Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[NH2:21])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:22](OCC)(OCC)OCC.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[C:15]3[CH:20]=[CH:19][N:18]=[CH:17][C:16]=3[N:21]=[CH:22]2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(OCC)OCC
Reactant: CC(C)(C)OC(=O)N1CCC(Nc2ccncc2N)CC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCC(n2cnc3cnccc32)CC1
Yield: 73.5 %

Procedure:
To a solution of 4-(3-amino-pyridin-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (10.0 g, 34.20 mmol, 1.0 equiv) and triethyl orthoformate (10.14 g, 68.40 mmol, 2.0 equiv) in anhydrous toluene (70 mL) was added toluene-4-sulfonic acid (0.59 g, 3.42 mmol, 0.1 equiv) and the reaction mixture heated to reflux for 16 h. The solvent was removed by evaporation under reduced pressure and the residue triturated with diethyl ether. The preciptate was filtered off, washed with diethyl ether and dried under reduced pressure to yield 7.6 g (73%) of the title compound. 1H NMR (400 MHz, DMSO): δ 1.43 (s, 9H), 1.92-2.04 (m, 4H), 2.95 (br s, 2H), 4.13 (br s, 2H), 4.64 (t, J=3.8 Hz, 1H), 7.75 (d, J=5.5 Hz, 1H), 8.34 (d, J=5.5 Hz, 1H), 8.55 (s, 1H), 8.95 (s, 1H). MS (ISP): 303.2 [M+H]1.
Reaction SMILES: [CH2:1]([C:3]1[C:11]2[O:10][CH2:9][O:8][C:7]=2[CH:6]=[CH:5][C:4]=1[CH2:12][C:13]([CH3:19])([CH3:18])[C:14]([O:16]C)=[O:15])[CH3:2].[OH-].[Na+].O.Cl>C(O)C>[CH2:1]([C:3]1[C:11]2[O:10][CH2:9][O:8][C:7]=2[CH:6]=[CH:5][C:4]=1[CH2:12][C:13]([CH3:18])([CH3:19])[C:14]([OH:16])=[O:15])[CH3:2]
Reactant: CCc1c(CC(C)(C)C(=O)OC)ccc2c1OCO2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCc1c(CC(C)(C)C(=O)O)ccc2c1OCO2
Yield: 44.4 %

Procedure:
A solution of the product from Stage (iii) (10 g) and 2N sodium hydroxide (50 ml) in ethanol (50 ml) was heated under reflux for 30 min. The solution was cooled, poured into water, acidified with 2N hydrochloric acid and extracted with ether. The extracts were dried and evaporated and the residue purified by FCC using hexane/ether (7:3) as eluent. The product was crystallised from hexane to give the title compound (4.2 g) as a white solid, m.p. 73°-74°.
Reaction SMILES: C(OC)(OC)OC.CN(C)C(N(C)C)=N.[CH2:16]=[C:17]([CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19].[PH2:36]([O:38][CH3:39])=[O:37]>>[CH3:39][O:38][PH:36]([CH2:16][CH:17]([CH2:28][CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:18]([O:20][CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)=[O:19])=[O:37]
Reactant: CO[PH2]=O
Reactant: C=C(CCc1ccccc1)C(=O)OCc1ccccc1
Agent: CN(C)C(=N)N(C)C
Solvent: COC(OC)OC
Product: CO[PH](=O)CC(CCc1ccccc1)C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 99.9 %

Procedure:
Trimethyl orthoformate (11.0 mL, 10.7 g, 101 mmol) was added to anhydrous hypophosphorous acid3 (4.0 mL, 6.0 g. 90 mmol) and the solution was stirred for 1.5 h at room temperature. In a separate flask, N,N,N',N'-tetramethylguanidine (1.50 mL, 1.38 g, 12.0 mmol) was added to benzyl 2-methylene-4-phenyl-butanoate (3.99 g, 15.0 mmol) and the solution was cooled to 0° C. by an ice bath. An portion of the methyl hypophosphite solution (12.0 mL, d=1.04 g/mL, approx. 68 mmol) was added over 1 h. The ice bath was removed and the solution was stirred an additional 1.25 h. The reaction was diluted with ethyl acetate (150 mL) and washed with 2N aqueous hydrochloric acid (50 mL), water (50 mL), and saturated aqueous sodium chloride (50 mL). The aqueous layers were extracted in succession with ethyl acetate (50 mL). The organic layers were dried (sodium sulfate), decanted, and evaporated. After drying overnight under vacuum, the crude product was 5.19 g (100% yield) of viscous colorless oil.
Reaction SMILES: [N+:1]([C:4]1[CH:22]=[CH:21][C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:6][CH:5]=1)([O-])=O.[Cl-].[NH4+].C(O)C.CN(C)C=O>[Fe].O>[C:15]1([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][C:9]=2[O:8][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:22][CH:21]=2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: O=[N+]([O-])c1ccc(Oc2ccncc2-c2ccccc2)cc1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCO
Product: Nc1ccc(Oc2ccncc2-c2ccccc2)cc1
Yield: 62.4 %

Procedure:
4-(4-Nitrophenoxy)-3-phenylpyridine (150 mg), iron powder (300 mg), ammonium chloride (600 mg), ethanol (5 ml), dimethylformamide (5 ml) and water (2.5 ml) were stirred at 100° C. for 15 minutes. The mixture was filtered with celite, water was added to the filtrate, and extraction was performed with ethyl acetate. The organic layer was washed 5 times with water, and then the solvent was distilled off under reduced pressure to obtain 4-(3-phenylpyridin-4-yl)oxyaniline (84 mg) as a yellow oil.
Reaction SMILES: [C:1]([CH2:3][CH2:4][S:5][C:6]1[CH:11]=[C:10]([NH2:12])[C:9]([S:13][CH2:14][CH2:15][C:16]#[N:17])=[CH:8][C:7]=1[NH:18][C:19](=[O:29])[C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=1)#[N:2].[OH:30][C:31]1[CH:39]=[CH:38][C:34]([C:35](O)=[O:36])=[CH:33][CH:32]=1>CN1C(=O)CCC1>[C:16]([CH2:15][CH2:14][S:13][C:9]1[CH:8]=[C:7]([NH:18][C:19](=[O:29])[C:20]2[CH:21]=[CH:22][C:23]([N+:26]([O-:28])=[O:27])=[CH:24][CH:25]=2)[C:6]([S:5][CH2:4][CH2:3][C:1]#[N:2])=[CH:11][C:10]=1[NH:12][C:35](=[O:36])[C:34]1[CH:38]=[CH:39][C:31]([OH:30])=[CH:32][CH:33]=1)#[N:17]
Reactant: N#CCCSc1cc(NC(=O)c2ccc([N+](=O)[O-])cc2)c(SCCC#N)cc1N
Reactant: O=C(O)c1ccc(O)cc1
Solvent: CN1CCCC1=O
Product: N#CCCSc1cc(NC(=O)c2ccc([N+](=O)[O-])cc2)c(SCCC#N)cc1NC(=O)c1ccc(O)cc1
Temperature: 25 °C
Yield: 76.3 %

Procedure:
2,5-Bis[(2-cyanoethyl)sulfanyl]-N-(4-nitrobenzoyl)-1,4-phenylenediamine (1.0 g, 2.34 mmol) as prepared from the above Example 1 was admixed with 4-hydroxybenzoic acid (0.328 g, 2.38 mmol) in 11.7 mL NMP under nitrogen purge, followed by addition of lithium chloride (LiCl, 0.58 g), triphenylphosphite (TPP, 2.92 mL) and pyridine (2.92 mL). The resultant mixture was heated to a temperature of 80˜95° C. for about 4 h, followed by cooling to room temperature. 400 mL of water was subsequently added with stirring for a few minutes, and the resultant precipitate was collected by filtration, washed with water (400 mL, twice) and methanol (400 mL, once), followed by drying at room temperature under vacuum overnight, giving the title compound in a yield of 76.3%.
Reaction SMILES: C1COCC1.Cl[C:7]1[C:12]([C:13]([F:16])([F:15])[F:14])=[CH:11][C:10]([Cl:17])=[CH:9][N:8]=1.[H-].[Na+].[CH3:20][O:21][N:22]=[C:23]([C:32]1[CH:36]=[C:35]([CH3:37])[O:34][N:33]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH2:30][OH:31]>O>[CH3:20][O:21][N:22]=[C:23]([C:32]1[CH:36]=[C:35]([CH3:37])[O:34][N:33]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH2:30][O:31][C:7]1[C:12]([C:13]([F:16])([F:15])[F:14])=[CH:11][C:10]([Cl:17])=[CH:9][N:8]=1
Reactant: CON=C(c1cc(C)on1)c1ccccc1CO
Reactant: FC(F)(F)c1cc(Cl)cnc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CON=C(c1cc(C)on1)c1ccccc1COc1ncc(Cl)cc1C(F)(F)F
Temperature: 25 °C
Reaction time: 8 h
Yield: 96.3 %

Procedure:
THF (3 ml), 2,5-dichloro-3-trifluoromethylpyridine (0.32 g, 1.5 mmol) and 60% sodium hydride (0.05 g, 1.2 mmol) were added to 2-hydroxymethylphenyl 5-methylisoxazol-3-yl ketone O-methyloxime (0.25 g, 1.0 mmol) under ice-cooling, and the mixture was stirred at room temperature overnight. Water (100 ml) was added to the reaction mixture, and the mixture was extracted with ether (150 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(5-chloro-3-trifluoromethyl-2-pyridyloxymethyl)phenyl 5-methylisoxazol-3-yl ketone O-methyloxime (0.41 g, yield: 96.3%) as colorless crystals.
Reaction SMILES: [CH3:1][CH:2]([CH3:30])[CH:3]([CH2:11][CH:12]([S:20][NH:21][C:22](=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:4]([O:6]C(C)(C)C)=[O:5].FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:1][CH:2]([CH3:30])[CH:3]([CH2:11][CH:12]([S:20][NH:21][C:22](=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:4]([OH:6])=[O:5]
Reactant: CC(C)C(CC(Cc1ccccc1)SNC(=O)c1ccccc1)C(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)C(CC(Cc1ccccc1)SNC(=O)c1ccccc1)C(=O)O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 21.1 mm t-butyl 3-methyl-2-(3-phenyl-2-benzamidothiopropyl)butyrate in 5 ml of methylene chloride is added 15 ml of trifluoroacetic acid. The solution is stirred at room temperature for approximately 21/2 hours. The solvent is then evaporated, yielding 3-methyl-2-(3-phenyl-2-benzamidothiopropyl)butyric acid.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[CH2:16][CH:17]1[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][NH:25][C:26](=[O:35])[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[NH:33][CH3:34])[CH2:19][CH2:18]1.[C:36]([O:39][C:40](=[O:42])[CH3:41])(=[O:38])[CH3:37].[OH-:43].[NH4+]>O>[C:40]([OH:39])(=[O:42])[C:41]([OH:1])=[O:43].[C:36]([CH2:34][NH:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[C:26]([NH:25][CH2:24][CH2:23][N:20]1[CH2:21][CH2:22][CH:17]([CH2:16][C:8]2[N:7]([CH2:6][C:2]3[O:1][CH:5]=[CH:4][CH:3]=3)[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=2)[CH2:18][CH2:19]1)=[O:35])(=[O:38])[CH3:37]
Reactant: [OH-]
Reactant: CNc1ccccc1C(=O)NCCN1CCC(Cc2nc3ccccc3n2Cc2ccco2)CC1
Reactant: CC(=O)OC(C)=O
Agent: [NH4+]
Solvent: O
Product: CC(=O)CNc1ccccc1C(=O)NCCN1CCC(Cc2nc3ccccc3n2Cc2ccco2)CC1
Product: O=C(O)C(=O)O
Temperature: 100 °C
Yield: 4.3 %

Procedure:
A mixture of 2.9 parts of N-[2-[4-[[1-(2-furanylmethyl)-1H-benzimidazol-2-yl]methyl]-1-piperidinyl]-ethyl]-2-(methylamino)benzamide, 10 parts of acetic acid anhydride and 20 parts of water was stirred and heated for 3 hours at 100° C. The reaction mixture was cooled, water was added and the whole was made alkaline with ammonium hydroxide. The product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified twice by column chromatography over silica gel using each time a mixture of trichloromethane and methanol, saturated with ammonia (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the ethanedioate salt in ethanol, yielding 0.2 parts (4.3%) of 2-(acetylmethylamino)-N-[2-[4-[[1-(2-furanylmethyl)-1H-benzimidazol-2-yl]-methyl]-1-piperidinyl]ethyl]benzamide ethanedioate (2:5); mp. 146.8° C. (511).
Reaction SMILES: [Br:1][CH2:2][C:3]([C:5]1[CH:10]=[C:9]([S:11](=[O:14])(=[O:13])[NH2:12])[C:8]([Cl:15])=[CH:7][C:6]=1[Cl:16])=[O:4].[CH3:17][NH:18][C:19]([NH:21][CH3:22])=[S:20]>CO>[BrH:1].[Cl:16][C:6]1[CH:7]=[C:8]([Cl:15])[C:9]([S:11](=[O:14])(=[O:13])[NH2:12])=[CH:10][C:5]=1[C:3]1([OH:4])[CH2:2][S:20][C:19](=[N:18][CH3:17])[N:21]1[CH3:22]
Reactant: CNC(=S)NC
Reactant: NS(=O)(=O)c1cc(C(=O)CBr)c(Cl)cc1Cl
Solvent: CO
Product: Br
Product: CN=C1SCC(O)(c2cc(S(N)(=O)=O)c(Cl)cc2Cl)N1C

Procedure:
7 g of 2-bromo-2',4'-dichloro-5'-sulfamoyl-acetophenone and 2.5 g of 1,3-dimethyl-thiourea were allowed to react for 20 hours in 50 ml of methanol, the precipitate of 4-(2,4-dichloro-5-sulfamoylphenyl)-3-methyl-2-methylimino-1,3-thiazolidine-4-ol-hydrobromide was filtered off and washed with acetone.
Reaction SMILES: C(Cl)(=O)C([Cl:4])=O.CN(C=O)C.C(O)(C)C.C(=O)=O.[CH2:19]([O:26][C:27]([O:29][CH:30]1[CH2:39][CH2:38][C:37]2[N:36]=[CH:35][C:34]([C:40]([O:42][CH2:43][CH3:44])=[O:41])=[C:33](O)[C:32]=2[CH2:31]1)=[O:28])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(Cl)Cl>[CH2:19]([O:26][C:27]([O:29][CH:30]1[CH2:39][CH2:38][C:37]2[N:36]=[CH:35][C:34]([C:40]([O:42][CH2:43][CH3:44])=[O:41])=[C:33]([Cl:4])[C:32]=2[CH2:31]1)=[O:28])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CCOC(=O)c1cnc2c(c1O)CC(OC(=O)OCc1ccccc1)CC2
Reactant: O=C(Cl)C(=O)Cl
Agent: O=C=O
Solvent: CC(C)O
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CCOC(=O)c1cnc2c(c1Cl)CC(OC(=O)OCc1ccccc1)CC2
Reaction time: 0.5 h

Procedure:
Oxalyl chloride (1.82 g) is added to 100 mL of DMF dropwise under stirring and cooling (isopropanol-dry ice) maintaining the temperature below -20°. Stirring is continued for 30 minutes at the same temperature. To the mixture, 2.66 g of ethyl 6-benzyloxycarbonyloxy-4-hydroxy-5,6,7,8-tetrahydroquinoline-3-carboxylate is added in one portion, and stirring is continued for 2 hours at -30° to -20°, then at room temperature overnight. The reaction mixture is evaported to dryness and the residue is taken up in CH2Cl2, washed with saturated NaHCO3, dried (MgSO4) and evaporated to leave an oil which is purified by flash chromatography on a silica gel column obtaining ethyl 6-benzyloxycarbonyloxy-4-chloro-5,6,7,8-tetrahydroquinoline-3-carboxylate.
Reaction SMILES: [CH2:1]([O:3][C:4]([C@H:6]1[NH:8][C@@H:7]1[C:9]([NH:11][C@H:12]([C:20]([OH:22])=O)[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:10])=[O:5])[CH3:2].[CH:23]1([CH2:29][NH2:30])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>>[CH2:1]([O:3][C:4]([C@H:6]1[NH:8][C@@H:7]1[C:9]([NH:11][C@H:12]([C:20]([NH:30][CH2:29][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)=[O:22])[CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[O:10])=[O:5])[CH3:2]
Reactant: CCOC(=O)[C@H]1N[C@@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)O
Reactant: NCC1CCCCC1
Product: CCOC(=O)[C@H]1N[C@@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC1CCCCC1

Procedure:
In substantially the same manner as Working Example 26, Compound 26b (1.22 g) was condensed with cyclohexanemethylamine (0.50 g, manufactured by Wako Pure Chemical Industries, Ltd.) to give the above-titled compound. (Compound 87; 0.85 g) as white crystals (yield 53%).
Reaction SMILES: C[C:2]1[C:32](C)=[CH:31][C:5]2[N:6](C(=O)CN3CCN(CCO)CC3)[C:7]3N=CC=C[C:8]=3[C:9]3[N:10](C(=O)NN=3)[C:4]=2[CH:3]=1.[H-].[Na+].CN(C)CCCCl.CN(C)C=[O:46]>C1(C)C(C)=CC=CC=1>[N:10]1[C:4]2[CH:3]=[CH:2][CH:32]=[CH:31][C:5]=2[N:6]=[CH:7][C:8](=[O:46])[CH:9]=1
Reactant: CN(C)C=O
Reactant: Cc1cc2c(cc1C)-n1c(n[nH]c1=O)-c1cccnc1N2C(=O)CN1CCN(CCO)CC1
Agent: CN(C)CCCCl
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1C
Product: O=c1cnc2ccccc2nc1
Reaction time: 22 h

Procedure:
In the manner given in Example 25, to 6,7-dimethyl-9-[[4-(2-hydroxyethyl)piperazino]acetyl]-3H-pyrido[3,2-c]-s-triazolo[4,3-a][1,5]benzodiazepin-3-one in dimethylformamide is added a solution of sodium hydride in mineral oil. The mixture is allowed to react at about 95° C. for 40 minutes and after cooling [3-(dimethylamino)propyl]-chloride in xylene is added. The mixture is kept at 95°-100° C. for a period of 22 hours, evaporated and worked up as in example 25 to give 6,7-dimethyl-2,9-dihydro-2-[3-(dimethylamino)propyl]-9-[[4-(2-hydroxyethyl)-piperazino]acetyl]-3H-pyrido[3,2-c]-s-triazolo]4,3-a]-[1,5]benzodiazepin-3-one.
Reaction SMILES: [C:1]1(=[O:17])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH:9]=[CH:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CC(C)=O.[H][H]>[Pd].O>[C:1]1(=[O:17])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C1CCCCCCC=CCCCCCCC1
Reactant: [H][H]
Agent: [Pd]
Solvent: O
Solvent: CC(C)=O
Product: O=C1CCCCCCCCCCCCCCC1

Procedure:
100 kg of 8-cyclohexadecenone (odoriferously good quality: GC ratio of (E) and (Z) isomers was 2.5:1), 45 kg of acetone and 100 g of palladium on activated charcoal (Pd content: 5 wt. %) with 40% water content were placed in a stirred autoclave equipped with a gassing stirrer. The reaction mixture was hydrogenated for 12 hours at 35° to 40° C. and at 15 bar hydrogen pressure and then filtered. After removing the acetone 99.2 kg of cyclohexadecanone were obtained (GC content of cyclohexadecanone: >98%). The product thereby obtained was of a good perfumery quality. The perfumery quality could be improved still further by recrystallisation from methanol.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:12])[N:3]=1.[CH2:13]([O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1)[CH3:14]>>[CH2:13]([O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[C:4]([CH3:12])[N:3]=2)=[CH:18][CH:17]=1)[CH3:14]
Reactant: Cc1nc(Cl)c2ccccc2n1
Reactant: CCOc1ccc(N)cc1
Product: CCOc1ccc(Nc2nc(C)nc3ccccc23)cc1

Procedure:
The title compound was prepared from 4-chloro-2-methylquinazoline and 4-ethoxyaniline by a procedure similar to example 28 (93%). 1H NMR (CDCl3): 7.83 (m, 1H), 7.81 (m, 1H), 7.42 (m, 1H), 7.65-7.71 (m, 2H), 7.46 (ddd, J=8.4, 6.9, 1.5, 1H), 7.37 (s, broad, 1H), 6.92-6.97 (m, 2H), 4.06 (q, J=6.9, 2H), 2.68 (s, 3H), 1.43 (t, J=6.9, 3H).
Reaction SMILES: [C:1](=O)([OH:3])[O-:2].[Na+:5].[C:6]([CH:9]([CH:11]([C:13]([O-:15])=[O:14])[OH:12])[OH:10])([OH:8])=[O:7].[K+:16]>O>[C:6]([CH:9]([CH:11]([C:13]([O-:15])=[O:14])[OH:12])[OH:10])([O-:8])=[O:7].[Na+:5].[K+:16].[C:1](=[O:3])=[O:2]
Reactant: O=C([O-])C(O)C(O)C(=O)O
Reactant: O=C([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: O
Product: O=C([O-])C(O)C(O)C(=O)[O-]
Product: O=C=O

Procedure:
The material selected for powder particles 16 should be inert with respect to the cellulosic material and reactive with respect to the moisture (e.g., water) to be absorbed. Preferably, the material selected for powder particles 16 should also generate water as a product of its chemical reaction with water. For example, if powder particles 16 comprise a mixture of sodium bicarbonate (NaHCO3) and citric acid (H3C6H5O7), a reaction of this mixture with water yields sodium citrate (Na3C6H5O7), carbon dioxide (CO2) and water (H2O). Another preferred example for powder particles 16 is a mixture of sodium bicarbonate (NaHCO3) and potassium hydrogen tartrate (KHC4H4O6). A reaction of this mixture with water yields potassium sodium tartrate (KNaC4H4O6), carbon dioxide and water. Note that any amount of water is sufficient to start the reaction. Once started, no additional water is needed as the reaction self-produces water.
Reaction SMILES: [NH:1]=[C:2]1[NH:6][C:5]([C:11]([F:14])([F:13])[F:12])([C:7]([F:10])([F:9])[F:8])[C:4](=[C:15]([F:20])[C:16]([F:19])([F:18])[F:17])[S:3]1.C(N(CC)CC)C.[F:28][C:29]([F:40])([F:39])[C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=1)[C:33](Cl)=[O:34]>C1(C)C=CC=CC=1>[F:28][C:29]([F:39])([F:40])[C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=1)[C:33]([NH:1][C:2]1[S:3][C:4](=[C:15]([F:20])[C:16]([F:17])([F:18])[F:19])[C:5]([C:7]([F:10])([F:9])[F:8])([C:11]([F:12])([F:13])[F:14])[N:6]=1)=[O:34]
Reactant: N=C1NC(C(F)(F)F)(C(F)(F)F)C(=C(F)C(F)(F)F)S1
Reactant: O=C(Cl)c1cccc(C(F)(F)F)c1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: O=C(NC1=NC(C(F)(F)F)(C(F)(F)F)C(=C(F)C(F)(F)F)S1)c1cccc(C(F)(F)F)c1
Temperature: 103 °C
Reaction time: 3 h

Procedure:
In toluene (40 ml) were dissolved 2-imino-4,4-bis(trifluoromethyl)-5-(tetrafluoroethylidene)-1,3-thiazolidine (2.0 g) and triethylamine (1.0 ml), and a solution of 3-trifluoromethylbenzoyl chloride (1.5 g) dissolved in toluene (10 ml) was gradually added thereto under cooling and the mixture was stirred at 103° C. for 3 hours.
Reaction SMILES: [C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[C:13]([C:24]([F:27])([F:26])[F:25])=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH:22]=O)[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[NH:28]1[CH2:31][CH:30]([C:32]([O:34][CH3:35])=[O:33])[CH2:29]1.[BH3-]C#N.[Na+]>C(O)C>[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[C:13]([C:24]([F:25])([F:26])[F:27])=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH2:22][N:28]2[CH2:31][CH:30]([C:32]([O:34][CH3:35])=[O:33])[CH2:29]2)[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)[C@H]1CC[C@H](Oc2ccc3cc(C=O)ccc3c2C(F)(F)F)CC1
Reactant: COC(=O)C1CNC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCO
Product: COC(=O)C1CN(Cc2ccc3c(C(F)(F)F)c(O[C@H]4CC[C@H](C(C)(C)C)CC4)ccc3c2)C1

Procedure:
A mixture of 6-(trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)-2-naphthaldehyde (300 mg, 0.8 mmol) and methyl azetidine-3-carboxylate (184 mg, 1.6 mmol, 2.0 equiv) in anhydrous ethanol (20 mL) was refluxed for 2 h. Then the solvent was removed in vacuo, fresh ethanol and NaBH3CN (150 mg, 2.4 mmol, 3.0 equiv) was added, the resulting mixture was refluxed for 1 h. The reaction mixture was concentrated and the residue was purified by chromatography with silica gel (dichloromethane:methanol 20:1) to give product methyl 1-((6-(trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)methyl)azetidine-3-carboxylate as a white solid (150 mg, yield: 40%), ESI-MS: 477.3 (M+H)+. HPLC: 85.67% 1H NMR (400 MHz, CD3OD) δ: 8.09 (dd, 1H), 8.01 (d, 1H), 7.56 (s, 1H), 7.46-7.51 (m, 2H), 4.42 (m, 1H), 3.77 (s, 2H), 3.71 (s, 3H), 3.57 (t, 2H), 3.45 (t, 2H), 3.35-3.39 (m, 1H), 2.18 (d, 2H), 1.88 (d, 2H), 1.43-1.52 (q, 2H), 1.09-1.22 (m, 3H), 0.89 (s, 9H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[CH:12][N:11]=[C:10]([C:20](O)=[O:21])[CH:9]=2)=[CH:4][CH:3]=1.[CH3:23][CH:24]([C:26]1[O:30][N:29]=[C:28]([CH2:31][NH2:32])[N:27]=1)[CH3:25]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:13]([O:14][CH2:15][C:16]([F:18])([F:17])[F:19])=[CH:12][N:11]=[C:10]([C:20]([NH:32][CH2:31][C:28]3[N:27]=[C:26]([CH:24]([CH3:25])[CH3:23])[O:30][N:29]=3)=[O:21])[CH:9]=2)=[CH:6][CH:7]=1
Reactant: CC(C)c1nc(CN)no1
Reactant: O=C(O)c1cc(-c2ccc(Cl)cc2)c(OCC(F)(F)F)cn1
Product: CC(C)c1nc(CNC(=O)c2cc(-c3ccc(Cl)cc3)c(OCC(F)(F)F)cn2)no1

Procedure:
The title compound was synthesized in analogy to Example 1, using 4-(4-chloro-phenyl)-5-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (example D) and 5-(1-methylethyl)-1,2,4-oxadiazole-3-methanamine, (CAN 936940-30-6) as starting materials; LC-MS (UV peak area/ESI) 100%, 455.1092 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=2)[CH:3]=1.C([Li])CCC.[CH3:24][Si:25]([CH3:51])([CH3:50])[O:26][C@@H:27]1[C@@H:32]([O:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C@H:31]([O:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[C@@H:30]([CH2:43][O:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[O:29][C:28]1=[O:49]>O1CCCC1>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C@@:28]2([OH:49])[C@H:27]([O:26][Si:25]([CH3:51])([CH3:50])[CH3:24])[C@@H:32]([O:33][Si:34]([CH3:35])([CH3:36])[CH3:37])[C@H:31]([O:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[C@@H:30]([CH2:43][O:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[O:29]2)=[CH:3][C:4]=1[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=1
Reactant: C[Si](C)(C)OC[C@H]1OC(=O)[C@H](O[Si](C)(C)C)[C@@H](O[Si](C)(C)C)[C@@H]1O[Si](C)(C)C
Reactant: CCOc1ccc(Cc2cc(Br)ccc2Cl)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCOc1ccc(Cc2cc([C@]3(O)O[C@H](CO[Si](C)(C)C)[C@@H](O[Si](C)(C)C)[C@H](O[Si](C)(C)C)[C@H]3O[Si](C)(C)C)ccc2Cl)cc1
Temperature: -78 °C
Reaction time: 0.67 h
Yield: 106.1 %

Procedure:
To a solution of 4-bromo-1-chloro-2-(4-ethoxyphenyl)methyl-benzene (30 g, 92.1 mmol, bought from Shanghai Kinsey pharmaceutical company) in anhydrous tetrahydrofuran (250 mL) was added n-butyllithium (40.3 mL, 96.7 mmol, 2.4 M in n-hexane) dropwise at −78° C. The mixture was stirred at −78° C. for 40 min and a solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-(trimethylsilyloxymethyl) tetrahydropyran-2-one 1b (47.3 g, 101.3 mmol) in anhydrous tetrahydrofuran (50 mL) was added dropwise. After the addition, the mixture was further stirred at −78° C. for 5 hours and then quenched with 100 mL of saturated aqueous ammonium chloride. The mixture was allowed to warm up to room temperature and concentrated in vacuo. To the residue was added 150 mL of water. The resulting mixture was extracted with ethyl acetate (150 mL×3). The combined organic layers were washed with saturated aqueous sodium chloride (200 mL), dried over anhydrous sodium sulfate and concentrated in vacuo to give the title compound 1c as pale yellow oil (69.7 g, 100%). This crude product was used in next step without further purification.