Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([N:9]1[CH2:14][CH2:13][CH2:12][C@H:11]([C:15]([O:17]CC)=O)[CH2:10]1)=[O:8].[BH4-].[Na+].[CH2:22](O)[CH3:23]>ClCCl>[CH2:22]([C@H:10]1[CH:11]([CH2:15][OH:17])[CH2:12][CH2:13][CH2:14][N:9]1[C:7](=[O:8])[CH2:6][C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[CH3:23]
Reactant: CCOC(=O)[C@H]1CCCN(C(=O)Cc2cccs2)C1
Reactant: CCO
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Product: CC[C@H]1C(CO)CCCN1C(=O)Cc1cccs1
Temperature: 25 °C

Procedure:
(S)-ethyl 1-(2-thiopheneacetyl)-3-piperidinecarboxylate (1.053 g; 3.75 mmol) was dissolved in absolute ethanol (40 ml). Sodium borohydride (2 g; 52.9 mmol) was added and this mixture was heated to reflux. The mixture was allowed to reflux for 1 hour and was then cooled to ambient temperature, diluted with dichloromethane and carefully quenched and washed with 1 N HCl. The dichloromethane was separated, washed with saturated sodium chloride solution, dried with anhydrous potassium carbonate, and evaporated under reduced pressure at ambient temperature. The crude product was purified by chromatography on silica eluting with 100% ethyl acetate, giving (S)-ethyl 1-(2-thiopheneacetyl)-3-hydroxymethylpiperidine (715.5 mg) as a thick colorless oil. MS m/z (positive ion) 501 (dimer+Na+; 50), 488 (30), 262 (M+Na+; 75), 249 (50), 240 (MH+; 80), 102 (Et3NH+; 100).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([O:24][CH2:25][CH:26]3[CH2:28][CH2:27]3)=[N:10][CH:11]=[C:12]([CH:23]=2)[C:13]([NH:15][C@H:16]2[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]2[OH:22])=[O:14])=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9]([O:24][CH2:25][CH:26]3[CH2:27][CH2:28]3)=[N:10][CH:11]=[C:12]([CH:23]=2)[C:13]([NH:15][C@H:16]2[CH2:21][CH2:20][CH2:19][CH2:18][C:17]2=[O:22])=[O:14])=[CH:6][CH:7]=1
Reactant: O=C(N[C@H]1CCCC[C@H]1O)c1cnc(OCC2CC2)c(-c2ccc(Cl)cc2)c1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: O=C(N[C@H]1CCCCC1=O)c1cnc(OCC2CC2)c(-c2ccc(Cl)cc2)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 88.9 %

Procedure:
To a solution of 1.651 g 5-(4-chloro-phenyl)-6-cyclopropylmethoxy-N-((1S,2R)-2-hydroxy-cyclohexyl)-nicotinamide in 25 ml methylene chloride, was added 2.62 g Dess-Martin periodinane as 15% solution in dichloromethane. The reaction mixture was stirred at room temperature for 18 h. The solvent was evaporated and the residue was purified by chromatography on silica gel using a gradient of heptane:ethyl acetate=95:5 to 40:60 to yield 1.46 g of the title compound as white foam. MS (EI): 399.1 (M+H).
Reaction SMILES: CC(C)([O-])C.[K+].C1COCC1.[CH3:12][C:13]1([CH3:25])[C:17]([CH3:19])([CH3:18])[O:16][B:15]([C:20]2[CH:21]=[N:22][NH:23][CH:24]=2)[O:14]1.Br[CH2:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29]>CN(C)C=O.C(OCC)(=O)C>[CH3:12][C:13]1([CH3:25])[C:17]([CH3:18])([CH3:19])[O:16][B:15]([C:20]2[CH:24]=[N:23][N:22]([CH2:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH:21]=2)[O:14]1
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: CC(C)(C)OC(=O)CBr
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
1.0 M Potassium tert-butoxide in THF (2.4 mL, 2.4 mmol) was added to a solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.39 g, 2.0 mmol) in N,N-dimethylformamide (6.0 mL) at 0° C. The reaction mixture was stirred at room temperature for 5 min. After cooled to 0° C., to the mixture was added t-butyl bromoacetate (0.5 mL, 3 mmol). The reaction was stirred at room temperature for 2 h, then diluted with ethyl acetate, washed with sat. NaHCO3, water, brine, dried over Na2SO4, filtered and concentrated. The product (0.5 g, 81%) was purified by chromatography eluting with hexanes/EtOAc (max. EtOAc 30%). LCMS calculated for C15H26BN2O4 (M+H)+: m/z=309.2; Found: 309.1
Reaction SMILES: [NH:1]1[C:6](=O)[CH2:5][NH:4][C@@H:3]2[CH2:8][CH2:9][CH2:10][C@@H:2]12.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[NH:1]1[CH2:6][CH2:5][NH:4][C@@H:3]2[CH2:8][CH2:9][CH2:10][C@@H:2]12
Reactant: O=C1CN[C@@H]2CCC[C@H]2N1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: C1C[C@H]2NCCN[C@@H]2C1
Temperature: 65 °C

Procedure:
To a cooled (0° C.) solution of (4aR,7aR)-octahydro-2H-cyclopenta[b]pyrazin-2-one (prepared in analogy to Example 3.120, Steps 1-3) (570 mg, 4.07 mmol) in THF (27 mL) was added dropwise LAH (4.07 mL of a 2.0M solution in THF, 8.14 mmol) over 5 minutes. After the addition was complete, the mixture was capped with a reflux condenser and heated to 65° C. for 14 hours. The resulting mixture was then cooled to room temperature and carefully quenched by the addition of sodium sulfate decahydrate (1.3 g). The reaction mixture was filtered through Celite®, and the filter cake was washed with ethyl acetate. The combined filtrate was dried over magnesium sulfate, filtered, evaporated under reduced pressure and dried in vacuo to give (4aR,7aR)-octahydro-1H-cyclopenta[b]pyrazine. 1H NMR (500 MHz, DMSO-d6) δ 2.75-2.69 (m, 2H), 2.55-2.50 (m, 2H), 2.13-2.07 (m, 4H), 1.66-1.59 (m, 2H), 1.57-1.51 (m, 2H), 1.22-1.12 (m, 2H). Example 5.1 3-(2-((R)-4-acetyl-2-methylpiperazin-1-yl)-4-(5-chloropyridin-3-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridin-6-yl)-1,2,4-oxadiazol-5(4H)-one
Reaction SMILES: [CH3:1][N:2]([CH3:19])[C:3](=[O:18])[C@@H:4]([O:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[C:9](=O)[NH:10][CH:11]=[N:12]2)[CH3:5].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)Cl.[N:44]1[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=1[CH2:50][N:51]1[C:59]2[C:54](=[CH:55][C:56]([NH2:60])=[CH:57][CH:58]=2)[CH:53]=[N:52]1>ClCCCl>[CH3:1][N:2]([CH3:19])[C:3](=[O:18])[C@@H:4]([O:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[C:9]([NH:60][C:56]1[CH:55]=[C:54]3[C:59](=[CH:58][CH:57]=1)[N:51]([CH2:50][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][N:44]=1)[N:52]=[CH:53]3)=[N:10][CH:11]=[N:12]2)[CH3:5]
Reactant: Nc1ccc2c(cnn2Cc2ccccn2)c1
Reactant: C[C@H](Oc1cccc2nc[nH]c(=O)c12)C(=O)N(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCCl
Solvent: ClC(Cl)(Cl)Cl
Product: C[C@H](Oc1cccc2ncnc(Nc3ccc4c(cnn4Cc4ccccn4)c3)c12)C(=O)N(C)C
Temperature: 45 °C
Reaction time: 2 h
Yield: 57.8 %

Procedure:
A mixture of (2S)—N,N-dimethyl-2-[(4-oxo-3,4-dihydroquinazolin-5-yl)oxy]propanamide (200 mg, 0.77 mmol), triphenylphosphine (603 mg, 2.3 mmol) and carbon tetrachloride (2.2 ml, 23 mmol) in 1,2-dichloroethane (5 ml) was stirred at 45° C. for 2 hours. 1-(Pyridin-2-ylmethyl)-1H-indazol-5-amine (179 mg, 0.8 mmol) was added and the solvent was evaporated under vacuum. Acetonitrile (5 ml) was added. The mixture was stirred at 75° C. for 2 hours. After cooling, 6N methanolic ammonia (3 ml) was added. The solvents were evaporated under vacuum. The residue was purified by chromatography on silica gel (eluant: 3% to 5% methanol in DCM) to give the title compound as a white foam (208 mg, 58%); NMR Spectrum (CDCl3) 1.72 (d, 3H), 3.06 (s, 3H), 3.14 (s, 3H), 5.43 (q, 1H), 5.75 (s, 2H), 6.81 (m, 2H), 7.17 (m, 1H), 7.41 (d, 1H), 7.48 (d, 1H), 7.62-7.53 (m, 2H), 7.81 (dd, 1H), 8.10 (s, 1H), 8.44 (d, 1H), 8.58 (d, 1H), 8.62 (s, 1H); Mass spectrum 468.
Reaction SMILES: [CH3:1][SiH:2]([CH3:4])[CH3:3].[CH3:5][C:6]([OH:10])([CH:8]=[CH2:9])[CH3:7].[SiH4]>C1(C)C=CC=CC=1>[CH3:5][C:6]([OH:10])([CH2:8][CH2:9][Si:2]([CH3:4])([CH3:3])[CH3:1])[CH3:7]
Reactant: C[SiH](C)C
Reactant: C=CC(C)(C)O
Agent: [SiH4]
Solvent: Cc1ccccc1
Product: CC(C)(O)CC[Si](C)(C)C
Temperature: 0 °C
Reaction time: 8 h

Procedure:
A 250 mL 3-neck round-bottom flask was equipped with a magnetic stirrer, dry-ice condenser with a nitrogen bubbler, thermocouple thermometer, ice water cooling bath, and a gas inlet tube attached through a back flow trap to a cylinder of trimethylsilane. The flask was charged with 68.9 g (0.80 mol) of 2-methyl-3-buten-2-ol and 600 mg of platinum-divinyl tetramethyl disiloxane complex in toluene (about 2 mol % platinum) and cooled to below 10° C. The reaction temperature was maintained between 5 and 10° C. as the silane (63 grams, 0.85 mol) was added slowly over 3 hours. The ice-water cooling bath was removed but the dry-ice condenser was maintained with dry-ice while stirring overnight. The condenser was removed and replaced with a distillation apparatus and the reaction mixture distilled under vacuum. The major fraction distilling at 105-108° C. at 200 milliTorr was collected, yielding 124 grams of product.
Reaction SMILES: [CH:1]([NH:4][S:5]([CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=1)(=[O:7])=[O:6])([CH3:3])[CH3:2].[CH2:17]([O:19][C:20]([C:22]1[C:23](=[O:42])[C:24]2[CH:29]=[N:28][C:27](S(C)(=O)=O)=[N:26][C:25]=2[N:34]([CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)[CH:35]=1)=[O:21])[CH3:18]>>[CH2:17]([O:19][C:20]([C:22]1[C:23](=[O:42])[C:24]2[CH:29]=[N:28][C:27]([NH:16][C:13]3[CH:12]=[CH:11][C:10]([CH2:9][CH2:8][S:5](=[O:7])(=[O:6])[NH:4][CH:1]([CH3:3])[CH3:2])=[CH:15][CH:14]=3)=[N:26][C:25]=2[N:34]([CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)[CH:35]=1)=[O:21])[CH3:18]
Reactant: CC(C)NS(=O)(=O)CCc1ccc(N)cc1
Reactant: CCOC(=O)c1cn(C2CCCCC2)c2nc(S(C)(=O)=O)ncc2c1=O
Product: CCOC(=O)c1cn(C2CCCCC2)c2nc(Nc3ccc(CCS(=O)(=O)NC(C)C)cc3)ncc2c1=O

Procedure:
Using the procedure outlined in Example 1(g) the title compound was prepared from 2-(4-amino-phenyl)-ethanesulfonic acid isopropylamide (from Example 33(B), 68 mg, 0.28 mmol) and 8-cyclohexyl-2-methanesulfonyl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (from Example 17(e), 100 mg, 0.26 mmol). The title compound was obtained as a yellow solid (50 mg, 35%). 1H NMR (400 MHz, CDCl3) δ (ppm): 9.34 (s, 1H), 8.54 (s, 1H), 7.88 (br, 1H), 7.61 (d, J=8.3 Hz, 2H), 7.25 (d, J=8.3 Hz, 2H), 5.10 (m, 1H), 4.40 (q, J=7.1 Hz, 2H), 4.17 (m, 1H), 3.66 (m, 1H), 3.29 (m, 2H), 3.14 (m, 2H), 2.06 (m, 4H), 1.86 (m, 1H), 1.68 (m, 2H), 1.51 (m, 2H), 1.41 (t, J=7.1 Hz, 3H), 1.31(m, 1H), 1.24 (s, 3H), 1.23 (s, 3H).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.[C:32]1(=[O:42])[NH:36][C:35](=[O:37])[C:34]2=[CH:38][CH:39]=[CH:40][CH:41]=[C:33]12.[CH2:43]([N:50]1[CH2:57][CH:56]2[CH:52]([CH2:53][C:54]([F:59])([F:58])[CH2:55]2)[CH:51]1[CH2:60]O)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C1COCC1.C1(C)C=CC=CC=1.CC(=O)OCC.CCCCCCC.CC(=O)OCC>[CH2:43]([N:50]1[CH2:57][C@H:56]2[C@H:52]([CH2:53][C:54]([F:59])([F:58])[CH2:55]2)[C@H:51]1[CH2:60][N:36]1[C:32](=[O:42])[C:33]2[C:34](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:35]1=[O:37])[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1
Reactant: O=C1NC(=O)c2ccccc21
Reactant: OCC1C2CC(F)(F)CC2CN1Cc1ccccc1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: O=C1c2ccccc2C(=O)N1C[C@@H]1[C@H]2CC(F)(F)C[C@H]2CN1Cc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 63.7 %

Procedure:
To a cold solution of triphenylphosphine (1.8 g) in dry THF (90 mL) was added dropwise DEAD 40% in toluene (3.15 mL). Then was added successively phthalimide (1.01 g) and a solution of (3-benzyl-7,7-difluoro-3-azabicyclo[3.3.0]oct-2-yl)-methanol (WO03/062265) (1.83 g) in dry THF (10 mL). The reaction mixture was stirred at RT overnight, diluted with EA, washed with water. The organic phase was washed with sat. NaHCO3 solution, dried (MgSO4), filtered and concentrated to yield a crude oil. FC (n-heptane/EA: 7/3 to 1/1) gave 1.73 g (64%) of the title compound as a white solid. LC-MS: tR=0.87 min; [M+H]+=397.47.
Reaction SMILES: [O:1]=[C:2]1[C:8]([CH3:10])([CH3:9])[CH2:7][C:5](=[O:6])[CH:4]=[C:3]1[CH3:11]>C(Cl)Cl>[CH3:10][C:8]1([CH3:9])[CH2:7][C:5](=[O:6])[CH2:4][C@@H:3]([CH3:11])[C:2]1=[O:1]
Reactant: CC1=CC(=O)CC(C)(C)C1=O
Solvent: ClCCl
Product: C[C@@H]1CC(=O)CC(C)(C)C1=O

Procedure:
The water phase (190 liters+5 liters of wash-water) is stirred out five times with 60 liters of methylene chloride each time. The solvent phase is separated, washed twice with 60 liters of water each time and concentrated to about 15 liters on a rotary evaporator. This concentrate is dehydrated with 1.5 kg of sodium sulphate, filtered and concentrated to dryness under reduced pressure. The residue (1755 g) is dissolved while hot in 6 liters of diisopropyl ether, decolourised with 80 g of active carbon, filtered over diatomaceous earth padding and rinsed with 1.8 liters of hot diisopropyl ether. From this solution, 2.6 liters of diisopropyl ether are distilled off at normal pressure, such that the product remains dissolved in a three-fold amount of diisopropyl ether. The product is crystallised overnight at 5° C., filtered off under suction, washed twice with 1500 ml of cold n-hexane each time and dried for 15 hours at 40° C. under reduced pressure. This first crystallisation produces 1280 g of optically pure [6R]-2,2,6-trimethyl-1,4-cyclohexanedione of melting point 91°-92° C. The mother liquor contains a further 447 g of substances. The latter is taken up in the same amount of n-hexane, treated with diisopropyl ether until the solution is clear, crystallised overnight at 5° C., filtered off under suction and washed twice with a small amount of cold n-hexane. The crystallisate is dried at 40° C. under reduced pressure. This second crystallisation produces 83.6 g of product with a melting point of 70°-88° C. After triple recrystallisation with the three-fold amount of diisopropyl ether, there are obtained a further 43 g of optically pure [6R]-2,2,6 -trimethyl-1,4-cyclohexanedione of melting point 90.5°-91.5° C.
Reaction SMILES: [F:1][C:2]([F:43])([F:42])[C:3]([C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[C:27]([C:32]([OH:41])([C:37]([F:40])([F:39])[F:38])[C:33]([F:36])([F:35])[F:34])[CH:26]=1)([C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([C:15]([C:21]([F:24])([F:23])[F:22])([OH:20])[C:16]([F:19])([F:18])[F:17])[CH:9]=1)[C:4]([F:7])([F:6])[F:5].C(N(CC)CC)C.[CH3:51][S:52](Cl)(=[O:54])=[O:53]>C(Cl)Cl>[F:1][C:2]([F:42])([F:43])[C:3]([C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[C:27]([C:32]([O:41][S:52]([CH3:51])(=[O:54])=[O:53])([C:37]([F:38])([F:39])[F:40])[C:33]([F:36])([F:35])[F:34])[CH:26]=1)([C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([C:15]([C:16]([F:18])([F:17])[F:19])([O:20][S:52]([CH3:51])(=[O:54])=[O:53])[C:21]([F:22])([F:23])[F:24])[CH:9]=1)[C:4]([F:7])([F:6])[F:5]
Reactant: CS(=O)(=O)Cl
Reactant: Cc1ccc(C(c2ccc(C)c(C(O)(C(F)(F)F)C(F)(F)F)c2)(C(F)(F)F)C(F)(F)F)cc1C(O)(C(F)(F)F)C(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc(C(c2ccc(C)c(C(OS(C)(=O)=O)(C(F)(F)F)C(F)(F)F)c2)(C(F)(F)F)C(F)(F)F)cc1C(OS(C)(=O)=O)(C(F)(F)F)C(F)(F)F
Temperature: 25 °C
Reaction time: 24 h
Yield: 73.8 %

Procedure:
10.1 g (15.2 mmol) of 1,1,1,3,3,3-hexafluoro-2,2-bis-[4-methyl-3-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-propane were dissolved in 50 ml of methylene chloride, and 3.4 g (33 mmol) of triethylamine were added at 0° C. 4.0 g (34.7 mmol) of methanesulfonyl chloride in 20 ml of methylene chloride were added dropwise at 0° to 5° C. The mixture was stirred for 24 hours at room temperature, separated off from the precipitated salt, washed with water, dried and evaporated down. The oily residue was recrystallized. 9.2 g of 1,1,1,3,3,3-hexafluoro-2,2-bis-[4-methyl-3-(2,2,2-trifluoro-1-methanesulfonyloxy-1-trifluoromethyl-ethyl)-phenyl]-propane were obtained (colorless crystals, m.p.: 135° C. [from toluene]).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[C:4]([N+:11]([O-])=O)[CH:3]=1.[CH3:14][NH:15][CH:16]=O>O>[Br:1][C:2]1[CH:3]=[C:4]2[C:5]([C:6](=[O:7])[N:15]([CH3:16])[CH:14]=[N:11]2)=[CH:9][CH:10]=1
Reactant: O=C(O)c1ccc(Br)cc1[N+](=O)[O-]
Reactant: CNC=O
Solvent: O
Product: Cn1cnc2cc(Br)ccc2c1=O
Temperature: 25 °C
Yield: 51 %

Procedure:
A solution of 4-bromo-2-nitrobenzoic acid (1 g, 4.1 mmol) and InCl3 (0.88 g, 4 mmol) in N-methylformamide (6 mL, 100 mmol) was stirred at reflux overnight (ca. 18 h). After it was cooled to room temperature, the mixture was diluted with H2O (30 mL) and extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with brine, and dried over Na2SO4. After filtration and concentration, the crude product was purified by column chromatography to give the desired product (0.5 g). MS (ESI): 239 (MH+).
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[N:14]=[C:13]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]3[CH2:23][CH2:24][O:25][CH2:26][CH:27]=3)[CH:17]=2)[C:12]([C:28]([NH2:30])=[O:29])=[CH:11][N:10]=1>CO.[Pd]>[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[N:14]=[C:13]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([CH:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)[CH:17]=2)[C:12]([C:28]([NH2:30])=[O:29])=[CH:11][N:10]=1
Reactant: NC(=O)c1cnc(N[C@@H]2CCCC[C@@H]2N)nc1Nc1cccc(C2=CCOCC2)c1
Agent: [Pd]
Solvent: CO
Product: NC(=O)c1cnc(N[C@@H]2CCCC[C@@H]2N)nc1Nc1cccc(C2CCOCC2)c1

Procedure:
The title compound was prepared from Example 175 using standard catalysis hydrogenation by treating the solution of Example 175 in methanol with 10% Pd/C under H2 balloon for overnight. MS found for C22H30N6O2 as (M+H)+ 411.4. UV λ=241, 290 nm.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11](O)=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:14]1[CH2:18][CH2:17][S:16](=[O:20])(=[O:19])[CH2:15]1.C1C=CC2N(O)N=[N:27]C=2C=1.N.O1CCOCC1>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:27])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:14]1[CH2:18][CH2:17][S:16](=[O:20])(=[O:19])[CH2:15]1
Reactant: O=C(O)c1cc(Br)cc2c(C3CCS(=O)(=O)C3)c[nH]c12
Reactant: On1nnc2ccccc21
Agent: N
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: C1COCCO1
Product: NC(=O)c1cc(Br)cc2c(C3CCS(=O)(=O)C3)c[nH]c12
Temperature: 100 °C

Procedure:
A 20 mL microwave reaction vessel was charged with 5-bromo-3-(1,1-dioxidotetrahydro-3-thienyl)-1H-indole-7-carboxylic acid (0.50 g, 1.40 mmol) EDC (0.81 g, 4.22 mmol), HOBT (0.22 g, 1.40 mmol), and dissolved in DMF (4.65 mL). A 0.5 M solution of ammonia in 1,4 dioxane (5.6 mL, 2.81 mmol) was then added and the reaction was heated in a microwave for 20 minutes, at 100° C. The solution was then dissolved in ethyl acetate and washed with water (3×'s). The aqueous layers were backwashed with ethyl acetate.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[N:4]=1)#[CH:2].Br[C:11]1[CH2:16][CH2:15][CH2:14][C:13](=[O:17])[CH:12]=1.C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:9][C:5]1[N:4]=[C:3]([C:1]#[C:2][C:11]2[CH2:16][CH2:15][CH2:14][C:13](=[O:17])[CH:12]=2)[CH:8]=[CH:7][CH:6]=1
Reactant: O=C1C=C(Br)CCC1
Reactant: C#Cc1cccc(C)n1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: Cc1cccc(C#CC2=CC(=O)CCC2)n1
Yield: 82.8 %

Procedure:
A solution of 2-ethynyl-6-methyl-pyridine (702 mg, 6 mmol), 3-bromo-cyclohex-2-enone (1.26 g, 7.2 mmol), bis-(triphenylphosphine)palladium-dichloride (168 mg, 0.24 mmol), copper(I) iodide (93 mg, 0.48 mmol), triethylamine (4.8 ml, 34.4 mmol) in 12 ml DMF is heated to 55° C. for 1 h. After that time the solution is diluted with ethyl acetate (500 ml) and washed with sat aq. NaHCO3 (1×150 ml). The water phase is extracted with ethyl acetate (1×150 ml) and the combined organic phases are dried over Na2SO4, filtered and concentrated in vacuo. The residue (1.88 g) is purified on column chromatography (silica gel, eluent hexane/ethyl acetate 3:1 v/v) and the fractions containing the desired compound are collected and concentrated in vacuo to yield 1.05 g (yield=82%) of the title compound as a light yellow oil.
Reaction SMILES: [CH2:1]([N:8]1[CH:13]=[CH:12][C:11]([O:14]CC2C=CC=CC=2)=[C:10](I)[C:9]1=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:33]1([C:39]#[C:40][Si:41]([CH2:46][CH3:47])([CH2:44][CH3:45])[CH2:42][CH3:43])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH2:1]([N:8]1[CH:13]=[CH:12][C:11](=[O:14])[C:10]2[C:39]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[C:40]([Si:41]([CH2:46][CH3:47])([CH2:42][CH3:43])[CH2:44][CH3:45])[O:23][C:9]1=2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC[Si](C#Cc1ccccc1)(CC)CC
Reactant: O=c1c(I)c(OCc2ccccc2)ccn1Cc1ccccc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC[Si](CC)(CC)c1oc2c(c1-c1ccccc1)c(=O)ccn2Cc1ccccc1
Temperature: 108 °C
Reaction time: 8 h

Procedure:
To a solution of 1-benzyl-4-benzyloxy-3-iodo-1H-pyridin-2-one (1.00 g, 2.40 mmol), diisopropylethylamine, (0.51 mL. 2.88 mmol) and Pd(dppf)2Cl2/CH2Cl2 (0.20 g, 0.24 mmol) in DMF (10.0 mL) was slowly added 1-phenyl-2-(triethylsilyl)acetylene (1.50 g, 7.20 mmol) at room temperature under N2. The resulting reaction mixture was degassed and stirred at 108° C. under nitrogen overnight. The reaction was cooled down to room temperature, and the solvent was removed. The residue was dissolved in DCM (250 mL). The solution was washed with NaHCO3 (30×2 mL) and brine (30 mL). The organic layer was dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography, eluting with ethyl acetate/methanol/100/1, to give the title compound. MS (m/z), M+H+ 416.2.
Reaction SMILES: [CH3:1][S:2][CH2:3][CH2:4][CH2:5][OH:6].N1C=CC=CC=1.C(Cl)(Cl)Cl.[S:17](Cl)([C:20]1[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=1)(=[O:19])=[O:18]>C(Cl)Cl>[S:17]([O:6][CH2:5][CH2:4][CH2:3][S:2][CH3:1])([C:20]1[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=1)(=[O:19])=[O:18]
Reactant: CSCCCO
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: CSCCCOS(=O)(=O)c1ccc(C)cc1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
To a mixture of 3-methylthio-1-propanol (17) (5.0 g, 47.1 mmol), pyridine (7.43 g, 94.0 mmol) and CHCl3 (47 mL) cooled in an ice bath, tosyl chloride (13.47 g, 70.6 mmol) was added in portions with stirring. The mixture was allowed to warm to room temperature after 1 hour and stirring was continued for an additional 15 hours. The mixture was diluted with CH2Cl2 (200 mL), washed with water (2×100 mL), and the organic phase as dried (Na2SO4). The solvent was evaporated and the resulting yellow oil purified by column chromatography (silica gel, 15 wt % ether/hexanes, 50 wt % ether/hexanes), to give a colorless oil (10.5 g, 86 wt %), namely 3-methylthio-1-propanol tosylate.