Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](=O)([O-])[O-].[K+].[K+].CI.[CH3:9][C:10]1[C:15]([C:16]([OH:18])=[O:17])=[CH:14][N:13]=[CH:12][CH:11]=1>CN(C)C=O>[CH3:9][C:10]1[C:15]([C:16]([O:18][CH3:1])=[O:17])=[CH:14][N:13]=[CH:12][CH:11]=1
Reactant: O=C([O-])[O-]
Reactant: Cc1ccncc1C(=O)O
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: COC(=O)c1cnccc1C
Temperature: 25 °C
Reaction time: 3 h
Yield: 33.4 %

Procedure:
In a nitrogen atmosphere, 6.89 g of potassium carbonate and 4.6 mL of methyl iodide were added in that order to N,N-dimethylformamide (100 mL) solution of 6.86 g of 4-methylnicotinic acid, and stirred at room temperature for 3 hours. The solvent was evaporated off under reduced pressure, then aqueous sodium hydrogencarbonate solution was added to the residue and extracted with chloroform. The chloroform layer was washed with saturated saline water, and dried with anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure, and the residue was separated and purified through silica gel column chromatography (hexane/ethyl acetate=50/50) to obtain 2.52 g of the entitled compound as a yellow oily substance.
Reaction SMILES: [CH3:1][S:2](Cl)=[O:3].[C:5]([NH:8][CH2:9][CH2:10][N:11]1[C:15]([CH3:16])=[CH:14][CH:13]=[C:12]1[CH3:17])(=[O:7])[CH3:6].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:5]([NH:8][CH2:9][CH2:10][N:11]1[C:12]([CH3:17])=[CH:13][C:14]([S:2]([CH3:1])=[O:3])=[C:15]1[CH3:16])(=[O:7])[CH3:6]
Reactant: CC(=O)NCCn1c(C)ccc1C
Reactant: CS(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)NCCn1c(C)cc(S(C)=O)c1C
Temperature: 0 °C
Reaction time: 0.75 h

Procedure:
19.7 g (0.2 mol) of methylsulphinyl chloride are dissolved in 500 ml of methylene chloride. 36.0 g (0.2 mol) of 1-(2-acetylaminoethyl)-2,5-dimethylpyrrole and 27.6 ml (0.2 mol) of triethylamine in 500 ml of methylene chloride are added dropwise at 0° C. and the mixture is stirred at 0° C. for 45 minutes and poured onto aqueous sodium bicarbonate solution. The organic phase is separated off and discarded. The aqueous phase is concentrated and the residue is boiled up with isopropanol and, after the mixture has been concentrated, the product is chromatographed.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]3[N:15]=[C:14]([O:16][C:17]4[C:23]([CH3:24])=[CH:22][C:20]([NH2:21])=[C:19]([CH3:25])[CH:18]=4)[S:13][N:12]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CO.CO[CH:30](OC)[N:31]([CH2:33][CH3:34])[CH3:32]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]3[N:15]=[C:14]([O:16][C:17]4[C:23]([CH3:24])=[CH:22][C:20]([N:21]=[CH:30][N:31]([CH2:33][CH3:34])[CH3:32])=[C:19]([CH3:25])[CH:18]=4)[S:13][N:12]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1
Reactant: CCN(C)C(OC)OC
Reactant: Cc1cc(Oc2nc(C3(c4ccc(Cl)cc4)CC3)ns2)c(C)cc1N
Solvent: Cc1ccccc1
Solvent: CO
Product: CCN(C)C=Nc1cc(C)c(Oc2nc(C3(c4ccc(Cl)cc4)CC3)ns2)cc1C
Yield: 61.6 %

Procedure:
0.30 g (0.81 mmol) of 4-({3-[1-(4-chlorophenyl)cyclopropyl]-1,2,4-thiadiazol-5-yl}oxy)-2,5-dimethylaniline is dissolved in 3 ml of toluene and 0.75 ml of methanol and treated with 0.32 g (2.42 mmol) of N-ethyl-N-methylformamide dimethylacetal. The reaction mixture is refluxed for 18 h, subsequently cooled, freed from the solvent under vacuum and purified by column chromatography. 0.22 g of product is obtained (99.3% purity, 61.7% yield; log P (pH2.3)=2.28).
Reaction SMILES: [C:1]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH:12]1[CH2:16][CH2:15][CH2:14][C:13]1=[O:17])([O:3][CH2:4][CH3:5])=[O:2].[C:18](OC(=O)C)(=[O:20])[CH3:19].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)(=O)C>[C:18]([O:17][C:13]1[CH2:14][CH2:15][CH2:16][C:12]=1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][C:1]([O:3][CH2:4][CH3:5])=[O:2])(=[O:20])[CH3:19]
Reactant: CC(=O)OC(C)=O
Reactant: CCOC(=O)CCCCCCC1CCCC1=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC(=O)O
Solvent: O
Product: CCOC(=O)CCCCCCC1=C(OC(C)=O)CCC1
Reaction time: 16 h

Procedure:
A stirred solution of 100 g. of 2-(6-carbethoxyhexyl)cyclopentan-1-one (Example 9) in 250 ml. of acetic anhydride containing 0.940 g. of p-toluenesulfonic acid monohydrate is heated to boiling under partial reflux allowing distillate at 118° C. or less (i.e., acetic acid) to escape through a Vigreaux column equipped with a condenser to collect the distillate. After 16 hours, during which period acetic anhydride is added in portions in order to keep the solvent level at at least 100 ml., the solution is cooled and poured cautiously into a stirred cold mixture of saturated sodium bicarbonate solution (400 ml.) and nexane (250 ml.). The resulting mixture is stirred for an additional 30 minutes during which period solid sodium bicarbonate is added periodically to insure a basic solution. The hexane layer is separated and washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness. Distillation of the residual oil gives 102 g. (87%) of pale yellow oil, b.p. 118° C. (0.07 mm.).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[CH:16]=2)[CH2:10][C@@H:9]1[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[Cl:30][C:31]1[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:32]=1[C:33](Cl)=[O:34]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:33](=[O:34])[C:32]3[CH:36]=[CH:37][C:38]([F:40])=[CH:39][C:31]=3[Cl:30])[CH:16]=2)[CH2:10][C@@H:9]1[CH3:22])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: C[C@H]1C[C@@H](Oc2cccc(N)c2)CCN1C(=O)OC(C)(C)C
Reactant: O=C(Cl)c1ccc(F)cc1Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C[C@H]1C[C@@H](Oc2cccc(NC(=O)c3ccc(F)cc3Cl)c2)CCN1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Combine 4-(3-amino-phenoxy)-cis-2-methyl-piperidine-1-carboxylic acid tert-butyl ester isomer 2 (preparation 39, 0.29 g), triethyl amine (95 mg), and 2-chloro-4-fluorobenzoyl chloride (0.201 g) in THF (10 mL) and stir at room temperature. After 18 hr., partition between ethyl acetate and saturated aqueous NaCl, dry over anhydrous sodium sulfate, evaporate and dry in vacuum to give the title compound (0.464 g). Mass spectrum (electrospray) m/z=461 (M−1); 1H NMR (CDCl3): 7.87 (br s, 1H), 7.72 (dd, 1H), 7.37 (t, 1H), 7.19 (dd, 1H), 7.13 (dd, 1H), 7.02 (ddd, 1H), 6.97 (dd, 1H), 6.64 (dd, 1H), 4.63 (m, 1H), 4.28 (m, 1H), 3.81 (m, 1H), 3.20 (m, 1H), 1.88 (m, 2H), 1.81 (m, 1H), 1.67 (m, 1H), 1.40 (s, 9H), 1.24 (d, J=7.1 Hz, 3H). (file: mn4-a01246-76).
Reaction SMILES: [ClH:1].[CH2:2]([NH:6][CH2:7][C@@H:8]([C@H:10]([C@@H:12]([C@@H:14]([CH2:16][OH:17])[OH:15])[OH:13])[OH:11])[OH:9])[CH2:3][CH2:4][CH3:5].[OH-].[Na+]>O>[ClH:1].[CH2:2]([NH:6][CH2:7][C@@H:8]1[O:9][C@:14]([OH:15])([CH2:16][OH:17])[C@@H:12]([OH:13])[C@@H:10]1[OH:11])[CH2:3][CH2:4][CH3:5]
Reactant: CCCCNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCCNC[C@@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O
Temperature: 15 °C
Reaction time: 23 h
Yield: 80 %

Procedure:
A reaction solution is prepared by adding 109 ml of a bulk solution of N-n-butylglucamine hydrochloride (prepared in Example 1) with a concentration of 500 gm/L by HPLC to 460 ml of water in a 1-L bioreactor. The solution is adjusted to pH 5 by adding dilute sodium hydroxide and cooled to about 15° C. A total of 30 gm (wet weight) of washed G. oxydans cell paste is added and the reaction mixture is agitated (500 rpm) and aerated (0.5 vvm) while controlling the temperature at 15° C. and pH at 5. After 23 hours, the HPLC assay indicates that over 99% of the substrate has been converted for a 80% yield of 6-n-butylamino-6-deoxy-α-L-sorbofuranose hydrochloride.
Reaction SMILES: [Si]([O:8][CH2:9][C:10]1[CH:11]=[C:12]([N:16]2[C:20]([NH2:21])=[CH:19][C:18]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[F:28])=[N:17]2)[CH:13]=[CH:14][CH:15]=1)(C(C)(C)C)(C)C.[Cl:29][C:30]1[C:35]([Cl:36])=[CH:34][CH:33]=[CH:32][C:31]=1[N:37]=[C:38]=[O:39]>>[Cl:29][C:30]1[C:35]([Cl:36])=[CH:34][CH:33]=[CH:32][C:31]=1[NH:37][C:38]([NH:21][C:20]1[N:16]([C:12]2[CH:13]=[CH:14][CH:15]=[C:10]([CH2:9][OH:8])[CH:11]=2)[N:17]=[C:18]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[F:28])[CH:19]=1)=[O:39]
Reactant: O=C=Nc1cccc(Cl)c1Cl
Reactant: CC(C)(C)[Si](C)(C)OCc1cccc(-n2nc(-c3ccccc3F)cc2N)c1
Product: O=C(Nc1cccc(Cl)c1Cl)Nc1cc(-c2ccccc2F)nn1-c1cccc(CO)c1
Yield: 59.4 %

Procedure:
Using general method A, 1-(3-((t-butyldimethylsilyloxy)methyl)phenyl)-3-(2-fluorophenyl)-1H-pyrazol-5-amine (available from ethyl 3-(5-amino-3-(2-fluorophenyl)-1H-pyrazol-1-yl)benzoate using general method C, followed by protection with TBSCl) (0.4 g, 1.0 mmol) was combined with 2,3-dichlorophenyl isocyanate (0.32 g, 1.2 mmol) to yield 1-(2,3-dichlorophenyl)-3-(3-(2-fluorophenyl)-1-(3-(hydroxymethyl)phenyl)-1H-pyrazol-5-yl)urea (0.28 g, 59% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.05 (s, 1H), 8.87 (s, 1H), 8.08 (m, 1H), 7.99 (dt, J=2.0, and 8.0 Hz, 1H), 7.58 (m, 1H), 7.55 (d, J=7.6 Hz, 1H), 7.50 (brd, J=7.6 Hz, 1H), 7.45 (brd, J=7.2 Hz, 1H), 7.41 (m, 1H), 7.32 (m, 3H), 6.91 (d, J=4.4 Hz, 1H), 5.39 (t, J=6.0 Hz, 1H), 4.62 (d, J=6.0 Hz, 2H); MS (EI) m/z: 471.0 (M+H+).
Reaction SMILES: [C:1]([C:3]1[C:4](=[O:19])[O:5][C:6]2[C:11]([C:12]=1[CH3:13])=[CH:10][CH:9]=[C:8]([O:14]CC=C)[C:7]=2[CH3:18])#[N:2].CO.C(N(CC)[C:25]1[CH:30]=CC=C[CH:26]=1)C>>[C:1]([C:3]1[C:4](=[O:19])[O:5][C:6]2[C:11]([C:12]=1[CH3:13])=[CH:10][C:9]([CH2:30][CH:25]=[CH2:26])=[C:8]([OH:14])[C:7]=2[CH3:18])#[N:2]
Reactant: CCN(CC)c1ccccc1
Reactant: C=CCOc1ccc2c(C)c(C#N)c(=O)oc2c1C
Solvent: CO
Product: C=CCc1cc2c(C)c(C#N)c(=O)oc2c(C)c1O
Yield: 76 %

Procedure:
A solution of 3-cyano-4,8-dimethyl-7-allyloxycoumarin (1.27 g, 4.97 mmoles) in 14 mL of N,N-diethylaniline was deoxygenated with argon for 30 minutes, and then was heated at reflux for 6 hours, while being purged by bubbling argon through the solution. The reaction mixture was chilled in ice, the resulting precipitate was collected by suction filtration and dried in vacuo. Recrystallisation from a mixture of benzene:methanol gave 0.97 g (76% yield) of 3-cyano-4,8-dimethyl-6-allyl-7-hydroxycoumarin (3, R═CN, R′=H) as a pale brown solid: mp 234-235° C.
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:34])[C@@H:5]([NH2:33])[CH2:6][C:7]1[CH:32]=[CH:31][C:10]2[O:11][C@@H:12]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=4)[CH:16]=3)[CH2:13][O:14][C:9]=2[CH:8]=1.C([O-])(O)=O.[Na+].[N+:40]([C:43]1[CH:48]=[CH:47][C:46]([S:49](Cl)(=[O:51])=[O:50])=[CH:45][CH:44]=1)([O-:42])=[O:41]>CCOC(C)=O>[CH3:2][O:3][C:4](=[O:34])[C@@H:5]([NH:33][S:49]([C:46]1[CH:45]=[CH:44][C:43]([N+:40]([O-:42])=[O:41])=[CH:48][CH:47]=1)(=[O:50])=[O:51])[CH2:6][C:7]1[CH:32]=[CH:31][C:10]2[O:11][C@@H:12]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=4)[CH:16]=3)[CH2:13][O:14][C:9]=2[CH:8]=1
Reactant: COC(=O)[C@@H](N)Cc1ccc2c(c1)OC[C@H](c1cccc(OCc3ccc(Cl)c(Cl)c3)c1)O2
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)Cl)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Product: COC(=O)[C@H](Cc1ccc2c(c1)OC[C@H](c1cccc(OCc3ccc(Cl)c(Cl)c3)c1)O2)NS(=O)(=O)c1ccc([N+](=O)[O-])cc1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 82.4 %

Procedure:
(S)-2-Amino-3-{(S)-2-[3-(3,4-dichloro-benzyloxy)-phenyl]-2,3-dihydro benzo[1,4]dioxin-6-yl}-propionic acid methyl ester hydrochloride (0.35 g) was taken in 2 mL of EtOAc and cooled to 0° C., NaHCO3 solution (1 mL) and 4-nitrobenzensulfonyl chloride (178 mg) were added and stirred for 10 minutes. Reaction was stirred at room temperature for 4 hours. EtOAc layer was separated and washed with water and brine, and then dried (Na2SO4), filtered and evaporated. The residue was purified by silica gel column (10% EtOAc in hexanes to 50% EtOAc in hexanes) to get pure (S)-3-{(S)-2-[3-(3,4-dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-2-(4-nitro-benzenesulfonylamino)-propionic acid methyl ester (0.37 g). 1H NMR (400 MHz, acetone-d6): 8.33 (m, 2H), 7.89 (m, 2H), 7.73 (d, 1H), 7.62 (d, 1H), 7.37-7.53 (m, 3H), 7.04-7.21 (m, 3H), 6.64-6.72 (m, 3H), 5.22 (s, 2H), 5.09 (m, 1H), 4.35 (m, 1H), 4.21 (m, 1H), 3.97 (m, 1H), 3.61 (s, 3H), 3.03 (m, 1H), 2.76 (m, 1H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:31])[CH2:4][CH2:5][NH:6][C:7]([C:9]1[S:10][C:11]([CH:14]([O:21][C:22]2[CH:27]=[C:26]([CH3:28])[C:25](I)=[C:24]([CH3:30])[CH:23]=2)[CH2:15][CH2:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:13]=1)=[O:8].[F:32][C:33]([F:45])([F:44])[O:34][C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1>>[CH3:1][O:2][C:3](=[O:31])[CH2:4][CH2:5][NH:6][C:7]([C:9]1[S:10][C:11]([CH:14]([O:21][C:22]2[CH:27]=[C:26]([CH3:28])[C:25]([C:38]3[CH:37]=[CH:36][C:35]([O:34][C:33]([F:32])([F:44])[F:45])=[CH:40][CH:39]=3)=[C:24]([CH3:30])[CH:23]=2)[CH2:15][CH2:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:13]=1)=[O:8]
Reactant: OB(O)c1ccc(OC(F)(F)F)cc1
Reactant: COC(=O)CCNC(=O)c1ccc(C(CCC(F)(F)F)Oc2cc(C)c(I)c(C)c2)s1
Product: COC(=O)CCNC(=O)c1ccc(C(CCC(F)(F)F)Oc2cc(C)c(-c3ccc(OC(F)(F)F)cc3)c(C)c2)s1

Procedure:
This compound is made by the general method as exemplified in Preparation 77 using 3-({5-[4,4,4-trifluoro-1-(4-iodo-3,5-dimethyl-phenoxy)-butyl]-thiophene-2-carbonyl}-amino)-propionic acid methyl ester - chiral Isomer 1 and 4-trifluoromethoxy-phenyl boronic acid as the starting materials. MS(ES): 604.3 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]([CH3:23])[C:13](=[O:22])[N:14]([C:15]4[C:16]([CH3:21])=[N:17][N:18]([CH3:20])[CH:19]=4)[C:5]=3[C:4]=2[CH:3]=1.NC1C(C)=NN(C[CH2:31][OH:32])C=1>>[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]([CH3:23])[C:13](=[O:22])[N:14]([C:15]4[C:16]([CH3:21])=[N:17][N:18]([CH2:20][CH2:31][OH:32])[CH:19]=4)[C:5]=3[C:4]=2[CH:3]=1
Reactant: Cc1nn(CCO)cc1N
Reactant: Cc1nn(C)cc1-n1c(=O)n(C)c2cnc3ccc(Br)cc3c21
Product: Cc1nn(CCO)cc1-n1c(=O)n(C)c2cnc3ccc(Br)cc3c21

Procedure:
Alternatively, the title compound was synthesized in a similar manner as described for intermediate A starting from 2-(4-amino-3-methyl-pyrazol-1-yl)-ethanol (Stage 103.1.2).
Reaction SMILES: [OH-:1].[Na+:2].[NH2:3][C@H:4]([C:9]([OH:11])=[O:10])[CH2:5][C:6]([OH:8])=[O:7]>O>[Na+:2].[Na+:2].[Na+:2].[Na+:2].[OH:1][CH:4]([C:9]([O-:11])=[O:10])[CH:5]([NH:3][CH:4]([CH2:5][C:6]([O-:8])=[O:7])[C:9]([O-:11])=[O:10])[C:6]([O-:8])=[O:7]
Reactant: N[C@@H](CC(=O)O)C(=O)O
Reactant: [OH-]
Agent: [Na+]
Solvent: O
Product: O=C([O-])CC(NC(C(=O)[O-])C(O)C(=O)[O-])C(=O)[O-]

Procedure:
8.0 g (0.2 mol) sodium hydroxide and then 17.6 g (0.1 mol) cis-epoxysuccinic acid disodium salt were added with stirring at room temperature to 13.3 g (0.1 mol) L-aspartic acid in 50 ml water. The clear, pale yellow solution was heated under reflux for 8 hours. The solvent was then removed in a rotary evaporator (vacuum). 3-Hydroxy-2,2'-iminodisuccinic acid tetrasodium salt (B1) in the form of a C(3) epimer mixture was obtained in a yield of 36.8 g. According to 1H-NMR, the colorless solid contained approx. 5% by weight disodium tartrate (signal at=4.40).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][NH:13][C:14](=[O:25])[C@@:15]([NH2:24])([S:19]([CH:21]([CH3:23])[CH3:22])=[O:20])[CH:16]([CH3:18])[CH3:17])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[Mn]([O-])(=O)(=O)=[O:27].[K+].[Mn]([O-])(=O)(=O)=O>CC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][NH:13][C:14](=[O:25])[C@@:15]([NH2:24])([S:19]([CH:21]([CH3:23])[CH3:22])(=[O:27])=[O:20])[CH:16]([CH3:18])[CH3:17])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: O=[Mn](=O)(=O)[O-]
Reactant: COc1ccc(CCNC(=O)[C@](N)(C(C)C)S(=O)C(C)C)cc1OC
Agent: [K+]
Solvent: CC(C)=O
Product: COc1ccc(CCNC(=O)[C@](N)(C(C)C)S(=O)(=O)C(C)C)cc1OC
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
3.7 g of (S)-2-(isopropylsulfinyl)-amino-3-methyl-butyric acid N-[2-(3,4-dimethoxyphenyl)-ethyl]-amide (Example 3.90) are dissolved in 50 ml of acetone at room temperature. An acetone solution saturated with potassium permanganate is added dropwise to this stirred solution until the reaction mixture retains the violet colour of the permanganate; the reaction mixture is then stirred at room temperature for 45 minutes. The resulting manganese dioxide is removed by filtration over Celite. The filtrate is evaporated to dryness and the resulting residue is dissolved in 500 ml of methyl acetate. This organic phase is washed once with 200 ml of water, dried over sodium sulfate and concentrated. The resulting residue is chromatographed over silica gel with a mixture of one part of methyl acetate and one part of n-hexane. (S)-2-(isopropylsulfonyl)-amino-3-methyl-butyric acid N-[2-(3,4-dimethoxyphenyl)-ethyl]-amide, which can be further purified by recrystallization from methyl acetate/n-hexane, is obtained, melting point 86°-87° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[O:8])=[CH:5][C:4]=1[C:11]1[C:20]([CH3:21])=[CH:19][C:18]2[C:17]([CH3:23])([CH3:22])[CH2:16][CH:15]([CH3:24])[CH:14]([CH3:25])[C:13]=2[CH:12]=1.[BH4-].[Na+]>CO>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][OH:8])=[CH:5][C:4]=1[C:11]1[C:20]([CH3:21])=[CH:19][C:18]2[C:17]([CH3:23])([CH3:22])[CH2:16][CH:15]([CH3:24])[CH:14]([CH3:25])[C:13]=2[CH:12]=1
Reactant: COc1ccc(C=O)cc1-c1cc2c(cc1C)C(C)(C)CC(C)C2C
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COc1ccc(CO)cc1-c1cc2c(cc1C)C(C)(C)CC(C)C2C
Temperature: 0 °C
Reaction time: 1 h
Yield: 97.6 %

Procedure:
To a solution of 4-methoxy-3-(3,5,5,8,7-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl) benzaldehyde (200 mg, 0.59 mmol) in methanol (5 mL) was added at 0° C. in small portions sodium borohydride (70 mg, 1.77 mmol). The solution was stirred 1 hour at 0° C. then quenched with 2N HCl. The reaction mixture was diluted with ethyl acetate and washed successively with water and brine, dried over anhydrous magnesium sulfate; filtered and evaporated to afford 195 mg (98%) of 4-methoxy-3-(3,5,5,8,7-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl) benzyl alcohol.
Reaction SMILES: [F:1][C:2]1[N:7]=[C:6]([F:8])[C:5]([S:9][CH3:10])=[C:4](F)[N:3]=1.[NH3:12]>>[NH2:12][C:4]1[C:5]([S:9][CH3:10])=[C:6]([F:8])[N:7]=[C:2]([F:1])[N:3]=1
Reactant: N
Reactant: CSc1c(F)nc(F)nc1F
Product: CSc1c(N)nc(F)nc1F

Procedure:
If, for example, 2,4,6-trifluoro-5-methylthiopyrimidine and ammonia are used as starting substances according to process (B), and the 4-amino-2,6-difluoro-5-methylthio-pyrimidine thereby formed is reacted with 3-methoxypropylamine, the course of the reaction can be represented in summary form by the following equation: ##STR10##
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:7]([CH3:10])([CH3:9])[CH3:8])=[N:5][N:6]=1.[CH2:11]([C:23]1[CH:28]=[CH:27][C:26]([S:29](Cl)(=[O:31])=[O:30])=[CH:25][CH:24]=1)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].Cl>N1C=CC=CC=1>[C:7]([C:4]1[S:3][C:2]([NH:1][S:29]([C:26]2[CH:27]=[CH:28][C:23]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:24][CH:25]=2)(=[O:31])=[O:30])=[N:6][N:5]=1)([CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)(C)c1nnc(N)s1
Reactant: CCCCCCCCCCCCc1ccc(S(=O)(=O)Cl)cc1
Agent: Cl
Solvent: c1ccncc1
Product: CCCCCCCCCCCCc1ccc(S(=O)(=O)Nc2nnc(C(C)(C)C)s2)cc1
Temperature: 95 °C
Reaction time: 1 h
Yield: 86.2 %

Procedure:
2-Amino-5-tert-butyl-1,3,4-thiadiazole (204 mg, 1.3 mmol) was suspended in pyridine (0.5 mL). p-Dodecylbenzenesulfonyl chloride (300 mg, 0.87 mmol) was added slowly at 0° C. The reaction mixture was then heated to 95° C. and was stirred at this temperature for 1 h. The reaction mixture was then added to aqueous 10% HCl (5 mL) and the resulting mixture extracted with ethyl acetate (3×10 mL). The organic extracts were washed with water, brine, dried over anhydrous Na2SO4, filtered, and volatiles evaporated to yield a solid mass. Chromatography on silica gel (70-230 mesh) eluted with 2% MeOH in CH2Cl2 gave the product (350 mg, 0.75 mmol, 87%). Recrystallization from hexanes:ethyl acetate (3:7) gave an analytical sample, mp 117-118° C.; 1H NMR (500 MHz, CDCl3) δ 0.88 (3, t, J=6.5 Hz), 1.20-1.36 (18, m), 1.38 (9, s), 1.56-1.64 (2, m), 2.63 (2, t, J=7.5 Hz), 7.25 (2, d, J=8.0 Hz), 7.86 (2, d, J=8.0 Hz), 12.24 (1, br s); 13C NMR (125 MHz, CDCl3) δ 14.1, 22.7, 29.2, 29.3, 29.4, 29.5, 29.6, 29.7, 31.1, 31.8, 35.8, 36.5, 126.5, 128.7, 138.5, 148.1, 167.8, 168.0; MS (ESI+, m/z) Calcd for C24H40N3O2S2 466.3. found 466.2 (M+H)+; HRMS (ESI+, m/z) Calcd for C24H40N3O2S2 466.2562. found 466.2562 (M+H)+.
Reaction SMILES: [CH3:1][CH:2]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][O:12][CH2:13][CH:14]1[O:16][CH2:15]1.[CH2:23]([CH2:25][NH2:26])[OH:24]>C(O)C>[OH:24][CH2:23][CH2:25][NH:26][CH2:15][CH:14]([OH:16])[CH2:13][O:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH:2]([CH3:1])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: NCCO
Reactant: CCCCCCC(C)CCCCCCCCCOCC1CO1
Solvent: CCO
Product: CCCCCCC(C)CCCCCCCCCOCC(O)CNCCO
Temperature: 80 °C

Procedure:
By use of ethanol (4 ml), 10-methylhexadecylglycidyl ether (100 mg, 0.32 mmol) was transferred to a 10 ml dropping funnel, which was fitted to a 20 ml round bottomed flask containing ethanolamine (1 ml) and ethanol (0.2 ml). The content of the flask was stirred at 80° C. in a nitrogen atmosphere. The ethanol solution was added dropwise over 10 minutes. The mixture was stirred for a further 1 hour, and then condensed under reduced pressure. The resulting residue was purified by silica gel flush chromatography. 94 mg of the title compound was obtained as a pale yellow Vaseline-like material (yield: 79%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[CH:4][C:3]=1[N:11]1[C:20](=[O:21])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][C:12]1=[O:22].O.O.[Sn](Cl)Cl.[OH-].[Na+]>C(OCC)(=O)C>[NH2:8][C:6]1[CH:5]=[CH:4][C:3]([N:11]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[NH:13][C:12]2=[O:22])=[C:2]([Br:1])[CH:7]=1
Reactant: O=c1[nH]c2ccccc2c(=O)n1-c1ccc([N+](=O)[O-])cc1Br
Agent: Cl[Sn]Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCOC(C)=O
Product: Nc1ccc(-n2c(=O)[nH]c3ccccc3c2=O)c(Br)c1
Temperature: 70 °C
Yield: 93.3 %

Procedure:
A suspension of 3-(2-bromo-4-nitrophenyl)-1,3-dihydroquinazoline-2,4-dione (0.18 g, 0.5 mmol) and tin (II) chloride dihydrate (0.45 g, 2.0 mmol) in ethyl acetate (5 mL) was heated at 70° C. for 4 hr. The reaction mixture was then cooled, mixed with Celite, made basic with 4N NaOH (3 mL), filtered through Celite, and concentrated in vacuo to give the desired compound (0.155 g, 94%). ES-MS (M+H)+=332, 334 (Br).
Reaction SMILES: [F:1][C:2]1[CH:18]=[CH:17][C:5]([C:6]([N:8]2[CH2:13][CH2:12][CH2:11][CH:10]([C:14]([OH:16])=O)[CH2:9]2)=[O:7])=[CH:4][CH:3]=1.[C:19]([O:23][C:24]([NH:26][NH2:27])=[O:25])([CH3:22])([CH3:21])[CH3:20].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[C:19]([O:23][C:24]([NH:26][NH:27][C:14]([CH:10]1[CH2:11][CH2:12][CH2:13][N:8]([C:6](=[O:7])[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:18][CH:17]=2)[CH2:9]1)=[O:16])=[O:25])([CH3:22])([CH3:21])[CH3:20]
Reactant: CC(C)(C)OC(=O)NN
Reactant: O=C(O)C1CCCN(C(=O)c2ccc(F)cc2)C1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NNC(=O)C1CCCN(C(=O)c2ccc(F)cc2)C1
Reaction time: 72 h
Yield: 72.4 %

Procedure:
To a solution of 1-(4-Fluoro-benzoyl)-piperidine-3-carboxylicacid (1.13 g, 4.50 mmol) in DCM (6.5 ml) was successively added Hydrazinecarboxylic acid tert-butyl ester (0.59 g, 4.50 mmol), HOBT (0.69 g, 4.50 g) anf EDCI.HCl (1.29 g, 6.758 mmol). The mixture was stirred at R.T for 72 h. The solvent was removed under reduced pressure and the residue was diluted with DCM was added. The organic layer was washed twice with water, twice with HCl 1N and twice with water. The organic layer was dried over Na2SO4, filtered and evaporated to afford 1.19 g (73%) of N′-[1-(4-Fluoro-benzoyl)-piperidine-3-carbonyl]-hydrazinecarboxylic acid tert-butyl ester as a colorless semi-solid.