Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[O:6][CH:5]=[N:4][C:3]=1[C:7]([OH:9])=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:43]1([C:48]2[CH:49]=[C:50]([NH2:60])[CH:51]=[N:52][C:53]=2[O:54][CH2:55][C:56]([F:59])([F:58])[F:57])[CH2:47][CH2:46][CH2:45][CH2:44]1>CN(C=O)C>[CH:43]1([C:48]2[CH:49]=[C:50]([NH:60][C:7]([C:3]3[N:4]=[CH:5][O:6][C:2]=3[CH3:1])=[O:9])[CH:51]=[N:52][C:53]=2[O:54][CH2:55][C:56]([F:57])([F:58])[F:59])[CH2:44][CH2:45][CH2:46][CH2:47]1
Reactant: Cc1ocnc1C(=O)O
Reactant: Nc1cnc(OCC(F)(F)F)c(C2CCCC2)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ocnc1C(=O)Nc1cnc(OCC(F)(F)F)c(C2CCCC2)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 21.4 %

Procedure:
To a solution of 5-methyl-4-oxazolecarboxylic acid (CAN 103879-58-9) (73 mg, 0.57 mmol) in DMF (4 mL) were added DIPEA (0.1 mL, 1.15 mmol) and HATU (219 mg, 0.57 mmol) at 25° C. The reaction mixture was stirred for 30 min at 25° C. Then, 5-cyclopentyl-6-(2,2,2-trifluoro-ethoxy)-pyridin-3-ylamine (Example 1c) (100 mg, 0.38 mmol) was added and the reaction mixture was stirred at 25° C. for 12 h. Volatiles were removed in vacuo and the resultant residue was purified by prep-HPLC to get the title compound (30 mg, 21.3%) as off-white solid. MS (ESI): 370 [M+H]+.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21]([OH:24])([CH3:23])[CH3:22])[CH:9]=2)=[C:4]([CH3:25])[CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C([Li])CCC.[Br-].C1C[O:45][CH2:44]C1>CCOCC.CCCCCC.CN(C=O)C>[Cl:20][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]([Cl:19])[C:13]=1[N:12]1[C:8]([C:5]2[CH:6]=[CH:7][C:2]([CH:44]=[O:45])=[CH:3][C:4]=2[CH3:25])=[CH:9][C:10]([C:21]([OH:24])([CH3:23])[CH3:22])=[N:11]1
Reactant: C1CCOC1
Reactant: Cc1cc(Br)ccc1-c1cc(C(C)(C)O)nn1-c1c(Cl)cccc1Cl
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Br-]
Agent: [Li+]
Solvent: CCOCC
Solvent: CN(C)C=O
Solvent: CCCCCC
Product: Cc1cc(C=O)ccc1-c1cc(C(C)(C)O)nn1-c1c(Cl)cccc1Cl
Temperature: -78 °C
Reaction time: 0.17 h

Procedure:
To a cold (−78° C.) solution of 2-(5-(4-bromo-2-methylphenyl)-1-(2,6-dichlorophenyl)-1H-pyrazol-3-yl)propan-2-ol (215 mg, 0.49 mmol) in a mixture of THF (4 mL) and Et2O (4 mL) was added lithium bis(trimethylsilyl)amide (0.5 mL of a 1.0M solution in THF, 0.5 mmol). After several minutes stirring at −78° C. the resulting alkoxide solution was treated with n-butyllithium (1.0 mL of a 1.6M solution in hexane, 1.6 mmol). After 10 minutes stirring at −78° C., LC/MS showed some starting bromide present in a quenched aliquot of the reaction. After 30 minutes additional n-butyllithium was added (0.5 mL of a 1.6M solution in hexane, 0.8 mmol). After an additional 15 minutes stirring at −78° C. the reaction mixture was treated with dry N,N-dimethylformamide (0.4 mL, 5.2 mmol). Several minutes after the addition of the DMF, the −78° C. bath was replaced with an ice bath and the reaction mixture was allowed to come to ambient temperature overnight. The reaction was quenched by the addition of saturated NH4Cl and diluted with EtOAc. The layers were separated and the aqueous was extracted with EtOAc (3×). Combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure to afford a yellow syrup. The crude product was purified by flash column chromatography eluting with 0% to 100% EtOAc/hexane to afford 4-(1-(2,6-dichlorophenyl)-3-(2-hydroxypropan-2-yl)-1H-pyrazol-5-yl)-3-methylbenzaldehyde which was carried on to the next step without further purification. MS(ES): 389 [M+H]+.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Br[CH2:8][CH2:9][Cl:10].[Se:11]1(=[O:20])[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]=[CH:12]1>CN(C)C=O>[Cl:10][CH2:9][CH2:8][N:13]1[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[Se:11](=[O:20])[CH2:12]1
Reactant: ClCCBr
Reactant: O=[Se]1C=Nc2ccccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=[Se]1CN(CCCl)c2ccccc21
Temperature: 50 °C
Reaction time: 6 h

Procedure:
0.06 mol of potassium carbonate and then 0.015 mol of 1-bromo-2-chloroethane are added to a solution of 0.015 mol of benzoselenazolinone in 30 cm3 of dimethylformamide. The mixture is heated to 50° C. with stirring for six hours. The inorganic precipitate is drained and then washed with dimethyl formamide. The DMF is evaporated off under reduced pressure and the residue is taken up with water. An extraction with ether is then carried out. The organic phase is dried over sodium sulfate and then filtered. The ether phase is evaporated to dryness under reduced pressure and the product is recrystallized in petroleum ether.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[CH:10][C:9]=2[C:13]([OH:15])=O)=[CH:4][CH:3]=1.[CH2:16]1[CH2:21][NH:20][CH2:19][CH:18]([C:22]([F:25])([F:24])[F:23])[CH2:17]1>>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:12][N:11]=[CH:10][C:9]=2[C:13]([N:20]2[CH2:21][CH2:16][CH2:17][CH:18]([C:22]([F:25])([F:24])[F:23])[CH2:19]2)=[O:15])=[CH:6][CH:7]=1
Reactant: FC(F)(F)C1CCCNC1
Reactant: Cc1ccc(-c2oncc2C(=O)O)cc1
Product: Cc1ccc(-c2oncc2C(=O)N2CCCC(C(F)(F)F)C2)cc1

Procedure:
The title compound was prepared from 5-(4-methylphenyl)isoxazole-4-carboxylic acid (10.2 mg, 0.050 mmol) and DL-3-(trifluoromethyl)piperidine (9.2 mg, 0.060 mmol) as described in synthetic method B and thereafter purified by preparative HPLC method B to give a solid (11.2 mg). HRMS calcd for C17H17F3N2O2: 338.1242, found 338.1242.
Reaction SMILES: [CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[Cl:19][Si:20]([Cl:26])([Cl:25])[CH2:21][SiH:22]([Cl:24])[Cl:23]>>[Cl:19][Si:20]([Cl:26])([Cl:25])[CH2:21][Si:22]([Cl:24])([Cl:23])[CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: Cl[SiH](Cl)C[Si](Cl)(Cl)Cl
Reactant: C=CCCCCCCCCCCCCCCCC
Product: CCCCCCCCCCCCCCCCCC[Si](Cl)(Cl)C[Si](Cl)(Cl)Cl

Procedure:
The 1,1,1,3,3-pentachloro-1,3-disilapropane may be reacted directly with an olefin by a hydrosilylation reaction or may be esterified to the corresponding pentaalkoxysilane derivative and then reacted with an olefin by a hydrosilylation reaction to yield the final desired product. As a simple example, octadecene may be reacted with 1,1,1,3,3-pentachloro-1,3-disilapropane (II) to form 1,1,1,3,3-pentachloro-1,3-disilaheneicosane. This compound may then be esterified with an alcohol to form, for example, 1,1,1,3,3-pentamethoxy-1,3-disilaheneicosane (from esterification with methanol) or reduced to form 1,3-disilaheneicosane. In some cases it is advantageous to form the esterified product, for example, 1,1,1,3,3-pentaethoxy-1,3-disilapropane, first, followed by hydrosilylation as the second step. This is especially important if the olefin reacts with chlorosilanes but does not react with alkoxy silanes. For example, the epoxy group of allylglycidyl ether reacts with chlorosilanes but is unreactive with alkoxy silanes.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:19][CH2:18][CH2:17][NH:16][C:15]2=[O:20])[CH2:10][CH2:9]1)C1C=CC=CC=1>[OH-].[OH-].[Pd+2]>[N:11]1([N:14]2[CH2:19][CH2:18][CH2:17][NH:16][C:15]2=[O:20])[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1
Reactant: O=C1NCCCN1N1CCN(Cc2ccccc2)CC1
Agent: [Pd+2]
Agent: [OH-]
Product: O=C1NCCCN1N1CCNCC1
Temperature: 25 °C
Reaction time: 60 h

Procedure:
To a solution of 1-(4-benzylpiperazin-1-yl)tetrahydropyrimidin-2(1H)-one obtained in Example 25a) (0.82 g) was added 20% palladium hydroxide on carbon (containing 50% water; 0.20 g), and the mixture was stirred at room temperature for 60 hours under a hydrogen atmosphere. The reaction mixture was filtered, and the solvent was distilled off under reduced pressure to obtain the title compound (0.56 g, quantitative) as colorless crystals.
Reaction SMILES: CCN(C(C)C)C(C)C.[CH3:10][O:11][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:21]=1[O:20][C:19](=[O:22])[C:18]([C:23]([OH:25])=O)=[CH:17]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:50][O:51][C:52]1[N:57]=[C:56]([O:58][CH3:59])[C:55]([C:60]2[CH:61]=[C:62]([NH2:66])[CH:63]=[CH:64][CH:65]=2)=[CH:54][N:53]=1>CN(C=O)C>[CH3:50][O:51][C:52]1[N:57]=[C:56]([O:58][CH3:59])[C:55]([C:60]2[CH:61]=[C:62]([NH:66][C:23]([C:18]3[C:19](=[O:22])[O:20][C:21]4[C:16]([CH:17]=3)=[CH:15][CH:14]=[CH:13][C:12]=4[O:11][CH3:10])=[O:25])[CH:63]=[CH:64][CH:65]=2)=[CH:54][N:53]=1
Reactant: COc1cccc2cc(C(=O)O)c(=O)oc12
Reactant: COc1ncc(-c2cccc(N)c2)c(OC)n1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1ncc(-c2cccc(NC(=O)c3cc4cccc(OC)c4oc3=O)c2)c(OC)n1
Temperature: 25 °C
Yield: 67.4 %

Procedure:
DIEA (0.012 mL, 0.071 mmol) was added to 8-methoxy-3-carboxy-coumarin (0.014 g, 0.065 mmol) and HATU (0.027 g, 0.071 mmol) in 0.5 mL of DMF with constant stirring at room temperature until a clear solution resulted. Subsequently, 3-(2,4-dimethoxy-pyrimidin-5-yl)-phenylamine (0.015 g, 0.065 mmol) was added and allowed to react overnight when a solid precipitated out of solution. The resulting precipitate was filtered, dried under suction, and finally dried overnight in vacuo to give 0.019 g of product in 69% yield: LCMS (ESI) m/z 434 (MH+).
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@H:14]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@@H:13]([CH2:32][O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:12][C:10]1=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li][CH3:42]>C1COCC1>[CH2:1]([O:8][C@@H:9]1[C@@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@H:14]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C@@H:13]([CH2:32][O:33][CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[O:12][C:10]1([OH:11])[CH3:42])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: [Li]C
Reactant: O=C1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Solvent: C1CCOC1
Product: CC1(O)O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 96.2 %

Procedure:
18 g (33 mmol) of 21a was dissolved in 200 mL of anhydrous THF under nitrogen. Cooled to −78° C. 45 mL of MeLi (1.6 M, 72 mmol) was added by a syringe. After 1 hour at −78° C., the reaction was quenched by a solution of 7 g of NH4Cl in 200 mL of H2O. TLC showed no starting material left, while a new spot corresponding to the product appeared. The mixture was extracted by 3×150 mL of ethyl acetate, washed by brine, dried over Na2SO4. After evaporation, a thick pale yellow oil was obtained which was turned into a white solid (17.6 g, 95% yield) with a melting point of 92–93° C. 300 MHz 1H NMR(CDCl3) δ: 1.41 (s, 3H, CH3); 2.58 (s, 1H, OH); 3.35–3.38 (d, 1H); 3.65–3.72 (m, 3H); 3.93–3.99 (m, 2H); 4.50–4.95 (m, 8H, 4-CH2), 7.14–7.36 (m, 20H). 13C NMR (CDCl3) δ: 26.59, 68.81, 71.55, 73.42, 74.85, 75.58, 75.68, 78.42, 83.18, 83.63, 97.36, 127.58, 127.65, 127.74, 127.82, 127.84, 127.91, 128.28, 128.32, 128.36, 128.41, 137.87, 138.21, 138.25, 138.64.
Reaction SMILES: [O-]CC.[Na+].[CH2:5]([SH:7])[CH3:6].Cl[C:9]1[C:10]([C:15](=[O:18])[CH2:16][CH3:17])=[N:11][CH:12]=[CH:13][N:14]=1.O>C(O)C>[CH2:5]([S:7][C:9]1[C:10]([C:15](=[O:18])[CH2:16][CH3:17])=[N:11][CH:12]=[CH:13][N:14]=1)[CH3:6]
Reactant: CCS
Reactant: CCC(=O)c1nccnc1Cl
Agent: CC[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCSc1nccnc1C(=O)CC
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 87 %

Procedure:
A mixture of sodium ethoxide (100 mg, 1.47 mmoles) and ethanethiol (110 mg, 1.77 mmoles) in 7 ml of absolute ethanol is stirred under nitrogen at room temperature for 10 minutes. 1-(3-Chloro-2-pyrazinyl)-1-propanone (250 mg, 1.47 mmoles) in 5 ml absolute ethanol is added to the above mixture, and the reaction mixture is stirred for 4 hours at which time thin layer chromatography indicates that all of the starting materials have reacted. The mixture is poured into water (100 ml) and extracted with methylene chloride (3×10 ml), and the extracts are combined and washed with water (1×50 ml) and saturated NaCl solution (1×50 ml). After drying (MgSO4), the solvent is removed under reduced pressure to give an 87% yield of 1-(3-ethylthio-2-pyrazinyl)-1-propanone (m.p. 45°-48° C.).
Reaction SMILES: [C:1]([C:5]1[CH:17]=[CH:16][C:15]2[C:14]3[C:9](=[CH:10][C:11]([C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:12][CH:13]=3)[CH2:8][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.CCCCCC.[C:33]([C:37]1[CH:38]=[C:39]([CH3:55])[C:40](=[C:42]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:41]=1)([CH3:36])([CH3:35])[CH3:34].Cl>C(OCC)C>[C:33]([C:37]1[CH:38]=[C:39]([CH3:55])[CH:40]([C:42]([C:10]2[C:9]3[CH2:8][C:7]4[C:15](=[CH:16][CH:17]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:6]=4)[C:14]=3[CH:13]=[CH:12][C:11]=2[C:18]([CH3:21])([CH3:20])[CH3:19])([C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH:41]=1)([CH3:34])([CH3:35])[CH3:36]
Reactant: CC1=CC(C(C)(C)C)=CC1=C(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)c1ccc2c(c1)Cc1cc(C(C)(C)C)ccc1-2
Agent: Cl
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: CCCCCC
Product: CC1=CC(C(C)(C)C)=CC1C(c1ccccc1)(c1ccccc1)c1c(C(C)(C)C)ccc2c1Cc1cc(C(C)(C)C)ccc1-2
Temperature: 25 °C

Procedure:
In a 200 ml three-necked flask equipped with a magnetic stirrer chip and three-way cock thoroughly purged with nitrogen, 2.53 g of 2,7-di-tert-butyl-fluorene (9.10 mmol) was dissolved in 70 ml of dehydrated diethyl ether in a nitrogen atmosphere. To the solution, 6.4 ml of a n-butyl lithium/hexane solution (1.56M: 9.98 mmol) was gradually added dropwise in an ice bath and stirred at room temperature over night. To the reaction solution, a solution prepared by dissolving 3.01 g of 3-tert-butyl-1-methyl-6,6-diphenyl fulvene (10.0 mmol) in 40 ml of dehydrated diethyl ether was added and stirred with refluxing for 7 days. The reaction mixture was added to 100 ml of a hydrochloric acid aqueous solution (1N) and thereafter diethyl ether was added to separate an organic phase. The organic phase was washed with a saturated sodium bicarbonate aqueous solution and saturated brine. The organic phase was dried with anhydrous magnesium sulfate, thereafter the drying agent was filtered off and the solvent was distilled off from the filtrate under reduced pressure to give a reddish-brown liquid. The liquid was purified by a column chromatography using 180 g of silica gel (developing solvent: n-hexane) and the developing solvent was distilled off under reduced pressure. The remainder was re-crystallized using methanol and dried under reduced pressure, and thereby the aimed compound was obtained in an amount of 1.65 g (2.85 mmol) as a pale yellow solid (yield: 31%).
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[Cl:11][C:12]1[CH:13]=[C:14]([CH:33]=[CH:34][C:35]=1[Cl:36])[CH2:15][N:16]1[CH2:21][CH2:20][O:19][CH:18]([CH2:22][NH:23][C:24]([NH:26][CH:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[O:25])[CH2:17]1.C(N(CC)C(C)C)(C)C>ClCCl>[C:1]([N:30]1[CH2:31][CH2:32][CH:27]([NH:26][C:24]([NH:23][CH2:22][CH:18]2[O:19][CH2:20][CH2:21][N:16]([CH2:15][C:14]3[CH:33]=[CH:34][C:35]([Cl:36])=[C:12]([Cl:11])[CH:13]=3)[CH2:17]2)=[O:25])[CH2:28][CH2:29]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(NCC1CN(Cc2ccc(Cl)c(Cl)c2)CCO1)NC1CCNCC1
Reactant: O=C(Cl)c1ccccc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NCC1CN(Cc2ccc(Cl)c(Cl)c2)CCO1)NC1CCN(C(=O)c2ccccc2)CC1
Temperature: 23 °C
Reaction time: 5 h

Procedure:
Benzoyl choride (0.014 ml) was added to a solution of Intermediate 16 (0.04 g) and N,N-diisopropylethylamine (0.048 ml) in dichloromethane (3 ml). The solution was stirred for 5 h at 23° C. The solvent was removed in vacuo and the residue purified by solid phase extraction (Isolute SCX sulphonic acid column) eluting with methanol followed by 10% 0.880 ammonia solution in methanol. The basic fraction was concentrated in vacuo and the residue was further purified using a silica gel solid phase extraction cartridge (1 g Varian Bond Elut), eluting sequentially with dichloromethane, ethyl acetate, acetone, acetonitrile, and methanol, to give the title compound as a clear gum (0.024 g).
Reaction SMILES: C(O[CH:4](OCC)[CH2:5][N:6]1[C:10](=[O:11])[C:9]2=[CH:12][CH:13]=[CH:14][CH:15]=[C:8]2[C:7]1=[O:16])C.Cl.[CH2:21]([N:28]1[C:34](=[O:35])[C@H:33]2[CH2:36][CH2:37][CH2:38][C@H:32]2[NH:31][C:30]2[CH:39]=[CH:40][CH:41]=[CH:42][C:29]1=2)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.O.ClCCl>[CH2:21]([N:28]1[C:34](=[O:35])[C@H:33]2[CH2:36][CH2:37][CH2:38][C@H:32]2[N:31]([CH2:4][CH2:5][N:6]2[C:7](=[O:16])[C:8]3=[CH:15][CH:14]=[CH:13][CH:12]=[C:9]3[C:10]2=[O:11])[C:30]2[CH:39]=[CH:40][CH:41]=[CH:42][C:29]1=2)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: O=C1[C@H]2CCC[C@H]2Nc2ccccc2N1Cc1ccccc1
Reactant: CCOC(CN1C(=O)c2ccccc2C1=O)OCC
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Solvent: ClCCl
Product: O=C1c2ccccc2C(=O)N1CCN1c2ccccc2N(Cc2ccccc2)C(=O)[C@H]2CCC[C@H]21
Temperature: 50 °C
Reaction time: 1.33 h
Yield: 57.3 %

Procedure:
To a solution of phthalimidoacetaldehyde diethyl acetal (790 mg, 3.0 mmol) in acetic acid (2.5 mL) was added conc.HCl (0.1 mL). The mixture was stirred for 80 minutes at 50° C. The reaction mixture was cooled to room temperature, to which was added (3aR*,10aS*)-9-benzyl-2,3,3a,4,9,10a-hexahydrobenzo[b]cyclopenta [e][1,4]diazepin-10(1H)-one (877 mg, 3.0 mmol), and the mixture was stirred for 25 minutes at room temperatures. To this solution was added, sodium triacetoxyborohydride (805 mg, 3.9 mmol) portionwise, and the mixture was stirred for 40 minutes at 45° C. The reaction mixture was cooled to room temperatures, to which were added dichloromethane (10 mL) and water (10 mL). The aqueous layer was separated, and the organic layer was washed with water and a saturated aqueous solution of sodium hydrogencarbonate, dried over magnesium sulfate and subjected to filtration. The filtrate was concentrated under reduced pressure. The concentrate was purified by silica-gel column chromatography (chloroform-methanol 20:1), followed by crystallization from ethanol-hexane to give 0.80 g (yield 57%) the titled compound. The sample for analytical experiment was prepared by recrystallization from dichloromethane-ethanol-hexane. m.p. 142.0°-142.6° C.
Reaction SMILES: C([O:3][C:4]([C:6]1([CH2:20][CH:21]=[CH2:22])[C:10]2[NH:11][C:12]3[C:13]([Cl:19])=[CH:14][CH:15]=[C:16]([Cl:18])[C:17]=3[C:9]=2[CH2:8][CH2:7]1)=[O:5])C.[OH-].[Li+]>C(O)C>[CH2:20]([C:6]1([C:4]([OH:5])=[O:3])[C:10]2[NH:11][C:12]3[C:13]([Cl:19])=[CH:14][CH:15]=[C:16]([Cl:18])[C:17]=3[C:9]=2[CH2:8][CH2:7]1)[CH:21]=[CH2:22]
Reactant: C=CCC1(C(=O)OCC)CCc2c1[nH]c1c(Cl)ccc(Cl)c21
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Product: C=CCC1(C(=O)O)CCc2c1[nH]c1c(Cl)ccc(Cl)c21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To 3-Allyl-5,8-dichloro-1,2,3,4-tetrahydro-cyclopenta[b]indole-3-carboxylic acid ethyl ester was added 1 mL of 2.0 M lithium hydroxide aqueous solution and 1 mL of ethanol. The reaction mixture was stirred at room temperature for 2 hours than concentrated. The residue was purified by reverse phase HPLC to give the desired product.
Reaction SMILES: [NH2:1][C:2]1[N:6]([C@@H:7]2[O:13][C@H:12]([CH2:14][OH:15])[C@@H:10]([OH:11])[C@H:8]2[OH:9])[CH:5]=[N:4][C:3]=1[C:16]([NH2:18])=[O:17].C([N:27]=[C:28]=[S:29])(=O)C1C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].C(O)(=O)C>CN(C=O)C.O.CO>[C@@H:7]1([N:6]2[C:2]([NH:1][C:28](=[S:29])[NH2:27])=[C:3]([C:16]([NH2:18])=[O:17])[N:4]=[CH:5]2)[O:13][C@H:12]([CH2:14][OH:15])[C@@H:10]([OH:11])[C@H:8]1[OH:9]
Reactant: O=C(N=C=S)c1ccccc1
Reactant: NC(=O)c1ncn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c1N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Solvent: CN(C)C=O
Product: NC(=O)c1ncn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c1NC(N)=S
Yield: 81.4 %

Procedure:
5-Amino-1-(β-D-ribofuranosyl)-1H-imidazole-4-carboxamide (5.0 g, 19.4 mM) and benzoylisothiocyanate (3.3 g, 20 mM) was stirred at room temperature in DMF (40 ml) for 1 hour. The solvent was stripped off in water-jet vacuo. The residue was dissolved in methanol (160 ml) and potassium carbonate (1.6 g, 11.6 mM) in water (8 ml) was added whereafter the mixture was refluxed at 2 hours. After cooling to room temperature acetic acid was added to pH 6. The reaction mixture was evaporated in water-jet vacuo, and the residue was crystallized from ethanol. Hereby was isolated 5.0 g of crude 1-(β-D-ribofuranosyl)-5-(thiocarbamoyl)amino-1H-imidazole-4-carboxamide. HPLC indicated a purity of about 65% (the remaining 35% was essentially potassium acetate).
Reaction SMILES: Cl.[NH2:2][CH:3]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[C:30]=1[Cl:36])[CH2:4][NH:5][C:6](=[O:28])[CH2:7][N:8]1[C:12](=[O:13])[N:11]([CH2:14][C@H:15]([OH:20])[C:16]([F:19])([F:18])[F:17])[C:10]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)=[N:9]1.[CH3:37][S:38](Cl)(=[O:40])=[O:39]>>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([C:10]2[N:11]([CH2:14][C@H:15]([OH:20])[C:16]([F:18])([F:17])[F:19])[C:12](=[O:13])[N:8]([CH2:7][C:6]([NH:5][CH2:4][CH:3]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[C:30]=3[Cl:36])[NH:2][S:38]([CH3:37])(=[O:40])=[O:39])=[O:28])[N:9]=2)=[CH:22][CH:23]=1
Reactant: NC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(C[C@H](O)C(F)(F)F)c1=O)c1cccc(Cl)c1Cl
Reactant: CS(=O)(=O)Cl
Agent: Cl
Product: CS(=O)(=O)NC(CNC(=O)Cn1nc(-c2ccc(Cl)cc2)n(C[C@H](O)C(F)(F)F)c1=O)c1cccc(Cl)c1Cl

Procedure:
Analogously to Example 16, treatment of 76 mg (0.13 mmol) of the compound of Example 55A with methanesulphonyl chloride gave 59 mg (73% of theory) of the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]3[CH2:14][CH2:15][CH2:16][C:11]3=[C:10]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C:25]([OH:27])=[O:26])=[CH:20][CH:19]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.Cl.[CH3:29]O>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]3[CH2:14][CH2:15][CH2:16][C:11]3=[C:10]([CH2:17][C:18]3[CH:19]=[CH:20][C:21]([CH2:24][C:25]([O:27][CH3:29])=[O:26])=[CH:22][CH:23]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)Cc1ccc(Cc2cc(-c3cccc(Cl)c3)nc3c2CCC3)cc1
Reactant: CO
Agent: Cl
Product: COC(=O)Cc1ccc(Cc2cc(-c3cccc(Cl)c3)nc3c2CCC3)cc1
Reaction time: 23 h
Yield: 10.6 %

Procedure:
A 25-mL flask, with stirrer bar, was charged with 2-(4-((2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)methyl)phenyl)acetic acid (0.066 g, 0.17 mol), 4M HCl/methanol (0.22 mL, 0.87 mmol) and methanol (4 mL). After 23 h, the reaction was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and saturated sodium bicarbonate (20 mL). The organic layer was washed with saturated sodium chloride (10 mL) then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica using hexanes/ethyl acetate (10:0 to 0:10) as eluent to afford the title compound (0.036 g, 48%) as an off-white solid. MW=391.89. 1H NMR (CDCl3, 500 MHz) δ 7.94-7.91 (m, 1H), 7.77 (dt, J=7.0, 2.0 Hz, 1H), 7.36-7.30 (m, 2H), 7.24 (s, 1H), 7.21 (d, J=8.0 Hz, 2H), 7.13 (d, J=8.0 Hz, 2H), 3.95 (s, 2H), 3.69 (s, 3H), 3.60 (s, 2H), 3.08 (t, J=8.0 Hz, 2H), 2.86 (t, J=7.5 Hz, 2H), 2.18-2.09 (m, 2H); APCI MS m/z 392 [M+H]+.