Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]([N:11]1[C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[Li]CCCC.[C:25](Cl)(=[O:29])[O:26][CH2:27][CH3:28].Cl>C1COCC1.O>[S:1]([N:11]1[C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[CH:13]=[C:12]1[C:25]([O:26][CH2:27][CH3:28])=[O:29])([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2]
Reactant: CCOC(=O)Cl
Reactant: Cc1ccc(S(=O)(=O)n2ccc3cnccc32)cc1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)c1cc2cnccc2n1S(=O)(=O)c1ccc(C)cc1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
A solution of compound 6-b (10 g, 367 mmol) in dry THF (150 mL) was cooled to −70° C. and n-BuLi (CAS 109-72-8) (2.5 M in hexane, 16.7 mL, 41.9 mmol) was added dropwise under N2. The mixture was stirred at −78° C. for 1 hour and then ethyl carbonochloridate (CAS 541-41-3) (fresh redistilled, 4.2 mL, 44 mmol) was added dropwise at −70° C. The mixture was warmed to 20° C. naturally and stirred at 20° C. for 1 hour. Then water (800 mL) was added. The mixture was acidified to pH=4 to 5 with a 1N HCl aqueous solution and extracted with ethyl acetate (400 mL×2). Then the pH of the aqueous layer was adjusted to pH=8 by addition of NaHCO3. The resulting mixture was extracted with ethyl acetate (200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and evaporated. The residue was washed with tert-butylmethyl ether. The solid was dried under high vacuum. The residue was purified by flash column chromatography, eluting with petroleum ether/ethyl acetate (3:2). After evaporation of the fractions, 6-c is obtained (6 g, 47%).
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([Cl:11])[N:10]=1)[C:5]([OH:7])=[O:6].[CH:12]([NH:15][CH3:16])([CH3:14])[CH3:13]>O>[Cl:11][C:9]1[CH:8]=[C:4]([CH:3]=[C:2]([N:15]([CH:12]([CH3:14])[CH3:13])[CH3:16])[N:10]=1)[C:5]([OH:7])=[O:6]
Reactant: CNC(C)C
Reactant: O=C(O)c1cc(Cl)nc(Cl)c1
Solvent: O
Product: CC(C)N(C)c1cc(C(=O)O)cc(Cl)n1
Temperature: 80 °C
Reaction time: 240 h
Yield: 67.6 %

Procedure:
A mixture of 2,6-dichloro-isonicotinic acid (572 mg, 2.98 mmol) in isopropyl-methylamine (2.18 g, 29.8 mmol) is stirred at 80° C. for 10 days. The mixture is cooled to rt, diluted with water (50 mL), and extracted with diethyl ether (6×50 mL). The aq. phase is acidified and extracted with diethyl ether (3×50 mL). The org. extracts are combined, dried over MgSO4, filtered and concentrated. The crude product is purified by MPLC on silica gel eluting with a gradient of EA in heptane to give the title compound (461 mg) as a yellow powder; LC-MS: tR=0.92 min, [M+1]+=229.01; 1H NMR (CD3OD): δ 1.19 (d, J=6.7 Hz, 6H), 2.88 (s, 3H), 4.78-4.87 (m, 1H), 6.94 (s, 1H), 7.01 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=3[F:20])=[CH:11][C:10]([C:21]([O:23]CC)=[O:22])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[OH-].[K+].Cl>CO>[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=3[F:20])=[CH:11][C:10]([C:21]([OH:23])=[O:22])=[N:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1cc(-c2cccc(F)c2F)n(-c2cccc(Cl)c2)n1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1cc(-c2cccc(F)c2F)n(-c2cccc(Cl)c2)n1

Procedure:
0.21 g (0.526 mmol) of the compound of Example 38A are provided in 3.5 ml of methanol and, at room temperature, 295 mg (5.26 mmol) of potassium hydroxide are added. The mixture is heated under reflux for 5 min, a 1N aqueous hydrogen chloride solution is subsequently added until the pH is 5, and the resulting precipitate is collected by suction filtration, washed with diethyl ether and dried under high vacuum. 145 mg (82% of theory) of the title compound are obtained.
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[C:7]([CH:13]=[CH:14][CH:15]=1)[O:8][CH2:9][CH2:10][CH2:11][NH2:12])[CH3:3].[NH2:16][C:17]1[C:20](=[O:21])[C:19](=[O:22])[C:18]=1OC>CO>[NH2:16][C:17]1[C:20](=[O:21])[C:19](=[O:22])[C:18]=1[NH:12][CH2:11][CH2:10][CH2:9][O:8][C:7]1[CH:13]=[CH:14][CH:15]=[C:5]([CH2:4][N:2]([CH3:3])[CH3:1])[CH:6]=1
Reactant: CN(C)Cc1cccc(OCCCN)c1
Reactant: COc1c(N)c(=O)c1=O
Solvent: CO
Product: CN(C)Cc1cccc(OCCCNc2c(N)c(=O)c2=O)c1
Yield: 94.9 %

Procedure:
A mixture of 3-(3-dimethylaminomethylphenoxy)propylamine (1.41 g; 6.77 mmoles) [prepared according to the procedure described in Belgian Patent No. 867,106]and 1-amino-2-methoxycyclobutene-3,4-dione (0.86 g; 6.77 mmoles) in 40 mL of methanol was stirred at ambient temperature for 20 hours and then filtered to give 1.95 g of the title compound.
Reaction SMILES: [N:1]([C@@H:4]1[C@@H:8]([CH2:9][OH:10])[O:7][C@@H:6]([N:11]2[CH:18]=[C:17]([CH2:19][CH3:20])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:5]1)=[N+]=[N-]>[Pd]>[NH2:1][C@@H:4]1[C@@H:8]([CH2:9][OH:10])[O:7][C@@H:6]([N:11]2[CH:18]=[C:17]([CH2:19][CH3:20])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:5]1
Reactant: CCc1cn([C@H]2C[C@H](N=[N+]=[N-])[C@@H](CO)O2)c(=O)[nH]c1=O
Agent: [Pd]
Product: CCc1cn([C@H]2C[C@H](N)[C@@H](CO)O2)c(=O)[nH]c1=O
Yield: 87.9 %

Procedure:
An aqueous solution (15 ml) of 3'-azido-5-ethyl-2',3'-dideoxyuridine (376 mg) is hydrogenated with 10% Pd/C (100 mg) at room temperature under 1 atmosphere for one hour. The mixture is filtered through a celite pad, evaporated down to ca. 2 ml, and then freeze-dried to obtain a foam (300 mg, 88%).
Reaction SMILES: [C:1]1([CH:7]([CH3:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.S(=O)(=O)(O)O.[C:16]1([OH:22])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CC(C)=O>[C:7]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[OH:22])([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)([CH3:9])[CH3:8]
Reactant: Oc1ccccc1
Reactant: CC(C)c1ccccc1
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(C)=O
Product: CC(C)(c1ccccc1)c1ccccc1O

Procedure:
A stock solution containing 6 wt% DCP, 15 wt% cumene, 1 wt% water and 50 ppm sulfuric acid with the balance composed of equimolar phenol and acetone was distributed among several melting point capillary tubes which were subsequently sealed and heated for various lengths of time in a stirred oil bath. The tubes were then quickly cooled by immersion in an ice bath and the contents were analyzed by gas chromatography. The amount of AMS formed increased with time up to a maximum yield and then declined as increased amounts of AMS dimers and cumylphenol were formed. Table IV records the maximum AMS yield obtained at each temperature as well as the heating time required to reach that yield. It is clear from the data of Table IV that best yields of AMS are obtained at temperatures over 100° C., e.g., 120° to 150° C.
Reaction SMILES: [Cl:1][C:2]1[C:9]([CH3:10])=[C:8]([N:11]2[CH:15]([CH3:16])[C:14](=[O:17])[C:13]([CH3:19])([CH3:18])[C:12]2=[O:20])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C([BH-](C(CC)C)C(CC)C)(CC)C.[Li+].C1COCC1>>[Cl:1][C:2]1[C:9]([CH3:10])=[C:8]([N:11]2[C@H:15]([CH3:16])[C@H:14]([OH:17])[C:13]([CH3:19])([CH3:18])[C:12]2=[O:20])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]
Reactant: Cc1c(N2C(=O)C(C)(C)C(=O)C2C)ccc(C#N)c1Cl
Agent: CCC(C)[BH-](C(C)CC)C(C)CC
Agent: [Li+]
Solvent: C1CCOC1
Product: Cc1c(N2C(=O)C(C)(C)[C@@H](O)[C@H]2C)ccc(C#N)c1Cl

Procedure:
Using 2-chloro-3-methyl-4-(3,3,5-trimethyl-2,4-dioxopyrrolidin-1-yl)benzonitrile (23 mg) and lithium tri(sec-butyl)borohydride-THF solution (0.119 mL, 1 mol/L), and in the same manner as in Example 5, the title compound was obtained as a colorless solid (yield: 15 mg, 66%).
Reaction SMILES: [CH3:1][C:2]1[C:10]([C:11]2[S:12][C:13]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[C:14](OS(C(F)(F)F)(=O)=O)[N:15]=2)=[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[C:29]1(B2OC(C)(C)C(C)(C)O2)[CH2:34][CH2:33][CH2:32][CH2:31][CH:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>COCCOC>[C:29]1([C:14]2[N:15]=[C:11]([C:10]3[C:2]([CH3:1])=[N:3][N:4]4[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=34)[S:12][C:13]=2[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:34][CH2:33][CH2:32][CH2:31][CH:30]=1
Reactant: CCOC(=O)c1sc(-c2c(C)nn3ccccc23)nc1OS(=O)(=O)C(F)(F)F
Reactant: CC1(C)OB(C2=CCCCC2)OC1(C)C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: COCCOC
Solvent: O
Product: CCOC(=O)c1sc(-c2c(C)nn3ccccc23)nc1C1=CCCCC1
Yield: 95.8 %

Procedure:
Using ethyl 2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-4-{[(trifluoromethyl)sulfonyl]oxy}-1,3-thiazole-5-carboxylate (220 mg, 0.5 mmol) produced in Example 15(i), 2-cyclohex-1-en-1-yl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (620 mg, 3.0 mmol), [1,1-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane complex (72 mg, 0.088 mmol), cesium carbonate (620 mg, 1.9 mmol), water (0.5 mL) and 1,2-dimethoxyethane (15 mL) as starting materials and in the same manner as in Example 13(iii), the title compound (176 mg, 95%) was obtained as a yellow solid.
Reaction SMILES: C1(C)C=CC=CC=1.[CH3:8][S:9]([O:12][CH2:13][CH:14]([C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=1)[O:15]C1CCCCO1)(=[O:11])=[O:10].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH3:8][S:9]([O:12][CH2:13][C@@H:14]([C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=1)[OH:15])(=[O:10])=[O:11]
Reactant: CS(=O)(=O)OCC(OC1CCCCO1)c1ccc(Cl)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Solvent: Cc1ccccc1
Product: CS(=O)(=O)OC[C@H](O)c1ccc(Cl)cc1
Temperature: 50 °C
Reaction time: 1 h

Procedure:
Into toluene (10 ml) were added 2-(4-chlorophenyl)-2-(3,4,5,6-tetrahydro-[2H]-pyran-2-yloxy)ethyl methanesulfonate (3.0 g), p-toluenesulfonic acid monohydrate (1.7 g) and methanol (0.5 g), and the resulting mixture was stirred at 50° C. for 1 hour. The reaction mixture was washed with a saturated aqueous sodium hydrogen carbonate solution, then with a saturated aqueous sodium chloride solution, and dried with anhydrous magnesium sulfate. The desiccant was filtered off and then the solvent was distilled off under reduced pressure to obtain a colorless oily compound mentioned above (2.0 g, 89.0%).
Reaction SMILES: O1CCBN1.B.C1COCC1.[Cl:12][C:13]1[CH:14]=[C:15]([C:20](=[O:22])[CH3:21])[CH:16]=[C:17]([F:19])[CH:18]=1>O1CCCC1>[Cl:12][C:13]1[CH:14]=[C:15]([C@@H:20]([OH:22])[CH3:21])[CH:16]=[C:17]([F:19])[CH:18]=1
Reactant: CC(=O)c1cc(F)cc(Cl)c1
Agent: B
Agent: B1CCON1
Solvent: C1CCOC1
Product: C[C@H](O)c1cc(F)cc(Cl)c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 89 %

Procedure:
To a stirred solution of (R)-MeCBS oxazaborolidine (2.9 ml, 1M solution in toluene) in dry tetrahydrofuran (5 ml) was added dropwise borane-THF complex (17.4 ml, 1M solution in tetrahydrofuran) under an argon atmosphere. The solution was cooled to 0° C. and 3′-chloro-5′-fluoroacetophenone (5.0 g) dissolved in dry tetrahydrofuran (5 ml) was added dropwise to the reaction mixture in 40 min. The reaction mixture was stirred for 1 h at 0° C. and was slowly quenched with methanol (5 ml) followed by addition of HCl 4M in ethanol (1 ml). After stirring the mixture for 5 min at 0° C., the cooling bath was removed and the white suspension was stirred at room temperature for 30 min. The suspension was filtered over celite and the filtrate was evaporated over silica gel for purification. Column chromatography (SiO2; heptane/EtOAc) afforded (S)-1-(3-chloro-5-fluoro-phenyl)-ethanol (4.50 g, 89%) as a colourless liquid. 1H NMR (300 MHz, CDCl3, δ): 1.48 (d, J=6.3 Hz, 3H), 1.92 (bs, 1H), 4.87 (q, J=6.6 Hz), 6.98 (m, 2H), 7.16 (s, 1H).
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:20])[C:7]([C:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=3)([CH3:12])[CH2:8][O:9]2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:23][O:24][CH2:25]Cl.O>CN(C)C=O>[OH:19][C:16]1[CH:17]=[CH:18][C:13]([C:7]2([CH3:12])[C:6](=[O:20])[C:5]3[C:10](=[CH:11][C:2]([O:1][CH2:23][O:24][CH3:25])=[CH:3][CH:4]=3)[O:9][CH2:8]2)=[CH:14][CH:15]=1
Reactant: COCCl
Reactant: CC1(c2ccc(O)cc2)COc2cc(O)ccc2C1=O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COCOc1ccc2c(c1)OCC(C)(c1ccc(O)cc1)C2=O
Reaction time: 0.5 h
Yield: 65.7 %

Procedure:
To a solution of 7-hydroxyl-3-(4-hydroxyphenyl)-3-methylchroman-4-one (4.65 g, 17.20 mmol) in dry dimethylformamide (120 ml) was added sodium hydride (454 mg, 18.92 mmol) at room tempetarure and stirred for 30 minutes. To the reaction mixture was then added methoxymethyl chloride (1.523 g, 18.92 mmol) at the same temperature and stirred for 2 h. When the reaction was completed, water was added to the reaction solution which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified with column chromatography (n-hexane:ethyl acetate=8:2 to 7:3) to give 3.55 g (yield: 66%) of the title compound as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:3]=1[C:4]([OH:6])=[O:5].[F-].[K+].[CH3:14][N:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]([CH3:24])=[C:16]1[C:25]([NH:27][C@H:28]([C:32]([NH:34][CH:35]([C:44](=[O:47])[CH2:45]Br)[CH2:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[O:33])[CH:29]([CH3:31])[CH3:30])=[O:26]>>[CH3:14][N:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]([CH3:24])=[C:16]1[C:25]([NH:27][C@H:28]([C:32]([NH:34][CH:35]([C:44](=[O:47])[CH2:45][O:5][C:4](=[O:6])[C:3]1[C:2]([Cl:1])=[CH:10][CH:9]=[CH:8][C:7]=1[Cl:11])[CH2:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[O:33])[CH:29]([CH3:31])[CH3:30])=[O:26]
Reactant: Cc1c(C(=O)N[C@H](C(=O)NC(CC(=O)OC(C)(C)C)C(=O)CBr)C(C)C)n(C)c2ccccc12
Reactant: O=C(O)c1c(Cl)cccc1Cl
Agent: [F-]
Agent: [K+]
Product: Cc1c(C(=O)N[C@H](C(=O)NC(CC(=O)OC(C)(C)C)C(=O)COC(=O)c2c(Cl)cccc2Cl)C(C)C)n(C)c2ccccc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 78.9 %

Procedure:
To a mixture of 2,6-dichlorobenzoic acid (0.023 g, 0.12 mmol) and potassium fluoride (0.015 g, 0.25 mmol) at room temperature under nitrogen was added N-[(1,3-dimethyl-indole-2-carbonyl)valinyl]-3-amino-5-bromo-4-oxo-pentanoic acid, tert-butyl ester (0.054 g, 0.10 mmol) in one portion. After stirring at room temperature for further 16 hrs, the mixture was partitioned between ethyl acetate and water. The organic layer was washed with water, saturated NaHCO3 solution, and brine, dried over sodium sulfate, and concentrated. Trituration with ether gave the title compound as a white powder (0.051 g, 79%). TLC(CH2Cl2/MeOH, 95/5): Rf=0.88.
Reaction SMILES: Cl[C:2]1[N:7]=[N:6][C:5]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([NH:14][CH3:15])=[O:13])=[C:10]([F:18])[CH:9]=2)=[CH:4][CH:3]=1.O.[NH2:20][NH2:21]>N1C=CC=CC=1>[F:18][C:10]1[CH:9]=[C:8]([C:5]2[N:6]=[N:7][C:2]([NH:20][NH2:21])=[CH:3][CH:4]=2)[CH:17]=[CH:16][C:11]=1[C:12]([NH:14][CH3:15])=[O:13]
Reactant: CNC(=O)c1ccc(-c2ccc(Cl)nn2)cc1F
Reactant: NN
Solvent: c1ccncc1
Solvent: O
Product: CNC(=O)c1ccc(-c2ccc(NN)nn2)cc1F
Temperature: 65 °C
Reaction time: 8 h
Yield: 84 %

Procedure:
A solution of 4-(6-chloro-pyridazin-3-yl)-2-fluoro-N-methyl-benzamide 34 g (128 mmol) in 500 mL of dry pyridine was cooled in an ice bath and 43.5 mL of hydrazine hydrate was added. The cooling was continued so as to keep the temperature below 30° C. at which time yellow needle separated. The mixture was then heated to 65° C. and stirred overnight. The mixture was filtered and the solid washed with water and Methanol to return the title compound (28.8 g, 84% yield) as a light yellow solid. 1H NMR (300 MHz, DMSO-d6): δ (ppm): 8.27 (s, 2H), 7.96˜7.99 (d, 1H), 7.86˜7.92 (m, 2H), 7.69˜7.75 (m, 1H), 7.09˜7.12 (d, 1H), 4.42 (s, 2H), 2.78˜2.80 (d, 3H); MS (m/z): 262.1 [M++1].
Reaction SMILES: [C:1]([C@:5]1(N)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]1[C@H:11](O)[CH3:12])([CH3:4])(C)C.C1CC(=[O:24])C2C(=CC=CC=2)C1>C1COCC1>[CH2:12]1[CH:4]([OH:24])[CH2:1][C:5]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:11]1
Reactant: O=C1CCCc2ccccc21
Reactant: C[C@@H](O)C1C=CC=C[C@@]1(N)C(C)(C)C
Solvent: C1CCOC1
Product: OC1CCc2ccccc2C1
Temperature: 0 °C
Reaction time: 16 h
Yield: 915.3 %

Procedure:
Borane methylsulfide complex (neat, ~10M, 0.44 mL, 4.4 mmol) was added to a solution of (1R, 2S)-2-tert-butyl-2-aminophenylethanol [Angew. Chem. Int. Ed. Engl. 26 1141 (1987)] (120 mg, 0.62 mmol) in THF (22 mL) at ambient temperature and stirred for 16 hrs; α-Tetralone (906 mg, 6.2 mmol) as a solution in THF (3 mL) was added to the preceding solution over a 1 hr, stirred for 15 min after addition was completed, cooled to 0° C., and quenched with methanol (20 mL). After stirring the quenched reaction for 18 hrs, the solvents were removed under vacuum, the residual oil was dissolved in methylene chloride (30 mL), washed with pH 4 phosphate buffer (30 mL), water (30 mL), treated with magnesium sulfate, and the solvent was removed under vacuum to give the (R) tetralol 841 mg (91% yield) 82% ee.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9]([NH:12][C:13]2[CH:14]=[C:15]([CH:25]=[CH:26][C:27]=2[O:28][CH3:29])[C:16]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=O)(=[O:11])=[O:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:39])=CC=1>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([NH:12][C:13]2[CH:14]=[C:15]([CH:25]=[CH:26][C:27]=2[O:28][CH3:29])[C:16]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[S:39])(=[O:11])=[O:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: COc1ccc(C(=O)Nc2ccccc2)cc1NS(=O)(=O)c1cc(Cl)cc(Cl)c1
Solvent: C1CCOC1
Product: COc1ccc(C(=S)Nc2ccccc2)cc1NS(=O)(=O)c1cc(Cl)cc(Cl)c1
Temperature: 50 °C
Reaction time: 8 h
Yield: 81.8 %

Procedure:
A mixture of 3-(3,5-dichloro-benzenesulfonylamino)-4-methoxy-N-phenyl-benzamide from Example 118 (3.61 g, 8.0 mmol) and Lawesson's reagent (3.57 g, 8.8 mmol) was stirred at room temperature overnight in tetrahydro-furan (250 mL). The reaction mixture was warmed to 50° C. for about one hour, then to 65° C. for about 4 hours then stirred at room temperature overnight. The mixture was concentrated to dryness and the residue dissolved in ethyl acetate and filtered through silica gel. Concentration of the eluant followed by trituration in hexanes/ethyl acetate (1:1) afforded the crude product (3.06 g). A portion (0.8 g) of this was chromatographed on silica gel in hexanes/ethyl acetate (1:1) to afford a pure sample (0.324 g); m.p. 206-208° C.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]2[NH:8][CH:9]=[CH:10][C:5]2=[C:4]([N+]([O-])=O)[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].S(S([O-])=O)([O-])=O.[Na+].[Na+].Cl.[NH2:29][C:30]1[CH:35]=[C:34]([F:36])[C:33]([OH:37])=[C:32]([F:38])[CH:31]=1>CS(C)=O.C(OCC)(=O)C>[Cl:1][C:2]1[N:7]=[C:6]2[NH:8][CH:9]=[CH:10][C:5]2=[C:4]([O:37][C:33]2[C:34]([F:36])=[CH:35][C:30]([NH2:29])=[CH:31][C:32]=2[F:38])[CH:3]=1
Reactant: O=[N+]([O-])c1cc(Cl)nc2[nH]ccc12
Reactant: Nc1cc(F)c(O)c(F)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: O=S([O-])S(=O)[O-]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: Nc1cc(F)c(Oc2cc(Cl)nc3[nH]ccc23)c(F)c1
Temperature: 120 °C

Procedure:
664 mg (3.36 mmol) of 6-chloro-4-nitro-1H-pyrrolo[2,3-b]pyridine (from example XXX), 1.39 g (10.1 mmol) of powdered potassium carbonate and 877 mg (5.04 mmol) of sodium dithionite are suspended in 10 ml of DMSO. The mixture is degassed, and 915 mg (5.04 mmol) of 4-amino-2,6-difluorophenol hydrochloride (from example XXXII) are added. The mixture is heated at 120° C. for 4 hours. After addition of ethyl acetate, the mixture is filtered off with suction through CELITE (diatomaceous earth) and the filtercake is washed with ethyl acetate. The filtrate is extracted three times with sat. sodium bicarbonate solution and with sat. sodium chloride solution. The filtrate is dried over sodium sulfate and the solvent is removed under reduced pressure. The residue is purified by column chromatography (silical gel 60, mobile phase: DCM:methanol=50:1).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][NH:2]1.Br[CH2:8][C:9]([NH:11][C:12]1[C:29]([OH:30])=[C:28]2[C:15]([CH2:16][CH:17]3[C:26]([C:27]2=[O:31])=[C:25]([OH:32])[C:24]2([OH:33])[CH:19]([CH:20]([N:39]([CH3:41])[CH3:40])[C:21]([OH:38])=[C:22]([C:35]([NH2:37])=[O:36])[C:23]2=[O:34])[CH2:18]3)=[C:14]([N:42]([CH3:44])[CH3:43])[CH:13]=1)=[O:10]>CN1C(=O)N(C)CCC1.C(#N)C>[CH3:41][N:39]([CH3:40])[C@H:20]1[C@H:19]2[C@:24]([OH:33])([C:25]([OH:32])=[C:26]3[C@H:17]([CH2:18]2)[CH2:16][C:15]2[C:28](=[C:29]([OH:30])[C:12]([NH:11][C:9](=[O:10])[CH2:8][N:2]4[CH2:3][CH2:4][CH2:5][CH2:6][O:1]4)=[CH:13][C:14]=2[N:42]([CH3:43])[CH3:44])[C:27]3=[O:31])[C:23](=[O:34])[C:22]([C:35]([NH2:37])=[O:36])=[C:21]1[OH:38]
Reactant: C1CCONC1
Reactant: CN(C)c1cc(NC(=O)CBr)c(O)c2c1CC1CC3C(N(C)C)C(O)=C(C(N)=O)C(=O)C3(O)C(O)=C1C2=O
Solvent: CN1CCCN(C)C1=O
Solvent: CC#N
Product: CN(C)c1cc(NC(=O)CN2CCCCO2)c(O)c2c1C[C@H]1C[C@H]3[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]3(O)C(O)=C1C2=O
Yield: 39.6 %

Procedure:
The compound of the example is prepared by the procedure of Example 1 using 2 g of [1,2]oxazinane, and 0.5 g of 9-(2-bromo-acetylamino)-4,7-bis-dimethylamino-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-naphthacene-2-carboxylic acid amide in 8 ml DMPU and 2 ml acetonitrile to give 0.2 g of the product.
Reaction SMILES: Cl.[CH2:2]([O:9][NH2:10])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[OH-].[Na+].[CH3:13][N:14]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:15](Cl)=[O:16]>O.C(OCC)C.C(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>[CH2:2]([O:9][NH:10][C:15]([N:14]([CH3:13])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:16])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CN(C(=O)Cl)c1ccccc1
Reactant: NOCc1ccccc1
Agent: Cl
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CCOCC
Product: CN(C(=O)NOCc1ccccc1)c1ccccc1
Yield: 64.3 %

Procedure:
O-Benzylhydroxylamine hydrochloride (3.0 g, 18.8 mmole) was dissolved in water (3.5 mL) then combined with diethyl ether (85 mL) followed by the addition of sodium hydroxide (0.75 g, 18.8 mmole) in water. After several minutes a solution of N-methyl-N-phenylcarbamoyl chloride (3.19 g, 18.8 mmole) in diethyl ether (25 mL) was added. A white precipitate formed. The solid was isolated by filtration then dissolved in water. The solution was diluted with saturated aqueous sodium bicarbonate and sufficient solid sodium carbonate was added to bring the pH to 9. The solution was extracted with diethyl ether (5×50 mL). The ether extracts were combined, dried and then concentrated to provide the crude product as a beige solid. The crude product was purified by silica gel chromatography (9:1 hexanes/ethyl acetate) to provide 3.1 g of 1-benzyloxy-3-methyl-3-phenylurea.