Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:3][CH:2]1[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][OH:13])=[CH:8][CH:7]=1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:29]3[C:28]([N:30]4[CH2:35][CH2:34][CH:33]([NH2:36])[CH2:32][CH2:31]4)=[N:27][CH:26]=[N:25][C:24]=3[S:23][CH:22]=2)=[CH:17][CH:16]=1>CC(O)C.CS(C)=O>[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:29]3[C:28]([N:30]4[CH2:35][CH2:34][CH:33]([NH:36][CH2:3][CH:2]([OH:1])[CH2:4][O:5][C:6]5[CH:11]=[CH:10][C:9]([CH2:12][OH:13])=[CH:8][CH:7]=5)[CH2:32][CH2:31]4)=[N:27][CH:26]=[N:25][C:24]=3[S:23][CH:22]=2)=[CH:17][CH:16]=1
Reactant: NC1CCN(c2ncnc3scc(-c4ccc(F)cc4)c23)CC1
Reactant: OCc1ccc(OCC2CO2)cc1
Solvent: CS(C)=O
Solvent: CC(C)O
Product: OCc1ccc(OCC(O)CNC2CCN(c3ncnc4scc(-c5ccc(F)cc5)c34)CC2)cc1
Yield: 29 %

Procedure:
Synthesis followed SP6 (iPrOH:DMSO 1:1, 12 h), using 150 μmol (4-(oxiran-2-ylmethoxy)phenyl)methanol and 1-(5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl)piperidin-4-amine to give the title compound with 29% yield upon purification by prep. HPLC (reversed phase) and subsequent by prep. TLC (1 mm silica gel, PE/CH2Cl2/MeOH 4:6:1).
Reaction SMILES: [O:1]1[CH2:15][CH:2]1[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12](=[O:14])[CH3:13])=[CH:7][CH:6]=1.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>C(O)C>[CH2:11]([C:8]1[CH:9]=[CH:10][C:5]([O:4][CH2:3][CH:2]([OH:1])[CH2:15][N:27]2[CH2:26][CH2:25][N:24]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[O:17][CH3:16])[CH2:29][CH2:28]2)=[CH:6][CH:7]=1)[C:12](=[O:14])[CH3:13]
Reactant: COc1ccccc1N1CCNCC1
Reactant: CC(=O)Cc1ccc(OCC2CO2)cc1
Solvent: CCO
Product: COc1ccccc1N1CCN(CC(O)COc2ccc(CC(C)=O)cc2)CC1
Yield: 61.2 %

Procedure:
30.0 g of 4-(2,3-epoxypropoxy)-phenylacetone and 25.6 g of 2-methoxyphenyl-piperazine are heated under reflux in 300 ml of ethanol for 3 hours. The solvent is then distilled off. The residue is made to crystallise with ethyl acetate/hexane. 32.5 g of 1-[4-(propan-2-on-yl)-phenoxy]-3-[4-(2-methoxyphenyl)-piperazin-1-yl]-propan-2-ol are obtained.
Reaction SMILES: F[C:2]1[CH:22]=[CH:21][C:5]([CH2:6][C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18]C)=[O:17])=[CH:13][CH:14]=3)[N:9]([CH3:20])[CH:8]=2)=[CH:4][CH:3]=1.O[Li].O>C1COCC1.O>[CH2:6]([C:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]([OH:18])=[O:17])=[CH:13][CH:14]=2)[N:9]([CH3:20])[CH:8]=1)[C:5]1[CH:4]=[CH:3][CH:2]=[CH:22][CH:21]=1
Reactant: COC(=O)c1ccc2c(Cc3ccc(F)cc3)cn(C)c2c1
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Product: Cn1cc(Cc2ccccc2)c2ccc(C(=O)O)cc21
Yield: 104.1 %

Procedure:
A solution of compound 25c (175 mg, 0.59 mmol), and LiOH.H2O (101 mg, 2.41 mmol) in THF/H2O (3/3 mL) was stirred at room temperature for 6 h. The resultant mixture was concentrated and partitioned between CH2Cl2 and water. The aqueous layer was acidified with 1N HCl(aq) to pH˜4. The organic layer was dried over Na2SO4 and concentrated to give compound 25d (163 mg), which was used in the next reaction without further purification.
Reaction SMILES: [CH2:1]([OH:6])[CH2:2][CH2:3][CH2:4][OH:5].[H-].[Na+].[CH2:9]([O:11][CH:12]([O:15][CH2:16][CH3:17])[CH2:13]Br)[CH3:10]>CN(C)C=O>[CH2:9]([O:11][CH:12]([O:15][CH2:16][CH3:17])[CH2:13][O:5][CH2:4][CH2:3][CH2:2][CH2:1][OH:6])[CH3:10]
Reactant: OCCCCO
Reactant: CCOC(CBr)OCC
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(COCCCCO)OCC
Temperature: 0 °C
Yield: 41.9 %

Procedure:
To a mixture of 56.3 g of 1,4-butanediol and 400 ml of N,N-dimethylformamide was slowly added 11.0 g of 60% sodium hydride (in oil) with stirring under ice cooling. After stirring at room temperature for 12 hours, 49.3 g of bromoacetaldehyde diethylacetal was added dropwise to the reaction mixture, which was stirred at 60° C. for 8 hours. The reaction mixture was poured into ice water and extracted twice with ethyl acetate. The ethyl acetate layers were combined, washed with water, dried over magnesium sulfate and then concentrated to give a crude product. The crude product was subjected to silica gel chromatography, which afforded 21.6 g of 4-(2,2-diethoxyethoxy)butanol (yield, 41%), nD23.2 1.4314.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:22][CH3:23])=[C:8]([C:10]2[C:11]([CH:20]=O)=[CH:12][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:14][CH:15]=2)[CH:9]=1)([CH3:3])[CH3:2].[F:24][C:25]([F:39])([F:38])[C:26]1[CH:27]=[C:28]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=1)[CH2:29][NH2:30].C(O)(=O)C.C(=O)(O)[O-].[Na+]>ClCCCl>[F:24][C:25]([F:38])([F:39])[C:26]1[CH:27]=[C:28]([CH:31]=[C:32]([C:34]([F:37])([F:35])[F:36])[CH:33]=1)[CH2:29][NH:30][CH2:20][C:11]1[CH:12]=[C:13]([C:16]([F:17])([F:18])[F:19])[CH:14]=[CH:15][C:10]=1[C:8]1[CH:9]=[C:4]([CH:1]([CH3:3])[CH3:2])[CH:5]=[CH:6][C:7]=1[O:22][CH3:23]
Reactant: COc1ccc(C(C)C)cc1-c1ccc(C(F)(F)F)cc1C=O
Reactant: NCc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCCl
Product: COc1ccc(C(C)C)cc1-c1ccc(C(F)(F)F)cc1CNCc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.5 %

Procedure:
5′-Isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-carbaldehyde (5.0 g) is dissolved in 1,2-dichloroethane (20 ml) and thereto are added 3,5-bis-(trifluoromethyl)benzylamine (3.8 g), acetic acid (1.1 ml) and triacetoxy-sodium borohydride (4.0 g), and the mixture is stirred at room temperature overnight. To the reaction mixture is added a saturated aqueous sodium bicarbonate solution and the mixture is extracted with chloroform. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by NH-silica gel column chromatography (hexane:ethyl acetate=10:1) to give (3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amine (7.2 g). MS (m/z): 550 [M+H]+
Reaction SMILES: [CH3:1][S:2]([CH3:5])(=[O:4])=[O:3].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH:16]1([S:19]([C:22]2[CH:27]=[CH:26][C:25]([CH:28]([C:36]3[NH:40][C:39]([C:41]4[N:46]=[CH:45][C:44]([CH:47]=[O:48])=[CH:43][CH:42]=4)=[CH:38][CH:37]=3)[CH2:29][CH:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH2:18][CH2:17]1.O>O1CCCC1>[CH:16]1([S:19]([C:22]2[CH:23]=[CH:24][C:25]([CH:28]([C:36]3[NH:40][C:39]([C:41]4[N:46]=[CH:45][C:44]([CH:47]([OH:48])[CH2:1][S:2]([CH3:5])(=[O:4])=[O:3])=[CH:43][CH:42]=4)=[CH:38][CH:37]=3)[CH2:29][CH:30]3[CH2:31][CH2:32][O:33][CH2:34][CH2:35]3)=[CH:26][CH:27]=2)(=[O:21])=[O:20])[CH2:18][CH2:17]1
Reactant: O=Cc1ccc(-c2ccc(C(CC3CCOCC3)c3ccc(S(=O)(=O)C4CC4)cc3)[nH]2)nc1
Reactant: CS(C)(=O)=O
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CS(=O)(=O)CC(O)c1ccc(-c2ccc(C(CC3CCOCC3)c3ccc(S(=O)(=O)C4CC4)cc3)[nH]2)nc1
Reaction time: 1 h
Yield: 22.5 %

Procedure:
To a solution of dimethylsulfone (446 mg) in tetrahydrofuran (10 mL) was added dropwise lithium hexamethyldisilazide (1.6M tetrahydrofuran solution) (2.7 mL) at −78° C., and the mixture was stirred for 1 hr. To the reaction mixture was added dropwise a solution of 6-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridine-3-carbaldehyde (1 g) in tetrahydrofuran (5 mL), and the mixture was stirred for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography to give a pale-yellow amorphous solid from a fraction eluted with ethyl acetate-methanol (9:1, volume ratio). The obtained pale-yellow amorphous solid was subjected to basic silica gel column chromatography to give a pale-yellow amorphous solid from a fraction eluted with ethyl acetate-methanol (9:1, volume ratio). The pale-yellow amorphous solid was purified by preparative HPLC to give the title compound (270 mg, yield 22%) as a colorless amorphous solid. MS: 559 (MH+).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[CH2:9]([N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)[CH3:10]>C1(C)C=CC=CC=1>[CH2:9]([N:11]1[CH2:16][CH2:15][N:14]([C:6]2[N:5]=[CH:4][N:3]=[C:2]([NH2:1])[CH:7]=2)[CH2:13][CH2:12]1)[CH3:10]
Reactant: CCN1CCNCC1
Reactant: Nc1cc(Cl)ncn1
Solvent: Cc1ccccc1
Product: CCN1CCN(c2cc(N)ncn2)CC1
Temperature: 110 °C

Procedure:
A mixture of 1 g (7.7 mmol) 4-amino-6-chloropyrimidine (commercially available) and 1.75 g (15.4 mmol) 1-ethyl piperazine (commercially available) in 10 mL toluene was heated to 110° C. for 16 h. After evaporation of all volatiles the residue was purified by flash column chromatography on silica eluting with a gradient formed from DCM (0.5% NEt3) and methanol. The combined product fractions were evaporated to dryness to yield the title compound. MS (m/e): 208.3 (MH+).
Reaction SMILES: O.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9](=[O:15])[C:8](=O)[C:7]2=[O:17].Cl.[C:19]1([NH:25][C:26](=[O:29])[NH:27][NH2:28])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[OH2:3].[CH3:14][O:13][C:12]1[CH:11]=[C:10]2[C:6](=[CH:5][C:4]=1[O:3][CH3:2])[C:7](=[O:17])[C:8](=[N:28][NH:27][C:26]([NH:25][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:29])[C:9]2=[O:15]
Reactant: COc1cc2c(=O)c(=O)c(=O)c2cc1OC
Reactant: NNC(=O)Nc1ccccc1
Agent: Cl
Solvent: O
Product: COc1cc2c(=O)c(=NNC(=O)Nc3ccccc3)c(=O)c2cc1OC

Procedure:
5,6-dimethoxyindan-1,2,3-trione, monohydrate, 4-phenyl semicarbazide hydrochloride
Reaction SMILES: C(N(C(C)C)CC)(C)C.[CH2:10]([O:17][CH2:18][C:19]1[O:24][C:23](=[O:25])[C:22]([CH3:26])=[C:21]([OH:27])[C:20]=1[CH3:28])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH3:29][O:30][CH2:31]Cl>C1COCC1>[CH2:10]([O:17][CH2:18][C:19]1[O:24][C:23](=[O:25])[C:22]([CH3:26])=[C:21]([O:27][CH2:29][O:30][CH3:31])[C:20]=1[CH3:28])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: COCCl
Reactant: Cc1c(COCc2ccccc2)oc(=O)c(C)c1O
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: COCOc1c(C)c(COCc2ccccc2)oc(=O)c1C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Diisopropylethylamine (2.1 ml) was added to a solution of 6-(benzyloxy)methyl-3,5-dimethyl-4-hydroxy-2H-pyran-2-one (2.60 g) in THF (50 ml), and after stirring the mixture at room temperature for one hour, chloromethyl methyl ether (921 μl) was added at 0° C. and the mixture was stirred at room temperature for one hour. After concentrating the reaction solution under reduced pressure, water was added to the residue, extraction was performed with AcOEt, and the organic layer was dried with Na2SO4 and then filtered and concentrated. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=5/1→1/1) to obtain 6-(benzyloxy)methyl-3,5-dimethyl-4-methoxymethoxy-2H-pyran-2-one.
Reaction SMILES: [C:1]([NH:9][C:10]1[C:11]2[N:12]=[CH:13][N:14]([C:30]=2[N:31]=[CH:32][N:33]=1)[C@@H:15]1[O:29][C@H:19]([CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[C@@H:17]([OH:18])[CH2:16]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:34][O:35][C:36]1[CH:57]=[CH:56][C:39]([C:40](Cl)([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:41]2[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=2)=[CH:38][CH:37]=1.C(=O)([O-])O.[Na+]>N1C=CC=CC=1>[C:1]([NH:9][C:10]1[C:11]2[N:12]=[CH:13][N:14]([C:30]=2[N:31]=[CH:32][N:33]=1)[C@@H:15]1[O:29][C@H:19]([CH2:20][O:21][Si:22]([C:25]([CH3:26])([CH3:27])[CH3:28])([CH3:24])[CH3:23])[C@@H:17]([O:18][C:40]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)([C:41]2[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=2)[C:39]2[CH:38]=[CH:37][C:36]([O:35][CH3:34])=[CH:57][CH:56]=2)[CH2:16]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(C(Cl)(c2ccccc2)c2ccc(OC)cc2)cc1
Reactant: CC(C)(C)[Si](C)(C)OC[C@H]1O[C@@H](n2cnc3c(NC(=O)c4ccccc4)ncnc32)C[C@@H]1O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Product: COc1ccc(C(O[C@H]2C[C@H](n3cnc4c(NC(=O)c5ccccc5)ncnc43)O[C@@H]2CO[Si](C)(C)C(C)(C)C)(c2ccccc2)c2ccc(OC)cc2)cc1
Temperature: 45 °C
Yield: 63.1 %

Procedure:
N6-bezoyl-5′-O-(tert-butyldimethylsilyl)-2′-deoxyadenosine (16.1 g) was dissolved in 100 ml of anhydrous pyridine. 4,4′-dimethoxytrityl chloride (12.8 g) and anhydrous pyridine (140 ml) were further added, follow by stirring at 45° C. After the reaction completed, the reaction mixture was neutralized by sodium hydrogen carbonate, and pyridine was distilled off. Extraction using chloroform was carried out and the extract was washed by a saturated aqueous solution of sodium chloride and dried with anhydrous magnesium sulfate. The extract was concentrated and then purified by column chromatography (ethyl acetate/hexane) to obtain 16.7 g of the titled compound (yield: 63%).
Reaction SMILES: [I:1]I.C([Sn](CCCC)(CCCC)[C:8]1[CH:9]=[C:10](/[CH:24]=[CH:25]/[C:26]2[CH:31]=[CH:30][C:29]([N:32]([CH3:34])[CH3:33])=[CH:28][CH:27]=2)[CH:11]=[N:12][C:13]=1[O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][F:23])CCC.C(Cl)Cl>C1COCC1>[I:1][C:8]1[CH:9]=[C:10](/[CH:24]=[CH:25]/[C:26]2[CH:31]=[CH:30][C:29]([N:32]([CH3:34])[CH3:33])=[CH:28][CH:27]=2)[CH:11]=[N:12][C:13]=1[O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][F:23]
Reactant: CCCC[Sn](CCCC)(CCCC)c1cc(/C=C/c2ccc(N(C)C)cc2)cnc1OCCOCCOCCF
Reactant: II
Solvent: C1CCOC1
Solvent: ClCCl
Product: CN(C)c1ccc(/C=C/c2cnc(OCCOCCOCCF)c(I)c2)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 43 %

Procedure:
A solution of iodine (I2, 0.063 g, 0.24 mmol) in THF (2 mL) was added dropwise to an ice bath cooled solution of 12a (0.114 g, 0.172 mmol) in THF (3 mL). After the addition, the reaction was stirred at 0° C. for 1 h. Following standard workup with CH2Cl2, the crude product was purified by FC (EtOAc/Hexanes, 25/75) to give a light yellow solid 13a (0.037 g, 48%).
Reaction SMILES: [Cl:1][C:2]1[C:3]([O:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([NH2:17])=[O:16])=[CH:13][CH:12]=2)=[N:4][CH:5]=[C:6]([CH:8]=O)[CH:7]=1.[Cl:20][C:21]1[CH:22]=[C:23]([CH2:27][CH2:28][NH2:29])[CH:24]=[CH:25][CH:26]=1>>[Cl:1][C:2]1[C:3]([O:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([NH2:17])=[O:16])=[CH:13][CH:12]=2)=[N:4][CH:5]=[C:6]([CH2:8][NH:29][CH2:28][CH2:27][C:23]2[CH:24]=[CH:25][CH:26]=[C:21]([Cl:20])[CH:22]=2)[CH:7]=1
Reactant: NC(=O)c1ccc(Oc2ncc(C=O)cc2Cl)cc1
Reactant: NCCc1cccc(Cl)c1
Product: NC(=O)c1ccc(Oc2ncc(CNCCc3cccc(Cl)c3)cc2Cl)cc1
Yield: 37.5 %

Procedure:
Using a method similar to Example 462, using 4-(3-chloro-5-formyl-pyridin-2-yloxy)-benzamide (101 mg, 0.365 mmol) and 2-(3-chloro-phenyl)-ethylamine (0.056 mL, 0.402 mmol) gives the title compound (57 mg, 36%). Mass spectrum (ion spray): m/z=415.9 (M+1); 1H NMR (CDCl3): 7.93 (d, J=1.7 Hz, 1H), 7.86 (d, J=8.7 Hz, 2H), 7.77 (d, J=1.7 Hz, 1H), 7.22-7.17 (m, 4H), 7.07 (d, J=7.0 Hz, 1H), 6.12 (bs, 2H), 3.74 (s, 2H), 2.87 (t, J=6.8 Hz, 2H), 2.78 (t, J=6.8 Hz, 2H), 1.42 (bs, 1H).
Reaction SMILES: Br[C:2]1[C:3]([NH:12][C@H:13]2[CH2:17][CH2:16][CH2:15][C@@H:14]2[NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:7]=1.[CH:26](B1OC(C)(C)C(C)(C)O1)=[CH2:27].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:26]([C:2]1[C:3]([NH:12][C@H:13]2[CH2:17][CH2:16][CH2:15][C@@H:14]2[NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:7]=1)=[CH2:27]
Reactant: CC(C)(C)OC(=O)N[C@H]1CCC[C@@H]1Nc1ncc(C(F)(F)F)nc1Br
Reactant: C=CB1OC(C)(C)C(C)(C)O1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: C=Cc1nc(C(F)(F)F)cnc1N[C@H]1CCC[C@@H]1NC(=O)OC(C)(C)C

Procedure:
A suspension of tert-butyl N-[(1S,2S)-2-{[3-bromo-5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]carbamate (650 mg, 1.53 mmol), 2-ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (CAS number 75927-49-0; 942 mg, 6.11 mmol), tetrakis(triphenylphosphine)palladium (177 mg, 0.15 mmol) and potassium carbonate (845 mg, 6.11 mmol) in 1,4-dioxane (5 ml) and water (0.8 ml) was subjected to microwave irradiation at 120° C. for 1 hour. The reaction was partitioned between ethyl acetate (10 ml) and water (10 ml). The aqueous layer was further extracted with ethyl acetate (3×20 ml). The combined organics were washed with brine (20 ml), filtered through a hydrophobic frit and concentrated in vacuo. The resulting residue was purified by column chromatography (silica, 0-50% ethyl acetate/petrol) to afford the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][O:10]C2CCCCO2)[CH:5]=[CH:4][C:3]=1[N:17]([CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])C(=O)C(F)(F)F.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>C(O)C>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][OH:10])[CH:5]=[CH:4][C:3]=1[NH:17][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26]
Reactant: CCOC(=O)CN(C(=O)C(F)(F)F)c1ccc(CCOC2CCCCO2)cc1Cl
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: O
Product: CCOC(=O)CNc1ccc(CCO)cc1Cl
Yield: 64.5 %

Procedure:
A solution of ethyl N-[2-chloro-4-[2-((RS)-tetrahydro-pyran-2-yloxy)ethyl]phenyl]-N-trifluoroacetylaminoacetate (830 mg) and p-toluenesulfonic acid monohydrate (80 mg) in ethanol (9.0 ml) was stirred for 2 hours at 40° C. To the reaction mixture was added potassium carbonate (314 mg), and the resulting mixture was heated under reflux for 5 hours with stirring. The insoluble material was filtered off, the filtrate was concentrated in vacuo, and the residue was dissolved in ethyl acetate. The solution was washed with a saturated aqueous sodium bicarbonate solution and brine, and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. Purification of the residue by medium pressure liquid column chromatography on silica gel (eluent: hexane/ethyl acetate=2/1) gave ethyl N-[2-chloro-4-(2-hydroxyethyl)phenyl]aminoacetate (315 mg).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:12]=[CH:11][C:10]=1[C:23](=[O:25])[CH3:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:26]N1C(=O)CCC1=O.O>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:12]([Br:26])=[CH:11][C:10]=1[C:23](=[O:25])[CH3:24])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: CC(=O)c1ccc(OCc2ccccc2)cc1OCc1ccccc1
Solvent: O
Solvent: CN(C)C=O
Product: CC(=O)c1cc(Br)c(OCc2ccccc2)cc1OCc1ccccc1
Temperature: 25 °C

Procedure:
51.2 g of 1-(2,4-Bis-benzyloxy-phenyl)-ethanone (0.154 mol, 1 eq) were dissolved in 250 ml DMF. 27.42 g N-bromosuccinimide (0.154 mol, 1 eq) in 100 ml DMF were added dropwise. The mixture was stirred at room temperature over night. The reaction mixture was poured onto 700 ml of water and the precipitate filtered off. The filter cake was rinsed with water and the colourless solid was recrystallised from 370 ml acetonitrile.
Reaction SMILES: [N:1]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]([CH:11]=[CH:12][CH:13]=2)[NH2:10])[CH:4]=[N:3][CH:2]=1.N1C=CC=CC=1.[C:20]1([C:33](Cl)=[O:34])[C:32]2[CH2:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24]=2[CH:23]=[CH:22][CH:21]=1>ClCCl>[N:1]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]([NH:10][C:33]([C:20]3[C:32]4[CH2:31][C:30]5[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=5)[C:24]=4[CH:23]=[CH:22][CH:21]=3)=[O:34])[CH:11]=[CH:12][CH:13]=2)[CH:4]=[N:3][CH:2]=1
Reactant: Nc1cccc(-c2cncnc2)c1
Reactant: O=C(Cl)c1cccc2c1Cc1ccccc1-2
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C(Nc1cccc(-c2cncnc2)c1)c1cccc2c1Cc1ccccc1-2
Reaction time: 2 h
Yield: 61.2 %

Procedure:
To a suspension of 3-(pyrimidin-5-yl)aniline (0. 17g) and pyridine (0.24 ml) in dichloromethane (3 ml) was dropwise added a solution of the fluorene-1-carbonyl chloride (0.23 g) in dichloromethane (5 ml) followed by stirring for 2 hours. The mixture was diluted with dichloromethane and washed with an aqueous solution of sodium hydrogen carbonate and brine. The separated organic layer was dried over sodium sulfate and evaporated. The residue was purified by a silica gel column chromatography eluting with 2% methanol in dichloromethane to give N-[3-(pyrimidin-5-yl)phenyl]fluorene-1-carboxamide (0.222 g, 61.2 %).
Reaction SMILES: [CH:1]1[C:6]([OH:7])=[CH:5][CH:4]=[C:3]([Br:8])[CH:2]=1.[C:9]12(O)[CH2:18][CH:13]3[CH2:14][CH:15]([CH2:17][CH:11]([CH2:12]3)[CH2:10]1)[CH2:16]2.S(=O)(=O)(O)O.C(=O)(O)[O-].[Na+]>ClCCl.O>[C:9]12([C:5]3[CH:4]=[C:3]([Br:8])[CH:2]=[CH:1][C:6]=3[OH:7])[CH2:18][CH:13]3[CH2:14][CH:15]([CH2:17][CH:11]([CH2:12]3)[CH2:10]1)[CH2:16]2
Reactant: Oc1ccc(Br)cc1
Reactant: OC12CC3CC(CC(C3)C1)C2
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: Oc1ccc(Br)cc1C12CC3CC(CC(C3)C1)C2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
34.6 g (200 mmol) of p-bromophenol and 30.4 g (200 mmol) of 1 -adamantanol are dissolved in 100 ml of dichloromethane. To the resulting solution there are slowly added 10 ml of concentrated sulfuric acid. The mixture is stirred for 8 hours at ambient temperature poured into water, neutralized with sodium bicarbonate, extracted with methylene chloride, dried and evaporated. After recrystallization in isooctane 52.8 g of the expected product are obtained. Yield--86%. Melting point: 140°-141° C.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.Cl[C:18]([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:19]>ClCCl>[C:21]1([O:20][C:18](=[O:19])[NH:1][C:2]2[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: Nc1ccncc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(Nc1ccncc1)Oc1ccccc1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
4-Amino pyridine (500 mg, 5.3 mmol) and N,N-diisopropylethylamine (685 mg, 5.3 mmol) are dissolved in dichloromethane (5 ml). Phenyl chloroformate (830 mg, 5.3 mmol) is added to the reaction mixture. The reaction mixture is stirred at room temperature for 72 hours. The reaction mixture is partitioned between dichloromethane and saturated NaHCO3 (aq). The aqueous is washed with dichloromethane (×2). The organics are combined, dried (MgSO4), filtered and reduced in vacuo to give the title compound.
Reaction SMILES: OO.C([OH:7])(C)(C)C.C=CCCCCC.[O:15]([CH:17]([CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:18][OH:19])O>[W].C(OC)(C)(C)C>[O:19]([CH2:18][CH:17]([OH:15])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[OH:7]
Reactant: CC(C)(C)O
Reactant: CCCCCC(CO)OO
Agent: [W]
Agent: C=CCCCCC
Agent: OO
Solvent: COC(C)(C)C
Product: CCCCCC(O)COO
Temperature: 40 °C
Yield: 22 %

Procedure:
To a 50 mL flask equipped with a magnetic stirrer and a reflux condenser were added 800 mg of the tungsten-containing mesoporous silicate prepared in Example 1, 800 mg of a 60% by weight aqueous hydrogen peroxide solution, 2 g of tert-butanol and 400 mg of 1-heptene, and the mixture was stirred and maintained at an inner temperature of 40° C. for 16 hours to react these materials. To the resulting reaction mixture was added 5 g of methyl tert-butyl ether, and the mixture was stirred, and then allowed to stand. The supernatant organic layer was analyzed by LC, and it was found that 2-hydroperoxy-l-hydroxyheptane and 1-hydroperoxy-2-hydroxyheptane were produced. When the organic layer was analyzed by GC, 2-hydroperoxy-1-hydroxyheptane and 1-hydroperoxy-2-hydroxyheptane were thermally decomposed at an injection inlet, and detected as 1-hexanal. Then, the yield of 1-hexanal was determined by GC analysis (internal standard method), and this was regarded as the yield of 2-hydroperoxy-1-hydroxyheptane and 1-hydroperoxy-2-hydroxyheptane. Yield: 22%. The recovery of 1-hexene was 67%.