Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:8][C:9]([CH:11]1[CH2:16][CH2:15][CH:14]([N:17]([C:28](=[O:56])[CH2:29][CH2:30][C@H:31]([N:38]2[CH2:43][C:42]3[CH:44]=[C:45]([O:48][C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=4)[N:46]=[CH:47][C:41]=3[N:40]=[C:39]2[NH2:55])[CH:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[CH2:18][CH2:19][O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:13][CH2:12]1)=[O:10])C1C=CC=CC=1>CCO.[Pd]>[NH2:55][C:39]1[N:38]([C@H:31]([CH:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[CH2:30][CH2:29][C:28]([N:17]([CH2:18][CH2:19][O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C@@H:14]2[CH2:13][CH2:12][C@H:11]([C:9]([OH:10])=[O:8])[CH2:16][CH2:15]2)=[O:56])[CH2:43][C:42]2[CH:44]=[C:45]([O:48][C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=3)[N:46]=[CH:47][C:41]=2[N:40]=1
Reactant: NC1=Nc2cnc(Oc3ccccc3)cc2CN1[C@@H](CCC(=O)N(CCOCc1ccccc1)C1CCC(C(=O)OCc2ccccc2)CC1)C1CCOCC1
Agent: [Pd]
Solvent: CCO
Product: NC1=Nc2cnc(Oc3ccccc3)cc2CN1[C@@H](CCC(=O)N(CCOCc1ccccc1)[C@H]1CC[C@@H](C(=O)O)CC1)C1CCOCC1

Procedure:
A solution of 4-[[4-(2-Amino-6-phenoxy-4H-pyrido[3,4-d]pyrimidin-3-yl)-4-(S)-(tetrahydro-pyran-4-yl)-butyryl]-(2-benzyloxy-ethyl)-amino]-cyclohexanecarboxylic acid benzyl ester (0.4 g, 0.42 mmol) and Pd (10% on carbon, 0.2 g) in EtOH (50 mL) was subjected to hydrogenation under 10 psi for 48 h. HPLC purification yielded 4-[[4-(2-Amino-6-phenoxy-4H-pyrido[3,4-d]pyrimidin-3-yl)-4-(S-(tetrahydro-pyran-4-yl)-butyryl]-(2-hydroxy-ethyl)-amino]-cyclohexanecarboxylic acid as a white solid and 4-[[4-(2-Amino-6-phenoxy-4H-pyrido[3,4-d]pyrimidin-3-yl)-4-(S)-(tetrahydro-pyran-4-yl)-butyryl]-(2-benzyloxy-ethyl)-amino]-cis-cyclohexanecarboxylic acid as a white solid.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([C:23]([OH:25])=[O:24])[CH:10]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)C.[Rh]>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:23]([OH:25])=[O:24])[CH:10]([CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[CH:11]1[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@@H](C(=O)O)C(c1ccccc1)c1ccccc1
Agent: [Rh]
Solvent: CCO
Product: CC(C)(C)OC(=O)N[C@@H](C(=O)O)C(C1CCCCC1)C1CCCCC1

Procedure:
A solution of N-tert-butoxycarbonyl-(2R)-3,3-diphenylalanine (10 mmol) in ethanol is placed under hydrogen for one night in the presence of Rh/C (0.5 g). After removal of the catalyst by filtration, the solvent is evaporated off to yield the expected product.
Reaction SMILES: C([O:3][C:4]([C:6]1[NH:7][N:8]=[C:9]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)[C:10]=1[C:11]#[N:12])=[O:5])C.[H-].[Na+].Br[CH2:21][C:22]1[CH:26]=[C:25]([C:27]2[S:28][C:29]([Cl:32])=[CH:30][CH:31]=2)[O:24][N:23]=1.[OH-].[Na+]>CN(C=O)C>[Cl:32][C:29]1[S:28][C:27]([C:25]2[O:24][N:23]=[C:22]([CH2:21][N:7]3[C:6]([C:4]([OH:3])=[O:5])=[C:10]([C:11]#[N:12])[C:9]([C:13]4[S:14][CH:15]=[CH:16][CH:17]=4)=[N:8]3)[CH:26]=2)=[CH:31][CH:30]=1
Reactant: Clc1ccc(-c2cc(CBr)no2)s1
Reactant: CCOC(=O)c1[nH]nc(-c2cccs2)c1C#N
Agent: [H-]
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: N#Cc1c(-c2cccs2)nn(Cc2cc(-c3ccc(Cl)s3)on2)c1C(=O)O
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
287 mg (1.2 mmol) of 4-Cyano-5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid ethyl ester was dissolved in 2 ml of DMF and 51.1 mg (1.3 mmol) of sodium hydride (60% in mineral oil) were added at RT. After stirring for 20 min at room temperature the solution was cooled to −70° C. and 355 mg (1.3 mmol) of 3-bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole were added. The reaction was stirred at room temperature for 3 h. The reaction solution was treated with 1 ml of 2N aqueous NaOH for 16h at room temperature. The product was purified by preparative RP-HPLC eluting with a gradient of 0-100% acetonitrile in water (+0.01% trifluoroacetic acid). After lyophilization the product was obtained asia white solid.
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9]C)=[CH:5][C:4]=1[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([NH2:18])[CH:13]=1.Br>>[NH2:18][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=1)[CH2:11][C:4]1[CH:5]=[C:6]([OH:9])[CH:7]=[CH:8][C:3]=1[OH:2]
Reactant: COc1ccc(OC)c(Cc2cccc(N)c2)c1
Agent: Br
Product: Nc1cccc(Cc2cc(O)ccc2O)c1
Yield: 67 %

Procedure:
27 g of 1,4-dimethoxy-2-(3'-aminobenzyl)benzene prepared in (c) was mixed with a 46% hydrobromic acid aqueous solution. The mixture was refluxed on an oil bath for 1 to 2 hours. Since crystals deposited when cooled with ice, the filtration was carried out under cooling. The crystals were dissolved in 200 ml of water, and the resulting solution was neutralized by adding 25 g of sodium acetate. The free amine separated was recrystallized from an ethanol-benzene mixture to obtain 16 g of the subject compound. The melting point was 151° to 152° C.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([N:8]=[C:9]([CH3:11])[N:10]=2)[N:7]=1.[C:12]1([CH:18]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][CH2:28][NH2:29])[CH2:22][CH2:21]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(C(C)C)C(C)C)C.C(=O)([O-])O.[Na+]>C(O)CCC.C(OCC)(=O)C>[C:30]1([CH:18]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][CH2:28][NH:29][C:2]3[CH:3]=[CH:4][C:5]4[N:6]([N:8]=[C:9]([CH3:11])[N:10]=4)[N:7]=3)[CH2:22][CH2:21]2)[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1
Reactant: Cc1nc2ccc(Cl)nn2n1
Reactant: NCCCN1CCC(OC(c2ccccc2)c2ccccc2)CC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCCCO
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nc2ccc(NCCCN3CCC(OC(c4ccccc4)c4ccccc4)CC3)nn2n1
Temperature: 0 °C
Yield: 30.9 %

Procedure:
6-Chloro-2-methyl[1,2,4]triazolo[1,5-b]pyridazine (655 mg) and 4-(diphenylmethoxy)-1-piperidinepropanamine (1.26 g) was suspended in 1-butanol (20 ml), followed by addition of N-ethyldiisopropylamine (1.94 ml). The mixture was refluxed under heating for 22 hours, followed by addition of ice-water and sodium hydrogen carbonate and extraction with ethyl acetate. The extract was washed with an aqueous sodium chloride saturated solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted with a mixture of ethyl acetate, methanol and triethylamine (50:5:1). Fractions containing the objective compound were collected and concentrated. The resulting crystals were washed with hexane and dried to yield the title compound (547 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9][C:10]2[N:14]([CH2:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[C:13]([CH2:23][OH:24])=[N:12][C:11]=2[CH:25]([CH3:27])[CH3:26])[CH:5]=[C:6]([Cl:8])[CH:7]=1.ClC(Cl)(Cl)[C:30]([N:32]=C=O)=[O:31].C(N(CC)CC)C.O>O1CCCC1.CO>[C:30]([O:24][CH2:23][C:13]1[N:14]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[C:10]([S:9][C:4]2[CH:3]=[C:2]([Cl:1])[CH:7]=[C:6]([Cl:8])[CH:5]=2)=[C:11]([CH:25]([CH3:27])[CH3:26])[N:12]=1)(=[O:31])[NH2:32]
Reactant: O=C=NC(=O)C(Cl)(Cl)Cl
Reactant: CC(C)c1nc(CO)n(CCc2ccccn2)c1Sc1cc(Cl)cc(Cl)c1
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: CC(C)c1nc(COC(N)=O)n(CCc2ccccn2)c1Sc1cc(Cl)cc(Cl)c1
Temperature: -40 °C
Yield: 91 %

Procedure:
In 20 ml of tetrahydrofuran was dissolved 521 mg of 5-(3,5-dichlorophenylthio)-4-isopropyl-2-hydroxymethyl-1-(2-(2-pyridyl)ethyl)-1H-imidazole (112a), and the mixture was cooled to -40° C. Under stirring, 221 μl of trichloroacetylisocyanate was added, the mixture was allowed to stand to reach room temperature, and stirred for 30 minutes. Added was 500 μl of triethylamine, 5 ml of water and 5 ml of methanol, and the mixture was stirred at 70° C. for 1 hour. After completion of the reaction, the soluvent was distilled off under reduced pressure, an aqueous sodium hydrogen carbonate solution was added, and extracted with ethyl acetate. The extract was dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1) to give 520 mg of Compound I-129 (yield 91%).
Reaction SMILES: CO[C:3]([C@@H:5]1[C@@H:12]2[C@@H:8]([O:9][C:10]([CH3:14])([CH3:13])[O:11]2)[C@H:7]([N:15]2[CH:23]=[N:22][C:21]3[C:16]2=[N:17][CH:18]=[N:19][C:20]=3[NH:24][CH:25]([CH3:27])[CH3:26])[O:6]1)=[O:4].O.[NH2:29][NH2:30]>CO>[CH:25]([NH:24][C:20]1[N:19]=[CH:18][N:17]=[C:16]2[C:21]=1[N:22]=[CH:23][N:15]2[C@H:7]1[C@@H:8]2[O:9][C:10]([CH3:14])([CH3:13])[O:11][C@@H:12]2[C@@H:5]([C:3]([NH:29][NH2:30])=[O:4])[O:6]1)([CH3:26])[CH3:27]
Reactant: NN
Reactant: COC(=O)[C@H]1O[C@@H](n2cnc3c(NC(C)C)ncnc32)[C@@H]2OC(C)(C)O[C@@H]21
Solvent: O
Solvent: CO
Product: CC(C)Nc1ncnc2c1ncn2[C@@H]1O[C@H](C(=O)NN)[C@H]2OC(C)(C)O[C@H]21
Temperature: 25 °C

Procedure:
A mixture of (3aS,4S,6R,6aR)-6-(6-isopropylamino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid methyl ester (3.76 g) and hydrazine hydrate (1.26 ml) in methanol (140 ml) was heated under reflux for 48 h. After cooling to room temperature, the mixture was concentrated in vacuo and the residue triturated with ethyl acetate to afford the title compound as a white solid (3.3 g).
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([C:10]#[N:11])=[C:6]([O:12][CH2:13][CH2:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:5]=1.[Li+].[BH4-]>C1COCC1>[C:19]([O:18][C:16](=[O:17])[NH:15][CH2:14][CH2:13][O:12][C:6]1[CH:5]=[C:4]([CH2:3][OH:2])[CH:9]=[CH:8][C:7]=1[C:10]#[N:11])([CH3:22])([CH3:20])[CH3:21]
Reactant: COC(=O)c1ccc(C#N)c(OCCNC(=O)OC(C)(C)C)c1
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCCOc1cc(CO)ccc1C#N
Temperature: 70 °C

Procedure:
3-(2-tert-Butoxycarbonylamino-ethoxy)-4-cyano-benzoic acid methyl ester from Step 2 (346 mg, 1.08 mmol) was dissolved in THF (5.5 ml). LiBH4 in THF (2 M, 1.1 ml, 2.16 mmol) was added. The reaction mixture was heated to 70° C. for 3 hours. The reaction was quenched carefully with 3N HCl and then extracted with EtOAc (3×10 mL). The organic layers were combined, washed with brine, dried (MgSO4), filtered and concentrated to yield the desired compound. 1H NMR (400 MHz, CDCl3) δ 7.48 (d, 1H, d, J=4.54 Hz), 7.10 (s, 1H), 6.98 (d, 1H, J=4.30 Hz), 5.10 (bs, 1H, NH), 4.76 (s, 2H), 4.12 (m, 2H), 3.55 (m, 2H), 1.40 (s, 9H).
Reaction SMILES: Cl[Si]1(Cl)CCC1.Cl[Si:8]1([CH3:12])[CH2:11][CH2:10][CH2:9]1.[C:13]([O:16]C(=O)C)(=[O:15])[CH3:14]>CO>[C:13]([O:16][Si:8]1([CH3:12])[CH2:11][CH2:10][CH2:9]1)(=[O:15])[CH3:14]
Reactant: CC(=O)OC(C)=O
Reactant: C[Si]1(Cl)CCC1
Agent: Cl[Si]1(Cl)CCC1
Solvent: CO
Product: CC(=O)O[Si]1(C)CCC1

Procedure:
Several silacyclobutane monomers are known. For example, see U.S. Pat. No. 3,046,291 to Leo H. Sommer, and U.S. Pat. No. 3,687,995 to David Jonas et al. Sommer prepared his silacyclobutanes by reacting ClCH2CHRCH2SiR'Cl2 with magnesium. Jonas et al. teach organosilicon compounds having the general formula ##STR4## where R represents an atom or radical selected from the group consisting of hydrogen atom and alkyl radicals having less than 7 carbon atoms and R' represents alkoxy radicals having less than 5 carbon atoms or a radical of the formula -NR"2, in which each R" is a hydrogen atom .COPYRGT.r an alkyl radical. In U.S. Pat. No. 3,694,427, issued Sept. 26, 1972, Jonas et al. teach that R' can also be acyloxy radical. As an example, the reaction of 1,1-dichlorosilacyclobutane with methylorthoformate gave 1,1-dimethoxysilacyclobutane ##STR5## in 78% yield Further, the same compound was prepared in only 59% yield by reaction of 1,1-dichlorosilacyclobutane and methanol (Bush, R. Ph.D. Thesis, Univ. of California at Davis, 1975; Diss. Abstr. Int. B 1976, 36, 5034). Similarly, the reaction of 1-chloro-1-methyl-silacyclobutane and acetic anhydride gave 1-acetoxy-1-methyl-silacyclobutane ##STR6## in 48% yield (Nametkin, N. S.; Vdovin, V. M.; Grinberg, P. L. Dokl. Akad. Nauk SSSR. 1964, 155, 849 [320]) Silacyclobutane silazanes have been prepared by metathesis reaction with formation of alkali metal salt or condensation reaction with formation of HCl (Nametkin, N. S.; Vdovin, V. M.; Babich, E. D.; Oppengeim, V. D. Khim. Geterotsikl. Soedin., 1965 455) and British Patent No. 1,328,514 to Bush et al. These reactions generally give less than quantitative yields and require additional processing steps in comparison to the invention process. The invention process also provides novel compounds. See also Nametkin, N.S.; Vdovin, J. M.; Babich, E. D. Khim. Geterotsikl. Soedin., 1967, 148. Transsilylation of silazanes is taught and transsilylation of 1-chloro-1-methylsilacyclobutane with disilazanes is shown.
Reaction SMILES: [OH:1][C@@H:2]([C:4]1[N:15]([CH:16]2[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]2)[C:7]2=[C:8]3[S:14][CH:13]=[CH:12][C:9]3=[N:10][CH:11]=[C:6]2[N:5]=1)[CH3:3].[ClH:29].O1CCOCC1>C(Cl)Cl>[ClH:29].[NH:19]1[CH2:20][CH2:21][CH:16]([N:15]2[C:7]3=[C:8]4[S:14][CH:13]=[CH:12][C:9]4=[N:10][CH:11]=[C:6]3[N:5]=[C:4]2[C@H:2]([OH:1])[CH3:3])[CH2:17][CH2:18]1
Reactant: C[C@@H](O)c1nc2cnc3ccsc3c2n1C1CCN(C(=O)OC(C)(C)C)CC1
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: C[C@@H](O)c1nc2cnc3ccsc3c2n1C1CCNCC1
Temperature: 25 °C
Reaction time: 6 h
Yield: 100 %

Procedure:
To a solution of tert-butyl 4-{2-[(1R)-1-hydroxyethyl]-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-1-yl}piperidine-1-carboxylate (71 mg, 0.18 mmol) in methylene chloride (1.2 mL) was added 4.0 M hydrogen chloride in dioxane (0.35 mL, 1.4 mmol). The reaction solution was stirred at room temperature for 6 h. The solvent was removed to give the desired product as white solid (60 mg, 100%). LCMS calculated for C15H19N4OS (M+H)+: m/z=303.1. Found: 303.1.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N+:26]([O-])=O)[CH:5]=[C:6]([Cl:25])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH:10]=1>[Pt].C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:6]([Cl:25])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH:10]=1)[NH2:26]
Reactant: COc1ccc(Oc2c(Cl)cc([N+](=O)[O-])cc2Cl)cc1Cc1ccc(F)cc1
Agent: [Pt]
Solvent: CCO
Product: COc1ccc(Oc2c(Cl)cc(N)cc2Cl)cc1Cc1ccc(F)cc1

Procedure:
3,5-Dichloro-4-[3'-(4-fluorobenzyl)-4'-methoxyphenoxy]nitrobenzene (3.64 g)and 360 mg of 10% platinum on carbon in 200 ml ethanol is hydrogenated on a Parr shaker. Catalyst is removed by fitration through Celite and the fitrate stripped to afford 3,5-dichloro-4-[3'-(4-fluorobenzyl)-4'-methoxyphenoxy]-aniline. This is redissolved with 1.10 ml ethyl bromoacetate and 1.28 g of diisopropylethylamine in 30 ml dimethylformamide and heated at 140° for 18 hours. Solvent is removed with high vacuum and the residue dissolved in ethyl acetate and extracted twice with water. The ethyl acetate is dried, filtered and stripped to give crude product Chromatography on silica gel with 80:20 to 70:30 hexane:ethyl acetate affords pure ethyl N-[3,5-dichloro-4-[3'-(4-fluorobenzyl)-4'-methoxyphenoxy]-phenyl]aminoacetate; NMR (CDCl3): δ 1.3 (3H,t), 3.7 (3H,s), 3.9 (2H,s), 3.9 (2H,s), 4.3 (2H,q), 6.6 (1H,d of d), 6.7 (1H, d), 6.8 (1H, d), 6.9 (2H,m), 7.1 (2H,m), 7.3 (2H,s).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[O:10]1[CH2:14][CH2:13][CH:12]([OH:15])[CH2:11]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[N:7]=[C:6]([O:15][CH:12]2[CH2:13][CH2:14][O:10][CH2:11]2)[C:5]([F:9])=[CH:4][N:3]=1
Reactant: Fc1cnc(Cl)nc1Cl
Reactant: OC1CCOC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Fc1cnc(Cl)nc1OC1CCOC1
Temperature: 80 °C
Yield: 28.4 %

Procedure:
A flask was charged with a solution of 2,4-dichloro-5-fluoropyrimidine (1.0 g, 5.99 mmol) in N,N′-dimethylformamide (20 ml). Tetrahydrofuran-3-ol (0.63 m, 7.19 mmol) and cesium carbonate (3.32 g, 10.18 mmol) were added and the resulting mixture was heated to 80° C. overnight. Upon completion, the mixture was diluted with ethyl acetate (20 mL) and washed with 1:1 water:brine (3×40 mL). The organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by CombiFlash (ethyl acetate/hexanes) provided 374 mg (1.7 mmol, 29%) of 2-chloro-5-fluoro-4-(tetrahydrofuran-3-yloxy)pyrimidine. MS APCI: [M+H]+ m/z 219.0.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[C@@H:11]1[O:28][C@H:27]([CH2:29][O:30]C(=O)C)[C@@H:22]([O:23]C(=O)C)[C@H:17]([O:18]C(=O)C)[C@H:12]1[O:13]C(=O)C.[O:34]1[CH:38]=[CH:37][C:36]2[CH:39]=[C:40]([C:43](Cl)=O)[CH:41]=[CH:42][C:35]1=2>>[O:34]1[CH:38]=[CH:37][C:36]2[CH:39]=[C:40]([CH2:43][C:4]3[C:3]4[C:7](=[CH:8][CH:9]=[CH:10][C:2]=4[CH3:1])[N:6]([C@@H:11]4[O:28][C@H:27]([CH2:29][OH:30])[C@@H:22]([OH:23])[C@H:17]([OH:18])[C@H:12]4[OH:13])[CH:5]=3)[CH:41]=[CH:42][C:35]1=2
Reactant: O=C(Cl)c1ccc2occc2c1
Reactant: CC(=O)OC[C@H]1O[C@@H](n2ccc3c(C)cccc32)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Product: Cc1cccc2c1c(Cc1ccc3occc3c1)cn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O

Procedure:
The titled compound was prepared from 4-methyl-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole obtained in Example 23-(1) and benzo[b]furan-5-carbonyl chloride in a manner similar to Example 3 as a colorless powder. APCI-Mass m/Z 424 (M−H). 1H-NMR (DMSO-d6) δ 2.40 (s, 3H), 3.23 (td, J=8.9, 5.5 Hz, 1H), 3.39 (td, J=8.8, 5.1 Hz, 1H), 3.42-3.47 (m, 2H), 3.65-3.70 (m, 2H), 4.30 (s, 2H), 4.52 (t, J=5.5 Hz, 1H), 5.07 (d, J=5.3 Hz, 1H), 5.13 (d, J=5.0 Hz, 1H), 5.17 (d, J=5.8 Hz, 1H), 5.35 (d, J=9.0 Hz, 1H), 6.70 (d, J=7.1 Hz, 1H), 6.87 (d, J=1.4 Hz, 1H), 6.98 (m, 1H), 7.14 (s, 1H), 7.17 (dd, J=8.6, 1.4 Hz, 1H), 7.35 (d, J=8.3 Hz, 1H), 7.38 (s, 1H), 7.50 (d, J=8.3 Hz, 1H), 7.93 (d, J=2.1 Hz, 1H).
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([NH:15][C:16]1[CH:28]=[C:27]([CH2:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:26]=[CH:25][C:17]=1[C:18]([O:20]C(C)(C)C)=[O:19])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>>[CH2:8]([NH:15][C:16]1[CH:28]=[C:27]([CH2:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:26]=[CH:25][C:17]=1[C:18]([OH:20])=[O:19])[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: CC(C)(C)OC(=O)c1ccc(CCc2ccccc2)cc1NCc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: O=C(O)c1ccc(CCc2ccccc2)cc1NCc1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 80.4 %

Procedure:
Trifluoroacetic acid 2.0 mL was added to tert-butyl 2-(benzylamino)-4-phenethylbenzoate 0.16 g, it was stirred at room temperature 4 hours, and the solvent was removed under reduced pressure. Toluene was added to it, and the solvent was removed under reduced pressure. Diisopropyl ether and hexane were added to the obtained residue, solid matter was filtrated to give 2-(benzylamino)-4-phenethylbenzoic acid 0.11 g of white solid.
Reaction SMILES: CC([O:4][CH2:5][C@H:6]1[O:11][C@@H:10]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C@H:9]([O:19]C(C)=O)[C@@H:8]([O:23]C(C)=O)[C@H:7]1[O:27]C(C)=O)=O.CO.C[O-].[Na+]>C(O)(=O)C>[CH:16]1[CH:15]=[CH:14][C:13]([O:12][C@@H:10]2[O:11][C@H:6]([CH2:5][OH:4])[C@H:7]([OH:27])[C@H:8]([OH:23])[C@H:9]2[OH:19])=[CH:18][CH:17]=1
Reactant: CC(=O)OC[C@H]1O[C@@H](Oc2ccccc2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@H]1OC(C)=O
Agent: C[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: OC[C@H]1O[C@@H](Oc2ccccc2)[C@H](O)[C@@H](O)[C@H]1O
Reaction time: 5 h
Yield: 76.6 %

Procedure:
To phenyl-2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside (21.2 g) were added methanol (120 ml) and 28% sodium methylate (0.28 ml) and the mixture was refluxed with stirring for 5 hours. After the reaction solution was cooled, acetic acid (0.1 ml) was added and the mixture was stirred for 30 minutes. Concentration of the reaction solution and crystallization with ethanol (180 ml) gave 9.8 g (yield 77%) of phenyl-β-D-galactopyranoside. Melting point: 154.5° C.
Reaction SMILES: C([NH:4][CH2:5][C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[C:9]=1[Cl:15])=[O:7])(=O)C>Cl>[ClH:14].[Cl:15][C:9]1[C:10]([Cl:14])=[CH:11][CH:12]=[CH:13][C:8]=1[C:6](=[O:7])[CH2:5][NH2:4]
Reactant: CC(=O)NCC(=O)c1cccc(Cl)c1Cl
Agent: Cl
Product: NCC(=O)c1cccc(Cl)c1Cl

Procedure:
50.0 g of the N-acetyl-2,3-dichlorophenacylamine obtained in (a) are heated for 2 hours under reflux in 500 ml of hydrochloric acid. The slightly turbid reaction solution is concentrated by evaporation and the residue is digested with ethyl acetate. The crystalline 2,3-dichlorophenacylamine hydrochloride is isolated by filtration and dried. Melting point: 217°-218° C. IR (solid/KBr) in cm-1 : 1695 (CO). (Another crystal modification shows two carbonyl resonance bands at 1690 and 1705 cm-1). 1H-NMR (DMSO, d6) in ppm: 4.54 (s, 2H); 7.6 (t, 1H); 7.9 (m, 2H); 8.6 (s, 3H, replaceable with D2O).
Reaction SMILES: COC1C=CC=CC=1C1NC(=O)C2C(=CC=CC=2)N=1.[NH2:20][C:21]1[CH:29]=[CH:28][C:27]([N:30]2[CH2:35][CH2:34][CH:33]([CH3:36])[CH2:32][CH2:31]2)=[CH:26][C:22]=1[C:23]([NH2:25])=[O:24].[CH3:37][O:38][C:39]1[CH:40]=[C:41]([CH:44]=[CH:45][CH:46]=1)[CH:42]=O>>[CH3:37][O:38][C:39]1[CH:40]=[C:41]([C:42]2[NH:25][C:23](=[O:24])[C:22]3[C:21](=[CH:29][CH:28]=[C:27]([N:30]4[CH2:35][CH2:34][CH:33]([CH3:36])[CH2:32][CH2:31]4)[CH:26]=3)[N:20]=2)[CH:44]=[CH:45][CH:46]=1
Reactant: CC1CCN(c2ccc(N)c(C(N)=O)c2)CC1
Reactant: COc1cccc(C=O)c1
Agent: COc1ccccc1-c1nc2ccccc2c(=O)[nH]1
Product: COc1cccc(-c2nc3ccc(N4CCC(C)CC4)cc3c(=O)[nH]2)c1
Yield: 59.9 %

Procedure:
According to the preparation of 42, 28 (1.0 g, 4.3 mmol) and 3-methoxybenzaldehyde (34) (0.6 g, 4.3 mmol) were used to afford 58 (0.9 g, 57.6%) as pale yellow prism crystals.
Reaction SMILES: CN1CCCCC1.ClC(OCC(C)C)=O.[CH:16]([O:19][C:20]([NH:22][C:23](=[CH:27][CH3:28])[C:24]([OH:26])=O)=[O:21])([CH3:18])[CH3:17].[CH3:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([CH:37]([NH2:39])[CH3:38])=[CH:33][CH:32]=1>ClCCl>[CH3:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([CH:37]([NH:39][C:24](=[O:26])[C:23]([NH:22][C:20]([O:19][CH:16]([CH3:17])[CH3:18])=[O:21])=[CH:27][CH3:28])[CH3:38])=[CH:33][CH:32]=1
Reactant: CC=C(NC(=O)OC(C)C)C(=O)O
Reactant: COc1ccc(C(C)N)cc1
Agent: CC(C)COC(=O)Cl
Solvent: ClCCl
Solvent: CN1CCCCC1
Product: CC=C(NC(=O)OC(C)C)C(=O)NC(C)c1ccc(OC)cc1
Reaction time: 0.17 h
Yield: 49.9 %

Procedure:
At -20° C., 0.5 g (0.005 mol) of N-methylpiperidine and then, dropwise with stirring at -20° C., 0.7 g (0.005 mol) of isobutyl chloroformate are added to 1.0 g (0.005 mol) of 2-(i-propoxycarbonylamino)-but-2-enoic acid in 10 ml of dichloromethane. After the addition is complete, stirring is continued at -20° C. for a further 10 minutes, and 0.75 g (0.005 mol) of 1-(4-methoxyphenyl)-ethylamine are added, the temperature being kept below -15° C. Stirring is then continued for a further 2 hours at -15° C. and for 15 hours at room temperature, the precipitated solid is filtered off and washed with dichloromethane, the filtrate is concentrated under reduced pressure, the residue is taken up in water and extracted repeatedly with ethyl acetate, the combined organic phases are washed with aqueous sodium bicarbonate solution and water and dried over sodium sulphate, and the solvent is removed under reduced pressure. 0.8 g (47% of theory) of N-[1-(4-methoxyphenyl)-ethyl]-2-(i-propoxycarbonylamino)-but-2-enoic acid amide are obtained as a colourless oil. 1H-NMR (CDCl3, TMS), δ (ppm): 1.25 (m, 6H), 1.50 (d, 3H); 1.74 (d, 3H); 3.79 (s, 3H).