Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][S:2]([F:15])([F:14])([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1.Cl.[CH3:17][O:18][NH:19][CH3:20].C(N(CC)CC)C>ClCCl>[CH3:17][O:18][N:19]([CH3:20])[C:7](=[O:8])[C:6]1[CH:10]=[CH:11][C:3]([S:2]([F:15])([F:14])([F:13])([F:12])[F:1])=[CH:4][CH:5]=1
Reactant: O=C(Cl)c1ccc(S(F)(F)(F)(F)F)cc1
Reactant: CNOC
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CON(C)C(=O)c1ccc(S(F)(F)(F)(F)F)cc1
Yield: 51 %

Procedure:
4-(Pentafluoro-λ6-sulfanyl)benzoyl chloride (1.00 g, 3.751 mmol), O,N-dimethyl-hydroxylamine hydrochloride (0.402 g, 4.13 mmol), and triethylamine (0.835 g, 8.25 mmol) were stirred in dichloromethane for 2 hours at room temperature. The reaction was concentrated in vacuo and diethyl ether added. The solid was collected by filtration and purified by silica gel column chromatography to afford the title compound as a solid (0.557 g, 51% yield).
Reaction SMILES: [C:1]([C:4]1[CH:17]=[CH:16][C:15]2[O:14][C:13]3[C:8](=[CH:9][C:10](Br)=[CH:11][CH:12]=3)[S:7][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].[CH3:19][N:20](C)C=O>O>[C:1]([C:4]1[CH:17]=[CH:16][C:15]2[O:14][C:13]3[C:8](=[CH:9][C:10]([C:19]#[N:20])=[CH:11][CH:12]=3)[S:7][C:6]=2[CH:5]=1)(=[O:3])[CH3:2]
Reactant: CN(C)C=O
Reactant: CC(=O)c1ccc2c(c1)Sc1cc(Br)ccc1O2
Solvent: O
Product: CC(=O)c1ccc2c(c1)Sc1cc(C#N)ccc1O2

Procedure:
A mixture of 2-acetyl-8-bromophenoxathiin (from Example 4, Step 1) (1.73 g, 5.39 mmol) and cuprous cyanide (1.94 g, 21.6 mmol) in N,N-dimethylformamide (DMF, 15 mL) was refluxed for 7 hours. After cooling, the mixture was diluted with water and the precipitated solid filtered. This solid was boiled with ethyl acetate (100 mL) and filtered. The process was repeated with THF (100 mL, then 50 mL) and the combined filtrates evaporated to afford a yellow solid. This was purified by column chromatography on silica gel, eluting with a 1:3 mixture of ethyl acetate-hexane, to afford the title nitrile (774 mg) as a yellow solid, m.p.: 179°-183° C.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][C:5]1[C:10]([CH2:11]O)=[C:9]([CH3:13])[N:8]=[C:7]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[N:6]=1.S(Cl)([Cl:26])=O>C(Cl)Cl>[Cl:26][CH2:11][C:10]1[C:5]([CH2:4][CH2:3][O:2][CH3:1])=[N:6][C:7]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)=[N:8][C:9]=1[CH3:13]
Reactant: COCCc1nc(-c2ccc(C(F)(F)F)cc2)nc(C)c1CO
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: COCCc1nc(-c2ccc(C(F)(F)F)cc2)nc(C)c1CCl
Temperature: 25 °C
Reaction time: 2 h
Yield: 93.8 %

Procedure:
A solution of 2.47 g (7.48 mmol) [4-(2-methoxy-ethyl)-6-methyl-2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-methanol in 25 ml Methylenchloride was treated with 0.57 ml (7.85 mmol) thionylchloride. After 2 h stirring at RT, the mixture was partitioned between ether and water. The ether-phase was concentrated under reduced pressure giving 2.42 g pure 5-chloromethyl-4-(2-methoxy-ethyl)-6-methyl-2-(4-trifluoromethyl-phenyl)-pyrimidine.
Reaction SMILES: [H-].[Na+].[CH2:3]([C:5]1[CH:37]=[CH:36][C:35]([CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH3:51])=[CH:34][C:6]=1[O:7][CH2:8][CH:9]([OH:33])[CH2:10][O:11][C:12]([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=1)([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH3:4].[CH2:52](Br)[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>CN(C)C=O>[CH2:3]([C:5]1[CH:37]=[CH:36][C:35]([CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH3:51])=[CH:34][C:6]=1[O:7][CH2:8][CH:9]([O:33][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[CH2:10][O:11][C:12]([C:25]1[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=1)([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[CH3:4]
Reactant: CCCCCCCCCCCCCCc1ccc(CC)c(OCC(O)COC(c2ccccc2)(c2ccccc2)c2ccc(OC)cc2)c1
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCc1ccc(CC)c(OCC(COC(c2ccccc2)(c2ccccc2)c2ccc(OC)cc2)OCc2ccccc2)c1
Reaction time: 0.25 h
Yield: 97.5 %

Procedure:
To a suspension of 1.87 g of prewashed 50% sodium hydride in 50 ml of dimethylformamide was added a solution of 17.26 g of 1-(2-ethyl-5-tetradecylphenoxy)-3-[(4-methoxyphenyl)diphenylmethoxy]-2-propanol in 50 ml of dimethylformamide. This mixture was stirred for 15 minutes, then 5.79 g of benzyl bromide was added. This mixture was stirred 3 hours, quenched slowly with water and extracted several times with ether. The ether extracts were combined, washed with water, dried and the solvent removed, giving 19.1 g of the desired compound.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([C:15]2[O:16][C:17]([C:20]3[S:24][C:23]([C:25]([O:27]C)=[O:26])=[CH:22][CH:21]=3)=[CH:18][N:19]=2)=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>CO.C(Cl)Cl>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([C:15]2[O:16][C:17]([C:20]3[S:24][C:23]([C:25]([OH:27])=[O:26])=[CH:22][CH:21]=3)=[CH:18][N:19]=2)=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)c1ccc(-c2cnc(C(=O)CCCCCCc3ccccc3)o2)s1
Solvent: ClCCl
Solvent: CO
Product: O=C(CCCCCCc1ccccc1)c1ncc(-c2ccc(C(=O)O)s2)o1
Yield: 43.5 %

Procedure:
The title compound was prepared from methyl 5-(2-(7-phenylheptanoyl)oxazol-5-yl)thiophene-2-carboxylate (7 mg, 0.018 mmol) following General Procedure E. Preparative thin layer chromatography (10% MeOH/CH2Cl2) yielded the title compound as a white solid (3 mg, 41%): 1H NMR (THF-d8, 500 MHz) δ 7.73 (d, 1H, J=3.5 Hz), 7.72 (s, 1H), 7.55 (d, 1H, J=4.0 Hz), 7.22-7.08 (m, 5H), 3.03 (t, 2H, J=7.0 Hz), 2.60 (t, 2H, J=7.5 Hz), 1.73-1.71 (m, 2H), 1.65-1.61 (m, 2H), 1.42-1.40 (m, 4H); 13C NMR NMR (THF-d8, 125 MHz) δ 185.1, 164.0, 155.8, 147.0, 141.0, 134.8, 132.7, 132.1, 126.7, 126.5, 124.9, 123.9, 123.3, 37.0, 34.3, 30.0, 27.6, 27.5, 22.2; MALDI-FTMS m/z 384.1272 (M+H+, C21H22NO4S, requires 384.1264).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([OH:11])=[O:10].NC(N)=[S:14].[OH-].[Na+].S(=O)(=O)(O)O>O>[SH:14][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([OH:11])=[O:10]
Reactant: NC(N)=S
Reactant: O=C(O)CCCCCCCBr
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)CCCCCCCS
Yield: 63.8 %

Procedure:
5.0 g 8-bromooctanoic acid (22.4 mmol), 2.24 g thiourea (29.4 mmol) and 22 ml water were placed in a round botton flask, and the mixture was refluxed for 3 hours. 15.1 ml 3M sodium hydroxide was then added and the mixture was refluxed for one additional hour. The reaction mixture was cooled in an ice bath, and dilute sulfuric acid was added dropwise until the solution had a pH of about 2. The cloudy solution was then extracted with ether (2×25 ml), dried over anhydrous MgSO4, and concentrated under reduced pressure to give a white solid (2.52 g, 64%). 1H-NMR (300 MHz, CDCl3) 1.37, (m, 7 H); 1.60, (m, 4 H); 2.35, (t, J=7.4 Hz, 2 H); 2.52, (q, J=7.4 Hz, 2 H).
Reaction SMILES: [OH:1][CH2:2][CH:3]([CH2:5][OH:6])[OH:4].[C:7]([OH:36])(=O)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34].[Sn]>>[C:7]([O:1][CH2:2][CH:3]([CH2:5][OH:6])[O:4][C:7](=[O:36])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])(=[O:36])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: CCCCCCCCCCCCCCCCCCCCCCCCCCCC(=O)O
Reactant: OCC(O)CO
Agent: [Sn]
Product: CCCCCCCCCCCCCCCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCCCCCCCCCCCCCC
Temperature: 210 °C

Procedure:
A three-necked flask equipped with a stirrer, thermometer and descending Liebig condenser was charged with 19 g glycerol (0.207 mole), 165 g montanic acid (0.413 mole; Hoechst-Wachs S) and 0.4 g tin powder. The mixture was heated with stirring to 210° C. with application of a gentle vacuum which was increased to 20 mbar over a period of 1.5 h. Thereafter, the acid value had fallen to approximately 1. The mixture was cooled to 100° C., bleached and filtered. A pale yellow hard wax having a dropping point of 79° C. was obtained.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH:7]=O)=[CH:3][CH:2]=1.[NH2:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:12][CH2:11]1>>[CH2:16]([N:13]1[CH2:14][CH2:15][CH:10]([N:9]=[CH:7][C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)[CH2:11][CH2:12]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: NC1CCN(Cc2ccccc2)CC1
Reactant: O=Cc1ccncc1
Product: C(=NC1CCN(Cc2ccccc2)CC1)c1ccncc1

Procedure:
Pyridine-4-carboxaldehyde was reacted with 4-amino-N-benzylpiperidine by the procedure of example 1(c) to afford the title compound as a yellow oil.
Reaction SMILES: [OH:1][C:2]1[C:7]2[CH:8]=[C:9]([CH3:11])[O:10][C:6]=2[CH:5]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:3]=1.F[C:18]1[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH3:11][C:9]1[O:10][C:6]2[CH:5]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:3]=[C:2]([O:1][C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[C:7]=2[CH:8]=1
Reactant: CS(=O)(=O)c1ccc(F)cc1
Reactant: CCOC(=O)c1cc(O)c2cc(C)oc2c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1cc(Oc2ccc(S(C)(=O)=O)cc2)c2cc(C)oc2c1
Temperature: 120 °C
Yield: 66.4 %

Procedure:
The mixture of ethyl 4-hydroxy-2-methylbenzofuran-6-carboxylate (4.5 g, 20.4 mmol), 1-fluoro-4-(methylsulfonyl)benzene (5.34 g, 30.7 mmol) and Cs2CO3 (9.99 g, 30.7 mmol) in DMF (10 mL) was heated in a microwave at 120° C. for 60 min. The sample was filtered and the filtrate was concentrated to give an oil residue. The oil was purified by HPLC to give the title compound (5.074 g, 66%) as an off-white solid. 1H NMR (300 MHz, CHLOROFORM-D) d ppm 1.39 (t, J=7.16 Hz, 3 H) 2.46 (s, 3 H) 3.06 (s, 3 H) 4.38 (q, J=7.16 Hz, 2 H) 6.21 (s, 1 H) 7.00-7.14 (m, 2 H) 7.62 (s, 1 H) 7.81-7.95 (m, 2 H) 8.01 (s, 1 H).
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[N:17]=[C:16]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:25])[C:4]=1[OH:26])[CH3:2].Cl[CH2:28][C@H:29]([OH:32])[CH2:30][OH:31]>C(O)(C)C.[OH-].[Na+].CC(=O)OCC>[CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[N:17]=[C:16]([CH2:21][CH:22]([CH3:23])[CH3:24])[CH:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:25])[C:4]=1[O:26][CH2:28][C@H:29]([OH:32])[CH2:30][OH:31])[CH3:2]
Reactant: CCc1cc(-c2noc(-c3cc(C)nc(CC(C)C)c3)n2)cc(C)c1O
Reactant: OC[C@@H](O)CCl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: CCOC(C)=O
Product: CCc1cc(-c2noc(-c3cc(C)nc(CC(C)C)c3)n2)cc(C)c1OC[C@H](O)CO
Reaction time: 144 h
Yield: 16.5 %

Procedure:
To a solution of 2-ethyl-4-[5-(2-isobutyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenol (200 mg, 0.569 mmol) in isopropanol (10 mL) and 3 N aq. NaOH (3 mL), (R)-3-chloro-1,2-propanediol (252 mg, 2.28 mmol) is added. The mixture is stirred at 60° C. for 24 h before another portion of (R)-3-chloro-1,2-propanediol (252 mg, 2.28 mmol) is added. Stirring is continued at 60° C. for 6 days. The mixture is diluted with EA and washed with sat. aq. NaHCO3 solution. The org. extract is dried over MgSO4, filtered and evaporated. The crude product is purified by chromatography on prep. TLC plates with EA to give 3-{2-ethyl-4-[5-(2-isobutyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-(R)-propane-1,2-diol (40 mg) as a pale yellow oil; LC-MS: tR=0.84 min; [M+1]+=426.16; 1H NMR (CDCl3): δ 7.90 (s, 1H), 7.88 (s, 1H), 7.76 (s, 1H), 7.70 (s, 1H), 4.20-4.14 (m, 1H), 3.95-3.85 (m, 4H), 2.80-2.74 (m, 4H), 2.70 (s, 3H), 2.42 (s, 3H), 2.24-2.16 (m, 1H), 1.34 (t, J=7.5 Hz, 3H), 1.00 (d, J=6.5 Hz, 6 H).
Reaction SMILES: [Zn](C)[CH3:2].[CH2:4]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH2:17][CH:16]([CH:20]=[O:21])[CH2:15]1)=[O:13])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>CCOCC.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[CH2:4]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH2:17][C@@H:16]([C@H:20]([OH:21])[CH3:2])[CH2:15]1)=[O:13])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: C[Zn]C
Reactant: O=CC1CCCN(C(=O)OCc2ccccc2)C1
Agent: [Ti+4]
Agent: CC(C)[O-]
Solvent: CCOCC
Product: C[C@@H](O)[C@@H]1CCCN(C(=O)OCc2ccccc2)C1
Temperature: -78 °C
Reaction time: 1 h
Yield: 52 %

Procedure:
Using Schlenck glassware and air-free conditions, anhydrous ethyl ether freshly distilled from sodium/benzophenone (2.43 mL) was added to catalyst 14 prepared according to Example 15, protocol 1. Freshly distilled titanium tetraisopropoxide (0.430 mL, 1.46 mmol) was added, and the reaction was cooled to −78° C. Commercial Me2Zn (1.21 mL, 2 M in toluene) was added, and the reaction was stirred at −78° C. for 1 hour. Aldehyde 9 (0.300 g, 1.21 mmol) in Et2O (0.3 mL) was added, and the reaction was warmed to −30° C. and stirred overnight. The reaction was then quenched at −30° C. with saturated aqueous NH4Cl. Et2O was added, and the reaction was filtered through Celite wet with Et2O. The reaction was dried with sodium sulfate, filtered, concentrated, and purified using an ISCO CombiFlash column (silica, 2:1 Hexane:EtOAc) to obtain 16 (0.167 g, 52%). HLPC analysis of the product is depicted in the Figures. 1H NMR (CDCl3, 300 MHz) 7.42-7.30 (5H, broad s), 5.15 (2H, s), 4.08 (2H, broad d, J=12.8 Hz), 3.67 (1H, dq, J=6.2, 6.2 Hz), 2.81 (1H, td, J=12.4, 3.1 Hz), 3.90-2.60 (1H, broad), 2.40-1.90 (2H, broad), 1.80-1.68 (1H, m), 1.56-1.40 (2H, m), 1.23 (3H, d, J=6.3 Hz) ppm. 13C NMR (CDCl3, 75 MHz) 155.58, 137.06, 128.61, 128.07, 127.91, 69.38, 67.14, 46.94, 44.81, 43.14, 25.71, 24.95, 21.03 ppm.
Reaction SMILES: C([O:3][C:4](=O)[C:5]([CH3:25])([CH3:24])[C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[CH:11][CH:10]=1)=[O:7])C.[OH-].[NH4+:28]>>[F:23][C:19]1[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=1)[CH2:16][O:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][C:6](=[O:7])[C:5]([CH3:25])([CH3:24])[C:4]([NH2:28])=[O:3])=[CH:10][CH:11]=1
Reactant: [NH4+]
Reactant: CCOC(=O)C(C)(C)C(=O)Nc1ccc(OCc2cccc(F)c2)cc1
Agent: [OH-]
Product: CC(C)(C(N)=O)C(=O)Nc1ccc(OCc2cccc(F)c2)cc1

Procedure:
The title compound is prepared in analogy to example 3 from N-[4-(3-fluoro-benzyloxy)-phenyl]-2,2-dimethyl-malonamic acid ethyl ester and ammonium hydroxide. Colorless solid. MS: m/e=331.4 (M++H).
Reaction SMILES: FC(F)(F)C([N:5]([CH2:12][P:13]([N:18]([CH3:20])[CH3:19])([N:15]([CH3:17])[CH3:16])=[S:14])[CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=O>C(O)C>[CH3:20][N:18]([P:13]([CH2:12][NH:5][CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])([N:15]([CH3:16])[CH3:17])=[S:14])[CH3:19]
Reactant: CCOC(=O)CN(CP(=S)(N(C)C)N(C)C)C(=O)C(F)(F)F
Solvent: CCO
Product: CCOC(=O)CNCP(=S)(N(C)C)N(C)C

Procedure:
N-trifluoroacetyl-N-[bis(dimethylamino)phosphinothioylmethyl]glycine, ethyl ester (1 g, 0.00275 mole), was dissolved in ethanol (20 ml). The resulting solution was stirred and sodium tetrahydrido boron (0.104 g, 0.00275 mole) was added portionwise over a ten minute period. The resulting solution was stirred for 60 minutes. The solvent was removed by evaporation under vacuum and the residue was washed with water. The water washings were saturated with sodium chloride and the aqueous layer and insoluble residue were simultaneously extracted with ethyl acetate three times. The combined ethyl acetate extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The resulting residue was then chromatographed on silica gel with ether to yield N-[bis(dimethylamino)phosphinothioylmethyl]glycine, ethyl ester, ND25 =1.5317.
Reaction SMILES: [CH3:1][C:2]([Si:7]([CH3:10])([CH3:9])Cl)([CH3:6])[CH:3]([CH3:5])[CH3:4].Cl.[F:12][C:13]([F:19])([F:18])[S:14]([OH:17])(=[O:16])=[O:15]>>[F:12][C:13]([F:19])([F:18])[S:14]([O:17][Si:7]([C:2]([CH3:6])([CH3:1])[CH:3]([CH3:5])[CH3:4])([CH3:10])[CH3:9])(=[O:16])=[O:15]
Reactant: CC(C)C(C)(C)[Si](C)(C)Cl
Reactant: O=S(=O)(O)C(F)(F)F
Agent: Cl
Product: CC(C)C(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Temperature: 60 °C

Procedure:
50 ml of trifluoromethanesulfonic acid are slowly added dropwise at room temperature under argon to 101.57 g (0.57 mol) of (1,1,2,2-tetramethyleth-1-yl)-dimethylchlorosilane. Subsequently, the mixture is heated for 8 hours at 60° C. After this time, the evolution of HCl ceases. 111 g (67% of theory) of a colourless oil of boiling point=123°-124° C./28.6 mbar are obtained by distillation. The 1H-NMR spectrum is in agreement with the structure.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:29]([NH2:30])=[N:28][C:12]2[N:13]=[C:14]([NH:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)[N:15]=[CH:16][C:11]=2[CH:10]=1.[CH3:31][O:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[N:39]=[C:40]=[O:41]>CO.CC#N>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:29]([NH:30][C:40]([NH:39][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=2[O:32][CH3:31])=[O:41])=[N:28][C:12]2[N:13]=[C:14]([NH:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)[N:15]=[CH:16][C:11]=2[CH:10]=1
Reactant: COc1ccccc1N=C=O
Reactant: CN1CCN(CCCNc2ncc3cc(-c4c(Cl)cccc4Cl)c(N)nc3n2)CC1
Solvent: CC#N
Solvent: CO
Product: COc1ccccc1NC(=O)Nc1nc2nc(NCCCN3CCN(C)CC3)ncc2cc1-c1c(Cl)cccc1Cl

Procedure:
6-(2,6-Dichlorophenyl)-N2 -[3-(4-methyl-piperazin-1-yl)-propyl]-pyrido[2,3-d]pyrimidine-2,7-diamine (1.0 g) from Example 36 was reacted with 0.334 of 2-methoxyphenyl isocyanate according to the general procedure of Example 37 to give 0.9232 g of 1-{6-(2,6-dichlorophenyl)-2-[3-(4-methyl-piperazin-1-yl)-propylamino]-pyrido[2,3-d]pyrimidin-7-yl}-3-(2-methoxy-phenyl)-urea, ESMS (20/80 MeOH/CH3CN+0.1% AcOH): M+ +H=595; mp 152.5-154° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:4]=1[CH2:5][N:6]1[C:9](=[O:10])[C@@H:8]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:7]1[CH2:22]I.[N-:30]=[N+:31]=[N-:32].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[N:30]([CH2:22][C@@H:7]1[C@H:8]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9](=[O:10])[N:6]1[CH2:5][C:4]1[CH:24]=[CH:25][C:26]([O:28][CH3:29])=[CH:27][C:3]=1[O:2][CH3:1])=[N+:31]=[N-:32]
Reactant: COc1ccc(CN2C(=O)[C@@H](NC(=O)OCc3ccccc3)[C@H]2CI)c(OC)c1
Reactant: [N-]=[N+]=[N-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: C1CCOC1
Product: COc1ccc(CN2C(=O)[C@@H](NC(=O)OCc3ccccc3)[C@H]2CN=[N+]=[N-])c(OC)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 81.5 %

Procedure:
To a solution of benzyl ((2S,3S)-1-(2,4-dimethoxybenzyl)-2-(iodomethyl)-4-oxoazetidin-3-yl)carbamate (5.00 g, 9.80 mmol) in THF (100 mL) at 0° C. was added TEA (2.73 g, 19.6 mmol) followed by a solution of tetrabutylammonium azide (3.62 g, 12.7 mmol) in THF. After stirring at rt for 16 h, it was filtered and concentrated in vacuo. The crude residue was purified via silica gel chromatography (MeOH-DCM, 2%), affording the title compound (3.4 g, 81%) as a white solid.
Reaction SMILES: C([CH:4]([C:20]1[CH:25]=[C:24]([O:26][CH3:27])[C:23]([O:28][CH3:29])=[C:22]([O:30][CH3:31])[CH:21]=1)[C:5]([CH2:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([O:16][CH3:17])=[C:10]([O:18][CH3:19])[CH:9]=1)=[O:6])C=C.[O:32]1CC[CH2:34][CH2:33]1.O.I([O-])(=O)(=O)=O.[Na+]>C(O)(C)(C)C.[Os](=O)(=O)(=O)=O>[CH3:27][O:26][C:24]1[CH:25]=[C:20]([CH:4]([C:5](=[O:6])[CH2:7][C:8]2[CH:13]=[C:12]([O:14][CH3:15])[C:11]([O:16][CH3:17])=[C:10]([O:18][CH3:19])[CH:9]=2)[CH2:34][CH2:33][OH:32])[CH:21]=[C:22]([O:30][CH3:31])[C:23]=1[O:28][CH3:29]
Reactant: C1CCOC1
Reactant: C=CCC(C(=O)Cc1cc(OC)c(OC)c(OC)c1)c1cc(OC)c(OC)c(OC)c1
Agent: O=[Os](=O)(=O)=O
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: O
Solvent: CC(C)(C)O
Product: COc1cc(CC(=O)C(CCO)c2cc(OC)c(OC)c(OC)c2)cc(OC)c1OC
Temperature: 25 °C

Procedure:
To a solution of 27.5 g of the compound prepared in (d) above in 640 ml of a mixture of tetrahydrofuran and water (in a 2:1 ratio) was added 9 ml of a 2.5% solution of osmium tetraoxide in tert.-butanol. The reaction mixture was then allowed to stir at room temperature until it darkened to a black opaque mixture, after which time 82.07 g of sodium metaperiodate was added. The resultant mixture was then stirred at room temperature for 20 hours, after which time it was filtered and the solvent was removed by evaporation to yield a residue that was extracted with a mixture of ethyl acetate and water. The organic layer was evaporated and the resultant residue was chromatographed on silica gel employing a mixture of methylene chloride and ethyl acetate in a ratio of 8:1 as the eluent to yield a solid.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].C([O:9][C:10](=O)[CH2:11][C:12]1[C:13]2[CH:24]=[CH:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:14]=2[O:15][CH:16]=1)C>C1COCC1>[O:15]1[CH:16]=[C:12]([CH2:11][CH2:10][OH:9])[C:13]2[CH:24]=[CH:23][C:22]3[C:17]([C:14]1=2)=[CH:18][CH:19]=[CH:20][CH:21]=3
Reactant: CCOC(=O)Cc1coc2c1ccc1ccccc12
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCCc1coc2c1ccc1ccccc12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred suspension of LiAlH4 (200 mg, excess) in THF at 0° C., naphtho[1,2-b]furan-3-yl-acetic acid ethyl ester (1.27 g, 5 mmol) in THF (20 mL) was added slowly. After the addition, reaction mixture was stirred at room temperature for 1 hr and quenched with saturated NH4Cl solution. The product was extracted with chloroform and washed well with water. It was dried over anhydrous MgSO4; filtered and concentrated. The product, 2-naphtho[1,2-b]furan-3-yl ethanol, was obtained as white oil, was pure enough and taken to the next step without purification. Yield: 900 mg (84%); 213 (M+H).
Reaction SMILES: [OH:1][C:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([C:5]3=[O:12])[CH2:3]1)[CH2:9]2.[CH3:13][C:14]([CH3:20])([CH3:19])[CH2:15][C:16](Cl)=[O:17].OP([O-])(O)=O.[K+]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[O:12]=[C:5]1[CH:6]2[CH2:11][C:2]3([O:1][C:16](=[O:17])[CH2:15][C:14]([CH3:20])([CH3:19])[CH3:13])[CH2:9][CH:8]([CH2:10][CH:4]1[CH2:3]3)[CH2:7]2
Reactant: O=C1C2CC3CC1CC(O)(C3)C2
Reactant: CC(C)(C)CC(=O)Cl
Agent: CN(C)c1ccncc1
Agent: O=P([O-])(O)O
Agent: [K+]
Solvent: ClCCl
Product: CC(C)(C)CC(=O)OC12CC3CC(C1)C(=O)C(C3)C2

Procedure:
A solution of 1.03 g of 5-hydroxy-2-adamantanone, 1.83 g of DMAP and 1.9 ml of 3,3-dimethylbutanoyl chloride in 10 ml of CH2Cl2 is stirred at 40° C. for 48 hours, 6 ml of aqueous 1M KH2PO4 solution are added and the mixture obtained is stirred. The layers obtained are separated, from the organic layer obtained solvent is evaporated and the evaporation residue obtained is subjected to chromatography. 3,3-Dimethyl-butyric acid 4-oxo-adamantan-1-yl ester in the form of an oil is obtained. 13C-NMR: 215.61, 171.52, 49.10, 47.02, 41.38, 39.93, 38.17, 30.74, 29.79, 29.62.