Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C:5]1[CH:14]=[CH:13][C:12]2[O:11][CH:10]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][O:23][CH3:24])=[CH:17][CH:16]=3)[CH:9]3[CH2:25][C:26](=[O:28])[CH2:27][CH:8]3[C:7]=2[CH:6]=1.[CH2:29]([Mg]Cl)[CH3:30]>C1COCC1>[CH2:29]([C:26]1([OH:28])[CH2:25][CH:9]2[CH:10]([C:15]3[CH:16]=[CH:17][C:18]([O:21][CH2:22][O:23][CH3:24])=[CH:19][CH:20]=3)[O:11][C:12]3[CH:13]=[CH:14][C:5]([O:4][CH2:3][O:2][CH3:1])=[CH:6][C:7]=3[CH:8]2[CH2:27]1)[CH3:30]
Reactant: COCOc1ccc(C2Oc3ccc(OCOC)cc3C3CC(=O)CC32)cc1
Reactant: CC[Mg]Cl
Solvent: C1CCOC1
Product: CCC1(O)CC2c3cc(OCOC)ccc3OC(c3ccc(OCOC)cc3)C2C1
Temperature: 120 °C
Reaction time: 0.75 h
Yield: 79.6 %

Procedure:
Heat CeCl3-7H2O (97 mg, 0.26 mmol) under vacuum at 70° C. for two hours and then warm slowly to 120° C. and continue heating overnight. Cool to room temperature and add THF (3 mL) followed by cyclopentanone 23 (100 mg, 0.26 mmol) and stir the solution for 45 minutes. Cool the reaction to −10° C., add EtMgCl (3.0 M in THF, 87 ul, 0.26 mmol) and stir the reaction for 30 minutes. Quench the reaction with saturated aqueous NH4Cl and extract with EtOAc (2×). Combine the organic extracts, wash with brine, dry (Na2SO4), filter and concentrate. Purify by flash chromatography (10 g silica gel, 40 mL/min, dry loading on 700 mg of silica gel, 0-30% EtOAc/hexanes for 20 minutes and 30% EtOAc/hexanes for 13 minutes) to afford Alcohol 31 (86 mg, 0.207 mmol, 81%). 1H NMR (δ, 400 MHz, CDCl3) 7.36 (d, 2H, J=8.8 Hz), 7.05 (d, 2H, J=8.8 Hz), 6.90-6.87 (m, 2H), 6.83 (dd, 1H, J=8.8, 2.6 Hz), 5.19 (s, 2H), 5.14 (d, 1H, J=6.8 Hz), 5.10 (d, 1H, J=6.8 Hz), 5.05 (d, 1H, J=2.2 Hz), 3.54 (dd, 1H, J=7.6, 7.6 Hz), 3.51 (s, 3H), 3.49 (s, 3H), 2.70 (ddd, 1H, J=2.2, 7.6, 9.6 Hz), 2.22 (dd, 1H, J=13.6, 7.9 Hz), 2.03 (d, 1H, J=13.6 Hz), 1.84 (dd, 1H, J=14.1, 10.1 Hz), 1.67 (dd, 1H, J=14.1, 9.2 Hz), 1.52 (m, 2H), 0.89 (t, 3H, J=7.3 Hz).
Reaction SMILES: C(N(CC)CC)C.[CH3:8][S:9](Cl)(=[O:11])=[O:10].[Cl:13][C:14]1[C:23]([Cl:24])=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[C:16]([C:25]2[NH:26][C:27](=[O:34])[C:28]3[S:33][CH:32]=[CH:31][C:29]=3[N:30]=2)[CH:15]=1>C(Cl)(Cl)Cl>[Cl:13][C:14]1[C:23]([Cl:24])=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[C:16]([C:25]2[N:26]=[C:27]([O:34][S:9]([CH3:8])(=[O:11])=[O:10])[C:28]3[S:33][CH:32]=[CH:31][C:29]=3[N:30]=2)[CH:15]=1
Reactant: CS(=O)(=O)Cl
Reactant: COC(=O)c1cc(Cl)c(Cl)cc1-c1nc2ccsc2c(=O)[nH]1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: COC(=O)c1cc(Cl)c(Cl)cc1-c1nc(OS(C)(=O)=O)c2sccc2n1
Reaction time: 0.5 h

Procedure:
Triethylamine and methanesulfonyl chloride were added to a chloroform solution of methyl 4,5-dichloro-2-(4-oxo-3,4-dihydrothieno[3,2-d]pyrimidine-2-yl)benzoate under ice cooling and stirred under ice cooling for 30 minutes to give methyl 4,5-dichloro-2-{4-[(methanesulfonyl)oxy]thieno[3,2-d]pyrimidine-2-yl}benzoate.
Reaction SMILES: C([O:3][C:4](=[O:18])[CH2:5][C:6]1[NH:11][C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[S:8](=[O:17])(=[O:16])[N:7]=1)C.C(Cl)(Cl)Cl>C1COCC1.Cl>[O:17]=[S:8]1(=[O:16])[C:9]2[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=2[NH:11][C:6]([CH2:5][C:4]([OH:18])=[O:3])=[N:7]1
Reactant: CCOC(=O)CC1=NS(=O)(=O)c2ccccc2N1
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Product: O=C(O)CC1=NS(=O)(=O)c2ccccc2N1
Reaction time: 0.25 h
Yield: 84.8 %

Procedure:
A solution of 4c (1.98 g, 7.36 mmol) in THF (10 mL) and 6 N HCl (20 mL) was stirred for 2 days at room temperature. Chloroform (20 mL) was added to the solution to induce precipitation upon vigorous stirring 15 min. The precipitate was collected by vacuum filtration to give 10b (1.50 g, 85%) as a yellow solid. 1H NMR (400 MHz, D6-DMSO) δ 12.25 (s, 1 H), 7.78 (d, J=8 Hz, 1 H), 7.66 (td, J=8, 1 Hz, 1 H), 7.44 (td, J=8, 1 Hz, 1 H), 7.32 (d, J=8 Hz, 1 H), 3.70 (br s, 1 H), 3.58 (s, 2 H).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([F:15])([F:14])[F:13])[N:3]=1.[NH2:16][NH2:17].C(=O)([O-])[O-].[K+].[K+]>O1CCCC1>[F:13][C:12]([F:15])([F:14])[C:4]1[N:3]=[C:2]([NH:16][NH2:17])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=1
Reactant: NN
Reactant: FC(F)(F)c1nc(Cl)c2ccccc2n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: NNc1nc(C(F)(F)F)nc2ccccc12
Yield: 56.1 %

Procedure:
To a solution of 4-chloro-2-(trifluoromethyl)quinazoline (2.0 g, 8.6 mmol) and hydrazine (0.27 mL, 8.6 mmol) in 20 mL of tetrahydrofuran was added 1.8 g (13 mmol) of potassium carbonate. The resultant suspension was stirred at ambient temperature for 2 hours. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organics were dried over magnesium sulfate. After filtration, the organics were concentrated in vacuo to yield a yellow solid that was recrystallized in ethyl acetate:hexanes. 1.1 g (56%) of yellow needle-like crystals were isolated.
Reaction SMILES: C1[C:6]([C:7]([OH:9])=[O:8])=[CH:5][C:4]2C([O:12][C:13](=[O:14])[C:3]=2C=1)=O.C1(O)C=CC=CC=1>>[C:13]([OH:14])(=[O:12])[CH2:3][CH2:4][CH2:5][CH2:6][C:7]([OH:9])=[O:8]
Reactant: O=C(O)c1ccc2c(c1)C(=O)OC2=O
Solvent: Oc1ccccc1
Product: O=C(O)CCCCC(=O)O
Yield: 59.2 %

Procedure:
A solution is formed by mixing 60.0 grams of trimellitic acid anhydride and 130.0 grams of p,p' diphenyl methane diisocyanate and 110.0 grams of Bis 2-ethoxy ethylether and 4.8 grams of phenol by heating the mixture. At approximately 135°C. a clear, homogeneous solution is obtained. Once clarity is obtained 27.0 grams of adipic acid is added slowly. The temperature of the mixture is raised to approximately 190°C. and slow reflux is maintained. After approximately 45 minutes, a brownish viscous resin is obtained and 346.2 grams of phenol are added to quench and stop the reaction. The solution is maintained at 130°C. until all the resin is dissolved. The resultant solution is cooled to room temperature and filtered. The viscosity of the product at 25°C. was measured at about 210 cps, utilizing a Brookfield viscometer, and a resin solution of approximately 30% weight resin.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:29])[N:7]([CH2:13][CH2:14][CH2:15][CH2:16][N:17]3[CH2:22][CH:21]=[C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:19][CH2:18]3)[C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1.C(O)(=O)C.[O-:34][C:35]#[N:36].[K+]>O>[C:23]1([C:20]2[CH2:21][CH2:22][N:17]([CH2:16][CH2:15][CH2:14][CH2:13][N:7]3[C:6](=[O:29])[C:5]4[C:10](=[CH:11][C:2]([NH:1][C:35]([NH2:36])=[O:34])=[CH:3][CH:4]=4)[NH:9][C:8]3=[O:12])[CH2:18][CH:19]=2)[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: N#C[O-]
Reactant: Nc1ccc2c(=O)n(CCCCN3CC=C(c4ccccc4)CC3)c(=O)[nH]c2c1
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Product: NC(=O)Nc1ccc2c(=O)n(CCCCN3CC=C(c4ccccc4)CC3)c(=O)[nH]c2c1
Reaction time: 3 h
Yield: 27.7 %

Procedure:
To a mixture of 7-amino-3-[4-(4-phenyl-1,2,3,6-tetrahydropyridin-1-yl)butyl]-1,2,3,4-tetrahydroquinazoline-2,4-dione (0.39 g), acetic acid (5 ml) and water (10 ml) was added a solution of potassium cyanate 0.16 g) in water (2 ml) and the resulting mixture was stirred for additional 3 hours. The reaction mixture was poured into water and precipitated solid was filtered, washed in turn with water and ethanol and dried to give 3-[4-(4-phenyl-1,2,3,6-tetrahydropyridin-1-yl)butyl]-7-ureido-1,2,3,4-tetrahydroquinazoline-2,4-dione (0.12 g).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([C:13]([NH:15][CH:16]([CH:21]([CH3:23])[CH3:22])[C:17]([O:19][CH3:20])=[O:18])=[O:14])[O:10][N:9]=2)=[CH:4][CH:3]=1.[F:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([N:31]=[C:32]=[O:33])[CH:26]=1>C1COCC1>[F:24][C:25]1[CH:26]=[C:27]([NH:31][C:32](=[O:33])[NH:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]3[CH:12]=[C:11]([C:13]([NH:15][CH:16]([CH:21]([CH3:23])[CH3:22])[C:17]([O:19][CH3:20])=[O:18])=[O:14])[O:10][N:9]=3)=[CH:4][CH:3]=2)[CH:28]=[CH:29][CH:30]=1
Reactant: O=C=Nc1cccc(F)c1
Reactant: COC(=O)C(NC(=O)c1cc(-c2ccc(N)cc2)no1)C(C)C
Solvent: C1CCOC1
Product: COC(=O)C(NC(=O)c1cc(-c2ccc(NC(=O)Nc3cccc(F)c3)cc2)no1)C(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 64.2 %

Procedure:
To methyl 2-(3-(4-aminophenyl)isoxazole-5-carboxamido)-3-methylbutanoate (500 mg) dissolved in THF (10 ml) was added 1-fluoro-3-isocyanatobenzene (260 mg) and stirred at RT overnight. The solid was filtered and washed with THF to yield 460 mg (64%) white solid. MS (ES+): m/z 455 (M+1); 1H NMR (DMSO-d6, 300 MHz): δ 9.19 (d, 1H), 9.16 (s, 1H), 9.13 (s, 1H), 7.84 (d, 2H), 7.67 (s, 1H), 7.62 (d, 2H), 7.5 (dd, 1H), 7.31 (m, 1H), 7.13 (dd, 1H), 6.78 (m, 1H), 4.29 (m, 1H), 3.66 (s, 3H), 2.2 (m, 1H), 0.95 (d, 6H).
Reaction SMILES: [C:1]([C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[CH:5][CH:4]=1)#[N:2].C(OCl)(C)(C)C.[CH3:16][CH2:17][C:18](OCC)=[S:19].C(N(CC)CC)C.Cl>ClCCl.C(OCC)C>[C:1]([C:3]1[CH:4]=[C:5]2[C:6](=[CH:8][CH:9]=1)[NH:7][C:18](=[S:19])[CH:17]2[CH3:16])#[N:2]
Reactant: N#Cc1ccc(N)cc1
Reactant: CCOC(=S)CC
Agent: CC(C)(C)OCl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: CC1C(=S)Nc2ccc(C#N)cc21
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A solution of 4-cyanoaniline (5.0 g, 42 mmol) in dry dichloromethane (100 mL) under N2 was cooled to about −78° C. To this stirred solution was added a solution of tert-butylhypochlorite (4.6 g, 42 mmol) in dry dichloromethane (10 mL) over 5 min. and the resulting solution stirred for 10 minutes. A solution of ethyl methylthioacetate (5.45 mL, 5.69 g, 42 mmol) in dry dichloromethane (10 mL) was than added dropwise and the mixture stirred for 1 hour. Triethylamine (5.9 mL, 4.28, 42 mmol) was added dropwise and the solution allowed to warm to room temperature over 1 hour. The reaction solution was washed with water (3×20 mL) and brine (1×20 mL), dried over anhydrous MgSO4 and the solvent evaporated under vacuum to leave an orange oil. This oil was dissolved in diethyl ether (100 mL) and 2N aqueous hydrochloric acid (5 mL) was added and the mixture stirred vigorously at room temperature for 18 hours. The resulting tan solid was collected by filtration and washed with diethyl ether and dried under vacuum to give 5-cyano-3-methylthiooxindole as a white solid, (6.4 g, 76%). 1H NMR (CDCl3) δ9.04 (br s, 1H) 7.64 (s, 1H), 7.57 (d, 1H, J=8.4 Hz), 6.99 (d, 1H, J=8.4 Hz), 4.28 (s, 1H), 2.04 (s, 3H). MS (−ve ES) 203 (100), (M−H).
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].O=[CH:14][C:15]([Cl:18])([Cl:17])[Cl:16].CC1C=CC(S(O)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[CH2:11]([OH:12])[C@@H:9]([OH:10])[C@H:7]1[O:8][C@@H:2]2[O:1][C@H:14]([C:15]([Cl:18])([Cl:17])[Cl:16])[O:4][C@@H:3]2[C@H:5]1[OH:6]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Reactant: O=CC(Cl)(Cl)Cl
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClC(Cl)Cl
Product: OC[C@@H](O)[C@H]1O[C@@H]2O[C@H](C(Cl)(Cl)Cl)O[C@@H]2[C@H]1O
Reaction time: 0.33 h

Procedure:
A mixture of 4.5 g of glucose, 19 g of chloral, 20 ml of chloroform and 0.05 g of 4-methyl-benzene-sulphonic acid is kept at reflux temperature for 7 hours and the formed water is separated by means of a Dean-Stark apparatus. The solvent is distilled off and the residue is kept at 60° C. for 20 minutes. The sedimented material is filtrated and the pH value of the mother lye adjusted to 6.5 with sodium hydroxide. The separated precipitate is filtered.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([O:15][C:16]1[CH:17]=[C:18]([CH2:24][C@H:25]([NH:30]C(OC(C)(C)C)=O)[C:26]([O:28][CH3:29])=[O:27])[CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>ClCCl>[NH2:30][C@@H:25]([CH2:24][C:18]1[CH:19]=[CH:20][C:21]([O:22][CH3:23])=[C:16]([O:15][CH2:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:17]=1)[C:26]([O:28][CH3:29])=[O:27].[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4]
Reactant: COC(=O)[C@H](Cc1ccc(OC)c(OCc2ccccc2)c1)NC(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)[C@@H](N)Cc1ccc(OC)c(OCc2ccccc2)c1

Procedure:
Trifluoroacetic acid (TFA; 25 mL) was added to a solution of (S)-methyl 3-(3-(benzyloxy)-4-methoxyphenyl)-2-((tert-butoxycarbonyl)amino)propanoate (5.00 g, 12.0 mmol) in dichloromethane (CH2Cl2; 50 mL) at 0° C. with stirring. The mixture was stirred for 1 h and then concentrated to dryness. The residue was azeotroped three times with EtOAc (20 mL for each portion) to remove residual TFA to afford crude compound (S)-methyl 2-amino-3-(3-(benzyloxy)-4-methoxyphenyl)propanoate as its TFA salt.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=[O:8])[CH2:3][CH2:2]1.S(Cl)(Cl)=O.[CH3:14]O>>[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH3:14])=[O:8])[CH2:3][CH2:2]1
Reactant: O=C(O)C1CCOCC1
Reactant: CO
Solvent: O=S(Cl)Cl
Product: COC(=O)C1CCOCC1
Temperature: 25 °C

Procedure:
Into a solution of oxane-4-carboxylic acid (50 mg, 0.38 mmol, 1.00 equiv) in methanol (10 mL) was added thionyl chloride (46 mg, 0.39 mmol, 1.01 equiv) dropwise with stirring at room temperature. The resulting solution was stirred for 3 h at room temperature. Concentration under reducing pressure gave the title compound, which was used directly for next step without further purification (brown oil).
Reaction SMILES: [F:1][C:2]1[CH:34]=[CH:33][C:5]([C:6]([NH:8][C:9]2([C:15]([NH:17][CH:18]3[CH2:23][CH2:22][N:21]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=4[NH2:31])[CH2:20][CH:19]3[OH:32])=[O:16])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[O:7])=[CH:4][CH:3]=1.[F:35][C:36]1[C:44]([F:45])=[C:43]([F:46])[CH:42]=[CH:41][C:37]=1[C:38](Cl)=[O:39]>>[F:1][C:2]1[CH:34]=[CH:33][C:5]([C:6]([NH:8][C:9]2([C:15]([NH:17][CH:18]3[CH2:23][CH2:22][N:21]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=4[NH:31][C:38](=[O:39])[C:37]4[CH:41]=[CH:42][C:43]([F:46])=[C:44]([F:45])[C:36]=4[F:35])[CH2:20][C:19]3=[O:32])=[O:16])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]2)=[O:7])=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccc(F)c(F)c1F
Reactant: Nc1cc(F)ccc1N1CCC(NC(=O)C2(NC(=O)c3ccc(F)cc3)CCCCC2)C(O)C1
Product: O=C(NC1(C(=O)NC2CCN(c3ccc(F)cc3NC(=O)c3ccc(F)c(F)c3F)CC2=O)CCCCC1)c1ccc(F)cc1

Procedure:
In accordance with the same procedure as in Example 87, except that 4-[N-[1-[N-(4-fluorobenzoyl)amino]cyclohexanecarbonyl]amino]-1-(4-fluoro-2-aminophenyl)piperidin-3-ol was used instead of 4-[N-[1-[N-(furan-2-ylcarbonyl)amino]cyclohexanecarbonyl]amino]-1-(4-fluoro-2-aminophenyl)piperidin-3-ol and 2,3,4-trifluorobenzoyl chloride was used instead of methoxyacetyl chloride in Step 3 thereof, 321 mg of the titled compound was prepared.
Reaction SMILES: [OH:1][C@@H:2]1[CH2:27][CH2:26][C@@:25]2([CH3:28])[C@@H:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:24]2[C:23](=[O:29])[CH2:22][C@@:21]2([CH3:30])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C:12](=[O:20])[CH:13]([CH2:15][O:16][C:17](=[O:19])[CH3:18])I)[CH2:3]1.[CH2:31]([NH:33][CH2:34][CH3:35])[CH3:32]>ClCCl>[CH2:31]([N:33]([CH2:18][C:17]([O:16][CH2:15][CH2:13][C:12](=[O:20])[C@@H:11]1[C@:21]2([CH3:30])[C@H:8]([C@H:7]3[C@H:24]([C:23](=[O:29])[CH2:22]2)[C@:25]2([CH3:28])[C@H:4]([CH2:3][C@H:2]([OH:1])[CH2:27][CH2:26]2)[CH2:5][CH2:6]3)[CH2:9][CH2:10]1)=[O:19])[CH2:34][CH3:35])[CH3:32]
Reactant: CC(=O)OCC(I)C(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)CC[C@]4(C)[C@H]3C(=O)C[C@]12C
Reactant: CCNCC
Solvent: ClCCl
Product: CCN(CC)CC(=O)OCCC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)CC[C@]4(C)[C@H]3C(=O)C[C@]12C

Procedure:
3α-hydroxy-21-iodo-acetoxymethyl-5α-pregnane-11,20-dione (235 mg) in dry dichloromethane (25 ml) was treated with diethylamine (1 ml) in similar manner to that described in Example 35 to give title compound (89 mg)[αD ] + 73° (c 0.42).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:21]=[CH:22][C:23]=1[O:24][CH2:25][C:26]1[N:27]=[C:28]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[S:29][C:30]=1[CH3:31])[CH2:6][O:7][C:8]1[C:12]([CH:13]=O)=[CH:11][N:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:9]=1.[CH2:38]([P:47](=[O:54])([O:51][CH2:52][CH3:53])[O:48][CH2:49][CH3:50])P(=O)(OCC)OCC.CN(C)C=O.[H-].[Na+]>O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:21]=[CH:22][C:23]=1[O:24][CH2:25][C:26]1[N:27]=[C:28]([N:32]2[CH2:33][CH2:34][O:35][CH2:36][CH2:37]2)[S:29][C:30]=1[CH3:31])[CH2:6][O:7][C:8]1[C:12](/[CH:13]=[CH:38]/[P:47](=[O:54])([O:48][CH2:49][CH3:50])[O:51][CH2:52][CH3:53])=[CH:11][N:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:9]=1
Reactant: CCOP(=O)(CP(=O)(OCC)OCC)OCC
Reactant: COc1cc(COc2nn(-c3ccccc3)cc2C=O)ccc1OCc1nc(N2CCOCC2)sc1C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOP(=O)(/C=C/c1cn(-c2ccccc2)nc1OCc1ccc(OCc2nc(N3CCOCC3)sc2C)c(OC)c1)OCC
Reaction time: 15 h
Yield: 50.5 %

Procedure:
To a mixture of 3-({3-methoxy-4-[(5-methyl-2-morpholin-4-yl-1,3-thiazol-4-yl)methoxy]benzyl}oxy)-1-phenyl-1H-pyrazole-4-carbaldehyde (0.52 g), tetraethyl methylenediphosphonate (0.32 g) and N,N-dimethylformamide (10 mL) was added sodium hydride (60% in oil, 0.050 g) at room temperature, and the mixture was stirred at the same temperature for 15 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give diethyl (E)-2-[3-({3-methoxy-4-[(5-methyl-2-morpholin-4-yl-1,3-thiazol-4-yl)methoxy]benzyl}oxy)-1-phenyl-1H-pyrazol-4-yl]ethenylphosphonate as colorless crystals (0.33 g, yield 51%) from a fraction eluted with ethyl acetate-hexane (9:1, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 88-90° C.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:7]([O-:11])(=[O:10])(=[O:9])=[O:8].CS[C:14]1[S:18][CH:17]=[CH:16][S+:15]=1>>[Cl:7]([O-:11])(=[O:10])(=[O:9])=[O:8].[S:15]1[CH:16]=[CH:17][S:18][C:14]1=[N+:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CSc1scc[s+]1
Reactant: C1CCNCC1
Agent: [O-][Cl+3]([O-])([O-])[O-]
Product: c1csc(=[N+]2CCCCC2)s1

Procedure:
1.0 ml of piperidine and 2.5 g of 2-methylthio-1,3-dithiolium perchlorate were treated in the same manner as in Example 26, and the product was recrystallized from acetone-ethyl ether, whereby 2.1 g (yield: 73.6%) of 1-(1,3-dithiol-2-ylidene)piperidinium perchlorate (Compound No. 34) was obtained as crystals having a melting point of from 171° to 172° C.
Reaction SMILES: C([O:8][CH2:9][C@H:10]1[C@@H:15]([CH3:16])[N:14]([S:17]([CH3:20])(=[O:19])=[O:18])[CH2:13][CH2:12][N:11]1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])C1C=CC=CC=1.C([O-])=O.[NH4+]>[Pd].O.CO>[C:24]([O:23][C:21]([N:11]1[CH2:12][CH2:13][N:14]([S:17]([CH3:20])(=[O:19])=[O:18])[C@H:15]([CH3:16])[C@@H:10]1[CH2:9][OH:8])=[O:22])([CH3:26])([CH3:27])[CH3:25]
Reactant: C[C@@H]1[C@H](COCc2ccccc2)N(C(=O)OC(C)(C)C)CCN1S(C)(=O)=O
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: O
Solvent: CO
Product: C[C@@H]1[C@H](CO)N(C(=O)OC(C)(C)C)CCN1S(C)(=O)=O
Yield: 92.3 %

Procedure:
10% Palladium on activated carbon (1.5 g) was suspended in H2O (10 ml) and the suspension was added to a solution of (2R,3R)-2-benzyloxymethyl-1-tert-butoxycarbonyl-4-methanesulfonyl-3-methyl-piperazine (2.1 g) and ammonium formate (3.3 g) in MeOH (25 ml). The mixture was refluxed for 1.5 hours. Ammonium formate (3.4 g) in H2O (10 ml) and MeOH (10 ml) were added to the reaction mixture, and the mixture was refluxed for 1.5 hours. 10% Palladium on activated carbon (1.5 g) in H2O (10 ml) and ammonium formate (3.4 g) were added to the reaction mixture and the mixture was refluxed for 2.5 hours. The catalyst was removed by filtration through a celite pad and the pad was washed with MeOH. The combined filtrate and washings were concentrated in vacuo. The residue was partitioned between AcOEt and brine. The organic layer was dried over MgSO4 and concentrated in vacuo to give 1.5 g of (2R,3R)-1-tert-butoxycarbonyl-2-hydroxymethyl-4-methane-sulfonyl-3-methylpiperazine as a solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:55])[O:7][C:6]2[CH:8]=[CH:9][C:10]([C@H:12]3[O:16]C(=O)[N:14]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][C:29]4[CH:30]=[C:31]([S:35]([N:38]([CH2:47][O:48][CH2:49][CH2:50][Si:51]([CH3:54])([CH3:53])[CH3:52])[CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])(=[O:37])=[O:36])[CH:32]=[CH:33][CH:34]=4)[CH2:13]3)=[CH:11][C:5]=2[CH2:4][O:3]1.C[Si](C)(C)[O-].[K+].P([O-])([O-])([O-])=O>C1COCC1>[CH3:1][C:2]1([CH3:55])[O:7][C:6]2[CH:8]=[CH:9][C:10]([C@@H:12]([OH:16])[CH2:13][NH:14][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][C:29]3[CH:30]=[C:31]([S:35]([N:38]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])[CH2:47][O:48][CH2:49][CH2:50][Si:51]([CH3:53])([CH3:52])[CH3:54])(=[O:37])=[O:36])[CH:32]=[CH:33][CH:34]=3)=[CH:11][C:5]=2[CH2:4][O:3]1
Reactant: CC1(C)OCc2cc([C@@H]3CN(CCCCCCOCCOCc4cccc(S(=O)(=O)N(COCC[Si](C)(C)C)COCC[Si](C)(C)C)c4)C(=O)O3)ccc2O1
Agent: C[Si](C)(C)[O-]
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC1(C)OCc2cc([C@@H](O)CNCCCCCCOCCOCc3cccc(S(=O)(=O)N(COCC[Si](C)(C)C)COCC[Si](C)(C)C)c3)ccc2O1
Yield: 206.5 %

Procedure:
A solution of 3-{[2-({6-[(5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxo-1,3-oxazolidin-3-yl]hexyl}oxy)ethoxy]methyl}-N,N-bis{[2-(trimethylsilyl)ethoxy]methyl}benzenesulfonamide (200 mg) in THF (10 ml) under nitrogen was treated with potassium trimethylsilanolate (125 mg) and the mixture heated to 70° for 5 h. The mixture was cooled to 20° and phosphate buffer solution (25 ml, pH6.5) was added. The mixture was extracted with EtOAc, the extract dried (Na2SO4) and the solvent evaporated in vacuo to give the title compound (400 mg). LCMS RT=3.6 min.
Reaction SMILES: I[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH:14]=[C:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][C:16]2=[O:24])=[CH:9][CH:8]=1.[CH3:25][N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1>>[CH3:25][N:26]1[CH2:31][CH2:30][N:29]([CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]2[CH:12]=[CH:11][C:10]([NH:13][CH:14]=[C:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[NH:17][C:16]3=[O:24])=[CH:9][CH:8]=2)[CH2:28][CH2:27]1
Reactant: CN1CCNCC1
Reactant: O=C1Nc2ccccc2C1=CNc1ccc(OCCCCI)cc1
Product: CN1CCN(CCCCOc2ccc(NC=C3C(=O)Nc4ccccc43)cc2)CC1

Procedure:
In a manner similar to that described in Example 207, 3-{[4-(4-Iodo-butoxy)-phenylamino]-methylene}-1,3-dihydro-indol-2-one and N-methylpiperazine are converted to the named compound.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[C:7](=[O:12])[CH2:6][CH2:5]2.[CH3:13][CH:14](O)[CH:15]=[CH2:16].C1(C)C=CC(S(O)(=O)=O)=CC=1.O>COC(OC)(C)C>[CH2:13]([CH:6]1[CH2:5][C:4]2[C:8](=[CH:9][C:10]([Cl:11])=[C:2]([Cl:1])[CH:3]=2)[C:7]1=[O:12])[CH:14]=[CH:15][CH3:16]
Reactant: O=C1CCc2cc(Cl)c(Cl)cc21
Reactant: C=CC(C)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: COC(C)(C)OC
Solvent: O
Product: CC=CCC1Cc2cc(Cl)c(Cl)cc2C1=O
Yield: 69 %

Procedure:
A solution of 12.3 g of 5,6-dichloro-1-indanone, 12.6 ml of 3-buten-2-ol and 125 mg of p-toluenesulfonic acid in 125 ml of 2,2-dimethoxy-propane was boiled under reflux for 68 hours on a water separator filled with molecular sieve (0.4 nm, 2 mm pearl shaped). The reaction mixture was subsequently concentrated in a vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 4:1). In addition to 4.3 g of educt, there were obtained 10.8 g (69%) of (RS)-2-(2-buten-1-yl)-5,6-dichloro-1-indanone as a yellow oil.