Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]([CH3:14])[CH:7]=[C:6]2[C:15]1[N:29](S(C2C=CC(C)=CC=2)(=O)=O)[C:18]2=[N:19][CH:20]=[CH:21][C:22]([CH2:23][N:24]([CH2:27][CH3:28])[CH2:25][CH3:26])=[C:17]2[CH:16]=1.[OH-].[K+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]([CH3:14])[CH:7]=[C:6]2[C:15]1[NH:29][C:18]2=[N:19][CH:20]=[CH:21][C:22]([CH2:23][N:24]([CH2:25][CH3:26])[CH2:27][CH3:28])=[C:17]2[CH:16]=1
Reactant: CCN(CC)Cc1ccnc2c1cc(-c1cn(C)c3cc(OC)c(OC)cc13)n2S(=O)(=O)c1ccc(C)cc1
Agent: [K+]
Agent: [OH-]
Product: CCN(CC)Cc1ccnc2[nH]c(-c3cn(C)c4cc(OC)c(OC)cc34)cc12
Yield: 78.9 %

Procedure:
[2-(5,6-Dimethoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl]diethylamine is prepared as described in Example 179a starting with 0.060 g of [2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl]diethylamine instead of the [2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl](4-trifluoromethylsulfanylbenzyl)amine used in Example 179a and 0.44 cm3 of 5N potassium hydroxide. 0.034 g of [2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl]diethylamine is obtained, the characteristics of which are as follows:
Reaction SMILES: C([Si](C)(C)OC(C1C=CC(CCCCCCCC)=CC=1)CC=C)(C)(C)C.C[N+]1([O-])CCOCC1.S([O-])([O-])(=O)=S.[Na+].[Na+].[Si]([O:49][CH:50]([C:56]1[CH:61]=[CH:60][C:59]([CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH3:69])=[CH:58][CH:57]=1)[CH2:51][CH:52]([OH:55])[CH2:53][OH:54])(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CC(C)=O.O.C1COCC1.[Os](=O)(=O)(=O)=O.CCOC(C)=O.CCCCCCC>[CH2:62]([C:59]1[CH:58]=[CH:57][C:56]([CH:50]([OH:49])[CH2:51][CH:52]([OH:55])[CH2:53][OH:54])=[CH:61][CH:60]=1)[CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH3:69]
Reactant: CCCCCCCCc1ccc(C(CC(O)CO)O[Si](C)(C)C(C)(C)C)cc1
Agent: O=[Os](=O)(=O)=O
Agent: C=CCC(O[Si](C)(C)C(C)(C)C)c1ccc(CCCCCCCC)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CCCCCCC
Solvent: CC(C)=O
Solvent: C1CCOC1
Product: CCCCCCCCc1ccc(C(O)CC(O)CO)cc1
Reaction time: 2 h
Yield: 113.9 %

Procedure:
Tert-butyldimethyl(1-(4-octylphenyl)but-3-enyloxy)silane (19.108 g, 51.0 mmol) and NMO (7.17 g, 61.2 mmol) were combined in acetone (227 ml) and water (28.3 ml). Osmium tetroxide (32.0 ml, 2.55 mmol) was added and the reaction stirred for about 2 h. TLC in 1:1 EtOAc/heptane showed reaction complete. Sodium thiosulfate (8.06 g, 51.0 mmol) was added and the reaction stirred for about 3 h resulting in a coarse black precipitate. The solution was poured over 150 mL of silica gel and washed product through thoroughly or washed product through?with ethyl acetate until no more product was eluting as shown by TLC (˜700 mL EtOAc). The resulting 4-(Tert-butyldimethylsilyloxy)-4-(4-octylphenyl)butane-1,2-diol (14.68 g, 35.9 mmol) and molecular sieves (5 g) (Aldrich) were combined in THF (359 ml) under nitrogen. TBAF (35.9 ml, 35.9 mmol) (Aldrich) was added and the reaction stirred for about 16 h. The mixture was filtered and the solvents evaporated to provide an orange/brown oil. The oil was passed through a pad of silica gel (150 mL) and washed through with ethyl acetate. Product eluted slowly and took almost 2 L of EtOAc for all product to elute. The solvents were removed under reduced pressure to provide 4-(4-octylphenyl)butane-1,2,4-triol (12.045 g, 40.9 mmol, 114% yield) as an orange oil: LC/MS (Purity QC) Rt=3.84, 3.89 min.; MS m/z: 294.40, 294.02 (M+H)+.
Reaction SMILES: C(O[C:4]1[CH2:10][C:9](=[O:11])[NH:8][C:7]2[CH:12]=[C:13]([F:17])[C:14]([F:16])=[CH:15][C:6]=2[N:5]=1)C.[C:18]([NH:26][NH2:27])(=O)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(O)(=O)C>[F:17][C:13]1[C:14]([F:16])=[CH:15][C:6]2[N:5]3[C:4]([CH2:10][C:9](=[O:11])[NH:8][C:7]=2[CH:12]=1)=[N:27][N:26]=[C:18]3[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: CCOC1=Nc2cc(F)c(F)cc2NC(=O)C1
Reactant: NNC(=O)c1ccccc1
Solvent: CC(=O)O
Product: O=C1Cc2nnc(-c3ccccc3)n2-c2cc(F)c(F)cc2N1
Temperature: 120 °C

Procedure:
To a solution of 4-ethoxy-7,8-difluoro-1,3-dihydro-benzo[b][1,4]diazepin-2-one (Preparation 3(B) (5.38 g, 22.4 mmol) in acetic acid (100 mL) was added benzoic hydrazide (3.11 g, 22.85 mmol). The reaction was heated to 120° C. for 18 hours and the volatiles were concentrated in vacuo. The residue was dissolved in CH2Cl2 and the organic solution was washed with aqueous NaHCO3 (1×), dried (Na2SO4), filtered and concentrated. The solid residue was triturated with a warm mixture of EtOAc and hexanes and was filtered. The solids were triturated in 50% hexanes in Et2O and filtered to provide 3.97 g of 8,9-difluoro-1-phenyl-4H,6H-2,3,6,10b-tetraaza-benzo[e]azulen-5-one. 1H NMR (DMSO-d6) δ 7.52-7.36 (m, 6H), 7.06 (m, 1H), 3.91 (d, 1H), 3.76 (d, 1H); MS 313.1 (M+1), 311.1 (M−1).
Reaction SMILES: [NH:1]1[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[C:9]1[CH:14]=[CH:13][C:12]([Br:15])=[CH:11][N:10]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Br:15][C:12]1[CH:13]=[CH:14][C:9]([N:1]2[CH2:7][CH2:6][CH2:5][N:4]([C:9]3[CH:14]=[CH:13][C:12]([Br:15])=[CH:11][N:10]=3)[CH2:3][CH2:2]2)=[N:10][CH:11]=1
Reactant: Brc1ccc(Br)nc1
Reactant: C1CNCCNC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Brc1ccc(N2CCCN(c3ccc(Br)cn3)CC2)nc1
Yield: 65.5 %

Procedure:
To a solution of hexahydro-1,4-diazepine (2.84 g, 28.4 mmol) in dimethylformamide (14 mL) were added 2,5-dibromopyridine (16.23 g, 68.5 mmol) and potassium carbonate powdered in a mortar (8.00 g, 57.9 mmol), and the resultant mixture was stirred at 120° for 15 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to yield crude crystals of the title compound (7.67 g, yield: 66%). The crude crystals were recrystallized from chloroform-hexane to give colorless fine needles (melting point: 178.0–181.0° C.
Reaction SMILES: [OH:1][C@H:2]1[C@H:7](OC2CCC(=O)C=2)[C:6]2[CH:15]=[C:16]([C:19]#[N:20])[CH:17]=[CH:18][C:5]=2[O:4][C:3]1([CH3:22])[CH3:21].[H-].[Na+].[CH3:25][NH:26][C:27]1[CH2:31][N:30]([CH3:32])[C:29](=[O:33])[CH:28]=1>CS(C)=O>[OH:1][C@H:2]1[C@H:7]([N:26]([CH3:25])[C:27]2[CH2:31][N:30]([CH3:32])[C:29](=[O:33])[CH:28]=2)[C:6]2[CH:15]=[C:16]([C:19]#[N:20])[CH:17]=[CH:18][C:5]=2[O:4][C:3]1([CH3:21])[CH3:22]
Reactant: CNC1=CC(=O)N(C)C1
Reactant: CC1(C)Oc2ccc(C#N)cc2[C@@H](OC2=CC(=O)CC2)[C@@H]1O
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CN1CC(N(C)[C@@H]2c3cc(C#N)ccc3OC(C)(C)[C@H]2O)=CC1=O

Procedure:
402 mg of the epoxide of example 1 in 4 ml of dimethylsulfoxide are reacted analogously to example 5 with 60 mg of sodium hydride and 25.2 mg of the amide obtained above. Usual work up yields the title compound having a m.p. of 266°-69° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[O:9])[CH:5]=[N:6][CH:7]=1.BrC1C=NC=C(C=1)C(O)=O.ClC(OCC)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][OH:9])[CH:5]=[N:6][CH:7]=1
Reactant: O=Cc1cncc(Br)c1
Agent: CCOC(=O)Cl
Agent: O=C(O)c1cncc(Br)c1
Agent: [Al+3]
Solvent: C1CCOC1
Product: OCc1cncc(Br)c1

Procedure:
The required aldehyde, 5-bromopyridine-3-carboxaldehyde, can be prepared from 5-bromonicotinic acid (commercially available from Aldrich Chemical Company and Lancaster Synthesis, Inc.). The 5-bromonicotinic acid can be treated with ethyl chloroformate producing the mixed anhydride, which can be reduced with lithium aluminum hydride in tetrahydrofuran (THF) at −78° C., to afford 5-bromo-3-hydroxymethylpyridine, as reported by A. Ashimori et al., Chem. Pharm. Bull. 38(9): 2446-2458 (1990). Alternatively, the 5-bromonicotinic acid can be esterified in the presence of sulfuric acid and ethanol, and the intermediate ethyl ester can be reduced with an excess of sodium borohydride to yield 5-bromo-3-hydroxymethylpyridine, according to the techniques reported in C. F. Nutaitis et al., Org. Prep. and Proc. Int. 24:143-146 (1992). The resulting 5-bromo-3-hydroxymethylpyridine can then be converted to 5-bromo-3-pyridinecarboxaldehyde by Swern oxidation using oxalyl chloride and dimethylsulfoxide according to the methods of M. J. Stocks et al., Tetrahedron Lett. 36(36): 6555-6558 (1995) and A. J. Mancuso et al., J. Org Chem. 44(23): 4148-4150 (1979). The aldehyde, 4-bromopyridine-3-carboxaldehyde can be synthesized according to methodology described by Chin et al. PCT WO 94/29893 or by methodology described by Ojea et al., Synlett. 6: 622-624 (1995). 6-Bromopyridine-3-carboxaldehyde can be prepared according to procedures described in Windschief and Voegtle, Synthesis 1: 87-92 (1994) or Fey et al German Patent No. 93/4320432.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][CH:8]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:10]=1)=[O:4]>CO>[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:8][NH:7][CH2:6]1)=[O:4]
Reactant: COC(=O)c1cncc(C(=O)OC)c1
Solvent: CO
Product: COC(=O)C1CNCC(C(=O)OC)C1

Procedure:
Pyridine-3,5-dicarboxylic acid dimethyl ester (5.3 g, 27 mmol) and Rh/PtO2 (0.5 g) in MeOH (200 mL) are stirred under hydrogen overnight. The resulting mixture is filtered and the solvents are evaporated to give a brown oil. MS (LC-MS): 202 [M+H]+
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[C:17]([CH2:18]O)=[CH:16][O:15][N:14]=3)=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)([Cl:22])=O>>[Cl:22][CH2:18][C:17]1[C:13]([C:10]2[CH:11]=[CH:12][C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:8][CH:9]=2)=[N:14][O:15][CH:16]=1
Reactant: OCc1conc1-c1ccc(-c2ccccc2)cc1
Reactant: O=S(Cl)Cl
Product: ClCc1conc1-c1ccc(-c2ccccc2)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 92 %

Procedure:
A mixture of 3-(4-phenylphenyl)-4-isoxazolylmethanol (4.16 g) and thionyl chloride (10.0 ml) was stirred at 0° C. for 30 min. The reaction mixture was concentrated, and saturated aqueous sodium hydrogencarbonate was added to the residue. The mixture was extracted with ethyl acetate and the ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained colorless crystals were filtrated to give 4-chloromethyl-3-(4-phenylphenyl)isoxazole (3.84 g, yield 92%). The crystals were recrystallized from ethyl acetate-hexane. melting point: 102–103° C.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1.[Cl:15][C:16]1[CH:24]=[C:23]([S:25]([CH2:28][CH:29]([OH:31])[CH3:30])(=[O:27])=[O:26])[CH:22]=[CH:21][C:17]=1[C:18](O)=[O:19]>>[Cl:15][C:16]1[CH:24]=[C:23]([S:25]([CH2:28][CH:29]([OH:31])[CH3:30])(=[O:26])=[O:27])[CH:22]=[CH:21][C:17]=1[C:18]([NH:6][C:5]1[CH:7]=[CH:8][C:2]([Cl:1])=[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:4]=1)=[O:19]
Reactant: Nc1ccc(Cl)c(-c2ccccn2)c1
Reactant: CC(O)CS(=O)(=O)c1ccc(C(=O)O)c(Cl)c1
Product: CC(O)CS(=O)(=O)c1ccc(C(=O)Nc2ccc(Cl)c(-c3ccccn3)c2)c(Cl)c1

Procedure:
2 g of 2-chloro-4-fluorobenzonitrile was reacted with 1-mercapto-2-propanol via Procedure Q to afford 2-chloro-4-(2-hydroxypropylthio)benzonitrile. 2.5 g of 2-chloro-4-(2-hydroxypropylthio)benzonitrile was reacted via Procedure T to give 2-chloro-4-(2-hydroxypropylthio)benzoic acid. 2.1 g of 2-chloro-4-(2-hydroxypropylthio)benzoic acid was reacted via Procedure R to give 2-chloro-4-(2-hydroxypropylsulfonyl)benzoic acid. 70 mg of 4-chloro-3-(pyridin-2-yl)aniline was coupled to 2-chloro-4-(2-hydroxypropylsulfonyl)benzoic acid via Procedure G. The product was purified on reverse phase HPLC to yield 2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(2-hydroxypropylsulfonyl)benzamide. MS (Q1) 465.2 (M)+.
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:11][CH2:10][C:9]2[C:4](=[C:5]([N:12]3[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]3)[CH:6]=[CH:7][CH:8]=2)[CH2:3]1.C(N(CC)CC)C.[C:26](Cl)(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(Cl)Cl>[CH3:18][N:15]1[CH2:16][CH2:17][N:12]([C:5]2[CH:6]=[CH:7][CH:8]=[C:9]3[C:4]=2[CH2:3][C@H:2]([NH:1][C:26](=[O:33])[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:11][CH2:10]3)[CH2:13][CH2:14]1
Reactant: CN1CCN(c2cccc3c2C[C@H](N)CC3)CC1
Reactant: O=C(Cl)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CN1CCN(c2cccc3c2C[C@H](NC(=O)c2ccccc2)CC3)CC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To an ice-cooled solution of (R)-2-amino-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalene (210 mg, 0.86 mmol) and triethylamine (180 μL, 1.28 mmol) in methylene chloride (30 mL) was added dropwise benzoyl chloride (130 mg, 0.90 mmol) in methylene chloride (5 mL). After the addition the reaction was allowed to stir at ambient temperature for 15 min and then washed with water. The phases were separated and the combined organic phases were dried (Na2SO4), filtered and evaporated in vacuo to give a crude product which was purified on a silica gel column using chloroform/ethanol saturated with NH3 (100:3) as the eluent. Yield: 250 mg (84%) of the title compound as white crystals: mp 195-196° C.; [α]21D -31° (c 1.0, CHCL3); EIMS (70 eV) m/z (relative intensity) 349 (53, M+).
Reaction SMILES: C(N1C(=O)C(N[C:12](=[O:23])[C:13]2[CH:18]=[C:17]([F:19])[C:16]([F:20])=[C:15]([F:21])[C:14]=2[F:22])(C)C(=O)NC1=O)C.[NH2:26][C:27]1([CH2:42][CH3:43])[C:32](=[O:33])[N:31]([CH:34]2[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]2)[C:30](=[O:40])[NH:29][C:28]1=[O:41]>>[CH:34]1([N:31]2[C:32](=[O:33])[C:27]([NH:26][C:12](=[O:23])[C:13]3[CH:18]=[C:17]([F:19])[C:16]([F:20])=[C:15]([F:21])[C:14]=3[F:22])([CH2:42][CH3:43])[C:28](=[O:41])[NH:29][C:30]2=[O:40])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1
Reactant: CCN1C(=O)NC(=O)C(C)(NC(=O)c2cc(F)c(F)c(F)c2F)C1=O
Reactant: CCC1(N)C(=O)NC(=O)N(C2CCCCC2)C1=O
Product: CCC1(NC(=O)c2cc(F)c(F)c(F)c2F)C(=O)NC(=O)N(C2CCCCC2)C1=O

Procedure:
Compound 20i was prepared by the same method described for 20f using 5-amino-1-cyclohexyl-5-ethylbarbituric acid (0.51 g, 2 mmol). The crude 1-cyclohexyl-5-ethyl-5-(tetrafluorobenzamido)barbituric acid (20i) was obtained as yellow crystals and did not require further purification.
Reaction SMILES: C(N(CC)CC)C.[CH3:8][O:9][NH:10][CH2:11][CH2:12][CH2:13][CH2:14][N:15]1[C:27]2[C:26]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[N:20]=[CH:19][C:18]=2[N:17]=[C:16]1[CH2:28][CH2:29][CH3:30].[C:31](OC(=O)C)(=[O:33])[CH3:32]>ClCCl.C(=O)(O)[O-].[Na+]>[CH3:8][O:9][N:10]([CH2:11][CH2:12][CH2:13][CH2:14][N:15]1[C:27]2[C:26]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[N:20]=[CH:19][C:18]=2[N:17]=[C:16]1[CH2:28][CH2:29][CH3:30])[C:31](=[O:33])[CH3:32]
Reactant: CCCc1nc2cnc3ccccc3c2n1CCCCNOC
Reactant: CC(=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCc1nc2cnc3ccccc3c2n1CCCCN(OC)C(C)=O
Temperature: 0 °C
Reaction time: 6 h
Yield: 98.7 %

Procedure:
Triethylamine (0.167 mL, 1.2 mmol) was added to O-methyl-N-[4-(2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]hydroxylamine (0.32 g, 1.0 mmol) in dichloromethane (10 mL) and cooled to 0° C. Acetic anhydride (0.103 mL, 1.1 mmol) was added dropwise and the reaction mixture was stirred for 6 hours. The reaction was then diluted with dichloromethane (40 mL) and saturated aqueous sodium bicarbonate (10 mL) and stirred overnight. The phases were separated and the aqueous phase was extracted with dichloromethane (50 mL). The combined organics were dried over potassium carbonate, filtered, and concentrated to afford 0.35 g of N-methoxy-N-[4-(2-propy-1H-imidazo[4,5-c]quinolin-1-yl)butyl]acetamide.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[N:8]2[C:9](=[O:22])[C:10]3[NH:11][C:12]([Br:21])=[N:13][C:14]=3[N:15]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:7]2=[N:6][N:5]=1.[CH3:23][O:24][C:25]1[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][CH:26]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C.O.C(#N)C>[Br:21][C:12]1[NH:11][C:10]2[C:9](=[O:22])[N:8]3[C:4]([CH2:3][CH2:2][NH:1][C:29](=[O:30])[C:28]4[CH:32]=[CH:33][C:25]([O:24][CH3:23])=[CH:26][CH:27]=4)=[N:5][N:6]=[C:7]3[N:15]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:14]=2[N:13]=1
Reactant: COc1ccc(C(=O)O)cc1
Reactant: CCCCCn1c2nc(Br)[nH]c2c(=O)n2c(CCN)nnc12
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CC#N
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCCCCn1c2nc(Br)[nH]c2c(=O)n2c(CCNC(=O)c3ccc(OC)cc3)nnc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 69.7 %

Procedure:
A mixture of 3-(2-aminoethyl)-7-bromo-9-pentyl-6,9-dihydro-5H-[1,2,4]triazolo[4,3-a]purin-5-one (70 mg, 0.20 mmol), 4-methoxybenzoic acid (32 mg, 0.21 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (92 mg, 0.21 mmol), and triethylamine (0.053 mL, 0.38 mmol) in DMF (5 mL) was stirred at room temperature overnight. The reaction mixture was diluted with water and acetonitrile and then purified by prep LCMS to give the desired product (70 mg, 73% yield). LCMS calculated for C21H25BrN7O3 (M+H): 502.1, 504.0; found: 502.0, 504.0.
Reaction SMILES: [OH:1][CH:2]([CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:3][CH2:4][N:5]1[C:9](=[O:10])[CH2:8][S:7][CH:6]1[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18].[C:25](OC(=O)C)(=[O:27])[CH3:26]>C(OCC)(=O)C>[C:25]([O:1][CH:2]([CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:3][CH2:4][N:5]1[C:9](=[O:10])[CH2:8][S:7][CH:6]1[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18])(=[O:27])[CH3:26]
Reactant: CCCCCC(O)CCN1C(=O)CSC1CCCCCCC(=O)O
Reactant: CC(=O)OC(C)=O
Solvent: CCOC(C)=O
Product: CCCCCC(CCN1C(=O)CSC1CCCCCCC(=O)O)OC(C)=O
Temperature: 60 °C

Procedure:
A mixture of 7-[3-(3-hydroxyoctyl)-4-oxo-2-thiazolidinyl]heptanoic acid (9.0 g., 0.025 mole) and acetic anhydride (0.1 g., 0.06 mole) is heated at 60° C. for 18 hours. The resulting mixture is cooled to room temperature and dissolved in ethyl acetate providing a clear solution which is extracted with an ice-cold solution of sodium hydroxide (8 g.) in water (150 ml.). The basic solution is quickly separated and acidified with concentrated hydrochloric acid. The oily acid which separates is extracted with ether. The organic extract is washed with water, dried over sodium sulfate, and filtered. Evaporation of the filtrate in vacuo at 40° to 50° C. leaves a residual oil which is purified via application to a silica gel (150 g.) column with chloroform. Elution with chloroform-methanol (99.1; v:v) provides the title compound as a colorless, viscous oil.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:11][CH2:12][CH2:13][O:14][C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=2)=[CH:6][CH:5]=1)([O-])=O>[Pd].CO>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([NH:10][CH2:11][CH2:12][CH2:13][O:14][C:15]2[CH:16]=[CH:17][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:23][CH:24]=2)=[CH:8][CH:9]=1
Reactant: COC(=O)c1ccc(OCCCNc2ccc([N+](=O)[O-])cc2)cc1
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1ccc(OCCCNc2ccc(N)cc2)cc1
Reaction time: 8 h
Yield: 87.7 %

Procedure:
Methanol (200 ml) and methyl 4-[3-[N-(4nitrophenyl)amino]propoxy]benzoate (6.9 g) were added to 5 % palladium/carbon (0.7 g) and catalytic reduction was carried out at room temperature overnight. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure, then, to the residue was added isopropyl ether. The insoluble product was collected by filtration to give methyl 4-[3-[N-(4-aminophenyl)amino]propoxy]benzoate (5.5 g).
Reaction SMILES: [CH:1]([C:3]1[N:4]=[CH:5][NH:6][CH:7]=1)=[O:2].C(#N)C.C(N(CC)CC)C.[C:18]1([S:24](Cl)(=[O:26])=[O:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C1COCC1.O>[C:18]1([S:24]([N:6]2[CH:7]=[C:3]([CH:1]=[O:2])[N:4]=[CH:5]2)(=[O:26])=[O:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=Cc1c[nH]cn1
Reactant: O=S(=O)(Cl)c1ccccc1
Solvent: CC#N
Solvent: C1CCOC1
Solvent: O
Product: O=Cc1cn(S(=O)(=O)c2ccccc2)cn1
Temperature: 25 °C
Yield: 69.5 %

Procedure:
4-Formylimidazole (11.7 g, 121.8 mmol) and acetonitrile (59 mL) were charged, and triethylamine (13.6 g, 133.9 mml) was added thereto at 30° C. or below. And then, a solution of benzenesulfonyl chloride (23.7 g, 133.9 mmol) in THF (35 mL) was added dropwise thereto at 30° C. or below, and the mixture was stirred at room temperature for 1 hr or more. After the reaction, water (94 mL) was added dropwise thereto at 30° C. or below for crystallization, and the mixture was stirred at room temperature for 1 hr or more, cooled to 10° C. or below, and stirred for 1 hr or more. The obtained crystals were collected by filtration, and washed with a mixed solvent (35 mL) of acetonitrile/water (1:2, volume ratio). The obtained wet crystals were dried under reduced pressure at an outside temperature of 50° C. to give 1-(phenylsulfonyl)-4-formyl-1H-imidazole (20.0 g, 84.7 mmol). yield 70%.
Reaction SMILES: [C:1]1([C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([CH3:13])[C:8]([N:10]=[C:11]=[O:12])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:20][C:21]([F:25])([F:24])[CH2:22][OH:23]>>[F:20][C:21]([F:25])([F:24])[CH2:22][O:23][C:11](=[O:12])[NH:10][C:8](=[O:9])[C:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:13]
Reactant: OCC(F)(F)F
Reactant: CC(C(=O)N=C=O)(c1ccccc1)c1ccccc1
Product: CC(C(=O)NC(=O)OCC(F)(F)F)(c1ccccc1)c1ccccc1

Procedure:
The title compound, white solid, m.p.=143-145° C., MS: m/e=351.3 (M+H+) was prepared in accordance with the general method of example 1 from 2,2-diphenylpropionyl isocyanate and 2,2,2-trifluoro-ethanol.
Reaction SMILES: [H-].[Na+].[CH2:3]([N:5]([CH2:13][CH3:14])[C:6](=[O:12])[CH2:7]P(O)(O)=O)[CH3:4].[C:15]([C:18]1[O:22][C:21]2[C:23]([O:27][CH:28]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH3:29])=[CH:24][CH:25]=[CH:26][C:20]=2[CH:19]=1)(=O)[CH3:16].[NH4+].[Cl-]>C1COCC1>[CH2:3]([N:5]([CH2:13][CH3:14])[C:6](=[O:12])/[CH:7]=[C:15](/[C:18]1[O:22][C:21]2[C:23]([O:27][CH:28]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH3:29])=[CH:24][CH:25]=[CH:26][C:20]=2[CH:19]=1)\[CH3:16])[CH3:4]
Reactant: CC(=O)c1cc2cccc(OC(C)c3ccccc3)c2o1
Reactant: CCN(CC)C(=O)CP(=O)(O)O
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCN(CC)C(=O)/C=C(\C)c1cc2cccc(OC(C)c3ccccc3)c2o1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
While replacing with nitrogen, NaH (0.13 g, 0.0054 mol) was suspended in absolute THF (20 mL), and N,N-diethylphosphonoacetamide (1.36 g, 0.0054 mol)/absolute THF (10 mL) was added dropwise at 0° C. Then, 2-acetyl-7-(1-phenylethoxy)benzo[b]furan (1.0 g, 0.0036 mol)/absolute THF (20 mL) was added dropwise. After stirring for 6 h while allowing to warm to room temperature, the disappearance of the starting materials was confirmed by TLC. The reaction mixture was poured into saturated aqueous NH4Cl solution, mixed and THF was evaporated under reduced pressure. The residue was extracted with ethyl acetate, washed with brine, dried over absolute magnesium sulfate, and evaporated under reduced pressure to give a pale-yellow oil. The obtained oil was purified by column chromatography to give the title compound as a pale-yellow oil. (0.75 g, 55.6%)
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15]Br)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[P:17]([O:24]CC)([O:21][CH2:22][CH3:23])[O:18][CH2:19][CH3:20]>>[CH2:19]([O:18][P:17]([CH2:15][C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:10]=1)(=[O:24])[O:21][CH2:22][CH3:23])[CH3:20]
Reactant: CCOP(OCC)OCC
Reactant: BrCc1cccc(OCc2ccccc2)c1
Product: CCOP(=O)(Cc1cccc(OCc2ccccc2)c1)OCC
Temperature: 150 °C

Procedure:
1-Benzyloxy-3-bromomethyl-benzene (4.95 g, 17.9 mmol) was treated with triethyl phosphite (3.2 mL, 18.7 mmol) and heated to 150° C. After 3 hours the reaction was cooled to room temperature and concentrated to give the title compound which was used without further purification (5.9 g).