17]=1.C(OC([Cl:39])=O)C.[CH3:40][N:41]([CH3:45])[CH2:42][CH2:43][NH2:44].[OH-].[Na+].[ClH:48]>C(Cl)Cl.CCOCC>[ClH:1].[ClH:39].[ClH:48].[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:44][CH2:43][CH2:42][N:41]([CH3:45])[CH3:40])=[O:8])=[CH:4][C:3]=1[O:11][C:12]1[C:13]([NH:27][C:28]2[S:29][CH:30]=[C:31]([CH3:33])[N:32]=2)=[N:14][CH:15]=[C:16]([S:18][CH:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)[CH3:20])[CH:17]=1
Reactant: CCOC(=O)Cl
Reactant: Cc1csc(Nc2ncc(SC(C)c3ccccn3)cc2Oc2cc(C(=O)O)ccc2Cl)n1
Reactant: CN(C)CCN
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CCOCC
Product: Cc1csc(Nc2ncc(SC(C)c3ccccn3)cc2Oc2cc(C(=O)NCCN(C)C)ccc2Cl)n1
Reaction time: 3 h
Yield: 14.8 %

Procedure:
4-chloro-3-(2-(4-methylthiazol-2-ylamino)-5-(1-(pyridin-2-yl)ethylthio)pyridin-3-yloxy)benzoic acid (prepared according to Example 73; 0.131 g, 0.263 mmol), TEA (d. 0.726) (0.0732 mL, 0.525 mmol), ethyl-carbonochloridate (0.057 g, 0.525 mmol), and N1,N1-dimethylethane-1,2-diamine (0.0231 g, 0.263 mmol) were reacted according the method of Example 72. 1N NaOH was added and the reaction mixture was stirred for 3 hours. The reaction mixture was extracted with CH2Cl2. The combined extracts were concentrated and purified by silica gel chromatography (4% MeOH in CH2Cl2, using 2% 7N ammonia in MeOH) and then purified by reverse phase chromatography to give the compound as the free base. The free base was dissolved in CH2Cl2 and HCl in ether was added. The mixture was concentrated to give 4-chloro-N-(2-(dimethylamino)ethyl)-3-(2-(4-methylthiazol-2-ylamino)-5-(1-(pyridin-2-yl)ethylthio)pyridin-3-yloxy)benzamide trihydrochloride (0.025 g, 14.8% yield). 1H NMR (d6-DMSO) δ 9.73 (s, 1H), 8.91 (m, 1H), 8.42 (m, 1H), 8.01 (d, 1H), 7.78 (m, 3H), 7.51 (s, 1H), 7.29 (m, 2H), 6.83 (s, 1H), 6.66 (m, 1H), 4.48 (q, 1H), 3.60 (m, 2H), 3.24 (m, 2H), 2.81 (d, 6H), 2.24 (s, 3H), 1.54 (d, 3H); Mass spectrum (esi) m/z=569.2 (100) (M+H-3HCl).
Reaction SMILES: [CH:1]1([NH:6][C@@H:7]2[CH2:12][C:11]3[C:13]([O:18][CH3:19])=[CH:14][CH:15]=[C:16]([F:17])[C:10]=3[O:9][CH2:8]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:20](=O)[CH2:21][CH3:22].[BH3-]C#N.[Na+]>CO>[CH:1]1([N:6]([C@@H:7]2[CH2:12][C:11]3[C:13]([O:18][CH3:19])=[CH:14][CH:15]=[C:16]([F:17])[C:10]=3[O:9][CH2:8]2)[CH2:20][CH2:21][CH3:22])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: COc1ccc(F)c2c1C[C@@H](NC1CCCC1)CO2
Reactant: CCC=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: CCCN(C1CCCC1)[C@H]1COc2c(F)ccc(OC)c2C1
Reaction time: 8 h
Yield: 97 %

Procedure:
To the solution of (R)-3-(N-cyclopentylamino)-8-fluoro-5-methoxy-3,4-dihydro-2H-1-benzopyran in methanol (25mL) were propanal (2 g, 36 mmol) and NaCNBH3 (2 g, 40 mmol) added. The solution was stirred overnight to give the desired compound in a 97% yield according to GC. The solvent was removed in vacuo and the residue was worked up by extraction to give 3.7 g of the title compound as a colorless oil. GC/MS (70 eV) M=307 (40%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:14][O:13][CH2:12][CH2:11][N:10]([C@@H](C3C=CC=CC=3)C)[CH2:9]2)=[CH:4][CH:3]=1.[Cl:23]C(OC(Cl)C)=O.CO>ClCCCl>[ClH:23].[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]2[CH2:14][O:13][CH2:12][CH2:11][NH:10][CH2:9]2)=[CH:6][CH:7]=1
Reactant: CC(Cl)OC(=O)Cl
Reactant: C[C@H](c1ccccc1)N1CCOC[C@@H](c2ccc(Br)cc2)C1
Solvent: CO
Solvent: ClCCCl
Product: Brc1ccc([C@H]2CNCCOC2)cc1
Product: Cl
Temperature: 25 °C
Yield: 85.7 %

Procedure:
To a solution of (S)-6-(4-bromophenyl)-4-((R)-1-phenylethyl)-[1,4]oxazepane (0.610 g, 1.69 mmol) in 1,2-dichloroethane (2.83 ml) was added 1-chloroethyl chloroformate (0.605 g, 4.23 mmol) at room temperature. The mixture was refluxed for 4 hours and cooled to room temperature. After addition of methanol (5.0 ml), the mixture was refluxed for 3 hours and concentrated under reduced pressure to afford the crude product. This crude product was washed with ether, dried under reduced pressure to afford (S)-6-(4-bromophenyl)-1,4-oxazepane hydrochloride as white solid (0.424 g, 86%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([F:13])[C@@H:10]([O:14][CH3:15])[C@H:9]1[C:16]([OH:18])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:19][C:20]1[C:21]([F:28])=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH2:23][NH2:24].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([F:13])[C@@H:10]([O:14][CH3:15])[C@H:9]1[C:16](=[O:18])[NH:24][CH2:23][C:22]1[CH:25]=[CH:26][CH:27]=[C:20]([Cl:19])[C:21]=1[F:28])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: NCc1cccc(Cl)c1F
Reactant: CO[C@H]1[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)C[C@@H]1F
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: O
Product: CO[C@H]1[C@@H](C(=O)NCc2cccc(Cl)c2F)N(C(=O)OC(C)(C)C)C[C@@H]1F
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of (2S,3S,4S)-4-fluoro-3-methoxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (500 mg, 1.90 mmol) in DMF (20 mL) were added 3-chloro-2-fluoro-benzylamine (330 mg, 2.1 mmol), HBTU (1.4 g, 3.8 mmol) and DIPEA (1.32 mL, 7.6 mmol). The reaction mixture was stirred at RT for 2 h then was poured into water (50 mL). After extraction with ETOAc (3×30 mL), the organic phases were joined, washed with brine, dried over Na2SO4, filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 1:1) to give (2S,3S,4S)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-3-methoxy-pyrrolidine-1-carboxylic acid tert-butyl ester: Rf, TLC (c-hexane/EtOAc 1:1)=0.37; MS (UPLC): 405.1/407.2 [M+H]+, 349.1/351.1 [MH−tBu]+, 449.2/451.2 [M+HCOO]−; tR (HPLC conditions f): 2.12 min. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.59 (m, 1H), 7.48 (m, 1H), 7.37 (m, 1H), 7.20 (m, 1H), 5.20 (br.d, 1H), 4.47-4.26 (m, 3H), 4.19 (ddd, 1H), 3.81-3.65 (m, 1H), 3.54-3.40 (m, 1H), 3.36 (s, 3H), 1.42 and 1.27 (2 s, 9H).
Reaction SMILES: C(OC(=O)[NH:7][C@H:8]([CH:16]1[CH2:20][CH:19]([CH3:21])[C:18](=[O:22])[O:17]1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:7][C@H:8]([C@H:16]1[O:17][C:18](=[O:22])[C@H:19]([CH3:21])[CH2:20]1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CC1CC([C@H](Cc2ccccc2)NC(=O)OC(C)(C)C)OC1=O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: C[C@@H]1C[C@@H]([C@@H](N)Cc2ccccc2)OC1=O

Procedure:
A solution of [(S)-1-(4-methyl-5-oxo-tetrahydrofuran-2-yl)-2-phenylethyl]-carbamic acid t-butyl ester (synthesis described in Journal of Organic Chemistry (1986) 51(21), 3921) (2 g, 6.27 mmol) in DCM (40 ml) was treated with trifluoroacetic acid (5 ml) for 2 h. The solvent was evaporated under reduced pressure, the residue dissolved in DCM, washed with aqueous sodium bicarbonate and dried (Na2SO4). The solvent was evaporated to afford the title compound (D48) as a pale yellow solid (1.25 g)
Reaction SMILES: [C:1](/[C:3](/[CH3:15])=[CH:4]/[C:5]1[CH:6]=[C:7]([CH:12]=[CH:13][CH:14]=1)[C:8]([O:10][CH3:11])=[O:9])#[N:2].O1CCCC1>C(O)C.[C].[Pd]>[C:1]([CH:3]([CH3:15])[CH2:4][C:5]1[CH:6]=[C:7]([CH:12]=[CH:13][CH:14]=1)[C:8]([O:10][CH3:11])=[O:9])#[N:2]
Reactant: COC(=O)c1cccc(/C=C(\C)C#N)c1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: COC(=O)c1cccc(CC(C)C#N)c1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of methyl 3-[(1E)-2-cyanoprop-1-en-1-yl]benzoate (108 mg, 537 μmol) in ethanol (4 mL)/tetrahydrofuran (1 mL) was added 10% palladium-carbon (20 mg), and the mixture was stirred at room temperature under a hydrogen atmosphere (1 atm) for 4 hr. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure to give methyl 3-(2-cyanopropyl)benzoate as a colorless oil.
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][CH:5]=[CH:4][C:3]=1[OH:11].[N+](C1C=C(S(O[CH2:25][C@H:26]2[O:28][CH2:27]2)(=O)=O)C=CC=1)([O-])=O.[C:29](=O)([O-])[O-:30].[K+].[K+]>CC(=O)CC>[O:28]1[CH2:27][C@H:26]1[CH2:25][O:11][C:3]1[C:2]2[NH:1][C:29](=[O:30])[NH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1
Reactant: O=C([O-])[O-]
Reactant: Nc1c(O)cccc1[N+](=O)[O-]
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)OC[C@@H]2CO2)c1
Agent: [K+]
Solvent: CCC(C)=O
Product: O=c1[nH]c2cccc(OC[C@@H]3CO3)c2[nH]1
Yield: 26.3 %

Procedure:
A mixture of 2-amino-3-nitrophenol (12.0 g, 77.8 mmol), (S)-(+)-glycidyl 3-nitrobenzenesulfonate (20.18, 77.8 mmol) and potassium carbonate (11.8 g, 77.8 mmol) in 2-butanone (100 mL) was heated at reflux for 18 hours essentially as described for Procedure A. The residue was purified by flash chromatography on silica gel Merck-60 (eluant: 2:1 hexane-diethyl ether) to yield the title compound (4.30 g, 20.46 mmol).
Reaction SMILES: [Si]([O:8][C@H:9]([C:17]#[C:18]/[CH:19]=[CH:20]/[CH:21]=[CH:22]/[C@H:23]([O:40][Si](C(C)(C)C)(C)C)[CH2:24][C:25]#[C:26]/[CH:27]=[CH:28]/[C@H:29]([O:32][Si](C(C)(C)C)(C)C)[CH2:30][CH3:31])[CH2:10][CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].O>C1COCC1>[OH:8][C@H:9]([C:17]#[C:18]/[CH:19]=[CH:20]/[CH:21]=[CH:22]/[C@H:23]([OH:40])[CH2:24][C:25]#[C:26]/[CH:27]=[CH:28]/[C@H:29]([OH:32])[CH2:30][CH3:31])[CH2:10][CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14]
Reactant: CC[C@H](/C=C/C#CC[C@H](/C=C/C=C/C#C[C@H](CCCC(=O)OC)O[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: CC[C@@H](O)/C=C/C#CC[C@@H](O)/C=C/C=C/C#C[C@@H](O)CCCC(=O)OC
Reaction time: 3 h
Yield: 90 %

Procedure:
A solution of the product of Example 4 (40 mg, 0.065 mmol) in THF (1 ml) was treated with 1.0 M TBAF (0.32 ml, 0.32 mmol) at 0° C. The reaction was stirred for 3 h and then poured into water and extracted with ether. The ether extracts were washed with brine, dried and concentrated. The ethereal solution was then treated with an excess of freshly prepared diazomethane in ether to convert the free acid to the product. Flash column chromatography (silica gel, 4% MeOH/CH2Cl2) afforded the pure product in 90% yield. 1H NMR (500 MHz, C6D6): δ 6.55 (dd, J=15.5 Hz and 10.9 Hz, 1H), 6.16 (dd, J=15.2 Hz and 11.0 Hz, 1H), 6.05 (dd, J=15.5 Hz and 5.3 Hz, 1H), 5.70 (d, J=16.2 Hz, 1H), 5.61 (dd, J=14.6 Hz and 5.5 Hz, 1H), 5.58 (d, J=14.7 Hz, 1H), 4.28 (t, J=5.8 Hz, 1H), 4.06 (dd, J=11.2 Hz and 5.3 Hz, 1H), 3.65 (dd, J=1.0 Hz and 6.7 Hz, 1H), 3.30 (s, 3H), 2.36 (m, 2H), 2.06 (t, J=6.9 Hz, 2H), 1.72 (m, 2H), 1.59 (m, 2H), 1.27 (m, 2H), 0.74 (t, J=7.4 Hz, 3H). 13C NMR (125 MHz, C6D6): δ 173.819, 145.219, 141.143, 136.647, 130.007, 111.340, 109.915, 92.672, 85.857, 84.082, 81.330, 73.505, 70.225, 62.533, 51.488, 37.097, 33.599, 29.912, 28.658, 20.615, 9.451. HPLC: Beckman Ultrasphere reverse phase column (30% water in MeOH, 3.8 ml/min, 252 bar): elution time=5.41 min.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Cl[C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[N:13]=[CH:12][C:11]=1[C:23]#[N:24].C(=O)(O)[O-].[Na+]>C(O)C>[I:1][C:2]1[CH:3]=[C:4]([NH:5][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:23]#[N:24])[CH:6]=[CH:7][CH:8]=1
Reactant: N#Cc1cnc2ccc([N+](=O)[O-])cc2c1Cl
Reactant: Nc1cccc(I)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: N#Cc1cnc2ccc([N+](=O)[O-])cc2c1Nc1cccc(I)c1
Yield: 82.9 %

Procedure:
A mixture of 3.10 ml (25.7 mmol) 3-iodoaniline, 200 ml ethanol, and 5.00 g (21.4 mmol) 4-chloro-6-nitro-3-quinolinecarbonitrile was heated to reflux under N2 for 3.5 hours. Cooled and made basic with a saturated sodium bicarbonate. Stripped solvents and azeotroped with ethanol. Slurried residue with hexane and collected. Air dried, washed solids with water, and dried in vacuo. Dissolved solids in 400 ml ethyl acetate, stirred with Darco, filtered and removed solvent. Dried solids in vacuo to give 7.38 g of yellow solid: mass spectrum (electrospray m/e): M+H=417.0.
Reaction SMILES: [CH3:1][N:2]([CH:7]1[CH:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][CH2:9][CH2:8]1)[CH2:3][C:4](O)=O.C(OC(=O)C)(=[O:19])C.[CH:24]([OH:26])=[O:25]>>[CH3:4][CH:3]([C:24]([OH:26])=[O:25])[N:2]([CH:7]1[CH:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][CH2:9][CH2:8]1)[CH:1]=[O:19]
Reactant: CN(CC(=O)O)C1CCCC2CCCCC21
Reactant: O=CO
Reactant: CC(=O)OC(C)=O
Product: CC(C(=O)O)N(C=O)C1CCCC2CCCCC21
Temperature: 5 °C
Reaction time: 17 h
Yield: 89.4 %

Procedure:
150 Parts of methyl N-(decahydro-1-naphthalenyl)glycine were added dropwise to 372 parts of formic acid while cooling (5° C.). Upon complete addition, 110 parts of acetic acid anhydride were added. The reaction mixture was stirred for 17 hours at room temperature. The whole was distilled in vacuo, yielding 142.8 parts (89.4%) of methyl N-(decahydro-1-naphthalenyl)-N-formylglycine as a residue (intermediate 6).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8]([NH:10][C:11](=[O:13])[CH3:12])[CH:7]=[CH:6][C:5]=1[O:14][CH3:15])([O-])=O.[C:16]([O:22][CH2:23][CH3:24])(=[O:21])[CH2:17][C:18]([CH3:20])=O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[H][H]>[Pt].C(O)(C)C>[CH3:15][O:14][C:5]1[CH:6]=[CH:7][C:8]([NH:10][C:11](=[O:13])[CH3:12])=[CH:9][C:4]=1[NH:1][CH:18]([CH3:20])[CH2:17][C:16]([O:22][CH2:23][CH3:24])=[O:21]
Reactant: [H][H]
Reactant: CCOC(=O)CC(C)=O
Reactant: COc1ccc(NC(C)=O)cc1[N+](=O)[O-]
Agent: [Pt]
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC(C)O
Product: CCOC(=O)CC(C)Nc1cc(NC(C)=O)ccc1OC
Yield: 98 %

Procedure:
A mixture of 105.0 g. (0.5 mole) of 2-nitro-4-acetamidoanisole, 67.0 g. (0.5 mole) of ethyl acetoacetate, 550 ml. of isopropyl alcohol, 10.0 g. of 5% Pt/C, and 3.0 g. of p-toluenesulfonic acid is treated in an autoclave at 165° C. and 1,000 psi of hydrogen until the uptake of hydrogen ceases. The solvent and catalysts are removed. Upon standing, 143.8 g. (98%) of ethyl 3-(2'-methoxy-5-acetamidoanilino)butyrate is obtained. NMR analysis of the product supports the proposed structure.
Reaction SMILES: [NH:1]([CH2:5][CH2:6]O)CCO.II.[C:10]1(=[O:16])O[C:13](=O)[CH:12]=[CH:11]1.S(=O)(=O)(O)O.[C:22]1([CH3:28])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>>[N-:1]=[C:10]=[O:16].[N-:1]=[C:10]=[O:16].[C:22]1([CH2:28][C:6]2[CH:5]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: OCCNCCO
Reactant: O=C1C=CC(=O)O1
Reactant: Cc1ccccc1
Agent: II
Agent: O=S(=O)(O)O
Product: [N-]=C=O
Product: c1ccc(Cc2ccccc2)cc1

Procedure:
The above amounts of diethanolamine and iodine were added to the above amount of soybean oil with stirring. The mixture was stirred for 22 hours at a temperature between about 180° F. and about 225° F. Then, the above amounts of maleic anhydride, toluene and sulfuric acid were added with stirring. The mixture was refluxed for 8 hours using a Dean-Stark distilling trap, then distilled out of solvent to give a liquid soybean oil based polyol with a hydroxyl number of 53. A reaction mixture of about 10.00 grams of the polyol and the above indicated amount of diphenylmethane diisocyanate yielded a solid soybean oil based polyurethane material.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[Cl-].[NH4+].C(O)C.CN(C)C=O>[Fe].O>[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1
Reactant: Nc1cc(Oc2ccc([N+](=O)[O-])cc2)ccn1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CN(C)C=O
Solvent: CCO
Solvent: O
Product: Nc1ccc(Oc2ccnc(N)c2)cc1
Temperature: 100 °C
Reaction time: 0.17 h

Procedure:
After adding 1 g of 2-amino-4-(4-nitrophenoxy)pyridine to a mixture of 2.0 g of iron powder, 4.0 g of ammonium chloride, 30 ml of ethanol, 30 ml of dimethylformamide and 15 ml of water, the mixture was vigorously stirred at 100° C. for 10 minutes. The reaction solution was filtered with celite and the solvent was distilled off under reduced pressure to obtain 0.53 g of the target substance as a solid.