Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([C:8]([NH2:10])=[O:9])[CH:5]=[CH:4][N:3]=1.[Br:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]#[CH:24].C1(NC2CCCCC2)CCCCC1.C>C(#N)C.CCOCC.C(O)C.C1(C)C=CC=CC=1.[Cu]I>[Br:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]#[C:24][C:2]1[CH:7]=[C:6]([C:8]([NH2:10])=[O:9])[CH:5]=[CH:4][N:3]=1
Reactant: NC(=O)c1ccnc(Br)c1
Reactant: C#CCCCCOCCCCCCBr
Agent: [Cu]I
Agent: C1CCC(NC2CCCCC2)CC1
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: NC(=O)c1ccnc(C#CCCCCOCCCCCCBr)c1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A mixture of 2-bromo-4-pyridinecarboxamide (1.1 g), BTPC (35 mg), copper (I) iodide (8 mg), 6-[(6-bromohexyl)oxy]-1-hexyne (1.43 g) and dicyclohexylamine (1.2 ml) in acetonitrile (20 ml) was stirred at room temperature, under nitrogen, for 20 h, then left to stand for 24 h. The yellow mixture was diluted with ether (50 ml), filtered, the filtrate dried and evaporated in vacuo to give a yellow waxy solid. The solid was purified by FCC eluting with System A (98:2:1) to give a pale yellow waxy solid. The solid was dissolved in ethanol:toluene (1:1), (20 ml) treated with activated charcoal (0.2 g), heated, filtered through hyflo and evaporated in vacuo to give the title compound as a pale yellow waxy solid (1.04 g), t.l.c. (toluene-ethanol: 0.880 ammonia, 90:10:1) Rf 0.31.
Reaction SMILES: C[O:2][C:3](=O)[CH:4]=[CH:5][CH:6]=[CH:7][CH2:8][S:9]([C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1)=[O:10].[NH2:19][OH:20].[OH-].[K+].CO>C1COCC1>[OH:20][NH:19][C:3](=[O:2])[CH:4]=[CH:5][CH:6]=[CH:7][CH2:8][S:9]([C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1)=[O:10]
Reactant: COC(=O)C=CC=CCS(=O)c1ccc(Cl)cc1
Reactant: NO
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(C=CC=CCS(=O)c1ccc(Cl)cc1)NO
Temperature: 0 °C
Reaction time: 1 h
Yield: 56.4 %

Procedure:
To a solution of the 6-(4-chlorobenzenesulfinyl)-hexa-2,4-dienoic acid methyl ester (0.80 g, 2.79 mmol) in distilled THF (15 mL) containing an aqueous solution of hydroxylamine (50%/o, 1.7 ml, 25.8 mmol) was added at 0° C. a solution of potassium hydroxide in methanol (1M, 4.5 ml, 4.5 mmol) over a period of 30 minutes. After stirring at 0° C. for 1 hour, distilled water (15 mL) was added and the mixture was made neutral by dropwise addition of concentrated hydrochloric acid (10 M) at 0° C. The aqueous solution was extracted with ethyl acetate (3×50 mL) and the combined extracts were dried over anhydrous MgSO4, and evaporated to dryness. The residue was recrystallised from acetone to give the title compound (0.45 g, 56%) as a pale brown powder, mp 159° C. (decomp).
Reaction SMILES: C(OC(=O)[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:22][N:21]4[N:30]=[C:31]([NH:33][C:34](=[O:36])[CH3:35])[N:32]=[C:20]4[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:22][N:21]4[N:30]=[C:31]([NH:33][C:34](=[O:36])[CH3:35])[N:32]=[C:20]4[N:19]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1
Reactant: CC(=O)Nc1nc2nc(-c3ccc(C4(NC(=O)OC(C)(C)C)CCC4)cc3)c(-c3ccccc3)cn2n1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(=O)Nc1nc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)cn2n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To the solution of 6-3 (50 mg, 0.1 mmol) in 1 mL of DCM was added TFA (1 mL) and the mixture was stirred at room temperature for 3 h. The mixture was concentrated by evaporation and the residue was purified by prep.HPLC to give the product 6-4.
Reaction SMILES: [C:1]([O:5][C:6](=[O:28])[N:7]([CH2:11][C:12]1[CH:17]=[C:16](/[CH:18]=[CH:19]/[CH2:20][O:21][CH3:22])[CH:15]=[C:14](/[CH:23]=[CH:24]/[CH2:25][O:26][CH3:27])[CH:13]=1)[CH:8]1[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C>CCOC(C)=O.[Pd]>[C:1]([O:5][C:6](=[O:28])[N:7]([CH2:11][C:12]1[CH:13]=[C:14]([CH2:23][CH2:24][CH2:25][O:26][CH3:27])[CH:15]=[C:16]([CH2:18][CH2:19][CH2:20][O:21][CH3:22])[CH:17]=1)[CH:8]1[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: COC/C=C/c1cc(/C=C/COC)cc(CN(C(=O)OC(C)(C)C)C2CC2)c1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COCCCc1cc(CCCOC)cc(CN(C(=O)OC(C)(C)C)C2CC2)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
tert-Butyl{3,5-bis[(1E)-3-methoxy-1-propen-1-yl]benzyl}cyclopropylcarbamate (1 eq.) from the previous step and 10% w/w palladium over charcoal (0.1 eq.) were suspended in EtOAc (0.05 M). The vessel was then evacuated and purged with H2. Under a balloon-filled H2 atmosphere, the reaction suspension was stirred at RT for 3 h. The reaction suspension was then quenched with dichloromethane and filtered through a bed of celite. Concentration of the filtrate in vacuo to afford the title compound as a yellow oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([CH:10]3[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][N:19]4[C:27]5[CH2:26][CH2:25][N:24]([S:28]([CH3:31])(=[O:30])=[O:29])[CH2:23][C:22]=5[C:21]([C:32]5[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=5)=[N:20]4)[CH2:12][CH2:11]3)=[C:8]([C:42](O)=[O:43])[S:7][C:6]=2[CH:45]=1.CN(C(O[N:54]1N=[N:61][C:56]2C=CC=C[C:55]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C(N)CN>CN(C=O)C>[NH2:54][CH2:55][CH2:56][NH:61][C:42]([C:8]1[S:7][C:6]2[CH:45]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[C:9]=1[CH:10]1[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][N:19]2[C:27]3[CH2:26][CH2:25][N:24]([S:28]([CH3:31])(=[O:29])=[O:30])[CH2:23][C:22]=3[C:21]([C:32]3[CH:33]=[CH:34][C:35]([C:38]([F:40])([F:39])[F:41])=[CH:36][CH:37]=3)=[N:20]2)[CH2:14][CH2:15]1)=[O:43]
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Reactant: CS(=O)(=O)N1CCc2c(c(-c3ccc(C(F)(F)F)cc3)nn2CCCN2CCC(c3c(C(=O)O)sc4cc(F)ccc34)CC2)C1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: NCCN
Solvent: CCN(C(C)C)C(C)C
Product: CS(=O)(=O)N1CCc2c(c(-c3ccc(C(F)(F)F)cc3)nn2CCCN2CCC(c3c(C(=O)NCCN)sc4cc(F)ccc34)CC2)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 65.8 %

Procedure:
A stirred solution of 300 mg (0.43 mmol) 6-fluoro-3-(1-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-benzo[b]thiophene-2-carboxylic acid in 5 mL of dry DMF was treated with 812 mg (2.14 mmol) of HBTU and 0.75 mL (4.28 mmol) of DIEA. The solution was stirred for 5 min before the addition of 0.28 mL (4.28 mmol) of ethylenediamine. The reaction was stirred at room temperature for 30 min then partitioned between EtOAc (30 mL) and saturated sodium bicarbonate (20 mL). The aqueous layer was further extracted with EtOAc (2×20 mL). The combined organic layers were then washed with brine, dried over Na2SO4, and concentrated. Purification by column chromatography (silica, 5-10% of (2 N NH3 in MeOH)/CH2Cl2) afforded 200 mg (66%) of a clear oil. MS (electrospray): exact mass calculated for C33H38F4N6O3S2: 706.24; m/z found, 707.2 [M+H]+. 1H NMR (CD3OD, 400 MHz): 8.14 (m, 1H), 7.84 and 7.72 (A and B of AB quartet, J=8.41 Hz, 4H), 7.68 (m, 1H), 7.21 (dt, J=8.81, 2.74 Hz, 1H), 4.54 (s, 2H), 4.27 (t, J=6.26 Hz, 2H), 4.00-3.90 (m, 2H), 3.76-3.61 (m, 8H), 3.28-3.23 (br m, 1H), 3.19-3.09 (br m, 3H), 2.98 (s, 3H), 2.97-2.93 (m, 2H), 2.67 (br m, 2H), 2.52-2.37 (m, 3H), 2.02 (br d, J=13.89 Hz, 2H).
Reaction SMILES: [H-].[Na+].[NH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.Br[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH:19]=[CH2:20].O>CS(C)=O>[CH2:20]([N:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH:11]=[CH2:10]
Reactant: C1CCNCC1
Reactant: C=CCCCCCCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: C=CCCCCCCCCCN1CCCCC1
Reaction time: 0.33 h
Yield: 262.8 %

Procedure:
This example illustrates a synthesis of N-(9,10-Oxidodecyl)piperidine (inventive compound no. 1619). Sodium hydride (95%) (864 mg, 36 mmol) was added to a solution of piperidine (2.554 g, 30 mmol) in dimethyl sulfoxide (75 mL). After 20 minutes of stirring, 1-bromundec-10-ene (6.99 g, 5 mmol) was added and stirred for 12 hours at room temperature. The reaction mixture was then poured into a separatory funnel containing 100 mL of water and extracted with dichlormethane (5×75 mL). The organic extracts were combined, washed with water (50 mL) and brine (50 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The crude product obtained was further purified by flash chromatography over silica gel using 5% methanol/dichloromethane eluant to yield 3.12 g (44% yield) N-(10-undecenyl)piperidine (inventive compound no. 1615).
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[N:3]=1.[CH3:17][O:18][C:19]1[CH:20]=[C:21]([CH2:27][CH2:28][NH2:29])[CH:22]=[CH:23][C:24]=1[O:25][CH3:26]>CO>[CH3:17][O:18][C:19]1[CH:20]=[C:21]([CH2:27][CH2:28][NH:29][C:2]2[N:10]=[C:9]3[C:5]([N:6]=[CH:7][NH:8]3)=[C:4]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[N:3]=2)[CH:22]=[CH:23][C:24]=1[O:25][CH3:26]
Reactant: COc1ccc(CCN)cc1OC
Reactant: Clc1nc(N2CCOCC2)c2nc[nH]c2n1
Solvent: CO
Product: COc1ccc(CCNc2nc(N3CCOCC3)c3nc[nH]c3n2)cc1OC
Temperature: 192.5 °C
Reaction time: 1 h
Yield: 74.8 %

Procedure:
As shown in Scheme 3 above, a mixture of 2,6-dichloropurine (1.90 g, 10 mmol) and morpholine (2.34 g, 30 mmol) in water (25 mL) was heated under reflux for 15 min. Solidified reaction mixture was cooled to room temperature. Solid was filtered out and washed with water, methanol and ether. The 2-chloro-6-morpholin-4-yl-9H-purine was obtained in 96% yield (2.30 g). A mixture of 2-chloro-6-morpholin-4-yl-9H-purine (1.92 g, 8 mmol) and 2-(3,4-dimethoxyphenyl)ethylamine (4.35 g, 24 mmol) in sealed tube and under nitrogen was stirred at 190-195° C. for 1 hour. The reaction mixture turned to clear solution initially and then formed a slurry. The reaction mixture was cooled to room temperature diluted with methanol (8 mL) and the solid was collected by filtration, washed with methanol and Et2O and dried to afford 2.30 g (74% yield) of [2-(3,4-dimethoxy-phenyl)-ethyl]-(6-morpholin-4-yl-9H-purin-2-yl)amine.
Reaction SMILES: [Br:1][C:2]1[C:7]2[C:8](=[O:19])[N:9]3[CH2:18][CH2:17][CH2:16][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][CH:15]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[I:20]I.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Br:1][C:2]1[C:7]2[C:8](=[O:19])[N:9]3[CH2:18][CH2:17][CH2:16][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[I:20])[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: II
Reactant: O=C1c2c(Br)cccc2-n2cncc2[C@@H]2CCCN12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C1c2c(Br)cccc2-n2cnc(I)c2[C@@H]2CCCN12
Reaction time: 0.5 h

Procedure:
15.90 g (50 mmol) of (S)-8-bromo-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one was stirred at 100° for 3 hours with 44 g (175 mmol) of iodine and 14 g (100 mmol) of potassium carbonate in 100 ml of N,N-dimethylformamide. The reaction mixture was poured into 1 l of water and, after stirring for 30 minutes, the precipitated product was filtered off. The filter residue was rinsed with water, dried and recrystallized from N,N-dimethylformamide. There was obtained (S)-8-bromo-11,12,13,13a-tetrahydro-1-iodo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one of melting point 301°-303°.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][CH:3]=1.[CH3:21][N:22](C)C=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.[C-]#N.[Zn+2].[C-]#N>[C:21]([C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][CH:3]=1)#[N:22]
Reactant: CN(C)C=O
Reactant: CC(C)(C)OC(=O)N1CCO[C@@H](c2ccc(Br)cc2)C1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Product: CC(C)(C)OC(=O)N1CCO[C@@H](c2ccc(C#N)cc2)C1
Temperature: 85 °C
Yield: 69 %

Procedure:
A mixture of (S)-tert-butyl 2-(4-bromophenyl)morpholine-4-carboxylate (400 mg, 1.17 mmol), tetrakis(triphenylphosphine)palladium(0) (405 mg, 0.35 mmol) and zinc cyanide (206 mg, 1.75 mmol) in dimethylformamide (6 ml) was degassed with argon and heated in a closed tube at 85° C. on a Büchi shaker overnight. After cooling water (30 ml) was added, and the reaction mixture was extracted with ethyl acetate (50 ml). The aqueous phase was re-extracted with ethyl acetate (50 ml). The combined organic layers were re-extracted with conc. Sodium chloride solution, dried (MgSO4) and evaporated. The residue was purified by flash chromatography (20 g silica gel, 10% ethyl acetate in heptane) to yield a white solid (233 mg, 69%). MS (ISP): 289.1 ([M+H]+), 306.2 ([M+NH4]+).
Reaction SMILES: [OH:1][C@:2]1([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Br:15])[CH:10]=2)[CH2:7][CH2:6][O:5][C@@H:4]([CH3:8])[CH2:3]1.[Si:16](Cl)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]>>[Si:16]([O:1][C@:2]1([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Br:15])[CH:10]=2)[CH2:7][CH2:6][O:5][C@@H:4]([CH3:8])[CH2:3]1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]
Reactant: C[C@H]1C[C@@](O)(c2cccc(Br)c2)CCO1
Reactant: CC(C)(C)[Si](C)(C)Cl
Product: C[C@H]1C[C@@](O[Si](C)(C)C(C)(C)C)(c2cccc(Br)c2)CCO1
Yield: 78 %

Procedure:
Using an analogous procedure to that described in the portion of Example 18 which is concerned with the preparation of starting materials, the 4-(3-bromophenyl)-2-methyltetrahydropyran so obtained was reacted with tert-butyldimethylsilyl chloride to give (2S,4R)-4-(tert-butyldimethylsilyloxy)-4-(3-bromophenyl)-2-methyltetrahydropyran in 78% yield as an oil.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([CH3:9])[N:3]=1.[CH3:10][NH:11][CH2:12][CH2:13][OH:14]>C(O)C>[Cl:1][C:2]1[N:3]=[C:4]([CH3:9])[CH:5]=[C:6]([N:11]([CH2:12][CH2:13][OH:14])[CH3:10])[N:7]=1
Reactant: CNCCO
Reactant: Cc1cc(Cl)nc(Cl)n1
Solvent: CCO
Product: Cc1cc(N(C)CCO)nc(Cl)n1
Yield: 34.5 %

Procedure:
Part A: A solution of 2,4-dichloro-6-methylpyrimidine (1.0 g) and 2-(methylamino)ethanol (0.4 g) in ethanol (50 mL) was refluxed for 24 hours. The solvent was evaporated to give a crude residue, which was chromatographed on silica gel using 5% methanol in chloroform to yield 2-chloro-4-methyl-6-(N-methyl-2-hydroxyethylamino)pyrimidine (370 mg). Mass spec. (NH3 --CI/DDIP): 202 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([CH2:30][CH3:31])[C:12]([NH:17][C@@H:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20][C@@H:19]2[O:27][CH2:28][CH3:29])=[N:13][C:14]=1[CH2:15][CH3:16].BrC[CH2:34][O:35]C>>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([CH2:30][CH3:31])[C:12]([NH:17][C@@H:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20][C@@H:19]2[O:27][CH2:28][CH2:29][O:35][CH3:34])=[N:13][C:14]=1[CH2:15][CH3:16]
Reactant: COCCBr
Reactant: CCO[C@H]1Cc2ccccc2[C@H]1Nc1nc(CC)c(-c2ccc(Cl)cc2Cl)nc1CC
Product: CCc1nc(-c2ccc(Cl)cc2Cl)c(CC)nc1N[C@@H]1c2ccccc2C[C@@H]1OCCOC

Procedure:
Following the procedure for the preparation of 5-(2,4-dichlorophenyl)-N-[(1R,2S)-2-ethoxy-2,3-dihydro-1H-inden-1-yl]-3,6-diethylpyrazin-2-amine but substituting 2-bromoethylmethylether and making non-critical variations provided the title compound as a light yellow syrup. IR (liq.) 3418, 2971, 2934, 2875, 1565, 1552, 1498, 1471, 1392, 1376, 1201, 1183, 1132, 1100, 748 cm−1; OAMS supporting ions at: ESI+ 485.8; MS (CI) m/z 486 (MH+); [α]25D=−102 (c 0.57, methylene chloride); Anal. Calcd for C26H29Cl2N3O2: C, 64.20; H, 6.01; N, 8.64. Found: C, 63.92; H, 6.14; N, 8.53.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH:10]1[CH2:14][CH2:13][NH:12][CH2:11]1)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.Cl[C:17]1[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=1.CCN(C(C)C)C(C)C>CC(O)C.C([O-])(O)=O.[Na+]>[CH3:9][N:8]([CH:10]1[CH2:14][CH2:13][N:12]([C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)[CH2:11]1)[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3]
Reactant: CN(C(=O)OC(C)(C)C)C1CCNC1
Reactant: Clc1ccncc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: CN(C(=O)OC(C)(C)C)C1CCN(c2ccncc2)C1
Yield: 61 %

Procedure:
3-(N-Tert-butoxycarbonyl-N-methylamino)pyrrolidine (4.993 mmol, 1 eq) and 4-chloropyridine hydrochloride (14.979 mmol, 3 eq) were dissolved in 2-propanol (15 ml) and DIPEA (19.972 mmol, 4 eq) and refluxed for 16 h. After monitoring by thin-layer chromatography, the reaction solution was diluted with sat. NaHCO3 solution and extracted with ethyl acetate (3×20 ml). The combined org. phases were washed with sat. NaCl solution, dried over magnesium sulfate and concentrated. The crude product was purified by column chromatography (silica gel, ethyl acetate:ethanol 10:1+ammonia (25% aq)). Yield: 61%.
Reaction SMILES: [Li]CCCC.[CH3:6][N:7]([CH3:30])[S:8]([N:11]1[C:15](SC2C=CC=CC=2)=[CH:14][N:13]=[C:12]1[Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])(=[O:10])=[O:9].[CH2:31]([O:33]CC)C>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:30][N:7]([CH3:6])[S:8]([N:11]1[C:15]([CH:31]=[O:33])=[CH:14][N:13]=[C:12]1[Si:23]([C:26]([CH3:28])([CH3:29])[CH3:27])([CH3:24])[CH3:25])(=[O:10])=[O:9]
Reactant: CCOCC
Reactant: CN(C)S(=O)(=O)n1c(Sc2ccccc2)cnc1[Si](C)(C)C(C)(C)C
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [Li]CCCC
Product: CN(C)S(=O)(=O)n1c(C=O)cnc1[Si](C)(C)C(C)(C)C
Temperature: -70 °C
Yield: 83 %

Procedure:
Methyl triphenylphosphonium bromide (2.75 g, 7.70 mmol) was suspended in 50 mL of diethyl ether. At −10° C., nBuLi (3.08 mL, 7.70 mmol, 2.5M soln in hexanes) was added. This mixture was stirred for 35 m before cooling to −70° C. A solution of (R)-(+)-4,4a,5,6,7,8-hexahydro-4a-methyl-2(3H)-naphthalenone (1) (1.0 g, 6.09 mmol) in 15 mL of ether was added via syringe. This mixture was warmed to 0° C. over 30 m and the stirred at rt for another 30 m. The solution was washed with brine (2×20 mL) dried over MgSO4, filtered and the solvent was removed. Chromatography on SiO2 with hexanes gave 0.82 g (83%) of the diene 2 as a clear colorless oil.
Reaction SMILES: [C:1]([O:5][CH:6]([C:11]1[C:12]([C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[O:27][CH2:26][CH2:25][CH2:24]3)=[C:13]2[CH:20]=[CH:19][NH:18][C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].Br[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([F:39])=[C:35]([CH3:40])[CH:34]=1>>[C:1]([O:5][CH:6]([C:11]1[C:12]([C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[O:27][CH2:26][CH2:25][CH2:24]3)=[C:13]2[CH:20]=[CH:19][N:18]([CH2:32][C:33]3[CH:38]=[CH:37][C:36]([F:39])=[C:35]([CH3:40])[CH:34]=3)[C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([OH:9])=[O:8])([CH3:2])([CH3:4])[CH3:3]
Reactant: COC(=O)C(OC(C)(C)C)c1c(C)nc2[nH]ccc2c1-c1ccc2c(c1)CCCO2
Reactant: Cc1cc(CBr)ccc1F
Product: Cc1cc(Cn2ccc3c(-c4ccc5c(c4)CCCO5)c(C(OC(C)(C)C)C(=O)O)c(C)nc32)ccc1F

Procedure:
The title compound was prepared in a manner similar to that described in Example 27, Step H from methyl 2-(tert-butoxy)-2-(4-(chroman-6-yl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)acetate and 4-(bromomethyl)-1-fluoro-2-methylbenzene. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.50-7.43 (m, 1 H), 7.23-7.17 (m, 1 H), 7.17-7.03 (m, 3 H), 7.00-6.90 (m, 2 H), 6.30 (dd, J=3.3, 10.1 Hz, 1 H), 5.63-5.53 (m, 2 H), 5.49-5.38 (m, 1 H), 4.29 (t, J=4.9 Hz, 2 H), 2.97-2.82 (m, 2 H), 2.80 (s, 3 H), 2.25 (s, 3 H), 2.14-2.04 (m, 2 H), 1.03-0.91 (s, 9 H); LC/MS (m/z) ES+=517.38 (M+1).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[CH:7][C:8]([C:14]([CH3:21])=[CH:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:9]2[C:13]=1[CH2:12][CH2:11][CH2:10]2)(=[O:3])[CH3:2]>C(O)C.[Pd]>[C:1]([NH:4][C:5]1[CH:6]=[CH:7][C:8]([CH:14]([CH3:21])[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:9]2[C:13]=1[CH2:12][CH2:11][CH2:10]2)(=[O:3])[CH3:2]
Reactant: CCOC(=O)C=C(C)c1ccc(NC(C)=O)c2c1CCC2
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)CC(C)c1ccc(NC(C)=O)c2c1CCC2
Yield: 86.8 %

Procedure:
A solution of ethyl 3-[7-acetylamino-indan-4-yl]-but-2-enoate (1.9 g, Reference Example 7) in ethanol (200 mL) was hydrogenated over 10% palladium on charcoal for 16 hours. The mixture was filtered through diatomaceous earth and the filtrate was evaporated to give the title compound (1.66 g).
Reaction SMILES: [NH2:1][C@@H:2]1[CH:7]2[CH2:8][CH2:9][N:4]([CH2:5][CH2:6]2)[CH2:3]1.[CH3:10][O:11][C:12]1[CH:22]=[CH:21][CH:20]=[CH:19][C:13]=1[C:14]([N:16]=[C:17]=[O:18])=[O:15].C([O-])(=O)/C=C/C([O-])=O>>[N:4]12[CH2:9][CH2:8][CH:7]([CH2:6][CH2:5]1)[C@@H:2]([NH:1][C:17]([NH:16][C:14](=[O:15])[C:13]1[CH:19]=[CH:20][CH:21]=[CH:22][C:12]=1[O:11][CH3:10])=[O:18])[CH2:3]2
Reactant: N[C@H]1CN2CCC1CC2
Reactant: COc1ccccc1C(=O)N=C=O
Agent: O=C([O-])/C=C/C(=O)[O-]
Product: COc1ccccc1C(=O)NC(=O)N[C@H]1CN2CCC1CC2

Procedure:
The above compound was prepared, following the procedure of Example 1, from (R)-3-aminoquinuclidine (0.63 g, 5 mmol) and 2-methoxybenzoyl isocyanate (1.33 g, 7.5 mmol). The product (1.49 g) was converted to the 1:1 fumarate, mp 158°-159° C. (dec).
Reaction SMILES: [C:1]([O:5]CCO)(=[O:4])[CH:2]=[CH2:3].[NH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11]>>[C:1]([OH:5])(=[O:4])[CH:2]=[CH2:3].[NH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: C=CC(=O)OCCO
Agent: CCOC(N)=O
Product: C=CC(=O)O
Temperature: 50 °C

Procedure:
Subsequently, in order to prevent the thermal polymerization of vinyl groups, a reactor was cooled to a temperature of about 50° C., and then 0.657 mol of hydroxyethyl acrylate was added to the urethane prepolymer and then stirred for 4˜6 hours until isocyanate groups were completely consumed. The fact that residual isocyanate does not exist according to the characteristic peak of N═C═O near a frequency of 2270 cm−1 using Fourier transfer infrared spectroscopy (FT-IR) was confirmed, and then the reaction was terminated to obtain a urethane acrylate oligomer.
Reaction SMILES: [CH:1]([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[C:10]1[CH:15]=[CH:14][N:13]2[N:16]=[CH:17][C:18]([C:19]3[CH:24]=[CH:23][C:22]([C:25]4[N:26](COCC[Si](C)(C)C)[CH:27]=[CH:28][N:29]=4)=[CH:21][CH:20]=3)=[C:12]2[N:11]=1)([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[NH:26]1[CH:27]=[CH:28][N:29]=[C:25]1[C:22]1[CH:23]=[CH:24][C:19]([C:18]2[CH:17]=[N:16][N:13]3[CH:14]=[CH:15][C:10]([N:5]4[C@@H:4]([CH:1]([CH3:2])[CH3:3])[CH2:8][O:7][C:6]4=[O:9])=[N:11][C:12]=23)=[CH:20][CH:21]=1
Reactant: CC(C)[C@H]1COC(=O)N1c1ccn2ncc(-c3ccc(-c4nccn4COCC[Si](C)(C)C)cc3)c2n1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)[C@H]1COC(=O)N1c1ccn2ncc(-c3ccc(-c4ncc[nH]4)cc3)c2n1
Temperature: 25 °C
Reaction time: 12 h
Yield: 61.4 %

Procedure:
(S)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one (2.09 g, 4.03 mmol) was dissolved in dichloromethane (20 mL) and trifluoroacetic acid (25 mL) was added and the mixture allowed to stir at ambient temperature for 12 hours. The reaction mixture was concentrated and the residue partitioned between saturated aqueous NaHCO3 (50 mL) and EtOAc (100 mL). The aqueous layer was washed with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated to give a light yellow solid. Purification of the crude material by column chromatography, eluting with a gradient of 0-4% (9:1 MeOH/NH4OH)/EtOAc, provided (S)-3-(3-(4-(1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one as a yellow solid (961.3 mg, 61%). LCMS (APCI+) m/z 389 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J=7.8 Hz, 1H), 8.39 (s, 1H), 8.04 (d, J=8.6 Hz, 2H), 8.03 (d, J=7.8 Hz, 1H), 7.89 (d, J=8.6 Hz, 2H), 7.19 (s, 2H), 4.95-4.91 (m, 1H), 4.36-4.45 (m, 2H), 2.83-2.91 (m, 1H), 1.04 (d, J=7.0 Hz, 3H), 0.92 (d, J=7.0 Hz, 3H).