Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(NC(C)C)(C)C.[Li]CCCC.[CH2:13]([CH:31]([C:50]([CH:52]([CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78]/[CH:79]=[CH:80]\[CH2:81]/[CH:82]=[CH:83]\[CH2:84][CH2:85][CH2:86][CH2:87][CH3:88])[CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60]/[CH:61]=[CH:62]\[CH2:63]/[CH:64]=[CH:65]\[CH2:66][CH2:67][CH2:68][CH2:69]C)=[O:51])CCCCCCCC/C=C\C/C=C\CCCCC)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]/[CH:21]=[CH:22]\[CH2:23]/[CH:24]=[CH:25]\[CH2:26][CH2:27][CH2:28][CH2:29]C.[Li].C1C[O:93]CC1>>[CH2:53]([CH:52]([CH:71]([OH:93])[CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78]/[CH:79]=[CH:80]\[CH2:81]/[CH:82]=[CH:83]\[CH2:84][CH2:85][CH2:86][CH2:87][CH3:88])[C:50](=[O:51])[CH2:31][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]/[CH:20]=[CH:21]\[CH2:22]/[CH:23]=[CH:24]\[CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59]/[CH:60]=[CH:61]\[CH2:62]/[CH:63]=[CH:64]\[CH2:65][CH2:66][CH2:67][CH2:68][CH3:69]
Reactant: C1CCOC1
Reactant: CCCCC/C=C\C/C=C\CCCCCCCCC(CCCCCCCC/C=C\C/C=C\CCCCC)C(=O)C(CCCCCCCC/C=C\C/C=C\CCCCC)CCCCCCCC/C=C\C/C=C\CCCCC
Agent: [Li]
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Product: CCCCC/C=C\C/C=C\CCCCCCCCC(=O)C(CCCCCCC/C=C\C/C=C\CCCCC)C(O)CCCCCCC/C=C\C/C=C\CCCCC
Temperature: -78 °C
Reaction time: 0.67 h
Yield: 62 %

Procedure:
To a cooled (−40° C.) solution of N,N,-di-isopropylamine (462 μL, 3.27 mmol) in THF (9 mL) was added nBuLi (1.45 mL, 3.63 mmol as a 2.5M solution in hexanes). After stirring (40 min) the solution was cooled (−78° C.) and treated with di-linoleylmethylketone (1.50 g, 2.85 mmol, neat) dropwise. After stirring (40 min) the newly generated lithium enoloate was added to a cold (−78° C.) solution of linoleyl aldehyde (804 mg, 3.04 mmol) in THF (4 mL). After stirring (1 h, −78° C.) the mixture was quenched by the addition of sat. aq. NH4Cl, then extracted with EtOAc, dried (Na2SO4), filtered and concentrated. The crude material was subjected to chromatography (0.5%→1% EtOAc-hexanes) to yield (6Z,9Z,29Z,32Z)-20-((8Z,11Z)-heptadeca-8,11-dien-1-yl)-21-hydroxyoctatriaconta-6,9,29,32-tetraen-19-one (10) (1.50 g, 62%) as a colorless oil. Rf 0.27 (5% EtOAc-hexanes), FW 791.39, C55H98O2.
Reaction SMILES: I([O-])(=O)(=O)=O.[Na+].[CH2:7]([N:9]1[C:15]2[CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=[CH:19][C:14]=2[O:13][CH2:12][C:11](CO)([OH:23])[CH2:10]1)[CH3:8]>CC(C)=O.O.O1CCCC1>[CH2:7]([N:9]1[C:15]2[CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=[CH:19][C:14]=2[O:13][CH2:12][C:11](=[O:23])[CH2:10]1)[CH3:8]
Reactant: CCN1CC(O)(CO)COc2ccc([N+](=O)[O-])cc21
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: CC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: CCN1CC(=O)COc2ccc([N+](=O)[O-])cc21
Reaction time: 1 h
Yield: 73.7 %

Procedure:
Sodium periodate (0.454 g, 2.12 mmol) was added to 9-Ethyl-7-hydroxymethyl-2-nitro-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-ol (0.114 g, 0.425 mmol) in Acetone (15 mL) and Water (5 mL). After 1 h, the heterogenous mixture was further diluted with Water (10 mL) and Tetrahydrofuran (10 mL), which did not create a homogenous mixture. The mixture was stirred overnight, then was partitioned between water and DCM. Extraction with DCM and washing with brine, followed by drying gave 9-Ethyl-2-nitro-8,9-dihydro-5-oxa-9-aza-benzocyclohepten-7-one (74 mg, 74%). 1H-NMR (CDCl3): 7.69 (s, 1H), 7.62 (d, 1H, J=8.8 Hz), 7.02 (d, 1H, J=8.8 Hz), 4.61 (s, 2H), 4.10 (s, 2H), 3.42 (q, 2H, J=7.2 Hz), 1.26 (t, 3H, J=7.2 Hz).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([N+:9]([O-])=O)=[C:7]([NH:12][C:13]([C:15]2[N:16]([CH3:25])[N:17]=[C:18]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:19]=2[Cl:20])=O)[CH:6]=[C:5]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[C:32]([F:35])([F:34])[F:33])[N:4]=1>CC(O)=O.[Fe]>[C:21]([C:18]1[C:19]([Cl:20])=[C:15]([C:13]2[NH:9][C:8]3[C:3]([O:2][CH3:1])=[N:4][C:5]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[C:32]([F:35])([F:34])[F:33])=[CH:6][C:7]=3[N:12]=2)[N:16]([CH3:25])[N:17]=1)([CH3:24])([CH3:23])[CH3:22]
Reactant: COc1nc(-c2ccccc2C(F)(F)F)cc(NC(=O)c2c(Cl)c(C(C)(C)C)nn2C)c1[N+](=O)[O-]
Agent: [Fe]
Solvent: CC(=O)O
Product: COc1nc(-c2ccccc2C(F)(F)F)cc2nc(-c3c(Cl)c(C(C)(C)C)nn3C)[nH]c12
Temperature: 100 °C
Reaction time: 0.17 h

Procedure:
A solution of 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [2-methoxy-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-yl]-amide (149 mg, 0.291 mmol, prepared as described in STEP A above) in AcOH (10 mL) was treated with iron powder (81.3 mg, 1.46 mmol), and the resulting mixture was heated to 100° C. for 1.5 h. The cooled mixture was concentrated in vacuo, taken up in saturated aqueous NaHCO3 (50 mL), and extracted twice with EtOAc (40 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 12-g SEPRA Si 50 SPE column (Flow rate=15 mL/min; Eluent=EtOAc-hexanes, 1:99 for 10 min, then 1:99 to 1:4 over 40 min) to yield 2-(5-tert-butyl-4-chloro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-6-(2-trifluoromethyl-phenyl)-3H-imidazo[4,5-c]pyridine as a white solid. Mass Spectrum (LCMS, ESI pos.): Calculated for C22H21N5OClF3: 464.1 (M+H). Measured: 464.2.
Reaction SMILES: [CH:1]([NH2:4])([CH3:3])[CH3:2].[CH2:5]([O:7][C:8]([N:10]=[C:11]=[S:12])=[O:9])[CH3:6]>C(OCC)C>[CH2:5]([O:7][C:8]([NH:10][C:11]([NH:4][CH:1]([CH3:3])[CH3:2])=[S:12])=[O:9])[CH3:6]
Reactant: CCOC(=O)N=C=S
Reactant: CC(C)N
Solvent: CCOCC
Product: CCOC(=O)NC(=S)NC(C)C

Procedure:
A solution of 7.1 grams of isopropylamine in 40 ml of anhydrous ethyl ether was added dropwise in 30 minutes with stirring to a solution of 15.5 grams of ethoxycarbonyl isothiocyanate (Preparation 1) in 10 ml of anhydrous ethyl ether. The reaction vessel was cooled with an ice-water bath. The reaction mixture was let stand at an ambient room temperature. After the reaction was complete, the solution was concentrated by stripping off most of the solvent under reduced pressure. The crystals were collected by filtering and washing with hexanes. The first crop weighed 8.1 grams, m.p. 52.5°-54° C. The second crop weighed 7 grams, m.p. 52°-54° C.
Reaction SMILES: [BH4-].[Na+].CO.[CH2:5]([N:7]1[C:13](=[O:14])[C:12]([CH3:16])([CH3:15])[C:11](=[O:17])[N:10]([CH3:18])[C:9]2[CH:19]=[C:20]([CH2:23][N:24]([CH2:38][C:39]3[CH:46]=[CH:45][CH:44]=[CH:43][C:40]=3[CH:41]=[O:42])[CH2:25][CH2:26][N:27]3[CH:32]=[CH:31][C:30]4[O:33][C:34]([CH3:36])=[CH:35][C:29]=4[C:28]3=[O:37])[CH:21]=[CH:22][C:8]1=2)[CH3:6]>O>[CH2:5]([N:7]1[C:13](=[O:14])[C:12]([CH3:16])([CH3:15])[C:11](=[O:17])[N:10]([CH3:18])[C:9]2[CH:19]=[C:20]([CH2:23][N:24]([CH2:38][C:39]3[CH:46]=[CH:45][CH:44]=[CH:43][C:40]=3[CH2:41][OH:42])[CH2:25][CH2:26][N:27]3[CH:32]=[CH:31][C:30]4[O:33][C:34]([CH3:36])=[CH:35][C:29]=4[C:28]3=[O:37])[CH:21]=[CH:22][C:8]1=2)[CH3:6]
Reactant: CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(CN(CCn3ccc4oc(C)cc4c3=O)Cc3ccccc3C=O)ccc21
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(CN(CCn3ccc4oc(C)cc4c3=O)Cc3ccccc3CO)ccc21
Temperature: 0 °C
Reaction time: 3 h
Yield: 70.9 %

Procedure:
Sodium borohydride (47 mg) were added to a methanol solution (10 ml) of 2-({N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)benzaldehyde (0.59 g) and the mixture was stirred for 3 hours at 0° C. Water was added to the reaction mixture, followed by extraction by ethyl acetate. The organic layer was dried by anhydrous sodium sulfate, and condensed under reduced pressure. The residue was recrystallized from ethyl acetate-ether mixture to give the title compound (0.42 g) as a pale brown white powder.
Reaction SMILES: COC1C=CC(NC(N)=O)=CC=1.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]=[C:22]=[O:23])=[CH:17][CH:16]=1.[CH2:24]([NH:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]>C1(C)C=CC=CC=1>[CH2:33]([N:32]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[C:22]([NH:21][C:18]1[CH:17]=[CH:16][C:15]([O:14][CH3:13])=[CH:20][CH:19]=1)=[O:23])[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40]
Reactant: COc1ccc(N=C=O)cc1
Reactant: CCCCCCCCNCCCCCCCC
Agent: COc1ccc(NC(N)=O)cc1
Solvent: Cc1ccccc1
Product: CCCCCCCCN(CCCCCCCC)C(=O)Nc1ccc(OC)cc1
Yield: 60 %

Procedure:
To study the reaction mechanism, 4-methoxyphenylurea was heated in boiling toluene. It was expected that 4-methoxyphenyl isocyanate would be formed, but instead the 4-methoxyphenylurea remained completely unchanged. On heating 4-methoxyphenylurea in boiling toluene with the addition of one equivalent of dioctylamine, N,N-dioctyl-N'-4-methoxyphenylurea was formed in 60% yield after one hour, no by-products, in particular no isocyanates or by-products derived from them, being produced. Proof that the reaction does not proceed via isocyanates was obtained using 1H-NMR and 13C-NMR spectroscopy.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=1)[N:6]=[CH:5]2.[O:18]1[CH2:23][CH2:22][N:21]([C:24]2[CH:32]=[CH:31][C:27]([C:28]([O-])=[O:29])=[CH:26][CH:25]=2)[CH2:20][CH2:19]1>>[NH2:17][C:14]1[CH:15]=[CH:16][C:11]([N:7]2[C:8]3[C:4](=[CH:3][C:2]([NH:1][C:28](=[O:29])[C:27]4[CH:26]=[CH:25][C:24]([N:21]5[CH2:22][CH2:23][O:18][CH2:19][CH2:20]5)=[CH:32][CH:31]=4)=[CH:10][CH:9]=3)[CH:5]=[N:6]2)=[CH:12][CH:13]=1
Reactant: Nc1ccc(-n2ncc3cc(N)ccc32)cc1
Reactant: O=C([O-])c1ccc(N2CCOCC2)cc1
Product: Nc1ccc(-n2ncc3cc(NC(=O)c4ccc(N5CCOCC5)cc4)ccc32)cc1

Procedure:
Compound 381 was prepared according to the procedure described in Scheme IV from 5-amino-1-(4-aminophenyl)indazole and 4-morpholinobenzoate. [M+H]+ calcd for C24H23N5O2: 414.19; found: 414.01.
Reaction SMILES: [O:1]([C:8]1[CH:17]=[CH:16][C:11]([O:12][CH2:13][CH2:14][NH2:15])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:18]([S:20][C:21](Cl)=[O:22])[CH3:19].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:18]([S:20][C:21](=[O:22])[NH:15][CH2:14][CH2:13][O:12][C:11]1[CH:16]=[CH:17][C:8]([O:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:9][CH:10]=1)[CH3:19]
Reactant: NCCOc1ccc(Oc2ccccc2)cc1
Reactant: CCSC(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCSC(=O)NCCOc1ccc(Oc2ccccc2)cc1
Yield: 45.1 %

Procedure:
4 g of 2-[(p-phenoxy)phenoxy]ethylamine and 11.2 g of chlorothioformic acid S-ethyl ester are dissolved in 150 ml of acetone. 14.5 g of potassium carbonate are added to the solution. This mixture is heated under reflux for 6 hours and then filtered. The residue is washed with acetone and the filtrate is evaporated in vacuo. The crystalline residue is suspended in cyclohexane and filtered to yield 2.5 g (53%) of 2-[(p-phenoxy)phenoxy]ethylthiocarbamic acid S-ethyl ester, m.p.--56°-58° C.
Reaction SMILES: [OH-].[K+].C1COCC1.C[O:9][C:10](=[O:28])[C:11]([N:17]([CH3:27])[C:18]([C:20]1[CH:25]=[CH:24][C:23]([I:26])=[CH:22][CH:21]=1)=[O:19])([CH3:16])[C:12]([NH:14][CH3:15])=[O:13].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO>[C:10]([C:11]([N:17]([CH3:27])[C:18]([C:20]1[CH:21]=[CH:22][C:23]([I:26])=[CH:24][CH:25]=1)=[O:19])([CH3:16])[C:12]([NH:14][CH3:15])=[O:13])([OH:28])=[O:9]
Reactant: CNC(=O)C(C)(C(=O)OC)N(C)C(=O)c1ccc(I)cc1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CNC(=O)C(C)(C(=O)O)N(C)C(=O)c1ccc(I)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 78.6 %

Procedure:
A 1.7 mol/L-potassium hydroxide aqueous solution (0.55 mL) was added to a THF (1.0 mL)-MeOH (1.0 mL) solution of 1-{[1-methoxy-2-methyl-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}-4-iodobenzene (Intermediate 10-2, 0.12 g), and the mixture was stirred for 3 hours at room temperature. The reaction mixture was adjusted to pH 5 with a 10% aqueous solution of citric acid, and extracted with a chloroform-methanol mixture. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The desiccant was filtered out, and then the solvent was distilled off under reduced pressure to obtain 1-{[2-carboxy-1-(methylamino)-1-oxopropan-2-yl](methyl)carbamoyl}-4-iodobenzene (Intermediate 11, orange solid) (91 mg, 80%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][CH:18]2[C:27]3[N:23]([C:24]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[N:25][N:26]=3)[C:22]3[CH:34]=[CH:35][CH:36]=[CH:37][C:21]=3[N:20]([CH2:38][C:39](=[O:50])[N:40]([CH:47]([CH3:49])[CH3:48])[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:19]2=[O:51])=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:52][Si]([N-][Si](C)(C)C)(C)C.[K+].CI>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][C:18]2([CH3:52])[C:27]3[N:23]([C:24]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[N:25][N:26]=3)[C:22]3[CH:34]=[CH:35][CH:36]=[CH:37][C:21]=3[N:20]([CH2:38][C:39](=[O:50])[N:40]([CH:47]([CH3:48])[CH3:49])[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:19]2=[O:51])=[CH:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: CC(C)N(C(=O)CN1C(=O)C(Cc2cn(C(=O)OC(C)(C)C)c3ccccc23)c2nnc(-c3ccccc3)n2-c2ccccc21)c1ccccc1
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Solvent: CCOC(C)=O
Product: CC(C)N(C(=O)CN1C(=O)C(C)(Cc2cn(C(=O)OC(C)(C)C)c3ccccc23)c2nnc(-c3ccccc3)n2-c2ccccc21)c1ccccc1
Temperature: -5 °C
Reaction time: 0.33 h
Yield: 33.3 %

Procedure:
To a solution of 3-{6-[(isopropyl-phenyl-carbamoyl)-methyl]-5-oxo-1-phenyl-5,6-dihydro-4H-2,3,6,10b-tetraaza-benzo[e]azulen-4-ylmethyl}-indole-1-carboxylic acid tert-butyl ester (100 mg, 0.147 mmol) in DMF (2 mL) at −5° C. was added KHMDS (0.5M in THF, 322 μL, 0.161 mmol). The solution was stirred at −5° C. for 20 minutes and methyl iodide (10 μL, 0.161 mmol) was added. The reaction was stirred at room temperature for 24 hours, was diluted with EtOAc and the organic solution was washed with brine (3×). The organic solution was dried (Na2SO4), filtered and concentrated. The residue was purified by preparative chromatography (2×) eluting with 50% EtOAc in hexanes to provide 34 mg of 3-{6-[(isopropyl-phenyl-carbamoyl)-methyl]-4-methyl-5-oxo-1-phenyl-5,6-dihydro-4H-2,3,6,10b-tetraaza-benzo[e]azulen-4-ylmethyl}-indole-1-carboxylic acid tert-butyl ester. 1H NMR (CD2Cl2) δ 8.05 (d, 1H), 7.67 (d, 1H), 7.36-7.54 (m, 10H), 7.08-7.30 (m, 6H), 6.90 (d, 1H), 5.02 (m, 1H), 4.29 (d, 1H), 4.11 (m, 1H), 2.78 (s, 2H), 1.80 (s, 3H), 1.64 (s, 9H), 1.10 (m, 6H); MS 695.3 (M+1).
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].Br[C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[CH:11]2.[Cl:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1>O>[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[NH:13][CH:12]=[CH:11]3)=[CH:20][CH:19]=1
Reactant: OB(O)c1ccc(Cl)cc1
Reactant: Brc1ccc2[nH]ccc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: Clc1ccc(-c2ccc3[nH]ccc3c2)cc1
Yield: 40.7 %

Procedure:
A stirred slurry of 6.35 g (60 mmol) K2CO3, 2.94 g (15 mmol) 5-bromoindole, 2.50 g (16 mmol) 4-chlorophenylboronic acid, and 0.48 g (0.42 mmol) tetrakistriphenylphosphine palladium was heated to reflux for 2½ hours. The reaction mixture was allowed to cool and was then poured into 200 ml water and extracted with EtOAc. The organic layer was separated, dried over MgSO4, and concentrated. The residue was chromatographed on silica to afford 1.39 g 5-(4-chlorophenyl)indole as a white solid.
Reaction SMILES: C([O:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]([NH:27][C:28](=[O:30])[CH3:29])[S:15][C:16]=2[C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=2)=[CH:8][CH:7]=1)(=O)C.C(=O)([O-])[O-].Cl>CO>[OH:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]([NH:27][C:28](=[O:30])[CH3:29])[S:15][C:16]=2[C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=2)=[CH:8][CH:7]=1
Reactant: CC(=O)Nc1nc(-c2ccc(COC(C)=O)cc2)c(-c2ccc(S(C)(=O)=O)cc2)s1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CO
Product: CC(=O)Nc1nc(-c2ccc(CO)cc2)c(-c2ccc(S(C)(=O)=O)cc2)s1
Reaction time: 1 h

Procedure:
To a suspension of 4-{2-(acetylamino)-5-[4-(methylsulfonyl)phenyl]-1,3-thiazol-4-yl}benzyl acetate (1.218 g) in metanol (24 ml) was added pottasium carbonate (379 mg) at 20° C., and the mixture was stirred for 1 h. To the reaction mixture was added 0.1N-hydrochloric acid (27.4 ml), and the mixture was extracted with chloroform (500 ml), dried over magnesium sulfate and evaporated to give N-{4-[4-(hydroxymethyl)phenyl]-5-[4-(methylsulfonyl)phenyl]-1,3-thiazol-2-yl}acetamide as a yellow solid.
Reaction SMILES: [C:1]([OH:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[OH-].[Na+:22]>CO>[C:1]([O-:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[Na+:22]
Reactant: CCCCCCCCCCCCCCCCCC(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCCCCCCCCCCCCCCCCC(=O)[O-]
Yield: 146.7 %

Procedure:
GPC in an amount of 5.14 g, 350 ml of methanol, 11.58 g of stearic acid and 1.63 g of sodium hydroxide were mixed to give a uniform solution at 50° C. and then concentrated to dryness to obtain 18.3 g of sodium stearate-supported GPC.
Reaction SMILES: [CH2:1]([N:8]=[CH:9][C:10]1[S:18][C:13]2[N:14]=[CH:15][N:16]=[CH:17][C:12]=2[CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO[C:21]1[CH:22]=[C:23]([CH:36]=[CH:37][C:38]=1OC)[CH2:24][N:25]=[CH:26]C1SC2N=CN=CC=2C=1>>[CH2:1]([N:8]1[C:9]([C:10]2[S:18][C:13]3[N:14]=[CH:15][N:16]=[CH:17][C:12]=3[CH:11]=2)=[C:24]([C:23]2[CH:36]=[CH:37][CH:38]=[CH:21][CH:22]=2)[N:25]=[CH:26]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C(=NCc1ccccc1)c1cc2cncnc2s1
Reactant: COc1ccc(CN=Cc2cc3cncnc3s2)cc1OC
Product: c1ccc(Cn2cnc(-c3ccccc3)c2-c2cc3cncnc3s2)cc1

Procedure:
The title compound was prepared by a similar process to that described for Example 6 but using N-benzyl-N-[thieno[2,3-d]pyrimidin-6-ylmethylidene]amine (Intermediate 51) in place of N-(3,4Dimethoxybenzyl)-N-[thieno[2,3-d]pyrimidin-6-ylmethylidene]amine (intermediate 14). Pale yellow solid (26 mg, 26%);
Reaction SMILES: [F:1][C:2]1[C:7]([CH:8]([CH3:11])[CH2:9][OH:10])=[C:6]([F:12])[C:5]([F:13])=[C:4]([F:14])[C:3]=1[F:15].S(=O)(=O)(O)[OH:17].[Mn]([O-])(=O)(=O)=O.[K+].S(=O)(O)[O-].[Na+]>CC(C)=O>[F:1][C:2]1[C:7]([CH:8]([CH3:11])[C:9]([OH:17])=[O:10])=[C:6]([F:12])[C:5]([F:13])=[C:4]([F:14])[C:3]=1[F:15]
Reactant: O=S(=O)(O)O
Reactant: CC(CO)c1c(F)c(F)c(F)c(F)c1F
Agent: O=[Mn](=O)(=O)[O-]
Agent: O=S([O-])O
Agent: [K+]
Solvent: CC(C)=O
Product: CC(C(=O)O)c1c(F)c(F)c(F)c(F)c1F
Reaction time: 0.5 h

Procedure:
To a vigorously stirred mixture of 9.05 g of (+)-2-(pentafluorophenyl)-1-propanol, 25 ml of acetone and 100 ml of 3N sulfuric acid, was added portionwise 12.6 g of potassium permanganate over six hours. After the mixture was further stirred for 30 minutes, this reaction mixture was poured into 150 ml of an aqueous solution of 15% sodium bisulfite, and extracted with ethyl acetate. The organic layer was extracted with an aqueous solution of 5% potassium carbonate. This aqueous layer was acidified with concentrated hydrochloric acid followed by extraction with ethyl acetate. This extracted solution was then dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the subsequent distillation under reduced pressure gave 8.23 g of (-)-2-(pentafluorophenyl)propionic acid having the aforementioned physical properties.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[NH:8][CH3:9].Cl[C:11](Cl)([O:13]C(=O)OC(Cl)(Cl)Cl)Cl>CC#N>[CH3:9][N:8]1[C:7]2[CH:6]=[CH:5][N:4]=[CH:3][C:2]=2[NH:1][C:11]1=[O:13]
Reactant: CNc1ccncc1N
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: CC#N
Product: Cn1c(=O)[nH]c2cnccc21
Reaction time: 1 h

Procedure:
To a stirred suspension of 3-amino-4-methylaminopyridine [U.S. Pat. No. 5,371,086 (1993)] (190 mg, 1.54 mmol) in CH3CN (10 mL) was added triphosgene (458 mg, 1.54 mmol) portionwise. After 1 h, the mixture was concentrated in vacuo and the residue was converted to the free base by ion exchange chromatography on a SCX cartridge, eluting with 2 M NH3 in MeOH to give the title compound. MS: m/z=150 (M+1).
Reaction SMILES: [N:1]([N:3]1[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1)=[O:2].N1C=CC=CC=1.[C:15]1([C:20](Cl)=[O:21])[S:19][CH:18]=[CH:17][CH:16]=1.C(OCC)(=O)C>O1CCOCC1.O>[N:1]([N:3]1[CH2:8][CH2:7][N:6]([C:20](=[O:21])[C:15]2[S:19][CH:18]=[CH:17][CH:16]=2)[CH2:5][CH2:4]1)=[O:2]
Reactant: O=C(Cl)c1cccs1
Reactant: O=NN1CCNCC1
Solvent: O
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: O=NN1CCN(C(=O)c2cccs2)CC1
Temperature: 0 °C

Procedure:
To a mixture of 1-nitrosopiperazine {1.21 g) and pyridine (2.4 ml) in dioxane (18 ml) was added dropwise 2-thenoyl chloride (1.2 ml) in an ice bath. The mixture was stirred for one hour in an ice.bath and then overnight at ambient temperature. The mixture was poured into a mixture of ethyl acetate (100 ml) and water (100 ml). The separated aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried and concentrated in vacuo. The residue was pulverized with diisopropyl ether to yield 1-nitroso-4-(2-thenoyl)-piperazine (1.78 g).
Reaction SMILES: C(OC([NH:8][CH:9]1[C:22](=[O:23])[CH2:21][C:20]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][C:11]=2[CH2:10]1)=O)(C)(C)C.[ClH:24]>C(OCC)C>[ClH:24].[NH2:8][CH:9]1[C:22](=[O:23])[CH2:21][C:20]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][C:11]=2[CH2:10]1
Reactant: CC(C)(C)OC(=O)NC1Cc2ccc3ccccc3c2CC1=O
Agent: Cl
Solvent: CCOCC
Product: NC1Cc2ccc3ccccc3c2CC1=O
Reaction time: 6 h

Procedure:
Under argon to a solution of 2-tertbutoxycarbonylamino-1,2-dihydro-3(4H)-phenanthrenone (74 mg) in anhydrous diethyl ether (5 ml) was added a saturated solution of hydrochloric acid in diethyl ether (5 ml). The mixture was stirred for 6 hours and the formed precipitate was filtered and dried under vacuum to afford the title compound as a white solid (42 mg)
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:23]2[CH2:28][C:27]([CH3:30])([CH3:29])[CH2:26][C:25]([CH3:32])([CH3:31])[CH2:24]2)[C:9]2[CH:14]=[CH:13][C:12]([C:15]#[C:16][CH2:17][CH2:18][C:19]([O:21]C)=[O:20])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[OH-].[Na+].Cl>CCO.C1COCC1>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:23]2[CH2:28][C:27]([CH3:30])([CH3:29])[CH2:26][C:25]([CH3:32])([CH3:31])[CH2:24]2)[C:9]2[CH:14]=[CH:13][C:12]([C:15]#[C:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1
Reactant: COC(=O)CCC#Cc1ccc(C(=C2CC(C)(C)CC(C)(C)C2)c2ccc(O)cc2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: CC1(C)CC(=C(c2ccc(O)cc2)c2ccc(C#CCCC(=O)O)cc2)CC(C)(C)C1
Temperature: 60 °C
Reaction time: 2 h
Yield: 94.8 %

Procedure:
To a solution of methyl 5-{4-[(4-hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}-4-pentynoate (243) (0.16 g, 0.38 mmol) in a mixture of EtOH (5 mL) and THF (5 mL) was added an aqueous solution of 1N NaOH (6 mL). The mixture was stirred at 60° C. for 2 h. Upon cooling, the mixture was acidified to pH=2 with an aqueous solution of 1 N HCl. The mixture was extracted with EtOAc (2×50 mL). The combined organic extract washed with brine and dried over Na2SO4. Concentration gave a white residue, which was triturated with hot hexanes containing 1% MeOH to yield the title compound (244) as white solid (0.15 g, 95%), mp 233-234° C. 1H NMR (400 MHz, CH3OH-d4): δ 0.91 (s, 6H), 0.92 (s, 6H), 1.29 (s, 2H), 1.94 (s, 2H), 1.98 (s, 2H), 2.50-2.60 (m, 2H), 2.60-2.70 (m, 2H), 6.68 (d, J=8.6 Hz, 2H), 6.94 (d, J=8.6 Hz, 2H), 7.07 (d, J=8.3 Hz, 2H), 7.25 (d, J=8.1 Hz, 2H). LCMS (ESI): m/z 417 (M+H)+, 415 (M−H)−.