Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:8]([S:26]([CH2:29]P(OCC)(OCC)=O)(=[O:28])=[O:27])[CH2:9][CH2:10][N:11]([C:19]1[CH:24]=[C:23]([CH3:25])[CH:22]=[CH:21][N:20]=1)[C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=O)(C)(C)C.[H-].[Na+].C(O[CH:43](O)[C:44]([F:47])([F:46])[F:45])C>C1COCC1>[CH3:25][C:23]1[CH:22]=[CH:21][N:20]=[C:19]([N:11]([CH2:10][CH2:9][NH:8][S:26](/[CH:29]=[CH:43]/[C:44]([F:47])([F:46])[F:45])(=[O:27])=[O:28])[C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17])[CH:24]=1
Reactant: CCOP(=O)(CS(=O)(=O)N(CCN(C(=O)OC(C)(C)C)c1cc(C)ccn1)C(=O)OC(C)(C)C)OCC
Reactant: CCOC(O)C(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1ccnc(N(CCNS(=O)(=O)/C=C/C(F)(F)F)C(=O)OC(C)(C)C)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 39.3 %

Procedure:
To a solution of tert-butyl N-[2-(tert-butoxycarbonyl(diethoxyphosphorylmethyl-sulfonyl)amino)-ethyl]-N-(4-methyl-2-pyridyl)carbamate (344 mg, 0.608 mmol) in anhydrous THF (30 ml) were added molsieve (4A) and sodium hydride (42.5 mg, 1.063 mmol, 60%) under nitrogen and the mixture was stirred at room temperature for 10 minutes. The mixture was cooled to 0° C. and 1-ethoxy-2,2,2-trifluoro-ethanol (220 mg, 1.525 mmol, 180 μl) was added. Stirring was continued for 30 minutes at 0° C. and overnight at room temperature. The mixture was filtered through kieselguhr and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica, gradient of 0 to 100% heptane in ethyl acetate) to yield 98 mg of a colourless oil (0.239 mmol, 39%) MS(ESI) m/z=410.1 [M+1]+.
Reaction SMILES: [N:1]1[NH:2][C:3](=[O:7])[CH:4]=[CH:5][CH:6]=1.[C:8]([O:12][CH2:13][CH3:14])(=[O:11])[CH:9]=[CH2:10]>C(O)C>[CH2:13]([O:12][C:8](=[O:11])[CH2:9][CH2:10][N:2]1[C:3](=[O:7])[CH:4]=[CH:5][CH:6]=[N:1]1)[CH3:14]
Reactant: C=CC(=O)OCC
Reactant: O=c1cccn[nH]1
Solvent: CCO
Product: CCOC(=O)CCn1ncccc1=O
Temperature: 0 °C
Yield: 82.4 %

Procedure:
To a stirred solution of 5.76 g (0.06 mole) of 3(2H)-pyridazinone and 8 g (0.08 mole) of ethyl acrylate in 100 ml of ethanol, 2 ml of Triton-B was added dropwise while maintaining the temperature at 0° C. The mixture was refluxed for 4 hours, then distilled to give an orange oil residue. The crude oil was extracted with chloroform. The extract was washed with water, dried over anhydrous sodium sulfate and distilled. The residual oil was distilled in a vacuum to give 9.7 g (83% yield) of ethyl-3-(3-oxo-2-pyridazinyl)propionate as a colorless liquid boiling at 120°/121° C./1 mm Hg.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:24])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[CH:11][CH:10]=1)([CH3:7])[CH3:6])[CH3:2].[H-].[Na+].[CH3:27]I.Cl>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:24])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][N:16]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH3:27])=[CH:11][CH:10]=1)([CH3:7])[CH3:6])[CH3:2]
Reactant: CCOC(=O)C(C)(C)Oc1ccc(CNC(=O)OC(C)(C)C)cc1
Reactant: CI
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)(C)Oc1ccc(CN(C)C(=O)OC(C)(C)C)cc1
Temperature: 0 °C

Procedure:
To an ice-cooled and stirred solution of 4.0 g (12 mmol) of the above prepared 2-[4-(tert-butoxycarbonylamino-methyl)-phenoxy]-2-methyl-propionic acid ethyl ester in 37 ml DMF was cooled (0° C.), and treated with 0.78 g (55% in oil, 18 mmol) of sodium hydride and, after 30 min, with 5.93 ml (95 mmol) of CH3I. The reaction was stirred at 0° C. to room temperature for 16 h. Subsequently, the solution was poured onto ice water, adjusted to pH 1 (with aqueous 1N HCl) and extracted with ether (two times). The organic layers were washed with water, dried (MgSO4), evaporated and purified by flash chromatography (SiO2, heptane/AcOEt=9:1) to finally give 3.68 g of the title compound as colorless oil.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][NH:15][C:16]([C:18]2[CH:19]=[CH:20][C:21]([NH:27][C:28]3[N:37]=[CH:36][C:35]4[N:34]([CH3:38])[C:33](=[O:39])[C@@H:32]([CH2:40][CH3:41])[N:31]([CH:42]5[CH2:46][CH2:45][CH2:44][CH2:43]5)[C:30]=4[N:29]=3)=[C:22]3[O:26][CH2:25][CH2:24][C:23]=23)=[O:17])[CH2:9]1)C1C=CC=CC=1.[H][H]>CO.[Pd]>[CH:42]1([N:31]2[C:30]3[N:29]=[C:28]([NH:27][C:21]4[CH:20]=[CH:19][C:18]([C:16]([NH:15][CH2:14][C@H:10]5[O:11][CH2:12][CH2:13][N:8]([CH3:1])[CH2:9]5)=[O:17])=[C:23]5[C:22]=4[O:26][CH2:25][CH2:24]5)[N:37]=[CH:36][C:35]=3[N:34]([CH3:38])[C:33](=[O:39])[C@H:32]2[CH2:40][CH3:41])[CH2:43][CH2:44][CH2:45][CH2:46]1
Reactant: [H][H]
Reactant: CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)NC[C@@H]4CN(Cc5ccccc5)CCO4)c4c3OCC4)nc2N1C1CCCC1
Agent: [Pd]
Solvent: CO
Product: CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)NC[C@@H]4CN(C)CCO4)c4c3OCC4)nc2N1C1CCCC1
Reaction time: 8 h
Yield: 18.5 %

Procedure:
N-[[(2R)-4-Benzylmorpholin-2-yl]methyl]-7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxamide 15b (370 mg, 0.59 mmol) was dissolved in 30 mL of methanol. The reaction solution was hydrogenated with H-Cube (column of catalyst: 10% palladium/carbon; the pressure of hydrogen: 10 atmosphere; temperature: 40° C.) for 8 hours. The reaction solution was concentrated under reduced pressure to obtain the title compound 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-[[(2R)-4-methylmorpholin-2-yl]methyl]-2,3-dihydrobenzofuran-4-carboxamide 15 (60 mg, yield: 18.5%) as a white solid.
Reaction SMILES: C(O[C@@H:5]1[O:27][C@H:26]([CH2:28][O:29][C:30](=[O:37])[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C@@H:16]([O:17][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@H:6]1[O:7][C:8](=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=O)C.[F:38][C:39]([F:51])([F:50])[C:40]([NH:42][C:43]1[CH:44]=[C:45]([OH:49])[CH:46]=[CH:47][CH:48]=1)=[O:41].B(F)(F)F.ClCCl>O1CCCC1>[C:8]([O:7][C@@H:6]1[C@H:16]([O:17][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@@H:26]([CH2:28][O:29][C:30](=[O:37])[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[O:27][C@H:5]1[O:49][C:45]1[CH:46]=[CH:47][CH:48]=[C:43]([NH:42][C:40](=[O:41])[C:39]([F:50])([F:51])[F:38])[CH:44]=1)(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CC(=O)O[C@@H]1O[C@H](COC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@H]1OC(=O)c1ccccc1
Reactant: O=C(Nc1cccc(O)c1)C(F)(F)F
Agent: FB(F)F
Solvent: ClCCl
Solvent: C1CCOC1
Product: O=C(OC[C@H]1O[C@@H](Oc2cccc(NC(=O)C(F)(F)F)c2)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 168 h
Yield: 25.8 %

Procedure:
A solution of 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (500 mg, 0.99 mmol), 3-trifluoroacetamidophenol (407 mg, 1.98 mmol) from Stage 1 and boron trifluoride diethyletherate (1.41 g, 9.93 mmol, 1.25 ml) in a mixture of dry dichloromethane (10 ml) and dry tetrahydrofuran (30 ml) was stirred at room temperature under argon for 7 days. Work-up as in Stage 1 of Example 1 and purification by flash chromatography on silica gel (2% acetone in toluene as eluant) gave the title compound as a colourless solid (166 mg. 21%).
Reaction SMILES: [OH-].[Na+].[C:3]([C:7]1[CH:12]=[CH:11][C:10]([C:13](=[O:15])[NH2:14])=[CH:9][C:8]=1[NH:16][C:17](=[O:38])[CH2:18][CH:19]([C:25]1[CH:30]=[CH:29][C:28]([CH2:31][O:32]C(=O)C)=[CH:27][C:26]=1[O:36][CH3:37])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])([CH3:6])([CH3:5])[CH3:4].C(Cl)Cl>CO>[C:3]([C:7]1[CH:12]=[CH:11][C:10]([C:13](=[O:15])[NH2:14])=[CH:9][C:8]=1[NH:16][C:17](=[O:38])[CH2:18][CH:19]([C:25]1[CH:30]=[CH:29][C:28]([CH2:31][OH:32])=[CH:27][C:26]=1[O:36][CH3:37])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])([CH3:4])([CH3:5])[CH3:6]
Reactant: CCCCCC(CC(=O)Nc1cc(C(N)=O)ccc1C(C)(C)C)c1ccc(COC(C)=O)cc1OC
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: ClCCl
Product: CCCCCC(CC(=O)Nc1cc(C(N)=O)ccc1C(C)(C)C)c1ccc(CO)cc1OC
Reaction time: 0.67 h
Yield: 88.4 %

Procedure:
3.0 ml of a 2 N aqueous solution of sodium hydroxide were added to a solution of 2.25 g (4.95 mmol) of N-(2-t-Butyl-5-carbamoylphenyl)-3-(4-acetoxymethyl-2-methoxyphenyl)octanamide (prepared as described in Example 108) in 15 ml of methanol, and the resulting mixture was stirred for 40 minutes. At the end of this time, the reaction mixture was freed from the solvent by distillation under reduced pressure, and the resulting residue was mixed with water. The aqueous mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of ammonium chloride and with a saturated aqueous solution of sodium chloride, in that order, after which it was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through 100 g of silica gel using a gradient elution method, with mixtures of methylene chloride and methanol ranging from 12:1 to 10:1 by volume as the eluent, to give 1.99 g (yield 96%) of the title compound as a foam-like substance.
Reaction SMILES: C(OC([NH:11][C:12]1[C:13](=[O:28])[N:14]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[N:15]=[CH:16][C:17]=1[CH3:18])=O)C1C=CC=CC=1>C(O)C.C(OCC)(=O)C.[Pd]>[NH2:11][C:12]1[C:13](=[O:28])[N:14]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[N:15]=[CH:16][C:17]=1[CH3:18]
Reactant: COc1ccc(Cn2ncc(C)c(NC(=O)OCc3ccccc3)c2=O)cc1
Agent: [Pd]
Solvent: CCO
Solvent: CCOC(C)=O
Product: COc1ccc(Cn2ncc(C)c(N)c2=O)cc1
Reaction time: 1.3 h
Yield: 100 %

Procedure:
A mixture of 4-benzyloxycarbonylamino-2-(4-methoxybenzyl)-5-methyl-3 -pyridazinone (0.39 g, 1.0 mmol) and 10% Pd/C (0.10 g) in ethanol (40 mL) and ethyl acetate (5 mL) was hydrogenated at 45 psi in a Parr apparatus for 1.3 hours. The catalyst was removed by filtration and the solvents were evaporated to give 4-amino-2-(4-methoxybenzyl)-5-methyl-3-pyridazinone (0.23 g, 1.0 mmol 910%).
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[CH:5][O:4][C:3]=1[C:7]([OH:9])=O.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:46][C:47]1[CH:48]=[C:49]([CH:53]2[CH2:67][N:57]3[C:58](=[O:66])[NH:59][C:60]4[CH:61]=[CH:62][CH:63]=[CH:64][C:65]=4[C:56]3=[N:55][CH2:54]2)[CH:50]=[CH:51][CH:52]=1>CN(C=O)C>[CH3:1][C:2]1[CH:6]=[CH:5][O:4][C:3]=1[C:7]([NH:46][C:47]1[CH:52]=[CH:51][CH:50]=[C:49]([CH:53]2[CH2:67][N:57]3[C:58](=[O:66])[NH:59][C:60]4[CH:61]=[CH:62][CH:63]=[CH:64][C:65]=4[C:56]3=[N:55][CH2:54]2)[CH:48]=1)=[O:9]
Reactant: Cc1ccoc1C(=O)O
Reactant: Nc1cccc(C2CN=C3c4ccccc4NC(=O)N3C2)c1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccoc1C(=O)Nc1cccc(C2CN=C3c4ccccc4NC(=O)N3C2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 47 %

Procedure:
A mixture of 3-methyl-furan-2-carboxylic acid (2.4 mg, 0.019 mmol), N,N-diisopropylethylamine (0.017 mL, 0.095 mmol), and BOP (10.1 mg, 0.023 mmol) in 0.6 mL DMF was stirred at rt for 1 hour, then 3-(3-aminophenyl)-2,3,4,7-tetrahydro-6H-pyrimido[1,2-c]quinazolin-6-one (5.0 mg, 0.017 mmol) added and the reaction continued at rt. After 2.5 hours, a small spatula tip of 3-methyl-furan-2-carboxylic acid and BOP was added and the reaction heated at 60° C. for 1 hour. The reaction mixture was partitioned between EtOAc and aqueous Na2CO3 solution, the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The residue was rinsed with 2 portions of 30% EtOAc/hexane and then chromatographed eluting with 10% MeOH/CHCl3. The resulting solid was chromatographed using a prep plate and eluting with 50% acetone/hexane. The obtained solid was then partitioned between EtOAc and aqueous Na2CO3 solution, the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and evaporated to give the title compound as a white solid (3.2 mg, 47%). 1H NMR (CD3OD/CDCl3 mixture) δ: 8.04 (dd, J=8.2, 1.2 Hz, 1H), 7.68 (t, J=1.8 Hz, 1H), 7.60 (ddd, J=8.1, 2.1, 0.9 Hz, 1H), 7.46-7.53 (m, 2H), 7.37 (t, J=7.9 Hz, 1H), 7.16 (ddd, J=8.1, 7.2, 1.2 Hz, 1H), 7.03-7.10 (m, 2H), 6.45 (dd, J=1.8, 0.6 Hz, 1H), 4.48-4.56 (m, 1H), 3.86-3.95 (m, 1H), 3.61-3.74 (m, 2H), 3.07-3.19 (m, 1H), 2.42 (s, 3H).
Reaction SMILES: Cl[C:2]([O:4][CH2:5][CH3:6])=[O:3].[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[C:26]2[C:25]3[C:20](=[CH:21][C:22]([OH:27])=[CH:23][CH:24]=3)[NH:19][C:18]=2[C:17]([C:28]([NH2:30])=[O:29])=[CH:16][CH:15]=1>N1C=CC=CC=1.CCOC(C)=O>[C:2](=[O:3])([O:4][CH2:5][CH3:6])[O:27][C:22]1[CH:23]=[CH:24][C:25]2[C:26]3[C:18](=[C:17]([C:28](=[O:29])[NH2:30])[CH:16]=[CH:15][C:14]=3[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=3[F:7])[NH:19][C:20]=2[CH:21]=1
Reactant: NC(=O)c1ccc(-c2ccccc2F)c2c1[nH]c1cc(O)ccc12
Reactant: CCOC(=O)Cl
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CCOC(=O)Oc1ccc2c(c1)[nH]c1c(C(N)=O)ccc(-c3ccccc3F)c12
Reaction time: 17 h
Yield: 30.8 %

Procedure:
Ethyl chloroformate (8.19 mg, 0.075 mmol) was added to a solution of 4-(2-fluorophenyl)-7-hydroxy-9H-carbazole-1-carboxamide (Example 40-1, 18.6 mg, 0.058 mmol) in pyridine (1 mL). After 17 h, additional ethyl chloroformate (8.19 mg, 0.075 mmol) was added. After 5 h more, additional ethyl chloroformate (0.05 mL) was added. After 15 h more, the mixture was diluted with EtOAc (30 mL), washed with water (10 mL) and brine (5 mL), dried and concentrated. The residue was purified by preparative HPLC to provide 8-carbamoyl-5-(2-fluorophenyl)-9H-carbazol-2-yl ethyl carbonate as a white solid (7.0 mg, 28%). 1H NMR (400 MHz, chloroform-d) δ 10.44 (1 H, br. s.), 7.62 (1 H, dd, J=7.92, 1.98 Hz), 7.41-7.57 (2 H, m), 7.20-7.40 (4 H, m), 7.16 (1 H, dd, J=7.81, 1.65 Hz), 6.79-6.92 (1 H, m), 6.60 (2H, br. s.), 4.34 (2 H, q, J=7.26 Hz), 1.41 (3 H, t, J=7.15 Hz). Mass spectrum m/z 393.0 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7]1([O:14][CH2:13][CH2:12][O:11]1)[CH2:6][CH2:5]2.C([Li])CCC.CN(C)[CH:22]=[O:23].[BH4-].[Na+].N>O1CCCC1.CO.O>[C:7]12([O:14][CH2:13][CH2:12][O:11]1)[C:8]1[C:4](=[CH:3][C:2]([CH2:22][OH:23])=[CH:10][CH:9]=1)[CH2:5][CH2:6]2
Reactant: Brc1ccc2c(c1)CCC21OCCO1
Reactant: CN(C)C=O
Agent: N
Agent: [BH4-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: OCc1ccc2c(c1)CCC21OCCO1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of Example 332A (13 g, 50.9 mmol) in tetrahydrofuran (150 mL) was added a 2.5 M solution of n-butyllithium in hexanes (30.5 mL, 76.4 mmol) dropwise at about −78° C. Then a solution of N,N-dimethylformamide (39.4 mL, 509.0 mmol) in tetrahydrofuran (40 mL) was added dropwise and the mixture was allowed to warm to ambient temperature. The mixture was poured into water and was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4, filtered, and evaporated in vacuum. The residue was re-dissolved in a mixture of tetrahydrofuran (15 mL) and methanol (150 mL) and sodium borohydride (2.6 g, 68.7 mmol) was added in portions at about 0° C. The reaction mixture was stirred at room temperature for about 2 hours, then the mixture was concentrated in vacuum, diluted with water, and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4), filtered and evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel using hexane/ethyl acetate (2:1) as the mobile phase to give the above intermediate. MS (DCI/NH3): m/z 207 (M+H)+.
Reaction SMILES: [H-].COCCO[Al+]OCCOC.[CH3:13][C:14]1[C@@H:31]([O:32][C:33]([CH3:35])=[O:34])[CH2:30][C@:26]2([OH:36])[C:27]([CH3:29])([CH3:28])[C:15]=1[C@@H:16]([O:57][C:58]([CH3:60])=[O:59])[C:17]([C@@:19]1([CH3:56])[C@H:24]([C@@H:25]2[O:37]C(C2C=CC=CC=2)=O)[C@:23]2([O:48][C:49]([CH3:51])=[O:50])[CH2:46][O:47][C@@H:22]2[CH2:21][C@@H:20]1[O:52][C:53]([CH3:55])=[O:54])=[O:18]>C1COCC1>[CH3:13][C:14]1[C@@H:31]([O:32][C:33]([CH3:35])=[O:34])[CH2:30][C@:26]2([OH:36])[C:27]([CH3:28])([CH3:29])[C:15]=1[C@@H:16]([O:57][C:58]([CH3:60])=[O:59])[C:17]([C@@:19]1([CH3:56])[C@H:24]([C@@H:25]2[OH:37])[C@:23]2([O:48][C:49]([CH3:51])=[O:50])[CH2:46][O:47][C@@H:22]2[CH2:21][C@@H:20]1[O:52][C:53]([CH3:55])=[O:54])=[O:18]
Reactant: CC(=O)O[C@H]1C(=O)[C@]2(C)[C@@H](OC(C)=O)C[C@H]3OC[C@@]3(OC(C)=O)[C@H]2[C@H](OC(=O)c2ccccc2)[C@]2(O)C[C@H](OC(C)=O)C(C)=C1C2(C)C
Agent: COCCO[Al+]OCCOC
Agent: [H-]
Solvent: C1CCOC1
Product: CC(=O)O[C@H]1C(=O)[C@]2(C)[C@@H](OC(C)=O)C[C@H]3OC[C@@]3(OC(C)=O)[C@H]2[C@H](O)[C@]2(O)C[C@H](OC(C)=O)C(C)=C1C2(C)C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 41.9 %

Procedure:
Bis(2-methoxyethoxy)-aluminum hydride (65+ wt % in toluene, 3 equiv.) was added dropwise to a stirred solution of 7,13-diacetylbaccatin III (170 mg, 253 μmol) in dry THF (2 mL) at 0° C. After stirring for 30 minutes at 0° C., the reaction was quenched by dropwise addition of saturated NH4Cl. The mixture was stirred for 10 minutes, then warmed to room temperature and diluted with EtOAc (50 mL), followed by addition of water (10 mL). The aqueous phase was separated and extracted again with EtOAc (2×25 mL). The combined organic fractions were washed with brine and water, then dried over anhydrous MgSO4. The solvent was evaporated and the crude product was purified by silica gel flash column chromatography (40–60% EtOAc gradient in hexane) to yield 2-debenzoyl-7,13-diacetylbaccatin III (see FIG. 11) (60 mg, 42% yield, 99% purity by 1H-NMR). 1H-NMR (300 MHz, CDCl3)δ: 1.04 (s, CH3), 1.22 (s, CH3), 1.77 (s, CH3), 1.85 (ddd, J=1.8, 10.8, and 14.4 Hz, H-6β), 1.90 (d, J=1.2 Hz, vinyl-CH3), 2.02 (s, C(O)CH3), 2.14 (s, C(O)CH3), 2.15 (s, C(O)CH3), 2.20 (s, C(O)CH3), 2.58 (ddd, J=7.2, 9.6, and 14.4 Hz, H-6α), 2.65 (d, J=5.1 Hz, OH at C-2), 3.58 (d, J=6.9 Hz, H-3), 3.90 (dd, J=5.4 and 6.5 Hz, H-2), 4.49 (d, J=9.6 Hz, H-20α), 4.63 (d, J=9.6 Hz, H-20β), 4.97 (dd, J=1.8 and 9.6 Hz, H-5), 5.55 (dd, J=7.2 and 10.7 Hz, H-7), 6.15 (dt, J=1.2 and 9.6 Hz, H-13), 6.18 (s, H-10), H-14 proton signal obscured. APCI-MS: m/z 567 (PH+)
Reaction SMILES: [C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:13][C:14](O)=[O:15])=[CH:5][CH:4]=1)#[N:2]>C1COCC1>[OH:15][CH2:14][CH2:13][C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]([C:1]#[N:2])=[CH:4][CH:5]=1
Reactant: N#Cc1ccc(CC(=O)O)c2ccccc12
Solvent: C1CCOC1
Product: N#Cc1ccc(CCO)c2ccccc12
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A suspension of (4-cyanonaphthalen-1-yl)acetic acid (100 mg, 0.47 mmol) in THF (6 mL) was treated with borane dimethyl sulfide complex (2M, 0.47 mL, 0.94 mmol) and the reaction was stirred for 3 hours at room temperature. The reaction was quenched with methanol and the mixture was partitioned with ethyl acetate and 2N HCl/water. The aqueous was extracted again with ethyl acetate and the organic layers were washed with brine, dried over sodium sulfate and evaporated. The residue was purified on a CombiFlash Rf (12 gm, gradient 10-80% ethyl acetate in hexanes) to afford the title alcohol as an oil. 1H-NMR (500 MHz, CDCl3) δ ppm 1.80 (br s, 1H), 3.48 (t, J=6.4 Hz, 2H), 4.10 (t, J=6.4 Hz, 2H), 7.52 (d, J=7.3 Hz, 1H), 7.75 (m, 2H), 7.92 (d, J=7.2 Hz, 1H), 8.22 (d, J=8.2 Hz, 1H). 8.34 (d, J=8.0 Hz, 1H).
Reaction SMILES: C[O:2][C:3]1[CH:4]=[N:5][C:6]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:11][CH:10]=2)=[N:7][CH:8]=1.C(O)COCCO.[OH-].[Na+]>C(O)(=O)C>[OH:2][C:3]1[CH:8]=[N:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:11][CH:10]=2)=[N:5][CH:4]=1
Reactant: CCCCCCCCc1ccc(-c2ncc(OC)cn2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: OCCOCCO
Solvent: CC(=O)O
Product: CCCCCCCCc1ccc(-c2ncc(O)cn2)cc1
Temperature: 200 °C
Reaction time: 2 h
Yield: 88.3 %

Procedure:
To 5-methoxy-2-(4-octylphenyl)pyrimidine (53.9 g, 0.18 mol) were added diethylene glycol (500 ml) and NaOH (43.4 g, 1.08 mol), followed by agitating the mixture at about 200° C. for 2 hours, pouring the resulting material in acetic acid (700 ml), collecting deposited crystals and recrystallizing the crystals from a mixed solvent of heptane (100 ml) with ethyl acetate (10 ml) to obtain 5-hydroxy-2-(4-octylphenyl)pyrimidine (45.2 g) (m.p.: 147.3-148.7 ° C.).
Reaction SMILES: C(O)(C(F)(F)F)=O.[Cl:8][C:9]1[CH:10]=[C:11]2[N:29](COCC[Si](C)(C)C)[C:28]([O:38][C@H:39]3[C@H:43]4[O:44][CH2:45][C@@H:46]([O:47][CH2:48][CH:49]([OH:52])[CH2:50][OH:51])[C@H:42]4[O:41][CH2:40]3)=[N:27][C:12]2=[N:13][C:14]=1[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][CH:16]=1.C[Si](C)(C)[O-].[K+]>C(Cl)Cl.C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]2[NH:29][C:28]([O:38][C@H:39]3[C@H:43]4[O:44][CH2:45][C@@H:46]([O:47][CH2:48][CH:49]([OH:52])[CH2:50][OH:51])[C@H:42]4[O:41][CH2:40]3)=[N:27][C:12]2=[N:13][C:14]=1[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][CH:16]=1
Reactant: C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@H]3[C@@H]2OC[C@H]3OCC(O)CO)nc2nc(-c3ccc(-c4ccccc4)cc3)c(Cl)cc21
Agent: C[Si](C)(C)[O-]
Agent: [K+]
Solvent: O=C(O)C(F)(F)F
Solvent: C1CCOC1
Solvent: ClCCl
Product: OCC(O)CO[C@@H]1CO[C@H]2[C@@H]1OC[C@H]2Oc1nc2nc(-c3ccc(-c4ccccc4)cc3)c(Cl)cc2[nH]1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
TFA (0.25 ml, 3.24 mmol) was added to a stirred solution of 3-[[(3R,3aR,6R,6aR)-6-[6-chloro-5-(4-phenylphenyl)-1-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-yl]oxy]propane-1,2-diol (6.1 mg, 9.32 μmol) in DCM (0.25 ml). The reaction mixture was stirred at room temperature. After 2.5 hours, the reaction mixture was evaporated under reduced pressure. Potassium trimethylsilanolate (9.2 mg, 0.072 mmol) was added to a stirred solution of the residue in THF (0.5 ml). The reaction mixture was stirred at room temperature. After 1.5 hours, additional potassium trimethylsilanolate (18.2 mg, 0.142 mmol) was added to the reaction mixture. After an additional 1.5 hours, the reaction mixture was evaporated under reduced pressure to give a pale amber residue. This material was purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-100% acetonitrile/water+0.05% TFA gradient followed by a 100% acetonitrile+0.05% TFA flush. The product fractions were combined, evaporated under reduced pressure, and lyophilized from ethanol and benzene to give the title compound as a white solid. LC-MS: calculated for C27H26ClN3O6 523.15 observed m/e: 524.22 (M+H)+ (Rt 1.16/2 min); 1H NMR δ (ppm) (CD3OD): 7.98 (s, 1H), 7.74-7.78 (m, 4H), 7.71 (d, J=7.4 Hz, 2H), 7.48 (t, J=7.7 Hz, 2H), 7.39 (t, J=7.4 Hz, 1H), 5.59 (qt, J=5.1 Hz, 1H), 5.01 (t, J=5.3 Hz, 1H), 4.65 (t, J=5.0 Hz, 1H), 4.13-4.17 (m, 3H), 3.98-4.01 (m, 1H), 3.54-3.81 (m, 6H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:11]=[C:12]([O:14][CH3:15])[CH:13]=1)[CH2:5]OS(C)(=O)=O.[N-:16]=[N+:17]=[N-:18].[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:11]=[C:12]([O:14][CH3:15])[CH:13]=1)[CH2:5][N:16]=[N+:17]=[N-:18]
Reactant: [N-]=[N+]=[N-]
Reactant: COc1cc(Cl)cc(COS(C)(=O)=O)c1
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cc(Cl)cc(CN=[N+]=[N-])c1
Reaction time: 3 h
Yield: 104.7 %

Procedure:
To a solution of methanesulfonic acid 3-chloro-5-methoxybenzyl ester (20 mmol, 5.01 g) in DMF (30 ml) was added NaN3 (60 mmol, 3.90 g). The mixture was stirred for 3 h and the contents subsequently separated between water (300 ml) and DCM (150 ml). The organic phase was washed with water (2×100 ml), then brine, and dried (MgSO4). Filtration and removal of solvents under reduced pressure yielded a yellow liquid (4.14 g). Purification by means of flash chromatography (silica, hexane/ether gradient 0-50%) provided the title compound (3.65 g, 93%). 1H NMR (CDCl3, 500 MHz) δ 3.80 (s, 3H), 4.27 (s, 2H), 6.73 (s, 1H), 6.85 (s, 1H) and 6.89 (s, 1H).