Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([CH:12]1[CH2:16][CH:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:14]([CH:23]=O)[CH2:13]1)[S:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)(=[O:5])=[O:4].[ClH:25].[CH2:26]([O:33][C:34]([N:36]([CH:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1)[CH2:37][CH3:38])=[O:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[ClH:25].[CH3:1][N:2]([CH:12]1[CH2:16][CH:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:14]([CH2:23][N:42]2[CH2:43][CH2:44][CH:39]([N:36]([C:34]([O:33][CH2:26][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[O:35])[CH2:37][CH3:38])[CH2:40][CH2:41]2)[CH2:13]1)[S:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)(=[O:4])=[O:5]
Reactant: CN(C1CC(C=O)C(c2ccccc2)C1)S(=O)(=O)c1ccccc1
Reactant: CCN(C(=O)OCc1ccccc1)C1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: ClCCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCN(C(=O)OCc1ccccc1)C1CCN(CC2CC(N(C)S(=O)(=O)c3ccccc3)CC2c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 93.6 %

Procedure:
To a solution of 1-(RS)-(N-(methyl)-N-(phenylsulfonyl)amino)-3-(SR)-(formyl)-4-(SR)-phenylcyclopentane (from Step D, derived from Higher Rf isomer in Step C) (10 mg, 0.029 mmol) (from Step F) in 1,2-dichloroethane (1 mL) was added 4-(N-(benzyloxycarbonyl)-N-(ethyl)amino)piperidine hydrochloride (18 mg, 0.058 mmol) and DIPEA (0.010 mL, 0.058 mmol). After 15 min, sodium triacetoxyborohydride (19 mg, 0.087 mmol) was added and the reaction was stirred at RT for 4-16 h. The reaction was evaporated under nitrogen, quenched with aq. sodium carbonate and extracted 3 times with ethyl acetate. The organic layers were each washed with brine, dried over sodium sulfate, combined and concentrated in vacuo. The residue was purified by Prep TLC eluting with 2-5% methanol in methylene chloride to give the title product (17 mg) as the free amine. The hydrochloride salt was prepared by taking up the free amine in ether, addition of excess 1M hydrogen chloride in ether and evaporation to dryness to afford the title compound usually as a white solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:32])[CH2:6][C:5]2[C:7]([O:11][C:12]3[N:17]=[CH:16][C:15]([NH:18][C:19]([C@H:21]([NH:24]C(=O)OC(C)(C)C)[CH2:22][CH3:23])=[O:20])=[CH:14][CH:13]=3)=[CH:8][CH:9]=[CH:10][C:4]=2[O:3]1.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>ClCCl>[NH2:24][C@H:21]([CH2:22][CH3:23])[C:19]([NH:18][C:15]1[CH:16]=[N:17][C:12]([O:11][C:7]2[C:5]3[CH2:6][C:2]([CH3:1])([CH3:32])[O:3][C:4]=3[CH:10]=[CH:9][CH:8]=2)=[CH:13][CH:14]=1)=[O:20]
Reactant: CC[C@@H](NC(=O)OC(C)(C)C)C(=O)Nc1ccc(Oc2cccc3c2CC(C)(C)O3)nc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC[C@@H](N)C(=O)Nc1ccc(Oc2cccc3c2CC(C)(C)O3)nc1
Reaction time: 4 h
Yield: 91.5 %

Procedure:
To a solution of tert-butyl N-[(1R)-1-[[6-[(2,2-dimethyl-3H-benzofuran-4-yl)oxy]-3-pyridyl]carbamoyl]propyl]carbamate (Intermediate 208, 14 mg, 0.032 mmol) in dry dichloromethane (1 ml) at 0° C., TFA (98 μl, 1.268 mmol) was slowly added and the reaction mixture was stirred for 4 hours at the same temperature. Some more dichloromethane (4 ml) was added to the reaction mixture. An aqueous saturated aqueous solution of NaHCO3 was then added while the pH was allowed to reach ˜8. Two phases were separated and the aqueous one was further extracted with DCM (3×3 ml). Combined organic layers were dried over Na2SO4, filtrated and evaporated affording the title compound (10 mg).
Reaction SMILES: Br[CH:2]([CH:12]([CH3:14])[CH3:13])[C:3](=O)[C:4]([N:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5].[NH2:15][C:16]([NH2:18])=[S:17]>C(O)C>[NH2:18][C:16]1[S:17][C:2]([CH:12]([CH3:14])[CH3:13])=[C:3]([C:4]([N:6]2[CH2:10][CH2:9][CH2:8][CH2:7]2)=[O:5])[N:15]=1
Reactant: CC(C)C(Br)C(=O)C(=O)N1CCCC1
Reactant: NC(N)=S
Solvent: CCO
Product: CC(C)c1sc(N)nc1C(=O)N1CCCC1
Yield: 1467.2 %

Procedure:
Add 3-bromo-4-methyl-1-pyrrolidin-1-yl-pentane-1,2-dione (3.0 g, 11.44 mmol, 1.0 eq.) to the solution of thiourea (1.31 mmol, 1.5 eq.) in ethanol (40 mL). Stir the reaction mixture at reflux for overnight. Concentrate in vacuo. Add dichloromethane (200 mL). Wash the organic layer with sodium bicarbonate (sat. 2×30 mL), aqueous saturated sodium chloride (2×20 mL) and water (2×30 mL). Dry the organic phase over MgSO4 and filter the drying reagent off. Concentrate in vacuo. Purify by column chromatography (0%→5% ethyl acetae in dichloromethane) to afford product (4.60 g, 66%). MS(ES), m/z 240 (M+1).
Reaction SMILES: ClN1[C:6](=[O:7])[CH2:5]CC1=O.[CH:9]12[S:16][CH:13]([CH2:14][CH2:15]1)[CH2:12][C:11](=[O:17])[CH2:10]2.[CH:18]([Mg]Br)(C)C.Cl>C1C=CC=CC=1.CCOCC>[CH3:18][CH:14]([CH:13]1[S:16][CH2:9][CH2:10][C:11]2([O:17][CH2:5][CH2:6][O:7]2)[CH2:12]1)[CH3:15]
Reactant: O=C1CC2CCC(C1)S2
Reactant: O=C1CCC(=O)N1Cl
Reactant: CC(C)[Mg]Br
Agent: Cl
Solvent: c1ccccc1
Solvent: CCOCC
Product: CC(C)C1CC2(CCS1)OCCO2
Reaction time: 0.25 h
Yield: 65.3 %

Procedure:
N-Chlorosuccinimide (14.0 g, 104.9 mmol) was added in three portions with stirring over 15 min to a cooled (0° C.) solution of 8-thiabicyclo[3.2.1]octan-3-one (16.0 g, 99.9 mmol) in dry benzene (400 mL) under nitrogen. The mixture was stirred for a further 2.5 h and was then filtered. The filtrate was added dropwise with stirring under nitrogen to a cooled (0° C.) solution of isopropylmagnesium bromide (from isopropyl bromide (28.3 g, 229.7 mmol), magnesium (5.7 g, 234.7 mmol) and CuI (1.52 g, 7.9 mmol)) in dry ether (300 mL). The mixture was stirred for a further 15 h and cold (0° C.), dilute hydrochloric acid was added cautiously. The organic layer was separated and washed successively with water, saturated aqueous sodium bicarbonate, and finally with water again. The dried (Na2SO4) ether-benzene solution was evaporated, giving 13.2 g of the title compound.
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[CH2:10][C:9]2[C:4](=[C:5]([CH3:17])[CH:6]=[C:7]([O:12]CC(C)=C)[C:8]=2[CH3:11])[N:3]1[CH:18]=[O:19].CCC[CH2:24][CH2:25][CH3:26].[CH2:27](N(CC)C1C=CC=CC=1)C>>[OH:12][C:7]1[C:8]([CH3:11])=[C:9]2[C:4](=[C:5]([CH3:17])[C:6]=1[CH2:27][C:25]([CH3:24])=[CH2:26])[N:3]([CH:18]=[O:19])[C:2]([CH3:1])([CH3:20])[CH2:10]2
Reactant: CCCCCC
Reactant: C=C(C)COc1cc(C)c2c(c1C)CC(C)(C)N2C=O
Reactant: CCN(CC)c1ccccc1
Product: C=C(C)Cc1c(C)c2c(c(C)c1O)CC(C)(C)N2C=O
Reaction time: 8 h
Yield: 84 %

Procedure:
A solution of 2,3-dihydro-2,2,4,7-tetramethyl-5-[(2-methyl-2-propenyl)oxy]-1H-indole-1-carbaldehyde (2.38 g, 8.71 mmol) in N,N-diethylaniline (5 ml) was stirred under nitrogen atmosphere at 200° C. for 8 hours. The reaction mixture was allowed to stand overnight, hexane was added thereto, and the crystal was collected by a filtration and recrystallized from ethanol-hexane to obtain 2.10 g of the title compound.
Reaction SMILES: [Br:1][C:2]1[C:15]([F:16])=[CH:14][C:5]([C:6]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:7])=[C:4]([F:17])[C:3]=1[F:18].[NH2:19][C@H:20]([CH3:23])[CH2:21][OH:22].[CH3:24]N(C)C=O>>[Br:1][C:2]1[C:15]([F:16])=[CH:14][C:5]([C:6]([C:8](=[CH:24][NH:19][C@H:20]([CH3:23])[CH2:21][OH:22])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:7])=[C:4]([F:17])[C:3]=1[F:18]
Reactant: CCOC(=O)CC(=O)c1cc(F)c(Br)c(F)c1F
Reactant: C[C@@H](N)CO
Reactant: CN(C)C=O
Product: CCOC(=O)C(=CN[C@H](C)CO)C(=O)c1cc(F)c(Br)c(F)c1F
Yield: 91 %

Procedure:
was prepared from ethyl 4-bromo-2,3,5-trifluorobenzoylacetate, dimethylformamide and (R)-2-amino-1-propanol by the procedure of Example 1(d) and obtained in 91% yield as an orange oil.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]=[C:12]=[S:13].[NH2:14][C@@H:15]([CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[CH3:16].Cl[CH:24]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:25](O)=[O:26]>>[CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]=[C:12]1[N:14]([C@@H:15]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[CH3:16])[C:25](=[O:26])[CH:24]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[S:13]1
Reactant: O=C(O)C(Cl)c1ccccc1
Reactant: C[C@@H](N)C1CCCCC1
Reactant: Cc1cc([N+](=O)[O-])ccc1N=C=S
Product: Cc1cc([N+](=O)[O-])ccc1N=C1SC(c2ccccc2)C(=O)N1[C@H](C)C1CCCCC1

Procedure:
2-Methyl-4-nitrophenyl isothiocyanate was reacted with (1R)-1-amino-1-cyclohexylethane followed by α-chloro-α-phenylacetic acid according to Method C8a to afford 2-(2-methyl-4-nitrophenylimino)-3-((1R)-1-cyclohexylethyl)-5-phenyl-1,3-thiazolidin4-one.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH2:3][CH:2]1[C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][CH:13]=1)[CH:9]=[O:10].N1C(C)=CC=CC=1C.[H][H]>C1COCC1>[O:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[C:6]1[CH:7]=[C:8]([CH2:9][OH:10])[CH:11]=[CH:12][CH:13]=1
Reactant: O=Cc1cccc(C2CC=CO2)c1
Reactant: [H][H]
Solvent: Cc1cccc(C)n1
Solvent: C1CCOC1
Product: OCc1cccc(C2CCCO2)c1
Yield: 70 %

Procedure:
EX-608C) A THF (15 mL) solution of the aldehyde from EX-608B (0.70 g, 4.0 mmol) and 2,6-lutidine (0.46 mL, 4.0 mmol) was stirred in a hydrogen 4.0 mmol) and 2,6-lutidine (0.46 mL, 4.0 mmol) was stirred in a hydrogen temperature. The slurry was filtered through celite, and the solvent was removed. The residue was taken up in ethyl acetate and washed with 1 N HCl and brine. The organic layer was dried (MgSO4) and evaporated to give 0.50 g (70%) of the desired 3-(tetrahydro-2-furanyl)phenylmethanol product as a yellow oil. The formation of the desired product was monitored by the disappearance of the aldehyde (δ˜10) and olefin peaks in the 1H NMR disappearance of the aldehyde (δ˜10) and olefin peaks in the 1H NMR spectrum. 2.8 mmol) and MnO2 (2.10 g, 24.3 mmol) in dichloromethane (15 mL) was refluxed for 3 h. The slurry was filtered through celite, and the filtrate was evaporated to a yellow oil. Purification by flash chromatography on silica gel eluting with 10% ethyl acetate in hexane gave 0.19 g (45%) of the desired aldehyde product as a pale yellow oil. GCMS: m/z=177 [M+H]+.
Reaction SMILES: CS[C:3]1[N:4]=[N:5][C:6]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][CH2:20][CH2:21][CH3:22])[NH:10][C:9](=[O:23])[C:7]=2[N:8]=1.[NH3:24]>>[NH2:24][C:3]1[N:4]=[N:5][C:6]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][CH2:20][CH2:21][CH3:22])[NH:10][C:9](=[O:23])[C:7]=2[N:8]=1
Reactant: CCCOc1ccccc1-c1nc2nnc(SC)nc2c(=O)[nH]1
Reactant: N
Product: CCCOc1ccccc1-c1nc2nnc(N)nc2c(=O)[nH]1

Procedure:
5,6-Dihydro-3-methylthio-5-oxo-7-(2-propoxyphenyl)pyrimido[5,4-e][1,2,4]triazine (0.7 g) was heated for 30 hours with ethanolic ammonia (50 ml) at 100° C. in a pressure vessel. The cooled mixture was filtered to give the crude product (0.21 g) which was recrystallised from ethanol to give the pure title compound, m.p. 322°-325° C.
Reaction SMILES: S(Cl)(Cl)=O.BrC1SC(C(O)=O)=CC=1.BrC1SC(C(Cl)=O)=CC=1.[Br:23][C:24]1[S:28][C:27]([C:29]([N:31]=[C:32]=[S:33])=[O:30])=[CH:26][CH:25]=1.[CH3:34][O:35][C:36]1[CH:37]=[C:38]2[C:43](=[CH:44][C:45]=1[O:46][CH3:47])[N:42]=[CH:41][CH:40]=[C:39]2[O:48][C:49]1[CH:55]=[CH:54][C:52]([NH2:53])=[C:51]([CH3:56])[CH:50]=1>C(O)C.C1(C)C=CC=CC=1>[Br:23][C:24]1[S:28][C:27]([C:29]([NH:31][C:32]([NH:53][C:52]2[CH:54]=[CH:55][C:49]([O:48][C:39]3[C:38]4[C:43](=[CH:44][C:45]([O:46][CH3:47])=[C:36]([O:35][CH3:34])[CH:37]=4)[N:42]=[CH:41][CH:40]=3)=[CH:50][C:51]=2[CH3:56])=[S:33])=[O:30])=[CH:26][CH:25]=1
Reactant: O=C(N=C=S)c1ccc(Br)s1
Reactant: COc1cc2nccc(Oc3ccc(N)c(C)c3)c2cc1OC
Agent: O=C(Cl)c1ccc(Br)s1
Agent: O=C(O)c1ccc(Br)s1
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: O=S(Cl)Cl
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)c4ccc(Br)s4)c(C)c3)c2cc1OC
Temperature: 100 °C
Reaction time: 18 h
Yield: 65 %

Procedure:
Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 5-bromo-2-thiophenecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 5-bromo-2-thiophene isothiocyanate was prepared using the resultant 5-bromo-2-thiophenecarbonyl chloride as a starting compound according to the description of the literature. 5-Bromo-2-thiophenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 18 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (58 mg, yield 65%).
Reaction SMILES: C.C1C(Br)=C(Br)[NH:4]C=1C(O)=O.N([O-])=O.[Na+].[CH2:16]([C:30]1[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=1)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].[N+:37]([O-:40])([OH:39])=[O:38]>C(O)(C)C.O.CC(C)=O>[N+:37]([O-:40])([O-:39])=[O:38].[CH2:16]([C:30]1[CH:31]=[CH:32][C:33]([N+:34]#[N:4])=[CH:35][CH:36]=1)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]
Reactant: O=C(O)c1cc(Br)c(Br)[nH]1
Reactant: O=[N+]([O-])O
Reactant: CCCCCCCCCCCCCCc1ccc(N)cc1
Agent: C
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Solvent: CC(C)O
Product: CCCCCCCCCCCCCCc1ccc([N+]#N)cc1
Product: O=[N+]([O-])[O-]

Procedure:
A carbon black with a CTAB surface area of 350 m2 /g and a DBPA of 120 ml/100 g was used. A suspension of 50 g of this carbon black was prepared by stirring it into 450 g of water that contained a few drops of isopropanol. A solution of 5.12 g of NaNO2 in 10 g of cold water was slowly added to a dispersion of 17.91 g of 4-tetradecylaniline, 11.88 g of concentrated nitric acid and 20 ml of acetone in 100 g of water that was cooled in an ice bath. 4-Tetradecylbenzenediazonium nitrate was formed. After 15 minutes of stirring, the mixture was added to the stirring carbon black suspension. Bubbles were released. After 30 minutes, the product was collected by filtration, washed with water and tetrahydrofuran (THF) and dried in an oven at 125° C. The carbon black product had attached p-C6H4C14H29 groups.
Reaction SMILES: [H-].[Na+].[I:3][C:4]1[CH:5]=[C:6]([C:9]([O:11][CH3:12])=[O:10])[NH:7][CH:8]=1.I[CH3:14].O>CN(C=O)C>[CH3:14][N:7]1[CH:8]=[C:4]([I:3])[CH:5]=[C:6]1[C:9]([O:11][CH3:12])=[O:10]
Reactant: CI
Reactant: COC(=O)c1cc(I)c[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1cc(I)cn1C
Reaction time: 2 h

Procedure:
780 mg (25.9 mmol) of sodium hydride (80% in oil) and 20 ml of DMF were introduced into a three-necked flask, a solution of 6.5 g (25.9 mmol) of methyl 4-iodo-2-pyrrolecarboxylate in 50 ml of DMF was added dropwise and stirring was carried out until gas evolution has ceased. 2.1 ml (33.6 mmol) of iodomethane were then added and stirring was carried out at room temperature for two hours. The reaction mixture was poured into water and extracted with ethyl ether. The organic phase was separated by settling, dried over magnesium sulfate and was evaporated. The residue obtained was purified by chromatography on a silica column eluted with a mixture of dichloromethane and hexane (40/60). 4.5 g (65%) of methyl N-methyl-4-iodo-2-pyrrolecarboxylate, with a melting point of 64°-65° C., were recovered.
Reaction SMILES: [OH:1][N:2]1[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:32][C:33]1([CH3:40])[O:37][C@H:36]([CH2:38]O)[CH2:35][O:34]1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH3:32][C:33]1([CH3:40])[O:37][C@H:36]([CH2:38][O:1][N:2]2[C:3](=[O:12])[C:4]3[C:5](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]2=[O:7])[CH2:35][O:34]1
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: CC1(C)OC[C@@H](CO)O1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC1(C)OC[C@@H](CON2C(=O)c3ccccc3C2=O)O1
Temperature: 25 °C
Reaction time: 18 h
Yield: 97.5 %

Procedure:
A 3-L round-bottomed flask equipped with mechanical stirrer and additional funnel was charged with N-hydroxyphthalimide (68.0 g, 0.416 mol) and tetrahydrofuran (1.2 L) under nitrogen atmosphere. To this solution was added triphenylphosphine (109.2 g, 0.416 mol) and (R)-(2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (55.0 g, 0.416 mol). The mixture was cooled to 3° C. to 5° C. and diethyl azodicarboxylate (85.2 mL, 0.541 mol) was added dropwise, while keeping the inner temperature below 15° C. The reaction mixture was warmed to ambient temperature, and stirred for 18 hours. The tetrahydrofuran was evaporated under reduced pressure. To the remaining orange solid was added dichloromethane (0.5 L) and the mixture was stirred for 1 hour. The white solid (Ph3PO) was filtered and washed with dichloromethane (0.1 L). The solvent was removed and ethanol (0.5 L) was added to the resulting solid. The mixture was stirred for 2 hours at 3° C. to 5° C. The white solid was filtered, washed with a small amount of cold EtOH and dried in vacuum oven at 40° C. to give (S)-2-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-isoindole-1,3-dione (112.5 g, 97%) as a white solid: 1H NMR (CDCl3): δ 1.33 (s, 3H), 1.99 (s, 3H), 3.96 (m, 1H), 4.15 (m, 2H), 4.30 (m, 1H), 4.48 (m, 1H), 7.59 (m, 2H), 7.84 (m, 2H); MS (APCI+)=278 (M++1).
Reaction SMILES: C[C:2](CC(C)C)=[O:3].[C:8]1([CH3:14])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>>[CH2:8]([CH:13]([CH2:12][CH2:11][CH2:10][CH3:9])[CH2:2][OH:3])[CH3:14]
Reactant: Cc1ccccc1
Reactant: CC(=O)CC(C)C
Product: CCCCC(CC)CO
Yield: 0 %

Procedure:
Subsequently, there were introduced into a four neck flask of the same type as used above 120 g of the aromatic polymer obtained above, 100 g of methylisobutyl ketone, 200 g of toluene, and 0.04 g of 2-ethylhexanol-modified chloroplatinic acid, followed vby azeotropic dehydration for 1 hour. Thereafter, 80 g of organopolysiloxanes indicated in Table 1 were, respectively, dropped at a refluxing temperature in 30 minutes and agitated for reaction at the same temperature for 4 hours. The resulting product was washed with water and the solvent was distilled off under reduced pressure to obtain reaction products (copolymers I, II, and III).
Reaction SMILES: [Cl:1][C:2]([Cl:35])([Cl:34])[CH2:3][O:4][C:5](=[O:33])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:19]=[CH:18][C:17]([C:20](=[O:29])[NH:21][C:22]3[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][N:23]=3)=[CH:16][C:15]=2[N+:30]([O-])=O)=[CH:9][CH:8]=1.[Cl-].[NH4+]>O1CCCC1.C(O)C.O.[Fe]>[Cl:35][C:2]([Cl:1])([Cl:34])[CH2:3][O:4][C:5](=[O:33])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:19]=[CH:18][C:17]([C:20](=[O:29])[NH:21][C:22]3[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][N:23]=3)=[CH:16][C:15]=2[NH2:30])=[CH:9][CH:8]=1
Reactant: O=C(Nc1ccc(Sc2ccc(C(=O)Nc3ccc(Br)cn3)cc2[N+](=O)[O-])cc1)OCC(Cl)(Cl)Cl
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Solvent: C1CCOC1
Product: Nc1cc(C(=O)Nc2ccc(Br)cn2)ccc1Sc1ccc(NC(=O)OCC(Cl)(Cl)Cl)cc1
Temperature: 25 °C
Yield: 95.3 %

Procedure:
A mixture of the product of Example 364C (1.63 g, 2.63 mmol), iron powder (0.737 g, 13.1 mmol, 5 equiv., from Acros, electrolytically reduced, reagent, powder), and ammonium chloride (0.211 g, 3.94 mmol, 1.5 equiv.) in tetrahydrofuran/ethanol/water (30/30/10 mL) was heated under reflux for 2.5 hours. The reaction mixture was cooled to room temperature and filtered through Celite, rinsing the Celite pad with 50 mL of ethanol. The resulting filtrate was evaporated under reduced pressure and the residue was partitioned between ethyl acetate (100 mL) and water (100 mL). The aqueous phase was washed with ethyl acetate (2×100 mL). The combined organic phases were washed with brine (50 mL), dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure to give the title compound (1.48 g, 95%) as a faintly yellow solid.
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH3:8])([CH3:7])[CH2:5][CH:4]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[C:3]1=[O:19].[H-].[Na+].Cl[C:23]1[N:28]=[CH:27][C:26]([C:29]#[C:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:25][N:24]=1>CN(C=O)C>[CH3:1][N:2]1[C:6]([CH3:8])([CH3:7])[CH2:5][C:4]([C:23]2[N:24]=[CH:25][C:26]([C:29]#[C:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[CH:27][N:28]=2)([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[C:3]1=[O:19]
Reactant: Clc1ncc(C#Cc2ccccc2)cn1
Reactant: CN1C(=O)C(C(=O)OCc2ccccc2)CC1(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN1C(=O)C(C(=O)OCc2ccccc2)(c2ncc(C#Cc3ccccc3)cn2)CC1(C)C
Temperature: 0 °C
Reaction time: 0.67 h
Yield: 79.6 %

Procedure:
A solution of (RS)-benzyl 1,5,5-trimethyl-2-oxopyrrolidine-3-carboxylate (206 mg, 787 μmol) in 4 ml of dry DMF was purged with argon and cooled to 0° C. Then a 60% suspension of sodium hydride (31.5 mg, 0.79 mmol) was added and the mixture was stirred for 40 min at room temperature whereby a white suspension was formed. Then 2-chloro-5-(phenylethynyl)pyrimidine (CAS: [1051388-40-9]) (130 mg, 606 μmol) was added, the mixture was stirred for 30 min at 80° C., and then quenched by addition of 1 ml of saturated ammonium chloride solution. After extraction with ethyl acetate/water, drying over sodium sulfate and concentration; the residue (440 mg, yellow oil) was taken up in ethyl acetate, adsorbed onto 3 g of silicagel and loaded onto a 20 g prepacked flash chromatography column. After elution with a 10% to 60% ethyl acetate in heptane gradient, the fractions containing the desired product were collected to yield 212 mg (80%) of the title compound as a light yellow waxy solid, MS: m/e=440.3 (M+H+).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][CH2:11][CH2:12][C:13]2([OH:26])[CH2:25][CH2:24][C:16]3([O:21]CC(C)(C)CO3)[CH2:15][CH2:14]2)[CH3:9])=[CH:4][CH:3]=1.Cl[C:28](Cl)([O:30]C(=O)OC(Cl)(Cl)Cl)Cl>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]([N:10]2[CH2:11][CH2:12][C:13]3([CH2:14][CH2:15][C:16](=[O:21])[CH2:24][CH2:25]3)[O:26][C:28]2=[O:30])[CH3:9])=[CH:6][CH:7]=1
Reactant: C[C@H](NCCC1(O)CCC2(CC1)OCC(C)(C)CO2)c1ccc(F)cc1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Product: C[C@@H](c1ccc(F)cc1)N1CCC2(CCC(=O)CC2)OC1=O
Yield: 50 %

Procedure:
The title compound is prepared from 9-{2-[(S)-1-(4-fluoro-phenyl)-ethylamino]-ethyl}-3,3-dimethyl-1,5-dioxa-spiro[5.5]undecan-9-ol and triphosgene following a procedure analogous to that described in Step 4 of Intermediate 2. Yield: 50% of theory; LC (method 5): tR=1.11 min; Mass spectrum (ESI+): m/z=306 [M+H]+.
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[OH:11]N1[C:16](=[O:17])[C:15]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:14]2C1=O.S(=O)(=O)(O)[OH:24]>C(O)(=O)C>[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[C:2]1=[O:11])[CH2:8]2.[OH:24][C:15]12[CH2:14][CH:21]3[CH2:20][CH:19]([CH2:10][CH:1]([CH2:2]3)[C:16]1=[O:17])[CH2:18]2
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: O=S(=O)(O)O
Reactant: C1C2CC3CC1CC(C2)C3
Solvent: CC(=O)O
Product: O=C1C2CC3CC(C2)CC1(O)C3
Product: O=C1C2CC3CC(C2)CC1C3
Yield: 25 %
Yield: 29 %

Procedure:
To 25 ml of acetic acid were added 10 mmol of adamantane, 1 mmol of N-hydroxyphthalimide, 0.05 mmol of 98% by weight sulfuric acid and 0.05 mmol of acetylacetonatovanadium V(AA)3, and the resultant mixture (pH 1.7) was stirred under an oxygen atmosphere at a temperature of 75° C. for 6 hours. The products in the reaction mixture were analyzed by gas chromatography, and, as a result, adamantane was converted into adamantanone (yield 25%) and 1-hydroxyadamantanone (yield 29%) with a conversion of 96%. Incidentally, excepting the above, 1-adamantanol (yield 10%), 1,3-adamantanediol (yield 12%) and other products (polyketone such as adamantanedione) (yield 20%) were formed.