Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)=[CH:14][N:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1.C([O:28][CH2:29][C:30]1[C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][C:33]([F:45])=[CH:32][C:31]=1[N:46]1[CH2:58][CH2:57][N:49]2[C:50]3[CH2:51][CH2:52][CH2:53][CH2:54][C:55]=3[CH:56]=[C:48]2[C:47]1=[O:59])(=O)C.C([O-])([O-])=O.[Cs+].[Cs+].O>CC#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:45][C:33]1[CH:34]=[C:35]([C:2]2[CH:3]=[C:4]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)=[CH:14][N:13]=3)[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[CH:7]=2)[C:30]([CH2:29][OH:28])=[C:31]([N:46]2[CH2:58][CH2:57][N:49]3[C:50]4[CH2:51][CH2:52][CH2:53][CH2:54][C:55]=4[CH:56]=[C:48]3[C:47]2=[O:59])[CH:32]=1
Reactant: CC(=O)OCc1c(B2OC(C)(C)C(C)(C)O2)cc(F)cc1N1CCn2c(cc3c2CCCC3)C1=O
Reactant: CN1CCN(c2ccc(Nc3cc(Cl)cn4ccnc34)nc2)CC1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CC#N
Product: CN1CCN(c2ccc(Nc3cc(-c4cc(F)cc(N5CCn6c(cc7c6CCCC7)C5=O)c4CO)cn4ccnc34)nc2)CC1
Temperature: 140 °C
Yield: 27.5 %

Procedure:
A 25 mL sealed tube was charged with 101b (300 mg, 0.88 mmol), 101l (423 mg, 0.88 mmol), Cs2CO3 (572 mg, 1.76 mmol), Pd2(dba)3 (80 mg, 0.09 mmol) suspended in CH3CN (25 mL), and H2O (1 mL). The mixture was heated at 140° C. under microwave irradiation for 1 hour. It was then evaporated and the residue was purified by silica-gel column eluting with 10:1 methylene chloride/methanol to give the crude product, which was further purified by reverse phase Combi-flash eluting with 0.3% NH4HCO3 in 1:4 water/CH3CN to afford 101 as a yellow solid (150 mg, 28%). MS: (M+H)+ 621. 1H NMR (500 MHz, DMSO) δ 8.94 (s, 1H), 8.27 (d, J=1.5, 1H), 8.16 (d, J=1.5, 1H), 7.96 (d, J=1.0, 1H), 7.91 (d, J=2.5, 1H), 7.58 (d, J=1.5, 1H), 7.33-7.42 (m, 3H), 7.25-7.28 (m, 1H), 6.53 (s, 1H), 4.88 (t, J=4.5, 1H), 4.30 (d, J=4.5, 2H), 4.12-4.20 (m, 3H), 3.90-3.92 (m, 1H), 3.06 (t, J=4.5, 4H), 2.53-2.65 (m, 2H), 2.43-2.48 (m, 6H), 2.21 (s, 3H), 1.76-1.81 (m, 2H), 1.67-1.71 (m, 2H)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]2[C:4]=1[C:5](=[O:16])[CH:6]=[CH:7][C:8]2=[O:15].[CH3:17][NH2:18].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[Na+].[Na+].S(=O)(=O)(O)O.[Cl-].[Na+].S([O-])([O-])(=O)=O.[Na+].[Na+]>CO.O>[CH3:17][NH:18][C:6]1[C:5](=[O:16])[C:4]2[C:9]([C:8](=[O:15])[CH:7]=1)=[C:10]([O:13][CH3:14])[CH:11]=[CH:12][C:3]=2[O:2][CH3:1]
Reactant: COc1ccc(OC)c2c1C(=O)C=CC2=O
Reactant: CN
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: O=S(=O)(O)O
Agent: O=S(=O)([O-])[O-]
Solvent: O
Solvent: CO
Product: CNC1=CC(=O)c2c(OC)ccc(OC)c2C1=O
Temperature: 25 °C
Reaction time: 0.05 h

Procedure:
0.45 mM 5,8-dimethoxy-1,4-naphthoquinone (4) which had been prepared above was dissolved in 30 ml of methanol in 100 ml one-neck round flask and then, 0.687 mmol methylamine was added thereto and stirred at room temperature for 3 hours 0.64 mM sodium dichromate and 0.18 mM sulfuric acid dissolved in water were slowly dropped to the reaction mixture and stirred at room temperature for 3 minutes. Then, 50 ml of saturated sodium chloride was added to the reaction mixture, followed by extraction three times with 50 ml of chloroform and obtained organic layers were gathered and dehydrated with anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was subjected to silicagel column chromatography, thereby producing 2-methylamino-5,8-dimethoxy-1,4-naphthoquinone that was reddish brown. The yield and properties of the synthesized compound are as follows.
Reaction SMILES: C([O:3][C:4](=[O:29])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:16]3[CH:17]=[CH:18][C:19]([C:21]4[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=4)=[CH:20][C:15]=3[N:14]=[CH:13]2)=[CH:8][CH:7]=1)C>C(Cl)Cl.CO>[CH3:28][O:27][C:24]1[CH:23]=[CH:22][C:21]([C:19]2[CH:18]=[CH:17][C:16]3[N:12]([C:9]4[CH:10]=[CH:11][C:6]([CH2:5][C:4]([OH:29])=[O:3])=[CH:7][CH:8]=4)[CH:13]=[N:14][C:15]=3[CH:20]=2)=[CH:26][CH:25]=1
Reactant: CCOC(=O)Cc1ccc(-n2cnc3cc(-c4ccc(OC)cc4)ccc32)cc1
Solvent: CO
Solvent: ClCCl
Product: COc1ccc(-c2ccc3c(c2)ncn3-c2ccc(CC(=O)O)cc2)cc1

Procedure:
The title compound is prepared as described in Step 20.1 (Procedure B) but using {4-[5-(4-methoxy-phenyl)-benzoimidazol-1-yl]-phenyl}-acetic acid ethyl ester. The title compound: ES-MS: 359.3 [M+H]+; single peak at tR=3.60 min (System 1); Rf=0.26 (CH2Cl2/MeOH+1% NH3aq, 9:1).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:27])[CH2:5][CH2:6][C:7]1[CH:12]=[C:11]([C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:16]=2)=[O:14])[CH:10]=[CH:9][C:8]=1[OH:26])[CH3:2].[Br:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]Br>>[CH2:1]([O:3][C:4](=[O:27])[CH2:5][CH2:6][C:7]1[CH:12]=[C:11]([C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:16]=2)=[O:14])[CH:10]=[CH:9][C:8]=1[O:26][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][Br:28])[CH3:2]
Reactant: BrCCCCCCCCBr
Reactant: CCOC(=O)CCc1cc(C(=O)c2cccc(C(=O)OCC)c2)ccc1O
Product: CCOC(=O)CCc1cc(C(=O)c2cccc(C(=O)OCC)c2)ccc1OCCCCCCCCBr
Yield: 72.6 %

Procedure:
Starting with 0.370 g (1.0 mmol) of 5-[[3-(ethoxycarbonyl)phenyl]carbonyl]-2-hydroxybenzenepropanoic acid ethyl ester, and 2.17 g (7.98 mmol) of 1,8-dibromooctane, the title compound was obtained as a colorless oil, in 72.6% yield, using the procedure of example 21.
Reaction SMILES: [CH3:1][N:2]([CH2:10][C:11]([N:13]1[CH2:18][CH2:17][S:16][C:15]2[CH:19]=[CH:20][C:21]([N+:23]([O-:25])=[O:24])=[CH:22][C:14]1=2)=O)[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].B.O1CCCC1>O1CCCC1>[CH3:1][N:2]([CH2:10][CH2:11][N:13]1[CH2:18][CH2:17][S:16][C:15]2[CH:19]=[CH:20][C:21]([N+:23]([O-:25])=[O:24])=[CH:22][C:14]1=2)[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:6])[CH3:7]
Reactant: CN(CC(=O)N1CCSc2ccc([N+](=O)[O-])cc21)C(=O)OC(C)(C)C
Agent: B
Solvent: C1CCOC1
Product: CN(CCN1CCSc2ccc([N+](=O)[O-])cc21)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.1 %

Procedure:
To a stirred solution of tert-butyl methyl(2-(6-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)-2-oxoethyl)carbamate (691 mg, 1.881 mmol) in tetrahydrofuran (5 mL) was added borane-tetrahydrofuran complex (1 M in tetrahydrofuran; 5.64 mL, 5.64 mmol). The resulting mixture was then stirred at room temperature for 2 hours and quenched carefully via the slow, dropwise addition of methanol (5 mL). The quenched mixture was then diluted with ethyl acetate and washed sequentially with a 1:1 mixture of water: saturated sodium carbonate (2×) and then with brine. The organic phase was dried, filtered, and concentrated giving a red oil (659 mg, 99%). 1H NMR (DMSO-d6) δ 7.56-7.39 (m, 1H), 7.39-7.31 (m, 1H), 7.24-7.14 (m, 1H), 3.68-3.61 (m, 2H), 3.60-3.49 (m, 2H), 3.48-3.36 (m, 2H), 3.13-3.05 (m, 2H), 2.83 (s, 3H), 1.30, 1.17 (2s, 9H); ESI-MS (m/z, %): 376 (M+Na, 85), 354 (MH+, 24), 298 (100).
Reaction SMILES: [CH3:1][C@H:2]1[CH2:7][NH:6][C:5](=O)[CH2:4][N:3]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:25])=CC=1>>[CH3:1][C@H:2]1[CH2:7][NH:6][C:5](=[S:25])[CH2:4][N:3]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10]
Reactant: C[C@H]1CNC(=O)CN1C(=O)OC(C)(C)C
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Product: C[C@H]1CNC(=S)CN1C(=O)OC(C)(C)C
Temperature: 80 °C
Yield: 148.2 %

Procedure:
To a suspension of (S)-tert-butyl 2-methyl-5-oxopiperazine-1-carboxylate (7.0 g, 32.7 mmol) was added Lawesson's reagent (6.9 g, 16.7 mmol) and the reaction mixture was heated to 80° C. for 2 hours. The reaction mixture was cooled to room temperature, concentrated onto silica gel and purified by flash column chromatography (0-100% 10% 4M NH3 in MeOH in DCM) to provide the desired compound (5.7 g, 76%). 1H NMR (400 MHz, DMSO) δ 10.64 (s, 1H), 4.48 (d, J=18.9 Hz, 1H), 4.31-4.14 (m, 1H), 4.06 (d, J=18.9 Hz, 1H), 3.49-3.41 (m, 1H), 3.13 (ddd, J=13.7, 4.8, 2.9 Hz, 1H), 1.43 (s, 9H), 1.07 (d, J=6.6 Hz, 3H).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]1[C:24]2[C:25]3=[C:26]4[C:21](=[CH:22][CH:23]=2)[CH:20]=[CH:19][C:18]([C:27]2[CH:36]=[CH:35][C:34]5[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=5)[CH:28]=2)=[C:17]4[CH:16]=[CH:15][C:14]3=[C:13]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:12]=1.C1C(=O)N([Br:50])C(=O)C1.O>CN(C=O)C>[Br:50][C:20]1[C:21]2[C:26]3=[C:25]4[C:24](=[CH:23][CH:22]=2)[C:11]([C:2]2[CH:3]=[CH:4][C:5]5[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=5)[CH:1]=2)=[CH:12][C:13]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)=[C:14]4[CH:15]=[CH:16][C:17]3=[C:18]([C:27]2[CH:36]=[CH:35][C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH:28]=2)[CH:19]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: c1ccc(-c2cc(-c3ccc4ccccc4c3)c3ccc4ccc(-c5ccc6ccccc6c5)c5ccc2c3c45)cc1
Solvent: CN(C)C=O
Solvent: O
Product: Brc1cc(-c2ccc3ccccc3c2)c2ccc3c(-c4ccccc4)cc(-c4ccc5ccccc5c4)c4ccc1c2c34

Procedure:
5.4 g of 1,6-dinaphthalene-2-yl-3-phenylpyrene was dispersed into 60 ml of DMF, and 1.9 g NBS in DMF solution was dropped therein at room temperature. After 3 days reaction, 150 ml of water was added to it and the deposited crystal was filtrated, followed by water and ethanol washing of the crystal.
Reaction SMILES: [O:1]=[C:2]1[O:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[C@H:3]1[CH2:17][CH2:18][C:19](O)=[O:20].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C1COCC1.C(Cl)Cl>[O:1]=[C:2]1[O:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)=[O:8])[C@H:3]1[CH2:17][CH2:18][CH:19]=[O:20]
Reactant: O=C(O)CC[C@H]1C(=O)OCN1C(=O)OCc1ccccc1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: C1CCOC1
Product: O=CCC[C@H]1C(=O)OCN1C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 51.4 %

Procedure:
A solution of 27 g (92.7 mmol) of the crude acid (43c) in 200 mL of THF is cooled to 0° C. and 13 mL (10.7 g, 141 mmol) of borane-methyl sulfide complex is added dropwise via an addition funnel. The reaction is allowed to warm gradually to room temperature and stirred for 12 h. The resulting mixture is concentrated in vacuo to give a white glassy material which is taken up in 500 mL of methylene chloride and treated with of pyridinium chlorochromate (61 g, 281 mmol) at 0° C. in the presence of 3 molecular sieve. The mixture is allowed to warm to room temperature and stirred for 3 h. The mixture is filtered through diatomaceous earth with ether (200 mL) then concentrated. The residue is taken up in ether and filtered again through diatomaceous earth with ether then concentrated to give 13.22 g of the crude aldehyde as a light green oil: NMR δ 9.80 (br s, 1H), 7.40 (m, 5H), 5.55 (br s, 1H), 5.20 (m, 3H), 4.38 (t, J=6.0 Hz, 1H), 2.6-2.1 (m, 4H).
Reaction SMILES: [F:1][C:2]([F:43])([F:42])[C:3]1[CH:41]=[CH:40][C:6]([CH2:7][N:8]([CH2:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=2)[C:9](=[O:28])[CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15]([CH2:18][C@H:19]([O:25][CH2:26][CH3:27])[C:20]([O:22]CC)=[O:21])=[CH:14][CH:13]=2)=[CH:5][CH:4]=1>C(#N)C.O.[Li+].[OH-]>[F:1][C:2]([F:42])([F:43])[C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]([CH2:29][C:30]2[CH:31]=[CH:32][C:33]([C:36]([F:37])([F:39])[F:38])=[CH:34][CH:35]=2)[C:9](=[O:28])[CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15]([CH2:18][C@H:19]([O:25][CH2:26][CH3:27])[C:20]([OH:22])=[O:21])=[CH:14][CH:13]=2)=[CH:40][CH:41]=1
Reactant: CCOC(=O)[C@H](Cc1ccc(OCC(=O)N(Cc2ccc(C(F)(F)F)cc2)Cc2ccc(C(F)(F)F)cc2)cc1)OCC
Agent: [Li+]
Agent: [OH-]
Solvent: CC#N
Solvent: O
Product: CCO[C@@H](Cc1ccc(OCC(=O)N(Cc2ccc(C(F)(F)F)cc2)Cc2ccc(C(F)(F)F)cc2)cc1)C(=O)O
Temperature: 25 °C
Reaction time: 8 h
Yield: 45.5 %

Procedure:
To a solution of ethyl(2S)-3-[4-(2-{bis[4-(trifluoromethyl)benzyl]amino}-2-oxoethoxy)phenyl]-2-ethoxypropanoate (0.662 g, 1.1 mmol) in acetonitrile (54 mL) was added aqueous 0.10 M LiOH (27 mL) and the solution was stirred at room temperature overnight. The solvent volume was reduced in vacuo and the remaining aqueous phase was diluted with water and aqueous 0.10 M LiOH (to a total volume of 300 mL, pH˜12) and washed with diethyl ether (2×100 mL). (The extraction process was complicated by the formation of emulsions.) The aqueous phase was acidified with 2 M HCl and extracted with ethyl acetate (3×100 mL). The combined organic phase was washed with brine (100 mL), dried over Na2SO4, and concentrated in vacuo to afford 0.292 g (46%) of a colourless oil.
Reaction SMILES: [C:1]1([CH2:7][S:8](Cl)(=[O:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br.[Br:13][CH2:14][CH2:15][CH2:16][NH2:17].CCN(CC)CC>C1COCC1>[Br:13][CH2:14][CH2:15][CH2:16][NH:17][S:8]([CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)(=[O:10])=[O:9]
Reactant: NCCCBr
Reactant: O=S(=O)(Cl)Cc1ccccc1
Agent: Br
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=S(=O)(Cc1ccccc1)NCCCBr
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 92.4 %

Procedure:
A solution of phenylmethanesulfonyl chloride (2.19 g, 10 mmol) was added into a suspension of 3-bromopropan-1-amine hydrobromide (2.19 g, 10 mmol) and Et3N (2.02 g, 20 mmol) in THF (50 mL) at 0° C. The mixture was stirred at 0° C. for 5 min. TLC confirmed the completion of reaction. Solid was filtered out with suction, and the filtrate was concentrated to provide compound N-(3-bromopropyl)(phenyl)methanesulfonamide (2.7 g, quant.) as a pale yellow solid which was used in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 7.40 (m, 5H), 4.48 (m, 1H), 4.27 (s, 2H), 3.41 (t, J=6.6 Hz, 2H), 3.16 (q, 2H), 2.01 (m, 2H). LCMS (ESI), m/z, 314 and 316 [M+Na]+, Br pattern found.
Reaction SMILES: [CH2:1]([N:3]([CH2:14][CH3:15])[C:4]([O:6][C:7]1[CH:8]=[N:9][CH:10]=[CH:11][C:12]=1[NH2:13])=[O:5])[CH3:2].CCOCC>COC(OC)N(C)C>[CH2:14]([N:3]([CH2:1][CH3:2])[C:4]([O:6][C:7]1[CH:8]=[N:9][CH:10]=[CH:11][C:12]=1[N:13]=[CH:1][N:3]([CH3:14])[CH3:4])=[O:5])[CH3:15]
Reactant: CCN(CC)C(=O)Oc1cnccc1N
Agent: COC(OC)N(C)C
Solvent: CCOCC
Product: CCN(CC)C(=O)Oc1cnccc1N=CN(C)C

Procedure:
4-Amino-3-pyridinol N,N-diethylcarbamate (5.80 g) was refluxed for 30 minutes in 50 mL of N,N-dimethylformamide dimethyl acetal. At the end of this time the reaction mixture was concentrated under reduced pressure and the residue was purified by flash chromatography (5% Et3N/ethyl acetate) to give, after concentration of the product-containing fractions, 4.63 g of chromatographically pure product. An analytically pure material was obtained by recrystallizatin from Et2O, m.p. 67°-69° C.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[CH:4][C:5]2[S:10][CH:9]=[C:8]([NH:11][C:12]3[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=3)[C:6]=2[N:7]=1.[H-].[Na+].I[CH3:27]>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[S:10][CH:9]=[C:8]([N:11]([CH3:27])[C:12]3[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=3)[C:6]=2[N:7]=1
Reactant: CI
Reactant: COc1cc(Nc2csc3cnc(Cl)nc23)cc(OC)c1OC
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1cc(N(C)c2csc3cnc(Cl)nc23)cc(OC)c1OC
Reaction time: 0.17 h
Yield: 90 %

Procedure:
2-Chloro-N-(3,4,5-trimethoxyphenyl)thieno[3,2-d]pyrimidin-7-amine (30 mg, 0.085 mmol) was dissolved in N,N-dimethylformamide (1 mL) and sodium hydride (5.2 mg, 0.13 mmol) was added at 0° C. After stirring for 10 minutes and adding iodomethane (15 mg, 0.10 mmol), the mixture was stirred for an hour, diluted with ethyl acetate, and washed with brine. The organic layer was dried with magnesium sulfate, filtered with celite, and then concentrated. The target compound (28 mg, 89% yield) was obtained without purification.
Reaction SMILES: [C:1]([CH2:4][O:5][C:6]1[CH:11]=[C:10]([O:12][CH2:13][CH:14]=[C:15]([CH3:17])[CH3:16])[CH:9]=[CH:8][C:7]=1[C:18](=[O:20])[CH3:19])([OH:3])=[O:2].[CH2:21]([C:24]1[CH:31]=[CH:30][C:27]([CH:28]=O)=[CH:26][CH:25]=1)[CH:22]=[CH2:23].[OH-].[K+]>C(O)C>[C:1]([CH2:4][O:5][C:6]1[CH:11]=[C:10]([O:12][CH2:13][CH:14]=[C:15]([CH3:16])[CH3:17])[CH:9]=[CH:8][C:7]=1[C:18](=[O:20])[CH:19]=[CH:28][C:27]1[CH:30]=[CH:31][C:24]([CH2:21][CH:22]=[CH2:23])=[CH:25][CH:26]=1)([OH:3])=[O:2]
Reactant: CC(=O)c1ccc(OCC=C(C)C)cc1OCC(=O)O
Reactant: C=CCc1ccc(C=O)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: C=CCc1ccc(C=CC(=O)c2ccc(OCC=C(C)C)cc2OCC(=O)O)cc1
Reaction time: 0.33 h
Yield: 29.6 %

Procedure:
To a solution of 834 mg of 2'-(1-carboxymethoxy)-4'-(3-methyl-2-butenyloxy)acetophenone and 500 mg of 4-(2-propenyl)benzaldehyde in 10 ml of ethanol was added 842 mg of potassium hydroxide, and the mixture was stirred for 20 minutes. After neutralization with dilute hydrochloric acid, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried, and the solvent was evaporated under reduced pressure. The residue was recrystallized from ethyl acetate - n-hexane to give 360 mg of the title compound as a pale yellow needles.
Reaction SMILES: [H-].[Na+].[CH3:3][S:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[NH:15][CH:14]=[C:13]([CH:16]=[O:17])[CH:12]=1.C1OCCOCCOCCOCCOC1.[N:33]1[CH:38]=[CH:37][CH:36]=[C:35]([S:39](Cl)(=[O:41])=[O:40])[CH:34]=1>O1CCCC1.O>[CH3:3][S:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[N:15]([S:39]([C:35]2[CH:34]=[N:33][CH:38]=[CH:37][CH:36]=2)(=[O:41])=[O:40])[CH:14]=[C:13]([CH:16]=[O:17])[CH:12]=1
Reactant: O=S(=O)(Cl)c1cccnc1
Reactant: CSc1ccccc1-c1cc(C=O)c[nH]1
Agent: C1COCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CSc1ccccc1-c1cc(C=O)cn1S(=O)(=O)c1cccnc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 68.7 %

Procedure:
To a suspension of sodium hydride (60% in oil, 40 mg) in tetrahydrofuran (3 mL) were added a solution of 5-[2-(methylthio)phenyl]-1H-pyrrole-3-carbaldehyde (150 mg) in tetrahydrofuran (5 mL), 15-crown-5 (182 mg) and pyridin-3-ylsulfonyl chloride (135 mg) under ice-cooling. After stirring at room temperature for 2 hr, water was added and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=4:1→2:1) to give the title compound as colorless crystals (yield 170 mg, 69%).
Reaction SMILES: [CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][NH:4][CH2:3]1.[C:9]([C:13]1[O:17][C:16]([CH:18]2[CH2:20][CH:19]2[C:21](Cl)=[O:22])=[CH:15][CH:14]=1)([CH3:12])([CH3:11])[CH3:10].O>[Na]>[C:9]([C:13]1[O:17][C:16]([CH:18]2[CH2:20][CH:19]2[C:21]([N:4]2[CH2:5][C@H:6]([CH3:8])[O:7][C@H:2]([CH3:1])[CH2:3]2)=[O:22])=[CH:15][CH:14]=1)([CH3:12])([CH3:10])[CH3:11]
Reactant: CC(C)(C)c1ccc(C2CC2C(=O)Cl)o1
Reactant: C[C@@H]1CNC[C@H](C)O1
Agent: [Na]
Solvent: O
Product: C[C@@H]1CN(C(=O)C2CC2c2ccc(C(C)(C)C)o2)C[C@H](C)O1
Temperature: 20 °C
Reaction time: 3 h

Procedure:
cis-2,6-Dimethylmorpholine (8.9 g, 0.077 mol) was added dropwise to a solution of 2-(5-t-butylfuran-2-yl)-cyclopropanecarbonyl chloride (3.5 g, 0.0154 mol) in sodium dried ether (40 ml) at 10° C. and after complete addition the solution was stirred at 20° C. for 3 hours. The reaction mixture was poured into water and extracted with diethyl ether (2×100 ml). The ethereal extracts were washed with water, dried over anhydrous sodium sulphate, and the solvent removed to give 2-(5-t-butylfuran-2-yl)-cyclopropanecarbonyl-2,6-cis-dimethylmorpholine as a yellow oil. This oil was separated by column chromatography [silica eluted with petroleum ether ethyl acetate (1:1)] to give 2-(5-t-butylfuran-2-yl)-trans-cyclopropanecarbonyl-2,6-cis-dimethylmorpholine (1.43 g, 30%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][C:10]1[CH:18]=[CH:17][CH:16]=[C:12]([C:13]([OH:15])=O)[C:11]=1[C:19]([OH:21])=O.Cl.[NH2:23][CH:24]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:25]1=[O:26]>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][C:10]1[CH:18]=[CH:17][CH:16]=[C:12]2[C:11]=1[C:19](=[O:21])[N:23]([CH:24]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:25]1=[O:26])[C:13]2=[O:15]
Reactant: NC1CCC(=O)NC1=O
Reactant: COc1ccccc1Nc1cccc(C(=O)O)c1C(=O)O
Agent: Cl
Solvent: c1ccncc1
Product: COc1ccccc1Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
Yield: 92 %

Procedure:
A mixture of 3-(2-methoxyphenylamino)phthalic acid (0.55 g, 1.9 mmol) and rac-α-aminoglutarimide hydrochloride (0.31 g, 1.9 mmol) in pyridine (10 mL) was heated to reflux for 16 hours. The mixture was cooled and evaporated under vacuum. The residue was dissolved in ethyl acetate (150 mL), washed with dilute aqueous HCl (2×100 mL) and water (2×100 mL), and evaporated. The residue was chromatographed in 95:5 methylene chloride-methanol, eluting 0.66 g of the product, in 92% yield: mp 223-225° C.; 1H NMR (CDCl3) δ 2.13-2.20 (m, 1H), 2.73-2.95 (m, 3H), 3.88 (s, 3H), 4.97 (dd, J=11.9 Hz, J=5.0 Hz, 1H), 6.94-7.00 (m, 2H), 7.09-7.15 (m, 1H), 7.21-7.26 (m, 1H), 7.38-7.52 (m, 3H), 8.08 (s, 1H), 8.15 (s, 1H); 13C NMR (CDCl3) δ 22.8, 31.4, 49.0, 55.7, 111.4, 112.1, 113.6, 118.8, 120.6, 121.1, 124.8, 128.2, 132.5, 135.7, 143.6, 151.4, 167.4, 168.1, 169.1, 170.8; Anal. calcd for C20H17N3O5.0.1H2O: C, 63.02; H, 4.55; N, 11.02. Found: C, 62.91; H, 4.42; N, 10.71.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])=[CH:12][CH:11]=2)[CH:5]=[CH:6][CH:7]=1.B([O-])O[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+].O>C1(C)C(CO)=CC=CC=1.O>[C:2]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])=[CH:12][CH:11]=2)[CH:3]=1
Reactant: [O-]BOc1ccccc1
Reactant: COC(=O)CCc1ccc(OCc2cccc(Br)c2)cc1
Agent: Cc1ccccc1CO
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: COC(=O)CCc1ccc(OCc2cccc(-c3ccccc3)c2)cc1
Yield: 93.4 %

Procedure:
Methyl 4-[(3-bromophenyl)methoxy]benzenepropanoate (0.60 g, 1.7 mmol), phenyl boronate (0.25 g, 2.1 mmol) and sodium carbonate (0.55 g, 5.2 mmol) were dissolved in toluene-methanol-water (5:1:1, 35 mL), the mixture was purged with argon, and then tetrakistriphenylphosphine palladium (99 mg, 0.086 mmol) was added thereto. The reaction solution was heated under reflux overnight under argon atmosphere. The reaction solution was cooled, and then water was added to the reaction solution, followed by extraction with ethyl acetate. The extract was washed with water, dried and then concentrated. The residue was purified with silica gel column chromatography (hexane/ethyl acetate=18:1) to give the title compound (0.55 g, yield 92%) as white powders.