Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9]([O:12][C:13]1[CH:14]=[C:15]([CH:32]=[C:33]([CH3:35])[CH:34]=1)[O:16][CH2:17][CH2:18][CH2:19][O:20][N:21]1C(=O)C2=CC=CC=C2C1=O)(=[O:11])=[O:10])#[N:2].[BH4-].[Na+].[OH-].[Na+]>C(O)C.O1CCCC1.O>[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9]([O:12][C:13]1[CH:14]=[C:15]([CH:32]=[C:33]([CH3:35])[CH:34]=1)[O:16][CH2:17][CH2:18][CH2:19][O:20][NH2:21])(=[O:11])=[O:10])#[N:2]
Reactant: Cc1cc(OCCCON2C(=O)c3ccccc3C2=O)cc(OS(=O)(=O)c2ccccc2C#N)c1
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Solvent: O
Product: Cc1cc(OCCCON)cc(OS(=O)(=O)c2ccccc2C#N)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 85.1 %

Procedure:
To a solution of N-[3-[3-(2-cyanophenylsulfonyloxy)-5-methylphenoxy]propoxy]phthalimide (600 mg, 1.2 mmol), as prepared in the preceding step, in 40 mL of ethanol/tetrahydrofuran/water (2:1:1) was added sodium borohydride (230 mg, 6.0 mmol). The reaction mixture was stirred at ambient temperature overnight. The mixture was acidified (pH 1-2) and heated to 50° C. for 2 hours. After cooling to room temperature, the solution was adjusted to pH 8-9 with 2N NaOH. The mixture was extracted into ethyl acetate (3×50 mL), and the organic phase was washed with brine (50 mL) and dried over Na2SO4. After removing the solvent, the residue was purified by flash column chromatography (dichloromethane to 2% methanol in dichloromethane) to give the title compound as a colorless oil (370 mg, 85%). 1H-NMR (300 MHz, CDCl3) δ8.06 (m, 1H), 7.93 (m, 1H), 7.76 (m, 2H), 6.61 (s, 1H), 6.53 (s, 2H), 5.36 (br s, 2H), 3.94 (t, J=6.3 Hz, 2H), 3.78 (t, J=6.2 Hz, 2H), 2.23 (s, 3H), 1.99 (m, 2H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:15][N:16]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH3:17])([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:27]I>CN(C)C=O.CCCCC>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([CH2:15][N:16]([CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH3:17])([O:14][CH3:27])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CN(Cc1ccccc1)CC1(O)CCN(C(=O)OC(C)(C)C)CC1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCCCC
Product: COC1(CN(C)Cc2ccccc2)CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
Alcohol (35)-(69.3 g, 200 mmol) was dissolved in dimethyl formamide (500 ml). NaH (9.2 g 230 mmol), washed with pentane, was added in 5 portions over 30 min. After complete addition the mixture was stirred at ambient temperature for 45 min. Methyl iodide (14.8 ml, 240 mmol) was added over 1.5 min. The mixture was stirred for 1.5 h at ambient temperature. TLC analysis revealed ca. 80-90% conversion. Extra NaH, 0.8 g, 20 mmol) and methyl iodide (1.2 ml, 20 mmol) was added and the mixture was stirred for another 2 h at ambient temperature. The excess of NaH was destroyed with water (100 ml) and the mixture was further diluted with water (3.5 l). The mixture was extracted with ethyl acetate (2×1 l, 500 ml). The organic layer was washed with brine (1 l), dried over Na2SO4 and concentrated to dryness. The traces of dimethyl formamide were removed by evaporation in vacuo (0.4 mbar, 80° C.). The remaining mixture was purified over silica (eluent: heptane/ethyl acetate, 4/1 to 3/1 v/v). Yield: 55.2 g of amine (36) (80%) as light yellow oil.
Reaction SMILES: [CH:1]([C:4]1[N:5]=[C:6]([C:32]2[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=2)[S:7][C:8]=1[CH2:9][CH2:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([NH:19][S:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[N+:29]([O-:31])=[O:30])(=[O:22])=[O:21])=[CH:15][CH:14]=1)=[O:12])([CH3:3])[CH3:2].IC.[C:44](=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O>[CH:1]([C:4]1[N:5]=[C:6]([C:32]2[CH:33]=[CH:34][C:35]([C:38]([F:41])([F:39])[F:40])=[CH:36][CH:37]=2)[S:7][C:8]=1[CH2:9][CH2:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([N:19]([CH3:44])[S:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[N+:29]([O-:31])=[O:30])(=[O:21])=[O:22])=[CH:15][CH:14]=1)=[O:12])([CH3:3])[CH3:2]
Reactant: O=C([O-])[O-]
Reactant: CC(C)c1nc(-c2ccc(C(F)(F)F)cc2)sc1CCC(=O)c1ccc(NS(=O)(=O)c2ccccc2[N+](=O)[O-])cc1
Agent: Cl
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: CC(C)c1nc(-c2ccc(C(F)(F)F)cc2)sc1CCC(=O)c1ccc(N(C)S(=O)(=O)c2ccccc2[N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 84.8 %

Procedure:
The obtained N-[4-[3-[4-isopropyl-2-[4-(trifluoromethyl)phenyl]thiazol-5-yl]propionyl]phenyl]-2-nitrobenzenesulfonamide (265 mg, 0.439 mmol) was dissolved in anhydrous dimethylformamide (10 mL). Iodomethane (30 μL, 0.483 mmol) and potassium carbonate (121 mg, 0.875 mmol) were added to the solution. The mixture was stirred at room temperature for 16 hours. The mixture was neutralized with 0.2 N aqueous solution of hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and saturated brine, and dried with anhydrous sodium sulfate to remove the solvent. The obtained residue was purified by silica gel column chromatography with hexane/ethyl acetate (7:3, v/v) to give the desired compound (230 mg) as yellow oil (yield 85%).
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[C:5]2[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][N:6]2[CH:13]=1.[Cl:14][C:15]1[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:16]=1[N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.C(N(CC)CC)C>C1COCC1>[Cl:14][C:15]1[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:16]=1[N:22]1[CH2:23][CH2:24][N:25]([CH2:2][C:3]2[N:4]=[C:5]3[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][N:6]3[CH:13]=2)[CH2:26][CH2:27]1
Reactant: COc1ccc2nc(CCl)cn2c1
Reactant: Clc1ccc(N2CCNCC2)c(Cl)c1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COc1ccc2nc(CN3CCN(c4ccc(Cl)cc4Cl)CC3)cn2c1
Temperature: 75 °C
Yield: 47.7 %

Procedure:
A mixture of 2-(chloromethyl)-6-methoxyimidazo[1,2-a]pyridine (0.1392 g), 1-(2,4-dichlorophenyl)piperazine (Example 31, Step 1; 0.1662 g), triethylamine (Aldrich; 0.11 mL), and THF (2 mL) is stirred at 75° C. until the reaction is complete by thin layer chromatography. The cooled mixture is concentrated under reduced pressure and partitioned between dichloromethane and saturated aq. sodium bicarbonate. The combined organic layers are dried with MgSO4 and concentrated under reduced pressure. The residue is chromatographed on silica gel using methanol/dichloromethane (4/96) and crystallized from ethyl acetate/ether to give 0.132 g of the title compound in two crops; mp 129.5-130.5° C.; MS m/z 390, 392; IR (mineral oil) 1479, 1166, 799, 1510, 1219 cm-1 ; 1H NMR (CDCl3) δ2.76, 3.08, 3.77, 3.81, 6.93, 6.97, 7.17, 7.34, 7.45, 7.49, 7.60.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[C:13](=[O:25])[N:14]([CH2:21][C:22]([OH:24])=O)[C:15]([CH:18]([CH3:20])[CH3:19])=[CH:16][CH:17]=2)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.CN([P+](ON1N=NC2C1=CC=CC=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C(OC([N:60]([O:71][CH2:72][CH2:73][NH2:74])[C:61]([NH:63]C(OC(C)(C)C)=O)=[NH:62])=O)(C)(C)C.C(N(CC)CC)C.C(Cl)[Cl:83]>>[ClH:83].[CH3:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[C:13](=[O:25])[N:14]([CH2:21][C:22]([NH:74][CH2:73][CH2:72][O:71][NH:60][C:61]([NH2:63])=[NH:62])=[O:24])[C:15]([CH:18]([CH3:20])[CH3:19])=[CH:16][CH:17]=2)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)NC(=N)N(OCCN)C(=O)OC(C)(C)C
Reactant: Cc1cccc(S(=O)(=O)Nc2ccc(C(C)C)n(CC(=O)O)c2=O)c1
Reactant: ClCCl
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Product: Cc1cccc(S(=O)(=O)Nc2ccc(C(C)C)n(CC(=O)NCCONC(=N)N)c2=O)c1
Product: Cl
Yield: 54 %

Procedure:
3-(3-Methylphenylsulfonyl)amino-6-isopropyl-1-(carboxymethyl)-2-pyridinone (0.71 g, 1.95 mmol), as prepared in the preceding step, Castro's reagent (BOP, 0.905 g, 2.05 mmol), and [N,N′-di(tert-butoxycarbonyl)] 2-aminoethoxyguanidine (0.710 g, 2.00 mmol), as prepared in step 4 of Example 2, were dissolved in methylene chloride (40 mL) and reacted with triethylamine (0.75 mL, 5.4 mmol) at ambient temperature for 3 days. After concentration in vacuo, the crude product was dissolved in methylene chloride, washed with 10% aqueous citric acid, saturated NaHCO3, and brine, dried over Na2SO4, and filtered. The evaporated filtrate was purified by flash column chromatography (5% methanol in methylene chloride) giving the title compound as a light yellow solid (0.70 g, 54%). 1H NMR (300 MHz, CDCl3) δ9.15 (s, 1H), 8.34 (br t, 1H, J=5.0 Hz), 7.67 (m, 3H), 7.59 (s, 1H), 7.40 (d, 1H, J=7.9 Hz), 7.34 (m, 2H), 6.06 (d, 1H, J=7.9 Hz), 4.86 (s, 2H), 4.09 (m, 2H), 3.58 (dd, 2H, J=8.8 Hz, 5.0 Hz), 2.86 (m, 1H), 2.38 (s, 3H), 1.52 (s, 9H), 1.47 (s, 9H), 1.20 (s, 3H), 1.17 (s, 3H).
Reaction SMILES: O[CH:2]([C:4]1[CH:17]=[CH:16][C:7]2[CH:8]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[S:10][C:6]=2[CH:5]=1)[CH3:3].C1(P([N:32]=[N+:33]=[N-:34])(C2C=CC=CC=2)=O)C=CC=CC=1.C1CCN2C(=NCCC2)CC1.[N-]=[N+]=[N-]>C1(C)C=CC=CC=1>[N:32]([CH:2]([C:4]1[CH:17]=[CH:16][C:7]2[CH:8]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[S:10][C:6]=2[CH:5]=1)[CH3:3])=[N+:33]=[N-:34]
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: CCOC(=O)c1cc2ccc(C(C)O)cc2s1
Agent: [N-]=[N+]=[N-]
Solvent: Cc1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Product: CCOC(=O)c1cc2ccc(C(C)N=[N+]=[N-])cc2s1
Reaction time: 24 h

Procedure:
To a solution of ethyl 6-(1-hydroxyethyl)-1-benzothiophene-2-carboxylate (2.0 g, 8.06 mmol) in toluene (30 mL) was added diphenylphosphorylazide (2.64 g, 9.58 mmol), then DBU (1.31 mL, 8.79 mmol) dropwise. After 24 h, added more azide (0.5 mL) and DBU (0.3 mL) to the thick solution. After an additional 24 h, the reaction mixture was concentrated and purified via column chromatography yielding the desired product. 1H NMR (CDCl3, 600 MHz) δ 8.03 (d, J=0.9 Hz, 1H), 7.87 (d, J=8.2 Hz, 1H), 7.81 (m, 1H), 7.36 (dd, J=8.2, 0.9 Hz, 1H), 4.75 (q, J=6.8 Hz, 1H), 4.40 (q, J=7.3 Hz, 2H), 1.58 (d, J=6.8 Hz, 3H), 1.41 (t, J=7.3 Hz, 3H). MS: cal'd 276 (MH+), exp 276 (MH+).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[C:4](=O)[CH:5](Cl)[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH3:13])[CH:7]=1.[C:17]([NH2:20])(=[S:19])[CH3:18]>>[CH3:1][O:2][C:3]([C:4]1[N:20]=[C:17]([CH3:18])[S:19][C:5]=1[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH3:13])[CH:7]=1)=[O:16]
Reactant: COC(=O)C(=O)C(Cl)c1cccc(OC)c1
Reactant: CC(N)=S
Product: COC(=O)c1nc(C)sc1-c1cccc(OC)c1

Procedure:
prepared by reaction of 3-chloro-3-(3-methoxy-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR=0.90 min; [M+H]+=263.9.
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([CH2:8][N:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[C:11]([C:20]([C:22]3[CH:23]=[N:24][C:25](Cl)=[CH:26][CH:27]=3)=[O:21])=[CH:10]2)[CH:5]=[CH:4][CH:3]=1.[N-:29]=[N+]=[N-].[Na+].C(N(CC)CC)C.Cl.C(CCP(CCC(O)=O)CCC(O)=O)(O)=O>CN(C=O)C.O>[NH2:29][C:25]1[N:24]=[CH:23][C:22]([C:20]([C:11]2[C:12](=[O:19])[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:9]([CH2:8][C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([Br:1])[N:7]=3)[CH:10]=2)=[O:21])=[CH:27][CH:26]=1
Reactant: O=C(c1ccc(Cl)nc1)c1cn(Cc2cccc(Br)n2)c2ccccc2c1=O
Reactant: [N-]=[N+]=[N-]
Agent: Cl
Agent: O=C(O)CCP(CCC(=O)O)CCC(=O)O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: Nc1ccc(C(=O)c2cn(Cc3cccc(Br)n3)c3ccccc3c2=O)cn1
Yield: 62.7 %

Procedure:
100 mg (0.22 mmol) of 1-(6-bromo-pyridin-2-ylmethyl)-3-(6-chloro-pyridine-3-carbonyl)-1H-quinolin-4-one and 72 mg (1.1 mmol) of sodium azide were heated at 100° C. in 1 mL of DMF for 1 h. The temperature of the solution was lowered to 70° C. and 1 mL of water was added, followed by 214 uL (155 mg, 1.54 mmol) of triethylamine and 378 mg (1.32 mmol) of tris(2-carboxyethyl)phosphine hydrochloride. After 1 h of reaction time the mixture was purified on reverse-phase HPLC, followed by flash chromatography to give 60 mg of a yellow powder. LC-MSD, m/z for C21H15BrN4O2 [M+H]+=435.0, 437.0; HPLC retention time: 0.6 min.
Reaction SMILES: [F:1][C:2]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:3]=1[O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([OH:17])=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]=[CH:7][CH:6]=1.CC(N(C)C)=O.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:37]([O:44][C:45]([N:47]1[CH2:51][CH:50]2[CH2:52][CH:53]([CH2:55]OS(C)(=O)=O)[CH2:54][CH:49]2[CH2:48]1)=[O:46])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>O>[CH2:37]([O:44][C:45]([N:47]1[CH2:48][CH:49]2[CH2:54][CH:53]([CH2:55][O:17][C:11]3[CH:10]=[C:9]4[C:14]([C:5]([O:4][C:3]5[CH:18]=[CH:19][C:20]([N+:22]([O-:24])=[O:23])=[CH:21][C:2]=5[F:1])=[CH:6][CH:7]=[N:8]4)=[CH:13][C:12]=3[O:15][CH3:16])[CH2:52][CH:50]2[CH2:51]1)=[O:46])[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1
Reactant: CS(=O)(=O)OCC1CC2CN(C(=O)OCc3ccccc3)CC2C1
Reactant: COc1cc2c(Oc3ccc([N+](=O)[O-])cc3F)ccnc2cc1O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: COc1cc2c(Oc3ccc([N+](=O)[O-])cc3F)ccnc2cc1OCC1CC2CN(C(=O)OCc3ccccc3)CC2C1
Temperature: 75 °C
Reaction time: 8 h
Yield: 94 %

Procedure:
To a round bottom flask equipped with a magnetic stir bar was added 4-(2-Fluoro-4-nitro-phenoxy)-6-methoxy-quinolin-7-ol (2.74 g, 6.7 mmol, 1.0 eq.), DMA (30 ml) and cesium carbonate (6.6 g, 20.2 mmol, 3.0 eq). The mixture was stirred at room temperature for 30 minutes at which time 5-methanesulfonyloxymethyl-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid benzyl ester (2.6 g, 7.3 mmol, 1.1 eq) was added. The reaction was heated to 75° C. and allowed to stir overnight. After allowing the reaction to cool to room temperature the reaction was poured into water. The solid was filtered and was then dissolved in EtOAc and washed 2× water, 1× brine and dried over NaSO4. The solvent was removed to yield 5-[4-(2-Fluoro-4-nitro-phenoxy)-6-methoxy-quinolin-7-yloxymethyl]-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid benzyl ester as a cream solid (3.7 g, 94% yield). 1H NMR (400 MHz), CDCl3): 8.55 (d, 1H), 8.15 (d, 1H), 8.09 (d, 1H), 7.32 (m, 8H), 6.52 (d, 1H), 5.11 (d, 2H), 4.13 (d, 2H), 3.95 (s, 3H), 3.57 (m, 2H), 3.43 (m, 2H), 2.93 (m, 3M, 2.16 (m, 2H), 1.39 (m, 2H); MS (EI) for C32H30FN3O7: 588 (M+H+).
Reaction SMILES: O=[C:2]1[CH2:19][CH2:18][C:5]2([CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]2)[CH2:4][CH2:3]1.[NH:20]1[CH2:23][CH2:22][CH2:21]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCCl>[N:20]1([CH:2]2[CH2:19][CH2:18][C:5]3([CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]3)[CH2:4][CH2:3]2)[CH2:23][CH2:22][CH2:21]1
Reactant: C1CNC1
Reactant: CC(C)(C)OC(=O)N1CCC2(CCC(=O)CC2)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCCl
Product: CC(C)(C)OC(=O)N1CCC2(CCC(N3CCC3)CC2)CC1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (step (iv) AMN-06) (1 g, 3.74 mmol) and azetidine (0.25 ml, 3.74 mmol) were initially introduced into 1,2-dichloroethane (15 ml), and sodium triacetoxyborohydride (1.1 g, 5.23 mmol) was added. The reaction mixture was stirred at room temperature for 3 d and saturated sodium bicarbonate solution was then added. After separation of the phases, the aqueous phase was extracted with methylene chloride (2×). The combined organic phases were washed with saturated sodium chloride solution (1×), dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, ethyl acetate/methanol/ammonia (25% aq.) 100:10:1). Yield: 1 g (89%)
Reaction SMILES: [OH:1][C@H:2]([C@H:10]1[O:15][CH2:14][CH2:13][N:12]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18](I)[CH:17]=2)[C:11]1=[O:23])[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[CH3:24][C:25]([O:28][C:29]([N:31]1[CH:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[N:32]1)=[O:30])([CH3:27])[CH3:26].S1C=CC=C1B(O)O>>[C:6]([O:5][C:3](=[O:4])[C@@H:2]([C@H:10]1[O:15][CH2:14][CH2:13][N:12]([C:16]2[CH:17]=[C:18]([C:34]3[CH:33]=[N:32][N:31]([C:29]([O:28][C:25]([CH3:27])([CH3:26])[CH3:24])=[O:30])[CH:35]=3)[CH:19]=[CH:20][CH:21]=2)[C:11]1=[O:23])[OH:1])([CH3:9])([CH3:8])[CH3:7]
Reactant: CC(C)(C)OC(=O)[C@H](O)[C@H]1OCCN(c2cccc(I)c2)C1=O
Reactant: CC(C)(C)OC(=O)n1ccc(B2OC(C)(C)C(C)(C)O2)n1
Agent: OB(O)c1cccs1
Product: CC(C)(C)OC(=O)[C@H](O)[C@H]1OCCN(c2cccc(-c3cnn(C(=O)OC(C)(C)C)c3)c2)C1=O
Yield: 62.7 %

Procedure:
According to the Step 22-1 in synthetic method for EXAMPLE 22, compound 107-1 (0.2 g) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylic acid 1,1-dimethylethyl ester (0.27 g) were used instead of 14-4 and 2-thiopheneboronic acid to obtain compound 107-2 (137 mg) as a pale yellow amorphous solid.
Reaction SMILES: COC1C=C(CNCCCNCCCCNCCCNCC2C=[CH:29][C:28]([OH:31])=[C:27](OC)C=2)C=CC=1O.C(C[CH:39]1[N:44]2[C:45]3[C:50]([CH2:51][CH2:52][CH:43]2[CH2:42][CH2:41][CH2:40]1)=[C:49]([OH:53])[CH:48]=[C:47]([O:54][CH:55]([CH2:57][CH2:58][CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)[CH3:56])[CH:46]=3)(O)=O.[CH3:66][Mg]I.[Cl-].[NH4+].O>C(OCC)C>[OH:53][C:49]1[CH:48]=[C:47]([O:54][CH:55]([CH2:57][CH2:58][CH2:59][C:60]2[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=2)[CH3:56])[CH:46]=[C:45]2[C:50]=1[CH:51]([CH2:27][C:28]([OH:31])([CH3:66])[CH3:29])[CH2:52][CH:43]1[CH2:42][CH2:41][CH2:40][CH2:39][N:44]12
Reactant: COc1cc(CNCCCNCCCCNCCCNCc2ccc(O)c(OC)c2)ccc1O
Reactant: CC(CCCc1ccccc1)Oc1cc(O)c2c(c1)N1C(CCCC1CC(=O)O)CC2
Reactant: C[Mg]I
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCOCC
Product: CC(CCCc1ccccc1)Oc1cc(O)c2c(c1)N1CCCCC1CC2CC(C)(C)O
Temperature: 25 °C
Reaction time: 14 h

Procedure:
A solution of 405 mg. (1 mmole) of the lactone of dl-6-carboxymethyl-7-hydroxy-9-(5-phenyl-2-pentyloxy)-2,3,4,4a,5,6-hexahydro-1H-pyrido[1,2-a]quinoline, provided in Example 29, in 10 ml. ethyl ether is cooled in an ice bath for 15 minutes. To the cold solution is added slowly by injection 0.80 ml. of 2.9 molar methylmagnesium iodide in ethyl ether. The resulting mixture is allowed to warm to room temperature and stirred for 14 hours. Crystalline ammonium chloride (ca. 100 mg.) is added, the mixture stirred for 20 minutes, water (5 ml.) added and the layers separated. The aqueous layer is extracted with 10 ml. of ether and the combined ether layers are washed with 30 ml. of saturated sodium bicarbonate solution, 30 ml. of brine and 30 ml. of water. The washed organic layer is dried (MgSO4) and solvent evaporated in vacuo to afford the title compound which is purified, if desired, by chromatography.
Reaction SMILES: [F:1][C:2]([F:25])([C:6]([F:24])([F:23])[C:7]([F:22])([F:21])[C:8]([F:20])([F:19])[C:9]([F:18])([F:17])[C:10]([F:16])([F:15])[C:11]([F:14])([F:13])[F:12])[C:3](Cl)=[O:4].[N+:26]([C:29]1[CH:36]=[CH:35][CH:34]=[CH:33][C:30]=1[CH2:31][OH:32])([O-:28])=[O:27].C(N(CC)CC)C.Cl.C(N(CC)CC)C>C1C=CC=CC=1>[F:1][C:2]([F:25])([C:6]([F:24])([F:23])[C:7]([F:22])([F:21])[C:8]([F:20])([F:19])[C:9]([F:18])([F:17])[C:10]([F:16])([F:15])[C:11]([F:14])([F:13])[F:12])[C:3]([O:32][CH2:31][C:30]1[CH:33]=[CH:34][CH:35]=[CH:36][C:29]=1[N+:26]([O-:28])=[O:27])=[O:4]
Reactant: O=[N+]([O-])c1ccccc1CO
Reactant: O=C(Cl)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: Cl
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: O=C(OCc1ccccc1[N+](=O)[O-])C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Reaction time: 0.5 h

Procedure:
Perfluorooctanoyl chloride (21.6 g, 0.05 mol) was added slowly with stirring to a solution of 2-nitrobenzyl alcohol (7.65 g, 0.05 mol) and triethylamine (5.2 g, 0.05 mol) in 100 ml benzene. During the addition, the temperature was allowed to rise to 50° C. and the triethylamine hydrochloride began to precipitate. After the addition was complete, the reaction was stirred an additional 30 minutes. The reaction was filtered and the filtrate evaporated in vacuo to give an oil which crystallized on cooling in an ice bath (m.p. 34°-35° C.). Benzene washings of the material retained on the filter paper gave a second fraction of oil which crystallized on cooling. Total yield was 11.97 g.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:3][C@H:4]([OH:32])[C@@H:5]([NH:19][C:20]([C@@H:22]([NH:27][C:28](=[O:31])[O:29][CH3:30])[C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1.[CH3:40][C@@H:41]([CH2:60][CH3:61])[C@H:42]([N:46]1[CH2:50][CH2:49][N:48]([CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[C:54]([CH3:58])[N:53]=2)[C:47]1=[O:59])[C:43](O)=[O:44].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>C1COCC1>[OH:32][C@@H:4]([CH2:3][C@@H:2]([NH:1][C:43](=[O:44])[C@@H:42]([N:46]1[CH2:50][CH2:49][N:48]([CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[C:54]([CH3:58])[N:53]=2)[C:47]1=[O:59])[CH:41]([CH3:40])[CH2:60][CH3:61])[CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[C@@H:5]([NH:19][C:20]([C@@H:22]([NH:27][C:28](=[O:31])[O:29][CH3:30])[C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1
Reactant: COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(-c2ccccn2)cc1)[C@@H](O)C[C@@H](N)Cc1ccccc1)C(C)(C)C
Reactant: CC[C@H](C)[C@@H](C(=O)O)N1CCN(Cc2cccc(C)n2)C1=O
Agent: CCOP(=O)(OCC)On1nnc2ccccc2c1=O
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CCC(C)[C@@H](C(=O)N[C@@H](Cc1ccccc1)C[C@H](O)[C@H](Cc1ccc(-c2ccccn2)cc1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)N1CCN(Cc2cccc(C)n2)C1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 54.5 %

Procedure:
A solution containing the product from Example 23S (0.025 g, 0.047 mmol) in THF (0.5 mL) was treated with the product from Example 7B (0.025 g, 0.060 mmol), DEPBT (0.025 g, 0.084 mmol), and N,N-diisopropylethylamine (0.040 mL, 0.230 mmol), stirred at 25° C. for 2 hours, and partitioned between ethyl acetate and 10% Na2CO3 solution. The organic phase was washed with additional 10% Na2CO3 solution and brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with 0-100% ethyl acetate/dichloromethane, followed by eluting with 0-10% methanol in ethyl acetate to give the title compound (0.021 g, 54% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.60 (d, J=6.62 Hz, 3 H), 0.73 (t, J=7.17 Hz, 3 H), 0.87(m, 10 H), 1.27 (m, 1 H), 1.54 (m, 2 H), 1.75 (m, 1 H), 2.43 (m, 4 H), 2.66 (m, 1 H), 2.77 (d, J=6.99 Hz, 2 H), 2.91 (m, 1 H), 3.12 (m, 3 H), 3.51 (s, 3 H), 3.59 (m, 1 H), 3.85 (d, J=11.03 Hz, 1 H), 3.94 (d, J=9.56 Hz, 1 H), 4.14 (m, 2 H), 4.33 (s, 2 H), 4.81 (d, J=5.15 Hz, 1 H), 6.80 (d, J=9.56 Hz, 1 H), 7.07 (m, 7 H), 7.30 (d, J=7.72 Hz, 3 H), 7.58 (d, J=8.82 Hz, 1 H), 7.65 (t, J=7.54 Hz, 1 H), 7.87 (m, 5 H), 8.63 (d, J=4.04 Hz, 1 H).
Reaction SMILES: Cl.O.[OH:3][CH2:4][C@H:5]([NH:10][C:11]1[C:12]2[S:40][C:39]([O:41]C)=[N:38][C:13]=2[N:14]=[C:15]([S:17][S:18][C:19]2[N:20]=[C:21]([NH:30][C@H:31]([CH2:34][CH:35]([CH3:37])[CH3:36])[CH2:32][OH:33])[C:22]3[S:27][C:26]([O:28]C)=[N:25][C:23]=3[N:24]=2)[N:16]=1)[CH2:6][CH:7]([CH3:9])[CH3:8]>O1CCOCC1>[OH:3][CH2:4][C@H:5]([NH:10][C:11]1[C:12]2[S:40][C:39](=[O:41])[NH:38][C:13]=2[N:14]=[C:15]([S:17][S:18][C:19]2[N:20]=[C:21]([NH:30][C@@H:31]([CH2:32][OH:33])[CH2:34][CH:35]([CH3:36])[CH3:37])[C:22]3[S:27][C:26](=[O:28])[NH:25][C:23]=3[N:24]=2)[N:16]=1)[CH2:6][CH:7]([CH3:8])[CH3:9]
Reactant: COc1nc2nc(SSc3nc(N[C@@H](CO)CC(C)C)c4sc(OC)nc4n3)nc(N[C@@H](CO)CC(C)C)c2s1
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Product: CC(C)C[C@H](CO)Nc1nc(SSc2nc(N[C@@H](CO)CC(C)C)c3sc(=O)[nH]c3n2)nc2[nH]c(=O)sc12
Temperature: 45 °C
Reaction time: 18 h
Yield: 41.8 %

Procedure:
A mixture of conc. hydrochloric acid (20 mL) and water (20 mL) was added to a solution of (2R)-2-{5-[7-((1R)-1-hydroxymethyl-3-methyl-butylamino)-2-methoxy-thiazolo[4,5-d]pyrimidin-5-yldisulfanyl]-2-methoxy-thiazolo[4,5-d]pyrimidin-7-ylamino}-4-methyl-pentan-1-ol (1.5 g, 2.4 mmol) in 1,4-dioxane (20 mL). The solution was then stirred at 45° C. for 18 h. The solvent was evaporated off and the residue was taken up in ethyl acetate. Any undissolved residue was collected by filtration. The filtrate was subjected to flash column chromatography (eluent ethyl acetate:methanol 95:5). The solid residue and the product collected from the chromatography were pooled together to give the title compound (600 mg, 42% yield).