Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:3][C:4](=[O:20])[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:8][CH2:7]1)C.CO.[OH-].[Li+].Cl>O>[C:12]([N:9]1[CH2:8][CH2:7][N:6]([CH2:5][C:4]([OH:20])=[O:3])[CH2:11][CH2:10]1)(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CCOC(=O)CN1CCN(C(=O)c2ccccc2)CC1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)CN1CCN(C(=O)c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 116.9 %

Procedure:
To (4-benzoylpiperazin-1-yl)acetic acid ethyl ester (8.19 g) were added methanol (300 ml) and water (50 ml), and lithium hydroxide (1.34 g) was added thereto in an ice water bath, followed by stirring for 10 min. The reaction mixture was allowed to warm up to room temperature and stirred for 24 hr. After addition of 1N hydrochloric acid (55.9 ml), the reaction mixture was concentrated under reduced pressure, and ethanol (200 ml) was added to the resultant residue. Precipitated insoluble matter was filtered through celite. The filtrate was concentrated to provide a crude product of (4-benzoylpiperazin-1-yl)acetic acid as a white solid (8.6 g). To (4-benzoylpiperazin-1-yl)acetic acid (2 g) was added N,N-dimethylformamide (80 ml) under a nitrogen atmosphere at room temperature, and azetidine hydrochloride (1.51 g), triethylamine (4.49 ml), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (3.09 g) and 1-hydroxybenzotriazole (2.18 g) were added thereto in this order, followed by stirring at room temperature for 66 hr. Liquid-liquid separation was carried out after addition of ethyl acetate (100 ml) and a saturated aqueous solution of sodium hydrogencarbonate (50 ml) to the reaction mixture. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (50 ml), water (50 ml) and brine (50 ml) in this order, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate). Fractions containing the target compound were concentrated under reduced pressure, the resultant residue was suspended in diethyl ether (10 ml). The solid was collected by filtration, and dried under aeration to provide the titled compound as white powder (731.5 mg).
Reaction SMILES: [Na].CO.[CH3:4][O:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[CH:8][CH:7]=1.[N+:14]([CH:17]([CH3:19])[CH3:18])([O-:16])=[O:15]>C(O)(=O)C>[CH3:4][O:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]([OH:11])[C:17]([CH3:19])([N+:14]([O-:16])=[O:15])[CH3:18])=[CH:8][CH:7]=1
Reactant: COc1ccc(C=O)cc1
Reactant: CC(C)[N+](=O)[O-]
Agent: [Na]
Solvent: CC(=O)O
Solvent: CO
Product: COc1ccc(C(O)C(C)(C)[N+](=O)[O-])cc1
Temperature: 13 °C
Reaction time: 0.42 h
Yield: 13.1 %

Procedure:
11.5 g of sodium are added to 300 ml of anhydrous methanol, and 67 g of 4-methoxybenzaldehyde and 105 g of 2-nitropropane are added thereto at 13° C. for 25 minutes under stirring. The mixture is stirred at 23° C. for 70 hours. 32 g of acetic acid are added to the mixture under ice-cooling, and said mixture is evaporated under reduced pressure to remove solvent. About 200 ml of water are added to the residue, and the aqueous mixture is extracted with benzene. The extract is washed with a saturated sodium chloride solution, a saturated sodium bisulfite solution, water and a saturated sodium chloride solution, successively. The washed extract is dried and then evaporated to remove solvent. The residue (yellow oil, 65 g) is distilled at 75° C. under reduced pressure (1-2 mm Hg) to recover 47 g of the starting compound (i.e., 4-methoxybenzaldehyde). On the other hand, 14.5 g of 1-(4 -methoxyphenyl)-2-methyl-2-nitropropanol (crude product) are obtained as the residue.
Reaction SMILES: C([O:5][C:6]([C:8]1([CH2:53][C:54]([O:56]C(C)(C)C)=[O:55])[O:12][N:11]=[C:10]([C:13]2[CH:18]=[C:17]([O:19][C:20](=[O:31])[C:21]3[CH:26]=[CH:25][C:24]([NH:27][C:28]([NH2:30])=[NH:29])=[CH:23][CH:22]=3)[CH:16]=[CH:15][C:14]=2[CH2:32][CH2:33][C:34]([NH:36][C@H:37]([C:46]([O:48]C(C)(C)C)=[O:47])[CH2:38][C:39]([O:41]C(C)(C)C)=[O:40])=[O:35])[CH2:9]1)=[O:7])(C)(C)C.[C:61]([OH:67])([C:63]([F:66])([F:65])[F:64])=[O:62]>>[F:64][C:63]([F:66])([F:65])[C:61]([OH:67])=[O:62].[NH:27]([C:24]1[CH:23]=[CH:22][C:21]([C:20]([O:19][C:17]2[CH:16]=[CH:15][C:14]([CH2:32][CH2:33][C:34]([NH:36][C@H:37]([C:46]([OH:48])=[O:47])[CH2:38][C:39]([OH:41])=[O:40])=[O:35])=[C:13]([C:10]3[CH2:9][C:8]([C:6]([OH:7])=[O:5])([CH2:53][C:54]([OH:56])=[O:55])[O:12][N:11]=3)[CH:18]=2)=[O:31])=[CH:26][CH:25]=1)[C:28]([NH2:30])=[NH:29]
Reactant: CC(C)(C)OC(=O)C[C@H](NC(=O)CCc1ccc(OC(=O)c2ccc(NC(=N)N)cc2)cc1C1=NOC(CC(=O)OC(C)(C)C)(C(=O)OC(C)(C)C)C1)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Product: N=C(N)Nc1ccc(C(=O)Oc2ccc(CCC(=O)N[C@@H](CC(=O)O)C(=O)O)c(C3=NOC(CC(=O)O)(C(=O)O)C3)c2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of di-tert-butyl N-(3-(2-(5-(tert-butoxycarbonyl)-5-(2-tert-butoxy-2-oxoethyl)-4,5-dihydro-1,2-oxazol-3-yl)-4-((4-carbamimidamidobenzoyl)oxy)phenyl)propanoyl)-L-aspartate (44.6 mg) and TFA (1 mL) was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and then, the residue was washed with diethyl ether to obtain the title compound (25.1 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:14]S(C2C=CC=CC=2)(=O)=O)=[C:6]([CH:13]=1)/[CH:7]=[CH:8]/[C:9]([O:11][CH3:12])=[O:10].Br.Br[CH2:26][C:27]([C:29]1[C:34]([CH3:35])=[CH:33][CH:32]=[CH:31][N:30]=1)=[O:28]>>[CH3:12][O:11][C:9](=[O:10])[CH2:8][C:7]1[C:6]2[C:5](=[CH:4][CH:3]=[C:2]([Cl:1])[CH:13]=2)[NH:14][C:26]=1[C:27]([C:29]1[C:34]([CH3:35])=[CH:33][CH:32]=[CH:31][N:30]=1)=[O:28]
Reactant: COC(=O)/C=C/c1cc(Cl)ccc1NS(=O)(=O)c1ccccc1
Reactant: Cc1cccnc1C(=O)CBr
Agent: Br
Product: COC(=O)Cc1c(C(=O)c2ncccc2C)[nH]c2ccc(Cl)cc12

Procedure:
The title compound was prepared according to the procedure described in Example 57 from methyl trans-5-chloro-2-(penylsulfonylamino)cinnamate (Example 36, step 3) and 2-bromoacetyl-3-methylpyridine hydrobromide (Preparation is described in Example 73).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19]C)[N:3]=1.B(Br)(Br)Br.C(N(CC)CC)C.[NH:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1>C(Cl)Cl>[CH3:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([N:32]3[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]3)=[N:3][C:4]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[OH:19])=[N:5]2)=[CH:10][CH:9]=1
Reactant: C1CNCCN1
Reactant: COc1ccccc1-c1nc(Cl)c2ccc(C)cc2n1
Agent: BrB(Br)Br
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc2c(N3CCNCC3)nc(-c3ccccc3O)nc2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.6 %

Procedure:
A stirring solution of 4-chloro-2-(2-methoxyphenyl)-7-methylquinazoline (91 g, 320 mmol) and CH2Cl2 (2.0 L) under an N2 atmosphere was cooled to −30° C. Boron tribromide (957 mL, 957 mmol, 1.0 M in CH2Cl2) was added dropwise over a period of 30 minutes at −30 to −40° C. The cooling bath was removed, and the mixture was allowed to warm to 25° C. The mixture was carefully poured into a stirring solution of saturated aqueous NaHCO3 (4.0 L). The organic portion was separated, dried over MgSO4, and evaporated to dryness. The resulting solid was suspended in CH2Cl2 (400 mL) under an N2 atmosphere, followed by the addition of triethylamine (64.8 g, 640 mmol). The solution was cooled to −10° C. A solution of piperazine (55.0 g, 640 mmol) in CH2Cl2 (400 mL) was added in a single portion, and the solution was stirred at ambient temperature for 1 hour. The solution temperature rose to 23° C. upon addition of the piperazine. The solution was partitioned between CH2Cl2 and H2O. The organic portion was dried over MgSO4 and evaporated to dryness. The residue was purified via silica gel chromatography using 5% MeOH in CH2Cl2 to obtain a tan solid. The resulting solid was triturated with 1:1 Et2O/hexanes to obtain a yellow solid which was vacuum dried to give 2-(7-methyl-4-piperazin-1-yl-quinazolin-2-yl)-phenol as a light yellow solid (93.0 g, 290 mmol, 91%). LC/MS: m/z 321.1 (M+H)+ at 2.34 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).
Reaction SMILES: [CH3:1][C:2]([C@:4]12[CH2:13][C@@:12]3([CH3:14])[C@:8]([CH3:15])([C@@H:9]1[CH2:10][CH2:11]3)[CH2:7][CH2:6][CH2:5]2)=[CH2:3].C(O)(=O)C1C(=CC=CC=1)[OH:19]>C(Cl)Cl>[CH3:14][C@:12]12[CH2:13][C@@:4]3([C:2]([CH2:1][OH:19])=[CH2:3])[CH:9]([C:8]1([CH3:15])[CH2:7][CH2:6][CH2:5]3)[CH2:10][CH2:11]2
Reactant: C=C(C)[C@@]12CCC[C@@]3(C)[C@@H]1CC[C@@]3(C)C2
Reactant: O=C(O)c1ccccc1O
Solvent: ClCCl
Product: C=C(CO)[C@@]12CCCC3(C)C1CC[C@@]3(C)C2
Temperature: 25 °C

Procedure:
Alloisolongifolene alcohol was prepared from alloisolongifolene via its corresponding aldehyde by SeO2, according to the protocol of Umbreit and Sharpless (1977). To a solution of 77 mg SeO2 and 68 mg salicylic acid in 30 mL CH2Cl2, 100 mg alloisolongifolene was added. Stirring at room temperature turned the reaction mixture yellow and a red solid precipitated in the first few hours. The reaction was monitored by GC-MS along with TLC and was stoppedby the addition of 60 mL demineralised water after 2.5 days. The reaction mixture was extracted with 45 mL ether, and the organic phase was subsequently washed with 30 mL brine. The red precipitate remained in the aqueous phase during extraction. After drying and evaporation, the organic phase yielded 214 mg of a crude solid that after flash chromatography on silica with pentane-CH2Cl2 (3:1) yielded 31 mg of alloisolongifolene aldehyde, a strong odorous compound (cedar-wood like). 1H NMR (200 MHz, C6D6) δ 0.71 (s, 3H, Me) δ 0.90 (s, 3H, Me), δ 0.93–2.04 (m, 13H), δ 5.42 (s, 1H, CH2═C), δ 5.73 (s, 1H, CH2═C), δ 9.35 (s, 1H, CH═O). 13C NMR (50 MHz, C6D6) δ 15.0 (q), δ 19.6 (q), δ 20.5 (t), δ 22.2 (t), δ 32.3 (t), δ 36.3 (t), δ 38.7 (t), δ 45.1 (t), δ 46.1 (s), δ 47.1 (s), δ 47.7 (s), δ 50.8 (d), δ 133.5 (t), δ 157.0 (s), δ 193.9 (d). EIMS (70 eV) m/z: 218 [M]+ (41), 203 (48), 189 (32), 185 (30), 175 (42), 161 (68), 147 (53), 145 (37), 133 (35), 119 (46), 107 (42), 105 (80), 95 (33), 93 (46), 91 (100), 81 (37), 79 (65), 77 (64), 55 (43), 53 (34), 41 (74), 39 (45). Fifteen milligrams of the aldehyde was added to a solution of 1.8 mg LiAlH4 in 0.5 mL ether. The grey suspension was stirred for 17.5 hours at room temperature and for an additional half our after the careful addition of one spatula Na2SO4.10H2O. One and a half millilitre of demineralised water was added to the mixture that was subsequently 3 times extracted with 1 mL of ether. The ether was passed through glasswool-plugged Pasteur pipette filled with silica and a spatula tip of MgSO4. The solvent was evaporated yielding 17 mg of alloisolongifolene alcohol. 1H NMR (200 MHz, C6D6) δ 0.77 (s, 3H, Me), δ 0.91 (s, 3H, Me), 0.96–1.63 (m, 13H), δ 3.96 (m, 2H), δ 4.95 (d, 1H, J=1.3 Hz) δ 5.30 (dd, 1H, J=3.26 Hz, 1.55 Hz). 13C NMR (50 MHz, C6D6) δ 15.1 (q),δ 19.7 (q), δ 20.7 (t), δ 22.3 (t), δ 32.4 (t), 37.5 (t), 38.7 (t), 44.0 (t), δ 46.1 (s), δ 47.8 (s), 6 48.2 (s), δ 51.6 (d), δ 63.4 (t), δ 107.9 (t), δ 155.9 (s). EIMS (70 eV) m/z: 220 [M]+ (5), 189 (35), 187 (36), 163 (30), 161 (56), 160 (37), 159 (30), 147 (36), 145 (38), 133 (32), 131 (37), 119 (44), 107 (61), (91), 95 (94), 93 (57), 91 (100), 81 (53), 79 (60), 77 (52), 67 (39), 55 (45), 41 (62).
Reaction SMILES: [CH3:1][CH:2]1[CH2:8][C:7]2[CH:9]=[C:10]3[O:15][CH2:14][O:13][C:11]3=[CH:12][C:6]=2[C:5]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)=[N:4][N:3]1[C:25](=[N:27][OH:28])[NH2:26].[C:29](OC(=O)C)(=O)[CH3:30]>O>[CH3:1][CH:2]1[CH2:8][C:7]2[CH:9]=[C:10]3[O:15][CH2:14][O:13][C:11]3=[CH:12][C:6]=2[C:5]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)=[N:4][N:3]1[C:25]1[N:26]=[C:29]([CH3:30])[O:28][N:27]=1
Reactant: CC1Cc2cc3c(cc2C(c2ccc([N+](=O)[O-])cc2)=NN1C(N)=NO)OCO3
Reactant: CC(=O)OC(C)=O
Solvent: O
Product: Cc1nc(N2N=C(c3ccc([N+](=O)[O-])cc3)c3cc4c(cc3CC2C)OCO4)no1
Temperature: 110 °C
Reaction time: 1 h
Yield: 50 %

Procedure:
A mixture of 3.0 g (7.82 mmol) of the starting material XXIV and 15 ml of acetic anhydride was stirred at 110° C. for 1 h, then after cooling it was diluted with water and extracted with dichloromethane. The organic layer was concentrated and the residue was purified by column chromatography using silica gel (MN Kieselgel 60) as adsorbent and a mire of n-hexane-ethyl acetate (2:1) as eluent to yield 1.58 g (50%) of the title compound; Mp.: 191-200° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:11]2[C:15]3[CH:16]=[C:17]([C:20]4[O:24][C:23]([NH2:25])=[N:22][N:21]=4)[CH:18]=[CH:19][C:14]=3[O:13][CH:12]=2)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:10])=[O:9].CN(C)C=[O:29]>>[Cl:1][C:2]1[CH:3]=[C:4]([C:11]2[C:15]3[CH:16]=[C:17]([C:20]4[O:24][C:23]([NH2:25])=[N:22][N:21]=4)[CH:18]=[CH:19][C:14]=3[O:13][CH:12]=2)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:10])(=[O:29])=[O:9]
Reactant: CN(C)C=O
Reactant: CS(=O)c1ccc(-c2coc3ccc(-c4nnc(N)o4)cc23)cc1Cl
Product: CS(=O)(=O)c1ccc(-c2coc3ccc(-c4nnc(N)o4)cc23)cc1Cl
Yield: 84 %

Procedure:
In the same manner as in Example 140 and using 5-[3-[3-chloro-4-(methylsulfinyl)phenyl]-1-benzofuran-5-yl]-1,3,4-oxadiazol-2-amine instead of 2-methyl-5-[3-[4-(methylthio)phenyl]-1-benzofuran-5-yl]-1,3,4-oxadiazole and using N,N-dimethylformamide instead of dichloromethane, the title compound (yield 84%) was obtained as colorless crystals.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[N:4]([CH:8]([C:10]2[C:11]3[CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31][C:12]=3[N:13]=[C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24]4)=[C:19]([O:29][CH3:30])[CH:18]=3)[N:15]=2)[CH3:9])[N:3]=1.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[N:4]([CH:8]([C:10]2[C:11]3[CH2:34][NH:33][CH2:32][CH2:31][C:12]=3[N:13]=[C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24]4)=[C:19]([O:29][CH3:30])[CH:18]=3)[N:15]=2)[CH3:9])[N:3]=1
Reactant: COc1cc(Nc2nc3c(c(C(C)n4nc(C)cc4C)n2)CN(C(=O)OC(C)(C)C)CC3)ccc1-n1cnc(C)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1cc(Nc2nc3c(c(C(C)n4nc(C)cc4C)n2)CNCC3)ccc1-n1cnc(C)c1
Yield: 76.8 %

Procedure:
A solution of tert-butyl 4-(1-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (397 mg, 0.71 mmol) and TFA (0.547 mL, 7.10 mmol) in DCM was stirred for one hour at 40° C. The reaction mixture was cooled and sat aqu NaHCO3 was added until the mixture was neutralized. The organic phase was separated and the water phase was washed repeatedly with DCM yielding 4-(1-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine (250 mg, 77%)
Reaction SMILES: Cl[CH2:2][C:3]([O:5][C:6]1[CH:11]=[CH:10][C:9](/[C:12](/[C:22]2[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31])=[CH:24][CH:23]=2)=[C:13](\[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)/[CH2:14][CH3:15])=[CH:8][CH:7]=1)=[O:4].[CH3:33][N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1>>[CH3:33][N:34]1[CH2:39][CH2:38][N:37]([CH2:2][C:3]([O:5][C:6]2[CH:11]=[CH:10][C:9](/[C:12](/[C:22]3[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31])=[CH:24][CH:23]=3)=[C:13](\[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)/[CH2:14][CH3:15])=[CH:8][CH:7]=2)=[O:4])[CH2:36][CH2:35]1
Reactant: CN1CCNCC1
Reactant: CC/C(=C(\c1ccc(/C=C/C(=O)O)cc1)c1ccc(OC(=O)CCl)cc1)c1ccccc1
Product: CC/C(=C(\c1ccc(/C=C/C(=O)O)cc1)c1ccc(OC(=O)CN2CCN(C)CC2)cc1)c1ccccc1

Procedure:
Treatment of compound 32 with N-methylpiperazine as described in Example 19 (Step 2) afforded the title compound, 34, as an off-white solid. 1HNMR (400 MHz, DMSO-d6): δ 0.85 (t, 3H), 2.11 (s, 3H), 2.27 (br, 4H), 2.39 (q, 2H), 2.50 (br, 4H), 3.38 (s, 2H), 6.49 (d, J=16 Hz, 1H), 6.79 (d, J=8.6 Hz, 2H), 6.85 (d, J=8.6 Hz, 2H), 7.09-7.19 (m, 5H), 7.23 (d, J=8.1 Hz, 2H), 7.49 (d, J=16 Hz, 1H), 7.65 (d, J=8 Hz, 2H), 12.36 (br, 1H); MS m/z 511 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8](F)[C:7]([N+:11]([O-:13])=[O:12])=[CH:6][C:3]=1[C:4]#[N:5].[OH-].[NH4+:15]>>[NH2:15][C:8]1[C:7]([N+:11]([O-:13])=[O:12])=[CH:6][C:3]([C:4]#[N:5])=[C:2]([F:1])[CH:9]=1
Reactant: N#Cc1cc([N+](=O)[O-])c(F)cc1F
Reactant: [NH4+]
Agent: [OH-]
Product: N#Cc1cc([N+](=O)[O-])c(N)cc1F
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 96 %

Procedure:
20 g (108 mmol) of 2,4-difluoro-5-nitrobenzonitrile was added to 200 ml of 25% ammonium hydroxide and the mixture was stirred for 90 min. at room temperature. The yellow precipitate was isolated by filtration and washed with water and a small amount of cold ethanol to give 18.8 g (96%) of the title compound. M.p. 197°-199° C.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N+:11]([O-:13])=[O:12])=O.[CH3:14][O:15][C:16]1[CH:24]=[CH:23][C:19]([C:20]([NH2:22])=[NH:21])=[CH:18][CH:17]=1>C(#N)C>[CH3:14][O:15][C:16]1[CH:24]=[CH:23][C:19]([C:20]2[NH:22][CH:2]=[C:3]([C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[N+:11]([O-:13])=[O:12])[N:21]=2)=[CH:18][CH:17]=1
Reactant: COc1ccc(C(=N)N)cc1
Reactant: O=C(CBr)c1ccccc1[N+](=O)[O-]
Solvent: CC#N
Product: COc1ccc(-c2nc(-c3ccccc3[N+](=O)[O-])c[nH]2)cc1
Temperature: 40 °C
Yield: 78.1 %

Procedure:
A mixture of 2-bromo-2′-nitroacetophenone (18 g), 4-methoxybenzamidine (20 g), and silica gel (20 g) in acetonitrile (500 ml) is heated at 40° C. for 24 hours. The reaction is evaporated and the residue put on a layer of silica gel and eluted with 50% ethyl acetate/hexane (1500 ml). The solution is evaporated under reduced pressure to approximately 250 ml and extracted with 5% HCl (3×250 ml). The combined aqueous solution is basified with K2CO3 and extracted with ethyl acetate (3×400 ml) to afford 2-(4-methoxyphenyl)-4-(2-nitrophenyl)-imidazole (17 g) as a dark yellow oil which is used in the next step without further purification.
Reaction SMILES: S(=O)(=O)(O)O.[C:6]1(=[O:20])[N:10]([CH2:11][C:12]([OH:14])=[O:13])[C:9](=[O:15])[C:8]2=[CH:16][CH:17]=[CH:18][CH:19]=[C:7]12.[N+:21]([O-])([OH:23])=[O:22]>>[N+:21]([C:17]1[CH:16]=[C:8]2[C:9](=[O:15])[N:10]([CH2:11][C:12]([OH:14])=[O:13])[C:6](=[O:20])[C:7]2=[CH:19][CH:18]=1)([O-:23])=[O:22]
Reactant: O=[N+]([O-])O
Reactant: O=C(O)CN1C(=O)c2ccccc2C1=O
Agent: O=S(=O)(O)O
Product: O=C(O)CN1C(=O)c2ccc([N+](=O)[O-])cc2C1=O
Temperature: 25 °C

Procedure:
To a mixture of concentrated sulfuric acid (350 ml) and fuming nitric acid (d=1.52)(60 ml) was added 2phthalimidoacetic acid (70 g) with stirring and under ice-cooling. The mixture was stirred for 1 hour under ice-cooling and for 2 hours at room temperature, and poured into ice-water (2 l). The resultant precipitate was collected by filtration and recrystallized from a mixture of water (2 l) and ethanol (1 l) to give the title compound (60 g) as light yellow sharp-pointed needles.
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[C:7]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][S:9][CH:10]=1)=[O:4].C(=O)([O-])[O-].[K+].[K+].[Cl:21][C:22]1[CH:23]=[C:24]([OH:29])[CH:25]=[CH:26][C:27]=1[Cl:28].O>CN(C)C=O>[CH3:14][O:13][C:11]([C:7]1[C:6]([NH:5][C:3](=[O:4])[CH2:2][O:29][C:24]2[CH:25]=[CH:26][C:27]([Cl:28])=[C:22]([Cl:21])[CH:23]=2)=[CH:10][S:9][CH:8]=1)=[O:12]
Reactant: Oc1ccc(Cl)c(Cl)c1
Reactant: COC(=O)c1cscc1NC(=O)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1cscc1NC(=O)COc1ccc(Cl)c(Cl)c1
Temperature: 90 °C
Reaction time: 8 h
Yield: 70.1 %

Procedure:
To a solution of methyl 4-(2-chloroacetamido)-3-thiophenecarboxylate ([51486-30-7], 100 mg, 0.428 mmol) in dimethylformamide (1.5 mL) was added potassium carbonate (88.7 mg, 0.642 mmol) and 3,4-dichlorophenol (83.7 mg, 0.514 mmol) and the reaction mixture was stirred at 90° C. overnight. After such time water was added. The precipitate was isolated by filtration, washed with water and dried in vacuo to yield the title compound as a white solid (108.1 mg, 70%).
Reaction SMILES: [CH3:1][C:2]([C:5]1[CH:6]=[C:7]([NH:15][C:16](=[O:25])[C:17]2[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=2[OH:24])[CH:8]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:10]=1)([CH3:4])[CH3:3].[C:26](Cl)(=[O:28])[CH3:27]>>[C:26]([O:24][C:18]1[CH:19]=[CH:20][C:21]([Cl:23])=[CH:22][C:17]=1[C:16]([NH:15][C:7]1[CH:8]=[C:9]([C:11]([CH3:12])([CH3:13])[CH3:14])[CH:10]=[C:5]([C:2]([CH3:1])([CH3:3])[CH3:4])[CH:6]=1)=[O:25])(=[O:28])[CH3:27]
Reactant: CC(C)(C)c1cc(NC(=O)c2cc(Cl)ccc2O)cc(C(C)(C)C)c1
Reactant: CC(=O)Cl
Product: CC(=O)Oc1ccc(Cl)cc1C(=O)Nc1cc(C(C)(C)C)cc(C(C)(C)C)c1
Yield: 66.1 %

Procedure:
Using N-{3,5-bis[(1,1-dimethyl)ethyl]phenyl}-5-chloro-2-hydroxybenzamide and acetyl chloride as the raw materials, the same operation as the example 96 gave the title compound.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[CH:5]=[C:6]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH2:10][CH2:9][C:8]2[CH:17]=[CH:18][CH:19]=[CH:20][C:7]1=2.C(OCC)(=O)C.[H][H]>C(O)C.[Pd]>[CH3:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[CH2:5][CH:6]1[C:7]2[CH:20]=[CH:19][CH:18]=[CH:17][C:8]=2[CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]1=2
Reactant: Cc1cccc(C=C2c3ccccc3CCc3ccccc32)c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: Cc1cccc(CC2c3ccccc3CCc3ccccc32)c1
Reaction time: 17 h

Procedure:
Add 5-(3-methyl-benzylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (0.18 g, 0.61 mmol), to a mixture of 10% Pd/C (0.045 g) suspended in absolute ethanol (4.0 mL) and ethyl acetate (2.0 mL) and hydrogenate under a balloon of hydrogen at room temperature and pressure. Stir for 17 h, remove the catalyst via filtration through a pad of Celite. Evaporate the filtrate and pass through a plug of silica gel equilibrated with hexanes. Concentrated the filtrate to give the title product. MS (m/e): 298 (M+). HPLC (ISO80-10M) t=1.00 (98%).
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[CH2:12]1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.ClCCl.CO>[I:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:6][CH:7]=1
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: O=C(O)Cc1ccc(I)cc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CO
Product: COC(=O)Cc1ccc(I)cc1
Temperature: 0 °C
Reaction time: 16 h
Yield: 81.5 %

Procedure:
4-iodophenylacetic acid (5.2 g, 0.02 mol) and DMAP (0.25 g, 0.002 mol) was dissolved in dichloromethane (40 mL) and methanol (3.2 mL), and the solution was cooled to 0° C. Then a solution of DCC (4.32 g, 0.021 mol) in dichloromethane was added dropwise over a period of 15 minutes. The reaction mixture was stirred at 0° C. for 1 hour and at room temperature for 16 hours, then filtered. The filtrate was diluted with dichloromethane (40 mL) and washed with 5% citric acid (4×25 mL), water (2×50 mL), dried (Na2SO4), filtered, and concentrated. The residual liquid was purified by silica gel flash column chromatography eluting with 20% EtOAc in hexane to give methyl 4-iodophenylacetate (4.5 g, 82%) as a colorless liquid: 1H-NMR (CDCl3) δ: 7.64 (d, 2H, J=8.4 Hz), 7.01 (2H, J=8.4 Hz), 3.69 (s, 3H), 3.57 (s, 2H); FAB-MS m/z=283 (M+Li). HRMS calcd. for C9H10IO2 (M+H), 276.9725, found 276.9726.