Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[OH:12].[CH3:13][C:14](=[CH2:27])[CH2:15][S:16][C:17]1[CH:22]=[C:21](F)[CH:20]=[CH:19][C:18]=1[N+:24]([O-:26])=[O:25].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:5]=[CH:4][C:3]=1[O:12][C:21]1[CH:20]=[CH:19][C:18]([N+:24]([O-:26])=[O:25])=[C:17]([S:16][CH2:15][C:14]([CH3:27])=[CH2:13])[CH:22]=1
Reactant: Oc1ccc(C(F)(F)F)cc1Cl
Reactant: C=C(C)CSc1cc(F)ccc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: C=C(C)CSc1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Temperature: 60 °C
Reaction time: 3 h
Yield: 66.6 %

Procedure:
A mixture of 1.85 g (0.00939 mole) of 2-chloro-4-trifluoromethylphenol (Example 1, Part A), 2.1 g (0.0093 mole) of 2-(2-methyl-2-propenylthio)-4-fluoronitrobenzene (Part A), and 1.3 g (0.0094 mole) of potassium carbonate in 25 ml of dimethyl formamide was stirred at 60° C. for three hours. The mixture was poured into water and extracted with chloroform. The chloroform extract was washed with water and dried over anhydrous magnesium sulfate. After filtration, the chloroform was evaporated under reduced pressure. The residue was subjected to a hagh vacuum, leaving 2.5 g of 3-(2-methyl-2-propenylthio)-4-nitrophenyl 2-chloro-4-trifluoromethylphenyl ether as an oil.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].[O:15]1[C:19]2([CH2:24][CH2:23][CH:22]([NH2:25])[CH2:21][CH2:20]2)[O:18][CH2:17][CH2:16]1.C(N(C(C)C)CC)(C)C>O1CCCC1.C(OCC)(=O)C>[O:15]1[C:19]2([CH2:24][CH2:23][CH:22]([NH:25][C:2]3[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][C:3]=3[N+:12]([O-:14])=[O:13])[CH2:21][CH2:20]2)[O:18][CH2:17][CH2:16]1
Reactant: NS(=O)(=O)c1ccc(F)c([N+](=O)[O-])c1
Reactant: NC1CCC2(CC1)OCCO2
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: NS(=O)(=O)c1ccc(NC2CCC3(CC2)OCCO3)c([N+](=O)[O-])c1
Reaction time: 8 h

Procedure:
To a solution of 4-fluoro-3-nitrobenzenesulfonamide (1.4 g) in tetrahydrofuran (30 mL) was added 1,4-dioxaspiro[4.5]decan-8-amine (1.0 g) and diisopropylethylamine (5 mL). The mixture was stirred overnight. The mixture was diluted with ethyl acetate (300 mL) and washed with water, brine and dried over Na2SO4. Filtration and evaporation of the solvent gave the title compound.
Reaction SMILES: [C:1]([CH2:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[C:10]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:9]([CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[C:8]2[C:28]1[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=1)#[N:2].[Cl-].O[NH3+].[C:38](=[O:41])([O-])[O-:39].[Na+].[Na+].C(N1C=CN=C1)([N:46]1C=CN=C1)=O>O.C(O)C>[CH2:15]([C:10]1[C:9]([CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[C:8]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)[C:7]2[C:12](=[CH:13][CH:14]=[C:5]([O:4][CH2:3][C:1]3[NH:46][C:38](=[O:41])[O:39][N:2]=3)[CH:6]=2)[N:11]=1)[CH:16]([CH3:17])[CH3:18]
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: O=C([O-])[O-]
Reactant: Cc1ccc(-c2c(CNC(=O)OC(C)(C)C)c(CC(C)C)nc3ccc(OCC#N)cc23)cc1
Agent: [Cl-]
Agent: [NH3+]O
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Cc1ccc(-c2c(CNC(=O)OC(C)(C)C)c(CC(C)C)nc3ccc(OCc4noc(=O)[nH]4)cc23)cc1
Temperature: 70 °C
Reaction time: 17 h
Yield: 34.7 %

Procedure:
A mixture of tert-butyl {[6-(cyanomethoxy)-2-isobutyl-4-(4-methylphenyl)quinolin-3-yl]methyl}carbamate (0.46 g, 1.0 mmol), hydroxyammonium chloride (0.21 g, 3.0 mmol), sodium carbonate (0.43 g, 4.0 mmol) and ethanol (10 ml) was stirred at 70° C. for 17 hrs. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (10 ml). 1,1′-Carbonylbis-1H-imidazole (0.32 g, 2.0 mmol) was added and the mixture was stirred at 70° C. for 24 hrs. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give tert-butyl ({2-isobutyl-4-(4-methylphenyl)-6-[(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)methoxy]quinolin-3-yl}methyl)carbamate (0.18 g, yield 35%) as pale-yellow crystals.
Reaction SMILES: CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[C:35]([O:43][CH2:44][C:45]1[O:49][N:48]=[C:47]([CH3:50])[C:46]=1Br)(=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.CCN(CC)CC.[CH3:59][C:60]1([CH3:67])[C:64]([CH3:66])([CH3:65])[O:63][BH:62][O:61]1>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:35]([O:43][CH2:44][C:45]1[O:49][N:48]=[C:47]([CH3:50])[C:46]=1[B:62]1[O:63][C:64]([CH3:66])([CH3:65])[C:60]([CH3:67])([CH3:59])[O:61]1)(=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1
Reactant: CC1(C)OBOC1(C)C
Reactant: Cc1noc(COC(=O)c2ccccc2)c1Br
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: Cc1noc(COC(=O)c2ccccc2)c1B1OC(C)(C)C(C)(C)O1
Temperature: 80 °C
Reaction time: 8 h

Procedure:
To a resealable vial was added Pd(OAc)2 (3.87 mg, 0.017 mmol) and X-phos (16.42 mg, 0.034 mmol) before the vial was sealed and evacuated and purged with N2 (3×). To this vial was added (4-bromo-3-methylisoxazol-5-yl)methyl benzoate (102 mg, 0.344 mmol) in dioxane (1 mL), Et3N (144 μl, 1.033 mmol), and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane solution (517 μl, 1M in THF, 0.517 mmol). The reaction was stirred overnight at 80° C., cooled to room temperature and filtered. The filtrate was concentrated to afford crude (3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazol-5-yl)methyl benzoate. To a resealable vial was added K2CO3 (47.5 mg, 0.344 mmol), PdCl2(dppf)-CH2Cl2 Adduct (20.06 mg, 0.025 mmol), (2-bromophenyl)(4-chlorophenyl)methanone (72.6 mg, 0.246 mmol). The vial was sealed and evacuated and purged with N2 (3×) before addition of crude (3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazol-5-yl)methyl benzoate (118 mg, 0.344 mmol) dissolved in dioxane (2 mL). Water (0.5 mL) was then added to this solution before the vial was heated to 110° C. overnight. The reaction was cooled to room temperature, diluted with EtOAc, filtered, and concentrated. The crude residue was purified via Biotage (EtOAc/hex) to afford (4-(2-(4-chlorobenzoyl)phenyl)-3-methylisoxazol-5-yl)methyl benzoate. LC/MS m/z 432 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([S:15]([NH:18][CH:19]3[CH:23]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH:22]([CH2:32][S:33][C:34]4[S:35][CH:36]=[CH:37][N:38]=4)[O:21][C:20]3=[O:39])(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[OH-:40].[Li+]>C1COCC1.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([S:15]([NH:18][CH:19]([CH:23]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:22]([OH:40])[CH2:32][S:33][C:34]3[S:35][CH:36]=[CH:37][N:38]=3)[C:20]([OH:21])=[O:39])(=[O:16])=[O:17])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1
Reactant: [OH-]
Reactant: COc1ccc(-c2ccc(S(=O)(=O)NC3C(=O)OC(CSc4nccs4)C3OCc3ccccc3)cc2)cc1
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(-c2ccc(S(=O)(=O)NC(C(=O)O)C(OCc3ccccc3)C(O)CSc3nccs3)cc2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
The 3-[(4′-Methoxy[1,1′-biphenyl]-4-yl)sulfonyl]amino-2-oxo-4-phenylmethoxy-5-[[(2-thiazolyl)thio]methyl]-tetrahydrofuran 63f, 154 mg, 0.258 mmol) is dissolved in THF/water (2 mL/2 mL) and lithium hydroxide (108 mg, 2.58 mmol) is added and the reaction is stirred for two hours at room temperature. The reaction is concentrated to remove the solvent, diluted with water and extracted (2 times) with ether. The aqueous layer is neutralized with 1N HCl to pH6 and extracted with ethyl acetate (3 times). The combined organic layer is washed with brine, dried over magnesium sulfate, and the solvent removed in vacuo. The crude material is adsorbed onto silica gel and purified over a short silica column eluting with hexane/ethyl acetate (1/1) followed with ethyl acetate and ethyl acetate/methanol (8/2). Product fractions are combined and dried to give the desired product as a white solid.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][OH:18])[CH2:12][CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26](Cl)[C:27]2[CH:31]=[CH:30][S:29][CH:28]=2)=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1>[F:19][C:20]1[CH:21]=[CH:22][C:23]([CH:26]([C:27]2[CH:31]=[CH:30][S:29][CH:28]=2)[O:18][CH2:17][CH2:16][N:13]2[CH2:12][CH2:11][N:10]([CH2:9][CH2:8][CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:15][CH2:14]2)=[CH:24][CH:25]=1
Reactant: OCCN1CCN(CCCc2ccccc2)CC1
Reactant: Fc1ccc(C(Cl)c2ccsc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: Fc1ccc(C(OCCN2CCN(CCCc3ccccc3)CC2)c2ccsc2)cc1

Procedure:
A mixture of 1.1 g (0.0044 mol) 4-(3-phenylpropyl)-1-piperazine-ethanol, 1.0 g (0.0044 mol)(4-fluorophenyl)-(3-thienyl)methyl chloride (as prepared in step A), 1.22 g (0.0088 mol) potassium carbonate and 50 ml toluene was stirred and heated to reflux for 16 h. The reaction mixture was cooled, diluted with toluene and washed with water. The toluene layer was then extracted with 10% tartaric acid. The aqueous phase was separated and rendered basic by addition of 4N sodium hydroxide in excess and extracted with toluene. Evaporation gave the crude product as an oil, which was purified on a silica column (eluent was toluene/ethanol 2:1). The pure fraction was evaporated, redissolved in diethyl ether and treated with a solution of hydrogen chloride in ether. The precipitate was filtered off and recrystallized from isopropanol. The yield was 0.265 g (=12%) of the title compound as the dihydrochloride. M.p. 212°-15° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5](Cl)=[O:6].[CH3:12][C:13]([N:20]([CH3:22])[CH3:21])([CH2:16][CH2:17][CH2:18][CH3:19])[CH2:14][NH2:15].[OH-].[Na+]>C1C=CC=CC=1.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5]([NH:15][CH2:14][C:13]([CH3:12])([N:20]([CH3:22])[CH3:21])[CH2:16][CH2:17][CH2:18][CH3:19])=[O:6]
Reactant: O=C(Cl)c1ccc(Cl)c(Cl)c1
Reactant: CCCCC(C)(CN)N(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: c1ccccc1
Product: CCCCC(C)(CNC(=O)c1ccc(Cl)c(Cl)c1)N(C)C

Procedure:
A solution of 3,4-dichlorobenzoyl chloride (2.1 g.,) in dry benzene (25 ml.) was added to a solution of 2-methyl-2-dimethylamino-hexylamine (1.58 g.,) in dry benzene (25 ml.) and the mixture heated under reflux for 1.5 hrs. The mixture was diluted with water, basified with 2N sodium hydroxide solution, and extracted with benzene (4 × 100 ml.). The combined benzene extracts were washed with water (4 × 50 ml.), dried (Na2SO4) and evaporated affording 3,4-dichloro-N-[2-methyl-2-dimethylamino-hexyl]benzamide as a colourless oil (3.6 g., ca 100%) which slowly crystallised.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[C:11]([OH:13])=O)[CH:4]=[CH:3][CH:2]=1.S(Cl)([Cl:16])=O>ClCCl>[ClH:16].[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[C:11]([Cl:16])=[O:13])[CH:4]=[CH:3][CH:2]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1cccc2cccnc12
Solvent: ClCCl
Product: Cl
Product: O=C(Cl)c1cccc2cccnc12
Temperature: 25 °C
Reaction time: 24 h
Yield: 95.6 %

Procedure:
To 8-quinolinecarboxylic acid (10.0 g, 57.8 mmol) in an ice/methanol bath was added thionyl chloride (90.0 ml, 123.4 mmol) in one portion. The reaction mixture was slowly warmed to room temperature and was stirred for 24 hours. Dichloromethane (100 ml) was added and the reaction mixture was refluxed for 1 hour. The solvents were removed by distillation under reduced pressure and the residue was dried for 24 hours at 80° C. in high vacuum to afford 12.6 g (96%) of 8-quinolinecarboxylic acid chloride hydrochloride as a tan powder, m.p. 232°-237° C.
Reaction SMILES: [C:1]([NH:9][C:10]1[S:11][C:12]([C:21]([O:23]CC)=[O:22])=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:14]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Li+]>O1CCCC1.O>[C:1]([NH:9][C:10]1[S:11][C:12]([C:21]([OH:23])=[O:22])=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:14]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)c1sc(NC(=O)c2ccccc2)nc1-c1ccccc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(Nc1nc(-c2ccccc2)c(C(=O)O)s1)c1ccccc1
Yield: 59.7 %

Procedure:
A mixture of ethyl 2-benzamido-4-phenylthiazole-5-carboxylate (1.62 g, 4.60 mmol) and lithium hydroxide (0.96 g, 23.00 mmol) was stirred at 50° C. in tetrahydrofuran/water mixture for 96 h. The organic solvent was removed in vacuo and the water layer was washed with ethyl acetate and then acidified by the addition of 15% hydrochloric acid solution to pH 5. The white precipitate obtained was collected by filtration and dried to afford 0.89 g of the title compound in 59% yield; 1H NMR (CDCl3, 300 MHz) δ 13.05 (s, 1H), 8.09 (d, J=7.1 Hz, 2H), 7.80-7.35 (m, 8H); MS (ES+) m/z 325.1 (M+1).
Reaction SMILES: [CH3:1][C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[S:13]([CH3:15])=[O:14])=[O:5].[I:20]N1C(C)(C)C(=O)N(I)C1=O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C(=O)C>[I:20][C:16]1[CH:17]=[CH:18][CH:19]=[C:2]([CH3:1])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[S:13]([CH3:15])=[O:14])=[O:5]
Reactant: Cc1ccccc1C(=O)Nc1ccccc1S(C)=O
Reactant: CC1(C)C(=O)N(I)C(=O)N1I
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CC(=O)N(C)C
Product: Cc1cccc(I)c1C(=O)Nc1ccccc1S(C)=O
Temperature: 90 °C
Reaction time: 2 h
Yield: 124 %

Procedure:
Into the same reactor as in Example 1 were charged 0.10 g of palladium acetate, 0.40 g of 2-methyl-2′-methylsulfinylbenzanilide, 0.33 g of 1,3-diiodo-5,5-dimethylhydantoin and 5 ml of N,N-dimethylacetamide. The mixture thus obtained was stirred at 90° C. for 2 hours. After cooling to room temperature, the reaction mixture was filtered with Celite, and the filtrate was poured into saturated aqueous solution of sodium thiosulfate and extracted with ethyl acetate. The organic layer was washed with 0.1N-aqueous hydrochloric acid and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The concentrate thus obtained was purified by silica gel dry column chromatography (hexane/ethyl acetate=1/2). Thus, 0.43 g (yield 72%) of 2-iodo-6-methyl-2′-methylsulfinylbenzanilide was obtained. Regioselectivity of iodination into the 2-position was 100%.
Reaction SMILES: [C:1](=[O:5])(OC)[NH2:2].N[C:7]1[S:11][C:10]2[CH2:12][CH2:13][CH2:14][CH2:15][C:9]=2[C:8]=1[C:16]#[N:17].[F:18][C:19]1[CH:28]=[CH:27][CH:26]=[CH:25][C:20]=1[C:21]([NH:23][NH2:24])=O.C(N(CCC)CCC)CC>COCCO>[F:18][C:19]1[CH:28]=[CH:27][CH:26]=[CH:25][C:20]=1[C:21]1[N:17]=[C:16]2[N:24]([C:1](=[O:5])[NH:2][C:7]3[S:11][C:10]4[CH2:12][CH2:13][CH2:14][CH2:15][C:9]=4[C:8]=32)[N:23]=1
Reactant: COC(N)=O
Reactant: N#Cc1c(N)sc2c1CCCC2
Reactant: NNC(=O)c1ccccc1F
Agent: CCCN(CCC)CCC
Solvent: COCCO
Product: O=c1[nH]c2sc3c(c2c2nc(-c4ccccc4F)nn12)CCCC3
Yield: 50 %

Procedure:
The methyl carbamate of 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo(b)thiophene (7.08 g), 2-fluorobenzhydrazide (4.66 g), 2-methoxyethanol (100 mL) and tri-n-propylamine (3 mL) are refluxed under nitrogen for 19 hours. The mixture is cooled and the precipitate collected. The mother liquor is treated with methanol (100 mL) and refrigerated 24 hours to produce a second crop of solid. The combined material is recrystallized from 2-methoxyethanol and dried 20 hours at 100°/0.01 mm to afford 2-(2-fluorophenyl)-8,9,10,11-tetrahydro[1]benzothieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)one, which decomposes above 316°. The yield is 50%.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[OH:11][C:12]1[CH:19]=[CH:18][C:15](C=O)=[CH:14][CH:13]=1.OOS([O-])=O.[K+].CC[O:28][C:29](C)=[O:30]>CN(C=O)C>[OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[CH:29]([O:30][C:15]1[CH:14]=[CH:13][C:12]([OH:11])=[CH:19][CH:18]=1)=[O:28]
Reactant: O=Cc1ccc(O)cc1
Reactant: CCOC(C)=O
Agent: O=C(O)c1ccc(O)cc1
Agent: O=S([O-])OO
Agent: [K+]
Solvent: CN(C)C=O
Product: O=COc1ccc(O)cc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To prepare 4-hydroxy benzoic acid, 4-hydroxybenzaldehyde (100 mg) was dissolved in DMF (10 mL), and OXONE (0.503 g) was added and stirred at room temperature for 18 hours with the reaction having a final volume (11 mL). The reaction was monitored by TLC or GC analysis. EtOAc was added to extract the products and 1N HCl was used to dissolve the salts. The organic extract was washed with 1N HCl (30 mL×3) and brine (30 mL), dried over Na2SO4, and the solvent was removed under reduced pressure to obtain 4-hydroxy benzoic acid in 19% yield and 4-hydroxyphenol formate in 62% yield after purification by silica gel column chromatography. 4-Hydroxyphenyl Formate: 1H NMR (CDCl3, 300 MHz): δ8.27 (s, 1H), 6.98(d, 2H, J=9.0), 6.78 (d, 2H,J=8.9), 5.35 (bs, 1H).
Reaction SMILES: [CH:1]1[C:6](N)=[CH:5][CH:4]=[C:3]([NH2:8])[CH:2]=1.[C:9]([O:12][C:13](=[O:15])[CH3:14])(=[O:11])[CH3:10]>>[CH:1]1[C:13]([CH2:14][C:6]2[CH:1]=[CH:2][C:3]([NH2:8])=[CH:4][CH:5]=2)=[CH:5][CH:4]=[C:3]([NH2:8])[CH:2]=1.[C:9]([O:12][C:13](=[O:15])[CH3:14])(=[O:11])[CH3:10]
Reactant: Nc1ccc(N)cc1
Solvent: CC(=O)OC(C)=O
Product: Nc1ccc(Cc2ccc(N)cc2)cc1

Procedure:
In a similar manner, if one substitutes for the reaction product of p-phenylene diamine and acetic anhydride in the above reaction, with the compound resulting from the reaction of 4,4'-diaminodiphenylmethane and acetic anhydride, i.e., ##STR30## a polyamide imide is obtained having the formula ##STR31##
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:15][CH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[C:7]([N+:12]([O-])=O)[CH:8]=[N:9]2)=[CH:4][CH:3]=1>ClCCl.C(OCC)(=O)C.[Pt]>[NH2:12][C:7]1[CH:8]=[N:9][C:10]2[C:5]([C:6]=1[NH:15][CH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[CH:4][CH:3]=[C:2]([Br:1])[CH:11]=2
Reactant: CC(C)(C)OC(=O)NCCCNc1c([N+](=O)[O-])cnc2cc(Br)ccc12
Agent: [Pt]
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCCCNc1c(N)cnc2cc(Br)ccc12
Reaction time: 8 h
Yield: 99.2 %

Procedure:
A solution of tert-butyl 3-[(7-bromo-3-nitroquinolin-4-yl)amino]propylcarbamate (56.4 g, 133 mmol) in dichloromethane (150 mL) and ethyl acetate (500 mL) and 5% platinum on carbon (15.52 g, 79.56 mmol) were added to a hydrogenation vessel, which was placed under hydrogen pressure (50 psi, 3.4×105 Pa) and shaken overnight. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was dried under reduced pressure to provide 52.17 g of tert-butyl 3-[(3-amino-7-bromoquinolin-4-yl)amino]propylcarbamate.
Reaction SMILES: [CH3:1][C:2]([CH2:4][C:5]([OH:7])=[O:6])=[O:3].[CH2:8]([OH:13])[CH:9]([OH:12])[CH2:10]O>C(OCC)(=O)C>[C:5]([O:7][CH2:10][CH:9]([CH2:8][OH:13])[O:12][C:5](=[O:6])[CH2:4][C:2]([CH3:1])=[O:3])(=[O:6])[CH2:4][C:2]([CH3:1])=[O:3]
Reactant: OCC(O)CO
Reactant: CC(=O)CC(=O)O
Solvent: CCOC(C)=O
Product: CC(=O)CC(=O)OCC(CO)OC(=O)CC(C)=O

Procedure:
A portion of the crude reaction product (3600 g) was dissolved in approximately 6 liters of ethyl acetate and extracted with distilled water (3×3 L) to provide a first aqueous fraction and again extracted with water (6× 3 L) to provide a second aqueous fraction. Analysis of the aqueous extracts by HPLC indicated that essentially all of the monoacetoacetin contained in the crude reaction product was removed in the first aqueous fraction. Using a freeze-dryer, water was removed from the second aqueous fraction until constant weight was achieved (1029.5 g, ca. 30%). This material was tested without further purification for efficacy as a parenteral nutrient.
Reaction SMILES: [CH:1]12[CH2:6][CH:5]1[C:4](=[O:7])O[C:2]2=[O:8].[NH2:9][C:10]1[CH:20]=[CH:19][C:13]([C:14]([O:16][CH2:17]C)=[O:15])=[CH:12][CH:11]=1.CC1(C)CC(=O)OC(=O)C1>>[O:7]=[C:4]1[N:9]([C:10]2[CH:11]=[CH:12][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:19][CH:20]=2)[C:2](=[O:8])[CH:1]2[CH:5]1[CH2:6]2
Reactant: O=C1OC(=O)C2CC12
Reactant: CCOC(=O)c1ccc(N)cc1
Agent: CC1(C)CC(=O)OC(=O)C1
Product: COC(=O)c1ccc(N2C(=O)C3CC3C2=O)cc1

Procedure:
The desired product was prepared by substituting methyl 4-aminobenzoate and 3-oxabicyclo(3.1.0)hexane-2,4-dione for ethyl 4-aminobenzoate and 3,3-dimethylglutaric anhydride, respectively, in Example 119A. MS (DCI) m/e 263 (M+NH4)+.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=O)=[CH:5]2.CCN=C=NCCCN(C)C.[NH2:25][CH2:26][CH2:27][CH2:28][OH:29]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[OH:29][CH2:28][CH2:27][CH2:26][NH:25][C:11]([C:6]1[NH:7][C:8]2[C:4]([CH:5]=1)=[CH:3][C:2]([F:1])=[CH:10][CH:9]=2)=[O:13]
Reactant: NCCCO
Reactant: O=C(O)c1cc2cc(F)ccc2[nH]1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: O=C(NCCCO)c1cc2cc(F)ccc2[nH]1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of 5-fluoro-1H-indole-2-carboxylic acid (2.27 g, 12.7 mmol) in CH2Cl2 (100 mL) is added DMAP (4.64 g, 38 mmol), EDCI (3.64 g, 19 mmol), 3-amino-propan-1-ol (1.90 g, 25 mmol). The mixture is stirred at room temperature for 24 hours. After the solvent is removed under vacuum, 5% HCl (100 mL) is added to the mixture. It is extracted with EtOAc (100 mL×3). The combined organic layers are washed with saturated aqueous NaHCO3 (100 mL), brine (100 mL) and dried with Na2SO4. Solvent is removed to give 5-fluoro-1H-indole-2-carboxylic acid (3-hydroxy-propyl)-amide; 1H NMR (DMSO-d6) δ 1.69 (quint, 2H, J=6.4 Hz), 3.34 (q, 2H, J=6.0 Hz), 3.48 (t, 2H, J=6.4 Hz), 4.48 (bs, 1H), 6.99-7.10 (m, 2H), 7.36-7.44 (m, 2H), 8.47 (t, 1H, J=5.6 Hz), 11.63 (s, 1H); m/z [M++1] 237.1.
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[N+:15]([O-])=O)=[C:3]1[C:18]([O:20][CH2:21][CH3:22])=[O:19].[H][H]>C(OCC)(=O)C.[Pd]>[NH2:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[NH:8][C:4]1[CH:5]=[C:6]([CH3:7])[N:2]([CH3:1])[C:3]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19]
Reactant: [H][H]
Reactant: CCOC(=O)c1c(Nc2ccccc2[N+](=O)[O-])cc(C)n1C
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCOC(=O)c1c(Nc2ccccc2N)cc(C)n1C

Procedure:
A catalytic amount of palladium-on-charcoal is added to a solution of 3.0 g (0.01 mole) of ethyl 1,5-dimethyl-3-(2-nitrophenyl)amino-1H-pyrrole-2-carboxylate in 50 ml of ethyl acetate, and the mixture is hydrogenated (in a circulatory hydrogenation apparatus under a slightly elevated pressure at room temperature) until the theoretical amount of hydrogen has been absorbed. After the catalyst has been filtered off, the filtrate is concentrated in vacuo, and the crystalline residue is recrystallized from a little isopropanol. Yield: 2.1 g.