Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:8]1[CH2:13][C@H:12]([O:14][CH2:15][C:16]2[CH:17]=[CH:18][C:19]3[O:24][CH2:23][CH2:22][N:21]([CH2:25][CH2:26][CH2:27][O:28][CH3:29])[C:20]=3[CH:30]=2)[C@@H:11]([C:31]2[CH:36]=[CH:35][C:34]([CH2:37][O:38][CH2:39][C@H:40]([O:42][CH2:43][CH3:44])[CH3:41])=[CH:33][CH:32]=2)[C@H:10]([CH:45]=O)[CH2:9]1)=O)(C)(C)C.[NH:47]1[CH2:51][CH2:50][CH2:49][CH2:48]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[CH2:43]([O:42][C@H:40]([CH3:41])[CH2:39][O:38][CH2:37][C:34]1[CH:35]=[CH:36][C:31]([C@H:11]2[C@H:10]([CH2:45][N:47]3[CH2:51][CH2:50][CH2:49][CH2:48]3)[CH2:9][NH:8][CH2:13][C@@H:12]2[O:14][CH2:15][C:16]2[CH:17]=[CH:18][C:19]3[O:24][CH2:23][CH2:22][N:21]([CH2:25][CH2:26][CH2:27][O:28][CH3:29])[C:20]=3[CH:30]=2)=[CH:32][CH:33]=1)[CH3:44]
Reactant: CCO[C@H](C)COCc1ccc([C@H]2[C@H](C=O)CN(C(=O)OC(C)(C)C)C[C@@H]2OCc2ccc3c(c2)N(CCCOC)CCO3)cc1
Reactant: C1CCNC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: CCO[C@H](C)COCc1ccc([C@H]2[C@H](CN3CCCC3)CNC[C@@H]2OCc2ccc3c(c2)N(CCCOC)CCO3)cc1
Reaction time: 5 h

Procedure:
To a solution of 1 mmol of (3S,4R,5R)-4-[4-((R)-2-ethoxy-propoxymethyl)-phenyl]-3-formyl-5-[4-(3-methoxy-propyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-piperidine-1-carboxylic acid tert-butyl ester in 5 ml of THF are added 1.2 mmol of pyrrolidine, 1.1 mmol of acetic acid and 1.5 mmol of sodium triacetoxyborohydride. The reaction mixture is stirred for 5 h, and poured on an ice H2O mixture. The mixture is extracted with TBME (3×). The combined organic phases are washed with H2O and brine, dried over sodium sulfate and concentrated under reduced pressure. The residue is purified by flash chromatography (SiO2 60F) to afford the title compound, which is identified based on the Rf value.
Reaction SMILES: [C:1]1(C)[CH:6]=[CH:5][C:4](S(Cl)(=O)=O)=[CH:3][CH:2]=1.[OH:12][CH:13]1[CH2:18][CH2:17][CH:16]([C:19]([O:21]CC)=[O:20])[CH2:15][CH2:14]1>N1C=CC=CC=1>[O:12]([CH:13]1[CH2:14][CH2:15][CH:16]([C:19]([OH:21])=[O:20])[CH2:17][CH2:18]1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CCOC(=O)C1CCC(O)CC1
Solvent: c1ccncc1
Product: O=C(O)C1CCC(Oc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
0.63 g of p-toluenesulfonyl chloride was added to a solution of 0.522 g of ethyl 4-hydroxycyclohexanecarboxylate in 5.0 ml of pyridine. The reaction was stirred at room temperature for 3 hours. The reaction mixture was concentrated in vacuo. The resulting solid was taken up in water and ethyl acetate, and the organic phase was washed three times with 2N hydrochloric acid and once with saturated NaCl solution. The organic phase was dried over sodium sulfate and concentrated in vacuo. The resulting product was employed without further purification in the next step. The resulting product (0.55 g) was dissolved in 11.2 ml of DMF, and 0.159 g of phenol and 0.549 g of cesium carbonate were added. The solution was then heated at 80° C. for 6 hours. After cooling, the mixture was concentrated in vacuo and purified by column chromatography on silica gel (eluent: ethyl acetate/n-heptane 1:1). The desired product was obtained. Molecular weight 248.32 (C15H20O3), MS: 249 (M+H+).
Reaction SMILES: [CH:1]1([C:4]2([C:14]3[C:22]4[C:17](=[C:18]([CH2:23][S:24][CH3:25])[CH:19]=[CH:20][CH:21]=4)[NH:16][CH:15]=3)[C:12]3[C:7](=[CH:8][C:9]([F:13])=[CH:10][CH:11]=3)[CH2:6][CH2:5]2)[CH2:3][CH2:2]1.ClCCl.ClC1C=CC=C(C(OO)=[O:37])C=1>CO>[CH:1]1([C:4]2([C:14]3[C:22]4[C:17](=[C:18]([CH2:23][S:24]([CH3:25])=[O:37])[CH:19]=[CH:20][CH:21]=4)[NH:16][CH:15]=3)[C:12]3[C:7](=[CH:8][C:9]([F:13])=[CH:10][CH:11]=3)[CH2:6][CH2:5]2)[CH2:3][CH2:2]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSCc1cccc2c(C3(C4CC4)CCc4cc(F)ccc43)c[nH]c12
Solvent: ClCCl
Solvent: CO
Product: CS(=O)Cc1cccc2c(C3(C4CC4)CCc4cc(F)ccc43)c[nH]c12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
62.0 mg (0.18 mmol) of the compound from Example 93 were introduced into 10 ml of dichloromethane at 0° C., 43.5 mg (0.18 mmol) of 70% pure meta-chloroperbenzoic acid were added, and the mixture was stirred at RT overnight. 2 ml of methanol were added, and the residue after concentration was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 48 mg (74% of theory) of the title compound as mixture of diastereomers.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][C:10]3[N:14]=[CH:13][N:12]([CH:15]4[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]4)[C:11]=3[CH:21]=2)=[N:4][N:3]=1.C(N(CC)CC)C.[CH3:29][S:30](Cl)(=[O:32])=[O:31]>O1CCCC1>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][C:10]3[N:14]=[CH:13][N:12]([CH:15]4[CH2:20][CH2:19][N:18]([S:30]([CH3:29])(=[O:32])=[O:31])[CH2:17][CH2:16]4)[C:11]=3[CH:21]=2)=[N:4][N:3]=1
Reactant: CS(=O)(=O)Cl
Reactant: Cc1nnc(-c2ccc3ncn(C4CCNCC4)c3c2)o1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: Cc1nnc(-c2ccc3ncn(C4CCN(S(C)(=O)=O)CC4)c3c2)o1
Temperature: 25 °C
Reaction time: 1 h
Yield: 59.7 %

Procedure:
To a solution of 6-(5-methyl-1,3,4-oxadiazol-2-yl)-1-(4-piperidinyl)-1H-benzimidazole (0.25 g, 0.88 mmol) and triethylamine (0.24 mL, 1.76 mmol) in tetrahydrofuran (5 mL) was added methanesulfonyl chloride (0.10 mL, 1.32 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 1 hr. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=1/0-19/1) and recrystallized from diethyl ether/methanol to give the title compound (0.19 g, yield 60%) as colorless crystals.
Reaction SMILES: [C:1]([C:3]([C:23](=O)[CH3:24])=[CH:4][C:5]1[O:13][C:12]2[CH:11]=[CH:10][N:9]=[C:8]([NH:14][C:15](=[O:22])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:7]=2[CH:6]=1)#[N:2].[CH3:26][C:27]1[CH:31]=[C:30]([NH2:32])[O:29][N:28]=1>CC(O)C>[C:1]([C:3]1[CH:4]([C:5]2[O:13][C:12]3[CH:11]=[CH:10][N:9]=[C:8]([NH:14][C:15](=[O:22])[C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[C:7]=3[CH:6]=2)[C:31]2[C:27]([CH3:26])=[N:28][O:29][C:30]=2[NH:32][C:23]=1[CH3:24])#[N:2]
Reactant: CC(=O)C(C#N)=Cc1cc2c(NC(=O)c3ccccc3)nccc2o1
Reactant: Cc1cc(N)on1
Solvent: CC(C)O
Product: CC1=C(C#N)C(c2cc3c(NC(=O)c4ccccc4)nccc3o2)c2c(C)noc2N1

Procedure:
A mixture of 200 mg (0.604 mmol) N-{2-(2-cyano-3-oxobut-1-en-1-yl)furo[3,2-c]pyridin-4-yl}benzamide (Example 4A), 59 mg (0.604 mmol) 3-methyl-1,2-oxazol-5-amine and a trace amount of powdered 4 Å molecular sieve in 2-propanol (2 ml) was stirred at 90° C. for 12 h. Upon cooling, the mixture was concentrated under reduced pressure, and the residue was directly purified by preparative RP-HPLC (methanol/water+0.1% TFA gradient, final mixture 100% methanol) to yield 64 mg (26% of th.) of the racemic title compound.
Reaction SMILES: [Br:1][C:2]1[C:3]([O:10][C:11]2[CH:12]=[CH:13][C:14]3[N:18]=[C:17]([CH2:19][O:20][C:21]4[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=4)[C:24]([O:26][CH3:27])=[O:25])[N:16]([CH3:31])[C:15]=3[CH:32]=2)=[N:4][CH:5]=[C:6]([Br:9])[C:7]=1Cl.[CH3:33][O-:34].[Na+].O>CO>[Br:1][C:2]1[C:3]([O:10][C:11]2[CH:12]=[CH:13][C:14]3[N:18]=[C:17]([CH2:19][O:20][C:21]4[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=4)[C:24]([O:26][CH3:27])=[O:25])[N:16]([CH3:31])[C:15]=3[CH:32]=2)=[N:4][CH:5]=[C:6]([Br:9])[C:7]=1[O:34][CH3:33]
Reactant: COC(=O)c1cccc(OCc2nc3ccc(Oc4ncc(Br)c(Cl)c4Br)cc3n2C)c1
Reactant: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COC(=O)c1cccc(OCc2nc3ccc(Oc4ncc(Br)c(OC)c4Br)cc3n2C)c1
Yield: 8.4 %

Procedure:
The reaction and post-treatment were carried out according to Example (3b) using methyl 3-({6-[(3,5-dibromo-4-chloropyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoate produced in Example (14c) (1.56 g, 2.68 mmol), sodium methoxide (5.0 M solution in methanol, 5.36 mL, 26.8 mmol), water (5 mL) and methanol (100 mL) to obtain the title compound (0.13 g, 8%) as a white solid.
Reaction SMILES: Cl.[NH2:2][C@H:3]([CH2:21][OH:22])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:13])=[CH:7][CH:6]=1.C(N(CC)C(C)C)(C)C.[CH2:32]([O:39][C:40]1[CH:50]=[CH:49][C:43]([O:44][CH2:45][C@@H:46]2[CH2:48][O:47]2)=[CH:42][CH:41]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(O)C>[CH2:32]([O:39][C:40]1[CH:41]=[CH:42][C:43]([O:44][CH2:45][C@@H:46]([OH:47])[CH2:48][NH:2][C@H:3]([CH2:21][OH:22])[CH2:4][C:5]2[CH:6]=[CH:7][C:8]([NH:11][C:12]([NH:14][C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)=[O:13])=[CH:9][CH:10]=2)=[CH:49][CH:50]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1
Reactant: N[C@H](CO)Cc1ccc(NC(=O)Nc2ccccc2)cc1
Reactant: c1ccc(COc2ccc(OC[C@@H]3CO3)cc2)cc1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CCO
Product: O=C(Nc1ccccc1)Nc1ccc(C[C@@H](CO)NC[C@H](O)COc2ccc(OCc3ccccc3)cc2)cc1
Temperature: 25 °C
Yield: 44.4 %

Procedure:
To a solution of N-[4-[(2S)-2-amino-3-hydroxypropyl]phenyl]-N′-phenylurea hydrochloride (222 mg) in ethanol (5.0 ml) were added successively N,N-diisopropylethylamine (264 μl) and (2S)-2-[[4-(benzyloxy)phenoxy)methyl]oxirane (212 mg) and the solution was refluxed for 13.5 hours. After cooling to room temperature, the precipitates were collected by filtration, washed with ethanol, and dried under reduced pressure to give N-[4-[(2S)-2-[[(2S)-3-[4-(benzyloxy)phenoxy]-2-hydroxypropyl]amino]-3-hydroxypropyl]phenyl]-N′-phenylurea (166 mg) as a white solid.
Reaction SMILES: [O:1]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8][O:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:13]12([CH2:23][C:24](Cl)=[O:25])[CH2:22][CH:17]3[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]3)[CH2:14]1)[CH2:20]2>>[C:13]12([CH2:23][C:24]([N:4]3[CH2:5][CH2:6][O:7][CH2:8][CH2:9][N:10]([C:24](=[O:25])[CH2:23][C:13]45[CH2:22][CH:17]6[CH2:16][CH:15]([CH2:21][CH:19]([CH2:18]6)[CH2:20]4)[CH2:14]5)[CH2:11][CH2:12][O:1][CH2:2][CH2:3]3)=[O:25])[CH2:22][CH:17]3[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]3)[CH2:14]1)[CH2:20]2
Reactant: O=C(Cl)CC12CC3CC(CC(C3)C1)C2
Reactant: C1COCCNCCOCCN1
Product: O=C(CC12CC3CC(CC(C3)C1)C2)N1CCOCCN(C(=O)CC23CC4CC(CC(C4)C2)C3)CCOCC1

Procedure:
Analogously to Example 2 from 1,7-dioxa-4,10-diazacyclododecane and (1-adamantyl ) acetyl chloride.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C:11]3[C:20]4[C:15](=[CH:16][C:17]([O:23][CH2:24][C@@H:25]5[CH2:27][O:26]5)=[C:18]([O:21][CH3:22])[CH:19]=4)[N:14]=[CH:13][N:12]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[CH3:28][NH:29][CH3:30]>C1COCC1.CN(C=O)C>[OH:26][C@@H:25]([CH2:27][N:29]([CH3:30])[CH3:28])[CH2:24][O:23][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([O:10][C:6]3[CH:5]=[C:4]4[C:9](=[CH:8][CH:7]=3)[NH:1][CH:2]=[CH:3]4)=[N:12][CH:13]=[N:14]2)=[CH:19][C:18]=1[O:21][CH3:22]
Reactant: COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1
Reactant: CNC
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN(C)C
Temperature: 75 °C
Reaction time: 3 h
Yield: 85 %

Procedure:
A mixture of (2S)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (100 mg, 0.28 mmol), (prepared as described for the starting material in Example 297), and dimethylamine (0.42 ml of a 2M solution in THF, 0.84 mmol) in DMF (5 ml) was stirred at 75° C. for 3 hours under an atmosphere of nitrogen and then allowed to cool to ambient temperature. The solvents were removed in vacuo and the residue purified by trituration with methanol to give (2S)-7-(2-hydroxy-3-dimethylaminopropoxy)-4-(indol-5-yloxy)-6-methoxyquinazoline (100 mg, 85%).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](=[O:28])[N:14]3[C:25]4[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=4)[C:19](=[O:27])[C:15]3=[N:16]2)=[CH:11][CH:10]=1)=O)(C)([CH3:3])[CH3:2].C(OC[C@@H]1OC1)(=[O:33])CCC.[H-].[Li+]>CN(C=O)C.C(Cl)(Cl)Cl>[OH:33][CH2:2][CH:1]1[O:5][CH2:6][N:8]([C:9]2[CH:18]=[C:17]3[C:12]([C:13](=[O:28])[N:14]4[C:25]5[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=5)[C:19](=[O:27])[C:15]4=[N:16]3)=[CH:11][CH:10]=2)[CH2:3]1
Reactant: CCCC(=O)OC[C@H]1CO1
Reactant: CC(C)(C)OC(=O)Nc1ccc2c(=O)n3c(nc2c1)C(=O)c1cc(F)ccc1-3
Agent: [H-]
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: ClC(Cl)Cl
Product: O=C1c2cc(F)ccc2-n2c1nc1cc(N3COC(CO)C3)ccc1c2=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 3-(N-t-butyloxycarbonylamino)-8-fluoroindolo[2,1-b]quinazoline-6,12-dione (0.5 mmol), (R)-glycidyl butyrate (0.55 mmol) and lithium hydride (0.60 mmol) in DMF is allowed to stir at room temperature overnight. The reaction mixture is diluted with CHCl3, washed with 0.1N HCl, sodium bicarbonate solution, dried (MgSO4) and the solvent is evaporated. Silica gel chromatography (1% MeOH/CHCl3) gives 3-(5-hydroxymethyloxazolidin-3-yl)-8-fluoroindolo[2,1-b]quinazoline-6,12-dione.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]([OH:12])=O)=[CH:9][C:4]=2[O:3][CH2:2]1.[NH2:13][C@H:14]([CH:19]([CH3:21])[CH3:20])[C:15]([O:17][CH3:18])=[O:16]>>[O:3]1[C:4]2[CH:9]=[C:8]([C:10]([NH:13][C@H:14]([CH:19]([CH3:21])[CH3:20])[C:15]([O:17][CH3:18])=[O:16])=[O:12])[CH:7]=[CH:6][C:5]=2[O:1][CH2:2]1
Reactant: COC(=O)[C@H](N)C(C)C
Reactant: O=C(O)c1ccc2c(c1)OCO2
Product: COC(=O)[C@H](NC(=O)c1ccc2c(c1)OCO2)C(C)C
Yield: 50 %

Procedure:
Prepared in a similar manner to example 4 using benzo[d][1,3]dioxole-5-carboxylic acid and (R)-methyl 2-amino-3-methylbutanoate. Yield: 50%. MS (M+H, 280.1).
Reaction SMILES: O[C:2]([CH3:14])([CH3:13])[CH2:3][C:4]1[C:5]([CH3:12])=[C:6]([OH:11])[C:7]([CH3:10])=[CH:8][CH:9]=1.[C-:15]#[N:16].[Na+].[Cl-]>O>[CH3:13][C:2]1([CH3:14])[CH2:3][C:4]2[C:9](=[CH:8][C:7]([CH3:10])=[C:6]([OH:11])[C:5]=2[CH3:12])[CH:15]=[N:16]1
Reactant: [C-]#N
Reactant: Cc1ccc(CC(C)(C)O)c(C)c1O
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Product: Cc1cc2c(c(C)c1O)CC(C)(C)N=C2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Tertiary alcohol 33 (12.5 g, 64.4 mmol) is subjected to the Ritter reaction according to general procedure B. The substrate is added to the acid/cyanide mixture (at rt) over a 2.5 h period, and the resulting red reaction mixture is stirred overnight at rt. Because of the high water solubility of the product, during the work-up the aqueous phase is saturated with NaCl, and extracted six times with EtOAc to obtain an acceptable recovery of material. The organic phase is dried (Na2SO4), filtered and concentrated. The residue is filtered through silica gel with 10:1 CH2Cl2 /MeOH, and the appropriate fractions are combined and diluted with hexane to produce 38 as yellow crystals, mp 220-234° C. (dec.). A lower Rf product is also isolated. This product displays the same type of TLC behavior (blue fluorescence), and a very similar 1H NMR spectrum, and is thought to be a symmetrical dimer. Upon standing in solution, this product is slowly converted into 38, which then precipitates. Three crops of the yellow crystals are collected for a total yield of 6.8 g (52%). 1H NMR (CD3OD, 3.30 ppm) 7.76 (s, 1), 7.10 (s, 1), 4.93 (s, 1), 2.82 (s, 2), 2.10 (s, 3), 2.07 (s, 3), 1.33 (s, 6); 13C NMR (CD3OD, 49.05 ppm) 158.21, 136.17, 134.91, 127.55, 126.90, 54.34, 38.15, 27.25, 17.02, 11.39; MS (MW=203.3, CI/CH4, eE=70 eV) m/z 204 [(M+H)+, base peak)], 188, 177, 122.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]2[O:11][CH:12]=[C:13]([CH2:15]Cl)[N:14]=2)=[CH:4][CH:3]=1.[CH3:17][S:18]([CH2:21][C:22]1[N:23]([CH2:27][CH2:28][CH2:29][CH2:30][C:31]2[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=2)[CH:24]=[CH:25][N:26]=1)(=[O:20])=[O:19].[H-].[Na+]>>[F:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]2[O:11][CH:12]=[C:13]([CH2:15][O:37][C:34]3[CH:33]=[CH:32][C:31]([CH2:30][CH2:29][CH2:28][CH2:27][N:23]4[CH:24]=[CH:25][N:26]=[C:22]4[CH2:21][S:18]([CH3:17])(=[O:20])=[O:19])=[CH:36][CH:35]=3)[N:14]=2)=[CH:4][CH:3]=1
Reactant: CS(=O)(=O)Cc1nccn1CCCCc1ccc(O)cc1
Reactant: Fc1ccc(/C=C/c2nc(CCl)co2)cc1
Agent: [H-]
Agent: [Na+]
Product: CS(=O)(=O)Cc1nccn1CCCCc1ccc(OCc2coc(/C=C/c3ccc(F)cc3)n2)cc1
Yield: 55.5 %

Procedure:
Using 2-[(E)-2-(4-fluorophenyl)ethenyl]-4-(chloromethyl)-1,3-oxazole (274 mg), 4-[4-[2-[(methylsulfonyl)methyl]-1H-imidazol-1-yl]butyl]phenol (300 mg) and 65% sodium hydride (39.5 mg), the same reaction as Example 11-(i) was carried out to yield the titled compound (275 mg) as a colorless crystal powder.
Reaction SMILES: [CH3:1][N:2]1[C:6]2=[N:7][CH:8]=[C:9]([C:11](O)=[O:12])[CH:10]=[C:5]2[N:4]=[C:3]1[NH:14][C:15]1[S:16][C:17]2[CH:23]=[C:22]([O:24][C:25]([F:28])([F:27])[F:26])[CH:21]=[CH:20][C:18]=2[N:19]=1.[CH3:29][CH2:30][NH2:31].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>>[CH2:30]([NH:31][C:11]([C:9]1[CH:10]=[C:5]2[N:4]=[C:3]([NH:14][C:15]3[S:16][C:17]4[CH:23]=[C:22]([O:24][C:25]([F:28])([F:27])[F:26])[CH:21]=[CH:20][C:18]=4[N:19]=3)[N:2]([CH3:1])[C:6]2=[N:7][CH:8]=1)=[O:12])[CH3:29]
Reactant: CCN
Reactant: Cn1c(Nc2nc3ccc(OC(F)(F)F)cc3s2)nc2cc(C(=O)O)cnc21
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: CCNC(=O)c1cnc2c(c1)nc(Nc1nc3ccc(OC(F)(F)F)cc3s1)n2C

Procedure:
3-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-3H-imidazo[4,5-b]pyridine-6-carboxylic acid ethylamide (58 mg) was prepared by following General Procedure F starting from 3-methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-3H-imidazo[4,5-b]pyridine-6-carboxylic acid (75 mg), 2-ethylamine (2 M in THF, 183 uL), HBTU (83 mg), and DIEA (48 uL). LC/MS: m/z 436.6. 1H NMR (DMSO-d6, 400 MHz): δ 12.39 (bs, 1H), 8.44 (s, 1H), 8.09 (s, 1H), 7.92 (s, 1H), 7.81-7.65 (m, 1H), 7.48 (d, 1H), 7.36 (d, 1H), 3.64 (s, 3H), 3.40-3.23 (m, 2H), 1.15 (t, 3H).
Reaction SMILES: O[CH:2]([C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][CH:13]=1)[CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:41]1(=[O:51])[NH:45][C:44](=[O:46])[C:43]2=[CH:47][CH:48]=[CH:49][CH:50]=[C:42]12.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[O:46]=[C:44]1[C:43]2[C:42](=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:41](=[O:51])[N:45]1[CH:2]([C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][CH:13]=1)[CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: CC(C)(C)OC(=O)NCC(O)c1cccc2ccccc12
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCC(c1cccc2ccccc12)N1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 64.6 %

Procedure:
To a solution of 1,1-dimethylethyl [2-hydroxy-2-(1-naphthalenyl)ethyl]carbamate (1.38 g, 4.8 mmol), triphenylphosphine (1.52 g, 5.76 mmol) and phthalimide (0.74 g, 5.04 mmol) in THF (50 mL) at 25° C. was added diethyl azodicarboxylate (0.87 mL, 5.52 mmol). After stirring at RT for 1 h, the reaction solution was concentrated under vacuum and the residue purified on silica gel (20% EtOAc in hexanes) affording the title compound (1.29 g, 3.1 mmol, 65%) as a white solid: LCMS (ES) m/z 387 (M+H)+.
Reaction SMILES: [CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[C:18]([C:23]([O:25]C(C)(C)C)=[O:24])=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:13][CH:12]=2)[C:8]2[CH:30]=[C:31]([O:34][C:35]([N:37]([CH3:39])[CH3:38])=[O:36])[CH:32]=[CH:33][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4].FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[C:18]([C:23]([OH:25])=[O:24])=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:15][CH:16]=2)[C:8]2[CH:30]=[C:31]([O:34][C:35]([N:37]([CH3:39])[CH3:38])=[O:36])[CH:32]=[CH:33][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc2ccc(OC(=O)N(C)C)cc2n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCCCc1nc2ccc(OC(=O)N(C)C)cc2n1Cc1ccc(-c2ccccc2C(=O)O)cc1

Procedure:
Prepared in analogous manner to Example 9 from tert.butyl 4'-[(2-n-butyl-6-dimethylaminocarbonyloxy-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylate and trifluoroacetic acid in methylene chloride.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:18][C@H:17]([CH2:19][OH:20])[C@@H:15]([OH:16])[C@H:12]2[O:13][CH3:14])=[C:4](N)[N:3]=1.[C@@H]1(N2C3N=CN=C(N)C=3N=C2)O[C@H](CO)[C@@H](O)[C@H]1[OH:24]>P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].CS(C)=O>[CH3:14][O:13][C@@H:12]1[C@H:15]([OH:16])[C@@H:17]([CH2:19][OH:20])[O:18][C@H:11]1[N:8]1[C:9]2[N:10]=[C:2]([NH2:1])[NH:3][C:4](=[O:24])[C:5]=2[N:6]=[CH:7]1
Reactant: Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Reactant: CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1cnc2c(N)nc(N)nc21
Agent: O=P([O-])([O-])[O-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1cnc2c(=O)[nH]c(N)nc21

Procedure:
2,6-Diamino-9- (2'-O-methyl-β-D-ribofuranosyl)purine (9.5 g) in 0.1M sodium phosphate buffer (200 ml, pH 7.4) and DMSO (25 ml) was treated with adenosine deaminase (Type II Sigma) at RT for 4 days. The resulting suspension was cooled and filtered and the resulting filter cake washed with H2O and dried to a white solid (4.0 g). The solid was recrystallized from hot H2O to yield 2.9 g of product. m.p. 236°-238° C. 1H NMR (DMSO-d6) δ3.3 (s, 3, OCH3), 3.53 and 3.6 (ABX, 2, H-5'), 3.87 (m, 1, H-4'), 4.15 (m, 1, H-2'), 4.25 (m, 1, H-3'), 5.13 (t, 1, 5'-OH), 5.23 (d, 1, 3'-OH), 5.8 (d, 1, H-1'), 6.48 (br s, 2, NH2), 7.96 (s, 1, H-8) and 10.68 (br s, 1, NH). Anal. Calcd. for C11H15N5O5.1/2H2O: C, 43.14; H, 5.26; N, 22.86. Found: C, 43.59; H, 5.34; N, 23.04.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:22])[CH2:5][NH:6][CH2:7][CH2:8][NH:9][S:10]([C:13]1[S:14][C:15]2[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=2[N:17]=1)(=[O:12])=[O:11])[CH3:2].[CH:23]([O:36][C:37]([NH:39][C:40]1[CH:45]=[CH:44][N:43]([CH2:46][C:47](O)=[O:48])[C:42](=[O:50])[N:41]=1)=[O:38])([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[CH2:1]([O:3][C:4](=[O:22])[CH2:5][N:6]([CH2:7][CH2:8][NH:9][S:10]([C:13]1[S:14][C:15]2[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=2[N:17]=1)(=[O:12])=[O:11])[C:47](=[O:48])[CH2:46][N:43]1[CH:44]=[CH:45][C:40]([NH:39][C:37]([O:36][CH:23]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:38])=[N:41][C:42]1=[O:50])[CH3:2]
Reactant: CCOC(=O)CNCCNS(=O)(=O)c1nc2ccccc2s1
Reactant: O=C(O)Cn1ccc(NC(=O)OC(c2ccccc2)c2ccccc2)nc1=O
Product: CCOC(=O)CN(CCNS(=O)(=O)c1nc2ccccc2s1)C(=O)Cn1ccc(NC(=O)OC(c2ccccc2)c2ccccc2)nc1=O
Yield: 84.9 %

Procedure:
The title compound (2.99 g, 85%) was synthesized by the reaction of N-[2-(benzothiazole-2-sulfonylamino)-ethyl]-glycine ethyl ester (1.72 g, 5 mmol) and [4-N-(benzhydryloxycarbonyl)-cytosin-1-yl]-acetic acid (1.90 g, 5 mmol) as per the procedure of Example 20. 1H NMR (500 MHz; DMSO-d6) δ 11.00 (s, 1H), 8.86 (brs, 1H), 8.27 (d, 1H), 8.18 (d, 1H), 7.89 (d, 0.6H), 7.83 (d, 0.4H), 7.68˜7.61 (m, 2H), 7.45˜7.26 (m, 10H), 6.94 (t, 1H), 6.79 (s, 1H), 4.91 (s, 1.2H), 4.62 (s, 0.8H), 4.35 (s, 0.8H), 4.13 (q, 0.8H), 4.06 (s, 1.2H), 4.03 (q, 1.2H), 3.59 (t, 1.2H), 3.44˜3.39 (m, 2H), 3.21 (t, 0.8H), 1.19 (t, 1.2H), 1.13 (t, 1.8H).