Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-:1].[K+].[CH3:3][C:4]1[N:8]([CH2:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][CH:11]=2)[C:7]2[CH:20]=[C:21]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[CH:22]=[C:23]([C:24]#[N:25])[C:6]=2[N:5]=1.OO>O.C1COCC1>[CH3:3][C:4]1[N:8]([CH2:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][CH:11]=2)[C:7]2[CH:20]=[C:21]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[CH:22]=[C:23]([C:24]([NH2:25])=[O:1])[C:6]=2[N:5]=1
Reactant: [OH-]
Reactant: Cc1nc2c(C#N)cc(N3CCOCC3)cc2n1Cc1cccc2ccccc12
Agent: OO
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: Cc1nc2c(C(N)=O)cc(N3CCOCC3)cc2n1Cc1cccc2ccccc12
Temperature: 35 °C
Yield: 72 %

Procedure:
A solution of KOH (45 mg, 0.8 mmol) in water (10 mL) was added dropwise to solution of 2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carbonitrile (prepared using the same procedure as Example 24, 150 mg, 0.4 mmol) and 30% H2O2 (3 ml) in THF (15 mL) at rt. The mixture was heated to 35° C. for 1 h. When TLC showed no starting material remaining, water (50 mL) was added, then it was filtered. The filter cake was purified by silica gel chromatography eluted with petroleum ether:EtOAc=1:2 to give the product (115 mg, 72%), as a white solid. 1H NMR (300 MHz, DMSO-d6): δ ppm 2.47 (s, 3H), 3.05 (t, 4H, J=4.8 Hz), 3.69 (t, 4H, J=4.8 Hz), 6.05 (s, 2H), 6.34 (d, 1H, J=7.2 Hz), 7.25 (d, 1H, J=2.4 Hz), 7.34 (t, 1H, J=7.8 Hz), 7.53 (d, 1H, J=2.4 Hz), 7.63-7.70 (m, 2H,), 7.77 (d, 1H, J=3.0 Hz), 7.86 (d, 1H, J=8.1 Hz), 8.01 (d, 1H, J=7.2 Hz), 8.24 (d, 1H, J=8.1 Hz), 9.24 (d, 1H, J=3.0 Hz); LC-MS: m/e=401 [M+1]+
Reaction SMILES: [NH2:1][CH2:2][C:3]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:16]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N:17][O:18][C:19]=2[CH3:20])=[CH:11][CH:10]=1)(=[O:8])=[O:7])=[O:4].C(N(CC)CC)C.[C:34](OC(=O)C)(=[O:36])[CH3:35]>C(#N)C>[C:34]([NH:1][CH2:2][C:3]([NH:5][S:6]([C:9]1[CH:10]=[CH:11][C:12]([C:15]2[C:16]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N:17][O:18][C:19]=2[CH3:20])=[CH:13][CH:14]=1)(=[O:8])=[O:7])=[O:4])(=[O:36])[CH3:35]
Reactant: Cc1onc(-c2ccccc2)c1-c1ccc(S(=O)(=O)NC(=O)CN)cc1
Reactant: CC(=O)OC(C)=O
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CC(=O)NCC(=O)NS(=O)(=O)c1ccc(-c2c(-c3ccccc3)noc2C)cc1
Reaction time: 2 h
Yield: 72.1 %

Procedure:
The 2-amino-N-[[4-(5-methyl-3-phenylisoxazol-4-yl)phenyl]sulfonyl]acetamide (Example 79)(4.08 g, 10.9 mmol) was mixed in acetonitrile at room temperature. Triethylamine (3.03 g, 30.0 mmol) and acetic anhydride (1.23 g, 12.1 mmol) were added and the heterogeneous solution was stirred for 2 hours. The solution was vacuum filtered through a pad of diatomaceous earth and solvent was removed at reduced pressure. Water was added and the solution was stirred for 30 minutes. White crystals formed, were collected by vacuum filtration and dried to afford the desired product as a white solid (3.25 g, 78%): mp 218.2-219.3° C. 1H NMR (CD3OD/300 MHz) 8.01 (d, 2H, J=8.2 Hz), 7.42-7.36 (m, 7H), 3.85 (s, 2H), 2.50 (s, 3H), 1.95 (s, 3H). FABLRMS m/z 414 (M+H). Anal. Calc'd for C20H19N3O5S: C, 58.10; H, 4.63; N, 10.16. Found: C, 58.18; H, 4.66; N, 10.14.
Reaction SMILES: FC1C=CC(S(CCC)(=O)=O)=CC=1C#C[Si](C)(C)C.[C:20]([O:24][C:25](=[O:37])[CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=1[C:35]#[CH:36])([CH3:23])([CH3:22])[CH3:21].Br[C:39]1[CH:44]=[CH:43][C:42]([C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([Cl:51])[CH:46]=2)=[C:41]([S:52]([CH3:55])(=[O:54])=[O:53])[CH:40]=1>>[C:20]([O:24][C:25](=[O:37])[CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=1[C:35]#[C:36][C:39]1[CH:44]=[CH:43][C:42]([C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([Cl:51])[CH:46]=2)=[C:41]([S:52]([CH3:55])(=[O:53])=[O:54])[CH:40]=1)([CH3:23])([CH3:22])[CH3:21]
Reactant: C#Cc1cc(Cl)ccc1OCC(=O)OC(C)(C)C
Reactant: CS(=O)(=O)c1cc(Br)ccc1-c1cccc(Cl)c1
Agent: CCCS(=O)(=O)c1ccc(F)c(C#C[Si](C)(C)C)c1
Product: CC(C)(C)OC(=O)COc1ccc(Cl)cc1C#Cc1ccc(-c2cccc(Cl)c2)c(S(C)(=O)=O)c1

Procedure:
Following the general method as outlined in Intermediate 107, starting from (4-chloro-2-ethynyl-phenoxy)-acetic acid tert-butyl ester (Intermediate 3) and 4-bromo-3′-chloro-2-(methylsulfonyl)biphenyl (Intermediate 213), the title compound was obtained as a brown sticky solid after purification by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc.
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[C@@H:7]1[CH2:11][C@@H:10]([OH:12])[CH2:9][N:8]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])([CH3:4])([CH3:3])[CH3:2].[CH3:21][S:22](Cl)(=[O:24])=[O:23]>N1C=CC=CC=1.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:20])[C@@H:7]1[CH2:11][C@@H:10]([O:12][S:22]([CH3:21])(=[O:24])=[O:23])[CH2:9][N:8]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])([CH3:4])([CH3:3])[CH3:2]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)[C@@H]1C[C@@H](O)CN1C(=O)OC(C)(C)C
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)[C@@H]1C[C@@H](OS(C)(=O)=O)CN1C(=O)OC(C)(C)C
Reaction time: 2 h

Procedure:
To a solution of (4R)-1-(tert-butyloxycarbonyl)-4-hydroxy-L-proline tert-butyl ester (573 mg, 1.99 mmol) in pyridine (3.5 mL) cooled to 0° C. was added methanesulfonyl chloride (0.31 mL, 3.99 mmol). The reaction mixture was stirred for 2 hours at ice temperature, diluted with ethyl acetate (30 mL), washed with 1M sodium hydrogencarbonate solution, 1M citric acid, water, dried (Na2SO4), and evaporated. The crude product was purified by flash silica gel chromatography eluting with 1% methanol/dichloromethane; yield 686 mg (94%). 400 MHz 1H NMR (CDCl3): δ1.42-1.44 (2s, 18H); 2.20 (m, 1H); 2.60 (m, 1H); 3.02 (s, 3H); 3.68-3.86 (m, 2H); 4.29 (m, 1H); 5.22 (m, 1H).
Reaction SMILES: [NH2:1][C:2](=[N:23][OH:24])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:16])[CH2:11][CH2:10]2)[CH:4]=1.[CH3:25][O:26][CH2:27]C(Cl)=O>N1C=CC=CC=1.C(OCC)(=O)C>[CH3:25][O:26][C:27]1[O:24][N:23]=[C:2]([C:3]2[CH:8]=[CH:7][N:6]=[C:5]([N:9]3[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:16])[CH2:11][CH2:10]3)[CH:4]=2)[N:1]=1
Reactant: CC(C)(C)COC(=O)N1CCN(c2cc(C(N)=NO)ccn2)CC1
Reactant: COCC(=O)Cl
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: COc1nc(-c2ccnc(N3CCN(C(=O)OCC(C)(C)C)CC3)c2)no1

Procedure:
2,2-Dimethylpropyl 4-{4-[amino(hydroxyimino)methyl]pyridin-2-yl}piperazine-1-carboxylate (84 mg) obtained in Example 26-1) was dissolved in pyridine (2 mL), and methoxyacetyl chloride (0.035 mL) was added thereto and heated under reflux for 90 minutes. The reaction liquid was diluted with ethyl acetate, washed with 1 N hydrochloric acid, aqueous saturated sodium hydrogencarbonate solution and saturated saline water, and dried with anhydrous sodium sulfate. The solvent was evaporated away, and the resulting residue was isolated and purified through silica gel column chromatography (hexane/ethyl acetate=7/3) to obtain 54 mg of the entitled compound as a colorless oil.
Reaction SMILES: [N+:1]([C:4]1[N:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18](=[O:21])[CH2:19][CH3:20])[CH:12]=2)=[CH:6][CH:5]=1)([O-])=O.[NH4+].[Cl-]>CO.C1COCC1.[Zn]>[NH2:1][C:4]1[N:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18](=[O:21])[CH2:19][CH3:20])[CH:12]=2)=[CH:6][CH:5]=1
Reactant: CCC(=O)Nc1cc(Oc2ccc([N+](=O)[O-])nc2)ccn1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: C1CCOC1
Solvent: CO
Product: CCC(=O)Nc1cc(Oc2ccc(N)nc2)ccn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 221.9 %

Procedure:
A solution of N-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)propionamide (0.513 g, 1.780 mmol) in MeOH (10 mL) and THF (10 mL) was treated with NH4Cl (3.81 g, 71.2 mmol) followed by zinc dust (1.164 g, 17.80 mmol) and stirred at RT overnight. Additional zinc dust (1 g) was added the mixture stirred at RT for 2 days. The solids were removed via filtration, washed with THF and filtrate concentrated to dryness. The material was suspended in THF, sonicated, the resulting solid removed via filtration and the filtrate concentrated to dryness to afford crude N-(4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)propionamide (1.02 g, 222%) which was carried on without further purification. MS (ESI) m/z: 259.1 (M+H+).
Reaction SMILES: [Br:1][CH2:2][CH2:3][NH:4][S:5]([C:7]([CH3:10])([CH3:9])[CH3:8])=[O:6].C1C=C(Cl)C=C(C(OO)=[O:19])C=1>>[Br:1][CH2:2][CH2:3][NH:4][S:5]([C:7]([CH3:10])([CH3:9])[CH3:8])(=[O:19])=[O:6]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(C)(C)S(=O)NCCBr
Product: CC(C)(C)S(=O)(=O)NCCBr
Temperature: 25 °C
Reaction time: 2 h
Yield: 46.8 %

Procedure:
To a solution of 2-methyl-propane-2-sulfinic acid (2-bromo-ethyl)-amide (0.8 g, 3.5 mmol) was added mCPBA (77%, 0.95 g, 4.2 mmol) and stirred at a temperature of about 25° C. for 2 hrs. The reaction mixture was condensed and purified to provide 2-methyl-propane-2-sulfonic acid (2-bromo-ethyl)-amide as a white solid (0.4 g, 46% yield).
Reaction SMILES: C(OC([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][S:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)=O)(C)(C)C.Cl>CO.C(OCC)C>[O:21]([C:18]1[CH:19]=[CH:20][C:15]([S:14][CH2:13][C@H:9]2[CH2:10][CH2:11][CH2:12][NH:8]2)=[CH:16][CH:17]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1CSc1ccc(Oc2ccccc2)cc1
Agent: Cl
Solvent: CO
Solvent: CCOCC
Product: c1ccc(Oc2ccc(SC[C@H]3CCCN3)cc2)cc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 67.1 %

Procedure:
To the product from step 1 (272 mg, 0.705 mmol) in methanol (3 mL) was added 2M HCl in diethyl ether (12 mL) and the resulting mixture was stirred at rt for 6 h. The solvent was removed in vacuo to obtain the title product as a solid (135 mg, 94%); MS; m/z 286 (M+H); LCMS (UV) 99%. 1H NMR (400 MHz, CD3OD) δ 1.73-1.81 (m, 1H), 2.0-2.11 (m, 2H), 2.21-2.27 (m, 1H), 3.08-3.13 (m, 2H), 3.26-3.36 (m, 2H), 3.61-3.64 (m, 1H), 7.50 (d, 2H, J=11.6 Hz), 7.35-7.39 (m, 2H), 7.15 (t, 1H, J=16 Hz); 6.96-7.01 (m, 4H)
Reaction SMILES: Cl.[CH3:2][C:3]1([CH3:31])[CH2:7][CH:6]2[CH:8]([CH3:30])[C:9]([S:14]([NH:17][C:18](=[NH:29])[NH:19][CH2:20][CH2:21][CH2:22][C@@H:23]([C:25]([O:27][CH3:28])=[O:26])[NH2:24])(=[O:16])=[O:15])=[C:10]([CH3:13])[C:11]([CH3:12])=[C:5]2[O:4]1.C(N(CC)CC)C.[F:39][C:40]1[CH:50]=[CH:49][CH:48]=[CH:47][C:41]=1[CH:42]=[CH:43][C:44](O)=[O:45].CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[F:39][C:40]1[CH:50]=[CH:49][CH:48]=[CH:47][C:41]=1[CH:42]=[CH:43][C:44]([NH:24][C@H:23]([C:25]([O:27][CH3:28])=[O:26])[CH2:22][CH2:21][CH2:20][NH:19][C:18](=[NH:29])[NH:17][S:14]([C:9]1[CH:8]([CH3:30])[CH:6]2[CH2:7][C:3]([CH3:31])([CH3:2])[O:4][C:5]2=[C:11]([CH3:12])[C:10]=1[CH3:13])(=[O:15])=[O:16])=[O:45]
Reactant: O=C(O)C=Cc1ccccc1F
Reactant: COC(=O)[C@@H](N)CCCNC(=N)NS(=O)(=O)C1=C(C)C(C)=C2OC(C)(C)CC2C1C
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)[C@H](CCCNC(=N)NS(=O)(=O)C1=C(C)C(C)=C2OC(C)(C)CC2C1C)NC(=O)C=Cc1ccccc1F
Yield: 98.9 %

Procedure:
The same procedures as in Example 2 were carried out from methyl Nω-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-L-argininate hydrochloride (5.0 g), triethylamine (1.8 mL), 2-fluorocinnamic acid (2.1 g), WSC.HCl (2.4 g), and methylene chloride (150 mL), to give the captioned compound (6.1 g, 99%) as an amorphous solid product.
Reaction SMILES: [N-:1]=[N+]=[N-].[Na+].Cl[CH2:6][C:7]([NH:9][C:10]([CH3:17])([CH3:16])[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])=[O:8]>O.CO.[Pd]>[NH2:1][CH2:6][C:7]([NH:9][C:10]([CH3:17])([CH3:16])[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])=[O:8]
Reactant: CCCCCC(C)(C)NC(=O)CCl
Reactant: [N-]=[N+]=[N-]
Agent: [Pd]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CCCCCC(C)(C)NC(=O)CN

Procedure:
A solution of sodium azide (6.7 g, 103 m mol) in water (56 ml) and methanol(104 ml) was treated with 2-chloro-N-(1,1-dimethylhexyl)acetamide (16.5 g, 80 m mol) and the mixture was refluxed for 5 hours. After cooling, the mixture was extracted with 40-60 petrol (3×200 ml), the extracts were dried over magnesium sulphate and evaporated under reduced pressure to give crude 2-azido-N-(1,1-dimethylhexyl)acetamide as a pale yellow oil.This oil was dissolved in methanol (200 ml) and hydrogenated over 10% palladium on charcoal (3.2 g) at atmospheric pressure and room temperaturefor 24 hours. The mixture was filtered and the filtrate evaporated to give a crude oil (13.6 g) which was distilled to give 2-amino-N-(1,1-dimethylhexyl)acetamide as a colourless oil, b.p. 88°-90° C. at 0.05 mm Hg.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[C:8]([C:10]2[CH:15]=[C:14]([S:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([OH:23])[CH:18]=3)[N:13]=[C:12]([NH2:24])[N:11]=2)[C:7]([CH3:25])=[CH:6][C:5]=1[O:26][CH3:27].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O.[C:40]([O:44][C:45](=[O:51])[NH:46][CH2:47][CH2:48][CH2:49]Br)([CH3:43])([CH3:42])[CH3:41]>C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[C:8]([C:10]2[CH:15]=[C:14]([S:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH2:49][CH2:48][CH2:47][NH:46][C:45]([O:44][C:40]([CH3:41])([CH3:43])[CH3:42])=[O:51])[CH:18]=3)[N:13]=[C:12]([NH2:24])[N:11]=2)[C:7]([CH3:25])=[CH:6][C:5]=1[O:26][CH3:27]
Reactant: COC(=O)c1cc(-c2cc(Sc3cccc(O)c3)nc(N)n2)c(C)cc1OC
Reactant: CC(C)(C)OC(=O)NCCCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)c1cc(-c2cc(Sc3cccc(OCCCNC(=O)OC(C)(C)C)c3)nc(N)n2)c(C)cc1OC
Temperature: 25 °C
Reaction time: 37 h
Yield: 92.9 %

Procedure:
5-[2-Amino-6-(3-hydroxyphenylsulfanyl)pyrimidin-4-yl]-2-methoxy-4-methylbenzoic acid methyl ester (80 mg, 0.2 mmol) obtained in Step 1 above, cesium carbonate (124 mg, 0.38 mmol), and N,N-dimethylformamide (1.0 ml) were added to a reaction vessel. Then 3-bromopropylcarbamic acid tert-butyl ester (100 mg, 0.42 mmol) was added to the mixture. The mixture was stirred at room temperature for 37 hours. The reaction solution was diluted with ethyl acetate (100 ml), and sequentially washed twice with a saturated aqueous ammonium chloride solution (50 ml), twice with water (50 ml), and with a saturated aqueous sodium chloride solution (50 ml). The washed ethyl acetate solution was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (developing solvent: ethyl acetate) to yield 5-{2-amino-6-[3-(3-tert-butoxycarbonylaminopropoxy)phenylsulfanyl]pyrimidin-4-yl}-2-methoxy-4-methylbenzoic acid methyl ester (103 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1.[Cl:18][CH2:19][C:20](Cl)=[O:21].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[N:10]([C:20](=[O:21])[CH2:19][Cl:18])[C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1
Reactant: O=C(Cl)CCl
Reactant: Cc1ccc(Nc2c(C)cc(F)cc2Cl)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: Cc1ccc(N(C(=O)CCl)c2c(C)cc(F)cc2Cl)cc1

Procedure:
1.32 g of N-(2′-Chloro-4′-fluoro-6′-methylphenyl)-4-methylaniline is reacted with chloracetylchloride (1.76 g) at 90° C. for 30 minutes. The cooled mixture is stirred with toluene (20 ml) and aqu. sodium carbonate for 30 minutes and the organic phase is evaporated. The residue is purified flash-chromatography on silica using toluene affording 1.04 g of N-(2′-chloro-4′-fluoro-6′-methylphenyl)-N-chloroacetyl-4-methylaniline as a solid which is recrystallised from heptane/2-propanol (9:1), mp.: 96-97° C.
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:9]([O:11][SiH:12]([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15])[CH3:10].C([Si](C=C)(C)O[Si](C)(C)C)=C>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH2:1]([Si:12]([O:16][CH2:17][CH3:18])([O:13][CH2:14][CH3:15])[O:11][CH2:9][CH3:10])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Reactant: CCO[SiH](OCC)OCC
Agent: C=C[Si](C)(C=C)O[Si](C)(C)C
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: CCO[Si](CCc1ccccc1)(OCC)OCC
Temperature: 41 °C
Yield: 8.5 %

Procedure:
200 mg Of styrene, 320 mg of triethoxysilane, and 370 mg of toluene were placed in a glass reaction tube and 0.004 ml of ethyl acetate was added. Next, 0.01 ml of a toluene solution of a 0-valent platinum complex of divinyltetramethyldisiloxane (platinum content: 0.4 Wt. %) was added to this mixture. The reaction tube was sealed with Teflon tape and heated for 30 minutes in an oil bath at 41° C. When the tube contents were analyzed by GC-MS following cooling, the conversion rate of styrene was 13.5%, phenethyltriethoxysilane was produced at a yield of 8.5%, and the yield of (α-methylbenzyl) triethoxysilane was 13.6%.
Reaction SMILES: [CH3:1][C@:2]1([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:6][CH2:5][NH:4][CH2:3]1.C(=O)([O-])O.[Na+].[CH2:20]([O:27][C:28](Cl)=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C(OCC)C>[C:10]([O:9][C:8]([NH:7][C@@:2]1([CH3:1])[CH2:6][CH2:5][N:4]([C:28]([O:27][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:29])[CH2:3]1)=[O:14])([CH3:13])([CH3:12])[CH3:11]
Reactant: CC(C)(C)OC(=O)N[C@@]1(C)CCNC1
Reactant: O=C(Cl)OCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Product: CC(C)(C)OC(=O)N[C@@]1(C)CCN(C(=O)OCc2ccccc2)C1
Temperature: 25 °C
Reaction time: 16 h
Yield: 99.7 %

Procedure:
tert-Butyl [(3S)-3-methylpyrrolidin-3-yl]carbamate (I-345) (240 mg, 1.20 mmol) was dissolved in diethyl ether (12 ml), then an aqueous saturated sodium hydrogencarbonate solution (12 ml) was added, and at room temperature, benzyloxycarbonyl chloride (222 μl, 1.56 mmol) was added, followed by stirring at room temperature for 16 hours. The reaction liquid was extracted with ethyl acetate, and the obtained organic layer was washed with saturated brine. After drying over anhydrous sodium sulfate, the insoluble matter was separated by filtration, and the residue obtained by concentration was purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=2:1, v/v) to obtain the entitled compound (400 mg, 100%) as a colorless oily substance.
Reaction SMILES: [C:1]1([O:7][CH2:8][CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:10][C:11]([Cl:18])([Cl:17])[CH2:12][C:13](Cl)([CH3:15])[CH3:14].[Al+3].[Cl-].[Cl-].[Cl-].O>ClCCl>[Cl:10][C:11]([Cl:18])([Cl:17])[CH2:12][C:13]([C:4]1[CH:5]=[CH:6][C:1]([O:7][CH2:8][CH3:9])=[CH:2][CH:3]=1)([CH3:15])[CH3:14]
Reactant: CCOc1ccccc1
Reactant: CC(C)(Cl)CC(Cl)(Cl)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: O
Product: CCOc1ccc(C(C)(C)CC(Cl)(Cl)Cl)cc1
Reaction time: 4 h
Yield: 20.3 %

Procedure:
A mixture of 61 g (0.5 mol) of phenetole and 105 g (0.5 mol) of 1,1,1,3-tetrachloro-3-methyl-butane is added slowly with stirring at 0° C. to a suspension of 66.5 g (0.5 mol) of AlCl3 in 100 ml of dichloromethane. After stirring for 4 hours, 1,000 ml of water are added to the reaction mixture with ice-cooling. The mixture is extracted several times with dichloromethane and, after drying, the combined extracts are worked up by distillation. 30 g (=20% of theory) of 1,1,1-trichloro-3-p-ethoxyphenyl-3methyl-butane (b.p.: 145°-150° C./0.1 mbar) are obtained in addition to unreacted starting material.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][C:4]([NH:7][C:8]([C:10]2[C:15]([NH:16][C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[CH:14][CH:13]=[C:12]([CH3:23])[N:11]=2)=[O:9])=[N:3]1.BrC1C=C(C#N)[CH:28]=[N:29]C=1>>[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([NH:7][C:8]([C:10]2[C:15]([NH:16][C:17]3[CH:18]=[N:19][CH:20]=[C:21]([C:28]#[N:29])[CH:22]=3)=[CH:14][CH:13]=[C:12]([CH3:23])[N:11]=2)=[O:9])=[N:3]1
Reactant: N#Cc1cncc(Br)c1
Reactant: Cc1ccc(Nc2cccnc2)c(C(=O)Nc2ccn(C)n2)n1
Product: Cc1ccc(Nc2cncc(C#N)c2)c(C(=O)Nc2ccn(C)n2)n1

Procedure:
The title compound, was prepared from 3-Amino-6-methyl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (example 16) in accordance with the general method of example 20 using 5-Bromo-3-cyanopyridine instead of 3-Bromo-4-methylpyridine to yield the final compound as a light yellow solid, MS (ISP): m/e=334.3 (M+H+).
Reaction SMILES: [CH3:1][CH:2]1[CH2:6][S:5][CH:4]([C:7]([O:9][CH3:10])=[O:8])[C:3]1=O.[CH3:12][CH:13]([CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH:14]([C:16]1[CH:17]=C(O)[CH:19]=[C:20]([CH:22]=1)[OH:21])[CH3:15].P(Cl)(Cl)(Cl)=O.C1(C=CC=C(O)C=1)O>C1C=CC=CC=1>[OH:21][C:20]1[C:19]2[C:3]3[CH:2]([CH3:1])[CH2:6][S:5][C:4]=3[C:7](=[O:8])[O:9][C:10]=2[CH:17]=[C:16]([CH:14]([CH:13]([CH3:12])[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH3:15])[CH:22]=1
Reactant: COC(=O)C1SCC(C)C1=O
Reactant: CCCCCC(C)C(C)c1cc(O)cc(O)c1
Agent: Oc1cccc(O)c1
Solvent: O=P(Cl)(Cl)Cl
Solvent: c1ccccc1
Product: CCCCCC(C)C(C)c1cc(O)c2c3c(c(=O)oc2c1)SCC3C

Procedure:
A solution in dry benzene of equimolar amounts of methyl 4-methyl-3-oxo-tetrahydrothiophene-2-carboxylate and 5-(3-methyl-2-octyl) resorcinol plus phosphorous oxychloride (5 ml. of benzene/g. of the resorcinol) was warmed for 13 days at 35°-37°C. in an oil bath. Most of the benzene and HCl were removed at reduced pressure, and the dark tarry residue was stirred with ether and water until solution was complete. The ether layer was washed successively with dilute solutions of sodium bicarbonate, sodium hydroxide and sodium carbonate, then with water and saturated sodium chloride. Drying and concentrating the final organic solution left a friable brick-red foamy solid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:14][S:15](Cl)(=[O:17])=[O:16].O>N1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([O:13][S:15]([CH3:14])(=[O:17])=[O:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)N1CCC(O)C1
Solvent: c1ccncc1
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)C1
Temperature: -5 °C

Procedure:
3-Hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester is dissolved in dry pyridine (20 ml) and cooled to −5° C. Methanesulphonyl chloride is added over a period of 10 minutes keeping the temperature between −5° C. and 0° C. after which the yellow solution is allowed to warm up to room temperature over a period of 30 minutes. Water (20 ml) is added and the mixture is then extracted using DCM (2×30 ml), the organic washings being combined and washed with 2N potassium hydrogen sulphate solution (2×30 ml). The organic phase is dried (using MgSO4), filtered and evaporated to give the title compound as a colourless oil.
Reaction SMILES: C1CCCCC1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:18]([SH:22])[CH:19]([SH:21])[CH3:20].[C:23]1([CH2:29][CH:30]=O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>O>[CH2:29]([CH:30]1[S:21][CH:19]([CH3:20])[CH2:18][S:22]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=CCc1ccccc1
Reactant: CC(S)CS
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: C1CCCCC1
Product: CC1CSC(Cc2ccccc2)S1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Into a 100 cc reaction flask equipped with reflux condenser, magnetic stirring bar and thermometer and hot plate equipped with magnetic stirring apparatus is placed 5 ml cyclohexane, 0.2 grams of para-toluenesulfonic acid and 5.4 grams (0.05 moles) of 1,2-propanedithiol. With stirring, over a period of 30 minutes, 6 grams (0.05 moles) of phenylacetaldehyde is added to the reaction mass. The reaction mass is then heated to reflux and refluxed for a period of 8 hours. During the refluxing period, water of reaction is removed. At the end of the refluxing period, the reaction mass is cooled to room temperature and transferred to a separatory funnel. The reaction mass is then washed with one 50 ml portion of saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and filtered. The resulting filtrate is distilled on a Microvigreux column yielding the following three fractions: