Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[C:3]1[CH2:11][N:12]([CH:28]1[C:37]2[N:36]=[CH:35][CH:34]=[CH:33][C:32]=2[CH2:31][CH2:30][CH2:29]1)[CH2:13][CH2:14][CH2:15][CH2:16][N:17]1C(=O)C2C(=CC=CC=2)C1=O.O.NN>C(O)C>[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[C:3]1[CH2:11][N:12]([CH:28]1[C:37]2[N:36]=[CH:35][CH:34]=[CH:33][C:32]=2[CH2:31][CH2:30][CH2:29]1)[CH2:13][CH2:14][CH2:15][CH2:16][NH2:17]
Reactant: Cn1c(CN(CCCCN2C(=O)c3ccccc3C2=O)C2CCCc3cccnc32)nc2ccccc21
Agent: NN
Solvent: CCO
Solvent: O
Product: Cn1c(CN(CCCCN)C2CCCc3cccnc32)nc2ccccc21
Temperature: 25 °C
Reaction time: 18 h
Yield: 32.2 %

Procedure:
To a solution of 2-{4-[(1-Methyl-1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-butyl}-isoindole-1,3-dione (0.1030 g, 0.21 mmol) in ethanol (1 mL) was added hydrazine monohydrate (0.51 mL, 10.5 mmol), and the reaction mixture was stirred at room temperature for 18 hours. The mixture was concentrated and purified first via column chromatography on silica gel (91:12:1 CH2Cl2—MeOH—NH4OH) and then by radial chromatography on silica (18:1:1 CH2Cl2—MeOH—NH4OH) to yield 0.0246 g (32%) of N1-(1-Methyl-1H-benzoimidazol-2-ylmethyl)-N1-(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine. 1H NMR (CDCl3) δ 1.32-1.42 (m, 5H), 1.91-2.02 (m, 2H), 2.05-2.11 (m, 1H), 2.55 (t, 2H, J=6.9 Hz), 2.60-2.64 (m, 3H), 2.76-2.86 (m, 1H), 3.98 (s, 3H), 4.04-4.17 (m, 3H), 7.00-7.04 (m, 1H), 7.21-7.27 (m, 2H), 7.30-7.33 (m, 2H), 7.68-7.72 (m, 1H), 8.47 (d, 1H, J=3.3 Hz).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[C:7]([OH:16])[C:8](=[CH:13][C:14]=1[Br:15])[C:9]([O:11][CH3:12])=[O:10])(=[O:3])[CH3:2].[I:17](Cl)(=O)=O.I(Cl)(=O)=O.C([N+](C)(C)C)C1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CO>[C:1]([NH:4][C:5]1[C:6]([I:17])=[C:7]([OH:16])[C:8](=[CH:13][C:14]=1[Br:15])[C:9]([O:11][CH3:12])=[O:10])(=[O:3])[CH3:2]
Reactant: COC(=O)c1cc(Br)c(NC(C)=O)cc1O
Reactant: O=I(=O)Cl
Agent: C[N+](C)(C)Cc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: COC(=O)c1cc(Br)c(NC(C)=O)c(I)c1O
Temperature: 25 °C
Reaction time: 30 h

Procedure:
Methyl 4-acetylamino-5-bromosalicylate (I-249) (576 mg, 2.0 mmol) was dissolved in a mixed liquid of methylene chloride (20 ml) and methanol (10 ml), then benzyltrimethylammonium dichloroiodate (835 mg, 2.4 mmol) and sodium bicarbonate (1.1 g, 13.0 mmol) were added, followed by stirring at room temperature for 30 hours. The reaction liquid was filtered, the filtrate was concentrated under reduced pressure, then saturated ammonium chloride water was added to the residue, followed by extraction twice with chloroform, then the organic layer was washed with saturated sodium thiosulfate water, and dried over anhydrous magnesium sulfate. After filtration and concentration under reduced pressure, the resulting residue was subjected to column chromatography, and the eluate with chloroform/methanol (50:1) gave the entitled compound (889 mg, quant.) as a pale yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:24])[CH2:4][CH:5]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([S:20](Cl)(=[O:22])=[O:21])[CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(N(CC)CC)C.Cl.[NH2:33][C:34]([NH2:36])=[NH:35]>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:24])[CH2:4][CH:5]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([S:20](=[O:22])(=[O:21])[N:33]=[C:34]([NH2:36])[NH2:35])[CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: COC(=O)CC(c1ccccc1)c1ccc(OC)c(S(=O)(=O)Cl)c1
Reactant: N=C(N)N
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)CC(c1ccccc1)c1ccc(OC)c(S(=O)(=O)N=C(N)N)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 3-(3-chlorosulfonyl-4-methoxy-phenyl)-3-phenyl-propionic acid methyl ester (500 mg, 1.36 mmol) in DCM (50 mL) is added triethylamine (0.57 ml, 4.08 mmol) and guanidine hydrochloride (0.14 g, 1.50 mmol). The reaction mixture is stirred at RT overnight, then diluted with DCM (100 mL). The reaction mixture is washed with an aqueous saturated solution of NaHCO3 (30 mL), water (30 mL) then brine (30 mL). The organic phase is then dried over MgSO4, filtered and concentrated in vacuo. Purification of the residue by reverse phase chromatography (Isolute™ C18, 0-100% acetonitrile in water with 0.1% TFA) affords the title compound.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH2:11][C:10](=[CH:13][C:14]([O:16][CH3:17])=[O:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N12CCCN=C1CCCCC2.[N+:29]([CH3:32])([O-:31])=[O:30]>>[CH2:1]([N:8]1[CH2:12][CH2:11][C:10]([CH2:13][C:14]([O:16][CH3:17])=[O:15])([CH2:32][N+:29]([O-:31])=[O:30])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)C=C1CCN(Cc2ccccc2)C1
Reactant: C[N+](=O)[O-]
Solvent: C1CCC2=NCCCN2CC1
Product: COC(=O)CC1(C[N+](=O)[O-])CCN(Cc2ccccc2)C1
Yield: 100 %

Procedure:
A solution of methyl (1-benzylpyrrolidin-3-ylidene)acetate a45 (3 g, 1.2 mmol, 1 eq), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.7 g, 4.6 mmol, 3.8 eq) in nitromethane (30 ml) is refluxed for 30 h. The solution is concentrated in vacuum and the resulting oil is purified by chromatography over silicagel (ethyl acetate/hexane 30/70) to afford 3.7 g of methyl [1-benzyl-3-(nitromethyl)pyrrolidin-3-yl]acetate a46 as a black oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH:6]=O.[CH2:11]([NH2:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>CCOCC>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH:6]=[N:18][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: COc1cccc(C=O)c1
Reactant: NCc1ccccc1
Solvent: CCOCC
Product: COc1cccc(C=NCc2ccccc2)c1

Procedure:
A solution of 100 gm. of 3-methoxybenzaldehyde. 78.7 gm. of benzylamine, and 800 ml. of anhydrous ether was refluxed for 14 hours and then concentrated in vacuo to an oil. Distillation provided 144.3 gm. of clear oil, b.p. 152°-154° (1.2 Torr).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[C:13]([CH3:15])[N:12]=[C:11]([N:16]3[CH:20]=[C:19](I)[N:18]=[CH:17]3)[CH:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[NH2:22][C:23]1[CH:28]=[CH:27][C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][N:24]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[C:13]([CH3:15])[N:12]=[C:11]([N:16]3[CH:20]=[C:19]([C:26]4[CH:27]=[CH:28][C:23]([NH2:22])=[N:24][CH:25]=4)[N:18]=[CH:17]3)[CH:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: Cc1cc(-c2ccc(Cl)c(Cl)c2)cc(-n2cnc(I)c2)n1
Reactant: CC1(C)OB(c2ccc(N)nc2)OC1(C)C
Product: Cc1cc(-c2ccc(Cl)c(Cl)c2)cc(-n2cnc(-c3ccc(N)nc3)c2)n1

Procedure:
The title compound was prepared from 4-(3,4-dichloro-phenyl)-2-(4-iodo-imidazol-1-yl)-6-methyl-pyridine (example E.84) (0.20 g, 0.47 mmol) and commercially available 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.113 g, 0.51 mmol) according to the general procedure VI. Obtained as an off-white solid (0.035 g, 17%). MS (ISP) 396.0 [(M+H)+], 398.1 [(M+2+H)+] and 400 [(M+4+H)+]; mp 245° C.
Reaction SMILES: [NH2:1][C@@H:2]([C:6]1[O:7][C:8]2[C:13]([C:14](=[O:23])[C:15]=1[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[CH:12][CH:11]=[C:10]([Cl:24])[CH:9]=2)[CH:3]([CH3:5])[CH3:4].C([O-])([O-])=O.[K+].[K+].Br[CH2:32][C:33](=[O:46])[CH2:34][N:35]1[C:39](=[O:40])[C:38]2=[CH:41][CH:42]=[CH:43][CH:44]=[C:37]2[C:36]1=[O:45]>CN(C=O)C>[C:36]1(=[O:45])[N:35]([CH2:34][C:33](=[O:46])[CH2:32][NH:1][C@@H:2]([C:6]2[O:7][C:8]3[C:13]([C:14](=[O:23])[C:15]=2[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:12][CH:11]=[C:10]([Cl:24])[CH:9]=3)[CH:3]([CH3:4])[CH3:5])[C:39](=[O:40])[C:38]2=[CH:41][CH:42]=[CH:43][CH:44]=[C:37]12
Reactant: CC(C)[C@@H](N)c1oc2cc(Cl)ccc2c(=O)c1Cc1ccccc1
Reactant: O=C(CBr)CN1C(=O)c2ccccc2C1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)[C@@H](NCC(=O)CN1C(=O)c2ccccc2C1=O)c1oc2cc(Cl)ccc2c(=O)c1Cc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 108 %

Procedure:
To 2-((R)-1-amino-2-methyl-propyl)-3-benzyl-7-chloro-chromen-4-one (0.5 g, 1.5 mMol) and K2CO3 (0.21 g, 1.5 mMol) in DMF (10 mL) was added N-(3-bromo-2-oxopropyl)-phthalimide (0.45 g, 1.5 mMol) (Nair et al.; J. Org. Chem.; 40; 1975; 1745). The reaction was stirred at RT for 3 h, concentrated under vacuum, taken up in EtOAc, washed with water, brine, dried (Na2SO4) and evaporated to give the title compound (0.88 g, 100%) as a yellow solid: MS (ES) m/e 543.2 (M+H)+.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH:12]=[CH:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:2]([CH3:4])[CH3:3].[H][H]>C(O)C.[C].[Pd]>[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:2]([CH3:4])[CH3:3]
Reactant: CCOC(=O)C=Cc1ccccc1OCC(C)C
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)CCc1ccccc1OCC(C)C
Yield: 50.3 %

Procedure:
In 15 ml of ethanol is dissolved 1.50 g of ethyl 3-(2-isobutoxyphenyl)-2-propenoate, to which is added 0.30 g of 5% palladium-carbon. The mixture is stirred at ambient temperature for one hour in a stream of hydrogen. The reaction mixture is filtered with Celite, and the solvent is distilled off from the filtrate under reduced pressure. The residue thus obtained is purified by silica gel column chromatography to obtain 0.76 g of ethyl 3-(2-isobutoxyphenyl)propionate as a colorless oily product.
Reaction SMILES: [C:1]1([S:7]([CH2:10][C@H:11]([NH2:13])[CH3:12])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O:22][C@@H:23]1[C@H:27]([O:28]C(=O)C2C=CC=CC=2)[C@@H:26]([CH2:37][O:38]C(=O)C2C=CC=CC=2)[O:25][C@H:24]1[N:47]1[CH:55]=[N:54][C:53]2[C:48]1=[N:49][C:50]([Cl:57])=[N:51][C:52]=2Cl)(=O)C1C=CC=CC=1.C(N(CC)CC)C>O1CCOCC1>[Cl:57][C:50]1[N:51]=[C:52]([NH:13][C@H:11]([CH3:12])[CH2:10][S:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)(=[O:8])=[O:9])[C:53]2[N:54]=[CH:55][N:47]([C:48]=2[N:49]=1)[C@@H:24]1[O:25][C@H:26]([CH2:37][OH:38])[C@@H:27]([OH:28])[C@H:23]1[OH:22]
Reactant: C[C@@H](N)CS(=O)(=O)c1ccccc1
Reactant: O=C(OC[C@H]1O[C@@H](n2cnc3c(Cl)nc(Cl)nc32)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: C[C@H](CS(=O)(=O)c1ccccc1)Nc1nc(Cl)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Temperature: 25 °C
Reaction time: 48 h
Yield: 41.3 %

Procedure:
(R)-1-Phenylsulphonyl-2-propylamine (0.4 g, 1.7 mmol) was reacted with 9-(2,3,5-tri- O-benzoyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (1.7 g, 1.0 mmol) in dioxan (20 ml) in the presence of triethylamine (0.4 g, 4.3 mmol). The reaction mixture was stirred at room temperature for 48 h, heated at 60° C. for 4 h, cooled, filtered and evaporated. The product (after purification by flash chromatography) was debenzoylated with methanolic ammonia to provide the title 2-chloro- N-[(R)-1-phenylsulphonyl-2-propyl]adenosine (after column chromatography) as a foam (0.2 g, 24%), 1H NMR (DMSO-d6)δ 1.24 (3H, d, --CH3), 3.45 (1H, dd, --C--H), 3.53-3.61 (2H, m, H-5'a and --C--H), 3.64-3.71 (1H, m, H-5'b), 3.86 (1H, dd, --C--H), 3.97 (1H, q, H-4'), 4.14 (1H, m, H-3'), 4.53 (1H, m, H-2'), 5.09 (1H, t, 5'-OH), 5.23, 5.50 (2H, 2 d, 2' and 3'-OH), 5.83 (1H, d, H-1'), 7.45-7.82 (5H, m, Ar--H), 8.21 (1H, s, --N--H), 8.38 (1H, s, H-8).
Reaction SMILES: [CH2:1]([CH:5]1[CH2:10][CH2:9][CH:8]([CH:11]([CH2:14][OH:15])[CH2:12][OH:13])[CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4].[C:16]([C:18]1[CH:25]=[CH:24][C:21]([CH:22]=O)=[CH:20][CH:19]=1)#[N:17].CC1C=CC(S(O)(=O)=O)=CC=1.O>ClCCl>[C:16]([C:18]1[CH:25]=[CH:24][C:21]([C@H:22]2[O:13][CH2:12][C@H:11]([C@H:8]3[CH2:7][CH2:6][C@H:5]([CH2:1][CH2:2][CH2:3][CH3:4])[CH2:10][CH2:9]3)[CH2:14][O:15]2)=[CH:20][CH:19]=1)#[N:17]
Reactant: CCCCC1CCC(C(CO)CO)CC1
Reactant: N#Cc1ccc(C=O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: O
Product: CCCC[C@H]1CC[C@H]([C@H]2CO[C@H](c3ccc(C#N)cc3)OC2)CC1

Procedure:
In dichloromethane, 4.6 g (0.02 mol) of 2-(4'-butylcyclohexyl) propane-1,3-diol, 3.2 g (0.024 mol) of 4-cyanobenzaldehyde, and 0.1 g of TsOH were refluxed for three hours over a hot water bath fitted with a Dean-Stark trap and the water formed was continuously removed from the reaction system. The reaction solution was washed with water and the dichloromethane was distilled off. The distillation residue was recrystallized from a solvent mixture of acetone and methanol to yield 1.1 g (0.004 mol) of trans-2-(4'-cyanophenyl)-5-(trans-4'-butylcyclohexyl)-1,3-dioxane. The phase transition points of this compound, measured by DSC, were: ##STR53##
Reaction SMILES: [C:1]([C:4]1[CH:5]=[N+:6]([O-])[CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].C[Si]([C:15]#[N:16])(C)C.CN(C)C(Cl)=O>[N+](CC)([O-])=O>[C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:15]#[N:16])=[N:6][CH:5]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)c1ccc[n+]([O-])c1
Reactant: C[Si](C)(C)C#N
Agent: CN(C)C(=O)Cl
Solvent: CC[N+](=O)[O-]
Product: CC(=O)c1ccc(C#N)nc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 18.7 %

Procedure:
3-Acetylpyridine N-oxide (2.0 g, 14.6 mmol) was dissolved in nitroethane (20 ml), and trimethylsilyl cyanide (1.7 g, 16.7 mmol) and N,N-dimethylcarbamoyl chloride (1.8 g, 16.7 mmol) were added thereto. The reaction mixture was stirred at room temperature for 16 hrs, concentrated under reduced pressure, combined with saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine and dried. The solvent was evaporated under reduced pressure. The residue was subjected to a silica gel column chromatography and eluted with hexane-ethyl acetate (3:1, v/v) to give the titled compound (0.40 g, 21%).
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1[CH:12]=[C:11]([OH:13])[CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=[O:7].[CH2:14](I)[CH2:15][CH2:16][CH3:17].Cl>C(O)C.O>[Cl:3][C:4]1[CH:12]=[C:11]([O:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=[O:7]
Reactant: CCCCI
Reactant: O=C(O)c1ccc(O)cc1Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCCCOc1ccc(C(=O)O)c(Cl)c1
Reaction time: 5 h
Yield: 71.7 %

Procedure:
9 g of caustic soda are dissolved in 200 ml of ethanol. To the thus-prepared solution there are added 17.25 g of 2-chloro-4-hydroxybenzoic acid and 18.4 g of butyl iodide. The resulting solution is heated at reflux under stirring for 5 hours, cooled, poured into 200 ml of water and acidified, to pH=1, with hydrochloric acid. The precipitate is filtered-off, washed with water and dried to give 16.4 g of ortho-chloro-para-n-butyoxybenzoic acid which is recrystallized from hexane. The yield of the recrystallized product is 13.8 g (60.5%), M.p. 92°-93° C.
Reaction SMILES: CC(C)([O-:4])C.[K+].O.CN(OC)[C:10](=[O:18])[C@@H:11]([OH:17])[CH2:12][CH:13]1[CH2:16][CH2:15][CH2:14]1>C1COCC1>[OH:17][C@@H:11]([CH2:12][CH:13]1[CH2:16][CH2:15][CH2:14]1)[C:10]([OH:18])=[O:4]
Reactant: CC(C)(C)[O-]
Reactant: CON(C)C(=O)[C@@H](O)CC1CCC1
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)[C@@H](O)CC1CCC1
Temperature: 25 °C
Reaction time: 20 h
Yield: 85.3 %

Procedure:
A suspension of 33.66 g (0.3 mol) of potassium t-butoxide in 50 mL of THF was treated with 5.40 mL (0.3 mol) of H2O. The resulting mixture was treated with a solution of 11.48 g (0.061 mol) of N-methyl-N-methoxy 2-(S)-hydroxy-3-cyclobutyl propanamide (from Step C) in 20 mL of THF and stirred at rt for 20 h. The mixture was concentrated and the residue was partitioned between 300 mL of ether and 200 mL of H2O and the layers were separated. The pH of the aqueous layer was adjusted to 2 with concentrated HCl and extracted with 300 mL of EtOAc. The extract was washed with 100 mL of sat'd NaCl, dried over MgSO4 and concentrated to afford 7.50 g (85%) of the title compound: 1H NMR (500 MHz) δ 1.66-1.76 (m, 2H), 1.78-1.98 (4H), 2.06-2.16 (m, 2H), 2.51-2.61 (m, 1H), 4.20 (dd, J=8.0, 4.0, 1H).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[C:8]1[C:16]([OH:18])=O.[CH3:19][CH:20]([CH3:44])[CH2:21][NH:22][C@H:23]1[CH2:28][C@@H:27]([C:29]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)=[O:30])[CH2:26][N:25]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:24]1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.ClC(N(C)C)=[N+](C)C>ClCCCl>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[C:8]1[C:16]([N:22]([CH2:21][CH:20]([CH3:44])[CH3:19])[C@H:23]1[CH2:28][C@@H:27]([C:29]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)=[O:30])[CH2:26][N:25]([C:37]([O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:38])[CH2:24]1)=[O:18]
Reactant: COCCCCn1c(C(=O)O)cc2ccccc21
Reactant: CC(C)CN[C@H]1C[C@@H](C(=O)N2CCOCC2)CN(C(=O)OC(C)(C)C)C1
Agent: CN(C)C(Cl)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCCl
Solvent: CCN(C(C)C)C(C)C
Product: COCCCCn1c(C(=O)N(CC(C)C)[C@H]2C[C@@H](C(=O)N3CCOCC3)CN(C(=O)OC(C)(C)C)C2)cc2ccccc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 19 %

Procedure:
1-(4-Methoxybutyl)-1H-indole-2-carboxylic acid (210 mg), tert-butyl (3S,5R)-3-[(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (270 mg) and N,N-diisopropylethylamine (560 μl) were dissolved in 1,2-dichloroethane (10 ml), chloro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate (360 mg) was added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated, and the residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (0:10-10:0) was concentrated under reduced pressure to give the object product (83 mg).
Reaction SMILES: [CH:1]1[C:5]([CH:6]=O)=[CH:4][O:3][CH:2]=1.[Br-].C1([P+](C2C=CC=CC=2)(C2C=CC=CC=2)[CH2:16][CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])C=CC=CC=1>>[O:3]1[CH:2]=[CH:1][C:5](/[CH:6]=[CH:16]/[CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:4]1
Reactant: CCOC(=O)CCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=Cc1ccoc1
Agent: [Br-]
Product: CCOC(=O)CC/C=C/c1ccoc1

Procedure:
3-Furfural and triphenyl-(3-ethoxycarbonylpropyl)phosphonium bromide were processed as in 5A to yield the title compound: 1H NMR (300 MHz, CDCl3) δ 7.46 (br s, 1H), 7.39 (t, J=1.36 Hz, 1H), 6.47 (d, J=2.03 Hz, 1H), 6.20 (d, J=11.53 Hz, 1H), 5.53 (dt, J=11.44, 6.99 Hz, 1H) 4.12 (q, J=7.12 Hz, 2H), 2.61 (t, J=6.78 Hz, 2H), 2.45 (td, J=7.63, 1.36 Hz, 2H), 1.25 (t, J=7.12 Hz, 3H); MS (DCI/NH3) m/z 197 (M+H)+.
Reaction SMILES: [CH:1]1[C:6]([CH2:7]O)=[CH:5][CH:4]=[N+:3]([O-])[CH:2]=1.C(Br)(Br)(Br)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:34][C:35]1[CH:36]=[CH:37][C:38]2[CH:48]([N:49]3[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]3)[C:43]3=[N:44][CH:45]=[CH:46][CH:47]=[C:42]3[CH2:41][CH2:40][C:39]=2[CH:55]=1.C(N(CC)CC)C>C(Cl)Cl>[Cl:34][C:35]1[CH:36]=[CH:37][C:38]2[CH:48]([N:49]3[CH2:50][CH2:51][N:52]([CH2:7][C:6]4[CH:5]=[CH:4][N:3]=[CH:2][CH:1]=4)[CH2:53][CH2:54]3)[C:43]3=[N:44][CH:45]=[CH:46][CH:47]=[C:42]3[CH2:41][CH2:40][C:39]=2[CH:55]=1
Reactant: Clc1ccc2c(c1)CCc1cccnc1C2N1CCNCC1
Reactant: [O-][n+]1ccc(CO)cc1
Agent: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Clc1ccc2c(c1)CCc1cccnc1C2N1CCN(Cc2ccncc2)CC1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 45.3 %

Procedure:
To a mixture of 188 mg (1.50 mmol) of 4-pyridylcarbinol N-oxide and 497 mg (1.50 mmol) of carbon tetrabromide in 12 mL of dry methylene chloride at room temperature and under an argon atmosphere was added in one portion 393 mg (1.50 mmol) of triphenylphosphine. After 40 minutes, 313 mg (0.997 mmol) of (-)-8-chloro-6,11-dihydro-11-(4-piperazinyl)-5H-benzo[5,6]cyclohepta-[1,2-b]pyridine was added followed by 209 mL (1.57 mmol) of triethylamine. The reaction mixture was then allowed to stir at room temperature for 3 hr, after which it was taken up in methylene chloride and washed once with 0.5M aqueous sodium bicarbonate and then brine. The organic portion was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified via flash chromatography (4% methanol saturated with ammonia in methylene chloride) to provide 183 mg of (-)-8-chloro-6,11-dihydro-11-[4 -(4-pyridinylmethyl)-1-piperazinyl]-5h-benzo[5,6]cyclohepta-[1,2-b]pyridine, N-oxide as a glass: MS (CI) m/z 421 (M+ +1);
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]2[N:9]=[C:10]([SH:12])[N:11]=[C:4]2[N:3]=1.Br[CH2:14][CH2:15][O:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1>>[CH:17]1([O:16][CH2:15][CH2:14][S:12][C:10]2[N:11]=[C:4]3[N:3]=[C:2]([CH3:1])[CH:7]=[C:6]([CH3:8])[N:5]3[N:9]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: Cc1cc(C)n2nc(S)nc2n1
Reactant: BrCCOC1CCCCC1
Product: Cc1cc(C)n2nc(SCCOC3CCCCC3)nc2n1
Yield: 78 %

Procedure:
The title compound was prepared according to the experimentals described for Example 1 above from 5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-thiol and 2-bromoethoxy cyclohexane in 78% yield; EM (calc.): 306.2; MS (ESI) m/e: 307.2 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=2)O1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>O1CCOCC1.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>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[CH:3]=[C:2]([C:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=2)[N:7]=[C:6]2[N:8]([CH:11]([CH3:13])[CH3:12])[N:9]=[CH:10][C:5]=12)=[O:15]
Reactant: Cc1cc(C)c(CNC(=O)c2cc(Br)nc3c2cnn3C(C)C)c(=O)[nH]1
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: Cc1cc(C)c(CNC(=O)c2cc(C3=CCN(C(=O)OC(C)(C)C)CC3)nc3c2cnn3C(C)C)c(=O)[nH]1
Temperature: 100 °C
Reaction time: 1 h
Yield: 72.7 %

Procedure:
A solution of 6-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (3.1 g, 7.4 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (2.7 g, 8.7 mmol) and Pd(PPh3)4 (0.428 g, 0.370 mmol.) in 1,4-dioxane (20 mL) was purged with argon for 10 min. Then, 2M Na2CO3 (2.8 g, 26.41) was added to it and again argon was purged through it for 10 min. The reaction mixture was stirred at 100° C. for 1 h. After completion of the reaction, water was added to it and extraction was carried out using EtOAc. The combined organic layers were washed with water, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford crude material which was purified by column chromatography to give the desired intermediate (2.8 g, 73.7%).
Reaction SMILES: [CH3:1][N:2]1[C:6]([C@H:7]([C:12]2[CH:17]=[CH:16][C:15]([O:18]CC3C=C(C4C=CC(C(F)(F)F)=CC=4)C=CC=3)=[CH:14][CH:13]=2)[CH2:8][C:9]([OH:11])=[O:10])=[N:5][N:4]=[N:3]1.[CH3:36]COC(C)=O>>[OH:18][C:15]1[CH:16]=[CH:17][C:12]([C@@H:7]([C:6]2[N:2]([CH3:1])[N:3]=[N:4][N:5]=2)[CH2:8][C:9]([O:11][CH3:36])=[O:10])=[CH:13][CH:14]=1
Reactant: Cn1nnnc1[C@@H](CC(=O)O)c1ccc(OCc2cccc(-c3ccc(C(F)(F)F)cc3)c2)cc1
Reactant: CCOC(C)=O
Product: COC(=O)C[C@@H](c1ccc(O)cc1)c1nnnn1C
Reaction time: 8 h

Procedure:
Methyltetrazole 7 (413 mg, 0.833 mmol) was dissolved in 5 mL of EtOAc and nitrogen was bubbled through the solution for 5 minutes. Palladium on carbon (200 mg, 5 wt. %, wet contains 50% water) was added, and a hydrogen balloon was attached. After 8 hours, the mixture was filtered through a plug of silica with 10% MeOH in EtOAc. The organic layer was concentrated under reduced pressure and partitioned between acetonitrile (10 mL) and hexane (5 mL). The acetonitrile layer was washed with hexane (4×5 mL). The acetonitrile layer was concentrated under reduced pressure to afford (s)-methyl 3-(4-hydroxyphenyl)-3-(1-methyl-1H-tetrazol-5-yl)propanoate (8.1) (203 mg, 0.775 mmol) as a colorless oil.