Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC(=O)C)(=O)C.[N+:8]([O-:11])(O)=[O:9].[OH:12][C:13]1[CH:22]=[CH:21][CH:20]=[C:15]([C:16]([O:18][CH3:19])=[O:17])[C:14]=1[C:23]([O:25][CH3:26])=[O:24]>C(#N)C.O>[OH:12][C:13]1[C:22]([N+:8]([O-:11])=[O:9])=[CH:21][CH:20]=[C:15]([C:16]([O:18][CH3:19])=[O:17])[C:14]=1[C:23]([O:25][CH3:26])=[O:24]
Reactant: O=[N+]([O-])O
Reactant: COC(=O)c1cccc(O)c1C(=O)OC
Solvent: CC#N
Solvent: O
Solvent: CC(=O)OC(C)=O
Product: COC(=O)c1ccc([N+](=O)[O-])c(O)c1C(=O)OC
Reaction time: 0.67 h
Yield: 94.5 %

Procedure:
Acetyl nitrate obtained by mixing acetic anhydride (3.6 g, 36 mmol) with fuming nitric acid (2.16 g, 36 mmol) at 0° C. was dropped into a solution of dimethyl 3-hydroxyphthalate (3.8 g, 18 mmol) in acetonitrile (60 ml) at 0° C. followed by stirring for 40 minutes. The reaction solution was diluted with water and extracted with ether. The organic layer was washed with water and a saturated sodium chloride solution successively and dried over anhydrous magnesium sulfate and the solvent was evaporated therefrom. A 3:2 mixture (4.34 g; yield 94%) of dimethyl 3-hydroxy-4-nitrophthalate and dimethyl 3-hydroxy-6-nitrophthalatewas obtained as a yellow solid. This was used in the next reaction without separation and purification.
Reaction SMILES: [C:1]1([CH:7]([CH3:27])[CH2:8][CH2:9][NH:10][C@H:11]2[CH2:16][CH2:15][C@H:14]([C:17]3[CH:26]=[CH:25][C:20]4[NH:21][C:22](=[O:24])[O:23][C:19]=4[CH:18]=3)[CH2:13][CH2:12]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.[BH4-].[Na+].[OH-].[Na+].[CH3:33]O>>[CH3:33][N:10]([CH2:9][CH2:8][CH:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH3:27])[C@H:11]1[CH2:12][CH2:13][C@H:14]([C:17]2[CH:26]=[CH:25][C:20]3[NH:21][C:22](=[O:24])[O:23][C:19]=3[CH:18]=2)[CH2:15][CH2:16]1
Reactant: CC(CCN[C@H]1CC[C@H](c2ccc3[nH]c(=O)oc3c2)CC1)c1ccccc1
Reactant: CO
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(CCN(C)[C@H]1CC[C@H](c2ccc3[nH]c(=O)oc3c2)CC1)c1ccccc1
Reaction time: 2 h

Procedure:
To a stirred solution of 6-{trans-4-[3-phenylbutylamino]-cyclohexyl}-3H-benzoxazol-2-one (638 mg, 1.75 mmol) in MeOH (10 mL) containing water (0.5 mL) was added p-formaldehyde (263 mg, 8.76 mmol). The reaction mixture was stirred for 2 hours, and NaBH4 (519 mg, 2.45 mmol) was added. The reaction mixture was stirred for 3 hours. The reaction was treated with solid NaOH until a clear solution resulted and concentrated under reduced pressure. Purification by flash chromatography (95:5:1 CH2Cl2:MeOH:NH4OH) gave 6-[trans-4-(methyl-3-phenylbutylamino)cyclohexyl]-3H-benzoxazol-2-one (231 mg, 35%), as a white solid: mp 61-70° C.; IR (KBr): 2928, 1774 cm−1; 1H NMR (500 MHz, DMSO-d6): δ 7.29-7.12 (m, 7H), 6.97 (s, 1H), 2.76 (m, 1H), 2.49-2.26 (m, 5H), 2.14 (s, 3H), 1.77 (m, 4H), 1.67 (m, 2H), 1.43 (m, 2H), 1.27 (m, 2H), 1.17 (d, J=4 Hz, 3H); API-MS (m/z): 379 [M+H]+; HPLC: method A, 5.99 minutes (94.3%); HPLC: method B, 10.97 minutes (>99%); Anal. Calcd for C24H30N2O2.0.5H2O: C, 74.39; H, 8.06; N, 7.23. Found: C, 74.41; H, 7.90; N, 7.31.
Reaction SMILES: ClC1C=CC=C([C:8](OO)=[O:9])C=1.[CH3:12][O:13][CH:14]1[C:19](=[O:20])[NH:18][C:17]([CH3:21])=[CH:16][S:15]1.C(=O)([O-])[O-].[K+].[K+]>CO>[CH3:12][O:13][C:14]1([O:9][CH3:8])[C:19](=[O:20])[NH:18][C:17]([CH3:21])=[CH:16][S:15]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COC1SC=C(C)NC1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: COC1(OC)SC=C(C)NC1=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 52.6 %

Procedure:
m-Chloroperbenzoic acid (25.6 g) was added dropwise to a stirred solution of 2-methoxy-5-methyl-2H-1,4-thiazin-3(4H)-one (16 g) in methanol (500 ml) under ice-cooling and the mixture was stirred at room temperature for 4 hours. Then, the reaction mixture was made alkaline by addition of anhydrous potassium carbonate and evaporated to dryness. The residue was extracted twice with chloroform and the combined extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was triturated with ethyl ether to give 2,2-dimethoxy-5-methyl-2H-1,4-thiazin-3(4H)-one (10 g, yield 53%) as pale yellow plates.
Reaction SMILES: [OH-].[Mg+2:2].[OH-].[C:4]([OH:7])(=[O:6])[CH3:5]>>[C:4]([O-:7])(=[O:6])[CH3:5].[Mg+2:2].[C:4]([O-:7])(=[O:6])[CH3:5]
Reactant: CC(=O)O
Agent: [Mg+2]
Agent: [OH-]
Product: CC(=O)[O-]
Temperature: 200 °C

Procedure:
To the reactor of Example 1 were charged 150 g high-boiling hydrocarbon oil, 28.2 g naphthenic acids, and 3.0 g commercial technical grade magnesium hydroxide. The contents were agitated and heated to 200° C. The contents were cooled and 20.3 g (0.35 mole) commercial technical grade magnesium hydroxide was added. The contents were heated to 135° C. Acetic acid (42.0 g, 0.7 mole) was added dropwise while maintaining the temperature at 125°-135° C. to form magnesium acetate in situ. After all of the acetic acid was in, the contents were heated above 280° C. to remove water and decomposition products from the magnesium acetate formed in situ. The resulting product was bright and weighed 185.8 g. Upon centrifugation of 90-gram sample, the sediment was 0.1 g. The magnesium content of the bright supernatant liquid was calculated at about 5.2%; the conversion of commercial technical grade magnesium hydroxide to the fluid dispersed form of MgO was calculated at 98.5%.
Reaction SMILES: C1CO[C:8]23OCC[O:12][C:3]2([C@:4]2([CH2:27][CH2:26][C@H:25]4[C@@H:15]([CH2:16][C:17](=[C:28]([F:30])[F:29])[CH:18]5[C@:23]4([CH3:24])[CH2:22][CH2:21][CH2:20][CH2:19]5)[C@@H:6]2[CH2:7]3)[CH3:5])O1.C([C@@H]1C2[C@](C)(CCC(=[O:51])C2)[C@@H]2[C@H]([C@H]3[C@@](CC2)(C)C(=O)CC3)C1)#N>>[F:29][C:28]([F:30])=[C:17]1[CH:18]2[C@:23]([CH3:24])([CH2:22][CH2:21][C:20](=[O:51])[CH2:19]2)[C@@H:25]2[C@H:15]([C@H:6]3[C@@:4]([CH2:27][CH2:26]2)([CH3:5])[C:3](=[O:12])[CH2:8][CH2:7]3)[CH2:16]1
Reactant: C[C@]12CCCCC1C(=C(F)F)C[C@@H]1[C@@H]2CC[C@@]2(C)[C@H]1CC13OCCOC12OCCO3
Reactant: C[C@]12CCC(=O)CC1[C@@H](C#N)C[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Product: C[C@]12CCC(=O)CC1C(=C(F)F)C[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Yield: 99 %

Procedure:
The title compound II-bf was prepared in 99% yield from 3,3:17,17-bis(ethylendioxy)-6-difluoromethyleneandrostane by the procedure described above for the preparation of 6α-cyanoandrostane-3,17-dione (II-ac, Prepn. 3). The combined organic extracts were washed with H2O, dried over Na2SO4 and evaporated to dryness. 1H-NMR (300 MHz, acetone-d6, ppm from TMS): δ 2.85-0.95 (m, 20H), 1.12 (s, 3H), 0.88 (s, 3H).
Reaction SMILES: [NH:1]([C:3]1[N:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[C:6]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:7]([C:13]1[CH:27]=[CH:26][C:16]([CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:15][CH:14]=1)=[N:8]2)[NH2:2].N1C=CC=CC=1.[Cl:40][CH2:41][C:42](OC(=O)CCl)=O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:40][CH2:41][C:42]1[N:12]2[C:3]([C:4]3[CH:5]=[C:6]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[C:7]([C:13]4[CH:14]=[CH:15][C:16]([CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:26][CH:27]=4)=[N:8][C:9]=3[CH:10]=[CH:11]2)=[N:1][N:2]=1
Reactant: CC(C)(C)OC(=O)NCc1ccc(-c2nc3ccnc(NN)c3cc2-c2ccccc2)cc1
Reactant: O=C(CCl)OC(=O)CCl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)NCc1ccc(-c2nc3ccn4c(CCl)nnc4c3cc2-c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a suspension of 16-2 (1.2 g, 2.7 mmol) in CH2Cl2 (10 ml) was added DMAP (0.03 g, 0.03 mmol) and pyridine (0.4 ml, 5.4 mmol) followed by chloroacetic anhydride (0.5 g, 3.0 mmol). The reaction mixture was stirred at room temperature for 2 h before adding additional chloroacetic anhydride (0.2 g, 0.9 mmol). After stirring for an additional 10 min the solvent was removed in vacuo. The residue was partitioned between saturated aqueous NaHCO3 and EtOAc (3×30 ml). The combined organic layers were washed with water, brine and dried (Na2SO4/MgSO4). Removal of the solvent afforded the desired product 26-1 as a red powder. MS calculated: 500.2. Found 500.1
Reaction SMILES: C(N(CC)CC)C.[F:8][C:9]([F:14])([F:13])[C:10]([O-:12])=[O:11].[NH2:15][C:16]1[C:17]([C:24]([NH:26][CH2:27][C@@H:28]([N+:32]([CH2:35][CH2:36][CH2:37][C:38]2[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=2)([CH3:34])[CH3:33])[CH2:29][CH2:30][CH3:31])=[O:25])=[N:18][C:19]([Cl:23])=[C:20]([NH2:22])[N:21]=1.[CH2:45]1[O:47][C@H:46]1[CH2:48][OH:49]>CCO>[F:8][C:9]([F:14])([F:13])[C:10]([O-:12])=[O:11].[NH2:15][C:16]1[C:17]([C:24]([NH:26][CH2:27][C@@H:28]([N+:32]([CH2:35][CH2:36][CH2:37][C:38]2[CH:43]=[CH:42][C:41]([O:44][CH2:45][C@@H:46]([OH:47])[CH2:48][OH:49])=[CH:40][CH:39]=2)([CH3:34])[CH3:33])[CH2:29][CH2:30][CH3:31])=[O:25])=[N:18][C:19]([Cl:23])=[C:20]([NH2:22])[N:21]=1
Reactant: OC[C@H]1CO1
Reactant: CCC[C@@H](CNC(=O)c1nc(Cl)c(N)nc1N)[N+](C)(C)CCCc1ccc(O)cc1
Agent: O=C([O-])C(F)(F)F
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCC[C@@H](CNC(=O)c1nc(Cl)c(N)nc1N)[N+](C)(C)CCCc1ccc(OC[C@@H](O)CO)cc1

Procedure:
Triethylamine (63.5 μL, 0.46 μmol) is added to a solution of ((S)-1-{[(3,5-Diamino-6-chloro-pyrazine-2-carbonyl)-amino]-methyl}-butyl)-[3-(4-hydroxy-phenyl)-propyl]-dimethyl-ammonium trifluoroacetate (Example 121)(50 mg, 0.091 mmol) in EtOH (5 mL) and the solution is heated to reflux. Once at reflux (S)-glycidol (6.04 μL, 0.091 mmol) is added and the reaction is heated at reflux overnight. Two further portions of (S)-glycidol (2×6.04 μl, 2×0.091 mmol) are added and the reaction is heated at reflux for 24 h. The reaction mixture is concentrated in vacuo and purification by reverse phase chromatography (Isolute™ C18, 0-30% acetonitrile in water with 0.1% TFA) affords the title compound. M+ 509. 1H NMR (400 MHz, DMSO-d6) δ 8.39 (1H, t), 8.20-7.18 (2H, br), 7.24-6.98 (2H, br), 6.99 (2H, d), 6.79 (2H, d), 5.70-3.98 (2H, br), 3.93-3.89 (1H, m), 3.85-3.67 (3H, m), 3.60-3.43 (3H, m), 3.42 (2H, d), 3.39-3.28 (1H, m), 3.04 (3H, s), 3.01 (3H, s), 2.48-2.32 (2H, m), 2.00-1.71 (3H, m), 1.61-1.37 (3H, m), 0.91 (3H, t).
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[C:10](=[CH:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([O:25][CH3:26])[CH:18]=1)[NH:9][CH2:8][CH2:7]2.N1C=CC=CC=1.[CH:33]1([C:36](Cl)=[O:37])[CH2:35][CH2:34]1>O>[CH:33]1([C:36]([N:9]2[CH2:8][CH2:7][C:6]3[C:11](=[CH:12][C:13]([O:14][CH3:15])=[C:4]([O:3][CH3:2])[CH:5]=3)/[C:10]/2=[CH:16]/[C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([O:25][CH3:26])[CH:18]=2)=[O:37])[CH2:35][CH2:34]1
Reactant: COc1ccc(C=C2NCCc3cc(OC)c(OC)cc32)cc1OC
Reactant: O=C(Cl)C1CC1
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: COc1ccc(/C=C2/c3cc(OC)c(OC)cc3CCN2C(=O)C2CC2)cc1OC

Procedure:
To a suspension of 6 parts of 3,4-dihydro-6,7-dimethoxy-1-[(3,4-dimethoxyphenyl)methylene]isoquinoline hydrochloride in 40 parts of pyridine is added 6 parts of cyclopropanecarbonyl chloride. The resultant mixture is stirred at room temperatures for 18 hours, then poured into 500 parts of water. The mixture thus obtained is extracted with chloroform. The chloroform extract is washed with 5% hydrochloric acid, dried over anhydrous sodium sulfate, and stripped of solvent by vacuum distillation. The residue is crystallized from a mixture of ethyl acetate and dichloromethane to give (Z)-2-cyclopropylcarbonyl-1,2,3,4-tetrahydro-6,7-dimethoxy-1-[(3,4-dimethoxyphenyl)methylene]isoquinoline melting at 148°-151°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[CH2:6][NH2:7].[CH2:13]1[CH2:19][S:16](=[O:18])(=[O:17])[O:15][CH2:14]1>CC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[CH2:6][NH:7][CH2:14][CH2:13][CH2:19][S:16]([OH:18])(=[O:17])=[O:15]
Reactant: COc1ccc(CN)cc1OC
Reactant: O=S1(=O)CCCO1
Solvent: CC(C)=O
Product: COc1ccc(CNCCCS(=O)(=O)O)cc1OC
Temperature: 25 °C
Yield: 42.4 %

Procedure:
To a solution of 3,4-dimethoxybenzylamine (2.2 mL, 15.0 mmol) in acetone (20 mL) was added 1,3-propane sultone (1.97 g, 15.8 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2×25 mL) and dried in vacuo. The crude product was suspended in 90% acetone/MeOH (75 mL). The suspension was stirred at reflux for 30 sec., the solid material was collected by filtration, and dried in vacuo. Compound S (1.84 g, 43%) was isolated as a white solid. 1H NMR (D2O, 500 MHz) 8 ppm 6.96 (m, 3H), 4.06 (s, 2H), 3.74 (s, 6H), 3.07 (t, 1H, J=7.8 Hz), 2.86 (t, 1H, J=7.8 Hz), 2.01 (m, 2H). 13C NMR (D2O, 125 MHz) 8 ppm 149.23, 148.50, 123.63, 123.37, 55.90, 55.86, 50.96, 48.06, 45.62, 21.39. ES-MS 290 (M+1).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([CH2:13][O:12][C:11]3=[CH:14][C:15]4[CH2:19][CH2:18][O:17][C:16]=4[CH:20]=[C:10]23)[C:2]1=[O:21].N1C2C(=CC=CC=2)[C:24]2([C:34]3=CC4OCOC=4[CH:41]=[C:33]3[O:32][CH2:31]2)C1=O.CC1C=CC(S(OC[C@H]2CCCO2)(=O)=O)=CC=1.CC1C=CC(S(OC[C@H]2COCCO2)(=O)=O)=CC=1>>[O:32]1[CH2:31][CH2:24][CH2:34][C@@H:33]1[CH2:41][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([CH2:13][O:12][C:11]3=[CH:14][C:15]4[CH2:19][CH2:18][O:17][C:16]=4[CH:20]=[C:10]23)[C:2]1=[O:21]
Reactant: O=C1Nc2ccccc2C12COc1cc3c(cc12)OCO3
Reactant: O=C1Nc2ccccc2C12COc1cc3c(cc12)OCC3
Agent: Cc1ccc(S(=O)(=O)OC[C@H]2CCCO2)cc1
Agent: Cc1ccc(S(=O)(=O)OC[C@H]2COCCO2)cc1
Product: O=C1N(C[C@H]2CCCO2)c2ccccc2C12COc1cc3c(cc12)OCC3

Procedure:
Following the procedure as described in EXAMPLE 8 and making non-critical variations using 6,7-dihydrospiro[benzo[1,2-b:4,5-b′]difuran-3,3′-indol]-2′(1′H)-one to replace spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one, and (R)-(tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonate to replace (R)-(1,4-dioxan-2-yl)methyl 4-methylbenzenesulfonate, 1′-[(2R)-tetrahydrofuran-2-ylmethyl]-6,7-dihydrospiro[benzo[1,2-b:4,5-b′]difuran-3,3′-indol]-2′(1′H)-one was obtained (57%) as a colorless solid: mp 162-164° C. (diethyl ether/hexanes); 1H NMR (300 MHz, CDCl3) (diastereomers) δ7.29 (dd, J=7.8, 7.8 Hz, 1H), 7.16-7.00 (m, 3H), 6.79 (s, 1H), 6.12 (s, 1H), 4.91 (d, J=9.0 Hz, 1H), 4.65 (d, J=9.0 Hz, 1H), 4.48 (t, J=8.7 Hz, 2H), 4.31-4.22 (m, 1H), 4.00-3.67 (m, 4H), 3.14 (t, J=8.7 Hz, 2H), 2.09-1.82 (m, 3H), 1.78-1.67 (m, 1H); 13C NMR (75 MHz, CDCl3) (diastereomers) δ178.0, 177.8, 155.1, 154.9, 143.1, 142.9, 132.3, 132.2, 128.94, 128.88, 128.7, 127.91, 127.86, 123.8, 123.7, 123.4, 109.9, 109.5, 107.1, 104.01, 103.96, 80.2, 80.1, 77.1, 76.8, 71.7, 68.4, 68.3, 58.52, 58.49, 44.7, 30.4, 29.4, 29.0, 25.9, 25.7; MS (ES+) m/z 364.0 (M+1).
Reaction SMILES: [C:1]([CH:5]1[O:11][CH:10]2[CH:7]([C:8](=[O:26])[N:9]2[C:12](=[C:23]([CH3:25])[CH3:24])[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[N:6]1[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28])([O:3]C)=[O:2].[OH-].[Na+].Cl>CC(C)=O>[C:1]([CH:5]1[O:11][CH:10]2[CH:7]([C:8](=[O:26])[N:9]2[C:12](=[C:23]([CH3:24])[CH3:25])[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[N:6]1[C:27]([O:29][CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)=[O:28])([OH:3])=[O:2]
Reactant: COC(=O)C1OC2C(C(=O)N2C(C(=O)OCc2ccccc2)=C(C)C)N1C(=O)OCc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Product: CC(C)=C(C(=O)OCc1ccccc1)N1C(=O)C2C1OC(C(=O)O)N2C(=O)OCc1ccccc1
Reaction time: 0.75 h
Yield: 88.2 %

Procedure:
To a solution of 1.482 g of benzyl α-(3ξ-carbomethoxy-2-carbobenzoxy-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate in 20 ml of acetone is added 5 ml of 0.6 M aqueous solution of sodium hydroxide under ice-cooling, and the mixture stirred for 45 minutes, then neutralized with 2N hydrochloric acid and extracted with ethyl acetate. The extract is washed with water, dried and concentrated under reduced pressure to yield 1.27 g of benzyl α-(3ξ-carboxy-2-carbobenzoxy-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate as crude product in 88.5% yield.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:7]=[C:8]([OH:12])[CH:9]=[CH:10][CH:11]=2)=[CH:2]1.[H-].[Na+].Br[CH2:16][C:17](=[O:22])[CH2:18][CH2:19][CH2:20][Br:21].C(OCC)C>CN(C)C=O.O>[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:7]=[C:8]([CH:9]=[CH:10][CH:11]=2)[O:12][CH2:16][C:17](=[O:22])[CH2:18][CH2:19][CH2:20][Br:21])=[CH:2]1
Reactant: O=C(CBr)CCCBr
Reactant: Oc1cccc(-c2ccsc2)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOCC
Solvent: O
Product: O=C(CCCBr)COc1cccc(-c2ccsc2)c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 10.4 %

Procedure:
0.25 g of 3-(3-thienyl)phenol was dissolved in 2.5 ml of dimethylformamide, and 28 mg of 60% oily sodium hydride was added. The mixture was stirred at room temperature for 15 minutes, and then a dimethylformamide solution (1 ml) of 0.45 g of 1,5-dibromo-2-pentanone [see J. Chem. Soc., 1948, 278] was added dropwise at -40° C. The mixture was stirred at this temperature for 2 hours, and ethyl ether and water were added. The organic layer separated was worked up in a customary manner, and the product was purified by silica gel column chromatography [hexane / ethyl acetate=30/1] to give 50 mg of the captioned compound as a colorless oil.
Reaction SMILES: [C:1]1([N:7]2[C:11]3[CH:12]=[C:13]([O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])[CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:31](=O)([O-])[O-].[Cs+].[Cs+].CI>CN(C)C=O.O>[CH3:31][O:23][C:22](=[O:24])[CH2:21][CH2:20][O:19][CH2:18][CH2:17][O:16][C:13]1[CH:14]=[CH:15][C:10]2[N:9]=[C:8]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:11]=2[CH:12]=1
Reactant: O=C([O-])[O-]
Reactant: O=C(O)CCOCCOc1ccc2nc(-c3ccccc3)n(-c3ccccc3)c2c1
Agent: [Cs+]
Solvent: O
Solvent: CI
Solvent: CN(C)C=O
Product: COC(=O)CCOCCOc1ccc2nc(-c3ccccc3)n(-c3ccccc3)c2c1
Reaction time: 30 h

Procedure:
35 mg of 3-[2-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]ethoxy]propanoic acid was dissolved in 0.4 ml of N,N-dimethylformamide, mixed with 28 mg of cesium carbonate and 50 μl of methyl iodide and stirred for 30 hours. Then, it was diluted with water and extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried on sodium sulfate and concentrated by evaporation in a vacuum. The residue was chromatographed on silica gel.
Reaction SMILES: [CH2:1](O)[CH:2](O)C.[C:6]([OH:15])(=[O:14])[CH2:7][CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12]>>[C:6]([OH:15])(=[O:14])[C:7]1[CH:2]=[CH:1][C:10]([C:11]([OH:13])=[O:12])=[CH:9][CH:8]=1.[C:6]([OH:15])(=[O:14])[CH2:7][CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12]
Reactant: CC(O)CO
Agent: O=C(O)CCCCC(=O)O
Product: O=C(O)c1ccc(C(=O)O)cc1

Procedure:
1,2-propylene glycol, terephthalic acd, adipic acid, and trilmellitic anhydride were placed in a reaction container equipped with a condenser, a stirrer, and a nitrogen-introducing tube in such a manner that the molar ratio ([OH]/[COOH]) of a hydroxy group to a carboxylic group was 1.3. Dicarboxylic acid was formed of 80% by mol of terephthalic acid and 20% by mol of adipic acid. Trilmellitic anhydride was set to be 2.5% by mol to the total of monomers. 1,000 ppm of titanium tetraisopropoxide was added to all of the monomers. Next, the system was heated to 200° C. in about four hours and to 230° C. in two hours and reacted until effluent water became nil. Furthermore, the reaction was continued with a reduced pressure of from 10 mmHg to 15 mmHG for five hours to obtain a polyester having a hydroxy group.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:14][CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]2)[CH:3]=1.[H-].[Na+].Cl[C:25]1[S:26][C:27]([C:30]#[N:31])=[CH:28][N:29]=1>>[N:8]1([C:4]2[N:5]=[CH:6][N:7]=[C:2]([NH:1][C:25]3[S:26][C:27]([C:30]#[N:31])=[CH:28][N:29]=3)[CH:3]=2)[CH2:14][CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1
Reactant: CC(C)(C)OC(=O)N1CCCN(c2cc(N)ncn2)CC1
Reactant: N#Cc1cnc(Cl)s1
Agent: [H-]
Agent: [Na+]
Product: N#Cc1cnc(Nc2cc(N3CCCNCC3)ncn2)s1

Procedure:
Tert-butyl 4-(6-aminopyrimidin-4-yl)-1,4-diazepane-1-carboxylate 15-2 (0.50 g, 1.70 mmol), sodium hydride (0.136 g, 3.4 mmol) and 2-chloro-1,3-thiazole-5-carbonitrile 2-2 (0.246 g, 1.70 mmol) were treated as in Scheme 4 above. The product was purified on a C18 preparative column after treating the crude product with trifluoroacetic acid and then isolated via lyophilization. Hi-Res MS: calc: 302.1182 found: 302.1184. 1NMR (CD3OD): 8.45 ppm (s, 1H); 8.01 ppm (s, 1H); 6.16 ppm (s, 1H); 4.08 ppm (m, 2H); 3.73 ppm (m, 2H); 3.40 ppm (m, 2H); 3.32 ppm (m, 2H); 2.21 ppm (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:45]2[CH:50]=[CH:49][C:48]([O:51][CH3:52])=[CH:47][CH:46]=2)([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[O:10][CH2:11][CH2:12][CH2:13][N:14]([C:21]2[CH:26]=[CH:25][C:24]([N:27]=[N:28][C:29]3[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][C:30]=3[Cl:38])=[CH:23][CH:22]=2)[CH2:15][CH2:16][CH2:17][C:18]([OH:20])=[O:19])=[CH:5][CH:4]=1.C(N(CC)CC)C.C(Cl)Cl.FC(F)(F)C(O[C:68]1[C:73]([F:74])=[C:72]([F:75])[C:71]([F:76])=[C:70]([F:77])[C:69]=1[F:78])=O>CCCCCC.C(OCC)(=O)C>[CH3:52][O:51][C:48]1[CH:49]=[CH:50][C:45]([C:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[O:10][CH2:11][CH2:12][CH2:13][N:14]([C:21]2[CH:26]=[CH:25][C:24]([N:27]=[N:28][C:29]3[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][C:30]=3[Cl:38])=[CH:23][CH:22]=2)[CH2:15][CH2:16][CH2:17][C:18]([O:20][C:68]2[C:69]([F:78])=[C:70]([F:77])[C:71]([F:76])=[C:72]([F:75])[C:73]=2[F:74])=[O:19])=[CH:46][CH:47]=1
Reactant: O=C(Oc1c(F)c(F)c(F)c(F)c1F)C(F)(F)F
Reactant: COc1ccc(C(OCCCN(CCCC(=O)O)c2ccc(N=Nc3ccc([N+](=O)[O-])cc3Cl)cc2)(c2ccccc2)c2ccc(OC)cc2)cc1
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: CCCCCC
Product: COc1ccc(C(OCCCN(CCCC(=O)Oc2c(F)c(F)c(F)c(F)c2F)c2ccc(N=Nc3ccc([N+](=O)[O-])cc3Cl)cc2)(c2ccccc2)c2ccc(OC)cc2)cc1
Yield: 41 %

Procedure:
To the flask containing 21 (10 mmol) is added 7 mL of triethylamine followed by 100 mL of methylene chloride, 2.05 mL of pentafluorophenyl trifluoroacetate (PFP-TFA) is then added. The solution is stirred for half an hour. At the end of this time, the reaction is usually complete. (TLC: 2:1 hexane/ethyl acetate). The solvent is removed on the rotary evaporator to give a syrup which is chromatographed on silica eluting with 1:3 ethyl acetate/hexane. Appropriate fractions are collected, combined, evaporated and dried under vacuum. The yield is 41%. 1H NMR (DMSO-d6) δ 8.43 (d, J=2.5 Hz, aromatic proton, 1H), 8.24 (dd, J1=9 Hz, J2=2.5 Hz, aromatic proton, 1H), 7.83 (d, J=9 Hz, aromatic proton, 1H), 7.78 (d, J=9 Hz, aromatic proton, 1H), 7.42-7.15 (m, aromatic protons, 10H), 7.07 (m, aromatic protons, 2H), 7.00-6.80 (m, aromatic protons, 4H), 3.72 (s, 2×CH3, 6H), 3.56 (m, aliphatic protons, 2H), 3.48 (t, J=6.3 Hz, aliphatic protons, 2H), 3.08 (t, J=5 Hz, aliphatic protons, 2H), 2.89 (t, J=7 Hz, aliphatic protons, 2H), 1.95 (m, aliphatic protons, 2H), 1.86 (m, aliphatic protons, 2H).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:34]/[OH:35])/[C:8]([NH:10][CH:11]2[C:32](=[O:33])[N:13]3[C:14]([C:29]([O-:31])=[O:30])=[C:15]([CH2:18][O:19][C:20]([N:22]4[CH2:26][CH2:25][CH2:24][C@H:23]4[CH2:27][OH:28])=[O:21])[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.[Na+].[C:37]([O:43][CH2:44]I)(=[O:42])[C:38]([CH3:41])([CH3:40])[CH3:39]>>[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:34]/[OH:35])/[C:8]([NH:10][CH:11]2[C:32](=[O:33])[N:13]3[C:14]([C:29]([O:31][CH2:44][O:43][C:37](=[O:42])[C:38]([CH3:41])([CH3:40])[CH3:39])=[O:30])=[C:15]([CH2:18][O:19][C:20]([N:22]4[CH2:26][CH2:25][CH2:24][C@H:23]4[CH2:27][OH:28])=[O:21])[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1
Reactant: CC(C)(C)C(=O)OCI
Reactant: Nc1nc(/C(=N/O)C(=O)NC2C(=O)N3C(C(=O)[O-])=C(COC(=O)N4CCC[C@H]4CO)CS[C@H]23)cs1
Agent: [Na+]
Product: CC(C)(C)C(=O)OCOC(=O)C1=C(COC(=O)N2CCC[C@H]2CO)CS[C@@H]2C(NC(=O)/C(=N\O)c3csc(N)n3)C(=O)N12

Procedure:
The compound obtained in Example 12 and iodomethyl pivalate were reacted, whereby the title compound was obtained.