Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[K+].CN(C)C=O.[CH:8]1[C:20]2[NH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]=2[CH:11]=[C:10]([CH:21]=O)[N:9]=1.[OH:23][NH:24]Cl>CO>[CH:8]1[C:20]2[NH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]=2[CH:11]=[C:10]([CH:21]=[N:24][OH:23])[N:9]=1
Reactant: O=Cc1cc2c(cn1)[nH]c1ccccc12
Reactant: ONCl
Agent: [K+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: CO
Product: ON=Cc1cc2c(cn1)[nH]c1ccccc12
Reaction time: 8 h
Yield: 67.3 %

Procedure:
A solution of 3.1 g of potassium hydroxide in 40 ml of methanol is added to a mixture of 150 ml of dimethylformamide, 6.9 g of beta-carboline-3-carboxaldehyde and 3.1 g of hydroxylamino-hydrochloride. The reaction mixture is allowed to stand at room temperature overnight. After evaporation, 50 ml of water is added. The reaction product is filtered off. 6.9 g of the air-dried product is heated in the steam bath together with 35 ml of 2 propanol and, after cooling, is filtered off. 5 g of beta-carboline-3-carboxaldehyde-oxime with a melting point of 229°-231° C. is obtained.
Reaction SMILES: [CH:1]([C:4]1[N:5]=[C:6]([C:9]2[CH:18]=[C:17](O)[C:16]3[C:11](=[C:12]([CH3:22])[C:13]([O:20][CH3:21])=[CH:14][CH:15]=3)[N:10]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2].P(Cl)(Cl)([Cl:25])=O.[OH-].[Na+]>>[CH:1]([C:4]1[N:5]=[C:6]([C:9]2[CH:18]=[C:17]([Cl:25])[C:16]3[C:11](=[C:12]([CH3:22])[C:13]([O:20][CH3:21])=[CH:14][CH:15]=3)[N:10]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2]
Reactant: COc1ccc2c(O)cc(-c3nc(C(C)C)cs3)nc2c1C
Reactant: O=P(Cl)(Cl)Cl
Agent: [Na+]
Agent: [OH-]
Product: COc1ccc2c(Cl)cc(-c3nc(C(C)C)cs3)nc2c1C
Temperature: 90 °C
Reaction time: 3 h
Yield: 91 %

Procedure:
2-(4-isopropylthiazol-2-yl)-4-hydroxy-7-methoxy-8-methyl-quinoline (4.63 g, 13.6 mmol., 1.0 eq.) was charged into a 100 mL round bottom flask. Phosphorous oxychloride (45 mL) was added and the reaction mixture stirred at 90° C. for 3 hours. Monitoring the reaction mixture by 1H NMR showed full consumption of the starting material. The reaction mixture was left to cool to ambient temperature and the solvent removed under vacuum. The residue was diluted with ethyl acetate (80 mL) and the reaction mixture cooled to 0° C. 2M aqueous sodium hydroxide solution was added portion wise until the pH of the aqueous phase was 14 (stir reaction mixture for 1 min between every NaOH addition). The two layers were separated and the organic layer was further washed with water (50 mL) and brine (50 mL). The organic layer was dried over sodium sulphate, filtered and the solvent removed under vacuum to give 4.11 g (91%) of the title compound as a pale brown solid. 1H NMR (500 MHz, CDCl3) δ ppm 8.28 (s, 1 H), 8.09 (d, J=9.16 Hz, 1 H), 7.38 (d, J=9.16 Hz, 1 H), 7.06 (s, 1 H), 4.02 (s, 3 H), 3.20 (spt, J=6.87 Hz, 1 H), 2.73 (s, 3 H), 1.40 (d, J=6.87 Hz, 6 H).
Reaction SMILES: [NH:1]([C:26]([CH3:28])=[O:27])[C@H:2]([C:11]([NH:13][C@H:14]([C:18]([NH:20][C@H:21]([C:23](O)=[O:24])[CH3:22])=[O:19])[CH:15]([CH3:17])[CH3:16])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.C(OC([NH:35][CH:36]([C:45](=[O:56])[CH2:46][O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=1[Cl:55])[CH2:37][C:38]([O:40]C(C)(C)C)=[O:39])=O)C=C>>[C:26]([NH:1][C@H:2]([C:11]([NH:13][C@H:14]([C:18]([NH:20][C@H:21]([C:23]([CH:37]([C@H:36]([NH2:35])[C:45](=[O:56])[CH2:46][O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=1[Cl:55])[C:38]([OH:40])=[O:39])=[O:24])[CH3:22])=[O:19])[CH:15]([CH3:17])[CH3:16])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=1)(=[O:27])[CH3:28]
Reactant: C=CCOC(=O)NC(CC(=O)OC(C)(C)C)C(=O)COCc1ccccc1Cl
Reactant: CC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)O)C(C)C
Product: CC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)C(C(=O)O)[C@H](N)C(=O)COCc1ccccc1Cl)C(C)C

Procedure:
N-Acetyl-(S)-tyrosinyl-(S)-valinyl-(S)-alaninyl-3(S)-amino-5-(2-chlorobenzyloxy)-4-oxo-pentanoic acid (89) was prepared from Ac-Tyr-Val-Ala-OH and (3S) t-butyl N-(allyloxycarbonyl)-3-amino-5-(2-chlorophenyl-methoxyl)-4-oxo-pentanoate (prepared by a similar method as 82) to give a white solid: 1H NMR (DMSO-d6) δ 9.15 (s, 1H), 8.5 (d, 1H), 7.98 (d, 1H), 7.75 (d, 1H), 7.55-7.3 (m, 4H), 7.0 (d, 1H), 6.6 (d, 2H), 4.6-4.3 (m, 6H), 4.3-4.1 (m, 2H), 2.9 (d, 1H), 2.76 (dd, 1H), 2.7-2.5 (m, 2H), 1.95 (m, 1H), 1.75 (s, 3H), 1.2 (d, 3H), 0.9-0.7 (dd, 6H)
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH2:10][C:11]([OH:13])=[O:12])[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].C(=O)([O-])[O-].[K+].[K+].[CH2:20](I)[CH3:21]>CN(C=O)C>[CH2:20]([O:12][C:11](=[O:13])[CH2:10][C:5]1[CH:6]=[CH:7][C:8]([F:9])=[C:3]([C:1]#[N:2])[CH:4]=1)[CH3:21]
Reactant: CCI
Reactant: N#Cc1cc(CC(=O)O)ccc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)Cc1ccc(F)c(C#N)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 87 %

Procedure:
To a suspension of (3-cyano-4-fluoro-phenyl)-acetic acid (500 mg, 2.79 mmol) (Preparation 126) and potassium carbonate (770 mg, 5.58 mmol) in DMF (5 mL) was added ethyl iodide (0.89 mL, 11.16 mmol) and the reaction mixture stirred at room temperature for 4 hours. The crude reaction mixture was poured onto water (10 mL) and extracted with ethyl acetate (3×15 mL). The combined organic layers were washed with water (5×10 mL), brine (10 mL), dried over sodium sulphate, filtered and concentrated under reduced pressure to afford the title compound as an off-white solid in 87% yield, 500 mg.
Reaction SMILES: I[C:2]1[C:3]2[C:8]([C:9]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[Br:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[C:16]1([C:9]2[C:10]3[C:15]([C:2]([C:26]4[CH:27]=[CH:28][C:23]([Br:22])=[CH:24][CH:25]=4)=[C:3]4[C:8]=2[CH:7]=[CH:6][CH:5]=[CH:4]4)=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: OB(O)c1ccc(Br)cc1
Reactant: Ic1c2ccccc2c(-c2ccccc2)c2ccccc12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: Brc1ccc(-c2c3ccccc3c(-c3ccccc3)c3ccccc23)cc1
Temperature: 80 °C
Reaction time: 9 h
Yield: 45 %

Procedure:
A mixture of 1.0 g (2.63 mmol) of 9-iodo-10-phenylanthracene, 542 mg (2.70 mmol) of p-bromo phenylboronic acid, 46 mg (0.03 mmol) of tetrakis(triphenylphosphine)palladium(0) (abbreviation: Pd(PPh3)4), 3 mL (6 mmol) of potassium carbonate aqueous solution (2 mol/L), and 10 mL of toluene was stirred for nine hours at 80° C. After reaction, toluene was added and filtration was carried out using florisil, celite, and alumina. A filtrate was washed with water and saturated saline, and then dried with magnesium sulfate. After the mixture was subjected to natural filtration, the filtrate was concentrated, and when it was recrystallized with chloroform and hexane, 562 mg of 9-phenyl-10-(4-bromophenyl)anthracene that was a target substance is obtained as a light brown solid at a yield of 45% (Synthesis scheme (b-4)).
Reaction SMILES: [C:1]1([O:7][C:8]2[C:13]([N+:14]([O-])=O)=[CH:12][CH:11]=[CH:10][C:9]=2[N+:17]([O-])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H][H]>C(O)C.[Pd]>[C:1]1([O:7][C:8]2[C:13]([NH2:14])=[CH:12][CH:11]=[CH:10][C:9]=2[NH2:17])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: [H][H]
Reactant: O=[N+]([O-])c1cccc([N+](=O)[O-])c1Oc1ccccc1
Agent: [Pd]
Solvent: CCO
Product: Nc1cccc(N)c1Oc1ccccc1

Procedure:
A suspension of 2,6-dinitrophenyl phenyl ether (6.5g.) in ethanol (100ml.) was shaken with hydrogen at room temperature and atmospheric pressure in the presence of palladium-on-charcoal (0.5g. of 5% w/w) as catalyst. When the theoretical amount of hydrogen (3.4 l.) had been absorbed, the mixture was filtered and the filtrate evaporated to dryness under reduced pressure. The solid residue (4.9g.) was crystallised from cyclohexane to give 2,6-diaminophenyl phenyl ether, m.p. 110°-111°C.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([C:8](=[C:11]([S:14][CH3:15])SC)[C:9]#[N:10])=O.[CH3:16][O:17][CH2:18][CH2:19][N:20]([CH2:22][C:23]1[CH:34]=[CH:33][C:26]([C:27]([NH:29][C:30]([NH2:32])=[NH:31])=[O:28])=[CH:25][CH:24]=1)[CH3:21].C(N(CC)CC)C>CN(C=O)C>[C:9]([C:8]1[C:6]([C:2]2[O:1][CH:5]=[CH:4][CH:3]=2)=[N:31][C:30]([NH:29][C:27](=[O:28])[C:26]2[CH:25]=[CH:24][C:23]([CH2:22][N:20]([CH2:19][CH2:18][O:17][CH3:16])[CH3:21])=[CH:34][CH:33]=2)=[N:32][C:11]=1[S:14][CH3:15])#[N:10]
Reactant: COCCN(C)Cc1ccc(C(=O)NC(=N)N)cc1
Reactant: CSC(SC)=C(C#N)C(=O)c1ccco1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COCCN(C)Cc1ccc(C(=O)Nc2nc(SC)c(C#N)c(-c3ccco3)n2)cc1

Procedure:
From 2-(furan-2-carbonyl)-3,3-bis-methylsulfanyl-acrylonitrile, N-(4-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-benzoyl)-guanidine and triethylamine in DMF. ES-MS m/e (%): 438 (M+H+, 100).
Reaction SMILES: Cl.[S:2]1[CH:6]=[CH:5][C:4]([C:7]([CH2:9][NH2:10])=[O:8])=[CH:3]1.C(=O)(O)[O-].[Na+].[Cl:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=1)[C:20](Cl)=[O:21]>>[Cl:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=1)[C:20]([NH:10][CH2:9][C:7]([C:4]1[CH:5]=[CH:6][S:2][CH:3]=1)=[O:8])=[O:21]
Reactant: O=C(Cl)c1cccc(Cl)c1
Reactant: NCC(=O)c1ccsc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: O=C(CNC(=O)c1cccc(Cl)c1)c1ccsc1
Yield: 93.1 %

Procedure:
7.5 g of N-[(3-thienylcarbonyl)methyl]amine hydrochloride, 10.0 g of sodium bicarbonate and 8.86 g of 3-chlorobenzoyl chloride are treated in the same manner as described in Preparation 1-(3). 11.0 g of N-(3-chlorobenzoyl)-N-[(3-thienylcarbonyl)methyl]amine are thereby obtained.
Reaction SMILES: [CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([CH2:10][C:11]([O:13][CH3:14])=[O:12])=[CH:4][C:3]=2[O:2]1.[N+:15]([C:18]1[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=1)([O-:17])=[O:16].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.C([O-])([O-])=O.[K+].[K+]>C(Cl)CCl.O>[CH2:1]1[O:2][C:3]2[C:8](=[CH:7][C:6]([C:22](=[O:23])[C:21]3[CH:20]=[CH:19][C:18]([N+:15]([O-:17])=[O:16])=[CH:26][CH:25]=3)=[C:5]([CH2:10][C:11]([O:13][CH3:14])=[O:12])[CH:4]=2)[O:9]1
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Reactant: COC(=O)Cc1ccc2c(c1)OCO2
Agent: O=C([O-])[O-]
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Agent: [K+]
Solvent: ClCCCl
Solvent: O
Product: COC(=O)Cc1cc2c(cc1C(=O)c1ccc([N+](=O)[O-])cc1)OCO2
Temperature: 25 °C
Yield: 50 %

Procedure:
To a solution of methyl 3,4-methylenedioxyphenylacetate (5.4 g, 28 mmol) in ClCH2CH2Cl (100 mL) was added 4-nitrobenzoic acid (7.2 g, 43 mmol) and P2O5 (18 g) at room temperature under argon. The mixture was refluxed for 28 h, cooled to room temperature, then cold water was added slowly. The resulting mixture was carefully neutralized with solid K2CO3, and extracted with 1:1 hexane/EtOAc (2×300 mL). The combined extracts were washed with water and brine, and dried over Na2SO4. The solvent was removed in vacuo and the resulting residue was separated by chromatography (3:1 hexane/EtOAc) to afford the title compound as a yellow solid (4.7 g, 14 mmol, 50%). 1H NMR (CDCl3) 8.32 (d, 2H, J=8.5), 7.92 (d, 2H, J=8.5), 6.85 (s, 1H), 6.81 (s, 1H), 6.07 (s, 2H), 3.88 (s, 2H), 3.63 (s, 3H).
Reaction SMILES: C([Sn](CCCC)(CCCC)[C:6]1[N:7]=[CH:8][N:9]([C:11]2[CH:16]=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)[CH:14]=[C:13]([C:27]([F:30])([F:29])[F:28])[N:12]=2)[CH:10]=1)CCC.[C:39]([NH:43][S:44]([C:47]1[S:48][C:49](Br)=[CH:50][CH:51]=1)(=[O:46])=[O:45])([CH3:42])([CH3:41])[CH3:40].CCCCCCC>C1(C)C=CC=CC=1>[C:39]([NH:43][S:44]([C:47]1[S:48][C:49]([C:6]2[N:7]=[CH:8][N:9]([C:11]3[CH:16]=[C:15]([C:17]4[CH:18]=[CH:19][C:20]([C:23]([F:25])([F:26])[F:24])=[CH:21][CH:22]=4)[CH:14]=[C:13]([C:27]([F:28])([F:29])[F:30])[N:12]=3)[CH:10]=2)=[CH:50][CH:51]=1)(=[O:45])=[O:46])([CH3:42])([CH3:40])[CH3:41]
Reactant: CCCC[Sn](CCCC)(CCCC)c1cn(-c2cc(-c3ccc(C(F)(F)F)cc3)cc(C(F)(F)F)n2)cn1
Reactant: CC(C)(C)NS(=O)(=O)c1ccc(Br)s1
Solvent: Cc1ccccc1
Solvent: CCCCCCC
Product: CC(C)(C)NS(=O)(=O)c1ccc(-c2cn(-c3cc(-c4ccc(C(F)(F)F)cc4)cc(C(F)(F)F)n3)cn2)s1
Temperature: 25 °C
Yield: 57.4 %

Procedure:
A stirred mixture of 2-(4-tributylstannanyl-imidazol-1-yl)-6-trifluoromethyl-4-(4-trifluoromethyl-phenyl)-pyridine (Example G.12) (0.570 g, 0.88 mmol), commercially available 5-bromo-thiophene-2-sulfonic acid tert-butylamide (0.295 g, 0.99 mmol), tetrakis(triphenyl-phosphine)palladium (0.061 g, 0.046 mmol) in toluene (6 mL) was heated under reflux conditions for 16 h. Cooled to rt, some precipitate occurred, diluted with toluene (˜5 mL), added heptane, filtered the precipitate off, washed with toluene/heptane, dried in HV to give the title compound as a white solid (290 mg, 57%). MS (ISP) 575.2 [(M+H)+]; mp>250° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].C(=O)([O-])[O-].[K+].[K+].[CH2:18](Cl)[C:19](=[CH2:21])[CH3:20]>CN(C)C=O>[CH3:18][C:19](=[CH2:21])[CH2:20][O:8][C:7](=[O:9])[C:6]1[CH:10]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=1[O:11][CH2:7][C:6]([CH3:10])=[CH2:5]
Reactant: C=C(C)CCl
Reactant: O=C(O)c1cc(Cl)ccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C=C(C)COC(=O)c1cc(Cl)ccc1OCC(=C)C

Procedure:
When this reaction was repeated employing 2.77 Kg of 5-chloro-2-hydroxybenzoic acid, 7.6 liters of dimethylformamide, 5.55 Kg of potassium carbonate, and 3.96 liters of methallyl chloride, the cooled reaction mixture was filtered and divided into two portions. Each portion was poured separately into a mixture of 2.8 liters of hexane, 1.4 liters of ethyl acetate and 7 liters of water. The layers were separated and the aqueous layer in each case extracted again with a mixture of 1.4 liters of hexane and 0.7 liters of ethyl acetate. The organic fractions were combined and washed with 4.1 liters of water followed by a sodium chloride solution of 800 grams of sodium chloride in 4.1 liters of water. The organic extracts were combined, dried over magnesium sulfate, filtered and concentrated in vacuo to provide 4.21 Kg of the desired intermediate.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12](Cl)(=[O:14])=[O:13])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4].[NH3:16]>>[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([NH2:16])(=[O:14])=[O:13])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOc1ccc(S(=O)(=O)Cl)cc1
Reactant: N
Product: CCCCOc1ccc(S(N)(=O)=O)cc1
Temperature: 20 °C
Reaction time: 0.5 h

Procedure:
100 ml of methanolic ammonia solution are added dropwise with ice-cooling to 10 g of 4-n-butoxybenzenesulfonyl chloride. After stirring at 20° C. for 1/2 hour, the mixture is concentrated, the residue is treated with water, acidified to pH 1-2 and filtered off with suction, M.p. 99°-101° C.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[N:12])[C:8]([O:13][CH3:14])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].O=S(Cl)Cl.[CH3:19]O>>[Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[N:12])[C:8]([O:13][CH3:14])=[CH:7][C:3]=1[C:4]([O:6][CH3:19])=[O:5]
Reactant: CO
Reactant: COc1cc(C(=O)O)c(Cl)cc1C#N
Solvent: O=S(Cl)Cl
Product: COC(=O)c1cc(OC)c(C#N)cc1Cl
Temperature: 0 °C
Reaction time: 24 h
Yield: 90 %

Procedure:
2-chloro-4-cyano-5-methoxybenzoic acid (600 mg; 2.84 mmol; 1 eq.) was dissolved in MeOH (12 mL). The solution was cooled down to 0° C. SOCl2 (0.62 mL; 8.51 mmol; 3 eq.) was added dropwise. The reaction mixture was stirred at RT for 24 hours. The reaction mixture was concentrated and the residue was taken up in EtOAc. The organic layer was washed with a saturated aqueous solution of NaHCO3, then brine, dried over MgSO4, concentrated affording the title compound as a yellow solid (0.58 g, 90%). 1H NMR (DMSO-d6, 300 MHz) δ 8.09 (s, 1H), 7.57 (s, 1H), 3.96 (s, 3H), 3.89 (s, 3H). HPLC (Method A) Rt 4.08 min (Purity: 94.3%).
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[N:7]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH2:16]O)[CH:11]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].C(Br)(Br)(Br)[Br:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Br:20][CH2:16][C:12]1[CH:11]=[C:10]([CH:15]=[CH:14][CH:13]=1)[CH2:9][N:7]([CH3:8])[C:6](=[O:18])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2]
Reactant: CN(Cc1cccc(CO)c1)C(=O)OC(C)(C)C
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CN(Cc1cccc(CBr)c1)C(=O)OC(C)(C)C
Reaction time: 96 h
Yield: 63.3 %

Procedure:
A stirred solution of tert-butyl-N-[3-(hydroxymethyl)benzyl]-N-methylcarbamate (4.2 g, 16.7 mmol) in CH2Cl2 (150 ml) at 0° C., was treated with carbon tetrabromide (8.0 g, 24.1 mmol) and triphenyl phosphine (6.35 g, 24.21 mmol). The resultant solution was warmed to room temperature and stirred for 4 days. The resultant mixture was evaporated to dryness and the residue purified by chromatography (SiO2, gradient elution with 100% hexane; 99:1 hexane:ethyl acetate; 95:5 hexane: ethyl acetate) to give the desired product (3.32 g, 60%). 1H NMR (CDCl3) δ 1.50 (s, 9H), 2.80 (s, br, 3H), 4.20 (s, 2H), 4.30 (s, 2H), 7.15 (m, 1H), 7.25 (m, 1H), 7.30 (m, 2H). LRMS m/z=333.2 (M+18)+.
Reaction SMILES: [CH2:1]([O:19][CH2:20][CH:21]([CH2:41][OH:42])[O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]/[CH:31]=[CH:32]\[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH3:43][N:44]([CH3:52])[CH2:45][CH2:46][NH:47][S:48](Cl)(=[O:50])=[O:49]>C(Cl)Cl.N1C=CC=CC=1.C(Cl)Cl>[CH3:43][N:44]([CH3:52])[CH2:45][CH2:46][NH:47][S:48]([O:42][CH2:41][CH:21]([O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]/[CH:31]=[CH:32]\[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH2:20][O:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])(=[O:50])=[O:49]
Reactant: CCCCCCCC/C=C\CCCCCCCCOCC(CO)OCCCCCCCC/C=C\CCCCCCCC
Reactant: CN(C)CCNS(=O)(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCCCCCC/C=C\CCCCCCCCOCC(COS(=O)(=O)NCCN(C)C)OCCCCCCCC/C=C\CCCCCCCC
Reaction time: 2 h
Yield: 18.3 %

Procedure:
In 4 ml of methylene chloride-pyridine (2:1) was dissolved 150 mg (0.25 mmol) of 1,2-O-dioleylglycerol. Then, 1 ml of a solution of 150 mg (0.75 mmol) (2-dimethylaminoethyl)sulfamoyl chloride in methylene chloride was added and the reaction was carried out at ambient temperature for 2 hours. After completion of the reaction, the solvent was distilled off under reduced pressure and the residue was treated with methylene chloride-saturated aqueous sodium hydrogen carbonate solution. The methylene chloride layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to column chromatography (silica gel/methylene chloride-methanol) to provide 34 mg (18%) of the title compound. 1H-NMR (200 MHz, CDCl3) δ:0.88 (6H, t, J=6 Hz), 1.20-1.40 (44H, m), 1.45-1.65 (4H, m), 1.90-2.10 (8H, m), 2.24 (6H, s), 2.48 (2H, t, J=6 Hz), 3.18 (2H, t, J=6 Hz), 3.40-3.60 (6H, m), 3.60-3.75 (1H, m), 4.08-4.30 (2H, m), 5.30-5.40 (4H, m) MS (FAB): 743 (M+H)+
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][NH2:8])[CH:2]=1.[C:9]([O:13][CH3:14])(=[O:12])[CH:10]=[CH2:11]>CO>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][NH:8][CH2:11][CH2:10][C:9]([O:13][CH3:14])=[O:12])[CH:2]=1
Reactant: C=CC(=O)OC
Reactant: NCc1cccnc1
Solvent: CO
Product: COC(=O)CCNCc1cccnc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 82.6 %

Procedure:
3-Pyridylmethylamine (10.81 g) is dissolved in methanol (50 ml), and thereto is added dropwise methyl acrylate (8.60 g) under ice-cooling. The mixture is stirred at room temperature for 18 hours. The mixture is distilled to remove the solvent, and then the residue is distilled under reduced pressure to give methyl 3-(3-pyridylmethylamino)propionate (16.02 g, 82.5%), b.p. 119°-120° C./0.4 mmHg.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][C:7](=[O:12])[CH:6]=[CH:5]2.[H-].[Na+].[CH3:15][C:16]([CH3:20])=[CH:17][CH2:18]Br>CN(C)C=O>[CH3:15][C:16]([CH3:20])=[CH:17][CH2:18][O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][C:7](=[O:12])[CH:6]=[CH:5]2
Reactant: O=c1ccc2cc(O)ccc2o1
Reactant: CC(C)=CCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)=CCOc1ccc2oc(=O)ccc2c1
Temperature: 0 °C

Procedure:
An oven-dried 50 mL round bottom flask was prepared with a magnetic stirring bar, a rubber septum cover, and a nitrogen inlet. 6-hydroxycoumarin (1) (114 mg, 0.7 mmol) and 4 mL of anhydrous N,N-dimethylformamide (DMF) were added to the round bottom flask. The solution was stirred and cooled to 0° C. in a salt-ice bath. Sodium hydride (28 mg of 60% mineral oil suspension, 0.7 mmol) was added to the flask and the solution was kept stirring at 0° C. for 30 minutes. 3,3-dimethylallyl bromide (192 μL, 1.66 mmol) in 1 mL of anhydrous DMF was cooled to 0° C. and added drop-wise to the flask through the rubber septum using a syringe. The reaction mixture was left stirring under nitrogen at room temperature for 14 hours. The desired product was isolated via column chromatography using a solvent system of 100% Hexanes, 20:1 Hexanes:Ethyl acetate, 15:1 Hexanes:Ethyl acetate, 10:1 Hexanes:Ethyl acetate, 7:3 Hexanes:Ethyl acetate, and 2:1 Hexanes:Ethyl acetate. The purified product was characterized by NMR spectroscopy (1H-NMR, 13C-NMR) and high-resolution mass spectrometry (HRMS). 1H-NMR (300 MHz, CDCl3): δ 1.76-1.87 (6H), 4.54 (d, 2H, J=6 Hz), 5.50 (m, 1H), 6.43 (m, 1H), 6.92-7.67 (4H); 13C-NMR (75 MHz, CDCl3): δ 18.68, 26.27, 65.86, 111.35, 117.42, 118.26, 119.44, 119.54, 120.53, 139.38, 143.69, 148.80, 155.71, 161.47. FIRMS (ES) Calcd. for C14H15O3: 231.1021. found: 231.1024.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Br:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13].[O:17]=[C:18]([C:27]1[CH:32]=[CH:31][N:30]=[N:29][CH:28]=1)[CH2:19][C:20](OC(C)(C)C)=[O:21]>>[Br:8][C:6]1[CH:5]=[CH:4][C:3]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:15])[CH3:14])=[C:2]([NH:1][C:20](=[O:21])[CH2:19][C:18](=[O:17])[C:27]2[CH:32]=[CH:31][N:30]=[N:29][CH:28]=2)[CH:7]=1
Reactant: CC(C)(C)OC(=O)Nc1ccc(Br)cc1N
Reactant: CC(C)(C)OC(=O)CC(=O)c1ccnnc1
Product: CC(C)(C)OC(=O)Nc1ccc(Br)cc1NC(=O)CC(=O)c1ccnnc1

Procedure:
The title compound was prepared from the reaction of tert-butyl 2-amino-4-bromophenylcarbamate (Example B1; 1 mmol) and tert-butyl 3-oxo-3-(pyridazin-4-yl)propanoate (Example C1; 1 mmol) according to the general procedure D. Obtained as a yellow solid (89%), MS (EI) 435 [(M+1)+].
Reaction SMILES: C[Si](C)(C)[O:3][C:4]([C:6]1[CH:10]=[CH:9][S:8][CH:7]=1)=[CH2:5].[F-].[Cs+].[OH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22](=[O:34])[CH:23]=[CH:24][C:25]1[CH:30]=[CH:29][C:28]2[O:31][CH2:32][O:33][C:27]=2[CH:26]=1>CS(C)=O>[OH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22](=[O:34])[CH2:23][CH:24]([C:25]1[CH:30]=[CH:29][C:28]2[O:31][CH2:32][O:33][C:27]=2[CH:26]=1)[CH2:3][C:4]([C:6]1[CH:10]=[CH:9][S:8][CH:7]=1)=[O:5]
Reactant: C=C(O[Si](C)(C)C)c1ccsc1
Reactant: O=C(C=Cc1ccc2c(c1)OCO2)c1ccccc1O
Agent: [Cs+]
Agent: [F-]
Solvent: CS(C)=O
Product: O=C(CC(CC(=O)c1ccccc1O)c1ccc2c(c1)OCO2)c1ccsc1
Temperature: 70 °C

Procedure:
1-Trimethylsilyloxy-1-(thiophen-3-yl)ethylene (7.0 mmol; prepared according to J. Chem. Soc., Perkin Trans. I 1989, 1585) and CsF (0.27 g, 1.76 mmol) were added to a suspension 1-(2-hydroxyphenyl)-3-(3,4-methylenedioxyphenyl)-2-propen-1-one on Wang resin (2.0 g, 1.76 mmol) in dimethyl sulfoxide (30 mL). The reaction mixture was heated to 70° C. for 3 h and the reaction was quenched with 10% AcOH/CH2Cl2. The resin was filtered, washed with DMF (×2) and alternating MeOH and CH2Cl2(×5), and dried under high vacuum overnight to give 1-(2-hydroxyphenyl)-3-(3,4-methylenedioxyphenyl)-5-(thiophen-3-yl)-1,5-pentanedione on Wang resin.