Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C@@H:1]12[CH2:7][N:6](C(OC(C)(C)C)=O)[C@@H:5]1[CH2:4][N:3]([C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])[CH2:2]2.FC(F)(F)C(O)=O>C(Cl)Cl>[C@@H:1]12[CH2:7][NH:6][C@@H:5]1[CH2:4][N:3]([C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])[CH2:2]2
Reactant: CC(C)(C)OC(=O)N1C[C@H]2CN(C(=O)OCc3ccccc3)C[C@H]21
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C(OCc1ccccc1)N1C[C@@H]2CN[C@@H]2C1
Yield: 39.8 %

Procedure:
The product of Example 38I (1.0 g, 6.92 mmol) in CH2Cl2 (5 mL) was treated with trifluoroacetic acid (5 mL) at room temperature for 1 hour. The mixture was concentrated and the residue was diluted with CHCl3 (50 mL). The brown chloroform solution was washed with saturated aqueous NaHCO3 (2×20 mL, pH=8-9) and brine (5 mL), dried (MgSO4), filtered, and the filtrate concentrated to provide the title compound as a brown oil (0.64 g, 97% yield) which was used in the next step without purification. 1H NMR (MeOH-d4, 300 MHz) δ 3.30-3.16 (m, 3H), 3.36 (m, 1H), 3.80 (m, 3H), 4.45 (dd, J=6.4 Hz, 4.8 Hz, 1H), 5.16 (s, 2H), 7.36 (m, 5H); MS (DCI/NH3) m/z 250 (M+NH4)+. 233 (M+H)+.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:14](=O)[CH3:15])[C:11](=[O:13])[CH3:12])=[CH:6][CH:5]=1)([O-:3])=[O:2].Cl.NO.[N:20]1C=CC=CC=1>C(O)C>[CH3:15][C:14]1[C:10]([C:7]2[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)=[C:11]([CH3:12])[O:13][N:20]=1
Reactant: c1ccncc1
Reactant: CC(=O)C(C(C)=O)c1ccc([N+](=O)[O-])cc1
Agent: Cl
Agent: NO
Solvent: CCO
Product: Cc1noc(C)c1-c1ccc([N+](=O)[O-])cc1
Yield: 91.7 %

Procedure:
A mixture of 3-(4-nitrophenyl)-pentane-2,4-dione (50 mg, 0.22 mmol), hydroxylamine hydrochloride (15 mg, 0.22 mmol) and pyridine (17 mg, 0.22 mmol) in ethanol (10 ml) was heated to reflux overnight. Evaporation of the solvent gave a residue which was partitioned between water and ethyl acetate. The organic layer was separated, washed with water, then brine and dried. Evaporation to dryness yielded 3,5-dimethyl-4-(4-nitrophenyl)-isoxazole (44 mg, 90%) as solid.
Reaction SMILES: [CH3:1][NH:2][C:3]([NH:5][CH2:6][CH2:7][CH2:8][C@:9]([C@@H:18]1[CH2:23][CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19]1)([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=1)[OH:10])=[O:4].Cl>CC#N>[Cl:17][C:13]1[CH:12]=[C:11]([C@@:9]([OH:10])([C@@H:18]2[CH2:23][CH2:22][CH2:21][NH:20][CH2:19]2)[CH2:8][CH2:7][CH2:6][NH:5][C:3]([NH:2][CH3:1])=[O:4])[CH:16]=[CH:15][CH:14]=1
Reactant: CNC(=O)NCCC[C@@](O)(c1cccc(Cl)c1)[C@@H]1CCCN(C(=O)OC(C)(C)C)C1
Agent: Cl
Solvent: CC#N
Product: CNC(=O)NCCC[C@@](O)(c1cccc(Cl)c1)[C@@H]1CCCNC1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A mixture of (R)-tert-butyl 3-((S)-4-(methylaminocarbonylamino)-1-(3-chlorophenyl)-1-hydroxybutyl)piperidine-1-carboxylate, CH3CN (20 mL) and 2 N aq HCl (15 mL) was vigorously stirred at rt for 2 d. The solvents were removed in vacuo to give the HCl salt of 1-((S)-4-(3-chlorophenyl)-4-hydroxy-4-((R)-piperidin-3-yl)butyl)-3-methylurea, which was used without further purification. LC-MS (3 min) tR=0.93 min, m/z 342, 340 (M+H+).
Reaction SMILES: [C:1]1([CH:7]([NH2:14])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[CH2:16][C:17]([NH2:19])=[O:18].C(=O)(O)[O-].[Na+]>C(O)C>[C:1]1([CH:7]([NH:14][CH2:16][C:17]([NH2:19])=[O:18])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NC(c1ccccc1)c1ccccc1
Reactant: NC(=O)CCl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: NC(=O)CNC(c1ccccc1)c1ccccc1

Procedure:
A reaction vessel was charged with 18.3 g (100 mmole) of diphenylmethylamine dissolved in 250 ml of ethanol. Then a mixture of 9.35 g (100 mmole) of chloroacetamide and 8.4 g (100 mmole) of sodium bicarbonate was added and the suspension was brought to reflux and held at reflux for 3 days. Solvent was evaporated under reduced pressure and the residue was dissolved in dichloromethane. The organic phase was washed with water, dried over potassium carbonate and solvent was evaporated. The resulting solid crystallized from a mixture of benzene and cyclohexane.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([NH:15][CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[C@H:25]([CH2:29][C:30]([O:32]CC)=[O:31])[CH2:24][CH2:23]4)[CH:12]=[CH:11][C:10]=2[C:35]([F:38])([F:37])[F:36])=[CH:5][CH:4]=1.CO.O.[Li+].[OH-]>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:14]=[C:13]([NH:15][CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[C@H:25]([CH2:29][C:30]([OH:32])=[O:31])[CH2:24][CH2:23]4)[CH:12]=[CH:11][C:10]=2[C:35]([F:37])([F:38])[F:36])=[CH:7][CH:8]=1
Reactant: CCOC(=O)C[C@@H]1CCc2cc(OCCCNc3ccc(C(F)(F)F)c(-c4ccc(OC)cc4)n3)ccc21
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc(-c2nc(NCCCOc3ccc4c(c3)CC[C@H]4CC(=O)O)ccc2C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 84.4 %

Procedure:
To a solution of ethyl [(1S)-5-(3-{[6-(4-methoxyphenyl)-5-(trifluoromethyl)-2-pyridinyl]amino}propoxy)-2,3-dihydro-1H-inden-1-yl]acetate (Example 304, 0.05 g, 0.09 mmol) in a mixture of THF (1 mL), methanol (1 mL), and water (0.5 mL) was added LiOH (0.02 g, 0.85 mmol). The mixture was stirred at rt for 18 h, and then concentrated under reduced pressure. The residue was taken up in water and acidified with 5% H3PO4. The aqueous solution was extracted with ethyl acetate. The combined organic phases dried (Na2SO4), filtered, and concentrated under reduced pressure to give the product (0.038 g, 88%). 1H NMR (400 MHz, CD2Cl2) δ 7.65 (d, 1H), 7.35 (d, 2H), 7.05 (d, 1H), 6.92 (d, 2H), 6.73 (s, 1H), 6.66 (dd, 1H), 6.49 (d, 1H), 4.02 (t, 2H), 3.84 (s, 3H), 3.55 (t, 3H), 3.45 (qt, 1H), 2.92-2.65 (m, 3H), 2.40-2.30 (m, 2H), 2.10-2.02 (m, 2H), 1.80-1.68 (m, 1H); LC-MS: RT=3.02 min, (M+H)+ 531.1.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]([C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[C:17](Br)[CH:16]=1)[CH2:9][C:8]2([CH3:24])[CH3:23])=[O:4].[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.Cl.CN(C)CC(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]([C:15]1[CH:16]=[C:17]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:18]=[C:19]([F:21])[CH:20]=1)[CH2:9][C:8]2([CH3:24])[CH3:23])=[O:4]
Reactant: COC(=O)c1ccc2c(c1)C(C)(C)CC(c1cc(F)cc(Br)c1)N2
Reactant: C1COCCN1
Agent: [Cu]I
Agent: CN(C)CC(=O)O
Agent: Cl
Solvent: CS(C)=O
Product: COC(=O)c1ccc2c(c1)C(C)(C)CC(c1cc(F)cc(N3CCOCC3)c1)N2
Temperature: 25 °C
Yield: 80.3 %

Procedure:
2-(3-bromo-5-fluoro-phenyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (3.9 g, 10.0 mmol), morpholine (9.0 mL, 95.0 mmol), copper(I) iodide (1.1 g, 6.0 mmol), N,N-dimethylglycine hydrochloride (1.1 g, 8.0 mmol), and potassium carbonate (4.1 g, 30.0 mmol) in dimethyl sulfoxide (20 mL) was stirred at 120° C. for 16 h. Then the reaction mixture was cooled to room temperature. The reaction mixture was extracted with ethyl acetate (200 mL×2), washed with saturated aqueous ammonium chloride solution (50 mL×3) and brine (50 mL×2), dried over anhydrous sodium sulfate and then concentrated in vacuo and the residue was purified by ISCO combi-flash chromatography (gradient elution, 30-50% ethyl acetate in petroleum ether) to afford 2-(3-fluoro-5-morpholin-4-yl-phenyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (3.2 g, 80%) as a white solid: MS (ESI) M+1=399.0.
Reaction SMILES: [CH2:1]([N:5]1[CH:10]=[CH:9][CH:8]=[C:7]([OH:11])[C:6]1=[S:12])[CH2:2][CH2:3][CH3:4]>C(O)C>[CH2:1]([N:5]1[CH:10]=[CH:9][C:8]([CH2:1][N:5]([CH3:10])[CH3:6])=[C:7]([OH:11])[C:6]1=[S:12])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCn1cccc(O)c1=S
Solvent: CCO
Product: CCCCn1ccc(CN(C)C)c(O)c1=S
Temperature: 75 °C
Reaction time: 24 h
Yield: 198.2 %

Procedure:
To a solution of 1-butyl-3-hydroxypyridine-2-thione (2-034-04) (1.0 g) in ethanol containing 10% water (20 mL) was added N,N,N′,N′-teteramethyldiaminomethane (1.70 g) at room temperature. After the reaction mixture was stirred at 75° C. for 24 h, the solvent was evaporated under reduced pressure to give 1-butyl-3-hydroxy-4(N,N-dimethylaminomethyl)pyridine-2-thione (2-034-05) (1.3 g, 95%) as an oil.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[CH:11]([C:20]3[CH:25]=[CH:24][C:23]([C:26]4[N:27]=[C:28]([C@@H:31]5[CH2:35][CH2:34][CH2:33][N:32]5[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[NH:29][CH:30]=4)=[CH:22][CH:21]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[C:43]([O:47][C:48]([N:50]1[CH2:54][CH2:53][CH2:52][C@H:51]1[C:55](O)=[O:56])=[O:49])([CH3:46])([CH3:45])[CH3:44].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.ClCCl>[C:39]([O:38][C:36]([N:32]1[CH2:33][CH2:34][CH2:35][C@H:31]1[C:28]1[NH:29][CH:30]=[C:26]([C:23]2[CH:24]=[CH:25][C:20]([CH:11]3[N:12]([C:13]4[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=4)[CH:8]([C:5]4[CH:6]=[CH:7][C:2]([NH:1][C:55]([C@@H:51]5[CH2:52][CH2:53][CH2:54][N:50]5[C:48]([O:47][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:49])=[O:56])=[CH:3][CH:4]=4)[CH2:9][CH2:10]3)=[CH:21][CH:22]=2)[N:27]=1)=[O:37])([CH3:42])([CH3:41])[CH3:40]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)O
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1c1nc(-c2ccc(C3CCC(c4ccc(N)cc4)N3c3ccc(F)cc3)cc2)c[nH]1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C([O-])[O-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)Nc1ccc(C2CCC(c3ccc(-c4c[nH]c([C@@H]5CCCN5C(=O)OC(C)(C)C)n4)cc3)N2c2ccc(F)cc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.1 %

Procedure:
Dissolved the product from Example 39G (285 mg, 0.502 mmol), (S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (162 mg, 0.753 mmol), HATU (305 mg, 0.803 mmol) and Hunig's base (0.263 mL, 1.506 mmol) in DMSO (5 mL) and stirred at room temperature for 1 h. Dichloromethane (50 mL) was added followed by extraction with water (2×50 mL), the organic extract dried, concentrated and the residue dissolved in methanol (10 mL) followed by the addition of potassium carbonate (400 mg, 2.89 mmol) and stirred the bright yellow solution at room temperature for 30 min. The solution was then filtered and the filtrate concentrated to an oil, which was dissolved in a 95/5 dichloromethane/methanol mixture (50 mL) and extracted with water (20 mL). The organic extract was dried and concentrated to give the title product (350 mg, 91%) as a light yellow solid and a 1/1 mixture of stereoisomers.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:14](=[O:15])[CH2:13][C:12](=[O:16])[NH:11][C:10]3[C:17]4[C:22]([CH:23]=[CH:24][C:9]2=3)=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:4][CH:3]=1.[F:25][C:26]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[C:27]=1[C:28](Cl)=[O:29].IC1C=CC=CC=1C(NCCN1C(=O)CC(=O)NC2C3C(C=CC1=2)=CC=CC=3)=O>>[F:25][C:26]1[C:27]([C:28]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([N:8]3[C:14](=[O:15])[CH2:13][C:12](=[O:16])[NH:11][C:10]4[C:17]5[C:22]([CH:23]=[CH:24][C:9]3=4)=[CH:21][CH:20]=[CH:19][CH:18]=5)=[CH:4][CH:3]=2)=[O:29])=[C:31]([O:35][CH3:36])[CH:32]=[CH:33][CH:34]=1
Reactant: COc1cccc(F)c1C(=O)Cl
Reactant: Nc1ccc(N2C(=O)CC(=O)Nc3c2ccc2ccccc32)cc1
Agent: O=C1CC(=O)N(CCNC(=O)c2ccccc2I)c2ccc3ccccc3c2N1
Product: COc1cccc(F)c1C(=O)Nc1ccc(N2C(=O)CC(=O)Nc3c2ccc2ccccc32)cc1
Yield: 78 %

Procedure:
By using 5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione obtained in Example 1, (3), and 2-fluoro-6-methoxybenzoyl chloride, the title compound (yield 78%) was obtained in the same manner as that of Example 1, (4).
Reaction SMILES: C(OC([NH:11][C@H:12]1[CH2:17][CH2:16][CH2:15][CH2:14][C@@:13]1([CH2:22][CH3:23])[C:18]([O:20][CH3:21])=[O:19])=O)C1C=CC=CC=1>CO.[Pd]>[NH2:11][C@H:12]1[CH2:17][CH2:16][CH2:15][CH2:14][C@@:13]1([CH2:22][CH3:23])[C:18]([O:20][CH3:21])=[O:19]
Reactant: CC[C@@]1(C(=O)OC)CCCC[C@@H]1NC(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CO
Product: CC[C@@]1(C(=O)OC)CCCC[C@@H]1N
Temperature: 25 °C
Reaction time: 1 h
Yield: 88 %

Procedure:
A solution of methyl (1R,2S)-2-benzyloxycarbonylamino-1-ethyl-cyclohexanecarboxylate, 38b, (0.27 g, 0.85 mmol) in MeOH (7.5 mL) was purged with nitrogen and a catalytic amount of Pd (5% Pd on carbon) was added. The solution was placed under H2 atmosphere and stirred at room temperature. After 1 hour, the MeOH solution suspension was filtered through celite, and concentrated in vacuo to provide the desired product (138 mg, 88% yield). The material was diluted in acetonitrile and concentrated to remove residual methanol.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH2:20])[C:5]([NH2:19])=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1.O.C(=O)(O)[O-].[Na+].[F:27][C:28]([F:36])([F:35])[C:29]([F:34])([F:33])[C:30](O)=O>>[Cl:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:16])[F:17])=[CH:11][CH:10]=2)=[CH:6][C:5]2[NH:19][C:30]([C:29]([F:34])([F:33])[C:28]([F:36])([F:35])[F:27])=[N:20][C:4]=2[CH:3]=1
Reactant: O=C(O)C(F)(F)C(F)(F)F
Reactant: Nc1cc(Cl)c(Oc2ccc(C(F)(F)F)cc2)cc1N
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: FC(F)(F)c1ccc(Oc2cc3[nH]c(C(F)(F)C(F)(F)F)nc3cc2Cl)cc1
Yield: 49.7 %

Procedure:
A solution of 4-chloro-5-[4-(trifluoromethyl)phenoxy]benzene-1,2-diamine (200 mg, 0.66 mmol) in pentafluoropropanoic acid (2 ml) was stirred overnight at 80° C. in an oil bath. The solution was poured into water (50 ml), adjusted pH to 8 with sodium bicarbonate (sat) and extracted with ethyl acetate (3×50 ml). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum to give a residue, which was purified by a silica gel column with 8% ethyl acetate in petroleum ether to produce 5-chloro-2-(pentafluoroethyl)-6-[4-(trifluoromethyl)phenoxy]-1H-1,3-benzodiazole as a white solid (141.7 g, 49.7%).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[N:10]([C:11]2[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=2)[CH:14]=[O:15])[N:9]=[C:8]([C:19]([F:22])([F:21])[F:20])[CH:7]=1.[CH2:23](O)[CH2:24][CH2:25][OH:26].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[O:15]1[CH2:23][CH2:24][CH2:25][O:26][CH:14]1[C:13]1[CH:12]=[C:11]([N:10]2[C:6]([C:2]3[O:1][CH:5]=[CH:4][CH:3]=3)=[CH:7][C:8]([C:19]([F:20])([F:22])[F:21])=[N:9]2)[CH:18]=[CH:17][CH:16]=1
Reactant: OCCCO
Reactant: O=Cc1cccc(-n2nc(C(F)(F)F)cc2-c2ccco2)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: FC(F)(F)c1cc(-c2ccco2)n(-c2cccc(C3OCCCO3)c2)n1
Yield: 78.5 %

Procedure:
To a stirred solution of 122 (3.25 g, 10.62 mmol) in PhMe (53 ml) was added 1,3-propanediol (1.616 g, 21.24 mmol) followed by p-toluenesulfonic acid monohydrate (0.202 g, 1.062 mmol) and the resulting solution was allowed to stir at reflux with a Dean-Stark trap for 16 h. The solution was evaporated to dryness, and saturated NaHCO3 aqueous solution was added and the mixture was extracted with EtOAc and the extracts were dried over Na2SO4 and evaporated. The residue was purified via Biotage (5% to 40% EtOAc/Hexane; 40+M column). The title product 146 (3.04 g, 8.34 mmol, 79% yield) was obtained as an off-white solid. LRMS (ESI): (calc.) 364.3; (found) 365.2 (MH)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[CH2:15][N:16]1[CH2:21][CH2:20][CH:19]([NH:22]C(=O)OC(C)(C)C)[CH2:18][CH2:17]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[CH2:15][N:16]1[CH2:17][CH2:18][CH:19]([NH2:22])[CH2:20][CH2:21]1
Reactant: COc1cc2nccc(CN3CCC(NC(=O)OC(C)(C)C)CC3)c2cc1OC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1cc2nccc(CN3CCC(N)CC3)c2cc1OC
Yield: 71887552 %

Procedure:
tert-Butyl 1-((6,7-dimethoxyquinolin-4-yl)methyl)piperidin-4-ylcarbamate (1 g, 2.49 nmol) was dissolved in DCM (25 mL). While stirring, TFA (1.9 mL, 25 mmol) was added dropwise at rt, and the reaction was allowed to stir for 15 hours. The solvent was removed and the crude compound was taken up in EtOAc (150 mL) and washed with sat. sodium bicarbonate (20 mL). The organics were washed with brine, dried with sodium sulfate, and concentrated. The mixture was columned using 100% DCM to 7% MeOH to give the desired product 1-((6,7-dimethoxyquinolin-4-yl)methyl)piperidin-4-amine (0.54 g, 1.79 mmol, 72% yield). MS (ESI pos. ion) m/z: 302.2 (MH+). Calc'd exact mass for C17H23N3O2: 301. 1HNMR (400 MHz, CDCl3): 8.63-8.64 (d, J=4.4 Hz, 1H), 7.63 (s, 1H), 7.41 (s, 1H), 7.22-7.23 (d, J=4.4 Hz, 1H), 4.03 (s, 3H), 4.01 (s, 3H), 3.83 (s, 2H), 2.84-2.87 (bd, J=12.0 Hz, 2H), 2.70-2.73 (m, 1H), 2.11-2.16 (bt, J=11.2 Hz, 2H), 1.78-1.82 (bd, J=12.8 Hz, 2 H), 1.37-1.41 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([Cl:11])=[C:9]([C:12](Cl)=[O:13])[S:8][C:7]=2[CH:15]=1.[CH3:16][OH:17].Cl[Si](C)(C)C.CCCCCC>C(O)C.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([Cl:11])=[C:9]([C:12]([O:17][CH3:16])=[O:13])[S:8][C:7]=2[CH:15]=1
Reactant: CO
Reactant: COc1ccc2c(Cl)c(C(=O)Cl)sc2c1
Agent: C[Si](C)(C)Cl
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: CCO
Product: COC(=O)c1sc2cc(OC)ccc2c1Cl
Temperature: 25 °C

Procedure:
Crude 6-methoxy-3-chlorobenzo[b]thiophene-2-carbonyl chloride (2 g, 7.67 mmoles) was transferred to a 100 ml round bottomed flask. Anhydrous methanol (Aldrich, 50 ml) was added and the acid chloride dissolved by stirring. To this stirred solution was added chlorotrimethylsilane (2.5 equivalents, 19.16 mmole, 2.08 g, 2.43 ml). The reaction mixture was stirred overnight at room temperature. TLC analysis (silica, 1:1 hexane:ethyl acetate, UV visualization) indicated complete conversion of the acid chloride to the methyl ester. The resulting slurry was concentrated in vacuo to give a yellow solid, which was shown by 1H NMR (DMSO-d6, 400 MHz) to be the desired material. The crude methyl ester was dissolved in hot ethanol (200 ml), the volume was reduced to 150 ml, and allowed to cool to room temperature. The resulting orange ethanolic solution was cooled to -10° C. for 15 minutes. The resulting precipitate was filtered off and dried in vacuo to give 1.25 g of the ester as an off-white solid.
Reaction SMILES: [CH3:1][CH:2]([OH:16])[CH2:3][C:4]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:9]=[CH:8][CH2:7][CH:6]=[CH:5]1.[S:17](Cl)([CH3:20])(=[O:19])=[O:18]>N1C=CC=CC=1>[CH3:1][CH:2]([O:16][S:17]([CH3:20])(=[O:19])=[O:18])[CH2:3][C:4]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:6][CH2:7][CH:8]=[CH:9]1
Reactant: CC(O)CC1(c2ccccc2)C=CCC=C1
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Product: CC(CC1(c2ccccc2)C=CCC=C1)OS(C)(=O)=O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
8 g. of α-methyl-1-phenyl-2,5-cyclohexadien-1-ethanol are dissolved in 50 ml. of pyridine and 6.4 g. of mesyl chloride are added dropwise at 0°-5° C. After stirring at room temperature for 2 hours, the mixture is worked-up as follows: The mixture is treated with ice-water and extracted with ether. The ether phase is washed with 3 N aqueous hydrochloric acid, then washed neutral, dried and concentrated. The crude product obtained is chromatographed on 100 g. of silica gel with ether/petroleum ether (1:1). There is obtained an oily product which crystallizes in the cold. After crystallization from methylene chloride/hexane, there is obtained methanesulfonic acid 1-methyl-2-(1-phenyl-2,5-cyclohexadien-1-yl)-ethyl ester having a melting point of 51°-53° C.
Reaction SMILES: [CH3:1][Si:2]([CH3:15])([CH3:14])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[CH:11]=[C:10]([CH2:12][OH:13])[N:9]=[CH:8]1.C(N(CC)CC)C.[Si:23](Cl)([C:36]([CH3:39])([CH3:38])[CH3:37])([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl.CN(C1C=CN=CC=1)C>[Si:23]([O:13][CH2:12][C:10]1[N:9]=[CH:8][N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:15])([CH3:14])[CH3:1])[CH:11]=1)([C:36]([CH3:39])([CH3:38])[CH3:37])([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: C[Si](C)(C)CCOCn1cnc(CO)c1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)[Si](OCc1cn(COCC[Si](C)(C)C)cn1)(c1ccccc1)c1ccccc1

Procedure:
1-(2-Trimethylsilylethoxymethyl)-1H-imidazole-4-methanol (100 g, WO 01/02145) was dissolved in dichloromethane (1 L), and triethylamine (hereinafter sometimes referred to as TEA) (122 mL), 4-(N,N-dimethylamino)pyridine (hereinafter sometimes referred to as DMAP) (5.35 g) and tert-butyldiphenylsilyl chloride (hereinafter sometimes referred to as TBDPSCl) (149 mL) were added under stirring. After stirring for a day, the reaction mixture was washed with water and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by flash chromatography (ethyl acetate/hexane=25%→50%) using a silica gel column (trade name: Ultrapack E, manufactured by Yamazen Corporation) to give the title compound (146 g).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])/[C:5]/2=[CH:14]/OC.CN(C)C=O.[NH2:22][CH2:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27]>CCOCC>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])/[C:5]/2=[CH:14]\[NH:22][CH2:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27]
Reactant: NCCCC(=O)O
Reactant: CO/C=C1/C(=O)NC(=O)c2ccc(Br)cc21
Solvent: CN(C)C=O
Solvent: CCOCC
Product: O=C(O)CCCN/C=C1\C(=O)NC(=O)c2ccc(Br)cc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of (E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (212 mg, 0.75 mmole), dimethylformamide (5 mL), and 4-aminobutanoic acid (78 mg, 0.75 mmole) is stirred at room temperature for 1 hour. The reaction mixture is diluted with ether, filtered, washed with fresh ether and dried to give a salmon solid, 164 mg, (61%), mp 260-2° C. dec; MS (ES+): m/z 353.0 (M+H).
Reaction SMILES: [OH:1][C:2]([C@@:4]1([O:50][C@@H:49]([C@@H:51]([C@@H:53]([CH2:55][OH:56])[OH:54])[OH:52])[C@H:44]([NH:45][C:46]([CH3:48])=[O:47])[C@@H:42]([OH:43])[CH2:41]1)[O:5][C@H:6]1[C@@H:36]([OH:37])[C@@H:35]([CH2:38][OH:39])[O:34][C@@H:8]([O:9][C@@H:10]2[C@@H:16]([CH2:17][OH:18])[O:15][CH:13]([OH:14])[C@H:12]([NH:19][C:20]([CH3:22])=[O:21])[C@H:11]2[O:23][C@@H:24]2[O:32][C@@H:31]([CH3:33])[C@@H:29]([OH:30])[C@@H:27]([OH:28])[C@@H:25]2[OH:26])[C@@H:7]1[OH:40])=[O:3].C[C@@H]1O[C@@H](O[C@@H]([C@H]([O:78][C@@H:79]2[O:84][C@H:83]([CH2:85][OH:86])[C@H:82]([OH:87])[C@H:81](O[C@@]3(C(O)=O)O[C@@H]([C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)[C@H:80]2[OH:109])[C@H](O)CO)[C@@H](NC(C)=O)C=O)[C@@H](O)[C@H](O)[C@@H]1O>>[OH:3][C:2]([C@@:4]1([O:50][C@@H:49]([C@@H:51]([C@@H:53]([CH2:55][OH:56])[OH:54])[OH:52])[C@H:44]([NH:45][C:46]([CH3:48])=[O:47])[C@@H:42]([OH:43])[CH2:41]1)[O:5][C@H:6]1[C@@H:36]([OH:37])[C@@H:35]([CH2:38][OH:39])[O:34][C@@H:8]([O:9][C@@H:10]2[C@@H:16]([CH2:17][OH:18])[O:15][C@@H:13]([O:14][C@H:81]3[C@@H:82]([OH:87])[C@@H:83]([CH2:85][OH:86])[O:84][C@@H:79]([OH:78])[C@@H:80]3[OH:109])[C@H:12]([NH:19][C:20]([CH3:22])=[O:21])[C@H:11]2[O:23][C@@H:24]2[O:32][C@@H:31]([CH3:33])[C@@H:29]([OH:30])[C@@H:27]([OH:28])[C@@H:25]2[OH:26])[C@@H:7]1[OH:40])=[O:1]
Reactant: CC(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)O[C@@](O[C@H]2[C@@H](O)[C@@H](CO)O[C@@H](O[C@@H]([C@H](O[C@@H]3O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]3O)[C@H](C=O)NC(C)=O)[C@H](O)CO)[C@@H]2O)(C(=O)O)C[C@@H]1O
Reactant: CC(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)O[C@@](O[C@H]2[C@@H](O)[C@@H](CO)O[C@@H](O[C@H]3[C@H](O[C@@H]4O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]4O)[C@@H](NC(C)=O)C(O)O[C@@H]3CO)[C@@H]2O)(C(=O)O)C[C@@H]1O
Product: CC(=O)N[C@H]1[C@H](O[C@@H]2[C@@H](O)[C@H](O)O[C@H](CO)[C@@H]2O)O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O[C@]3(C(=O)O)C[C@H](O)[C@@H](NC(C)=O)[C@H]([C@H](O)[C@H](O)CO)O3)[C@H]2O)[C@@H]1O[C@@H]1O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]1O

Procedure:
NeuAcα2→3Galβ1→4(Fucα1→3)GlcNAc=Slex.