Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=2[O:15]C)[CH:5]=[CH:4][N:3]=1.Cl.[NH:18]1[CH2:21]C[CH2:19]1.C(N(CC)C(C)C)(C)C.CN(C)C(=O)C.[Cl-].[NH4+]>O>[Cl:14][C:12]1[CH:11]=[CH:10][C:9]([OH:15])=[C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([N:18]([CH3:21])[CH3:19])[CH:7]=2)[CH:13]=1
Reactant: C1CNC1
Reactant: COc1ccc(Cl)cc1-c1ccnc(Cl)c1
Agent: Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(=O)N(C)C
Solvent: O
Product: CN(C)c1cc(-c2cc(Cl)ccc2O)ccn1
Temperature: 170 °C
Yield: 32.5 %

Procedure:
A mixture of 2-chloro-4-(5-chloro-2-methoxyphenyl)pyridine (Preparation 866, 157 mg, 0.618 mmol), azetidine hydrochloride (120 mg, 1.2 mmol), and N,N-diisopropylethylamine (220 uL, 1.2 mmol) in N,N-dimethylacetamide (4.1 mL, 44 mmol) was heated 20 minutes at 170° C. under microwave irradiation. The reaction mixture was poured into water and saturated aqueous ammonium chloride and extracted with ethyl acetate (3×). The combined organic layers were washed with water then brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was taken up in methylene chloride, concentrated onto diatomaceous earth, and purified by automated flash chromatography (12 g SiO2, hexanes to 9:1 ethyl acetate-methanol). A single peak containing the major products eluted from the column. The appropriate fractions were concentrated in vacuo. The residue was dissolved in 1 mL of dimethylsulfoxide, filtered through a plug of cotton, and purified by reverse-phase HPLC to afford 4-chloro-2-[2-(dimethylamino)pyridin-4-yl]phenol as a tan solid (50 mg, 33%) followed by 4-chloro-2-(2-chloropyridin-4-yl)phenol as a light pink solid (24 mg, 16%). Unexpectedly 4-chloro-2-[2-(dimethylamino)pyridin-4-yl]phenol was isolated as the main product and none of the intended product was isolated. This presumably occurred due to decomposition of the dimethylacetamide to provide dimethylamine which reacted preferentially to give 4-chloro-2-[2-(dimethylamino)pyridin-4-yl]phenol
Reaction SMILES: S(Cl)([Cl:3])=O.[PH:5](=[O:8])([OH:7])[OH:6].[CH2:9]([C:11]([CH2:39][CH3:40])([CH:13](O)[C:14]1[N:18]=[CH:17][N:16]([C:19]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:15]=1)[CH3:12])[CH3:10]>N1C=CC=CC=1>[PH:5](=[O:6])([OH:8])[OH:7].[CH2:9]([C:11]([CH2:39][CH3:40])([CH:13]([Cl:3])[C:14]1[N:18]=[CH:17][N:16]([C:19]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:15]=1)[CH3:12])[CH3:10]
Reactant: CCC(C)(CC)C(O)c1ncn(C(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Reactant: O=S(Cl)Cl
Agent: O=[PH](O)O
Solvent: c1ccncc1
Product: CCC(C)(CC)C(Cl)c1ncn(C(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Thionyl chloride (20 ml) was added dropwise to a stirred solution of diethyl 3-hydroxy-3(1-trityl-1,2,4-triazol-3-yl)propane phosphonate (1.0 g, prepared as described in Example 24) in pyridine (10 ml), whilst maintaining the temperature below 5° C. The mixture was allowed to warm to room temperature, stirred for three hours, then evaporated under reduced pressure. The residue was dissolved in ethyl acetate, washed with water and brine, dried over magnesium sulphate and evaporated under reduced pressure. This residue was chromatographed on silica, using dichloromethane-ethanol (49:1) as eluant, to give diethyl 3-chloro-3(1-trityl-1,2,4-triazol-3-yl)propane phosphonate (0.64 g, m.p. 123-124° C.). NMR (CDCl3): δ 1.3(6H,t), 1.8-2.1(2H,m), 2.4-2.6(2H,m), 4.1(4H,m), 5.1(1H,t), 7.1(6H,m), 7.4(9H,m), 7.95(1H,s). M/S: M+ 523,525.
Reaction SMILES: [CH2:1](O)[C@H:2]1[O:7][C@H:6]([O:8][C@]2(CO)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@H:5]([OH:20])[C@@H:4](O)[C@@H:3]1O.C1C2C(=CC=CC=2)C=CC=1.C(OCC)(=O)C(C)O>C(O)C>[OH:20][CH:5]([CH:4]=[CH2:3])[C:6]([O:7][CH2:2][CH3:1])=[O:8]
Reactant: OC[C@H]1O[C@@](CO)(O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O)[C@@H]1O
Solvent: c1ccc2ccccc2c1
Solvent: CCOC(=O)C(C)O
Solvent: CCO
Product: C=CC(O)C(=O)OCC
Temperature: 160 °C
Yield: 48 %

Procedure:
An autoclave (50 cc microclave) is charged with 8.0 g of ethanol, 0.2252 g of sucrose (0.6578 mmol), 118.9 mg naphthalene (internal standard) and finally with 160.0 mg Sn-BEA (prepared according to U.S. Pat. No. 6,306,364). The autoclave is closed, charged with 20 bar of argon and heated to 160° C. After the temperature reaches 100° C., the mechanical stirrer is started (500 rpm) and the mixture is heated for 20 hours under these conditions. GC-analysis of the reaction mixture shows that 1.03 mmol of ethyl lactate is formed (39%) together with 0.316 mmol ethyl 2-hydroxy-3-butenoate (16%).
Reaction SMILES: [NH2:1]/[C:2](/[C:9]([F:12])([F:11])[F:10])=[CH:3]\[C:4]([O:6]CC)=O.[H-].[Na+].[Cl:15][C:16]1[C:21]([O:22][CH:23]([CH3:25])[CH3:24])=[CH:20][C:19]([N:26]=[C:27]=[O:28])=[C:18]([F:29])[CH:17]=1.Cl>C1(C)C=CC=CC=1.CN(C)C=O.O>[Cl:15][C:16]1[C:21]([O:22][CH:23]([CH3:24])[CH3:25])=[CH:20][C:19]([N:26]2[C:4](=[O:6])[CH:3]=[C:2]([C:9]([F:10])([F:11])[F:12])[NH:1][C:27]2=[O:28])=[C:18]([F:29])[CH:17]=1
Reactant: CC(C)Oc1cc(N=C=O)c(F)cc1Cl
Reactant: CCOC(=O)/C=C(\N)C(F)(F)F
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: CC(C)Oc1cc(-n2c(=O)cc(C(F)(F)F)[nH]c2=O)c(F)cc1Cl
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
A solution of 1.0 g of ethyl 3-amino-4,4,4-trifluorocrotonate in 10 ml of absolute toluene is added dropwise while stirring at 0° C. during 15 minutes to a suspension of 0.24 g of a 55% sodium hydride dispersion in 20 ml of absolute dimethylformamide and the mixture is stirred at 0° C. for 15 minutes. The reaction mixture is subsequently cooled to -30° C. and treated with a solution of 1.26 g of 4-chloro-2-fluoro-5-isopropoxyphenyl isocyanate in 10 ml of absolute toluene. The temperature rises rapidly to -10° C. and the reaction mixture is thereafter stirred at room temperature for 2 hours. The reaction mixture is poured into a solution of 3 ml of 2N hydrochloric acid and 500 ml of water and the aqueous mixture is extracted twice with 100 ml of ethyl acetate each time, and the organic phases are washed twice with 50 ml of water each time, dried over anhydrous sodium sulphate and evaporated to dryness under reduced pressure. The residue is recrystalized from diethyl ether/n-hexane. There is obtained 3-(4-chloro-2-fluoro-5-isopropoxyphenyl)-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione, m.p. 195°-197° C.
Reaction SMILES: [C:1](Cl)(Cl)=[O:2].[CH:5]1([C:10]2[S:14][C:13]([NH2:15])=[N:12][N:11]=2)[CH2:9][CH2:8][CH2:7][CH2:6]1>C(OCC)(=O)C>[CH:5]1([C:10]2[S:14][C:13]([N:15]=[C:1]=[O:2])=[N:12][N:11]=2)[CH2:6][CH2:7][CH2:8][CH2:9]1
Reactant: Nc1nnc(C2CCCC2)s1
Reactant: O=C(Cl)Cl
Solvent: CCOC(C)=O
Product: O=C=Nc1nnc(C2CCCC2)s1
Reaction time: 16 h

Procedure:
A saturated solution of phosgene in ethyl acetate (100 ml) is charged into a glass reaction vessel equipped with a mechanical stirrer. A slurry of 5-cyclopentyl-2-amino-1,3,4-thiadiazole (50 grams) in ethyl acetate (300 ml) is added to the reaction vessel and the resulting mixture is stirred for a period of about 16 hours, resulting in the formation of a precipitate. The reaction mixture is then purged with nitrogen gas to remove unreacted phosgene. The purged mixture is then filtered to recover the precipitate. The precipitate is then recrystallized to yield the desired product 5-cyclopentyl-1,3,4-thiadiazol-2-yl isocyanate dimer.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[S:11](=[O:13])(=[O:12])[CH2:10][CH2:9][C:8]([C:14]([O:16][CH3:17])=[O:15])=[CH:7][C:6]=2[CH:18]=1.B([O-])([O-])O[C:21]1[CH:26]=[CH:25][C:24]([N:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.O.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>[N:27]1([C:24]2[CH:25]=[CH:26][C:21]([C:2]3[CH:3]=[CH:4][C:5]4[S:11](=[O:13])(=[O:12])[CH2:10][CH2:9][C:8]([C:14]([O:16][CH3:17])=[O:15])=[CH:7][C:6]=4[CH:18]=3)=[CH:22][CH:23]=2)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1
Reactant: COC(=O)C1=Cc2cc(Br)ccc2S(=O)(=O)CC1
Reactant: [O-]B([O-])Oc1ccc(N2CCCCC2)cc1
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: O
Solvent: CCO
Solvent: Cc1ccccc1
Product: COC(=O)C1=Cc2cc(-c3ccc(N4CCCCC4)cc3)ccc2S(=O)(=O)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 85.5 %

Procedure:
Under argon atmosphere, a mixture of methyl 7-bromo-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylate (0.80 g), 4-piperidinophenyl borate (0.55 g) and potassium carbonate (0.67 g) in toluene/ethanol/water (30/3/3 ml) was stirred at room temperature for 1 hour. To the mixture was added tetrakistriphenylphosphinepalladium (0.14 g), and the mixture was refluxed for 15 hours, cooled, extracted with ethyl acetate, washed with saturated brine, dried with magnesium sulfate and concentrated under reduced pressure to give crystals, which were recrystallized from ethyl acetate to give yellow crystals of methyl 7-(4-piperidinophenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylate (0.85 g).
Reaction SMILES: Br[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([O:9][Si:10]([CH:17]([CH3:19])[CH3:18])([CH:14]([CH3:16])[CH3:15])[CH:11]([CH3:13])[CH3:12])=[CH:4][C:3]=1[CH3:20].C([Li])CCC.[F:26][C:27]1[CH:34]=[CH:33][C:30]([CH:31]=[O:32])=[CH:29][C:28]=1[C:35]([CH3:37])=[CH2:36]>C1COCC1.CCOC(C)=O>[CH3:20][C:3]1[CH:4]=[C:5]([O:9][Si:10]([CH:17]([CH3:19])[CH3:18])([CH:14]([CH3:16])[CH3:15])[CH:11]([CH3:13])[CH3:12])[CH:6]=[C:7]([CH3:8])[C:2]=1[CH:31]([C:30]1[CH:33]=[CH:34][C:27]([F:26])=[C:28]([C:35]([CH3:37])=[CH2:36])[CH:29]=1)[OH:32]
Reactant: C=C(C)c1cc(C=O)ccc1F
Reactant: Cc1cc(O[Si](C(C)C)(C(C)C)C(C)C)cc(C)c1Br
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: C=C(C)c1cc(C(O)c2c(C)cc(O[Si](C(C)C)(C(C)C)C(C)C)cc2C)ccc1F
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
To a solution of 4-bromo-3,5-dimethyl-triisopropylsilanoxybenzene (1.29 g, 3.6 mmol, G. Chiellini et al. Biorg. Med. Chem. Lett. 2000, 10, 2607) in THF at −78° C. was added n-butyllithium (1.58 mL, 3.96 mmol, 2.5 M in THF). After 30 min, a solution of 4-fluoro-3-isopropenylbenzaldehyde (500 mg, 3.0 mmol) in THF was added. The reaction mixture was stirred at −78° C. for 1 h, allowed to warm to room temperature, diluted with EtOAc and quenched with water. The organic layer was dried over MgSO4, filtered and concentrated to afford crude 1-(2,6-dimethyl-4-triisopropylsilanyloxyphenyl)-1-(4′-fluoro-3′-isopropenylphenyl)methanol as an oil: 1H NMR (200 MHz, CDCl3): δ 7.18 (m, 1 H), 7.02 (m, 1 H), 6.94 (m, 1 H), 6.56 (s, 2 H), 6.22 (s, 1 H), 5.18 (m, 2 H), 2.20 (s, 6 H), 2.08 (s, 3 H), 1.25 (m, 3 H), 1.11 (m, 18).
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[Cl-].[NH4+].CN(C)C=O.[CH2:12]([O:19][C:20]1[CH:42]=[CH:41][C:40]([N:43]2[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]2)=[CH:39][C:21]=1[C:22]([NH:24][C:25]1[CH:26]=[C:27]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:28]=[CH:29][C:30]=1[C:31]#[N:32])=[O:23])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>O.C(Cl)(Cl)Cl>[CH2:12]([O:19][C:20]1[CH:42]=[CH:41][C:40]([N:43]2[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]2)=[CH:39][C:21]=1[C:22]([NH:24][C:25]1[CH:26]=[C:27]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:28]=[CH:29][C:30]=1[C:31]1[NH:32][N:3]=[N:2][N:1]=1)=[O:23])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: N#Cc1ccc(-c2ccccc2)cc1NC(=O)c1cc(N2CCCCC2)ccc1OCc1ccccc1
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClC(Cl)Cl
Solvent: O
Product: O=C(Nc1cc(-c2ccccc2)ccc1-c1nnn[nH]1)c1cc(N2CCCCC2)ccc1OCc1ccccc1
Temperature: 110 °C
Reaction time: 2 h
Yield: 66.2 %

Procedure:
Sodium azide (0.065 g) and ammonium chloride (0.053 g) were added to an N,N-dimethylformamide (2.5 mL) suspension of 2-(benzyloxy)-N-(4-cyanobiphenyl-3-yl)-5-(piperidin-1-yl)benzamide (0.25 g), followed by stirring at 110° C. for 2 hours. The reaction mixture was cooled to room temperature, and then sodium azide (0.065 g) and ammonium chloride (0.053 g) were added thereto, followed by stirring at 110° C. for 1 hour and 30 minutes. The reaction mixture was cooled to room temperature, and then sodium azide (0.032 g) and ammonium chloride (0.026 g) were added thereto, followed by stirring at 110° C. for 1 hour and 30 minutes. The reaction mixture was cooled to room temperature, and then sodium azide (0.032 g) and ammonium chloride (0.026 g) were added thereto, followed by stirring at 110° C. for 1 hour. The reaction mixture was cooled to room temperature, and then chloroform and water were added thereto. The organic layer was separated and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 100-90% chloroform/methanol] and then purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 100-93% chloroform/methanol] to obtain 0.18 g of 2-(benzyloxy)-N-(5-phenyl-2-(1H-tetrazol-5-yl)phenyl)-5-(piperidin-1-yl)benzamide as a brown solid.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[CH:3]=1.C([O:13][B:14](OC(C)C)[O:15]C(C)C)(C)C.C([Li])CCC.Cl>O1CCCC1.CCCCCC>[Cl:9][C:4]1[CH:3]=[C:2]([B:14]([OH:15])[OH:13])[CH:7]=[C:6]([Cl:8])[CH:5]=1
Reactant: Clc1cc(Cl)cc(Br)c1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: OB(O)c1cc(Cl)cc(Cl)c1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To a cold (-78° C.) solution of 1-bromo-3,5-dichlorobenzene (14 g) and triisopropoxyborane (20.8 ml) in tetrahydrofuran (140 ml) was added dropwise n-butyllithium in hexane (1.66 M, 52.3 ml). The mixture was stirred at -78° C. for one hour and warmed to room temperature over two hours. The reaction mixture was poured onto 2M hydrochloric acid solution (120 ml) and stirred for 10 minutes. The product was extracted with ether (200 ml) 3 times, and the organic layers were combined, washed with brine, dried over magnesium sulfate and evaporated in vacuo. To the residue was added petroleum ether and the crystalline was collected, washed with petroleum ether and dried to give 3,5-dichlorophenyl-dihydroxyborane.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([O:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[C:10]=2[N:11]=1.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[C:29]([NH:33][S:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)(=[O:36])=[O:35])[CH:30]=[N:31][CH:32]=2)O1.C([O-])(O)=O.[Na+]>O1CCOCC1>[O:16]1[CH2:17][CH2:18][CH:13]([O:12][C:9]2[C:10]3[N:11]=[C:2]([C:27]4[CH:28]=[C:29]([NH:33][S:34]([C:37]5[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=5)(=[O:35])=[O:36])[CH:30]=[N:31][CH:32]=4)[CH:3]=[CH:4][C:5]=3[N:6]=[CH:7][N:8]=2)[CH2:14][CH2:15]1
Reactant: CC1(C)OB(c2cncc(NS(=O)(=O)c3ccccc3)c2)OC1(C)C
Reactant: Clc1ccc2ncnc(OC3CCOCC3)c2n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Product: O=S(=O)(Nc1cncc(-c2ccc3ncnc(OC4CCOCC4)c3n2)c1)c1ccccc1
Temperature: 25 °C
Yield: 19.1 %

Procedure:
To a solution of 6-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidine (Intermediate 1) (60.0 mg, 0.226 mmol) in 1,4-dioxane (1.20 mL) was added N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide (Intermediate 2) (122 mg, 0.339 mmol), PdCl2(dppf)2CH2Cl2 (18.0 mg, 0.0230 mmol), and 1N aq. NaHCO3 (0.452 mL, 0.452 mmol) at room temperature. The reaction mixture was subjected to microwave irradiation for 30 min at 120° C., and cooled to room temperature. The reaction mixture was filtered through a Celite pad and washed with EtOAc. The filtrate was diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=3:1) to give N-(5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfonamide (20.0 mg, 19%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 2.02-2.11 (2H, m), 2.23-2.27 (2H, m), 3.68-3.74 (2H, m), 4.10-4.15 (2H, m), 5.64-5.69 (1H, m), 7.07 (1H, brs), 7.47-7.51 (2H, m), 7.56-7.60 (1H, m), 7.85-7.88 (2H, m), 8.21 (1H, d, J=8.8 Hz), 8.36 (1H, d, J=8.8 Hz), 8.38 (1H, s), 8.43 (1H, t, J=2.2 Hz), 8.83 (1H, s), 9.16 (1H, s); m/z=464.2 [M+1]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH2:12][C:13]1[N:14]=[C:15]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:16][C:17]=1[CH3:18])[CH:6]=[O:7].[BH4-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH2:12][C:13]1[N:14]=[C:15]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:16][C:17]=1[CH3:18])[CH2:6][OH:7]
Reactant: COc1cc(C=O)ccc1OCc1nc(-c2ccccc2)oc1C
Agent: [BH4-]
Agent: [Na+]
Product: COc1cc(CO)ccc1OCc1nc(-c2ccccc2)oc1C
Yield: 93.9 %

Procedure:
In substantially the same manner in Reference Example 93, 3-methoxy-4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzaldehyde (6.47 g) was reduced by sodium borohydride (760 mg) to obtain 3-methoxy-4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl alcohol (6.11 g, yield 93%) as crystals.
Reaction SMILES: ClC1C=CC=C(Cl)C=1Cl.[N+]([O-])(O)=O.S(=O)(=O)(O)O.[N+]([O-])(O)=O.ClC1C([N+]([O-])=O)=CC([N+]([O-])=O)=C(Cl)C=1Cl.[OH:38][C:39]1[C:44]([N+:45]([O-])=O)=[CH:43][C:42]([N+:48]([O-])=O)=[C:41]([OH:51])[C:40]=1Cl>CO.O.[Pd]>[NH2:45][C:44]1[C:39]([OH:38])=[CH:40][C:41]([OH:51])=[C:42]([NH2:48])[CH:43]=1
Reactant: O=[N+]([O-])c1cc([N+](=O)[O-])c(O)c(Cl)c1O
Agent: [Pd]
Agent: Clc1cccc(Cl)c1Cl
Agent: O=S(=O)(O)O
Solvent: O
Solvent: O=[N+]([O-])O
Solvent: CO
Product: Nc1cc(N)c(O)cc1O

Procedure:
Because of the difficulties mentioned it has been tried to obtain diaminoresorcinol from another starting material. Thus, in EP 266,222 it is proposed to nitrate 1,2,3-trichlorobenzene in a sulphuric acid/nitric acid mixture to 1,2,3-trichloro-4,6-dinitro-benzene and to convert this compound, using an alkali metal hydroxide in methanol/water, into 1,3-dihydroxy-2-chloro-4,6-dinitrobenzene. The reduction of the latter compound on a Pd/activated charcoal catalyst gives diaminoresorcinol. However this process has the disadvantage that the dihydroxy compound of the second process step must be extracted with ethyl acetate, as a consequence of which the space yield drops to about 75 g/l (0.32 mole/l); after the said extraction the dihydroxy compound is isolated by evaporation of the ethyl acetate phase.
Reaction SMILES: [CH3:1][C@@H:2]1[CH2:6][C@@H:5]([CH:7]2[CH2:9][N@@:8]2[S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N+:19]([O-:21])=[O:20])(=[O:12])=[O:11])[O:4][C:3]1=[O:22].[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=1[N:31]1[CH2:36][C:35]([CH3:38])([CH3:37])[NH:34][CH2:33][C:32]1=[O:39]>C1(C)C=CC=CC=1>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=1[N:31]1[C:32](=[O:39])[CH2:33][N:34]([CH2:9][C@H:7]([NH:8][S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N+:19]([O-:21])=[O:20])(=[O:12])=[O:11])[C@@H:5]2[CH2:6][C@@H:2]([CH3:1])[C:3](=[O:22])[O:4]2)[C:35]([CH3:38])([CH3:37])[CH2:36]1
Reactant: CC1(C)CN(c2cc(F)ccc2Cl)C(=O)CN1
Reactant: C[C@@H]1C[C@@H](C2C[N@@]2S(=O)(=O)c2ccccc2[N+](=O)[O-])OC1=O
Agent: C[C@@H]1C[C@@H](C2C[N@]2S(=O)(=O)c2ccccc2[N+](=O)[O-])OC1=O
Solvent: Cc1ccccc1
Product: C[C@@H]1C[C@@H]([C@H](CN2CC(=O)N(c3cc(F)ccc3Cl)CC2(C)C)NS(=O)(=O)c2ccccc2[N+](=O)[O-])OC1=O
Yield: 94.2 %

Procedure:
A solution of 730 mg of (3R,5S)-3-methyl-5-[(S)-1-(2-nitrobenzenesulfonyl)aziridin-2-yl]dihydrofuran-2-one obtained in Example (76g) (2.24 mmol) and 689 mg of 1-(2-chloro-5-fluorophenyl)-5,5-dimethylpiperazin-2-one obtained in Example (62d) (2.68 mmol) in toluene (22 ml) was stirred at 110° C. for two hours. After cooling, the reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:methylene chloride/ethyl acetate=3/1-2/1) to obtain 1.23 g of the title compound (yield: 94%).
Reaction SMILES: Br.[Br-].[CH3:3][N:4]([CH3:27])[CH2:5][CH2:6][CH2:7][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCCCCC.C([Li])CCC.O=[C:40]1[C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=2[CH2:44][O:43][C:42]2[CH:51]=[CH:52][C:53]([C:55]([O:57][CH3:58])=[O:56])=[CH:54][C:41]1=2>O1CCCC1>[CH3:3][N:4]([CH3:27])[CH2:5][CH2:6][CH:7]=[C:40]1[C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=2[CH2:44][O:43][C:42]2[CH:51]=[CH:52][C:53]([C:55]([O:57][CH3:58])=[O:56])=[CH:54][C:41]1=2
Reactant: COC(=O)c1ccc2c(c1)C(=O)c1ccccc1CO2
Reactant: CN(C)CCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Br
Agent: [Br-]
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COC(=O)c1ccc2c(c1)C(=CCCN(C)C)c1ccccc1CO2

Procedure:
In this Example, 45 g of (3-dimethylaminopropyl)triphenylphosphonium bromide hydrobromide is suspended in 200 ml of tetrahydrofuran under a nitrogen atmosphere and 82 ml of 1.6N-n-butyl lithium hexane solution is added thereto under ice-cooling. The mixture is stirred under ice-cooling for one hour. To the mixture is dropwise added under ice-cooling a solution obtained by dissolving 10 g of methyl 11-oxo-6,11-dihydrodibenz[b,e]oxepin-2-carboxylate in 200 ml of tetrahydrofuran. After stirring the mixture at room temperature for 2 hours, the mixture is extracted with 800 ml of ethyl acetate. After washing the extract with saturated aqueous sodium chloride solution and drying the extract over anhydrous sodium sulfate, the solvent is distilled away under reduced pressure. The residue is purified by column chromatography on silica gel (eluent: hexane:ethyl acetate:triethylamine=10:10:1) to obtain 2.0 g of trans form and 5.6 g of cis form of the desired product.