Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[C:2]1([C:8]([OH:10])=O)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[CH2:11]1COCC1>>[CH3:11][CH:8]([CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1)[OH:10]
Reactant: CC1(C(=O)O)CCCCC1
Reactant: C1CCOC1
Product: CC(O)C1CCCCC1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
A three liter three necked round bottom flask was equipped with a thermometer, magnetic stirrer, argon inlet and outlet adapters and a one liter addition funnel containing 922 ml of 1.0 molar BH3 ·THF. 1-Methyl cyclohexanecarboxylic acid (119.2 g; 0.84 mole) was added to the reaction vessel and dissolved in 100 ml of THF. The reaction mixture was cooled with an ice bath to 5° C. the BH3 ·THF was added dropwise over 25 min maintaining the temperature between 5°-15° C. After the addition was complete, the ice bath was removed. After about 5 min, the reaction exothermed and foamed violently. A much slower addition rate and constant cooling should help to avoid this exotherm. The reaction was allowed to stir for 2 hr at room temperature under nitrogen, then 150 ml of methanol was added cautiously. When the foaming ceased, the reaction was concentrated in vacuo using low heat and the residue was treated with 100 ml of 5% acetic acid. After stirring for 30 min, the reaction was transferred to a one liter separatory funnel, diluted with water (slurry dissolved) and extracted three times with ether. The combined ether extracts were washed twice with saturated sodium bicarbonate, twice with brine, dried over anhydrous magnesium sulfate, filtered through celite and concentrated in vacuo (low heat) to give 79.09 g of a clear water-white oil. The oil was distilled on a Kugelrohr apparatus at 75°-130° C. (25 mm of Hg). Most distilled at 90° C. to give 72.11 g of 1-methyl-1-cyclohexylmethanol.
Reaction SMILES: [OH-].[Na+].[C:3]12([C:13]3[CH:14]=[C:15]([C:28]4[CH:29]=[C:30]5[C:35](=[CH:36][CH:37]=4)[CH:34]=[C:33]([C:38]([O:40]C)=[O:39])[CH:32]=[CH:31]5)[CH:16]=[CH:17][C:18]=3[O:19][CH2:20][CH:21]3[CH2:25][O:24][C:23]([CH3:27])([CH3:26])[O:22]3)[CH2:12][CH:7]3[CH2:8][CH:9]([CH2:11][CH:5]([CH2:6]3)[CH2:4]1)[CH2:10]2>CO>[C:3]12([C:13]3[CH:14]=[C:15]([C:28]4[CH:29]=[C:30]5[C:35](=[CH:36][CH:37]=4)[CH:34]=[C:33]([C:38]([OH:40])=[O:39])[CH:32]=[CH:31]5)[CH:16]=[CH:17][C:18]=3[O:19][CH2:20][CH:21]3[CH2:25][O:24][C:23]([CH3:26])([CH3:27])[O:22]3)[CH2:12][CH:7]3[CH2:6][CH:5]([CH2:11][CH:9]([CH2:8]3)[CH2:10]1)[CH2:4]2
Reactant: COC(=O)c1ccc2cc(-c3ccc(OCC4COC(C)(C)O4)c(C45CC6CC(CC(C6)C4)C5)c3)ccc2c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC1(C)OCC(COc2ccc(-c3ccc4cc(C(=O)O)ccc4c3)cc2C23CC4CC(CC(C4)C2)C3)O1
Reaction time: 48 h
Yield: 88.5 %

Procedure:
2 g (50 mmol) of sodium hydroxide and 25 ml of methanol (i.e., 25 ml of a 2N solution of methanolic sodium hydroxide) are added to 1 g (1.9 mmol) of methyl 6-[3-adamantan-1-yl-4-(2,2-dimethyl[1,3]dioxolan-4-ylmethoxy)phenyl]naphthalene-2-carboxylate. The reaction medium is heated at the reflux of methanol for 6 h and then at ambient temperature for 2 days and, finally, evaporated to dryness. The solid residue is taken up in water, and the aqueous phase is acidified to pH=2-3 and extracted with ether. The organic phase is washed with water and then with brine, dried over magnesium sulfate, filtered, and evaporated until only approximately 10 ml of a suspension of the product in ether remains. The crystals are then filtered off and dried. After drying, 862 mg (88%) of a yellowish powder are obtained (mp=287° C.). 1H NMR (CDCl3+drop DMSO-d6) (250 MHz): 1.43 (s, 3H), 1.49 (s, 3H), 1.80 (s, 6H), 2.12 (broad s, 3H), 2.18 (s, 6H), 4.05 (m, 2H), 4.16-4.30 (m, 2H), 4.60 (m, 1H), 7.0 (d, J=8.5 Hz, 1H), 7.55 (d, J=8.5 Hz, 1H), 7.6 (s, 1H), 7.78 (d, J=8.5 Hz, 1H), 7.89-8.00 (m, 3H), 8.09 (d, J=10.0 Hz, 1H), 8.63 (s, 1H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].CO.C(Cl)[Cl:17]>>[Cl:17][CH2:9][C:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[C:3]([N+:11]([O-:13])=[O:12])[CH:4]=1)=[O:10]
Reactant: ClCCl
Reactant: CC(=O)c1ccc(F)c([N+](=O)[O-])c1
Solvent: CO
Product: O=C(CCl)c1ccc(F)c([N+](=O)[O-])c1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
1-(4-Fluoro-3-nitrophenyl)ethanone (18.4249 g; manufactured by Sigma-Aldrich Co.) was dissolved in CH2Cl2 (400 mL), and methanol (3.04 mL) was added thereto. The mixture was purged with nitrogen, and was cooled to 0° C. To this solution, a SO2Cl2—CH2Cl2 Solution [109.32 mL; solution prepared by dissolving SO2Cl2 (9.32 mL; manufactured by Wako Pure Chemical Industries, Ltd.) in CH2Cl2 (100 mL)] was added dropwise over 30 minutes, and the mixture was stirred overnight while the temperature was raised to room temperature. The reaction solution was cooled to 0° C., and methanol (1.52 mL) was added thereto. Subsequently, a SO2Cl2—CH2Cl2 solution [64.66 mL; solution prepared by dissolving SO2Cl2 (4.66 mL; manufactured by Wako Pure Chemical Industries, Ltd.) in CH2Cl2 (60 mL)] was added dropwise to the mixture, and while the temperature was raised to room temperature, the mixture was stirred for 3 hours. The reaction solution was washed once with a saturated aqueous solution of sodium carbonate, and once with brine. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. Subsequently, the resulting residue was purified by column chromatography (“COLUMN-A”; n-hexane:ethyl acetate=88:12→67:33), and in the middle of the chromatographic process, crystals solidified in the silica gel were extracted with ethyl acetate and filtered. The solvent of the filtrate was evaporated under reduced pressure, and thus the title compound (6.403 g) was obtained.
Reaction SMILES: [CH3:1][C:2]1[C:6]2[C:7]([O:11][CH2:12][CH2:13][CH2:14][NH:15][CH2:16][C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[CH2:23][S:24][CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C1C=C(Cl)C=C(C(OO)=[O:41])C=1>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH3:1][C:2]1[C:6]2[C:7]([O:11][CH2:12][CH2:13][CH2:14][NH:15][CH2:16][C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[CH2:23][S:24]([CH2:25][CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)=[O:41]
Reactant: Cc1c(CSCCc2ccccc2)oc2cccc(OCCCNCc3cccnc3)c12
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1c(CS(=O)CCc2ccccc2)oc2cccc(OCCCNCc3cccnc3)c12
Temperature: 25 °C
Reaction time: 2 h
Yield: 40.5 %

Procedure:
To a solution of the compound in Example 56 (20 mg, 0.04 mmol) in CH2Cl2/TFA (8/2) (1 ml) was added m-CPBA (14 mg, 80%, 0.06 mmol) at 0° C. The mixture was stirred for 2 hours at room temperature. The solvent was removed under reduced pressure. The residue was purified over preparative TLC (CH2Cl2/MeOH=100/1) to give the desired compound (7.5 mg, 36%) as a colorless oil. FAB-MS: m/z 463 (MH+); 1H-NMR (CDCl3): δ 1.97 (2H, m), 2.24 (3H, s), 2.81 (2H, t, J=6.9 Hz), 2.88-3.07 (4H, m), 3.77 (2H, s), 4.04-4.10 (4H, m), 6.52 (1H, d, J=7.6 Hz), 6.91 (1H, d, J=7.6 Hz), 7.05-7.22 (7H, m), 7.58 (1H, d, J=7.8 Hz) 8.41 (1H, brd, J=4.5 Hz), 8.48 (1H, brs).
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[C:11]([F:12])=[CH:10][CH:9]=[CH:8][C:7]=2[C@:13]([C@@H:21]2[CH2:26][CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22]2)([OH:20])[CH2:14][CH2:15][CH2:16][CH2:17][O:18][CH3:19])[CH2:3][CH2:2]1.C([O-])(O)=O.[Na+]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH:1]1([CH2:4][O:5][C:6]2[C:11]([F:12])=[CH:10][CH:9]=[CH:8][C:7]=2[C@:13]([C@@H:21]2[CH2:26][CH2:25][CH2:24][NH:23][CH2:22]2)([OH:20])[CH2:14][CH2:15][CH2:16][CH2:17][O:18][CH3:19])[CH2:3][CH2:2]1
Reactant: COCCCC[C@@](O)(c1cccc(F)c1OCC1CC1)[C@@H]1CCCN(C(=O)OC(C)(C)C)C1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COCCCC[C@@](O)(c1cccc(F)c1OCC1CC1)[C@@H]1CCCNC1
Yield: 42.5 %

Procedure:
A solution of (R)-tert-butyl 3-((S)-1-(2-(cyclopropylmethoxy)-3-fluorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxylate (120 mg) in 20% TFA/CH2Cl2 (20 mL) was stirred at 0° C. for 5 min. The solvent was neutralized by addition of sat'd aq NaHCO3, and the mixture was extracted with CH2Cl2 (3×). The combined organic layers were dried over Na2SO4 and evaporated to give the crude product. LC-MS analysis of the crude product indicated the presence of two isomers (10:1). The crude product was purified by reverse phase prep HPLC to afford the major isomer, (S)-1-(2-(cyclopropylmethoxy)-3-fluorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol (40 mg, 42%). 1H NMR (400 MHz, CD4O): 0.36 (m, 2H), 0.63 (m, 2H), 0.86 (m, 1H), 1.55-1.11 (m, 11H), 1.82 (m, 1H), 2.29 (m, 2H), 2.45 (m, 1H), 2.66 (t, 1H), 2.94 (d, 1H), 3.24 (s, 3H), 3.31(m, 2H), 3.91 (m, 2H), 6.98 (m, 2H), 726 (m, 1H). MS (E/Z): 366 (M+1). In addition, 2-fluoro-6-((S)-1-hydroxy-5-methoxy-1-((R)-piperidin-3-yl)pentyl)phenol was isolated as a byproduct.
Reaction SMILES: [NH2:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6](=[O:14])[NH:7][C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[CH:10][N:9]=3.Br[CH2:18][C:19]1[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=1[C:21]#[N:22]>>[O:14]=[C:6]1[C:5]2[CH:15]=[CH:16][C:2]([NH:1][CH2:18][C:19]3[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=3[C:21]#[N:22])=[CH:3][C:4]=2[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[NH:7]1
Reactant: N#Cc1ccccc1CBr
Reactant: Nc1ccc2c(=O)[nH]c3ncccc3c2c1
Product: N#Cc1ccccc1CNc1ccc2c(=O)[nH]c3ncccc3c2c1
Yield: 20.9 %

Procedure:
The title compound was synthesized according to the procedure described for the preparation of Example 458 using 70 (140 mg, 0.66 mmol) and 2-(bromomethyl)benzonitrile (156 mg, 0.80 mmol) to provide 462 (45 mg, 21% yield) as a white powder. LC-MS (M+H=327, obsd.=327). 1H NMR (400 MHz, DMSO-D6) δ 8.56 (dd, J=1.6, 8.0, 1H), 8.47 (dd, J=1.6, 4.7, 1H), 8.06 (d, J=8.7, 1H), 7.87 (dd, J=1.2, 7.7, 1H), 7.47 (m, 1H), 7.41 (m, 1H), 7.40 (d, J=7.7, 1H), 7.36 (dd, J=4.7, 7.9, 1H), 6.98 (d, J=7.9, 1H), 6.91 (dd, J=2.0, 8.7, 1H), 6.25 (s, 1H), 5.81 (s, 2H).
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[N:11]=[C:10]([C:12]([OH:14])=O)[CH:9]=[CH:8][C:7]=2[C:15]([F:18])([F:17])[F:16])[CH2:3][CH2:2]1.[CH3:19][C:20]([CH3:28])([C:22]1[N:26]=[C:25]([CH3:27])[O:24][N:23]=1)[NH2:21]>>[CH3:19][C:20]([NH:21][C:12]([C:10]1[CH:9]=[CH:8][C:7]([C:15]([F:18])([F:17])[F:16])=[C:6]([O:5][CH2:4][CH:1]2[CH2:2][CH2:3]2)[N:11]=1)=[O:14])([C:22]1[N:26]=[C:25]([CH3:27])[O:24][N:23]=1)[CH3:28]
Reactant: Cc1nc(C(C)(C)N)no1
Reactant: O=C(O)c1ccc(C(F)(F)F)c(OCC2CC2)n1
Product: Cc1nc(C(C)(C)NC(=O)c2ccc(C(F)(F)F)c(OCC3CC3)n2)no1

Procedure:
The title compound was synthesized in analogy to Example 1, using 6-cyclopropylmethoxy-5-trifluoromethyl-pyridine-2-carboxylic acid (Example 113 d) and α,α,5-trimethyl-1,2,4-oxadiazole-3-methanamine (CAN 1153831-97-0) as starting materials, MS (EI): m/e=385.1 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([NH:20][C:21]([N:23]2[CH2:32][CH2:31][C:30]3[CH:29]=[N:28][C:27]([NH:33][CH:34]([CH3:36])[CH3:35])=[N:26][C:25]=3[CH2:24]2)=[O:22])[CH2:10][CH2:11][NH:12]C(=O)OC(C)(C)C)[CH:5]=[CH:6][C:7]=1[Cl:8].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:12][CH2:11][CH2:10][CH:9]([NH:20][C:21]([N:23]1[CH2:32][CH2:31][C:30]2[CH:29]=[N:28][C:27]([NH:33][CH:34]([CH3:36])[CH3:35])=[N:26][C:25]=2[CH2:24]1)=[O:22])[C:4]1[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=1
Reactant: CC(C)Nc1ncc2c(n1)CN(C(=O)NC(CCNC(=O)OC(C)(C)C)c1ccc(Cl)c(Cl)c1)CC2
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)Nc1ncc2c(n1)CN(C(=O)NC(CCN)c1ccc(Cl)c(Cl)c1)CC2
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 300 (29 mg, 0.0540 mmol) in DCM (2 mL) was added TFA (1 mL, 13.0 mmol). The reaction was stirred at RT 30 min, concentrated, and partitioned between DCM (15 mL) and satd. aq. NaHCO3 (15 mL). The phases were separated and the aqueous phase extracted with DCM (15 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated. The crude product was purified on a preparative SiO2 TLC plate (0.5 mm) developed with MeOH/DCM/NH4OH (9/90/1) to afford 11 mg (47%) of I-110 as a colorless glass: 1H NMR (400 MHz, CDCl3) δ 8.07 (s, 1H), 7.63 (br s, 1H), 7.39 (d, 1H), 7.36 (d, J=8.2 Hz, 1H), 7.15 (dd, 1H), 4.97 (m, 1H), 4.83 (d, 1H), 4.38 (m, 2H), 4.10 (m, 1H), 3.70 (m, 1H), 3.60 (m, 1H), 2.89 (br s, 2H), 2.64 (t, 2H) 1.97 (m, 1H), 1.81 (m, 1H), 1.21 (d, 6H); LRMS (APCI pos) m/e=437.1 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:31])[C@H:4]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[CH2:29]O)=[CH:19][CH:18]=1)[NH:5][C:6](=[O:15])[C:7]1[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:14].C(Br)(Br)(Br)[Br:33].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:31])[C@H:4]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[CH2:29][Br:33])=[CH:19][CH:18]=1)[NH:5][C:6](=[O:15])[C:7]1[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:14]
Reactant: BrC(Br)(Br)Br
Reactant: COC(=O)[C@H](Cc1ccc(-c2ccccc2CO)cc1)NC(=O)c1c(Cl)cccc1Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COC(=O)[C@H](Cc1ccc(-c2ccccc2CBr)cc1)NC(=O)c1c(Cl)cccc1Cl
Temperature: 25 °C
Reaction time: 18 h
Yield: 70.3 %

Procedure:
A mixture of N-(2,6-dichlorobenzoyl)-4-[2-(hydroxymethyl)phenyl]-L-phenylalanine methyl ester (0.15 g), CBr4 (0.22 g) and PPh3 (0.173 g) in CH2Cl2 (5 mL) was stirred at room temperature for 18 h. The solvent was evaporated and the residue was purified by flash column chromatography (silica gel; eluent: CH2Cl2/EtOAc 9:1 to 8:1) to yield 0.12 g of N-(2,6-dichlorobenzoyl)-4-[2-(bromomethyl)phenyl]-L-phenylalanine methyl ester. ESMS: m/z 522 (MH+).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.Cl.[Cl:19][C:20]1[C:29]2[C:24](=[CH:25][C:26]([O:32][CH3:33])=[C:27]([O:30][CH3:31])[CH:28]=2)[N:23]=[CH:22][N:21]=1>>[ClH:19].[CH3:31][O:30][C:27]1[CH:28]=[C:29]2[C:24](=[CH:25][C:26]=1[O:32][CH3:33])[N:23]=[CH:22][N:21]=[C:20]2[NH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](=[O:10])(=[O:9])[NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:4][CH:3]=1
Reactant: COc1cc2ncnc(Cl)c2cc1OC
Reactant: Nc1ccc(S(=O)(=O)Nc2ccccc2)cc1
Agent: Cl
Product: COc1cc2ncnc(Nc3ccc(S(=O)(=O)Nc4ccccc4)cc3)c2cc1OC
Yield: 95 %

Procedure:
Using an analogous procedure to that described in Example 1, 4-amino-N-phenylbenzenesulphonamide was reacted with 4-chloro-6,7-dimethoxyquinazoline hydrochloride to give 6,7-dimethoxy-4-[4-(N-phenylsulphamoyl)anilino]quinazoline hydrochloride salt in 95% yield,
Reaction SMILES: [Cl-].[CH2:2]([O:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]([OH:15])=O)=[CH:8][CH:7]=1)[CH3:3].CN(C)C=O.O[NH:23][C:24](=[NH:35])[CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=1>C1C=CC=CC=1>[CH2:2]([O:4][C:5](=[O:16])[C:6]1[CH:7]=[CH:8][C:9]([CH2:12][C:13]2[O:15][N:23]=[C:24]([CH2:25][O:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[N:35]=2)=[CH:10][CH:11]=1)[CH3:3]
Reactant: COc1ccc(OCC(=N)NO)cc1
Reactant: CCOC(=O)c1ccc(CC(=O)O)cc1
Agent: [Cl-]
Solvent: CN(C)C=O
Solvent: c1ccccc1
Product: CCOC(=O)c1ccc(Cc2nc(COc3ccc(OC)cc3)no2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 31.2 %

Procedure:
Add oxaxyl chloride (1.25 mL, 14 mmol) to 4-carboxymethyl-benzoic acid ethyl ester (365 mg, 1.75 mmol) in benzene (11 mL) and a drop of dimethylformamide at room temperature under argon gas over a 5 minute period. Stir the reaction mixture for 2 hours at room temperature. Concentrate the reaction mixture to an oil. Redissolve the oil in dimethylformamide (10 mL) and N-hydroxy-2-(4-methoxy-phenoxy)-acetamidine (380 mg, 1.9 mmol) is added. Stir the reaction mixture at room temperature for 3 hours. Heat the reaction mixture to 120° C. and stir for 7 hours. After cooling to room temperature, quench the reaction mixture with water and extract with ethyl acetate (3×). Combine the organic layers, wash with brine, dry over sodium sulfate, and concentrate. Purify the residue by flash column chromatography using 20% ethyl acetate/hexane to give the title compound (201 mg, 31%). LC-MS (m/e): 369 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]([C@@H:5]1[CH2:19][C@H:18]2[C@@H:8]([CH2:9][C:10]3[C:20]4[C:13](=[CH:14][CH:15]=[CH:16][C:17]2=4)[NH:12][C:11]=3[CH:21]=[CH2:22])[N:7]([CH2:23][CH2:24][CH3:25])[CH2:6]1)=[O:4]>CO.[Pd]>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:19][C@H:18]2[C@@H:8]([CH2:9][C:10]3[C:20]4[C:13](=[CH:14][CH:15]=[CH:16][C:17]2=4)[NH:12][C:11]=3[CH2:21][CH3:22])[N:7]([CH2:23][CH2:24][CH3:25])[CH2:6]1)=[O:4]
Reactant: C=Cc1[nH]c2cccc3c2c1C[C@@H]1[C@@H]3C[C@@H](C(=O)OC)CN1CCC
Agent: [Pd]
Solvent: CO
Product: CCCN1C[C@H](C(=O)OC)C[C@@H]2c3cccc4[nH]c(CC)c(c34)C[C@H]21
Reaction time: 0.17 h

Procedure:
0.83 g of 6-n-propyl-2-vinyl-8beta-ergoline-carboxylic acid methyl ester (2.5 mmol) is dissolved in 50 ml of methanol, mixed with 80 g of palladium/carbon 10% and hydrogenated at standard pressure and room temperature. After 10 minutes, the absorption is completed, it is filtered off and the filtrate is concentrated by evaporation. The residue is crystallized, yield of 800 mg (94% of theory) [α]D =-63° (0.1% in chloroform).
Reaction SMILES: [N:1]1[C:9]([NH:10][C@H:11]([C:13]2[N:14]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:15](=[O:24])[C:16]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[CH:18][C:17]=3Cl)[CH3:12])=[C:8]2[C:4]([NH:5][CH:6]=[N:7]2)=[N:3][CH:2]=1.[NH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1>O1CCOCC1>[N:1]1[C:9]([NH:10][C@H:11]([C:13]2[N:14]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:15](=[O:24])[C:16]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[CH:18][C:17]=3[N:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)[CH3:12])=[C:8]2[C:4]([NH:5][CH:6]=[N:7]2)=[N:3][CH:2]=1
Reactant: C1CCNC1
Reactant: C[C@H](Nc1ncnc2[nH]cnc12)c1cc2cccc(Cl)c2c(=O)n1-c1ccccc1
Solvent: C1COCCO1
Product: C[C@H](Nc1ncnc2[nH]cnc12)c1cc2cccc(N3CCCC3)c2c(=O)n1-c1ccccc1
Temperature: 135 °C
Reaction time: 17 h

Procedure:
To a solution of (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one (3) (100 mg, 0.24 mmol) in 1,4-dioxane (3 mL) in a sealed tube, pyrrolidine (1.25 mL, excess amount) was added and the resulting mixture was stirred at 135° C. for 17 h. The mixture was allowed to cool to RT, partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by ISCO (silica gel cartridge, 0-10% MeOH-DCM) to afford the product, (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-2-phenyl-8-(pyrrolidin-1-yl)isoquinolin-1(2H)-one (4) as an off-white solid. ESI-MS m/z: 452.2 [M+H]+.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]=[CH:10][CH:9]=1)(C)(C)C.[OH-].[Na+]>Cl.O>[NH2:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]=[CH:10][CH:9]=1
Reactant: CC(C)(C)OC(=O)Nc1ccnc2ccccc12
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Nc1ccnc2ccccc12
Yield: 87.7 %

Procedure:
A solution of quinolin-4-yl carbamic acid tert butyl ester (16.8 g) in 5N HCl (200 ml) was boiled for 5 h. The reaction mixture was diluted with water made basic with sodium hydroxide and washed with dichloromethane. The aqueous phase was separated and evaporated to dryness at reduced pressure. The residue was dissolved in propan-1-ol, insoluble material separated by filtration and the filtrate evaporated to dryness. The residue was dissolved in dichloromethane/ethyl acetate, filtered to remove insoluble inorganic salts and solvent removed at reduced pressure to give 4-aminoquinoline (8.7 g).
Reaction SMILES: C/C=C(/C(N[C@H]([C@@H](O)C([O:18][C@@H:19]1[C:40]([CH3:41])=[C:39]2[C:42]([CH3:44])([CH3:43])[C@:21]([OH:59])([C@@H:22]([O:50][C:51]([C:53]3[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=3)=[O:52])[C@@H:23]3[C@:28]4([O:31][C:32]([CH3:34])=[O:33])[CH2:29][O:30][C@@H:27]4[CH2:26][C@H:25]([OH:35])[C@@:24]3([CH3:49])[C:36]([C@@H:38]2[O:45][C:46]([CH3:48])=[O:47])=[O:37])[CH2:20]1)=O)C1C=CC=CC=1)=O)\C.CC1[C@@H](OC([C@H](O)[C@@H](NC(C2C=CC=CC=2)=O)C2C=CC=CC=2)=O)C[C@]2(O)C(C)(C)C=1[C@@H](OC(C)=O)C([C@@]1(C)[C@H]([C@@H]2OC(C2C=CC=CC=2)=O)[C@]2(OC(C)=O)CO[C@@H]2C[C@@H]1O)=O>>[CH3:41][C:40]1[C@@H:19]([OH:18])[CH2:20][C@:21]2([OH:59])[C:42]([CH3:43])([CH3:44])[C:39]=1[C@@H:38]([O:45][C:46]([CH3:48])=[O:47])[C:36]([C@@:24]1([CH3:49])[C@H:23]([C@@H:22]2[O:50][C:51]([C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=2)=[O:52])[C@:28]2([O:31][C:32]([CH3:34])=[O:33])[CH2:29][O:30][C@@H:27]2[CH2:26][C@@H:25]1[OH:35])=[O:37]
Reactant: C/C=C(\C)C(=O)N[C@@H](c1ccccc1)[C@@H](O)C(=O)O[C@H]1C[C@@]2(O)[C@@H](OC(=O)c3ccccc3)[C@@H]3[C@]4(OC(C)=O)CO[C@@H]4C[C@H](O)[C@@]3(C)C(=O)[C@H](OC(C)=O)C(=C1C)C2(C)C
Agent: CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)c4ccccc4)c4ccccc4)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O
Product: CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](O)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O

Procedure:
In the third embodiment, the addition of 10% tin chloride (based on the taxol in the starting material) to tetrabutylammonium borohydride in dichloromethane at 0° C. for one hour resulted in a 121.7% yield of Baccatin III. It would appear material other then just the cephalomannine and taxol in the starting material was cleaved to produce Baccatin III. It is hypothesized that certain taxol compounds may be bound to sugars and other biological material and that these may have been converted to Baccatin III in this process.
Reaction SMILES: [C:1]1([C:7]2[N:11]=[C:10]([N:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[S:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH3:25][C:26]1[CH:27]=[C:28]([N:32]=[C:33]=[O:34])[CH:29]=[CH:30][CH:31]=1>O1CCCC1>[CH3:25][C:26]1[CH:27]=[C:28]([NH:32][C:33]([N:15]2[CH2:16][CH2:17][N:12]([C:10]3[S:9][N:8]=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[N:11]=3)[CH2:13][CH2:14]2)=[O:34])[CH:29]=[CH:30][CH:31]=1
Reactant: c1ccc(-c2nsc(N3CCNCC3)n2)cc1
Reactant: Cc1cccc(N=C=O)c1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1cccc(NC(=O)N2CCN(c3nc(-c4ccccc4)ns3)CC2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 38.9 %

Procedure:
To a solution of 1-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine (200 mg, 0.812 mmol) and triethylamine (0.113 ml, 0.812 mmol) in tetrahydrofuran (2 ml) was added 3-methylphenyl isocyanate (0.152 ml, 1.22 mmol) at room temperature, and the mixture was stirred at room temperature for 1 hour. The solvent was distilled off under reduced pressure, and the residue was recrystallized from a mixed solvent of hexane and tetrahydrofuran to give 120 mg (38.8%) of the desired product as a solid.