Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[NH:9][C:8]2=[O:16])[CH2:3][CH2:2]1.Cl[C:18]1[N:23]=[CH:22][N:21]=[C:20]([NH:24][C:25]2[CH:34]=[C:33]([CH3:35])[C:28]3[NH:29][C:30](=[O:32])[O:31][C:27]=3[CH:26]=2)[CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>CN1C(=O)CCC1.CN(C=O)C>[CH3:35][C:33]1[C:28]2[NH:29][C:30](=[O:32])[O:31][C:27]=2[CH:26]=[C:25]([NH:24][C:20]2[N:21]=[CH:22][N:23]=[C:18]([N:1]3[CH2:2][CH2:3][CH:4]([N:7]4[C:15]5[C:10](=[N:11][CH:12]=[CH:13][CH:14]=5)[NH:9][C:8]4=[O:16])[CH2:5][CH2:6]3)[CH:19]=2)[CH:34]=1
Reactant: Cc1cc(Nc2cc(Cl)ncn2)cc2oc(=O)[nH]c12
Reactant: O=c1[nH]c2ncccc2n1C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CN1CCCC1=O
Product: Cc1cc(Nc2cc(N3CCC(n4c(=O)[nH]c5ncccc54)CC3)ncn2)cc2oc(=O)[nH]c12
Temperature: 25 °C

Procedure:
276 mg (1.26 mmol) 1-piperidin-4-yl-1,3-dihydroimidazo[4,5-b]pyridin-2-one, 350 mg (0.987 mmol) 6-(6-chloro-pyrimidin-4-ylamino)-4-methyl-3H-benzoxazol-2-one and 350 mg (2.53 mmol) potassium carbonate in 2 mL NMP were stirred for 2 h at 130° C. After cooling to RT the reaction mixture was diluted with DMF and purified by preparative HPLC. The product-containing fractions were combined and freeze-dried.
Reaction SMILES: [C:1]([O:5][P:6]([O-:13])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N+](CCCC)(CCCC)CCCC)CCC.[NH2:31][C:32]1[N:41]=[C:40]([C:42]([N:44]2[CH2:52][C:51]3[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=3)[CH2:45]2)=[O:43])[C:39]2[C:34](=[CH:35][CH:36]=[C:37]([C:53]3[CH:58]=[C:57]([F:59])[C:56]([F:60])=[CH:55][C:54]=3[CH2:61]Cl)[CH:38]=2)[N:33]=1>C(#N)C>[P:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])([O:13][CH2:61][C:54]1[CH:55]=[C:56]([F:60])[C:57]([F:59])=[CH:58][C:53]=1[C:37]1[CH:38]=[C:39]2[C:34](=[CH:35][CH:36]=1)[N:33]=[C:32]([NH2:31])[N:41]=[C:40]2[C:42]([N:44]1[CH2:45][C:46]2[C:51](=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH2:52]1)=[O:43])=[O:7]
Reactant: CC(C)(C)OP(=O)([O-])OC(C)(C)C
Reactant: Nc1nc(C(=O)N2Cc3ccccc3C2)c2cc(-c3cc(F)c(F)cc3CCl)ccc2n1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CC#N
Product: CC(C)(C)OP(=O)(OCc1cc(F)c(F)cc1-c1ccc2nc(N)nc(C(=O)N3Cc4ccccc4C3)c2c1)OC(C)(C)C
Temperature: 80 °C

Procedure:
800 mg of tetrabutylammonium di-tert-butylphosphate are added to 270 mg of [2-amino-6-(2-chloromethyl-4,5-difluorophenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone dissolved in 20 ml of acetonitrile, and the solution obtained is heated at 80° C. for 2 h. After cooling to 25° C., undissolved material is filtered off, and the filtrate is evaporated to dryness in vacuo. The residue is dissolved in 1 ml of dimethyl sulfoxide and purified by chromatography (reversed phase).
Reaction SMILES: [NH2:1][C:2]1[C:3]([NH:13][CH2:14][CH2:15][CH2:16][OH:17])=[C:4]([CH:9]=[CH:10][C:11]=1[Cl:12])[C:5]([O:7][CH3:8])=[O:6].[Cl:18][C:19]1[C:20]([N:26]=[C:27]=[S:28])=[N:21][CH:22]=[C:23]([Cl:25])[CH:24]=1>O1CCCC1>[Cl:12][C:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[C:3]([NH:13][CH2:14][CH2:15][CH2:16][OH:17])[C:2]=1[NH:1][C:27](=[S:28])[NH:26][C:20]1[C:19]([Cl:18])=[CH:24][C:23]([Cl:25])=[CH:22][N:21]=1
Reactant: S=C=Nc1ncc(Cl)cc1Cl
Reactant: COC(=O)c1ccc(Cl)c(N)c1NCCCO
Solvent: C1CCOC1
Product: COC(=O)c1ccc(Cl)c(NC(=S)Nc2ncc(Cl)cc2Cl)c1NCCCO
Temperature: 25 °C
Reaction time: 72 h
Yield: 61.1 %

Procedure:
A mixture of methyl 3-amino-4-chloro-2-[(3-hydroxypropyl)amino]benzoate (3.13 g, 12.1 mmol) and 3,5-dichloro-2-isothiocyanatopyridine (3.23 g, 15.7 mmol) in tetrahydrofuran (40 mL) was stirred at room temperature for 3 days. The mixture was concentrated in vacuo, and the residue was washed with ethyl acetate/diisopropyl ether to give the title compound as a colorless crystal (3.43 g, 7.4.0 mmol, 61%).
Reaction SMILES: Cl[C:2]1[CH:14]=[CH:13][C:5]([C:6]([N:8]([CH2:11][CH3:12])[CH2:9][CH3:10])=[O:7])=[C:4]([C:15]([F:18])([F:17])[F:16])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:25]([Zn]CC)[CH3:26]>CN(C)C=O.C1(C)C=CC=CC=1>[CH2:9]([N:8]([CH2:11][CH3:12])[C:6](=[O:7])[C:5]1[CH:13]=[CH:14][C:2]([CH2:25][CH3:26])=[CH:3][C:4]=1[C:15]([F:18])([F:17])[F:16])[CH3:10]
Reactant: CCN(CC)C(=O)c1ccc(Cl)cc1C(F)(F)F
Reactant: CC[Zn]CC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: CCc1ccc(C(=O)N(CC)CC)c(C(F)(F)F)c1
Temperature: 120 °C
Yield: 75 %

Procedure:
To a solution of 4-chloro-N,N-diethyl-2-(trifluoromethyl)benzamide (5.04 g, 18 mmol) in 100 mL of N,N-dimethylformamide was added potassium carbonate (6.2 g, 45 mmol) and diethylzinc (29.5 mL of a 1.1 M solution in toluene, 32.4 mmol). The mixture was degassed and then there was added POPd (Combiphos) (0.27 g, 0.54 mmol). The resulting solution was heated at 120° C. in a sealed tube for 18 h. The mixture was allowed to cool and was diluted with water and extracted with ethyl acetate. The organics were washed with water and brine, dried (MgSO4) and concnentrated in vacuo. The residue was purified (ISCO, elution with 0-25% EtOAc/hexane) to afford 3.7 g (75%) of the title compound as an oil. LRMS (ESI): 274.2 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:10][C:11]([O:13][CH3:14])=[O:12])[NH2:9])=[CH:4][C:3]=1[CH3:15].[O-:16][C:17]#[N:18].[Na+].FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[NH2:18][C:17]([NH:9][N:8]([CH2:10][C:11]([O:13][CH3:14])=[O:12])[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[C:3]([CH3:15])[CH:4]=1)=[O:16]
Reactant: COC(=O)CN(N)c1ccc(F)c(C)c1
Reactant: N#C[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: Cc1ccccc1
Product: COC(=O)CN(NC(N)=O)c1ccc(F)c(C)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A mixture of methyl [1-(4-fluoro-3-methylphenyl)hydrazino]acetate (Intermediate 64, 0.8, 38 mml), sodium cyanate (0.84 g, 0.0129 mol) and trifluoroacetic acid (0.95 ml, 0.0114 mol) in toluene (15 ml) was stirred under nitrogen at room temperature for 24 hours. The mixture was poured into 8% sodium bicarbonate solution (40 ml) and extracted with ethyl acetate (2×30 ml). The organic extract was dried (MgSO4) and evaporated to give a red oil. This was crystallised by trituration with ether to give a white solid (Intermediate 65, 228 mg; 24%), m.p. 132°-133° C.
Reaction SMILES: [OH:1][C:2]1([CH2:13][NH2:14])[CH2:8][O:7][C:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=2[O:4][CH2:3]1.[CH2:15]1[O:23][CH:16]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[ClH:24]>CO.CCOCC>[ClH:24].[OH:1][C:2]1([CH2:13][N:14]([CH2:15][CH:16]([OH:23])[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:15][CH:16]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[OH:23])[CH2:3][O:4][C:5]2[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=2[O:7][CH2:8]1
Reactant: c1ccc(C2CO2)cc1
Reactant: NCC1(O)COc2ccccc2OC1
Agent: Cl
Solvent: CO
Solvent: CCOCC
Product: OC(CN(CC(O)c1ccccc1)CC1(O)COc2ccccc2OC1)c1ccccc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
3-Hydroxy-3-aminomethyl-3,4-dihydro-2H-1,5-benzodioxepin (2.30 g., 11.8 millimole) and styrene oxide (1.42 g., 11.8 millimole) are dissolved in methanol (12 ml.) and the solution then is stirred at ambient temperature for 48 hours. Evaporation of the reaction mixture gives 3.64 g. of a syrup which is chromatographed on a dry silica gel (150 g.) column which had been deactivated with about 25 ml. of water and packed in a 1 3/4 inches glass column. The first three fractions obtained upon elution with a 1:1 mixture of ether and chloroform are combined and dissolved in dry ether (50 ml.) and treated with a slight excess of ethanolic hydrogen chloride. The solid material is separated and dissolved in boiling ethanol (16 ml.) clarified with charcoal and filtered. The solvent was removed from the filtrate by evaporation yielding 3-hydroxy-3-[di-(2-hydroxy-2-phenylethyl)aminomethyl)-3,4-dihydro-2H-1,5-benzodioxepin hydrochloride, m.p. 221°-222° C. (dec.).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7](COCC[Si](C)(C)C)[CH:6]=[CH:5]2.Cl[C:20]1[CH:25]=[CH:24][N:23]=[C:22]([NH:26][CH:27]2[CH2:32][C:31]([CH3:34])([CH3:33])[NH:30][C:29]([CH3:36])([CH3:35])[CH2:28]2)[N:21]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:24]1[CH:25]=[CH:20][N:21]=[C:22]([NH:26][CH:27]2[CH2:32][C:31]([CH3:34])([CH3:33])[NH:30][C:29]([CH3:36])([CH3:35])[CH2:28]2)[N:23]=1
Reactant: C[Si](C)(C)CCOCn1ccc2cc(F)ccc21
Reactant: CC1(C)CC(Nc2nccc(Cl)n2)CC(C)(C)N1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Product: CC1(C)CC(Nc2nccc(-c3c[nH]c4ccc(F)cc34)n2)CC(C)(C)N1

Procedure:
The title compound was prepared as described in Example 215, starting from 5-fluoro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indole (prepared by SEM protection of 5-fluoro-1H-indole using standard procedures) and (4-chloro-pyrimidin-2-yl)-(2,2,6,6-tetramethyl-piperidin-4-yl)-amine, followed by cleavage of the SEM protecting group with TBAF.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([NH:15][C:16]2[CH:17]=[C:18]3[C:24]([CH3:25])=[N:23][N:22](CC4C=CC(OC)=CC=4)[C:19]3=[N:20][CH:21]=2)[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]1.FC(F)(F)C(O)=O>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([NH:15][C:16]2[CH:17]=[C:18]3[C:24]([CH3:25])=[N:23][NH:22][C:19]3=[N:20][CH:21]=2)[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]1
Reactant: COc1ccc(Cn2nc(C)c3cc(Nc4ccc(N5CCN(C)CC5)c(F)c4)cnc32)cc1
Solvent: ClC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: Cc1n[nH]c2ncc(Nc3ccc(N4CCN(C)CC4)c(F)c3)cc12
Temperature: 60 °C

Procedure:
To a stirred solution of N-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-5-amine (169) (30 mg, 0.063 mmol) in CHCl3 (15 mL) was added trifluoroacetic acid (6 mL) and the reaction mass heated to 60° C. overnight. After completion of the reaction the solvents were completely distilled off and diluted with water and the pH was adjusted to 9 and extracted with chloroform twice. The combined organic layer was washed with brine solution and dried over sodium sulphate and the solvents were removed and the crude material was passed through 100-200 mesh silica gel, eluting with 8% MeOH/CH2Cl2 obtained pure N-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-5-amine 170 as a pale yellow colored solid (10 mg). 1H NMR (400 MHz, CDCl3) δ: 8.36 (s, 1H), 7.71 (s, J=2.31, 1H), 6.90 (m, 1H), 6.71 (m, 2H), 5.56 (s, 1H), 3.07 (bs, 4H), 2.62 (bs, 4H), 2.54 (bs, 3H), 2.36 (s, 3H); MS m/z 341.0 (M+H)+.
Reaction SMILES: [S:1]([O:8]S(C(F)(F)F)(=O)=O)([C:4]([F:7])([F:6])[F:5])(=[O:3])=[O:2].[N:16]1([C:21]2[CH:26]=[CH:25][C:24](O)=[CH:23][CH:22]=2)[CH:20]=[CH:19][N:18]=[CH:17]1.C(N(CC)CC)C>ClCCl>[O:8]([C:24]1[CH:25]=[CH:26][C:21]([N:16]2[CH:20]=[CH:19][N:18]=[CH:17]2)=[CH:22][CH:23]=1)[S:1]([C:4]([F:7])([F:6])[F:5])(=[O:3])=[O:2]
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: Oc1ccc(-n2ccnc2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=S(=O)(Oc1ccc(-n2ccnc2)cc1)C(F)(F)F
Reaction time: 18 h

Procedure:
Triflic anhydride (2.82 g) was added dropwise to a mixture of 4-(1-imidazolyl)phenol (Aldrich Chemical Company) and triethylamine (1.1 g) in dichloromethane (30 ml). The mixture was stirred for 18 hours. The mixture was evaporated and the residue partitioned between diethyl ether and water. The organic phase was separated, washed with water, dried (MgSO4) and evaported. The residue was triturated with cyclohexane to give crude 4-(1-imidazolyl)phenyl triflate (1.7 g) as a solid, which was used without further purification; m/Z 293 (M+H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:14]2[CH2:18][C@H:17]([CH2:19][NH2:20])[O:16][C:15]2=[O:21])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[CH3:22][S:23][C:24]1[CH:29]=[CH:28][C:27]([C:30](=[O:36])[CH2:31][CH2:32][C:33](O)=[O:34])=[CH:26][CH:25]=1.C1C=CC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC>C1COCC1.O>[CH3:22][S:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]([CH2:31][CH2:32][C:33]([NH:20][CH2:19][C@@H:17]2[O:16][C:15](=[O:21])[N:14]([C:4]3[CH:5]=[CH:6][C:7]([N:8]4[CH2:9][CH2:10][O:11][CH2:12][CH2:13]4)=[C:2]([F:1])[CH:3]=3)[CH2:18]2)=[O:34])=[O:36])=[CH:28][CH:29]=1
Reactant: CSc1ccc(C(=O)CCC(=O)O)cc1
Reactant: NC[C@H]1CN(c2ccc(N3CCOCC3)c(F)c2)C(=O)O1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: C1CCOC1
Product: CSc1ccc(C(=O)CCC(=O)NC[C@H]2CN(c3ccc(N4CCOCC4)c(F)c3)C(=O)O2)cc1
Temperature: 0 °C
Reaction time: 24 h
Yield: 79 %

Procedure:
(S)-N-[3-(3-fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinyl]methyl amine (0.200 gm, 0.00068 moles) was taken up in 1:1 THF-water mixture (20 ml). To this was added 4-(4-methlythiophenyl)-4-oxobutanoic acid (0.152 g, 0.00068 moles and HOBt (0.091 gm, 0.00068 moles) and the resulting mixture was cooled to 0° C., and then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.142 g, 0.00074 moles) was added. The resulting mixture was allowed to warm to room temperature and then stirred for 24 hr. The reaction mixture was concentrated, 15 ml of saturated aqueous sodium bicarbonate was added to, stirred for 15 min and then extracted with ethyl acetate. The ethyl acetate layer was separated and evaporated off. The residue was chromatographed over silica gel (100-200 mesh, 20 g). The column was eluted with mixture of ethyl acetate:hexane, and finally with ethyl acetate. The combined fractions were concentrated to give the title compound (0.270 gm, 79%) as a white solid.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[N:8][N+:9]([O-:11])=[O:10])[NH:6][CH2:5][O:4][CH2:3]1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19]Cl)=[CH:15][N:14]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:6]2[CH2:5][O:4][CH2:3][N:2]([CH3:1])[C:7]2=[N:8][N+:9]([O-:11])=[O:10])=[CH:15][N:14]=1
Reactant: CN1COCNC1=N[N+](=O)[O-]
Reactant: ClCc1ccc(Cl)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CN1COCN(Cc2ccc(Cl)nc2)C1=N[N+](=O)[O-]

Procedure:
A mixture of 1.44 g of 3-methyl-4-nitroiminoperhydro-1,3,5-oxadiazine, 2.2 g of 2-chloro-5-chloromethylpyridine, 3.7 g of potassium carbonate and 20 ml of N,N-dime-thylformamide is heated for 4 hours at 50° and filtered, the filtrate is evaporated in vacuo on a rotary evaporator, and the residue is purified by chromatography [silica gel; dichloromethane/methanol (95:5)]. This gives the title compound which melts at 116 to 118°.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([S:9][CH3:10])[N:3]=1.C([Li])CCC.[O:16]1[CH2:20][CH2:19]OS1(=O)=O.C(=O)=O.Cl.CC1CCCO1>C1COCC1>[Cl:1][C:2]1[C:7]([CH2:19][CH2:20][OH:16])=[C:6]([Cl:8])[N:5]=[C:4]([S:9][CH3:10])[N:3]=1
Reactant: CSc1nc(Cl)cc(Cl)n1
Reactant: O=S1(=O)OCCO1
Agent: Cl
Agent: O=C=O
Agent: [Li]CCCC
Solvent: CC1CCCO1
Solvent: C1CCOC1
Product: CSc1nc(Cl)c(CCO)c(Cl)n1
Reaction time: 0.5 h
Yield: 758.5 %

Procedure:
To a vial containing 4,6-dichloro-2-(methylsulfanyl)pyrimidine (200 mg, 0.102 mmol) in THF (10 mL) was added n-butyllithium (0.554 mL, 1.38 mmol, 2.5 M in hexane) at −78° C. and the resulting mixture was stirred for 30 min. 1,3,2-dioxathiolane 2,2-dioxide (172 mg, 1.39 mmol) was added at −78° C. and stirring was continued for 2 h. The reaction vial was removed from the dry ice bath, 6 N HCl (3.5 mL, 21 mmol) was added, and the mixture was stirred at room temperature for 18 h. 2-Methyltetrahydrofuran (20 mL) was added and the solution was washed with a 1:1 mixture of brine/water and then with saturated aqueous NaHCO3. The organic layer was dried over Na2SO4, filtered, concentrated and purified via silica gel chromatography using a gradient of EtOAC/heptane (30-50%) to give the title compound (185 mg, 76% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 4.84 (t, J=5.4 Hz, 1 H), 3.61 (q, J=6.3 Hz, 2 H), 2.93 (t, J=6.8 Hz, 2 H), 2.52 (s, 3 H). m/z (APCI+) for C7H8Cl2N2OS 239.0 (M+H)+.
Reaction SMILES: [C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:12]=1[CH2:13][CH2:14][C:15]2=[O:20].C(Cl)Cl.O=O>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.C(N(CC)CC)C>[O:10]([C:11]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:12]=1[CH2:13][CH2:14][C:15]2=[O:20])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OB(O)c1ccccc1
Reactant: O=C1CCc2c(O)cccc21
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: O=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C1CCc2c(Oc3ccccc3)cccc21
Yield: 72.7 %

Procedure:
To phenyl boronic acid (1.0 g) and 4-hydroxy-2,3-dihydro-1H-inden-1-one (1.0 g), methylene chloride (67 mL) was added and thereto, copper (II) acetate (1.4 g), molecular sieves 4A (1.9 g), and triethylamine (4.7 mL) were added, followed by stirring the resultant reaction mixture at room temperature in an oxygen atmosphere for 19 hours. The reaction mixture was filtered through a pad of Celite and the filtered substance was washed with ethyl acetate. To the resultant filtrate, a 1M aqueous solution of sodium hydroxide was added and the resultant mixture was filtered through a pad of Celite again. The resultant filtrate was phase-separated into an aqueous phase and an organic phase and the aqueous phase was extracted with ethyl acetate to combine the resultant organic phase with the above organic phase. The combined organic phase was washed with saturated saline and was dried over sodium sulfate anhydride. From the organic phase, the solvent was distilled off under reduced pressure and the resultant residue was purified by silica gel column chromatography to obtain the subject compound (1.1 g) as an orange solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[O:9][C:10]([CH2:12][C:13]([OH:15])=O)=[CH:11][C:7]=2[CH:6]=[CH:5][CH:4]=1.C(Cl)(=O)C([Cl:19])=O>>[CH3:1][O:2][C:3]1[C:8]2[O:9][C:10]([CH2:12][C:13]([Cl:19])=[O:15])=[CH:11][C:7]=2[CH:6]=[CH:5][CH:4]=1
Reactant: O=C(Cl)C(=O)Cl
Reactant: COc1cccc2cc(CC(=O)O)oc12
Product: COc1cccc2cc(CC(=O)Cl)oc12
Yield: 100 %

Procedure:
A solution of 15.0 g of 7-methoxy-3-benzofuranacetic acid in 86 ml of oxalyl chloride was stirred at 25° for 1 hour. Removal of the solvent gave 16.35 g (100%) of crude 7-methoxy-3-benzofuranacetic acid chloride. NMR spectrum (200 mHz in CDCl3): δ4.0 (s, 3H), 4.23 (s, 2H), 6.83 (d, J=7 Hz, 1H), 7.07 (d, J=7 Hz, 1H), 7.18 (d, J=8 Hz, 1H) and 7.68 (s, 1H).
Reaction SMILES: [NH2:1][O:2][CH2:3][C:4]1[N:5]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:6]2[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[N:9]=[C:8]([NH2:16])[C:7]=2[N:17]=1.[CH3:22][C:23]([CH3:25])=O>CO.C(#N)C>[NH2:16][C:8]1[C:7]2[N:17]=[C:4]([CH2:3][O:2][N:1]=[C:23]([CH3:25])[CH3:22])[N:5]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:6]=2[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[N:9]=1
Reactant: CC(C)=O
Reactant: CC(C)Cn1c(CON)nc2c(N)nc3c(c21)CCCC3
Solvent: CC#N
Solvent: CO
Product: CC(C)=NOCc1nc2c(N)nc3c(c2n1CC(C)C)CCCC3

Procedure:
A solution of 2-[(aminooxy)methyl]-1-(2-methylpropyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine (700 mg, 2.42 mmol) in methanol (12 mL) and acetone (12 mL) was stirred at room temperature for 1 day, then was concentrated under reduced pressure to yield an oil. The oil was diluted with acetonitrile and concentrated under reduced pressure to yield a solid that was recrystallized from acetonitrile. The crystals were isolated by filtration, washed with acetonitrile, and dried in a vacuum oven to yield 379 mg of acetone O-{[4-amino-1-(2-methylpropyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-2-yl]methyl}oxime as white crystals, mp 176-177° C.
Reaction SMILES: [O:1]=[C:2]1[CH:11]=[C:10]([C:12]([O:14][CH3:15])=[O:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:16][CH:17]=O.[C:19]([O:23][C:24](=[O:43])[N:25]([CH2:32][C:33]1[CH:42]=[CH:41][C:36]2[O:37][CH2:38][CH2:39][O:40][C:35]=2[CH:34]=1)[CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)([CH3:22])([CH3:21])[CH3:20].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(O)(=O)C.C(Cl)(Cl)Cl>[C:19]([O:23][C:24](=[O:43])[N:25]([CH2:32][C:33]1[CH:42]=[CH:41][C:36]2[O:37][CH2:38][CH2:39][O:40][C:35]=2[CH:34]=1)[CH:26]1[CH2:31][CH2:30][N:29]([CH2:17][CH2:16][N:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[C:10]([C:12]([O:14][CH3:15])=[O:13])=[CH:11][C:2]2=[O:1])[CH2:28][CH2:27]1)([CH3:22])([CH3:20])[CH3:21]
Reactant: COC(=O)c1cc(=O)n(CC=O)c2ccccc12
Reactant: CC(C)(C)OC(=O)N(Cc1ccc2c(c1)OCCO2)C1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClC(Cl)Cl
Product: COC(=O)c1cc(=O)n(CCN2CCC(N(Cc3ccc4c(c3)OCCO4)C(=O)OC(C)(C)C)CC2)c2ccccc12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To 4 mL of a chloroform solution containing methyl 2-oxo-1-(2-oxoethyl)-1,2-dihydroquinoline-4-carboxylate, 0.12 g of tert-butyl(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(piperidin-4-yl)carbamate and 0.03 g of acetic acid were added, and stirred at room temperature for 2 hours. To the reaction mixture, 0.11 g of sodium triacetoxyborohydride was added, and stirred for 1.5 hours. Aqueous saturated sodium hydrogen carbonate solution was added, the organic layer was separated. The organic layer was washed with aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [Silica Gel; Kanto Chemical Co., Inc., Silica Gel 60N, eluent; ethyl acetate], to give 109 mg of tert-butyl(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(4-methoxycarbonyl-2-oxoquinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate as a yellow oil.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[S:10][C:11]([C:15]([OH:17])=[O:16])=[C:12]([CH3:14])[N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].IC.[C:22](=O)(O)[O-].[Na+]>CN(C)C=O>[C:1]([O:5][C:6]([N:8]([CH3:22])[C:9]1[S:10][C:11]([C:15]([OH:17])=[O:16])=[C:12]([CH3:14])[N:13]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1nc(NC(=O)OC(C)(C)C)sc1C(=O)O
Reactant: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CI
Product: Cc1nc(N(C)C(=O)OC(C)(C)C)sc1C(=O)O
Temperature: 25 °C

Procedure:
To a stirred solution of 2-(tert-butoxycarbonylamino)-4-methylthiazole-5-carboxylic acid (0.13 g, 0.50 mmol) in N,N-dimethylformamide (2.5 mL) at 0° C. was added sodium hydride (0.044 g, 1.10 mmol, 60% dispersed in mineral oil). The resultant mixture was stirred at 0° C. for 40 min, followed by the dropwise addition of iodomethane (31.2 mL, 0.50 mmol). The resultant solution was allowed to warm to ambient temperature over 18 h, followed by the addition of saturated sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography eluting with ethyl acetate/hexanes (50/50 to 100/0) to afford 2-(tert-butoxycarbonyl(methyl)amino)-4-methylthiazole-5-carboxylic acid (0.070 g, 0.26 mmol).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[OH:12])#[N:2].[C:13]([O-])([O-])=O.[K+].[K+].CI>CC(C)=O>[N+:9]([C:7]1[CH:6]=[CH:5][C:4]([O:12][CH3:13])=[C:3]([CH:8]=1)[C:1]#[N:2])([O-:11])=[O:10]
Reactant: N#Cc1cc([N+](=O)[O-])ccc1O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CI
Product: COc1ccc([N+](=O)[O-])cc1C#N

Procedure:
A mixture of 2-cyano-4-nitrophenol (3.5 g, 21 mmol), K2CO3 (5.9 g, 42 mmol), and MeI (9.08 g, 64 mmol) in acetone (50 mL) was heated at reflux overnight. The mixture was cooled and concentrated, taken up in H2O, stirred, filtered the yellow solid, dried by air (3.0 g, 79%). 1H NMR (400 MHz, CDCl3): d 4.08 (s, 3H), 7.12 (d, J=9.2 Hz, 1H), 8.5 (m, 2H).