Azzindani/Open_Reaction_Data huggingface dataset:
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]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][N:24]([CH3:31])[CH:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[CH:19][CH:18]=3)=[O:15])=[CH:7][C:6]=2[CH:32]=1.C1(C)C=CC=CC=1.C(O)C.O.B([O-])([O-])O[C:46]1[CH:51]=[CH:50][C:49]([O:52][CH2:53][CH2:54][CH2:55][O:56][CH2:57][CH3:58])=[CH:48][CH:47]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH2:57]([O:56][CH2:55][CH2:54][CH2:53][O:52][C:49]1[CH:48]=[CH:47][C:46]([C:2]2[CH:3]=[CH:4][C:5]3[S:11](=[O:13])(=[O:12])[CH2:10][CH2:9][C:8]([C:14]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([CH2:23][N:24]([CH3:31])[CH:25]5[CH2:26][CH2:27][O:28][CH2:29][CH2:30]5)=[CH:21][CH:22]=4)=[O:15])=[CH:7][C:6]=3[CH:32]=2)=[CH:51][CH:50]=1)[CH3:58]
Reactant: CCOCCCOc1ccc(OB([O-])[O-])cc1
Reactant: CN(Cc1ccc(NC(=O)C2=Cc3cc(Br)ccc3S(=O)(=O)CC2)cc1)C1CCOCC1
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: CCO
Solvent: O
Solvent: Cc1ccccc1
Product: CCOCCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CN(C)C4CCOCC4)cc2)CCS3(=O)=O)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 29.4 %

Procedure:
To 7-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (400 mg) was added toluene/ethanol/water (10/1/1, 19.2 ml) and then were added 4-(3-ethoxypropoxy)phenyl borate (207 mg) and potassium carbonate (234 mg), and the mixture was stirred at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (36 mg), and the mixture was refluxed for 12 hours and cooled to room temperature. The mixture was added to water, and the mixture was extracted with ethyl acetate, washed with saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column chromatography (ethyl acetate/ethanol=3/1) and recrystallized from ethanol to give 7-[4-(3-ethoxypropoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 99) (140 mg).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]=1[CH3:14].[CH3:16]CN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.BrC[C:36]1[CH:45]=[CH:44][C:39]2[N:40]([CH3:43])[N:41]=[N:42][C:38]=2[CH:37]=1>CN(C=O)C>[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH2:16][C:45]2[CH:36]=[CH:37][C:38]3[N:42]=[N:41][N:40]([CH3:43])[C:39]=3[CH:44]=2)[C:6]=1[CH3:14]
Reactant: CCN(CC)P1(=NC(C)(C)C)N(C)CCCN1C
Reactant: COC(=O)Cc1c(C)[nH]c2ncccc12
Reactant: Cn1nnc2cc(CBr)ccc21
Solvent: CN(C)C=O
Product: COC(=O)Cc1c(C)n(Cc2ccc3nnn(C)c3c2)c2ncccc12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of (2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetic acid methyl ester ((0.025 g, 0.122 mmol) in dry DMF (1 ml) under an inert atmosphere of Argon is added dropwise, BEMP (56.6 μl, 0.196 mmol). The mixture is agitated at room temperature for 1 hour before cooling to 0° C. with an ice-bath. A solution of 5-bromomethyl-1-methyl-1H-benzotriazole (0.044 g, 0.196 mmol) in DMF (1 ml) is added to the cooled solution and the resulting mixture is agitated at room temperature for 2 days. The solvent is removed in vacuo and purification of the crude by chromatography on silica eluting with iso-hexane/ethyl acetate (0%-20% ethyl acetate) yields the titled product. (MH+ 350).
Reaction SMILES: [OH2:1].B(O)(O)O.[H][H].[CH3:8][C:9]1([CH3:25])[O:24][CH:12]2[CH:13]([O:20][CH2:21][O:22][CH3:23])[CH2:14][C:15]3[CH:16]([CH2:17][O:18]N=3)[CH:11]2[O:10]1>[Ni].CO.C(OCC)C>[OH:18][CH2:17][CH:16]1[CH:11]2[O:10][C:9]([CH3:25])([CH3:8])[O:24][CH:12]2[CH:13]([O:20][CH2:21][O:22][CH3:23])[CH2:14][C:15]1=[O:1]
Reactant: O
Reactant: COCOC1CC2=NOCC2C2OC(C)(C)OC12
Reactant: [H][H]
Agent: [Ni]
Agent: OB(O)O
Solvent: CO
Solvent: CCOCC
Product: COCOC1CC(=O)C(CO)C2OC(C)(C)OC12
Reaction time: 5 h
Yield: 61 %

Procedure:
Raney nickel W-2 (NDHF-90: a trademark for a product of Kawaken Fine Chemical K.K.; 550 mg) was subjected to decantation once with water and once with methanol. Forty eight milligrams of boric acid were added. The atmosphere was replaced with argon and then with hydrogen. Methanol (1.5 ml) and water (0.3 ml) were added and boric acid was dissolved therein. Then, a solution of 80 mg of 4,5-(dimethylmethylenedioxy)-6-(methoxymethoxy)-3,3a,4,5,6,7-hexahydro-2,1-benzoisooxazole in 3.5 ml of methanol was added at room temperature, and the mixture was stirred for 5 hours. The reaction mixture was diluted with diethyl ether and filtered through florisel. The filtrate was washed with a saturated sodium chloride aqueous solution and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography to afford 49 mg of 2-hydroxymethyl-3,4-(dimethylmethylenedioxy)-5-(methoxymethoxy)cyclohexanone having the following properties (yield 61%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[C:3]=1[C:10]1[C:18]2[O:17][CH:16]([CH2:19][NH2:20])[CH2:15][C:14]=2[CH:13]=[CH:12][CH:11]=1.C(N(C(C)C)CC)(C)C.Cl[C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32]>>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[C:3]=1[C:10]1[C:18]2[O:17][CH:16]([CH2:19][NH:20][C:31](=[O:32])[O:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH2:15][C:14]=2[CH:13]=[CH:12][CH:11]=1
Reactant: NCC1Cc2cccc(-c3c(Cl)cc(Cl)cc3Cl)c2O1
Reactant: O=C(Cl)OCc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NCC1Cc2cccc(-c3c(Cl)cc(Cl)cc3Cl)c2O1)OCc1ccccc1
Yield: 96.9 %

Procedure:
Treatment of (±)-{[7-(2,4,6-trichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine (1.1 g, 3.57 mmol) with diisopropylethylamine (0.69 g, 5.35 mmol) and benzyl chloroformate (0.0.82 g, 4.28 mmol) generally according to the procedure described for Intermediate 12 provided 1.6 g (99%) of (±)-benzyl {[7-(2,4,6-trichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}carbamate as a colorless oil.
Reaction SMILES: C1COCC1.O.[NH2:7][C@@H:8]([CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:9]([OH:11])=[O:10].[CH:20]1[C:28]2[C:27]3[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=3[O:25][C:24]=2[CH:23]=[CH:22][C:21]=1[S:33](Cl)(=[O:35])=[O:34]>C(N(CC)CC)C>[CH:20]1[C:28]2[C:27]3[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=3[O:25][C:24]=2[CH:23]=[CH:22][C:21]=1[S:33]([NH:7][C@@H:8]([CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:9]([OH:11])=[O:10])(=[O:35])=[O:34]
Reactant: O=S(=O)(Cl)c1ccc2oc3ccccc3c2c1
Reactant: N[C@@H](CCc1ccccc1)C(=O)O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)[C@H](CCc1ccccc1)NS(=O)(=O)c1ccc2oc3ccccc3c2c1
Yield: 38.8 %

Procedure:
To a THF/water (5:3, 8 mL) solution of (S)α-amino4-phenyl-butyric acid (0.61 g, 0.0034 mol) and triethylamine (1 mL) at 10° C. was added dibenzofuran-2-sulfonyl chloride (1.0 g, 0.00375 mol) in one portion with stirring. The resulting solution was stirred at room temperature for 24 hours. The solution was then concentrated in vacuo and the residue redissolved in water (10 mL). This solution was cooled in an ice bath and then acidified with 1N HCl. An oil was deposited, which was then triturated with ethyl acetate and hexane to give the title product (0.54 g, 35%), Melting point=130-132° C.
Reaction SMILES: [O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[CH:12]=[C:11]([CH3:13])[C:10]([C:14]3[CH:15]=[CH:16][C:17]4[C:18]5[N:38]([CH:39]6[CH2:44][CH2:43][O:42][CH2:41][CH2:40]6)[N:37]=[CH:36][C:19]=5[C:20](=[O:35])[N:21](CC5C=CC(OC)=CC=5OC)[C:22]=4[CH:23]=3)=[C:9]([CH3:45])[CH:8]=2)[CH2:3][CH2:2]1.C1COCC1.[H][H]>C(O)C.[C].[Pd]>[CH3:13][C:11]1[CH:12]=[C:7]([CH:4]2[CH2:3][CH2:2][O:1][CH2:6][CH2:5]2)[CH:8]=[C:9]([CH3:45])[C:10]=1[C:14]1[CH:15]=[CH:16][C:17]2[C:18]3[N:38]([CH:39]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)[N:37]=[CH:36][C:19]=3[C:20](=[O:35])[NH:21][C:22]=2[CH:23]=1
Reactant: [H][H]
Reactant: COc1ccc(Cn2c(=O)c3cnn(C4CCOCC4)c3c3ccc(-c4c(C)cc(C5=CCOCC5)cc4C)cc32)c(OC)c1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: Cc1cc(C2CCOCC2)cc(C)c1-c1ccc2c(c1)[nH]c(=O)c1cnn(C3CCOCC3)c12
Temperature: 60 °C
Reaction time: 14 h
Yield: 44.5 %

Procedure:
10% palladium carbon (50% wet, 15 mg) was added to a solution of 7-[4-(3,6-dihydro-2H-pyran-4-yl)-2,6-dimethylphenyl]-5-(2,4-dimethoxybenzyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one (44 mg) in ethanol (2 mL)-THF (2 mL). The reaction mixture was stirred at mom temperature for four hours and 35 minutes in a hydrogen atmosphere. The catalyst was removed from the reaction mixture by filtration, and the filtrate was then concentrated under reduced pressure. TFA (1.5 mL) was added to the resulting residue. The reaction mixture was stirred at 60° C. for 14 hours. The reaction mixture was returned to room temperature, and the reaction mixture was then concentrated under reduced pressure. Chloroform and a saturated aqueous sodium bicarbonate solution were added to the residue, and the organic layer was separated. The aqueous layer was re-extracted with chloroform. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform 100%, then ethyl acetate 100%). The target fraction was collected and concentrated. Ethyl acetate and MTBE were added to the resulting residue. The precipitated solid was collected by filtration and dried under reduced pressure to give the title compound (14.8 mg).
Reaction SMILES: N1C=CC=CC=1.[C:7]1([CH3:17])[CH:12]=[CH:11][C:10]([S:13](Cl)(=[O:15])=[O:14])=[CH:9][CH:8]=1.[CH3:18][C:19]1[CH:23]([CH3:24])[CH:22]=[C:21]([CH3:25])[C:20]=1[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[NH2:32].Cl>>[CH3:18][C:19]1[CH:23]([CH3:24])[CH:22]=[C:21]([CH3:25])[C:20]=1[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[NH:32][S:13]([C:10]1[CH:11]=[CH:12][C:7]([CH3:17])=[CH:8][CH:9]=1)(=[O:15])=[O:14]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CC1=CC(C)C(C)=C1c1ccccc1N
Agent: Cl
Solvent: c1ccncc1
Product: CC1=CC(C)C(C)=C1c1ccccc1NS(=O)(=O)c1ccc(C)cc1
Yield: 63.9 %

Procedure:
0.131 g (1.505 mmol) of pyridine and 0.316 g (1.656 mmol) of p-toluenesulfonyl chloride were added to 0.300 g (1.505 mmol) of 2-(2,3,5-trimethylcyclopenta-1,4-dienyl)phenylamine melted in 3 mL of MC, and then reacted at room temperature for 12 hours. 3 mL of 2 N HCl was added to the reaction product and strongly stirred for a few minutes. The organic layer was collected. The collected organic layer was neutralized with 3 mL of H2O without delay and dried over MgSO4. The product was filtered using a column chromatography with hexane/ethylacetate (v/v=3:1). The solvent contained in the purified product was dried in vacuum, thereby obtaining white solid (0.340 g, 64%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([O:9][CH3:10])=[CH:4][C:3]=1[C:11](=O)[CH2:12]Cl.O1CCOCC1.[BH4-].[Na+].Cl>C(Cl)Cl.O>[CH3:10][O:9][C:5]1[CH:4]=[C:3]2[C:2](=[C:7]([CH3:8])[CH:6]=1)[NH:1][CH:12]=[CH:11]2
Reactant: COc1cc(C)c(N)c(C(=O)CCl)c1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: C1COCCO1
Solvent: O
Product: COc1cc(C)c2[nH]ccc2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 76.1 %

Procedure:
To a solution of 4-methoxy-2-methylanaline (0.36 mole, 50.0 g) in methylene chloride (450 mL) cooled to 10° C. (acetone/ice) was added a solution of 1.0 M boron trichloride in methylene chloride (0.50 mole, 500 mL) while maintaining the reaction temperature below −10° C. Chloroacetonitrile (1.82 mole, 137.6 g) was added to the reaction while maintaining the internal temperature below 0° C. This was followed by the addition of diethylaluminum chloride (0.40 mole, 48.34 g, 50 mL) while maintaining the reaction temperature below 0° C. The solution was then refluxed for 5.25 hours. The reaction was cooled to room temperature and carefully treated with 5N hydrochloric acid (0.450 L) and water (1 L). The suspension was heated to reflux and cooled to room temperature. The phases were separated and the aqueous phase was extracted with methylene chloride (3×500 mL). The combined organic phases were filtered through a pad of silica (height of silica=8 cm) in a scintered glass funnel (inner diameter of funnel=12 cm). Material eluted from silica pad with methylene chloride (3×500 mL) to afford 1-(2-amino-5-methoxy-3-methylphenyl)-2-chloroethanone plus chloroacetonitrile. The mixture was concentrated in vacuo to afford 40.1 g (51%) 1-(2-amino-5-methoxy-3-methylphenyl)-2-chloroethanone that slowly crystallized. A solution of 1-(2-amino-5-methoxy-3-methylphenyl)-2-chloroethanone (0.19 mole, 40.1 g) in 9:1 dioxane:water (935 mL) was added sodium borohydride (0.19 mole, 7.1 g). The reaction was stirred one hour at room temperature refluxed for 4.5 hours. The reaction was cooled to room temperature and treated with 1N hydrochloric acid (310 mL). This mixture was heated to 80° C. and cooled to room temperature. The reaction was treated with water (500 mL), extracted with ethyl acetate (3×500 mL) and the organic phases were combined, concentrated in vacuo to afford an oil. The oil was dissolved in methylene chloride and filtered through a pad of silica (height of silica=10 cm) in a scinter glass funnel (inner diameter of funnel=14.5 cm). Material eluted with methylene chloride. Fractions containing the title compound were combined, concentrated in vacuo to afford 23.32 g (77%) of the title compound as an oil: mass spectrum (ion spray): m/z=161 (M); 1H NMR (DMSOd6): 7.25 (t, J=2.93 Hz, 1H), 6.84 (d, J=2.20 Hz, 1H), 6.53 (d, J=1.46 Hz, 1H), 6.32 (dd, J=2.93, 1.83 Hz, 1H), 3.71 (s, 3H), 2.41 (s, 3H).
Reaction SMILES: Cl.Cl.[NH:3]([C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]=[C:7]([CH3:15])[N:6]=1)[NH2:4].C(N(CC)CC)C.[CH3:23][C:24]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)=O>C(O)C>[CH3:33][O:32][C:29]1[CH:30]=[CH:31][C:26]([C:24](=[N:4][NH:3][C:5]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=[C:7]([CH3:15])[N:6]=2)[CH3:23])=[CH:27][CH:28]=1
Reactant: COc1ccc(C(C)=O)cc1
Reactant: Cc1nc(NN)c2ccccc2n1
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: COc1ccc(C(C)=NNc2nc(C)nc3ccccc23)cc1
Yield: 40.8 %

Procedure:
To a solution of 4-hydrazino-2-methylquinazoline dihydrochloride (100 mg, 0.40 mmol) and triethylamine (0.14 mL, 0.81 mmol) in ethanol (3 mL) was added 61 mg (0.4 mmol) of 4-methoxyacetophenone. The resultant solution was refluxed overnight and the resultant reaction mixture was absorbed directly on Si gel. Purification by automated Si gel chromatography (gradient 100% hexanes to 100% ethyl acetate) on the Flashmaster II was performed yielding 50 mg (36%) of the titled compound as a bright yellow solid. HPLC Purity: 91%.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH2:8][CH2:7][CH:6]([C:9]([OH:12])([CH3:11])[CH3:10])[CH2:5][CH:4]=1.Cl.C(N(CC)CCCl)C.[F:22][C:23]1[CH:38]=[CH:37][C:26]([O:27][C:28]2[N:36]=[CH:35][CH:34]=[CH:33][C:29]=2[C:30](O)=[O:31])=[CH:25][CH:24]=1.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(Cl)Cl>[F:22][C:23]1[CH:24]=[CH:25][C:26]([O:27][C:28]2[N:36]=[CH:35][CH:34]=[CH:33][C:29]=2[C:30]([NH:1][CH2:2][C:3]2[CH2:8][CH2:7][CH:6]([C:9]([OH:12])([CH3:10])[CH3:11])[CH2:5][CH:4]=2)=[O:31])=[CH:37][CH:38]=1
Reactant: O=C(O)c1cccnc1Oc1ccc(F)cc1
Reactant: CC(C)(O)C1CC=C(CN)CC1
Agent: CCN(CC)CCCl
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: CC(C)(O)C1CC=C(CNC(=O)c2cccnc2Oc2ccc(F)cc2)CC1
Yield: 9.8 %

Procedure:
A solution of 2-(4-Aminomethyl-cyclohex-3-enyl)-propan-2-ol (0.360 grams, 2.127 mmole), 2-diethylaminoethyl chloride hydrochloride (0.530 grams, 2.765 mmole), 2-(4-Fluoro-phenoxy)-nicotinic acid (0.645 grams, 2.765 mmole), 1-hydroxybenzotriazole hydrate (0.374 grams, 2.765 mmole) and triethyl amine (0.430 grams, 4.254 mmole) in methylene chloride (40 ml) was added and stirred over night. The mixture was concentrated and partitioned between ethyl acetate and 1 N HCl. The organic extracts were washed with saturated sodium hydrogencarbonate and brine, dried over MgSO4, filtered and concentrated to give an oil which was purified by chromatography on silica eluting with 50% ethyl acetate/hexane to 100% ethyl acetate to give a yellow oil (0.080 g); M.W. 384.455; MS 385 (M++1).
Reaction SMILES: [C:1]1(=[O:7])[NH:5][C:4](=[O:6])[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.Br[CH2:18][C:19]1[CH:28]=[C:27]2[C:22]([C:23]([Cl:31])=[CH:24][C:25]([C:29]#[N:30])=[N:26]2)=[CH:21][CH:20]=1>C(#N)C>[Cl:31][C:23]1[C:22]2[C:27](=[CH:28][C:19]([CH2:18][N:5]3[C:4](=[O:6])[CH2:3][CH2:2][C:1]3=[O:7])=[CH:20][CH:21]=2)[N:26]=[C:25]([C:29]#[N:30])[CH:24]=1
Reactant: N#Cc1cc(Cl)c2ccc(CBr)cc2n1
Reactant: O=C1CCC(=O)N1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: N#Cc1cc(Cl)c2ccc(CN3C(=O)CCC3=O)cc2n1
Temperature: 100 °C

Procedure:
To a room temperature solution of succinimide (4.22 g, 42.6 mmol, 1.2 equiv.) in anhydrous acetonitrile (89 mL, 0.4 M) was added Hunig's base (12.4 ml, 71.0 mmol, 2.0 equiv.) and 7-(bromomethyl)-4-chloroquinoline-2-carbonitrile (2-4, 10.0 g, 35.5 mmol). The resulting mixture was warmed in the microwave to 100° C. for 1 h. The reaction was then cooled to 0° C. and a precipitate formed. The solids were then collected by vacuum filtration and washed with cold acetonitrile to afford 4-chloro-7-[(2,5-dioxopyrrolidin-1-yl)methyl]quinoline-2-carbonitrile (2-5) which was taken to the next step without further purification. LRMS m/z (M+H)+ 300.2. found, 300.0 required.
Reaction SMILES: [CH2:1]([C:11]1[CH:29]=[CH:28][C:14]([CH2:15][NH:16][C:17]2[CH:27]=[CH:26][C:20]([C:21]([O:23]CC)=[O:22])=[CH:19][CH:18]=2)=[CH:13][CH:12]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[OH-].[K+].C(O)C.Cl>O>[CH2:1]([C:11]1[CH:29]=[CH:28][C:14]([CH2:15][NH:16][C:17]2[CH:27]=[CH:26][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=2)=[CH:13][CH:12]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCCCCCCc1ccc(CNc2ccc(C(=O)OCC)cc2)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CCCCCCCCCCc1ccc(CNc2ccc(C(=O)O)cc2)cc1

Procedure:
A mixture of 10 g. of ethyl p-{[(p-decyl)benzyl]amino}benzoate (prepared as described in Example 58) and 2.84 g. of potassium hydroxide in 90 ml. of 95% ethanol is refluxed for 5 hours. Concentrated hydrochloric acid is added and the mixture diluted with 100 ml. of water. Filtration gives crystals which are washed with water to give a crude product. Recrystallization from ethanol gives white crystals, m.p. 135°-136° C.
Reaction SMILES: [F:1][C:2]1[C:10]([F:11])=[C:9]([F:12])[C:8]([F:13])=[C:7]([F:14])[C:3]=1[C@H:4]1[O:6][CH2:5]1.[Br-:15].[Li+].P([O-])([O-])([O-])=O>O1CCCC1>[Br:15][CH2:5][C@@H:4]([C:3]1[C:2]([F:1])=[C:10]([F:11])[C:9]([F:12])=[C:8]([F:13])[C:7]=1[F:14])[OH:6]
Reactant: Fc1c(F)c(F)c([C@@H]2CO2)c(F)c1F
Reactant: [Br-]
Agent: O=P([O-])([O-])[O-]
Agent: [Li+]
Solvent: C1CCOC1
Product: O[C@@H](CBr)c1c(F)c(F)c(F)c(F)c1F
Temperature: 0 °C
Reaction time: 1 h
Yield: 81.9 %

Procedure:
To an ice-cooled solution of 10.51 g of (R)-(+)-2,3,4,5,6-pentafluorostyrene oxide in 100 ml of tetrahydrofuran, was added dropwise a solution of Li2CuBr4, which was prepared by adding 16.75 g of cupric bromide to a suspension of 13.03 g of lithium bromide suspended in 150 ml of tetrahydrofuran. After completion of addition, the solution was stirred for one hour in an ice bath, and for another two hours at room temperature. The resulted reaction mixture was poured into a 0.05 mol phosphate buffer, and was extracted with ether. The resultant extract was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure, thereby obtaining 11.92 g of (R)-(-)-2-bromo-1-(pentafluorophenyl)ethanol containing 20% of (+)-2-bromo-2-(pentafluorophenyl)ethanol. This was subjected to isolation by silica gel column chromatography, thereby obtaining (R)-(-)-2-bromo-1-(pentafluorophenyl)ethanol and (+)-2-bromo-2-(pentafluorophenyl)ethanol respectively possessing the aforementioned physical properties.
Reaction SMILES: C([O:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][O:19]C(=O)C)=[CH:14][CH:13]=2)=[CH:8][CH:7]=1)(=O)C.[OH-].[Na+]>C(O)C>[OH:4][CH2:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][OH:19])=[CH:14][CH:13]=2)=[CH:10][CH:11]=1
Reactant: CC(=O)OCc1ccc(-c2ccc(COC(C)=O)cc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: OCc1ccc(-c2ccc(CO)cc2)cc1
Yield: 80 %

Procedure:
0.1 moles 4,4'bis(acetoxymethyl)biphenyl (prepared by method C above), 0.4 mole sodium hydroxide as 23 percent aqueous solution and 50 mls ethanol were refluxed for 3 hours with stirring. The reaction mixture was filtered and the precipitate washed with water and dried to yield 0.08 moles product=80 percent of theory. m.p. 195°97° C.
Reaction SMILES: I([O-])(=O)(=O)=O.[Na+].[CH2:7]([O:9][C:10]([N:12]1[CH2:17][CH2:16][C:15]2[N:18]=[C:19]([CH:21]([OH:30])C(O)C3C=CC=CC=3)[O:20][C:14]=2[CH2:13]1)=[O:11])[CH3:8].CO>C1COCC1.O>[CH2:7]([O:9][C:10]([N:12]1[CH2:17][CH2:16][C:15]2[N:18]=[C:19]([CH:21]=[O:30])[O:20][C:14]=2[CH2:13]1)=[O:11])[CH3:8]
Reactant: CCOC(=O)N1CCc2nc(C(O)C(O)c3ccccc3)oc2C1
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: CCOC(=O)N1CCc2nc(C=O)oc2C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 102.9 %

Procedure:
Sodium periodate (1.7 g, 7.8 mmol) was added to a stirred solution of 2-(1,2-dihydroxy-2-phenylethyl)-6,7-dihydro-oxazolo[5,4-c]pyridine-5(4H)-carboxylic acid ethyl ester (1.7 g, 5.2 mmol) in a mixture of THF (34 mL), MeOH (17 mL) and H2O (8.5 mL). The mixture was stirred at room temperature for 2 hours, diluted with H2O and extracted with AcOEt. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo to yield 2-formyl-6,7-dihydro-oxazolo[5,4-c]pyridine-5(4H)-carboxylic acid ethyl ester (1.2 g, 99% yield) as a dark oil that was used in the next step without further purification. C10H12N2O4 LCMS: Rt 1.13, m/z 243 [M+H2O+H]+ (using method, LC-MS Method 3).