Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1](=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[ClH:12].Cl.[C:14]([C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]([NH:27][C:28]([NH2:30])=[NH:29])=[NH:26])=[CH:20][CH:19]=1)([CH3:17])([CH3:16])[CH3:15]>C(O)C>[ClH:12].[NH2:26][C:25]1[N:24]([C:21]2[CH:22]=[CH:23][C:18]([C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:19][CH:20]=2)[CH:1]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[N:29]=[C:28]([NH2:30])[N:27]=1
Reactant: CC(C)(C)c1ccc(NC(=N)NC(=N)N)cc1
Reactant: CCCCCCCCCC=O
Agent: Cl
Solvent: CCO
Product: CCCCCCCCCC1N=C(N)N=C(N)N1c1ccc(C(C)(C)C)cc1

Procedure:
100 ml of ethanol, 5.2 g (33.3 mmol) of 1-decanal and 0.9 ml of concentrated hydrochloric acid were added to 6.0 g (22.2 mmol) of N1-(4-tert-butylphenyl)-biguanide hydrochloride, and the mixture was refluxed for 7 hours. The solvent was concentrated under reduced pressure, and the residue was cooled. The resulting precipitated crystals were filtered, and recrystallized from 80% aqueous ethanol to obtain 3.1 g of colorless crystals having a melting point of 238 to 240° C.
Reaction SMILES: [CH3:1][C:2]1[C:10]2[O:9][CH:8](OC)[CH2:7][C:6]=2[CH:5]=[CH:4][C:3]=1[C:13]([O:15][CH3:16])=[O:14]>P(=O)(O)(O)O>[CH3:1][C:2]1[C:10]2[O:9][CH:8]=[CH:7][C:6]=2[CH:5]=[CH:4][C:3]=1[C:13]([O:15][CH3:16])=[O:14]
Reactant: COC(=O)c1ccc2c(c1C)OC(OC)C2
Agent: O=P(O)(O)O
Product: COC(=O)c1ccc2ccoc2c1C
Temperature: 100 °C
Reaction time: 0.25 h
Yield: 54 %

Procedure:
A solution of methyl 7-methyl-2-(methyloxy)-2,3-dihydro-1-benzofuran-6-carboxylate in phosphoric acid (3 mL) was stirred at room temperature for 10 minutes and then was stirred at 100° C. for 15 minutes. The reaction mixture was cooled to room temperature and then was partitioned between water and diethyl ether. The aqueous portion was extracted three times with diethyl ether. The combined organic portion was washed three times with water and twice with 10% aqueous potassium carbonate. The basic portion was extracted three times with diethyl ether and the combined organic portions were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a brown residue which was purified by column chromatography eluting with 5% ethyl acetate in hexanes. Pure fractions were concentrated in vacuo to afford (371 mg, 54%) of methyl 7-methyl-1-benzofuran-6-carboxylate as a colorless oil.
Reaction SMILES: C(C1C=CC2NC[C@@H](CC3C=CC=CC=3)N(C(=[O:28])CC3C=CC=CC=3)CC=2C=1)#N.[ClH:30].[Br:31][C:32]1[CH:33]=[CH:34][C:35]2[N:41]([CH2:42][C:43]3[N:44]=[CH:45][NH:46][CH:47]=3)[CH2:40][C@@H:39]([CH2:48]C3C=CC=CC=3)[N:38]([S:55]([CH3:58])(=[O:57])=[O:56])[CH2:37][C:36]=2[CH:59]=1>>[ClH:30].[Br:31][C:32]1[CH:33]=[CH:34][C:35]2[N:41]([CH2:42][C:43]3[N:44]=[CH:45][NH:46][CH:47]=3)[CH2:40][CH:39]([CH2:48][OH:28])[N:38]([S:55]([CH3:58])(=[O:57])=[O:56])[CH2:37][C:36]=2[CH:59]=1
Reactant: N#Cc1ccc2c(c1)CN(C(=O)Cc1ccccc1)[C@H](Cc1ccccc1)CN2
Reactant: CS(=O)(=O)N1Cc2cc(Br)ccc2N(Cc2c[nH]cn2)C[C@H]1Cc1ccccc1
Agent: Cl
Product: CS(=O)(=O)N1Cc2cc(Br)ccc2N(Cc2c[nH]cn2)CC1CO
Yield: 12 %

Procedure:
Example 306 was prepared as an offwhite solid in 12% yield from Compound C of Example 305 as described for Compound D of Example 224.
Reaction SMILES: [CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][NH:3]1.[CH:7]1([C:10]2[N:15]=[C:14]([C:16]([NH:18][C:19]3[CH:27]=[N:26][CH:25]=[CH:24][C:20]=3[C:21](O)=[O:22])=[O:17])[C:13]([NH:28][C:29]3[CH:30]=[N:31][CH:32]=[N:33][CH:34]=3)=[CH:12][CH:11]=2)[CH2:9][CH2:8]1>>[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:21]([C:20]1[CH:24]=[CH:25][N:26]=[CH:27][C:19]=1[NH:18][C:16]([C:14]1[C:13]([NH:28][C:29]2[CH:30]=[N:31][CH:32]=[N:33][CH:34]=2)=[CH:12][CH:11]=[C:10]([CH:7]2[CH2:9][CH2:8]2)[N:15]=1)=[O:17])=[O:22]
Reactant: O=C(O)c1ccncc1NC(=O)c1nc(C2CC2)ccc1Nc1cncnc1
Reactant: CC1CCCN1
Product: CC1CCCN1C(=O)c1ccncc1NC(=O)c1nc(C2CC2)ccc1Nc1cncnc1
Yield: 14 %

Procedure:
According to the general method described in step 3 of example 53, reaction of 2-methyl-pyrolidine with 3-{[6-cyclopropyl-3-(pyrimidin-5-ylamino)-pyridine-2-carbonyl]-amino}-isonicotinic acid provided the title compound (14%) as sticky yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[OH:9].[Br:10][CH2:11][CH2:12][CH2:13]Br.[OH-].[Na+]>O>[Br:10][CH2:11][CH2:12][CH2:13][O:9][C:3]1[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=1[Cl:8]
Reactant: Oc1c(Cl)cccc1Cl
Reactant: BrCCCBr
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Clc1cccc(Cl)c1OCCCBr
Temperature: 100 °C
Yield: 71.3 %

Procedure:
A mixture of 2,6-dichlorophenol (163 g, 1 mol) and 1,3-dibromopropane (262 g, 1.3 mol) was heated to 100° C., and a solution of sodium hydroxide (40 g) in water (1000 ml) was added dropwise over 75 min. The mixture was heated under reflux for 5 h and then cooled to room temperature upon which a biphasic solution developed. The organic layer was separated and the aqueous layer was extracted with diethyl ether (3×250 ml). The combined organic fractions were washed with 2N aqueous sodium hydroxide solution (4×250 ml) and water (250 ml), dried (MgSO4), filtered and concentrated in vacuo to afford the crude product. The residue was distilled at 100-120° C./0.3 mm of mercury to afford the title compound as an oil (202.5 g, 71%).
Reaction SMILES: FC(F)(F)C(O)=O.C(OC(=O)[NH:14][CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]([CH3:38])[C:25]([OH:37])([C:30]2[CH:35]=[N:34][C:33]([CH3:36])=[CH:32][N:31]=2)[C:26]([F:29])([F:28])[F:27])=[C:20]([Cl:39])[CH:19]=1)(C)(C)C.C([O-])(O)=O.[Na+]>ClCCl.O>[NH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]([CH3:38])[C:25]([C:30]2[CH:35]=[N:34][C:33]([CH3:36])=[CH:32][N:31]=2)([OH:37])[C:26]([F:29])([F:28])[F:27])=[C:20]([Cl:39])[CH:19]=1
Reactant: Cc1cnc(C(O)(C(C)c2ccc(OCCNC(=O)OC(C)(C)C)cc2Cl)C(F)(F)F)cn1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cnc(C(O)(C(C)c2ccc(OCCN)cc2Cl)C(F)(F)F)cn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Under an atmosphere of nitrogen, trifluoroacetic acid was added to a solution of (2-{3-chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(5-methyl-pyrazin-2-yl)-propyl]-phenoxy}-ethyl)-carbamic acid tert-butyl ester (example 84) in dichloromethane. The reaction mixture was stirred for 1 h at r.t., and then diluted with water, neutralized (satd. NaHCO3) and extracted (ethyl acetate). The combined organic layers were dried, filtered, and evaporated. Flash chromatography provided the title compound. MS (m/e)=390.3 (MH+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:16])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:5][CH:4]=1.[F:17][C:18]([F:28])([F:27])[C:19]1[CH:26]=[CH:25][C:22]([CH2:23]Br)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9](=[O:16])[CH:10]([CH2:23][C:22]2[CH:21]=[CH:20][C:19]([C:18]([F:17])([F:27])[F:28])=[CH:26][CH:25]=2)[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7][CH:8]=1
Reactant: FC(F)(F)c1ccc(CBr)cc1
Reactant: CCOC(=O)CC(=O)c1ccc(OC)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)C(Cc1ccc(C(F)(F)F)cc1)C(=O)c1ccc(OC)cc1
Temperature: 60 °C
Reaction time: 2 h
Yield: 59.7 %

Procedure:
To a solution of ethyl 3-(4-methoxyphenyl)-3-oxopropionate (20 g, 84.6 mmol) in acetonitrile (200 ml) were added 4-trifluoromethylbenzyl bromide (20.2 g, 84.6 mmol) and potassium carbonate (23.4 g, 169 mmol) and the mixture was stirred at 60° C. for 2 hrs. The reaction solution was evaporated under reduced pressure, diluted with water (500 ml) and extracted with ethyl acetate (500 ml×2). The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (toluene:hexane=1:1-toluene) to give ethyl 3-(4-methoxyphenyl)-3-oxo-2-((4-(trifluoromethyl)phenyl)methyl)propionate (19.2 g, 56%) as a colorless oil.
Reaction SMILES: C(C1N=C(N2CCC(F)(F)C2)C2N=NN(CC)C=2N=1)(C)(C)C.[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][C:39]([F:42])([F:41])[C:38]([F:44])([F:43])[CH2:37]2)[C:30]2[N:35]=[N:34][NH:33][C:31]=2[N:32]=1)([CH3:26])([CH3:25])[CH3:24].Cl[CH2:46][C:47]1[O:51][N:50]=[C:49]([CH3:52])[N:48]=1>>[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][C:39]([F:41])([F:42])[C:38]([F:43])([F:44])[CH2:37]2)[C:30]2[N:35]=[N:34][N:33]([CH2:46][C:47]3[O:51][N:50]=[C:49]([CH3:52])[N:48]=3)[C:31]=2[N:32]=1)([CH3:26])([CH3:24])[CH3:25]
Reactant: Cc1noc(CCl)n1
Reactant: CC(C)(C)c1nc(N2CC(F)(F)C(F)(F)C2)c2nn[nH]c2n1
Agent: CCn1nnc2c(N3CCC(F)(F)C3)nc(C(C)(C)C)nc21
Product: Cc1noc(Cn2nnc3c(N4CC(F)(F)C(F)(F)C4)nc(C(C)(C)C)nc32)n1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3-ethyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 61), the title compound was prepared from 5-tert-Butyl-7-(3,3,4,4-tetrafluoro-pyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 5-(chloromethyl)-3-methyl-1,2,4-oxadiazole and isolated as light-yellow gum. MS(m/e): 415.3 (MH+).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[CH2:12][CH2:13][N:14]([CH2:17][CH2:18][C:19]([N:21]4[C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[CH2:23][CH2:22]4)=O)[CH2:15][CH:16]=3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[CH2:12][CH2:13][N:14]([CH2:17][CH2:18][CH2:19][N:21]4[C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[CH2:23][CH2:22]4)[CH2:15][CH:16]=3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1
Reactant: O=C(CCN1CC=C(c2c[nH]c3cc(Cl)ccc23)CC1)N1CCc2ccccc21
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: Clc1ccc2c(C3=CCN(CCCN4CCc5ccccc54)CC3)c[nH]c2c1

Procedure:
The compound was prepared from 41a as described in Example 11 but by the use of alane instead of LiAlH4 for the reduction.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=1)[C:5]([NH:7][CH:8](Br)[C:9]([NH2:11])=[O:10])=[O:6].[CH3:16][SH:17].C(N(CC)CC)C.CCOCC>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=1)[C:5]([NH:7][CH:8]([S:17][CH3:16])[C:9]([NH2:11])=[O:10])=[O:6]
Reactant: NC(=O)C(Br)NC(=O)c1cccc(Cl)c1
Reactant: CS
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: CSC(NC(=O)c1cccc(Cl)c1)C(N)=O
Reaction time: 72 h

Procedure:
To a solution of 3-chlorobenzoylamino(bromo)acetamide (5.5 g) in anhydrous tetrahydrofuran (100 ml) containing methyl mercaptan (slight excess) was added 1 equivalent of triethylamine and the mixture kept for 72 hrs. The solution was filtered and the filtrate evaporated to give an oil which solidified on treatment with ether. Crystallisation of the solid from ethyl acetate gave the product (0.67 g).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:27])[CH:4]([C:9]1[CH:10]=[C:11]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([C:23]([F:26])([F:25])[F:24])[CH:17]=2)[CH:12]=[C:13]([OH:15])[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7].[F:28][C:29]([F:40])([F:39])[C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1>>[CH3:1][O:2][C:3](=[O:27])[CH:4]([C:9]1[CH:10]=[C:11]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([C:23]([F:26])([F:24])[F:25])[CH:17]=2)[CH:12]=[C:13]([O:15][C:34]2[CH:33]=[CH:32][CH:31]=[C:30]([C:29]([F:40])([F:39])[F:28])[CH:35]=2)[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7]
Reactant: OB(O)c1cccc(C(F)(F)F)c1
Reactant: COC(=O)C(CC(C)C)c1cc(O)cc(-c2ccc(Cl)c(C(F)(F)F)c2)c1
Product: COC(=O)C(CC(C)C)c1cc(Oc2cccc(C(F)(F)F)c2)cc(-c2ccc(Cl)c(C(F)(F)F)c2)c1
Yield: 71 %

Procedure:
The title compound was prepared in 71% yield from 2-(5-hydroxy-4′-chloro-3′-trifluoromethyl-biphenyl-3-yl)-4-methyl-pentanoic acid methyl ester (prepared in Example A) and 3-trifluoromethylphenylboronic acid under the conditions described in Example 15, step (g).
Reaction SMILES: [N:1]1[O:5][N:4]=[C:3]2[CH:6]=[C:7]([C:10]3[CH:15]=[CH:14][C:13]([N:16]([CH3:18])[CH3:17])=[CH:12][C:11]=3[O:19]C)[CH:8]=[CH:9][C:2]=12.[Al](Br)(Br)Br>C(Cl)Cl>[N:1]1[O:5][N:4]=[C:3]2[CH:6]=[C:7]([C:10]3[CH:15]=[CH:14][C:13]([N:16]([CH3:17])[CH3:18])=[CH:12][C:11]=3[OH:19])[CH:8]=[CH:9][C:2]=12
Reactant: COc1cc(N(C)C)ccc1-c1ccc2nonc2c1
Agent: Br[Al](Br)Br
Solvent: ClCCl
Product: CN(C)c1ccc(-c2ccc3nonc3c2)c(O)c1
Temperature: 25 °C
Reaction time: 19 h

Procedure:
140 mg (0.52 mmol) of (4-benzo[1,2,5]oxadiazol-5-yl-3-methoxy-phenyl)-dimethyl-amine are stirred at −10 to 0° C. in 1.7 mL of CH2Cl2, then over 5 minutes treated with 1.7 mL AlBr3 (1.0 M solution in CH2Br2, 3.3 eq.) and stirred another 19 h under warming to rt. Then, the mixture is extracted with brine/ethyl acetate, the combined organic layers dried with sodium sulfate and concentrated. The crude product is column chromatographed with ethyl acetate/hexanes 1:4 to yield after evaporation of the product-containing fractions the desired product as a red solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8](C#N)[C:9](=[O:20])[CH2:10][C:11]([CH3:19])([CH3:18])[CH2:12][C:13]([O:15]CC)=O)[CH:5]=[CH:6][CH:7]=1.C(O)(=O)C.S(=O)(=O)(O)O>O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:9](=[O:20])[CH2:10][C:11]([CH3:18])([CH3:19])[CH2:12][C:13]2=[O:15])[CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CC(C)(C)CC(=O)C(C#N)c1cccc(Cl)c1
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Solvent: O
Product: CC1(C)CC(=O)C(c2cccc(Cl)c2)C(=O)C1
Yield: 46.4 %

Procedure:
Starting with 108.08 g (0.351 mol) of ethyl 6-(3'-chlorophenyl)-6-cyano-5-keto-3,3-dimethylhexanoate, 316 ml of acetic acid, 105 ml of water, and 105 ml of concentrated sulfuric acid, and utilizing the procedure described in Example 1, Part B, 40.82 g (46% yield) of 2-(3'-chlorophenyl)-5,5-dimethyl-1,3-cyclohexanedione was obtained as a white solid, m.p. 155°-58° C.
Reaction SMILES: C(O[CH2:9][C:10]1[C:11](=[O:25])[NH:12][C:13](=[O:24])[N:14]([CH:23]=1)[C@@H:15]1[O:22][C@H:19]([CH2:20][OH:21])[C@@H:17]([OH:18])[CH2:16]1)C1C=CC=CC=1>C(O)C.[Pd]>[C@@H:15]1([N:14]2[CH:23]=[C:10]([CH3:9])[C:11](=[O:25])[NH:12][C:13]2=[O:24])[O:22][C@H:19]([CH2:20][OH:21])[C@@H:17]([OH:18])[CH2:16]1
Reactant: O=c1[nH]c(=O)n([C@H]2C[C@H](O)[C@@H](CO)O2)cc1COCc1ccccc1
Agent: [Pd]
Solvent: CCO
Product: Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 90.6 %

Procedure:
To a solution of 5-(benzyloxy)methyl-2′-deoxyuridine (29 mg, 0.082 mmol) in absolute ethanol (2 mL) under a nitrogen atmosphere was added 10 mg of palladium on activated carbon (10 wt. %, 10 mg) (CAUTION: flammable solid! Ensure handling in oxygen-free atmosphere). The mixture was flushed with hydrogen gas and stirred at room temperature for 30 minutes while being monitored by TLC every five minutes. The mixture was filtered, concentrated under reduced pressure, and dried under vacuum to yield thymidine (18 mg, 88%) that was identified by comparison to the authentic sample (TLC and 1H NMR).
Reaction SMILES: [C:1]12([CH2:8][CH2:9][Si:10]([O:15][CH3:16])([O:13][CH3:14])[O:11][CH3:12])[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]=[CH:2]2.[CH2:17]([SiH](CC)CC)[CH3:18].C(O)C>ClCCl.C1COCC1.C1(C)C=CC=CC=1>[CH2:8]([C:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]=[CH:2]2)[CH2:9][CH2:17][CH3:18].[C:1]12([CH2:8][CH2:9][Si:10]([O:15][CH3:16])([O:11][CH3:12])[O:13][CH3:14])[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]=[CH:2]2
Reactant: CC[SiH](CC)CC
Agent: CO[Si](CCC12C=CC(CC1)C2)(OC)OC
Solvent: CCO
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CCCCC12C=CC(CC1)C2
Temperature: 80 °C

Procedure:
BuNB (25.44 g, 0.169 mol), Norbornenylethyltrimethoxysilane (TMSENB, CAS 68245-19-2) (4.56 g, 0.019 mol), triethyl silane (0.11 g, 9.41E-04 mol), ethanol (0.10 g, 2.26E-03 mol) and toluene (170.0 g) were combined in a 300 mL serum bottle and heated to 80° C. in an oil bath to form a solution. To this solution were injected Pd1446 (0.022 g, 1.50E-05 mol) and DANFABA (0.036 g, 4.51E-5 mol), each in the form of a concentrated solution in dichloromethane. After addition, the resulting mixture was maintained at 80° C. for 4 hours. The copolymer was precipitated by adding methanol drop wise into the vigorously stirred reaction mixture. The precipitated copolymer was collected by filtration and dried in an oven at 60° C. under vacuum. After drying, 22.60 g was obtained (69%). The molecular weight of the copolymer was determined by GPC in THF solvent (polystyrene standard) to be Mw=20,000 and Mn=13,000. The composition of the copolymer was determined by 1H-NMR to be (91/9) BuNB/TMSENB copolymer. The refractive indices of this polymer were measured by prism coupling method and determined to be 1.5106 in TE mode and 1.5105 in TM mode at a wavelength of 633 nm The dried copolymer was dissolved in sufficient toluene to result in a 30 wt % copolymer solution.
Reaction SMILES: [I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:12]=[C:13]([C:17]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[O:18])[CH:14]=[CH:15][CH:16]=3)[CH:9]=2)[NH:4][CH:3]=1.[C:25]1([CH3:35])[CH:30]=[CH:29][C:28]([S:31](Cl)(=[O:33])=[O:32])=[CH:27][CH:26]=1.[OH-].[K+].[OH-].C([N+](CCCC)(CCCC)CCCC)CCC>C1(C)C=CC=CC=1.O>[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:12]=[C:13]([C:17]([N:19]4[CH2:20][CH2:21][O:22][CH2:23][CH2:24]4)=[O:18])[CH:14]=[CH:15][CH:16]=3)[CH:9]=2)[N:4]([S:31]([C:28]2[CH:29]=[CH:30][C:25]([CH3:35])=[CH:26][CH:27]=2)(=[O:33])=[O:32])[CH:3]=1
Reactant: O=C(c1cccc(-c2cnc3[nH]cc(I)c3c2)c1)N1CCOCC1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [K+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: O
Product: Cc1ccc(S(=O)(=O)n2cc(I)c3cc(-c4cccc(C(=O)N5CCOCC5)c4)cnc32)cc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 74 %

Procedure:
A mixture of (3-(3-iodo-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)(morpholino)methanone (600 mg, 1.38 mmol), p-toluenesulfonyl chloride (528 mg, 2.77 mmol), potassium hydroxide (50% w/v in water, 0.387 mL, 3.45 mmol) and tetrabutylammonium hydroxide (40% w/v in water, 0.448 mL, 0.69 mmol) in toluene (5 mL) was stirred at room temperature for 15 hours. Water was added to the mixture and the aqueous mixture was extracted by ethyl acetate (3×). The organic layers were combined, dried over sodium sulfate, filtered and concentrated to dryness. Silica gel chromatography of the crude product afforded (3-(3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)(morpholino)methanone (600 mg, 74% yield) as yellow solids. MS: m/z 588.1 (M+H+).
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=1)#[N:2].[C:12]1([Si:18]2(CCCCC)[CH2:23][CH2:22][CH:21]([SiH:24]3[CH2:29][CH2:28][CH:27](O)[CH2:26][CH2:25]3)[CH2:20][CH2:19]2)C=[CH:16][CH:15]=[CH:14][CH:13]=1>>[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([O:9][C@H:27]2[CH2:28][CH2:29][Si@H:24]([CH:21]3[CH2:22][CH2:23][SiH:18]([CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:19][CH2:20]3)[CH2:25][CH2:26]2)=[O:8])=[CH:5][CH:4]=1)#[N:2]
Reactant: CCCCC[Si]1(c2ccccc2)CCC([SiH]2CCC(O)CC2)CC1
Reactant: N#Cc1ccc(C(=O)O)cc1
Product: CCCCC[SiH]1CCC([Si@H]2CC[C@H](OC(=O)c3ccc(C#N)cc3)CC2)CC1

Procedure:
The general procedure of Example 31 was repeated using 4-cyanobenzoic acid and 4-(4-phenyl-4-n-pentyl-4-silacyclohexyl)-4-silacyclohexanol, thereby obtaining the intended product.
Reaction SMILES: [CH2:1]([NH:5][C:6]1[C:11]([NH:12][C:13](=O)[CH2:14][C:15]2[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:16]=2[O:23][CH3:24])=[C:10]([Cl:26])[N:9]=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4].CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Cl:26][C:10]1[N:9]=[CH:8][N:7]=[C:6]2[C:11]=1[N:12]=[C:13]([CH2:14][C:15]1[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:16]=1[O:23][CH3:24])[N:5]2[CH2:1][CH2:2][CH2:3][CH3:4]
Reactant: CCCCNc1ncnc(Cl)c1NC(=O)Cc1cc(OC)ccc1OC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: CCCCn1c(Cc2cc(OC)ccc2OC)nc2c(Cl)ncnc21

Procedure:
A mixture of N-(4-butylamino-6-chloro-pyrimidin-5-yl)-2-(2,5-dimethoxyphenyl) acetamide (1 mmol) and p-TSA (0.5 mmol) in toluene was refluxed for 72 h. Solvent was removed, diluted with EtOAc and washed with water, bicarbonate and dried. Purification on a silica gel column (200-400 mesh, Fisher Scientific, Tustin, Calif., USA) gave 6-chloro-8-(2,5-dimethoxybenzyl)-N9-butyl purine. Rf=0.65 in 1:1 EtOAc:hexane. 1H NMR (DMSO-d6) δ 8.7 (s, 1H), 6.96 (d, 1H), 6.84 (m, 1H), 6.8 (dd, 1H), 4.28 (s, 2H), 4.23 (t, 2H), 3.69 (s, 3H), 3.67 (s, 3H), 1.62 (m, 2H), 1.25 (m, 2H), 0.88 (t, 3H).
Reaction SMILES: [CH:1](=[O:7])[CH:2]=[CH:3][CH2:4][CH2:5][CH3:6].[CH3:8][N:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10]1.C(O)(C(F)(F)F)=O.C([C@@H]1N[C@H](C(C)(C)C)N(C)C1=O)C1C=CC=CC=1>C(Cl)Cl.C(O)(C)C>[CH3:8][N:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([C@H:3]([CH2:4][CH2:5][CH3:6])[CH2:2][CH:1]=[O:7])=[CH:10]1
Reactant: Cn1ccc2ccccc21
Reactant: CCCC=CC=O
Agent: CN1C(=O)[C@H](Cc2ccccc2)N[C@@H]1C(C)(C)C
Solvent: ClCCl
Solvent: CC(C)O
Solvent: O=C(O)C(F)(F)F
Product: CCC[C@H](CC=O)c1cn(C)c2ccccc12
Yield: 80.2 %

Procedure:
Prepared according to the general procedure from 2-hexenal (174 μL, 1.50 mmol), 1-methyl-1H-indole (64 μL, 0.50 mmol), TFA (7.7 μL, 0.10 mmol) and (2S,5S)-5-benzyl-2-tert-butyl-3-methyl-imidazolidin-4-one (24.6 mg, 0.100 mmol) in CH2Cl2 (0.85 mL) and isopropanol (0.15 mL) at −60° C. for 6 h to provide, after silica gel chromatography (5:95 EtOAc/hexanes), the title compound as a colorless oil (92 mg, 80% yield, 93% ee). IR (film) 2959, 2923, 2870, 1720, 1483, 1470, 1425, 1376, 1327, 1244, 1159, 1132, 1016, 734 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.71 (dd, J=2.1, 2.1 Hz, 1H, CHO), 7.67 (d, J=8.4 Hz, 1H, ArH), 7.35-7.24 (m, 2H, ArH), 7.12 (ddd, J=1.5, 7.2, 8.1 Hz, 1H, ArH), 6.87 (s, 1H, NCH), 3.76 (s, 3H, NCH3), 3.55 (m, 1H, ArCH), 2.83 (m, 2H, CH2CO), 1.79 (m, 2H, CHCH2CH2), 1.34 (dt, J=7.2, 22.8 Hz, 2H, CHCH2CH3), 0.92 (dd, J=7.2, 7.2 Hz, 3H, CH2CH3); 13C NMR (75 MHz, CDCl3) δ 203.0, 137.2, 127.0, 126.0, 121.6, 119.2, 118.7, 117.0, 109.4, 49.7, 38.5, 32.8, 31.4, 20.8, 14.2; HRMS (CI) exact mass calcd for (C15H19NO) requires m/z 229.1467, found m/z 229.1464. [α]D=−1.7 (c=1.0, CHCl3). The enantiomeric ratio was determined by HPLC analysis of the alcohol, obtained by NaBH4 reduction of the aldehyde, using a Chiracel AS and AS guard column (2:98 ethanol/hexanes, 1 mL/min); S isomer tr=16.1 min and R isomer tr=18.1 min.
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:8]1[C:9]([CH:14]2[CH2:19][CH2:18][N:17]([C:20](=[O:22])[CH3:21])[CH2:16][CH2:15]2)=[N:10][CH:11]=[CH:12][N:13]=1.[Cl:23][C:24]1[N:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=1>CN1C(=O)CCC1>[Cl:23][C:24]1[N:29]=[CH:28][C:27]([O:30][C:8]2[C:9]([CH:14]3[CH2:19][CH2:18][N:17]([C:20](=[O:22])[CH3:21])[CH2:16][CH2:15]3)=[N:10][CH:11]=[CH:12][N:13]=2)=[CH:26][CH:25]=1
Reactant: Oc1ccc(Cl)nc1
Reactant: CC(=O)N1CCC(c2nccnc2Cl)CC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN1CCCC1=O
Product: CC(=O)N1CCC(c2nccnc2Oc2ccc(Cl)nc2)CC1
Temperature: 130 °C

Procedure:
To a mixture of cesium carbonate (0.505 g, 1.55 mmol), 1-(4-(3-chloropyrazin-2-yl)piperidin-1-yl)ethanone (0.129 g, 0.538 mmol), and 6-chloropyridin-3-ol (0.140 g, 1.08 mmol) was added NMP (2 mL). The reaction mixture was degassed and heated to 130° C. for 2 h. The reaction mixture was diluted with Teac. The organic phase was washed with water (1×), brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (50% to 100% Teac (10% MeOH) in hexanes) gave 1(4-(3-(6-chloropyridin-3-yloxy)pyrazin-2-yl)piperidin-1-yl)ethanone as a colorless oil that was used in the next step without further purification. MS (ESI, pos. ion) m/z: 333.2 (M+1).