Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:5][C:6]([C:8]1[CH:13]=[CH:12][C:11](CP(=O)O)=[CH:10][CH:9]=1)=[O:7])(C)(C)C.[CH2:18]([O:20][P:21]([C:24]1[CH:36]=[CH:35][C:27](C(OC(C)(C)C)=O)=[CH:26][CH:25]=1)(C)=[O:22])C.[OH-].[K+].Cl>O1CCOCC1>[CH3:18][O:20][P:21]([C:11]1[CH:10]=[CH:9][C:8]([C:6]([OH:5])=[O:7])=[CH:13][CH:12]=1)([C:24]1[CH:36]=[CH:35][CH:27]=[CH:26][CH:25]=1)=[O:22]
Reactant: CC(C)(C)OC(=O)c1ccc(C[PH](=O)O)cc1
Reactant: CCOP(C)(=O)c1ccc(C(=O)OC(C)(C)C)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: C1COCCO1
Product: COP(=O)(c1ccccc1)c1ccc(C(=O)O)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
[4-(tert-Butoxycarbonyl)phenyl]methylphosphinic acid]. tert-Butyl 4-[ethoxy(methyl) phosphoryl]benzoate (510 mg, 1.79 mmol) was made 0.25 M in dioxane and to this stirring solution was added potassium hydroxide (5.38 mL, 5.38 mmol). The resulting mixture was stirred at ambient temperature for 10 minutes. The reaction mixture was neutralized with 1 eq aq HCl then concentrated in vacuo. The residue was diluted with MeOH, the inorganic salts were filtered off and the filtrate was concentrated in vacuo. MS: cal'd 257 (MH+), exp 257 (MH+).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4](O)=[O:5].C(O)(=O)C.[O:16]([C:18]#[N:19])[Na].[OH-].[Na+]>O>[Cl:11][C:8]1[CH:7]=[C:3]2[C:2](=[CH:10][CH:9]=1)[NH:1][C:18](=[O:16])[NH:19][C:4]2=[O:5]
Reactant: N#CO[Na]
Reactant: Nc1ccc(Cl)cc1C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Product: O=c1[nH]c(=O)c2cc(Cl)ccc2[nH]1
Temperature: 30 °C
Reaction time: 0.5 h

Procedure:
Into a 500-mL 3-necked round-bottom flask, was placed a solution of 2-amino-5-chlorobenzoic acid (10 g, 58.48 mmol, 1.00 equiv) in water (100 mL), acetic acid (8 g, 133.33 mmol, 2.24 equiv). This was followed by the addition of NaOCN (8.2 g, 126.15 mmol, 2.13 equiv). The mixture was stirred for 30 mins at 30° C. To this was added sodium hydroxide (86 g, 2.15 mol, 37.00 equiv). The resulting solution was stirred overnight at 30° C. The solids were collected by filtration. The residue was dissolved in water. The pH value of the solution was adjusted to 7 with hydrogen chloride (12 mol/L). The solids were collected by filtration. This resulted in 5 g (44%) of 6-chloroquinazoline-2,4(1H,3H)-dione as a white solid.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=O)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:35][O:36][C:37]1[CH:38]=[C:39]([C:45]2[NH:46][C:47]3[C:52]([C:53]=2[CH2:54][CH2:55][NH2:56])=[CH:51][CH:50]=[CH:49][CH:48]=3)[CH:40]=[CH:41][C:42]=1[O:43][CH3:44]>>[CH3:35][O:36][C:37]1[CH:38]=[C:39]([C:45]2[NH:46][C:47]3[C:52]([C:53]=2[CH2:54][CH2:55][NH:56][C:10](=[O:12])[CH2:9][CH2:8][C:5]2[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=2)=[CH:51][CH:50]=[CH:49][CH:48]=3)[CH:40]=[CH:41][C:42]=1[O:43][CH3:44]
Reactant: O=C(O)CCc1ccc(O)cc1
Reactant: COc1ccc(-c2[nH]c3ccccc3c2CCN)cc1OC
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Product: COc1ccc(-c2[nH]c3ccccc3c2CCNC(=O)CCc2ccc(O)cc2)cc1OC
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 106.1 %

Procedure:
To a stirred solution of 3-(4-hydroxyphenyl)propionic acid (80 mg in 4 mL N,N-dimethylformamide) was added 1-hydroxybenzotriazole (78 mg) and the mixture cooled to 0° C. After 10 minutes, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (130 mg) was added. The mixture was warmed to room temperature and 2-[2-(3,4-dimethoxyphenyl)-1H-indol-3-yl]ethylamine (272 mg) was added. After 17 hours the reaction was quenched by the addition of water and extracted with ethyl acetate. The organic portion was washed with water, 0.5M sodium bisulfate and brine, dried over sodium sulfate and concentrated in vacuo. Purification by flash chromatography on silica gel (methylene chloride:methanol, 95:5) gave the title compound (227 mg). m/e=444 (M)
Reaction SMILES: [CH3:1]C(C)([O-])C.[K+].[CH3:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:15][CH:16]1[CH:21]([CH3:22])[C:20](=O)[CH2:19][CH2:18][NH:17]1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[CH3:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:15][CH:16]1[CH:21]([CH3:22])[C:20](=[CH2:1])[CH2:19][CH2:18][NH:17]1
Reactant: CC(C)(C)[O-]
Reactant: COc1ccccc1CC1NCCC(=O)C1C
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [K+]
Solvent: C1CCOC1
Product: C=C1CCNC(Cc2ccccc2OC)C1C

Procedure:
20.1 g (56 mmol) of methyl-triphenylphosphonium bromide, 6.3 g (56 mmol) of potassium tert-butoxide and 11 g (47 mmol) of 2-(2-methoxyphenyl)methyl-3-methyl-4-piperidone 15 in 200 mL of abs. THF are used. The product is crystallized from acetone as the oxalate. Yield: 13.1 g (87%); melting point: 145° C.
Reaction SMILES: [F:1][C:2]1[C:7]2[N:8]=[CH:9][S:10][C:6]=2[CH:5]=[C:4]2[NH:11][C:12](=[O:22])[N:13]([C:14]3[CH:19]=[CH:18][C:17]([I:20])=[CH:16][C:15]=3[F:21])[C:3]=12.C(N(CC)CC)C.[CH2:30]([C:33]1([S:36](Cl)(=[O:38])=[O:37])[CH2:35][CH2:34]1)[CH:31]=[CH2:32]>C(Cl)Cl>[CH2:30]([C:33]1([S:36]([N:11]2[C:4]3=[CH:5][C:6]4[S:10][CH:9]=[N:8][C:7]=4[C:2]([F:1])=[C:3]3[N:13]([C:14]3[CH:19]=[CH:18][C:17]([I:20])=[CH:16][C:15]=3[F:21])[C:12]2=[O:22])(=[O:38])=[O:37])[CH2:35][CH2:34]1)[CH:31]=[CH2:32]
Reactant: C=CCC1(S(=O)(=O)Cl)CC1
Reactant: O=c1[nH]c2cc3scnc3c(F)c2n1-c1ccc(I)cc1F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=CCC1(S(=O)(=O)n2c(=O)n(-c3ccc(I)cc3F)c3c(F)c4ncsc4cc32)CC1

Procedure:
To a solution of 4-fluoro-5-(2-fluoro-4-iodophenyl)-5H-imidazo[4′,5′:4,5]benzo[1,2-d]thiazol-6(7H)-one (50 mg, 0.12 mmol) in DCM (5 mL) was added triethylamine (35 mg, 0.74 mmol) at 0° C. followed by 1-allylcyclopropane-1-sulfonyl chloride (32 mg, 0.18 mmol) and
Reaction SMILES: [O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4][CH:3]1[CH2:12][NH:13][CH2:14][CH2:15][C:16]1[CH:26]=[CH:25][C:19]([NH:20][S:21]([CH3:24])(=[O:23])=[O:22])=[CH:18][CH:17]=1.[BH4-].[Na+].CC(C)=O>CO>[OH:1][CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4][CH:3]1[CH2:12][NH:13][CH2:14][CH2:15][C:16]1[CH:17]=[CH:18][C:19]([NH:20][S:21]([CH3:24])(=[O:23])=[O:22])=[CH:25][CH:26]=1
Reactant: CS(=O)(=O)Nc1ccc(CCNCC2CCc3ccccc3C2=O)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: CO
Product: CS(=O)(=O)Nc1ccc(CCNCC2CCc3ccccc3C2O)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Compound (XXI) (0.75 g) was combined with NaBH4 (0.14 g) in MeOH (30 ml) and stirred at ambient temperature for 31/2 hours. A further 0.14 g NaBH4 was added and the reaction was stirred a further 1/2 hour. Acetone (10 ml) was added. After stirring 18 hours, the solvent was evaporated and the residue was partitioned between EtOAc and aqueous NaHCO3. The EtOAc was evaporated, and the residue was chromatographed on a silica column, eluting the product with CH2Cl2 /MeOH as a gummy solid (0.5 g). This was converted to its HCl salt using EtOH/concentrated HCl and recrystallized from EtOH to yield Compound XXII.HCl (0.2 g), m.p. 214°-220° (dec.). The elemental analysis for C, H, and N and mass spectra were consistent with the structure indicated. The NMR spectrum suggested that the 1,2-trans-isomer was the principal constituent, though some of the 1,2-cis-isomer was present also.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:17])[C:10]1[CH:15]=[CH:14][C:13](Cl)=[N:12][CH:11]=1.[CH2:18]([NH2:22])[CH2:19][CH2:20][NH2:21]>>[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:17])[C:10]1[CH:15]=[CH:14][C:13]([NH:21][CH2:20][CH2:19][CH2:18][NH2:22])=[N:12][CH:11]=1
Reactant: Nc1ccccc1NC(=O)c1ccc(Cl)nc1
Reactant: NCCCN
Product: NCCCNc1ccc(C(=O)Nc2ccccc2N)cn1
Yield: 59 %

Procedure:
N-(2-Aminophenyl)-6-chloronicotinamide (248 mg, 1 mmol) and 6 ml of 1,3-propanediamine were heated to 80° C. for 3 hours. The excess 1,3-propanediamine was removed under vacuum. To the residue was added 5 ml of 0.20 M NaOH. The mixture was extracted with 100 ml of ethyl acetate. The ethyl acetate was removed under vacuum to give the title compound (168 mg, 59% yield) as a brown solid. LC-MS (m/z) 286 (M+1).
Reaction SMILES: [CH3:1][C:2]1([CH3:18])[C:11]2[C:6](=[C:7]([N+:13]([O-:15])=[O:14])[C:8]([NH2:12])=[CH:9][CH:10]=2)[C:5](=[O:16])[NH:4][C:3]1=[O:17].[CH3:19][O:20][C:21]1[CH:29]=[C:28]([S:30][CH3:31])[CH:27]=[CH:26][C:22]=1[C:23](Cl)=[O:24]>>[CH3:1][C:2]1([CH3:18])[C:11]2[C:6](=[C:7]([N+:13]([O-:15])=[O:14])[C:8]([NH:12][C:23](=[O:24])[C:22]3[CH:26]=[CH:27][C:28]([S:30][CH3:31])=[CH:29][C:21]=3[O:20][CH3:19])=[CH:9][CH:10]=2)[C:5](=[O:16])[NH:4][C:3]1=[O:17]
Reactant: CC1(C)C(=O)NC(=O)c2c1ccc(N)c2[N+](=O)[O-]
Reactant: COc1cc(SC)ccc1C(=O)Cl
Product: COc1cc(SC)ccc1C(=O)Nc1ccc2c(c1[N+](=O)[O-])C(=O)NC(=O)C2(C)C

Procedure:
Prepared analogous to Example 2a from 5 gm of 4,4-dimethyl-7-amino-8-nitro-2H,4H-isoquinoline-1,3-dione and 2-methoxy-4-methylmercapto-benzoyl chloride.
Reaction SMILES: [C:1]1(=[O:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.[Br:12][CH2:13][CH2:14][CH2:15][CH2:16]Br>>[Br:12][CH2:13][CH2:14][CH2:15][CH2:16][N:2]1[CH2:3][CH2:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:1]1=[O:11]
Reactant: BrCCCCBr
Reactant: O=C1NCCc2ccccc21
Product: O=C1c2ccccc2CCN1CCCCBr

Procedure:
from 3,4-dihydroisoquinolin-1(2H)-one and 1,4-dibromobutane
Reaction SMILES: [C:1]([NH:5][C:6]1[C:7](F)=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:16](=[O:18])[CH3:17])[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2].O1CCOCC1.[ClH:26]>>[C:1]([NH:5][C:6]1[C:7]([Cl:26])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:16](=[O:18])[CH3:17])[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(=O)c1cccc2nc(F)c(NC(C)(C)C)nc12
Reactant: Cl
Solvent: C1COCCO1
Product: CC(=O)c1cccc2nc(Cl)c(NC(C)(C)C)nc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 89 %

Procedure:
A mixture of 1-(3-(tert-butylamino)-2-fluoroquinoxalin-5-yl)ethanone (343b) (300 mg, 1.14 mmol) in 4 M HCl in dioxane (2.87 mL, 11.48 mmol) was stirred at RT for 16 h under a drying tube. Lcms indicated the reaction was not completed. The reaction mixture was heated at 70° C. for 1.5 h. The reaction was quenched with saturated aq. NaHCO3 (200 mL), diluted with DCM (100 mL), added to a separatory funnel, and extracted with DCM (3×100 mL) before the organic layer was separated, dried over Na2SO4, and concentrated to give 1-(3-(tert-butylamino)-2-chloroquinoxalin-5-yl)ethanone (345a, 285 mg, 1.02 mmol, 89% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.57 (s, 9H) 2.86 (s, 3H) 5.73 (br. s., 1H) 7.39 (t, J=8.02 Hz, 1H) 7.83 (dd, J=7.43, 1.56 Hz, 1H) 7.89 (dd, J=8.22, 1.57 Hz, 1H). MS (ESI, pos. ion) m/z: 278.2 (M+1).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[Cl:11][CH2:12][CH2:13]O>S(=O)(=O)(O)O.C(OCC)(=O)C>[OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([O:7][CH2:13][CH2:12][Cl:11])=[O:6]
Reactant: O=C(O)c1cccc(O)c1
Reactant: OCCCl
Agent: O=S(=O)(O)O
Solvent: CCOC(C)=O
Product: O=C(OCCCl)c1cccc(O)c1
Yield: 95.2 %

Procedure:
A solution of 3-hydroxybenzoic acid (15.0 g, 0.11 mol) in 2-chloroethanol (70 mL, 1.0 mol) and 1 mL of concentrated sulfuric acid was refluxed for overnight. TLC analysis (silica gel/20% ethyl acetate/hexane) showed clean conversion to a new material. The excess chloroethanol was removed by evaporation to obtain a brown solution which was dissolved in ethyl acetate and washed with water . The organic layer was dried with MgSO4 and concentrated to obtain 21.0 g of the product as a white solid: mp 50° C.; 1H NMR (CDCl3) δ3.81 (t, 2H, J=5.9 MHz), 4.57 (t, 2H, J=5.9 MHz), 4.77 (s, 1H), 7.06-7.66 (m, 4H); 13C NMR (CDCl3) δ41.52, 64.75, 116.43, 120.77, 121.98, 129.80, 130.71, 156.04, 166.57; MS m/e (rel intensity) 200 (26), 138 (59), 121 (100), 93 (31), 65 (21), 39 (12); Exact mass: calcd 200.0240, found 200.0242. ##STR27##
Reaction SMILES: [NH2:1][C:2]1[C:3]([Cl:20])=[CH:4][C:5]([F:19])=[C:6]([N:8]2[C:16](=[O:17])[C:11]3=[CH:12][CH2:13][CH2:14][CH2:15][N:10]3[C:9]2=[O:18])[CH:7]=1.[CH3:21][S:22](Cl)(=[O:24])=[O:23]>N1C=CC=CC=1>[Cl:20][C:3]1[C:2]([NH:1][S:22]([CH3:21])(=[O:24])=[O:23])=[CH:7][C:6]([N:8]2[C:16](=[O:17])[C:11]3=[CH:12][CH2:13][CH2:14][CH2:15][N:10]3[C:9]2=[O:18])=[C:5]([F:19])[CH:4]=1
Reactant: CS(=O)(=O)Cl
Reactant: Nc1cc(N2C(=O)C3=CCCCN3C2=O)c(F)cc1Cl
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1cc(N2C(=O)C3=CCCCN3C2=O)c(F)cc1Cl
Yield: 72.8 %

Procedure:
To a pyridine (5 mL) solution of 2-(5-amino-4-chloro-2-fluorophenyl)-5,6-dihydroimidazo [1,5-a] pyridine-1, 3[2H, 7H]-dione (0.50 g, 1.69 mmol) was added methanesulfonyl chloride (0.14 mL, 1.86 mmol) with stirring under cooling in an ice-water bath and the reaction mixture was stirred for 2 hours at 0° C. The resulting mixture was quenched with 1N hydrochloric acid (60 mL) and extracted with ethyl acetate (20 mL×3 times). The organic layer combined was washed with saturated sodium chloride solution (20 mL) and dried over anhydrous magnesium sulfate. After removal of magnesium sulfate by filtration, the filtrate was evaporated to give crude product, which was purified by silica gel column (Wakogel C-200, ethyl acetate/hexane=1/1) to obtain a white solid of 2-(4-chloro-2-fluoro-5-methanesulfonylaminophenyl)-5,6-dihydroimidazo [1,5-a] pyridine-1,3[2H, 7H]-dione (0.46 g, yield:73.0%).
Reaction SMILES: [CH3:1][NH2:2].[Br:3][C:4]1[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8]([CH:16]=O)=[CH:9]2.[O-]S([O-])(=O)=O.[Mg+2]>C(O)C.C(Cl)Cl>[Br:3][C:4]1[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8]([CH:16]=[N:2][CH3:1])=[CH:9]2
Reactant: CN
Reactant: COc1ccc2cc(C=O)ccc2c1Br
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Solvent: ClCCl
Solvent: CCO
Product: CN=Cc1ccc2c(Br)c(OC)ccc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
Methylamine (2.35 mL of an 8.03 M solution in ethanol, 18.8 mmol) in 5 mL of methylene chloride was added under nitrogen dropwise over 5 minutes to a mixture of 5-bromo-6-methoxy-naphthalene-2-carbaldehyde (1.00 g, 3.77 mmol), prepared in the previous step, and 3 g of anhydrous MgSO4 in 20 mL of methylene chloride at room temperature. After the addition the reaction was stirred at room temperature for 21 h (overnight). The reaction was filtered and the filtrate concentrated under reduced pressure to give (5-bromo-6-methoxy-naphthalen-2-ylmethylene)-methyl-amine (1.05 g, 100%) as a light tan solid, mp 105-107° C.
Reaction SMILES: [Cl-].[NH4+].C(O)C.[N+:6]([C:9]1[C:14]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])([O-])=O>[Fe].O>[NH2:6][C:9]1[C:14]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24]
Reactant: CCOC(=O)Cc1cccc(Oc2ccccc2)c1[N+](=O)[O-]
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: CCOC(=O)Cc1cccc(Oc2ccccc2)c1N

Procedure:
To a mixture of iron powder (9 g.), ammonium chloride (0.9 g.), ethanol (80 ml.) and water (40 ml.) was added ethyl 2-(2-nitro-3-phenoxyphenyl)acetate (10.9 g.) over 5 minutes under mild reflux and stirring and the mixture was stirred for 1.5 hours at the same temperature. The reaction mixture was filtered under heating and ethanol was distilled off from the filtrate under reduced pressure. To the residue was added water and the mixture was extracted with diethyl ether. The extract was washed with water and dried over magnesium sulfate, and diethyl ether was distilled off under reduced pressure to give the viscous captioned compound (9.5 g.).
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[C:9]2[CH:38]=[CH:37][CH:36]=[CH:35][C:10]=2[S:11][C:12]=1[N:13]([S:26]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)(=[O:28])=[O:27])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]([C:22]([F:25])([F:24])[F:23])[CH:16]=1)(C)(C)C>Cl.O1CCOCC1.C(OCC)C>[NH2:7][C:8]1[C:9]2[CH:38]=[CH:37][CH:36]=[CH:35][C:10]=2[S:11][C:12]=1[N:13]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]([C:22]([F:25])([F:24])[F:23])[CH:16]=1)[S:26]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)(=[O:27])=[O:28]
Reactant: CC(C)(C)OC(=O)Nc1c(N(Cc2ccc(F)c(C(F)(F)F)c2)S(=O)(=O)c2ccccc2)sc2ccccc12
Agent: Cl
Solvent: CCOCC
Solvent: C1COCCO1
Product: Nc1c(N(Cc2ccc(F)c(C(F)(F)F)c2)S(=O)(=O)c2ccccc2)sc2ccccc12
Temperature: 25 °C
Reaction time: 18 h
Yield: 78.6 %

Procedure:
Compound 509-A (1.0 g, 1.72 mmol) was dissolved in 4N HCl in dioxane (20 mL) and stirred at ambient temperature for 18 h. The resultant suspension was diluted with diethyl ether, filtered, washed with diethyl ether and dried under vacuo to afford 0.65 g of compound 509-B. MS: m/z 481.0 (MH+).
Reaction SMILES: C([O:3][C:4](=[O:38])[CH:5]([O:35][CH2:36][CH3:37])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH:14]([C:18]2[S:22][C:21]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)=[N:20][C:19]=2[CH3:33])[CH:15]([CH3:17])[CH3:16])=[CH:9][C:8]=1[CH3:34])C.[Li+].[OH-]>>[CH2:36]([O:35][CH:5]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH:14]([C:18]2[S:22][C:21]([C:23]3[CH:24]=[CH:25][C:26]([C:29]([F:30])([F:31])[F:32])=[CH:27][CH:28]=3)=[N:20][C:19]=2[CH3:33])[CH:15]([CH3:16])[CH3:17])=[CH:9][C:8]=1[CH3:34])[C:4]([OH:38])=[O:3])[CH3:37]
Reactant: CCOC(=O)C(Cc1ccc(OC(c2sc(-c3ccc(C(F)(F)F)cc3)nc2C)C(C)C)cc1C)OCC
Agent: [Li+]
Agent: [OH-]
Product: CCOC(Cc1ccc(OC(c2sc(-c3ccc(C(F)(F)F)cc3)nc2C)C(C)C)cc1C)C(=O)O

Procedure:
In analogy to the procedure described in example 10 d], 2-ethoxy-3-(2-methyl-4-{2-methyl-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-phenyl)-propionic acid ethyl ester (mixture of two diastereomeric racemates) was treated with LiOH to obtain 2-ethoxy-3-{2-methyl-4-(2-methyl-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-phenyl)-propionic acid as a mixture of two diastereomeric racemates as colorless foam.
Reaction SMILES: [CH2:1]=[CH:2][CH:3]=[CH2:4].O=O.[C:7]([OH:10])(=[O:9])[CH3:8]>>[C:7]([O:10][CH:2]([CH:3]([O:10][C:7](=[O:9])[CH3:8])[CH3:4])[CH3:1])(=[O:9])[CH3:8]
Reactant: C=CC=C
Reactant: CC(=O)O
Agent: O=O
Product: CC(=O)OC(C)C(C)OC(C)=O

Procedure:
The conventional butadiene process starts with reaction of butadiene with acetic acid and oxygen-containing gas, followed by hydrogenation to obtain diacetoxybutane (see FIG. 1). As shown in FIG. 2, the resulting diacetoxybutane is hydrolyzed, and acetic acid and water are distilled off from the liquid reaction mixture containing crude 1,4-butanediol (hydrolyzate) in a first distillation tower. Diacetoxybutane and hydroxyacetoxybutane are separated from the hydrolyzate in a second distillation tower. The resulting crude 1,4-butanediol is hydrogenated with hydrogen gas in the presence of a catalyst for hydrogenation. After tetrahydrofuran (hereinafter abbreviated as THF) is concentrated in a third distillation tower, high purity 1,4-butanediol is recovered from a fourth distillation tower as a side stream or a bottom.
Reaction SMILES: [CH3:1][C:2]([CH3:9])([CH2:5][N:6]([CH3:8])[CH3:7])[CH:3]=O.CC(N)C.[NH2:14][CH2:15][CH2:16][CH2:17][Si:18]([O:23][CH3:24])([O:21][CH3:22])[O:19][CH3:20]>>[CH3:1][C:2]([CH3:9])([CH2:5][N:6]([CH3:8])[CH3:7])[CH:3]=[N:14][CH2:15][CH2:16][CH2:17][Si:18]([O:23][CH3:24])([O:19][CH3:20])[O:21][CH3:22]
Reactant: CO[Si](CCCN)(OC)OC
Reactant: CN(C)CC(C)(C)C=O
Solvent: CC(C)N
Product: CO[Si](CCCN=CC(C)(C)CN(C)C)(OC)OC

Procedure:
13.57 g 2,2-dimethyl-3-dimethylaminopropanal, 7.45 g 2-propanamine and 17.93 g 3-aminopropyltrimethoxysilane were reacted according to the general manufacturing procedure (iminosilanes). The product was distilled after manufacture in order to remove oligomer portions. Yield: 28.4 g of a clear, colorless oil having an amine content of 6.61 mmol N/g and a purity of 95%.
Reaction SMILES: [OH:1][C:2]1[C:3]([CH3:24])=[C:4]2[C:9](=[C:10]([CH3:13])[C:11]=1[CH3:12])[O:8][C:7]([CH3:23])([C:14]([NH:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][OH:22])=[O:15])[CH2:6][CH2:5]2.[O:25]=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+]>>[OH:25][C:7]([CH3:23])([CH2:6][CH2:5][C:4]1[C:9](=[O:8])[C:10]([CH3:13])=[C:11]([CH3:12])[C:2](=[O:1])[C:3]=1[CH3:24])[C:14]([NH:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][OH:22])=[O:15]
Reactant: Cc1c(C)c2c(c(C)c1O)CCC(C)(C(=O)NCCCCCO)O2
Reactant: O=[N+]([O-])[O-]
Agent: [Ce+4]
Agent: [NH4+]
Product: CC1=C(C)C(=O)C(CCC(C)(O)C(=O)NCCCCCO)=C(C)C1=O
Yield: 92.3 %

Procedure:
Oxidation as described in protocol B, using 96 mg (0.286 mmol) of 6-hydroxy-N-(5-hydroxypentyl)-2,5,7,8-tetramethylchroman-2-carboxamide and 345 mg CAN (0.629 mmol) yielded 92.8 mg of 2-hydroxy-N-(5-hydroxypentyl)-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide as a yellow oil.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.N1C=CC=CC=1.[C:17](Cl)(=[O:19])[CH3:18]>CN(C)C1C=CN=CC=1.C(#N)C>[N+:8]([C:5]1[CH:4]=[N:3][C:2]([NH:1][C:17](=[O:19])[CH3:18])=[N:7][CH:6]=1)([O-:10])=[O:9]
Reactant: CC(=O)Cl
Reactant: Nc1ncc([N+](=O)[O-])cn1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: CC#N
Product: CC(=O)Nc1ncc([N+](=O)[O-])cn1
Temperature: 100 °C
Reaction time: 1 h
Yield: 31.3 %

Procedure:
To a solution of 2-amino-5-nitropyrimidine (3.00 g, 21.4 mmol), 4-dimethylaminopyridine (2.61 g, 21.4 mmol) and pyridine (10.4 ml, 128 mmol) in acetonitrile (100 ml) was added acetyl chloride (3.04 ml, 42.8 mmol), the mixture was stirred at 100° C. for 1 hour. To the mixture was added acetyl chloride (2.00 ml, 28.1 mmol) and the mixture was stirred at 100° C. for 12 hours. The reaction mixture was poured into ice-water and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was recrystallized from a mixed solvent of hexane and ethyl acetate to obtain the desired product (1.22 g, 31.3%) as a solid.
Reaction SMILES: [NH:1]1[CH2:6][CH:5]=[CH:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[CH2:14]([O:21][C:22](Cl)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>ClCCl>[CH2:14]([O:21][C:22]([N:1]1[CH2:2][CH:3]=[CH:4][CH2:5][CH2:6]1)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: C1=CCNCC1
Reactant: O=C(Cl)OCc1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(OCc1ccccc1)N1CC=CCC1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of 1,2,3,6-tetrahydropyridine (5.0 g) in dichloromethane (200 mL) was cooled to 0° C. and treated with triethylamine (10.1 mL) followed by benzylchloroformate (10.3 mL). The reaction mixture was stirred for 1 hour at 0° C., diluted with dichloromethane, washed (dilute hydrochloric acid, sodium bicarbonate solution), dried and evaporated. The crude product was distilled to give the N-protected derivative (11.01 g); bp 160°-165° C. (26.7 Pa); NMR (CDCl3): 2.15 (broad, 2), 3.5 (t,2, J=6), 3.96 (m, 2), 5.15 (s, 2), 5.8 (2 broad peaks, 2), 7.4(m, 5); MS: m/z=218(M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[S:14]1[CH:18]=[CH:17][N:16]=[C:15]1[NH2:19]>>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:19][C:15]2[S:14][CH:18]=[CH:17][N:16]=2)=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12]
Reactant: O=C(Cl)c1ccc(Cl)c([N+](=O)[O-])c1
Reactant: Nc1nccs1
Product: O=C(Nc1nccs1)c1ccc(Cl)c([N+](=O)[O-])c1

Procedure:
A mixture of 4-chloro-3-nitrobenzoyl chloride was reacted with Thiazol-2-ylamine to produce 4-Chloro-3-nitro-N-thiazol-2-yl-benzamide according to the procedure of Example 49A, which was treated sequentially using the procedures from Examples 53A and 53B to provide the title product.