Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:9][CH:8]=2)[O:4][N:3]=1.[H][H]>[Pt](=O)=O.C(O)C>[NH2:3][C:2]([CH3:1])=[CH:6][C:5]([C:7]1[CH:8]=[CH:9][C:10]([C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:11][CH:12]=1)=[O:4]
Reactant: Cc1cc(-c2ccc(C(C)(C)C)cc2)on1
Reactant: [H][H]
Agent: O=[Pt]=O
Solvent: CCO
Product: CC(N)=CC(=O)c1ccc(C(C)(C)C)cc1

Procedure:
3-Methyl-5-[4-(tert-butyl)phenyl]isoxazole (900 mg, 4.18 mmol) is introduced into 20 ml of ethanol, platinum(IV) oxide catalyst (90 mg) is added and the mixture is then hydrogenated under atmospheric pressure hydrogen for 12 h. The catalyst is filtered off and the filtrate is concentrated. 897 mg (99% of theory) of the title compound are obtained as a white solid.
Reaction SMILES: [CH3:1][SiH:2]([Cl:4])[Cl:3].Cl[SiH](Cl)Cl.[CH2:9](Cl)C=C.C[C:14]1([CH:21]=[CH:20][CH:19]=[CH:18][CH2:17]1)[CH:15]=[CH2:16]>>[C:14]1([CH:15]([CH3:16])[CH2:1][Si:2]([CH3:9])([Cl:4])[Cl:3])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: C[SiH](Cl)Cl
Reactant: C=CCCl
Reactant: C=CC1(C)C=CC=CC1
Agent: Cl[SiH](Cl)Cl
Product: CC(C[Si](C)(Cl)Cl)c1ccccc1

Procedure:
The process described in Example 2 is repeated, except that 1.3 liters of methyldichlorosilane, 1.7 liters of 1-methylstyrene and 5 ml of the catalytic solution are substituted for the trichlorosilane, allyl chloride and catalytic solution and the process is carried out at a temperature of 140° C. instead of 120° C. About 97.9 mol percent of the methyldichlorosilane used is converted and 12.8 moles per hour of 2-phenyl-2-methylethyl (methyl) dichlorosilane are obtained having a purity of 97.2 percent by weight as determined by gas chromatography.
Reaction SMILES: [C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[K].[CH2:13]([O:15][C:16](=[O:22])[CH:17](Br)[CH2:18][CH2:19][CH3:20])[CH3:14].C(Cl)(Cl)Cl.O>CN(C)C=O>[C:1]1(=[O:11])[N:5]([CH:17]([CH2:18][CH2:19][CH3:20])[C:16]([O:15][CH2:13][CH3:14])=[O:22])[C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12
Reactant: CCCC(Br)C(=O)OCC
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: ClC(Cl)Cl
Solvent: O
Solvent: CN(C)C=O
Product: CCCC(C(=O)OCC)N1C(=O)c2ccccc2C1=O
Temperature: 60 °C

Procedure:
To a solution of potassium phthalimide (0.1 mole) in about 50 ml of dimethylformamide (DMF) is added 1 equivalent of ethyl-2-bromopentanoate. The temperature is maintained at about 60° C. for 10 minutes. Chloroform is added to the cooled DMF solution and the mixture is poured into water. The phases are separated and the aqueous phase is extracted with chloroform. The chloroform extracts are combined, extracted with 0.1 N sodium hydroxide and with water. After drying over sodium sulfate, the chloroform is removed to give ethyl α-phthalimidopentanoate.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][CH:9]([OH:18])[CH2:10][CH2:11][CH:12]2[NH:16][C:15](=[O:17])[CH2:14][CH2:13]2)[CH:5]=[CH:6][CH:7]=1.[Si:19](Cl)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]>>[C:22]([Si:19]([CH3:21])([CH3:20])[O:18][CH:9]([CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1)[CH2:10][CH2:11][CH:12]1[NH:16][C:15](=[O:17])[CH2:14][CH2:13]1)([CH3:25])([CH3:24])[CH3:23]
Reactant: O=C1CCC(CCC(O)Cc2cccc(Cl)c2)N1
Reactant: CC(C)(C)[Si](C)(C)Cl
Product: CC(C)(C)[Si](C)(C)OC(CCC1CCC(=O)N1)Cc1cccc(Cl)c1
Yield: 81.1 %

Procedure:
Analogous to the procedure described for Example 1A, Step C, 5-[4-(3-chloro-phenyl)-3-hydroxy-butyl]-pyrrolidin-2-one (1.53 g, 5.71 mmol) was reacted with tert-butyldimethylsilyl chloride (0.97 g, 6.4 mmol). Purification by medium pressure chromatography using a solvent gradient (1:1 hexanes:EtOAc to EtOAc to 1% MeOH in CH2Cl2 to 2% MeOH in CH2Cl2 to 4% MeOH in CH2Cl2) provided 5-[3-(tert-butyl-dimethyl-silanyloxy)-4-(3-chloro-phenyl)-butyl]-pyrrolidin-2-one (1.77 g). 1H NMR (CDCl3) δ7.16 (m, 3H), 7.01 (m, 1H), 5.61 (d, 1H), 3.83 (m, 1H), 3.58 (m, 1H), 2.68 (m, 2H), 2.28 (m, 3H), 1.73–1.36 (m, 5H), 0.84 (s, 9H), −0.05 (s, 3H), −0.2 (d, 3H).
Reaction SMILES: [Cl:1]CCCC=O.[Cl:7][CH2:8][CH2:9][CH2:10][C:11](Cl)=O.Cl.[NH2:15][CH2:16][CH2:17][C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[NH:20][CH:19]=1.C(O)(C)C>C1(C)C(C)=CC=CC=1>[ClH:1].[Cl:7][CH2:8][CH2:9][CH2:10][CH:11]1[C:19]2[NH:20][C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:18]=2[CH2:17][CH2:16][NH:15]1
Reactant: NCCc1c[nH]c2ccccc12
Reactant: O=CCCCCl
Reactant: O=C(Cl)CCCCl
Agent: Cl
Solvent: Cc1ccccc1C
Solvent: CC(C)O
Product: ClCCCC1NCCc2c1[nH]c1ccccc21
Temperature: 88 °C
Reaction time: 4 h
Yield: 87 %

Procedure:
1,280 parts of a 20.7% strength by weight solution of γ-chlorobutyraldehyde in xylene (prepared by a method similar to that described in Houben-Weyl, Volume 7/1, pages 285-290, by catalytic hydrogenation of a solution of γ-chlorobutyric acid chloride in xylene), 490 parts of 3-(β-aminoethyl)-indole hydrochloride and 1,000 parts of isopropanol were stirred for 4 hours at 88° C., and the mixture was cooled and then filtered under suction to give 618 parts (87%) of 1-(γ-chloropropyl)-1,2,3,4-tetrahydro-β-carboline hydrochloride. After recrystallization from methanol, the substance had a melting point of 219°-221° C.
Reaction SMILES: Cl.Cl.[NH2:3][C@H:4]([C:6]1[N:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)[C:8]2[C:14]([C:15]#[N:16])=[C:13]([F:17])[CH:12]=[CH:11][C:9]=2[N:10]=1)[CH3:5].Cl[C:25]1[N:33]=[CH:32][N:31]=[C:30]2[C:26]=1[N:27]=[CH:28][N:29]2C1CCCCO1.CCN(C(C)C)C(C)C>CC(O)C>[F:17][C:13]1[CH:12]=[CH:11][C:9]2[N:10]=[C:6]([C@@H:4]([NH:3][C:25]3[N:33]=[CH:32][N:31]=[C:30]4[C:26]=3[N:27]=[CH:28][NH:29]4)[CH3:5])[N:7]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[C:8]=2[C:14]=1[C:15]#[N:16]
Reactant: Clc1ncnc2c1ncn2C1CCCCO1
Reactant: C[C@H](N)c1nc2ccc(F)c(C#N)c2n1-c1ccccn1
Agent: Cl
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: C[C@H](Nc1ncnc2[nH]cnc12)c1nc2ccc(F)c(C#N)c2n1-c1ccccn1
Temperature: 90 °C
Reaction time: 2 h
Yield: 61.4 %

Procedure:
To a solution of 2-((S)-1-aminoethyl)-5-fluoro-3-pyridin-2-yl-3H-benzoimidazole-4-carbonitrile dihydrochloride (250 mg, 0.71 mmol) in IPA (7 mL) was added 6-chloro-9-(tetrahydro-pyran-2-yl)-9H-purine (220 mg, 0.92 mmol) and DIPEA (361 μL, 2.1 mmol) and the reaction mixture heated at 90° C. for 16 h. The reaction mixture was concentrated in vacuo and the resultant residue subjected to flash chromatography (SiO2, eluting with 0-10% methanol in EtOAc). LCMS (Method C): RT=2.86 min, [M+H]+=484. The product was dissolved HCl in methanol (5 mL, 2.5M) and the reaction stirred at RT for 2 h. The reaction mixture was concentrated in vacuo and the resultant residue loaded onto an SCX 2 cartridge, washed with methanol then eluted with ammonia in methanol (2M). The eluent was concentrated in vacuo and the residue triturated with diethyl ether to give 290 as a white solid (174 mg, 51%) 1H NMR 400 MHz (DMSO-d6): δ 12.57 (1H, br s), 8.53-8.50 (1H, m), 8.04 (1H, dd, J=9.0, 4.72 Hz), 8.00 (1H, s), 7.96-7.88 (1H, m), 7.74 (1H, d, J=8.0 Hz), 7.47 (1H, dd, J=7.2, 4.9 Hz), 7.43-7.34 (1H, m), 7.30 (1H, dd, J=10.3, 9.2 Hz), 5.71 (1H, br s), 1.62 (3H, d, J=7.0 Hz). LCMS (Method K): RT=2.88 min, [M+H]+=400
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([C:15]2[C:16]([C:22](=[O:31])[C:23]3[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=3[Cl:30])=[N:17][CH:18]=[C:19]([Cl:21])[CH:20]=2)COC)(=[O:10])=[O:9])=[CH:4][C:3]=1[C:32]([F:35])([F:34])[F:33].O>Cl.O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:15]2[C:16]([C:22](=[O:31])[C:23]3[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=3[Cl:30])=[N:17][CH:18]=[C:19]([Cl:21])[CH:20]=2)(=[O:9])=[O:10])=[CH:4][C:3]=1[C:32]([F:33])([F:34])[F:35]
Reactant: COCN(c1cc(Cl)cnc1C(=O)c1c(F)cccc1Cl)S(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Product: O=C(c1ncc(Cl)cc1NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1)c1c(F)cccc1Cl
Temperature: 25 °C
Yield: 69.1 %

Procedure:
A mixture of 4-chloro-N-[5-chloro-2-(2-chloro-6-fluoro-benzoyl)-pyridin-3-yl]-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (100 mg, 0.17 mmol) in 4 M HCl in dioxane (5 mL) and water (1 mL) was heated at reflux for 3 h. The reaction mixture was cooled to room temperature, evaporated to dryness, and neutralized with saturated aqueous NaHCO3 solution to pH 7-8. The mixture was extracted with EtOAc (2×25 mL), dried (Na2SO4), filtered and concentrated. The residual solid was purified by flash column chromatography (70% EtOAc-hexanes) on silica gel to afford 4-chloro-N-[5-chloro-2-(2-chloro-6-fluoro-benzoyl)-pyridin-3-yl]-3-trifluoromethyl-benzenesulfonamide (62 mg) as an off white solid in 67% yield. MS m/z: 527 (M+H), 549 (M+Na).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][C:10]([CH3:15])([CH3:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[Cl:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[CH:30]=[C:29]([S:34](Cl)(=[O:36])=[O:35])[CH:28]=[CH:27]2.[Cl-].[Na+]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([S:34]([C:29]2[CH:28]=[CH:27][C:26]3[C:31](=[CH:32][CH:33]=[C:24]([Cl:23])[CH:25]=3)[CH:30]=2)(=[O:35])=[O:36])[C:10]([CH3:15])([CH3:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC1(C)CN(C(=O)OC(C)(C)C)CCN1
Reactant: O=S(=O)(Cl)c1ccc2cc(Cl)ccc2c1
Agent: [Cl-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCN(S(=O)(=O)c2ccc3cc(Cl)ccc3c2)C(C)(C)C1
Temperature: 25 °C
Reaction time: 84 h

Procedure:
To a solution of 1-(tert-butoxycarbonyl)-3,3-dimethylpiperazine (125 mg) in methylene chloride (3.0 ml) were added triethylamine (90 ml) and 6-chloronaphthalene-2-sulfonyl chloride (167 mg). The resulting mixture was stirred at room temperature for 84 hours. The reaction mixture was diluted with methylene chloride and added with a saturated aqueous solution of sodium chloride to form two layers. The organic layer obtained by separation was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crudely purified product was purified by chromatography on a silica gel column (hexane:ethyl acetate=8:1), whereby the title compound (155 mg) was obtained as a colorless solid.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([N:28]1[C:33](=[O:34])[CH:32]=[CH:31][NH:30][C:29]1=[O:35])(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[C:36]([O:55][CH2:56][CH:57]=[CH:58][CH2:59]O)([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.CCCCCC.CCOC(C)=O>[C:20]([N:28]1[C:33](=[O:34])[CH:32]=[CH:31][N:30]([CH2:59]/[CH:58]=[CH:57]\[CH2:56][O:55][C:36]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C:29]1=[O:35])(=[O:27])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: O=C(c1ccccc1)n1c(=O)cc[nH]c1=O
Reactant: OCC=CCOC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCCCCC
Product: O=C(c1ccccc1)n1c(=O)ccn(C/C=C\COC(c2ccccc2)(c2ccccc2)c2ccccc2)c1=O
Temperature: 25 °C
Reaction time: 24 h
Yield: 28.6 %

Procedure:
Polymer bound triphenylphosphine (0.75 g; 2.25 mmol) was shaken in THF (5 ml) for 15 minutes, then 3-benzoyluracil (290 mg, 1.35 mmol) and tritylated alcohol (1) (300 mg; 0.90 mmol) were added to the suspension of the resin. A solution of DIAD (0.354 ml, 1.80 mmol) in THF (2 ml) was added to the mixture. The reaction was shaken 24 hours at room temperature and monitored by TLC (Hexane/EtOAc 50:50). The resin was filtered and washed twice with THF (5 ml). The filtrate was concentrated under reduced pressure and taken in EtOAc (5 ml), a white solid precipitated. The precipitate was filtered, the filtrate was concentrated again and purified by flash chromatography using Hexane/EtOAc as eluent which gave the title compound as a colourless oil (136 mg, 29%).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:13]/[OH:14])/[C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1.[CH2:15]([N:17]([CH2:22][CH3:23])[C:18](=[O:21])[CH2:19]Cl)[CH3:16].C(N(C(C)C)C(C)C)C.[I-].[Na+]>C(#N)C.C(OCC)(=O)C>[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:13]/[O:14][CH2:19][C:18](=[O:21])[N:17]([CH2:22][CH3:23])[CH2:15][CH3:16])/[C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1
Reactant: CCOC(=O)/C(=N\O)c1csc(N)n1
Reactant: CCN(CC)C(=O)CCl
Agent: [I-]
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CCOC(=O)/C(=N\OCC(=O)N(CC)CC)c1csc(N)n1
Yield: 77.9 %

Procedure:
57.3 g of ethyl 2-(2-amino-4-thiazolyl)-2-(Z)-hydroxyimino-acetate, 80 g of N,N-diethylchloroacetamide, 138.7 ml of N-ethyldiisopropylamine and 80 g of sodium iodide are stirred at room temperature for 12 hours in 1.1 l of acetonitrile. The mixture is subsequently diluted with 5 l of ethyl acetate, washed with water, dried over magnesium sulphate and concentrated to a small volume. The compound which crystallizes out is filtered off and dried. There are obtained 68.1 g of ethyl 2-(2-amino-4-thiazolyl)-2-[(Z)-[(diethylcarbamoyl)methoxy]imino]-acetate of melting point 161° C.
Reaction SMILES: [C:1]([N:4]([CH:6]1[CH2:10][CH2:9][NH:8][CH2:7]1)[CH3:5])(=[O:3])[CH3:2].[CH3:11][O:12][C:13]1[N:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[CH:18][CH:17]=[C:16]2OS(C(F)(F)F)(=O)=O.C(N(CC)CC)C>O1CCOCC1>[CH3:11][O:12][C:13]1[N:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[CH:18][CH:17]=[C:16]2[N:8]1[CH2:9][CH2:10][CH:6]([N:4]([CH3:5])[C:1](=[O:3])[CH3:2])[CH2:7]1
Reactant: CC(=O)N(C)C1CCNC1
Reactant: COc1ccc2nccc(OS(=O)(=O)C(F)(F)F)c2n1
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: COc1ccc2nccc(N3CCC(N(C)C(C)=O)C3)c2n1
Temperature: 50 °C
Reaction time: 8 h
Yield: 106 %

Procedure:
3-(N-acetyl-N-methylamino)pyrrolidine (1.00 g, 7.0 mmol) was dissolved in dioxane (15 mL) and treated with 1,1,1-Trifluoro-methanesulfonic acid 6-methoxy-[1,5]naphthyridin-4-yl ester (1.67 g, 5.4 mmol) and triethylamine (0.98 mL, 7.0 mmol). After stirring at 50° C. overnight the reaction mixture was cooled, concentrated to dryness and purified via column chromatography (silica, 2% MeOH in chloroform) to afford the title compound as an off-white solid (1.72 g, quantitive): LC-MS m/z 301 (M+H)+
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][O:5][C:6]=1[C:7]1[CH:15]=[CH:14][C:10]([C:11](Cl)=[O:12])=[CH:9][CH:8]=1.[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([NH:29][CH:30]2[CH2:32][CH2:31]2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].C(N(C(C)C)C(C)C)C>ClCCl>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([N:29]([CH:30]2[CH2:31][CH2:32]2)[C:11](=[O:12])[C:10]2[CH:14]=[CH:15][C:7]([C:6]3[O:5][CH:4]=[N:3][C:2]=3[CH3:1])=[CH:8][CH:9]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]
Reactant: Cc1ncoc1-c1ccc(C(=O)Cl)cc1
Reactant: CC(C)(C)OC(=O)N1CCC(NC2CC2)CC1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1ncoc1-c1ccc(C(=O)N(C2CC2)C2CCN(C(=O)OC(C)(C)C)CC2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
4-(4-Methyl-oxazol-5-yl)-benzoyl chloride (340 mg) is added portionwise to a mixture of 4-cyclopropylamino-piperidine-1-carboxylic acid tert-butyl ester (369 mg) and ethyldiisopropylamine (274 μL) in dichloromethane (10 mL). The mixture is stirred for 1 h at room temperature, washed with water, aqueous citric acid solution and 0.5 M NaOH, dried over Na2SO4 and concentrated in vacuo. The residue is chromatographed on silica gel (dichloromethane/methanol 50:1) to afford the title compound. Mass spectrum (ESI+): m/z=426 [M+H]+.
Reaction SMILES: Cl.[NH2:2][CH:3]([CH3:7])[C:4]([NH2:6])=[O:5].[OH2:8]>>[CH3:7][C@H:3]([NH2:2])[C:4]([OH:8])=[O:5].[CH3:7][C@@H:3]([NH2:2])[C:4]([NH2:6])=[O:5]
Reactant: O
Reactant: CC(N)C(N)=O
Agent: Cl
Product: C[C@@H](N)C(N)=O
Product: C[C@H](N)C(=O)O
Yield: 50 %
Yield: 50 %

Procedure:
The treatment of one solution at 6% of hydrochloride of α-aminopropionamide in water (pH included between 6.5 to 8.5) can be effected by a suspension of cells of strain A4 at 20 to 40 g of dry matter per liter. Quantitatively L-α-alanine (50%) and D-α-aminopropionamide (50%) is obtained. This amide D can either be hydrolized in D-α-alanine by action of strain R 312 (CBS 717.73) or racemized and recycled with a view to the preparation of L-α-alanine.
Reaction SMILES: [C:1]([C:5]1[N:10]=[C:9]([CH2:11][CH2:12][O:13][CH3:14])[CH:8]=[C:7]([N:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:21]([O:25][C:26](=[O:37])[NH:27][C@H:28]1[CH2:33][CH2:32][C@H:31]([CH2:34][CH:35]=O)[CH2:30][CH2:29]1)([CH3:24])([CH3:23])[CH3:22].CC(O)=O.[Na]>ClCCCl.O>[C:21]([O:25][C:26](=[O:37])[NH:27][C@H:28]1[CH2:29][CH2:30][C@H:31]([CH2:34][CH2:35][N:18]2[CH2:17][CH2:16][N:15]([C:7]3[CH:8]=[C:9]([CH2:11][CH2:12][O:13][CH3:14])[N:10]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[N:6]=3)[CH2:20][CH2:19]2)[CH2:32][CH2:33]1)([CH3:24])([CH3:23])[CH3:22]
Reactant: COCCc1cc(N2CCNCC2)nc(C(C)(C)C)n1
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@H](CC=O)CC1
Agent: [Na]
Solvent: ClCCCl
Solvent: O
Solvent: CC(=O)O
Product: COCCc1cc(N2CCN(CC[C@H]3CC[C@H](NC(=O)OC(C)(C)C)CC3)CC2)nc(C(C)(C)C)n1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A mixture of 2-tert-butyl-4-(2-methoxy-ethyl)-6-piperazin-1-yl-pyrimidine (500 mg, 1.796 mmol), trans-[4-(2-oxo-ethyl)-cyclohexyl]-carbamic acid tert-butyl ester (433 mg, 1.796 mmol) and AcOH (108 mg, 1.796 mmol) in DCE (30 ml) was stirred at room temperature for 10 min. Sodium triacetoxyhydroborate (571 mg, 2.69 mmol) was added. After 4 h, water was added. The aqueous layer was extracted with ethyl acetate (3×5 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the yellow title compound (900 mg, 1.680 mmol, 94% yield) which was used next step without purification.
Reaction SMILES: [BH4-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=O.[NH:12]1[CH2:16][CH2:15][CH2:14][CH2:13]1>C(O)C>[N:12]1([CH2:7][C:6]2[CH:5]=[C:4]([OH:3])[CH:11]=[CH:10][CH:9]=2)[CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: C1CCNC1
Reactant: O=Cc1cccc(O)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: Oc1cccc(CN2CCCC2)c1

Procedure:
Sodium borohydride (15.2 g) was added to a solution of 3-hydroxybenzaldehyde (48.8 g) and pyrrolidine (66.4 ml) in ethanol. After 18 hours the ethanol was removed and the residual oil was acidified with hydrochloric acid and washed with ethyl acetate. The aqueous solution was then basified with ammonia and extracted with ethyl acetate. Evaporation of the organic extracts yielded the title compound as an off-white solid (21.4 g), m.p. 100°-102°. TLC Silica; methanol; 0.88 ammonia (80:1)Rf 0.48.
Reaction SMILES: N1C=CC=CC=1C.Cl[S:9]([OH:12])(=O)=[O:10].[CH2:13]([O:20][C:21]([NH:23][C@H:24]([C:28]([NH2:30])=[O:29])[C@@H:25]([CH3:27])[OH:26])=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.P([O-])([O-])([O-])=O>C(Cl)Cl>[S:9](=[N:30][C:28](=[O:29])[C@H:24]([C@@H:25]([CH3:27])[OH:26])[NH:23][C:21]([O:20][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:22])(=[O:12])=[O:10]
Reactant: C[C@@H](O)[C@H](NC(=O)OCc1ccccc1)C(N)=O
Reactant: O=S(=O)(O)Cl
Agent: O=P([O-])([O-])[O-]
Solvent: ClCCl
Solvent: Cc1ccccn1
Product: C[C@@H](O)[C@H](NC(=O)OCc1ccccc1)C(=O)N=S(=O)=O

Procedure:
A solution of 2-picoline (17.8 ml) in 90 ml of methylene chloride was cooled to -5° C. (ice-brine) and chlorosulfonic acid (5.97 ml) was added at such a rate as to maintain the internal reaction temperature below 5° C. The resulting solution was added via canula, to a suspension of 7.56 g of benzyloxycarbonylthreonine amide, O-mesylate in 120 ml of methylene chloride. The resulting heterogeneous mixture was refluxed for about 16 hours yielding a clear solution. The solution was poured into 500 ml of pH 4.5 phosphate buffer (0.5M) and further diluted with 120 ml of methylene chloride. The separated organic layer was washed once with 100 ml of buffer solution and the combined aqueous phases were treated with 10.2 g of tetra-n-butyl-ammonium hydrogensulfate and extracted with methylene chloride (one 300 ml portion and two 150 ml portions). After drying the combined organic extracts over sodium sulfate, the solution was concentrated to yield 12.7 g of N-sulfonyl benzyloxycarbonylthreonine amide, O-mesylate, tetrabutylammonium salt.
Reaction SMILES: [CH3:1][C@H:2]([CH2:6][CH2:7][CH2:8][C@H:9]([CH3:16])[CH2:10][CH2:11][CH2:12][CH:13]([CH3:15])[CH3:14])[CH2:3][CH2:4]Br.[Mg].CO[C:20]1[C:25](C)=C(C)C(OC)=[C:22](C)[C:21]=1[CH2:31]C[C@]1(C)OC1.[NH4+].C(OCC)(=[O:40])C>C(OCC)C>[CH3:1][C:2]([OH:40])([CH2:6][CH2:7][CH2:8][CH:9]([CH3:16])[CH2:10][CH2:11][CH2:12][CH:13]([CH3:15])[CH2:14][CH2:25][CH2:20][CH:21]([CH3:31])[CH3:22])[CH2:3][CH3:4]
Reactant: COc1c(C)c(C)c(OC)c(CC[C@@]2(C)CO2)c1C
Reactant: CCOC(C)=O
Reactant: CC(C)CCC[C@@H](C)CCC[C@@H](C)CCBr
Agent: [Mg]
Agent: [NH4+]
Solvent: CCOCC
Product: CCC(C)(O)CCCC(C)CCCC(C)CCCC(C)C
Reaction time: 8 h

Procedure:
5.8 mmol of (3R,7R)-3,7,11-trimethyldodecyl bromide are heated at reflux for 1/4 hour in 20 ml of ethyl acetate with activated magnesium. Then, there are added at 0° C. 1 g of (S)-4-(2',5'-dimethoxy-3',4',6'-trimethylphenyl)-2-methyl-1,2-epoxybutane and 0.9 g of copper(I)-2-propylacetylide (or 1.2 g of copper(I) bromide/dimethyl sulphide complex). The temperature of the reaction mixture is subsequently left to rise to room temperature and the mixture is stirred overnight. 10 ml of ammonium with ethyl ether. The extract is dried and concentrated, and the residue is distilled in a bulb-tube (b.p.0.01 =140° C.). There are obtained 1.28 g (72%) (or 1.41 g (79%) of (3R,7R,11R)-1-)2',5'-dimethoxy-3',4',6'-trimethylphenyl)-3,7,11,15-tetramethylhexadecan-3-ol as a colourless oil.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([N:8]2[CH:13]=[C:12]([OH:14])[C:11](=[O:15])[CH:10]=[C:9]2[CH2:16][OH:17])[CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32]Cl)=[CH:28][CH:27]=1.O>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([N:8]2[CH:13]=[C:12]([O:14][CH2:32][C:29]3[CH:30]=[CH:31][C:26]([O:25][CH3:24])=[CH:27][CH:28]=3)[C:11](=[O:15])[CH:10]=[C:9]2[CH2:16][OH:17])[CH:5]=[CH:6][CH:7]=1
Reactant: O=c1cc(CO)n(-c2cccc(Br)c2)cc1O
Reactant: COc1ccc(CCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc(COc2cn(-c3cccc(Br)c3)c(CO)cc2=O)cc1
Temperature: 80 °C
Reaction time: 3 h

Procedure:
To a mixture of 1-(3-bromo-phenyl)-5-hydroxy-2-hydroxymethyl-1H-pyridin-4-one and K2CO3 (5.17 g, 37.5 mmol) in 50 mL of DMF was added 2.35 g of PMBCl (15 mmol) dropwise, and the reaction mixture was stirred at 80° C. for 3 h. After cooling to room temperature, the mixture was poured into 200 mL of water and extracted with EtOAc (50 mL) three times. The combined organic layers were washed with water, brine, and dried over anhydrous MgSO4. Most of the volatiies were removed in vacuo and the resulting solid was collected and washed with EtOAc to obtain 1-(3-bromophenyl)-2-hydroxymethyl-5-(4-methoxy-benzyloxy)-1H-pyridin-4-one.