Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:12]C(=O)[N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:9]2[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)=[CH:4][CH:3]=1.[OH-].[Na+]>CO.Cl.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:12])[CH:9]([NH:10][C:14](=[O:15])[O:16][C:17]([CH3:18])([CH3:19])[CH3:20])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1C(=O)OC(c2ccc(F)cc2)C1Cc1ccc(C(F)(F)F)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(C)(C)OC(=O)NC(Cc1ccc(C(F)(F)F)cc1)C(O)c1ccc(F)cc1
Reaction time: 3 h
Yield: 77.1 %

Procedure:
To a solution of 1,1-dimethylethyl (4RS,5SR)-5-(4-fluorophenyl)-2-oxo-4-((4-(trifluoromethyl)phenyl)methyl)-1,3-oxazolidine-3-carboxylate (4.0 g, 9.10 mmol) in methanol (22 ml) was gradually added a solution of sodium hydroxide (0.44 g, 10.92 mmol) in methanol (22 ml) under ice-cooling. The reaction solution was stirred for 3 hrs., diluted with 1N hydrochloric acid (12 ml) and water (100 ml), and extracted with ethyl acetate (100 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) and recrystallized from ethyl acetate-hexane to give the title compound (2.90 g, 77%).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:12]([OH:14])=[O:13])[CH2:10][OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:18][CH3:19].Cl>CS(C)=O.O>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:12]([OH:14])=[O:13])[CH2:10][O:11][CH2:18][CH3:19])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCBr
Reactant: CC(C)(C)OC(=O)N[C@@H](CO)C(=O)O
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CCOC[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reaction time: 1 h

Procedure:
To a solution of N-(tert-butoxycarbonyl)serine (10.26 g, 50.00 mmol) in DMSO (500 mL) was added sodium hydride (2.0 g, 50 mmol) at room temperature. After 1 hour, bromoethane (5.45 g, 50.0 mmol) was added and then additional sodium hydride (2.0 g, 50 mmol) was added immediately. After 16 hours, hydrochloric acid (1.0 M in water, 50 mL, 50 mmol) and water (2 L) were added. The mixture was extracted with ethyl acetate, and the organics were dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford N-(tert-butoxycarbonyl)-O-ethylserine which was used without further purification. MS ESI calc'd. for C10H20NO5 [M+H]+ 234. found 234.
Reaction SMILES: [CH:1]([N:4]1[CH2:8][CH2:7][CH:6]([O:9][C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[NH:15][C:14]([C:19]([OH:21])=O)=[CH:13]3)[CH2:5]1)([CH3:3])[CH3:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH:44]1([CH2:47][NH:48][CH2:49][CH2:50][CH3:51])[CH2:46][CH2:45]1.C(N(C(C)C)C(C)C)C>CN(C=O)C.CO>[CH:44]1([CH2:47][N:48]([CH2:49][CH2:50][CH3:51])[C:19]([C:14]2[NH:15][C:16]3[C:12]([CH:13]=2)=[CH:11][C:10]([O:9][CH:6]2[CH2:7][CH2:8][N:4]([CH:1]([CH3:2])[CH3:3])[CH2:5]2)=[CH:18][CH:17]=3)=[O:21])[CH2:46][CH2:45]1
Reactant: CCCNCC1CC1
Reactant: CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)O)cc3c2)C1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CO
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCCN(CC1CC1)C(=O)c1cc2cc(OC3CCN(C(C)C)C3)ccc2[nH]1
Yield: 37 %

Procedure:
A mixture of 0.07 mmol 5-(1-isopropyl-pyrrolidin-3-yloxy)-1H-indole-2-carboxylic acid, 1.25 equiv. 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl uronium tetrafluoroborat, 1.25 equivalents cyclopropylmethyl-propyl-amine and 5 equivalents N-ethyldiisopropyl-amine in 0.7 ml DMF was stirred for 16 h at room temperature. The mixture was diluted with 0.8 ml methanol and subjected to preparative HPLC purification on reversed phase material eluting with a gradient of acetonitrile/water/triethyamine. The product fractions were evaporated to dryness to yield 9.1 mg (37%) of the title compound as light brown solid. MS (m/e): 384.5 (MH+, 100%).
Reaction SMILES: [N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20](O)=[O:21])=[CH:16][CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:29][C:30]1[CH:31]=[CH:32][C:33]([Cl:52])=[C:34]([N:36]2[CH2:45][C:44]3[C:39](=[N:40][C:41]([S:46]([CH3:49])(=[O:48])=[O:47])=[N:42][CH:43]=3)[N:38]([CH3:50])[C:37]2=[O:51])[CH:35]=1>O1CCCC1.ClCCl>[Cl:52][C:33]1[CH:32]=[CH:31][C:30]([NH:29][C:20]([C:17]2[CH:16]=[CH:15][C:14]([C:11]3[CH:12]=[CH:13][C:8]([CH2:7][N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)=[CH:9][CH:10]=3)=[CH:19][CH:18]=2)=[O:21])=[CH:35][C:34]=1[N:36]1[CH2:45][C:44]2[C:39](=[N:40][C:41]([S:46]([CH3:49])(=[O:47])=[O:48])=[N:42][CH:43]=2)[N:38]([CH3:50])[C:37]1=[O:51]
Reactant: CN1C(=O)N(c2cc(N)ccc2Cl)Cc2cnc(S(C)(=O)=O)nc21
Reactant: O=C(O)c1ccc(-c2ccc(CN3CCOCC3)cc2)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: C1CCOC1
Solvent: ClCCl
Product: CN1C(=O)N(c2cc(NC(=O)c3ccc(-c4ccc(CN5CCOCC5)cc4)cc3)ccc2Cl)Cc2cnc(S(C)(=O)=O)nc21
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
300 mg of 4′-Morpholin-4-ylmethyl-biphenyl-4-carboxylic acid in 15 ml dry tetrahydrofuran (THF) were treated dropwise with 129 mg oxalyl chloride under cooling with ice. The mixture was subsequently stirred for 20 min at room temperature (RT) before a suspension of 200 mg aniline derivative from example d in 5 ml dichloromethane was added slowly. The mixture was stirred over night and then diluted with 50 ml dichloromethane. Precipitate was filtered off and the filtrate was washed several times with conc. aqueous sodium carbonate solution. The organic phase was dried, evaporated and purified by flash chromatography on silica, using a gradient from dichloromethane to dichloromethane/methanol (60/1) to dichloromethane/methanol/concentrated ammonia (60/1/0.2).
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.O.Cl.[NH:10]1[CH2:15][CH2:14][C:13](=[O:16])[CH2:12][CH2:11]1>O1CCOCC1>[N:3]1[CH:4]=[CH:5][CH:6]=[N:7][C:2]=1[N:10]1[CH2:15][CH2:14][C:13](=[O:16])[CH2:12][CH2:11]1
Reactant: O=C1CCNCC1
Reactant: Clc1ncccn1
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Product: O=C1CCN(c2ncccn2)CC1
Temperature: 80 °C
Yield: 69 %

Procedure:
To a solution of 2-chloropyrimidine (300 mg, 2.619 mmol) in dioxane (5 ml), was added piperidin-4-one hydrochloride monohydrate (402.3 mg, 2.619 mmol) at room temperature. The mixture was heated at 80° C. overnight and concentrated under reduced pressure. The residue was treated with EtOAc (30 ml) and saturated NaHCO3 (10 ml). After separation of the layers, the aqueous phase was extracted with EtOAc (2×10 ml). The combined organic layers were washed with brine (10 ml), dried (MgSO4), filtered, and concentrated under reduced pressure to furnish a crude product. This material was purified by column chromatography (40% EtOAc/hexanes) to give 1-pyrimidin-2-yl-piperidin-4-one (320 mg, 53%) as an off-white solid: 1H NMR (CDCl3, 400 MHz) δ 8.38 (d, J=6.4 Hz, 2H), 6.61 (t, J=6.4 Hz, 9H), 4.16 (t, J=5.6 Hz, 2H), 2.53 (t, J=5.6 Hz, 2H).
Reaction SMILES: C(O)(C(F)(F)F)=O.CC1(C)[O:13][CH:12]([CH2:14][O:15][C:16]2[C:24]3[C:19](=[N:20][CH:21]=[CH:22][C:23]=3[N:25]3[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]3)[N:18](CC3C=CC(OC)=CC=3)[N:17]=2)[CH2:11][O:10]1.C(Cl)[Cl:49]>>[ClH:49].[ClH:49].[N:25]1([C:23]2[CH:22]=[CH:21][N:20]=[C:19]3[NH:18][N:17]=[C:16]([O:15][CH2:14][CH:12]([OH:13])[CH2:11][OH:10])[C:24]=23)[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1
Reactant: ClCCl
Reactant: COc1ccc(Cn2nc(OCC3COC(C)(C)O3)c3c(N4CCN(C(=O)OC(C)(C)C)CC4)ccnc32)cc1
Solvent: O=C(O)C(F)(F)F
Product: Cl
Product: OCC(O)COc1n[nH]c2nccc(N3CCNCC3)c12
Temperature: 25 °C
Reaction time: 2 h
Yield: 70 %

Procedure:
TFA (1 mL) was added to tert-butyl 4-(3-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (0.068 g, 0.123 mmol) in DCM (1 mL) and stirred at room temperature for 2 hours. The reaction was then concentrated to dryness and dried under vacuum for 1 hour. TFA (2 mL) was added, and the mixture was heated at 100° C. in a sealed tube for 20 hours. The reaction was concentrated to dryness. The resulting residue was dissolved in DCM (1 mL), and HCl in ether (1 mL, 2N) was added. The resulting solid was collected by filtration to give 3-(4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-3-yloxy)propane-1,2-diol dihydrochloride (0.042 g, 70%). MS APCI (+) m/z 294.2 detected.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.C(P(CCCC)CCCC)CCC.[CH:26]1[C:38]2[CH2:37][C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:30]=2[CH:29]=[CH:28][C:27]=1/[C:39](/[CH3:43])=[CH:40]/[CH2:41]O>C1C=CC=CC=1.O.C(OCC)(=O)C>[CH3:12][O:11][C:9](=[O:10])[CH2:8][C:5]1[CH:4]=[CH:3][C:2]([O:1][CH2:41]/[CH:40]=[C:39](/[C:27]2[CH:28]=[CH:29][C:30]3[C:31]4[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=4)[CH2:37][C:38]=3[CH:26]=2)\[CH3:43])=[CH:7][CH:6]=1
Reactant: COC(=O)Cc1ccc(O)cc1
Reactant: C/C(=C\CO)c1ccc2c(c1)Cc1ccccc1-2
Agent: CCCCP(CCCC)CCCC
Solvent: CCOC(C)=O
Solvent: c1ccccc1
Solvent: O
Product: COC(=O)Cc1ccc(OC/C=C(\C)c2ccc3c(c2)Cc2ccccc2-3)cc1
Temperature: 25 °C
Reaction time: 17 h
Yield: 62.4 %

Procedure:
Under a atmosphere of nitrogen, methyl 4-hydroxyphenylacetate (183 mg, 1.1 mmol) was added to a stirred cooled solution of azodicarboxylic dipiperidide (378 mg, 1.5 mmol), tributylphosphine (304 mg, 1.5 mmol) and (E)-3-(9H-fluoren-2-yl)-but-2-en-1-ol (236 mg, 1.0 mmol) in dry benzene (30 ml), the mixture warmed to room temperature, and stirred for 17 h. The reaction mixture was diluted with water (100 ml) and ethyl acetate (100 ml each). The aqueous layer was collected and further extracted with ethyl acetate (2×50 ml). The organic layers were combined, washed with brine, dried (MgSO4) and evaporated. The crude product was then purified by column chromatography on silica (eluent: 15% ethyl acetate in toluene) to give 240 mg (62%) of the title compound.
Reaction SMILES: [CH2:1]([N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C@@H:7]([NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:6]1=O)[C:2]([CH3:4])=O.C([O-])(=O)C.[NH4+:32].[OH-].[NH4+]>C(O)(=O)C>[NH3:5].[CH3:4][C:2]1[N:32]=[C:6]2[CH:7]([NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:5]2[CH:1]=1
Reactant: CC(=O)CN1C(=O)[C@H](NC(=O)OCc2ccccc2)CCc2ccccc21
Reactant: [NH4+]
Agent: CC(=O)[O-]
Agent: [OH-]
Solvent: CC(=O)O
Product: Cc1cn2c(n1)C(NC(=O)OCc1ccccc1)CCc1ccccc1-2
Product: N
Temperature: 25 °C
Reaction time: 16 h
Yield: 10 %
Yield: 63.3 %

Procedure:
Combine benzyl N-[(3R)-1-acetonyl-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]carbamate (0.7 g, 1.91 mmol) with ammonium acetate (2.94 g, 38.2 mmol) in acetic acid (20.0 mL) and heat at 115° C. for 24 hours, and then stir the mixture at ambient temperature for approximately 16 hours. Pour the reaction mixture into ice-water, basify it with ammonium hydroxide (28-30%), and extract with dichloromethane. Wash with water and brine, dry over sodium sulfate, and concentrate the organic layer under reduced pressure. Purify the residue by flash chromatography (10% ethyl acetate/hexane to 50% ethyl acetate/hexane), then an SCX column (methanol, then 10% 2N ammonia in methanol/CH2Cl2) to give the title compound (0.21 g, 32%) as a white solid: MS (m/z): 348 (M+1). (Based on the final compounds made from this intermediate, the title compound is partially racemized.)
Reaction SMILES: [C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[CH:10]=2)([O:3][CH2:4][CH3:5])=[O:2].[H-].[Na+].O.[CH2:26](I)[CH3:27]>CN(C)C=O>[CH2:26]([N:8]1[C:9]2[C:14](=[CH:13][CH:12]=[C:11]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[CH:10]=2)[C:15](=[O:16])[C:6]([C:1]([O:3][CH2:4][CH3:5])=[O:2])=[CH:7]1)[CH3:27]
Reactant: CCI
Reactant: CCOC(=O)c1cnc2cc(C3CCCCC3)ccc2c1O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1cn(CC)c2cc(C3CCCCC3)ccc2c1=O
Temperature: 25 °C

Procedure:
A suspension of 32.7 g of 3 -carboethoxy-4-hydroxy-7-cyclohexyl-quinoline and 7.1 g of sodium hydride (50% strength in mineral oil) in 400 ml of absolute dimethylformamide is stirred for 45 minutes at room temperature with exclusion of water. In the course thereof, the temperature of the reaction mixture rises to 35°C and a homogeneous solution is produced. 39 g of ethyl iodide are added dropwise to this solution over the course of 10 minutes whilst stirring and the mixture is stirred for a further 21/2hours at 55°C. It is then cooled to room temperature and 500 ml of water are added slowly, whilst stirring. The resulting precipitate is filtered off, well washed with water and recrystallised from ethanol-ether. 1-Ethyl-3-carboethoxy-4-oxo-7-cyclohexyl-1,4 -dihydroquinoline, thus obtained, melts at 176°-178°C.
Reaction SMILES: C([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[CH:5]C=1)#N.BrC1C=CC2[N:27]([CH:29]=[N:30][N:31]=2)C=1>>[N:31]1[N:30]=[CH:29][N:27]2[CH:5]=[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:13][CH2:14]3)[CH:7]=[CH:8][C:3]=12
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(C#N)cc2)CC1
Reactant: Brc1ccc2nncn2c1
Product: CC(C)(C)OC(=O)N1CCC(c2ccc3nncn3c2)CC1

Procedure:
The title compound was prepared using standard chemical manipulations and procedures similar to those used for the preparation of compound 1.1, except 6-bromo-[1,2,4]triazolo[4,3-a]pyridine was used in place of 4-bromobenzonitrile. m/z (ES+) 303 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1F.[CH3:12][O:13][CH2:14][CH2:15][NH:16][CH2:17][CH2:18][O:19][CH3:20].C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[F:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[N:16]([CH2:17][CH2:18][O:19][CH3:20])[CH2:15][CH2:14][O:13][CH3:12]
Reactant: O=[N+]([O-])c1ccc(F)c(F)c1
Reactant: COCCNCCOC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: COCCN(CCOC)c1ccc([N+](=O)[O-])cc1F
Temperature: 80 °C

Procedure:
1.13 g (7.1 mmol) of 3,4-difluoronitrobenzene (Aldrich, Buchs, Switzerland), 1.04 g (7.81 mmol) of bis(2-methoxyethyl)amine (Fluke, Buchs, Switzerland) and 1.96 g (14.2 mmol) of K2CO3 in 7 ml of DMSO are stirred for 1.5 h at rt and then heated at 80° C. for 4 h. The reaction mixture is quenched with H2O and extracted with EtOAc (2×). The organic layers are washed with brine (3×), dried over MgSO4, filtered and evaporated. The residue is purified by flash chromatography on silica gel (hexane-EtOAc 6:1 to 5:1) to give the title compound as a yellow oil. ES-MS: 273 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:17])=[C:11]([CH2:13][C:14](O)=[O:15])[N:12]=2)=[CH:4][CH:3]=1.[K+].[Br-]>C1COCC1.CO.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]([CH3:17])=[C:11]([CH2:13][CH2:14][OH:15])[N:12]=2)=[CH:6][CH:7]=1
Reactant: Cc1oc(-c2ccc(Br)cc2)nc1CC(=O)O
Agent: [Br-]
Agent: [K+]
Solvent: CO
Solvent: C1CCOC1
Solvent: ClCCl
Product: Cc1oc(-c2ccc(Br)cc2)nc1CCO
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 2-(4-bromophenyl)-5-methyl-4-oxazoleacetic acid (39.1 g, 0.13 mol) in dry THF (175 mL) was treated dropwise with borane-THF complex (227 mL of a 1.0 M solution in THF, 1.3 mol) over 2 h (reaction temperature to 35° C.). After stirring 2 h at room temperature under N2, the reaction was quenched with slow addition of methanol (60 mL) and stirred overnight at room temperature. The reaction was diluted with 1 N NaOH (50 mL) and extracted with CH2Cl2 (2×200 mL). The organic layer was washed with H2O (3×100 mL), dried (MgSO4), and the solvent removed in vacuo to give 38.7 g of crude product that was recrystallized from toluene (200 mL, wash solid with cold hexanes) to give 26.9 g (72%) of 2-(4-bromophenyl)-5-methyl-4-oxazoleethanolas a white powder: Rf=0.37 in 10% MeOH/CH2Cl2; 1H NMR (500 MHz, CDCl3) 7.84-7.82 (m, 2H), 7.57-7.55 (m, 2H), 3.91 (q, J=5.5 Hz, 2H), 3.14 (t, J=6 Hz, OH), 2.72 (t, J=5.5 Hz, 2H), 2.33 (s, 3H); 13C (125 MHz, CDCl3) 158.7, 144.5, 134.2, 131.9, 127.4, 126.4, 124.3, 61.8, 28.1, 10.1; IR (KBr) 3293, 2948, 1642, 15985, 1480, 1472, 1401, 1053, 1003, 836, 734 cm−1; UV (EtOH)max 290 run (20860); Anal. Calculated for C12H12BrNO2: C, 51.09; H, 4.29; N, 4.96; Br, 28.32. Found C, 51.31; H 4.06; N, 4.90; Br, 28.19.
Reaction SMILES: C([NH+]([CH2:6][CH3:7])CC)C.[C:8]12(C(Cl)=O)C[CH:12]3[CH2:13][CH:14](C[CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2>C(#N)C.N1C=CC=CC=1>[CH3:14][CH2:15][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:6][CH3:7]
Reactant: CC[NH+](CC)CC
Reactant: O=C(Cl)C12CC3CC(CC(C3)C1)C2
Solvent: CC#N
Solvent: c1ccncc1
Product: CCCCCCCCCC

Procedure:
The dimethoxytrityl group of the derivatized CPG from Example 9 is removed by a treatment with 2% dichloroacetic acid followed by washing with dry acetonitrile. The CPG is washed with acetonitrile-pyridine (4:1) followed by a simultaneous treatment of the CPG with 20-30 equivalents of the 10-O-(dimethoxytrityl) decyl-phosphonic acid as the triethylammonium salt, 20-30 equivalents of adamantane carbonyl chloride in acetonitrile-pyridine. The mixture is agitated by circulating the reagents in the synthesis vessel for 10-15 minutes. The CPG is then briefly washed with acetonitrile-pyridine and then treated with diisopropyl phosphite adamantane carbonyl chloride to cap all unreacted hydroxyl groups. Finally, the CPG is washed with acetonitrile-pyridine and then acetonitrile. An estimate of coupling efficiency is derived from the treatment of the CPG with dichloracetic acid in acetonitrile followed by a measurement of the absorbance of an aliquot at 498 nm. Repeating the above procedure n times will yield an oligomer with n+1 decane units and n H-phosphonate linkages. The oligomer is tethered to a LCAA CPG by a succinate group as described above.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][C:11]([CH3:15])([CH3:14])[CH2:10][O:9]2)=[CH:4][CH:3]=1.[Mg].[CH2:17](Br)[CH:18]=[CH2:19]>C1COCC1>[CH2:19]([C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][C:11]([CH3:15])([CH3:14])[CH2:10][O:9]2)=[CH:4][CH:3]=1)[CH:18]=[CH2:17]
Reactant: CC1(C)COC(c2ccc(Br)cc2)OC1
Reactant: C=CCBr
Agent: [Mg]
Solvent: C1CCOC1
Product: C=CCc1ccc(C2OCC(C)(C)CO2)cc1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 58.9 %

Procedure:
In a dry apparatus a solution of 12 (2.05 g, 7.60 mmol) in THF (15 mL) was added dropwise to magnesium powder (0.22 g, 9.1 mmol) under argon. After the addition was completed the mixture was refluxed for 45 min. Then the mixture was cooled to rt and allyl bromide (720 μL, 8.30 mmol) dissolved in THF (10 mL) was added slowly. The mixture was stirred for 4.5 h, then quenched with satd aq NH4Cl (25 mL) and extracted with ether. The combined organic phases were washed with aq NaHCO3 (5%) and brine and dried (Na2SO4). The solvents were removed under reduced pressure and the residue was crystallized from hexanes and filtered. The filtrate was purified by column chromatography (silica, ether/hexanes, 1:4), affording a light yellow oil (1.04 g, 59%). IR (neat): {tilde over (v)} 3077, 2955, 2904, 2846, 1639, 1619, 1517; 1H NMR δ 0.79 (s, 3H), 1.29 (s, 3H), 3.38 (d, 3J=6.6 Hz, 2H), 3.64 (d, 2J=11.0 Hz, 2H), 3.76 (d, 2J=11.0 Hz, 2H), 5.00–5.10 (m, 2H), 5.37 (s, 1H), 5.86–6.01 (m, 1H), 7.19, 7.43 (AA′BB′, 2×2H); 13C NMR (APT) δ 21.7 (−), 22.9 (−), 30.0 (+), 39.8 (+), 77.5 (+), 101.5 (−), 115.6 (+), 126.1 (−), 128.4 (−), 136.3 (+), 137.2 (−), 140.5 (+); GC-MS (EI) obsd 232, 231, 191, 163, 145, 115, 105, 91, 69, 56, 41; Anal. Calcd for C15H20O2: C, 77.55; H, 8.68; Found: C, 77.52; H, 8.77.
Reaction SMILES: S([S:11]([OH:14])(=[O:13])=[O:12])(C1C=CC(C)=CC=1)(=O)=O.[N+:15]([C:18]1[CH:41]=[CH:40][C:21]([CH:22]=[CH:23][C:24]([O:26][C:27]2[CH:36]=[CH:35][C:34]3[C:29](=[CH:30][CH:31]=[C:32]([C:37](=[NH:39])[NH2:38])[CH:33]=3)[CH:28]=2)=[O:25])=[CH:20][CH:19]=1)([O-])=O>C(O)(=O)C.[Zn]>[CH3:18][S:11]([OH:14])(=[O:13])=[O:12].[CH3:18][S:11]([OH:14])(=[O:13])=[O:12].[NH2:15][C:18]1[CH:19]=[CH:20][C:21]([CH:22]=[CH:23][C:24]([O:26][C:27]2[CH:36]=[CH:35][C:34]3[C:29](=[CH:30][CH:31]=[C:32]([C:37](=[NH:38])[NH2:39])[CH:33]=3)[CH:28]=2)=[O:25])=[CH:40][CH:41]=1
Reactant: N=C(N)c1ccc2cc(OC(=O)C=Cc3ccc([N+](=O)[O-])cc3)ccc2c1
Reactant: Cc1ccc(S(=O)(=O)S(=O)(=O)O)cc1
Agent: [Zn]
Solvent: CC(=O)O
Product: CS(=O)(=O)O
Product: N=C(N)c1ccc2cc(OC(=O)C=Cc3ccc(N)cc3)ccc2c1
Yield: 16 %

Procedure:
In 60 ml of acetic acid, was suspended 3 g of 6-amidino-2-naphthyl 4-nitrocinnamate tosylsulfonate. To the suspension, while being cooled in ice and stirred, was added 1.8 g of zinc dust. The mixture was stirred for 24 hours and removed of insolubles by filtration. The filtrate was neutralized, admixed with a saturated aqueous sodium hydrogencarbonate solution and the precipitate was suspended in methanol and admixed with methanesulfonic acid to dissolve the precipitate. Ethyl ether was added to the solution and the resulting oily substance was left standing at room temperature to solidify. Upon recrystallization from a methano-ethyl ether mixture, there was obtained 0.14 g of 6-amidino-2-naphthyl 4-aminocinnamate dimethanesulfonate.
Reaction SMILES: Cl[C:2]1[N:3]=[CH:4][C:5]2[N:10]=[C:9]([NH:11]C(=O)OCC)[S:8][C:6]=2[N:7]=1.[CH3:17][O-:18].[Na+].O>CO>[CH3:17][O:18][C:2]1[N:3]=[CH:4][C:5]2[N:10]=[C:9]([NH2:11])[S:8][C:6]=2[N:7]=1
Reactant: CCOC(=O)Nc1nc2cnc(Cl)nc2s1
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: COc1ncc2nc(N)sc2n1
Temperature: 25 °C
Yield: 82 %

Procedure:
Ethyl 5-chlorothiazolo[5,4-d]pyrimidin-2-ylcarbamate (250 mg, 0.966 mmol) was suspended in MeOH (10 mL) and a 25% (w/w) solution of sodium methoxide in methanol was added (10 mL, 46.3 mmol). The resulting solution was refluxed overnight, cooled to ambient temperature, poured into an equal volume of water and extracted with chloroform (4×). A significant amount of compound was still present in the aqueous phase, so this was concentrated to residue, and then dissolved in a small amount of 1N HCl (not enough to make the resulting solution acidic) and extracted again with EtOAc (5×). The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. 5-Methoxythiazolo[5,4-d]pyrimidin-2-amine (144 mg, 0.790 mmol, 82% yield) was thus obtained as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.43 (s, 1H) 7.81 (s, 2H) 3.90 (s, 3H). MS (LC/MS) R.T.=0.73; [M+H]+=183.03.
Reaction SMILES: [Cl:1][C:2]1[C:3](=[O:19])[NH:4][N:5]=[C:6]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])[C:7]=1Cl.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[CH2:25][NH2:26].O1CCOCC1>O>[Cl:1][C:2]1[C:3](=[O:19])[NH:4][N:5]=[C:6]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])[C:7]=1[NH:26][CH2:25][C:24]1[CH:27]=[CH:28][C:29]([O:30][CH3:31])=[C:22]([O:21][CH3:20])[CH:23]=1
Reactant: COC(=O)CCCCCOc1n[nH]c(=O)c(Cl)c1Cl
Reactant: COc1ccc(CN)cc1OC
Solvent: C1COCCO1
Solvent: O
Product: COC(=O)CCCCCOc1n[nH]c(=O)c(Cl)c1NCc1ccc(OC)c(OC)c1
Reaction time: 8 h

Procedure:
A mixture comprising 4.13 g of 4,5-dichloro-6-(5-methoxycarbonylpentyloxy)-3(2H)-pyridazinone, 6.70 g of 3,4-dimethoxybenzylamine, 130 ml of 1,4-dioxane and 130 ml of water, was refluxed with stirring overnight. The solvent was evaporated under reduced pressure, and water was poured to the residue, whereupon the product was extracted with chloroform. The extract was washed with dilute hydrochloric acid, water and brine in order, and was dried over sodium sulfate. Thereafter, the solvent was distilled off, and the residue was crystallized from chloroform-n-hexane-diethyl ether to obtain 5.28 g of the above identified compound as colorless crystals having a melting point of from 111° C. to 112° C.