Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1([C@@H](N)C)C=CC=CC=1.[CH3:10][C@:11]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([CH2:15][CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:12]([OH:14])=O.Cl.CN(C)C=O.C(Cl)(=O)C(Cl)=O.[C:39]([O:47][CH2:48][CH3:49])(=[O:46])[CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42].[Mg+2].[Cl-].[Cl-].C(N(CC)CC)C>C(OCC)(=O)C.C(#N)C.O>[CH3:10][C@:11]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([CH2:15][CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:12]([CH:40]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[C:39]([O:47][CH2:48][CH3:49])=[O:46])=[O:14]
Reactant: CCOC(=O)CC(=O)OCC
Reactant: CC(C)(C)CC[C@@](C)(C(=O)O)c1ccccc1
Agent: C[C@H](N)c1ccccc1
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: CC#N
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)C(C(=O)OCC)C(=O)[C@](C)(CCC(C)(C)C)c1ccccc1
Temperature: 25 °C
Yield: 92.9 %

Procedure:
A suspension of Example 49-2 (63.5 g, 0.179 mol) in ethyl acetate (400 mL) was treated with water (200 mL) then enough 3 M HCl to bring the pH to <2. The solution was mixed and the layers were separated. The organic phase was concentrated to thick oil. The oil was dissolved in heptane (500 mL) and concentrated then redissolved in heptane (210 mL). To this solution was added N,N-dimethylformamide (1.2 g, 17.1 mmol) and oxalyl chloride (34.0 g, 0.268 mol). The solution was mixed at room temperature overnight, filtered through celite and concentrated to a residue. The crude acid chloride was dissolved in CH3CN (50 mL). To a separate vessel containing a 0° C. solution of diethyl malonate (30.0 g, 0.187 mol), and MgCl2 (17.8 g, 0.187 mol) in acetonitrile (240 mL) was added triethylamine (38.0 g, 0.376 mol). The solution was warmed to room temperature and mixed for 1 h, then cooled back to 0-10° C. The acid chloride/CH3CN solution was added over 30 minutes and the reaction mixture was heated to 50° C. for 3 h. The reaction mixture was cooled and concentrated to a thick sludge. Ethyl acetate (400 mL) and water (400 mL) were added and the pH was adjusted to 6 with concentrated HCl. The layers were separated and the organic solution was washed with 10% NaCl. The organic layer was concentrated to a thick oil then chased with heptane (300 mL) to give the title compound (assayed for 62.6 g, 93%).
Reaction SMILES: C(O)=O.Cl[S:5]([N:8]=C=O)(=[O:7])=[O:6].[CH3:11][CH:12]([CH2:16][CH3:17])[CH2:13][CH2:14][OH:15].N1C=CC=CC=1>ClCCl.O.CCOC(C)=O>[S:5](=[O:6])(=[O:7])([O:15][CH2:14][CH2:13][CH:12]([CH3:11])[CH2:16][CH3:17])[NH2:8]
Reactant: CCC(C)CCO
Reactant: O=C=NS(=O)(=O)Cl
Solvent: O=CO
Solvent: O
Solvent: CCOC(C)=O
Product: CCC(C)CCOS(N)(=O)=O
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
Formic acid (65 mL, 17.2 mmol) was added dropwise to neat chlorosulfonyl isocyanate (1.5 mL, 17.2 mmol) at 0° C. with rapid stirring. Vigorous gas evolution was observed during the addition process. The resulting viscous suspension was stirred for 5 min at 0° C. during which time the mixture solidified. Dichloromethane (9 mL) was added and the solution was stirred for 1 h at 0° C. then 8 h at 25° C. The reaction mixture was cooled to 0° C. and a solution of 3-methylpentan-1-ol (11.5 mmol) and pyridine (1.4 mL, 17.2 mmol) in 8 mL of dichloromethane was added dropwise. The contents were warmed to 25° C. and stirred for 3 h. The reaction mixture was treated with EtOAc (80 mL) and water (50 mL), and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic phase was washed with brine, dried over MgSO4, filtered and then concentrated. The crude product was purified by multiple flash chromatographies (7% ethyl acetate/dichloromethane) to give 3-methylpentyl sulfamate.
Reaction SMILES: [C:1]1([O:11][CH3:12])[C:2](=[CH:4][CH:5]=[C:6]([CH:10]=1)[CH:7]=[CH:8][CH3:9])[OH:3].C(OC(=O)C)(=[O:15])C.C([O-])(=O)C.[Na+].S(=O)(O)[O-].[Na+]>C(O)(=O)C.C1(C)C=CC=CC=1>[CH3:9][C:8]([CH2:7][C:6]1[CH:5]=[CH:4][C:2]([OH:3])=[C:1]([O:11][CH3:12])[CH:10]=1)=[O:15]
Reactant: CC(=O)OC(C)=O
Reactant: CC=Cc1ccc(O)c(OC)c1
Agent: CC(=O)[O-]
Agent: O=S([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Product: COc1cc(CC(C)=O)ccc1O
Temperature: 20 °C
Yield: 85.3 %

Procedure:
A mixture of isoeugenol (8.21 g., 50 mm.), acetic anhydride (5.62 g., 55 mm.) and anhydrous sodium acetate (0.41 g., 5 mm.) is heated at 100° C.-105° C. under nitrogen atmosphere for 2.5 hours. The reaction mixture is cooled and diluted with 65 ml. of toluene before a solution (11 ml.) of 38.6% peracetic and 0.85 g. of sodium acetate in acetic acid is added slowly. After heating at 50° C.-60° C. for 2-3 hours, the reaction mixture is cooled to 20° C. and treated with aqueous sodium bisulfite (2.8 g.) to destroy excess peracetic acid. The entire mixture is mixed with 8 ml. of toluene, 50 ml. of 14% aqueous sulfuric acid, and is heated with stirring to reflux for 12.5 hours. After cooling to ambient temperature, the toluene layer is separated, and the aqueous layer extracted 3×20 ml. of toluene. The toluene layers are combined, washed with saturated aqueous sodium sulfate, dried over anhydrous magnesium sulfate and concentrated in vacuo to give methylvanillyl ketone in 85.3% yield.
Reaction SMILES: CC(OC(/N=N/C(OC(C)C)=O)=O)C.[Cl:15][C:16]1[C:17]2[C:24]([I:25])=[CH:23][NH:22][C:18]=2[N:19]=[CH:20][N:21]=1.[C:26]([N:33]1[CH2:36][CH:35](O)[CH2:34]1)([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[Cl:15][C:16]1[C:17]2[C:24]([I:25])=[CH:23][N:22]([CH:35]3[CH2:34][N:33]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:36]3)[C:18]=2[N:19]=[CH:20][N:21]=1
Reactant: Clc1ncnc2[nH]cc(I)c12
Reactant: CC(C)(C)OC(=O)N1CC(O)C1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CC(n2cc(I)c3c(Cl)ncnc32)C1
Reaction time: 1 h
Yield: 68.8 %

Procedure:
DIAD (1.41 ml) was added to a solution of 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (1.00 g), N-Boc-3-hydroxyazetidine (930 mg), and triphenylphosphine (1.85 g) in tetrahydrofuran (40 ml), and the reaction mixture was stirred for 1 hour. After concentrating, the reaction mixture was washed with ethyl acetate to obtain the title compound as a white solid (1.07 g). Physical properties: m/z [M+H]+ 435.0
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:22])=[C:6]([C@:8]2([CH3:21])[C@@H:13]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[CH2:12][O:11][C:10]([NH2:20])=[N:9]2)[CH:7]=1.[C:23]([C:25]1[CH:26]=[CH:27][C:28]([C:31](O)=[O:32])=[N:29][CH:30]=1)#[N:24]>>[NH2:20][C:10]1[O:11][CH2:12][C@H:13]([O:14][CH2:15][C:16]([F:18])([F:19])[F:17])[C@:8]([C:6]2[CH:7]=[C:2]([NH:1][C:31]([C:28]3[CH:27]=[CH:26][C:25]([C:23]#[N:24])=[CH:30][N:29]=3)=[O:32])[CH:3]=[CH:4][C:5]=2[F:22])([CH3:21])[N:9]=1
Reactant: C[C@]1(c2cc(N)ccc2F)N=C(N)OC[C@@H]1OCC(F)(F)F
Reactant: N#Cc1ccc(C(=O)O)nc1
Product: C[C@]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)N=C(N)OC[C@@H]1OCC(F)(F)F

Procedure:
The condensation of (4R,5R)-4-(5-amino-2-fluoro-phenyl)-4-methyl-5-(2,2,2-trifluoro-ethoxy)-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (A8.4) and 5-cyano-pyridine-2-carboxylic acid following procedure I yielded the title compound as a white solid. MS (ISP): m/z=452.1 [M+H]−.
Reaction SMILES: [C:1]([C:3]1[C:8]2[N:9]=[C:10]([C:12]([N:14]([O:16][CH3:17])[CH3:15])=[O:13])[O:11][C:7]=2[C:6](F)=[C:5]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:4]=1[CH3:25])#[N:2].C(N(CC)CC)C.[CH3:33][N:34]([CH3:40])[C@H:35]1[CH2:39][CH2:38][NH:37][CH2:36]1.C(OCC)(=O)C>CS(C)=O.[Cl-].[Na+].O>[C:1]([C:3]1[C:8]2[N:9]=[C:10]([C:12]([N:14]([O:16][CH3:17])[CH3:15])=[O:13])[O:11][C:7]=2[C:6]([N:37]2[CH2:38][CH2:39][C@H:35]([N:34]([CH3:40])[CH3:33])[CH2:36]2)=[C:5]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:4]=1[CH3:25])#[N:2]
Reactant: CN(C)[C@H]1CCNC1
Reactant: CON(C)C(=O)c1nc2c(C#N)c(C)c(-c3ccccc3)c(F)c2o1
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Solvent: CCOC(C)=O
Product: CON(C)C(=O)c1nc2c(C#N)c(C)c(-c3ccccc3)c(N3CC[C@H](N(C)C)C3)c2o1
Temperature: 150 °C
Reaction time: 1.5 h
Yield: 31.7 %

Procedure:
4-Cyano-7-fluoro-N-methoxy-N,5-dimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide (I-115) (200 mg, 0.59 mmol) was dissolved in dimethyl sulfoxide (10 ml), and at room temperature, triethylamine (99 μl, 0.71 mmol) was added. Next, the solution was heated at 150° C., and a solution of (3S)-3-(dimethylamino)pyrrolidine (90 μl, 0.71 mmol) dissolved in dimethyl sulfoxide (2 ml) was added all at a time, followed by further stirring for 1.5 hours. The mixture liquid was cooled to room temperature, then this was fractionated with ethyl acetate and saturated brine. The aqueous layer was separated, this was extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away, and the resulting residue was purified by preparative TLC (eluent, chloroform:methanol=94:6) to obtain the entitled compound (81 mg, 32%) as a brown amorphous substance.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:19])[CH2:4][CH:5]([NH:12]S(C(C)(C)C)=O)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[ClH:20]>CO.O1CCOCC1>[ClH:20].[CH3:1][O:2][C:3](=[O:19])[CH2:4][CH:5]([NH2:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: COC(=O)CC(NS(=O)C(C)(C)C)c1ccccc1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: COC(=O)CC(N)c1ccccc1
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
3-(2-Methyl-propane-2-sulfinylamino)-3-phenyl-propionic acid methyl ester (1.73 mmol, 1 eq) is dissolved in 10 mL methanol (J. Org. Chem., 2002, 67, 7819-7832). A solution of HCl in dioxane (4 M, 10 mL) is added. The solution is stirred at room temperature for 45 min and concentrated in vacuo. 3-Amino-3-phenyl-propionic acid methyl ester hydrochloride is obtained as yellow viscous oil (135% crude product); ES-MS (MH+)=181.1.
Reaction SMILES: [NH2:1][C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][CH2:4][CH2:5]NC(=N)N.[NH2:13][C@H:14](C(O)=O)CCC(=O)N.N[C@H](C(O)=O)CCC(=O)O>>[NH2:1][C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][CH2:4][CH2:5][CH2:14][NH2:13]
Reactant: NC(=O)CC[C@H](N)C(=O)O
Reactant: N=C(N)NCCC[C@H](N)C(=O)O
Agent: N[C@@H](CCC(=O)O)C(=O)O
Product: NCCCC[C@H](N)C(=O)O

Procedure:
Arg, Gln, Glu
Reaction SMILES: CN(C=O)C.[Br:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[SH:13].C(=O)([O-])[O-].[K+].[K+].[CH2:20]([O:22][CH:23]([O:26][CH2:27][CH3:28])[CH2:24]Br)[CH3:21]>C(OCC)(=O)C.O>[CH2:20]([O:22][CH:23]([O:26][CH2:27][CH3:28])[CH2:24][S:13][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[Br:6])[CH3:21]
Reactant: CCOC(CBr)OCC
Reactant: Sc1ccccc1Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: CCOC(CSc1ccccc1Br)OCC
Temperature: 25 °C
Reaction time: 5 h
Yield: 85.4 %

Procedure:
A 500 mL round bottom flask was charged with anhydrous DMF (100 mL), 2-bromothiophenol (10.0 g, 52.88 mmol), potassium carbonate (11.0 g, 79.59 mmol) and bromoacetaldehyde diethyl acetal (8.35 mL, 55.5 mmol). The reaction was stirred at room temperature for 5 hours. Water (50 mL) and ethyl acetate (100 mL) were then added with mixing. The layers were separated and the organic layer was washed with water (5×50 mL), dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to provide 2-(2-bromophenylthio) acetaldehyde diethyl acetal (13.78 g, 85%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:12]2[C:13]([Cl:20])=[N:14][CH:15]=[C:16]([C:17](O)=[O:18])[C:11]=2[C:10]([CH3:21])=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:22]1[CH2:27][CH2:26][CH:25]([NH2:28])[CH2:24][CH2:23]1>>[C:1]([O:5][C:6]([N:8]1[C:12]2=[C:13]([Cl:20])[N:14]=[CH:15][C:16]([C:17](=[O:18])[NH:28][CH:25]3[CH2:26][CH2:27][O:22][CH2:23][CH2:24]3)=[C:11]2[C:10]([CH3:21])=[CH:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]
Reactant: NC1CCOCC1
Reactant: Cc1cn(C(=O)OC(C)(C)C)c2c(Cl)ncc(C(=O)O)c12
Product: Cc1cn(C(=O)OC(C)(C)C)c2c(Cl)ncc(C(=O)NC3CCOCC3)c12

Procedure:
Prepared in a similar manner to Example 11 (b) from 7-chloro-3-methyl-pyrrolo[2,3-c]pyridine-1,4-dicarboxylic acid 1-tert-butyl ester and using tetrahydro-pyran-4-ylamine (195 mg) instead of morpholine. The title compound was further purified by trituration with ether/isohexane to give an off-white solid (324 mg).
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[C:5](/[CH:8]=[CH:9]/[C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[O:6][CH:7]=1.[Cl:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[Cl:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]1[CH:26]=[CH:27][C:28]([O:31][CH2:2][C:3]2[N:4]=[C:5](/[CH:8]=[CH:9]/[C:10]3[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=3)[O:6][CH:7]=2)=[CH:29][CH:30]=1
Reactant: FC(F)(F)c1ccc(/C=C/c2nc(CCl)co2)cc1
Reactant: Oc1ccc(CCCCCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: FC(F)(F)c1ccc(/C=C/c2nc(COc3ccc(CCCCCl)cc3)co2)cc1
Temperature: 60 °C
Reaction time: 24 h
Yield: 96 %

Procedure:
A suspension of 4-chloromethyl-2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazole (13.4 g), 4-(4-chlorobutyl)phenol (8.63 g) and potassium carbonate (6.46 g) in DMF (200 ml) was stirred at 60° C. for 24 hr. The reaction mixture was combined with water to give crystals, which were collected by filtration and washed with methanol-water (2:1) to give crude 4-[[4-(4-chlorobutyl)phenoxy]methyl]-2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazole (19.5 g) as colorless powders. A suspension of this product (18.5 g) and sodium iodide (31.8 g) in acetonitrile (240 ml) was refluxed for 22 hr. The reaction mixture was concentrated, diluted with ethyl acetate, successively washed with water, hypo-water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was washed with hexane to give the titled compound (12.3 g) as colorless needle crystals.
Reaction SMILES: Cl.[CH3:2][C:3]1[N:4]=[CH:5][NH:6][C:7]=1[CH2:8][OH:9].[C:10]([Si:14](Cl)([CH3:16])[CH3:15])([CH3:13])([CH3:12])[CH3:11].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Si:14]([O:9][CH2:8][C:7]1[NH:6][CH:5]=[N:4][C:3]=1[CH3:2])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:16])[CH3:15]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: Cc1nc[nH]c1CO
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1nc[nH]c1CO[Si](C)(C)C(C)(C)C
Reaction time: 72 h
Yield: 27.3 %

Procedure:
13.0 g(87.5 mmol) of 4-methyl-5-imidazolemethanol hydrochloride, 13.5 g(89.6 mmol) of t-butylchlorodimethylsilane and 14.5 g(105 mmol) of potassium carbonate were added to 200 ml of dimethylformamide and the resulting mixture was stirred for 3 days. After dimethylformamide was removed under reduced pressure, 500 ml of ethylacetate was added to the residue which was then washed with aqueous sodium chloride solution (200 ml×3). The organic layer was dried over anhydrous magnesium sulfate and concentrated to give 5.4 g(23.9 mmol, Yield 27%) of the title compound.
Reaction SMILES: O.Cl.[CH2:3]=[C:4]1[C:9](=[O:10])[CH:8]2[CH2:11][CH2:12][N:5]1[CH2:6][CH2:7]2.C([O-])([O-])=O.[K+].[K+]>CO.O=[Pt]=O>[CH3:3][CH:4]1[C:9](=[O:10])[CH:8]2[CH2:11][CH2:12][N:5]1[CH2:6][CH2:7]2
Reactant: C=C1C(=O)C2CCN1CC2
Agent: O=[Pt]=O
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CO
Solvent: O
Product: CC1C(=O)C2CCN1CC2
Reaction time: 1 h
Yield: 57.8 %

Procedure:
A mixture of 10.1 g (58.4 mmol) of 2-methylene-1-azabicyclo[2.2.2]octan-3-one hydrochloride hydrate, 8.1 g of K2CO3 and 100 mg of PtO2 in 100 mL of MeOH was hydrogenated at 10–15 psi H2 for about 1 hr. The solution was filtered through dicalite and the solvent was evaporated in vacuo. The residue was dissolved in CHCl3 and again filtered through dicalite. The filtrate was evaporated in vacuo to give 4.7 g (58% yield) of 2-methyl-1-azabicyclo[2.2.2]octan-3-one Compound 8A as a yellow oil. 1H NMR (CDCl3) 1.3 (d, 3H), 2.0 (m, 4H), 2.4 (t, 1H), 2.9 (m, 1H), 3.05 (, 1H), 3.2 (m, 3H). This material was used without further purification in the next step.
Reaction SMILES: C1([C@H]([NH:9][C@H:10]([CH3:23])[CH2:11][C:12]2[CH:13]=[C:14]([CH2:18][C:19]([O:21][CH3:22])=[O:20])[CH:15]=[CH:16][CH:17]=2)C)C=CC=CC=1.C([O-])=O.[NH4+]>C(O)C.[OH-].[OH-].[Pd+2]>[NH2:9][C@H:10]([CH3:23])[CH2:11][C:12]1[CH:13]=[C:14]([CH2:18][C:19]([O:21][CH3:22])=[O:20])[CH:15]=[CH:16][CH:17]=1
Reactant: COC(=O)Cc1cccc(C[C@@H](C)N[C@H](C)c2ccccc2)c1
Agent: [Pd+2]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCO
Product: COC(=O)Cc1cccc(C[C@@H](C)N)c1
Temperature: 25 °C
Yield: 100 %

Procedure:
A solution of methyl [3-((2R)-2-{[(1R)-1-phenyl-ethyl]-amino}-propyl)-phenyl]-acetate (Preparation 89) (13.65 g, 40.9 mmol) and ammonium formate (12.9 g, 204 mmol) in ethanol (200 ml) was heated at reflux in the presence of 20% of palladium hydroxide on charcoal (Pd(OH)2/C, 1.36 g). After 3 hours the reaction mixture was cooled to room temperature, filtered through arbocel and the filtrate concentrated in vacuo. The residue was partitioned between dichloromethane (200 ml) and 880 ammonia (100 ml) and the organic phase separated. The aqueous phase was extracted with further dichlorormethane (3×100 ml) and the combined organic extracts washed with brine (100 ml), dried (sodium sulfate) and reduced in vacuo to give the title compound (8.48 g) as a pale yellow oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([N:11]=[CH:12][CH2:13][N+:14]([O-:16])=[O:15])=[C:6]([CH:10]=1)[C:7](O)=[O:8].C([O-])(=O)C.[K+]>C(OC(=O)C)(=O)C>[F:1][C:2]1[CH:10]=[C:6]2[C:5](=[CH:4][CH:3]=1)[N:11]=[CH:12][C:13]([N+:14]([O-:16])=[O:15])=[C:7]2[OH:8]
Reactant: O=C(O)c1cc(F)ccc1N=CC[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: CC(=O)OC(C)=O
Product: O=[N+]([O-])c1cnc2ccc(F)cc2c1O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
4 g (17.6 mmol) of 5-fluoro-2-[2-nitro-ethylideneamino]-benzoic acid (Example 19a) in 35 ml acetic anhydride are heated (ca. 100° C.) until a clear solution is obtained. 2 g (21.2 mmol) of potassium acetate are added and stirring is continued for 30 min (tlc-control). The reaction mixture is cooled to rt and the formed crystals are filtered off and washed several times with acetic acid and water. mp: 313° C.; MS: 207 (M+−1); HPLC: tret=9.94 min (Grad 3).
Reaction SMILES: C(Cl)Cl.[C:4]([O:12][CH:13]1[CH2:18][CH2:17][C:16](=[O:19])[CH2:15][CH2:14]1)(=O)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(N(CC)C(C)C)(C)C.FC(F)(F)S(O[Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])(=O)=O>C(OCC)(=O)C.CCCCCC.O>[CH2:4]([O:12][CH:13]1[CH2:18][CH2:17][C:16]([O:19][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])=[CH:15][CH2:14]1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: O=C1CCC(OC(=O)c2ccccc2)CC1
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)OC1=CCC(OCc2ccccc2)CC1
Temperature: 25 °C
Yield: 86.2 %

Procedure:
A methylene chloride (200 mL) solution of 4-oxocyclohexyl benzoate [Macromolecules 2000, 33, 4619] (17.2 g, 84.5 mmol) in N,N-diisopropylethylamine (29.4 mL, 169 mmol) was cooled in an ice bath under nitrogen. A methylene chloride (50 mL) solution of tert-butyldimethylsilyl trifluormethanesulfonate (20.3 mL, 88.7 mmol) was added dropwise over 0.5 h. After warming to room temperature the contents of the reaction flask were poured into water. The organic layer was separated, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Flash column chromatography (hexane:ethyl acetate, 95:5) gave a pale oil (23.2 g, 86% yield).
Reaction SMILES: C([O:3][C:4](=[O:10])[C@H:5]([CH3:9])[NH:6][CH2:7][CH3:8])C.[C:11](Cl)(=[O:23])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>>[CH2:7]([N:6]([C:11](=[O:23])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[C@H:5]([C:4]([OH:10])=[O:3])[CH3:9])[CH3:8]
Reactant: CCN[C@@H](C)C(=O)OCC
Reactant: CCCCCCCCCCCC(=O)Cl
Product: CCCCCCCCCCCC(=O)N(CC)[C@@H](C)C(=O)O

Procedure:
Example 1A was repeated, replacing starting materials with N-ethyl alanine ethyl ester and dodecanoyl chloride and followed by hydrolysis to give N-Ethyl-N-(1-oxododecyl)alanine.
Reaction SMILES: [NH2:1][C@H:2]([C:4]([OH:6])=[O:5])[CH3:3].[NH:7]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:8]([C:10](ON1C(=O)CCC1=O)=[O:11])[CH3:9].CN1CCOCC1>CN(C=O)C>[NH:7]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[C@H:8]([C:10]([NH:1][C@H:2]([C:4]([OH:6])=[O:5])[CH3:3])=[O:11])[CH3:9]
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)ON1C(=O)CCC1=O
Reactant: C[C@H](N)C(=O)O
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: C[C@H](NC(=O)[C@H](C)NC(=O)OC(C)(C)C)C(=O)O

Procedure:
L-Alanine (3.57 g, 40 mmol) was dissolved in 18.8 ml of Triton B (40 mmol), evaporated to dryness, and the oily residue re-evaporated twice with DMF (30 ml each). The salt obtained was stirred with 11.45 g of Boc-Ala-OSu (40 mmol) in 40 ml DMF, with 4 ml of NMM added, for 20 hours. The solvent was removed and the residue taken up in 10% HOAc (100 ml). The product was extracted into EtOAc (4 times 100 ml), washed twice with a small volume of H2O, dried over Na2SO4, evaporated to a small volume, and treated with petroleum ether until cloudiness developed. A crystalline product formed on storage in the refrigerator overnight: Yield, 8.2 g (76.3%); mp 115°-118°.
Reaction SMILES: [C:1]([NH:4][C:5]1[N:6]=[CH:7][S:8][CH:9]=1)(=[O:3])[CH3:2].[C:10]([O-])(=[O:12])[CH3:11].[Na+].C(Cl)(Cl)Cl>C(OC(=O)C)(=O)C.N1C=CC=CC=1>[C:1]([N:4]([C:10](=[O:12])[CH3:11])[C:5]1[N:6]=[CH:7][S:8][CH:9]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1cscn1
Reactant: CC(=O)[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)N(C(C)=O)c1cscn1
Temperature: 100 °C

Procedure:
A solution of 4-acetylaminothiazole (2.85 g, 20 mM) in a mixture of acetic anhydride (30 ml) and pyridine (10 ml) was heated at 100° C. for 16 hours. The reaction mixture was cooled and poured onto an ice cold mixture of 20% aqueous sodium acetate (200 ml) and chloroform (200 ml.). The layers were separated the organic layer was washed with water, dried (MgSO4) and the solvents removed under vacuum to give an oil. Trituration with hexane followed by recrystallisation from di-isopropyl ether gave the title compound (1.8 g, 49%) m.p. 55° C. (Found: C, 45.8; H, 4.4; N, 15.5%. C7H8N2O2S requires: C, 45.6; H, 4.4; N, 15.2%)
Reaction SMILES: [CH:1]1([S:4]([C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[CH:15][CH:14]=2)(=[N:6][C:7](=[O:12])[C:8]([F:11])([F:10])[F:9])=[O:5])[CH2:3][CH2:2]1>C(O)C.C1COCC1.[Pd]>[NH2:19][C:16]1[CH:15]=[CH:14][C:13]([S:4]([CH:1]2[CH2:3][CH2:2]2)(=[N:6][C:7](=[O:12])[C:8]([F:11])([F:9])[F:10])=[O:5])=[CH:18][CH:17]=1
Reactant: O=C(N=S(=O)(c1ccc([N+](=O)[O-])cc1)C1CC1)C(F)(F)F
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: Nc1ccc(S(=O)(=NC(=O)C(F)(F)F)C2CC2)cc1
Reaction time: 4.5 h
Yield: 93 %

Procedure:
A solution of (RS)—S-cyclopropyl-S-(4-nitrophenyl)-N-(trifluoroacetyl)sulphoximide in ethanol and THF was admixed with palladium on carbon and hydrogenated for 1 hour under atmospheric pressure at 25° C. Palladium on carbon was added again and the mixture was hydrogenated for a further 4.5 hours at atmospheric pressure. The mixture was filtered, the filtrate was again admixed with palladium on carbon and finally hydrogenated for 45 minutes. The mixture was filtered and concentrated by evaporation (yield: 93%).