Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: II.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[C:29]([O:33][C:34](=[O:45])[NH:35][CH2:36][CH2:37][C:38]([NH:40][NH:41][C:42](=[O:44])[CH3:43])=O)([CH3:32])([CH3:31])[CH3:30]>C(Cl)Cl>[C:29]([O:33][C:34](=[O:45])[NH:35][CH2:36][CH2:37][C:38]1[O:44][C:42]([CH3:43])=[N:41][N:40]=1)([CH3:32])([CH3:31])[CH3:30]
Reactant: CC(=O)NNC(=O)CCNC(=O)OC(C)(C)C
Agent: II
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1nnc(CCNC(=O)OC(C)(C)C)o1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Iodine (0.261 g, 1.028 mmol) is added to a stirred solution of polymer supported triphenylphosphine (3 mmol/g, 0.34 g, 1.03 mmol) in DCM (10 ml). After stirring for 10 min at room temperature triethylamine (0.287 ml, 2.06 mmol) and [3-(N′-acetyl-hydrazino)-3-oxo-propyl]-carbamic acid tert-butyl ester (0.126 g, 0.514 mmol) are added. The reaction is stirred at room temperature for 18 h then filtered through a Celite™ filter material plug, washing with DCM. The solvent is removed and the residue is purified by chromatography on silica, eluting with EtOAc, to afford the titled compound.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:27])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:23](=[CH:24][CH:25]=1)[O:22][C:11]1([CH2:14][N:13]([C:15](OC(C)(C)C)=O)[CH2:12]1)[CH2:10][C:9]2=[O:26].C=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[CH3:1][O:2][C:3](=[O:27])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:23](=[CH:24][CH:25]=1)[O:22][C:11]1([CH2:14][N:13]([CH3:15])[CH2:12]1)[CH2:10][C:9]2=[O:26]
Reactant: COC(=O)/C=C/c1ccc2c(c1)C(=O)CC1(CN(C(=O)OC(C)(C)C)C1)O2
Agent: C=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: COC(=O)/C=C/c1ccc2c(c1)C(=O)CC1(CN(C)C1)O2

Procedure:
(E)-3-[1′-Methyl-4-oxo-spiro(chromane-2,3′-azetidine)-6-yl]-acrylic acid methyl ester was synthesized starting from Intermediate 4 (500 mg, 1.62 mmol), according to the procedure for preparation of Example 31, Step A, using aqueous 37% formaldehyde solution (0.088 ml, 3.2 mmol), and NaBH(OAc)3 (515 mg, 2.43 mmol). The product was obtained as pale yellow oil (430 mg).
Reaction SMILES: [CH:1]1([C:4]2[O:5][CH:6]=[C:7]([C:9]([OH:11])=O)[N:8]=2)[CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.[NH2:21][C:22]1[C:23]([N:41]2[CH2:46][CH2:45][N:44]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=3[CH3:53])[CH2:43][CH2:42]2)=[CH:24][C:25]([F:40])=[C:26]([CH:39]=1)[C:27]([NH:29][CH2:30][CH2:31][CH2:32][N:33]1[CH2:37][CH2:36][CH2:35][C:34]1=[O:38])=[O:28].[Cl-].[Li+]>CN(C=O)C>[F:40][C:25]1[C:26]([C:27](=[O:28])[NH:29][CH2:30][CH2:31][CH2:32][N:33]2[CH2:37][CH2:36][CH2:35][C:34]2=[O:38])=[CH:39][C:22]([NH:21][C:9]([C:7]2[N:8]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[O:5][CH:6]=2)=[O:11])=[C:23]([N:41]2[CH2:42][CH2:43][N:44]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=3[CH3:53])[CH2:45][CH2:46]2)[CH:24]=1
Reactant: O=C(O)c1coc(C2CC2)n1
Reactant: Cc1ccccc1N1CCN(c2cc(F)c(C(=O)NCCCN3CCCC3=O)cc2N)CC1
Agent: [Cl-]
Agent: [Li+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Cc1ccccc1N1CCN(c2cc(F)c(C(=O)NCCCN3CCCC3=O)cc2NC(=O)c2coc(C3CC3)n2)CC1
Reaction time: 0.05 h

Procedure:
To a solution of 2-cyclopropyl-oxazole-4-carboxylic acid 1h (22.8 mg, 0.149 mmol) in DMF (5.0 mL) HATU (75.4 mg, 0.198 mmol) was added and stirred for 3 min. N, N-diisopropylethylamine (0.086 mL, 0.496 mmol) was added to this followed by 5-amino-2-fluoro-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-4-(4-o-tolyl-piperazin-1-yl)-benzamide 3d (45.0 mg, 0.099 mmol) in DMF (2.0 mL) and the reaction was stirred at room temperature for 16 h. Saturated solution of lithium chloride was added to this and the contents were extracted with ethyl acetate dried on anhydrous sodium sulfate, concentrated and the crude 3e was dissolved in methanol and purified on preparative HPLC using water/methanol as eluent.
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[N:5][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24]([CH2:27][C:28](O)=[O:29])=[C:23]([F:31])[CH:22]=3)[CH2:11][CH2:10]2)=[N:7][CH:8]=1)[CH3:2].[NH:32]1[CH2:35][CH2:34][CH2:33]1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[N:32]1([C:28](=[O:29])[CH2:27][C:24]2[CH:25]=[CH:26][C:21]([O:20][CH2:19][CH2:18][C@@H:16]3[CH2:17][C@@H:15]3[CH:12]3[CH2:11][CH2:10][N:9]([C:6]4[N:7]=[CH:8][C:3]([CH2:1][CH3:2])=[CH:4][N:5]=4)[CH2:14][CH2:13]3)=[CH:22][C:23]=2[F:31])[CH2:35][CH2:34][CH2:33]1
Reactant: CCc1cnc(N2CCC([C@H]3C[C@H]3CCOc3ccc(CC(=O)O)c(F)c3)CC2)nc1
Reactant: C1CNC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCc1cnc(N2CCC([C@H]3C[C@H]3CCOc3ccc(CC(=O)N4CCC4)c(F)c3)CC2)nc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of [4-(2-{(1S,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]acetic acid (20.0 mg, 0.047 mmol) in 1 ml anhydrous DMF at RT was added azetidine (4.01 mg, 0.070 mmol) and N,N-diisopropylethylamine (0.201 ml, 1.15 mmol). o-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (30.2 mg, 0.234 mmol) was added and the mixture stirred at RT for 4 hrs. The mixture was filtered and purified by reversed-phase HPLC (SunFire Prep C18 OBD 5 um 19×100 mm column; 45-90% acetonitrile in 0.1% formic acid in water gradient) to afford the title compound. LC/MS (m/z): 467.2 (M+H)+. GPR119 Human EC50: 0.40 nM.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([NH2:12])[S:11][C:7]=2[C:6]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:5][CH:4]=1.C1([O:25][C:26]([C:28]2[N:29]([CH3:39])[C:30]([CH2:33][N:34]3[CH2:38][CH2:37][CH2:36][CH2:35]3)=[N:31][CH:32]=2)=O)C=CC=CC=1>>[CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([NH:12][C:26]([C:28]3[N:29]([CH3:39])[C:30]([CH2:33][N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)=[N:31][CH:32]=3)=[O:25])[S:11][C:7]=2[C:6]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:5][CH:4]=1
Reactant: COc1ccc(N2CCOCC2)c2sc(N)nc12
Reactant: Cn1c(C(=O)Oc2ccccc2)cnc1CN1CCCC1
Product: COc1ccc(N2CCOCC2)c2sc(NC(=O)c3cnc(CN4CCCC4)n3C)nc12

Procedure:
Using 4-methoxy-7-morpholin-4-yl-benzothiazol-2-ylamine and 3-methyl-2-pyrrolidin-1-ylmethyl-3H-imidazole-4-carboxylic acid phenyl ester, the title compound was obtained as off-white solid (76% yield). MS: m/e=457(M+H+), mp 255° C.
Reaction SMILES: C([O:3][C:4]([C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([CH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:7]1)=[O:5])C.[OH-].[Na+].CC(C)=O.[ClH:29]>C(O)C.O>[ClH:29].[O:16]([CH2:15][CH2:14][CH2:13][CH2:12][N:8]1[CH2:9][CH2:10][CH2:11][C@@H:6]([C:4]([OH:5])=[O:3])[CH2:7]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: CCOC(=O)[C@@H]1CCCN(CCCCOc2ccccc2)C1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Solvent: O
Solvent: CCO
Product: O=C(O)[C@@H]1CCCN(CCCCOc2ccccc2)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The above ester (3.5 g, 11.5 mmol) was dissolved in ethanol (35 ml) and 4N sodium hydroxide (5.7 ml) was added. The mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with water and 4M hydrochloric acid (11.5 ml) was added. The mixture was concentrated in vacuo and dichloromethane (50 ml) and acetone were added to the residue. The mixture was concentrated in vacuo to give a residue which was heated at reflux with acetone (700 ml). The mixture was filtered while still hot and the filtrate was left for crystallisation. The solid which formed was isolated by filtration and dried to give 1.9 g of the title compound as a solid.
Reaction SMILES: [F:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10](=[O:17])[NH:9][N:8]=2)=[CH:4][C:3]=1[N:20]=[C:21]=[O:22].C[O:24][C:25](=O)[CH:26]([NH:28][CH2:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH3:27]>C(Cl)Cl>[C:33]([O:32][C:30](=[O:31])[CH2:29][N:28]1[CH:26]([CH3:27])[C:25](=[O:24])[N:20]([C:3]2[CH:4]=[C:5]([CH2:6][C:7]3[C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[C:10](=[O:17])[NH:9][N:8]=3)[CH:18]=[CH:19][C:2]=2[F:1])[C:21]1=[O:22])([CH3:35])([CH3:34])[CH3:36]
Reactant: COC(=O)C(C)NCC(=O)OC(C)(C)C
Reactant: O=C=Nc1cc(Cc2n[nH]c(=O)c3ccccc23)ccc1F
Solvent: ClCCl
Product: CC1C(=O)N(c2cc(Cc3n[nH]c(=O)c4ccccc34)ccc2F)C(=O)N1CC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To a suspension of 4-(3-isocyanato-benzyl)-2H-phthalazin-1-one (2)(3.12 mmol) in dry DCM (80 ml) in the presence of activated 4 Å molecular sieves (ca 5 g) was added 2-(tert-butoxycarbonylmethyl-amino)-propionic acid methyl ester (33A)(1.07 g, 4.7 mmol). The reaction was then stirred for 48 hours at ambient temperature. HPLC analysis showed there to a mixture of cyclised and uncyclised ureas 1:1 ratio. The mixture was filtered and concentrated in vacuo. The crude oil was then subjected to flash chromatography eluent: 1:1 hexane ethyl acetate, Rf=0.09. Single peak in LC-MS analysis, (1.3 g, 95% purity) and required no further purification; m/z (LC-MS, ESP), RT=3.66 mins (M+H) 481—compound cyclised on column
Reaction SMILES: O.[N+:2]([C:5]1[CH:6]=[C:7]([C:15]([OH:17])=O)[C:8]2[O:13][CH2:12][CH2:11][O:10][C:9]=2[CH:14]=1)([O-:4])=[O:3].CC(C)=O.[CH3:22][N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>C(N(CC)CC)C>[CH3:22][N:23]1[CH2:28][CH2:27][N:26]([C:15]([C:7]2[C:8]3[O:13][CH2:12][CH2:11][O:10][C:9]=3[CH:14]=[C:5]([N+:2]([O-:4])=[O:3])[CH:6]=2)=[O:17])[CH2:25][CH2:24]1
Reactant: CN1CCNCC1
Reactant: O=C(O)c1cc([N+](=O)[O-])cc2c1OCCO2
Solvent: CCN(CC)CC
Solvent: CC(C)=O
Solvent: O
Product: CN1CCN(C(=O)c2cc([N+](=O)[O-])cc3c2OCCO3)CC1
Temperature: 10 °C
Yield: 66.8 %

Procedure:
22 ml of water, 22.5 g of 7-nitro-1,4-benzodioxane-5-carboxylic acid, 65 ml of acetone and 10.5 g of triethylamine were introduced into a 250 ml balloon flask provided with an agitator and a thermometer. The mixture was cooled to 10° C. and then 14 g of isobutyl chloroformiate was added. The mixture was agitated and the temperature allowed to rise. The oily compound formed was cooled to 10° C., 11 g of N-methyl piperazine was added and then the mixture was agitated, allowing the temperature to rise. The crystals formed were washed with water. 20.5 g of 5-[(4-methyl-1-piperazinyl)-carbonyl]-7-nitro-1,4-benzodioxane was produced (M.P.: 218° C.; yield: 66.7%).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:10])[CH3:9].B1(C)OC(C2C=CC=CC=2)(C2C=CC=CC=2)[C@@H]2N1CCC2>>[C:3]1([C@@H:8]([OH:10])[CH3:9])[CH:4]=[CH:5][CH:6]=[CH:7][CH:2]=1
Reactant: CC(=O)c1ccccc1Cl
Agent: CB1OC(c2ccccc2)(c2ccccc2)[C@H]2CCCN12
Product: C[C@H](O)c1ccccc1

Procedure:
2′-Chloroacetophenone and (R)-(+)-2-methyl-CBS-oxazaborolidine were reacted as described in Example 35, Step 1 to provide (S)-1-phenyl-ethanol.
Reaction SMILES: [N:1]1([CH2:6][C:7]2[CH:12]=[CH:11][C:10]([NH:13][CH2:14][C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)=[C:9]([N+:21]([O-])=O)[CH:8]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.S1C=CC=C1.[H][H]>CO.[Pt]>[N:1]1([CH2:6][C:7]2[CH:8]=[C:9]([NH2:21])[C:10]([NH:13][CH2:14][C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)=[CH:11][CH:12]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: O=[N+]([O-])c1cc(Cn2ccnc2)ccc1NCc1cccnc1
Reactant: [H][H]
Agent: [Pt]
Solvent: CO
Solvent: c1ccsc1
Product: Nc1cc(Cn2ccnc2)ccc1NCc1cccnc1
Yield: 100 %

Procedure:
(b-1) A mixture of 6.2 parts of N-[4-(1H-imidazol-1-ylmethyl)-2-nitrophenyl]-3-pyridinemethanamine, 1 part of a solution of thiophene in methanol 4% and 200 parts of methanol was hydrogenated at normal pressure and at 50° C. with 2 parts of platinum-on-charcoal catalyst 5%. After the calculated amount of hydrogen was taken up, the catalyst was filtered off and the filtrate was evaporated, yielding 5.6 parts (100%) of 4-(1H-imidazol-1-ylmethyl)-N1 -(3-pyridinylmethyl)-1,2-benzenediamine as a residue (int. 80).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[CH:14]=[N:15][OH:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:17]N1C(=O)CCC1=O>CN(C=O)C.C(OCC)(=O)C>[Cl:17][C:14](=[N:15][OH:16])[C@H:9]1[CH2:10][CH2:11][CH2:12][CH2:13][N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7]
Reactant: O=C1CCC(=O)N1Cl
Reactant: CC(C)(C)OC(=O)N1CCCC[C@@H]1C=NO
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCCC[C@@H]1C(Cl)=NO
Reaction time: 1 h
Yield: 86.1 %

Procedure:
To the title compound of Example 3.1 (3.1 g, 13.7 mmol) in DMF (30 mL) at 40° C. was added N-chlorosuccinimide (2.0 g, 15.1 mmol) in 3 portions. After stirring for 1 hour, the reaction mixture was diluted with ethyl acetate and then the organic layer washed with water (3 times) and brine, dried over anhydrous Na2SO4, filtered and concentrated to give the title product (3.1 g, 85%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][CH2:9][CH2:10][C:11]([O:13]CC)=[O:12].[OH-].[Na+]>C(O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12]
Reactant: CCOC(=O)CCCCc1ccccn1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)CCCCc1ccccn1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 81.1 %

Procedure:
Ethyl 5-(2-pyridyl)valerate (3.6 g, 17.2 mmol) was dissolved in ethanol (12 ml), and 2 M aqueous sodium hydroxide solution (12.9 ml, 25.8 mmol) was added thereto. The reaction mixture was stirred at room temperature for 1.5 hrs. The solvent was evaporated, and the residue was combined with ethanol and filtered to remove the insolubles. The filtrate was concentrated to give the titled compound (2.5 g, 82%)
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6](Cl)[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[C:12]1([S:18]([O-:20])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[Na+].CN(C)C=O>O>[NH2:1][C:2]1[CH:7]=[C:6]([S:18]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)(=[O:20])=[O:19])[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10]
Reactant: Nc1cc(Cl)ccc1[N+](=O)[O-]
Reactant: O=S([O-])c1ccccc1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Nc1cc(S(=O)(=O)c2ccccc2)ccc1[N+](=O)[O-]

Procedure:
2.0 g. of 2 amino-4-chloro-1-nitrobenzene and 5.0 g. sodium benzene-sulfinate in 20 ml. dimethylformamide is heated at reflux for 3 hours. The mixture is cooled, diluted with water and the product filtered off to give 2-amino-1-nitro-4-phenylsulfonylbenzene.
Reaction SMILES: ClC(Cl)(Cl)COC(=O)C([N:8]1[C@H:11]([S:12][C:13](=[O:15])[CH3:14])[C@@H:10]([O:16][CH3:17])[C:9]1=[O:18])=O>CO.C(OC)(=O)C.O>[C:13]([S:12][C@H:11]1[NH:8][C:9](=[O:18])[C@@H:10]1[O:16][CH3:17])(=[O:15])[CH3:14]
Reactant: CO[C@H]1C(=O)N(C(=O)C(=O)OCC(Cl)(Cl)Cl)[C@@H]1SC(C)=O
Solvent: CO
Solvent: COC(C)=O
Solvent: O
Product: CO[C@H]1C(=O)N[C@@H]1SC(C)=O

Procedure:
A solution of 1.52 g of 2-[(3S,4R)-4-acetylthio-3-methoxy-2-oxoazetidin-1-yl]-2-oxoacetic acid 2,2,2-trichloroethyl ester (crude product) in 290 ml of methanol, 40 ml of methyl acetate and 5.9 ml of water is refluxed for 20 minutes under nitrogen. The solvent is evaporated off in vacuo. After chromatography over silica gel with toluene/ethyl acetate (3:1) the residue yields the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]=[C:5]2[OH:13].[N+:14]([O-])([OH:16])=[O:15]>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[C:6]([N+:14]([O-:16])=[O:15])=[C:5]2[OH:13]
Reactant: O=c1cc(O)c2cc(Br)ccc2[nH]1
Reactant: O=[N+]([O-])O
Solvent: CC(=O)O
Product: O=c1[nH]c2ccc(Br)cc2c(O)c1[N+](=O)[O-]
Temperature: 100 °C

Procedure:
A suspension of 6-bromo-4-hydroxycarbostyril (2.23g; 0.0093 mole) in glacial acetic acid (15 ml) was swirled during the addition of concentrated nitric acid (2.5 ml, d, 1.42). On heating at 100°C for several minutes a thick yellow solid separated. After cooling, ethanol (40 ml) was added and the mixture filtered and the solid washed free of nitric acid with ethanol. Drying in vacuo over P2O5 gave the title compound, m.p. 213°-4°C (d). (Found; C, 37.83; H, 1.74; N, 9.77; Br, 28.33; C9H5N2BrO4 requires; C, 37.92; H, 1.77; N, 9.83; Br, 28.03%).
Reaction SMILES: O=C[C@@H]([C@H]([C@@H](CO)O)O)O.[CH2:11]([OH:33])[C@H:12]1[O:17][C@@H:16]([O:18][C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H:15]([OH:30])[C@@H:14]([OH:31])[C@@H:13]1[OH:32]>C(O)C>[O:18]=[CH:16][C@@H:15]([C@H:14]([C@@H:13]([C@@H:12]([CH2:11][OH:33])[OH:17])[OH:32])[OH:31])[OH:30]
Reactant: OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O
Agent: O=C[C@H](O)[C@@H](O)[C@H](O)CO
Solvent: CCO
Product: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
When evaluated for growth on glucose, xylose, and cellobiose in 250-mL flasks, mutagenized strains 22-1-12 and 14-2-6 achieved the highest ethanol levels, productivities, and fermentation efficiencies on glucose, strains WT-2-1 and 22-1-1 performed slightly better than the other strains on cellobiose, and strains 14-2-6 and 22-1-12 performed best on xylose. However, compared to the results with glucose at 48 h (about 18 g/L ethanol), these strains produced only about 3 g/L with xylose at 96 h. Less than half the consumed xylose was converted to ethanol.
Reaction SMILES: FC(F)(F)C(OC(=O)C(F)(F)F)=O.CS(C)=O.[Si:18]([N:25]1[C@H:28]([CH2:29][C:30]([S:35][CH3:36])([S:33][CH3:34])[S:31][CH3:32])[CH:27]([CH:37]([OH:39])[CH3:38])[C:26]1=[O:40])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19].C(N(CC)CC)C>C(Cl)Cl>[Si:18]([N:25]1[C@H:28]([CH2:29][C:30]([S:35][CH3:36])([S:33][CH3:34])[S:31][CH3:32])[C@@H:27]([C:37](=[O:39])[CH3:38])[C:26]1=[O:40])([C:21]([CH3:23])([CH3:24])[CH3:22])([CH3:20])[CH3:19]
Reactant: CSC(C[C@@H]1C(C(C)O)C(=O)N1[Si](C)(C)C(C)(C)C)(SC)SC
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CSC(C[C@@H]1[C@@H](C(C)=O)C(=O)N1[Si](C)(C)C(C)(C)C)(SC)SC
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
Trifluoroacetic anhydride (400 mg., 1.905 mmol) is added by syringe to a solution of dimethyl sulfoxide (2.53 mmol) in dry methylene chloride (5 ml) at -78° C. The resulting mixture is stirred at -78° C. for 30 minutes prior to the addition of a solution of (3RS,4R)-1-(t-butyldimethylsilyl)-3-[(RS)-1-hydroxyethyl]-4-[2,2,2-tri(methylthio)ethyl]azetidin-2-one (500 mg., 1.27 mmol) in dry CH2 cl2 (1 ml). The resulting solution is stirred for 30 minutes prior to the addition of triethylamine (360 mg., 3.56 mmol). The cooling bath is removed. After 40 minutes, the reaction mixture is diluted with CH2Cl2, washed with water and brine and dried over magnesium sulfate. Removal of solvents in vacuo gives an oil which is purified as above. Yields 432 mg. (86%).
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[C:13]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)=[C:12]([CH3:21])[C:11]([CH:22]2[O:27][CH2:26][CH2:25][NH:24][CH2:23]2)=[N:10]1.C(N(CC)CC)C.[CH:35]([S:38](Cl)(=[O:40])=[O:39])([CH3:37])[CH3:36]>ClCCl>[Cl:20][C:17]1[CH:16]=[CH:15][C:14]([C:13]2[N:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[Cl:2])[N:10]=[C:11]([CH:22]3[O:27][CH2:26][CH2:25][N:24]([S:38]([CH:35]([CH3:37])[CH3:36])(=[O:40])=[O:39])[CH2:23]3)[C:12]=2[CH3:21])=[CH:19][CH:18]=1
Reactant: Cc1c(C2CNCCO2)nn(-c2ccccc2Cl)c1-c1ccc(Cl)cc1
Reactant: CC(C)S(=O)(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1c(C2CN(S(=O)(=O)C(C)C)CCO2)nn(-c2ccccc2Cl)c1-c1ccc(Cl)cc1
Reaction time: 18 h

Procedure:
To a stirred suspension of 2-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazol-3-yl]-morpholine hydrochloride 5A-2 (75 mg, 0.18 mmol) and triethylamine (49 μL, 0.36 mmol) in dichloromethane (0.5 ml) was added isopropylsulfonyl chloride (0.22 μL 0.2 mmol) dropwise. After stirring for 18 h, the reaction was partitioned between ethyl acetate and saturated sodium bicarbonate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by chromatography (silica, 40–50% ethyl acetate/hexanes) to give the title compound 6A-1 as a colorless foam (49 mg).
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.N1C=CC=CC=1.C(Cl)(Cl)(Cl)Cl.[C:22](Cl)(=[O:31])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]>O>[CH2:23]([C:22]([O:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1)=[O:31])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]
Reactant: CCCCCCCCC(=O)Cl
Reactant: O=C(O)c1ccc(O)cc1
Solvent: c1ccncc1
Solvent: ClC(Cl)(Cl)Cl
Solvent: O
Product: CCCCCCCCC(=O)Oc1ccc(C(=O)O)cc1

Procedure:
Four point five grams of 4-hydroxy benzoic acid were dissolved with a mixed solvent of 5 ml of pyridine and 30 ml of carbon tetrachloride. 3.7 g of nonanic acid chloride was dropped into the mixture solution with refluxing for three hours, a small amount of water was added to the residue removed the solvent from the refluxing solution to decompose unreacted nonanic chloride. Then 4-octylcarbonyloxy benzoic acid (C) was obtained after washing methanol. (C) was dispersed in 20 ml of carbon tetrachloride, after adding 5 ml of thionyl chloride, the mixture was refluxed for three hours to obtain 6.5 g of 4-octylcarbonyloxybenzoic acid chloride. 1.5 g of (D) was dissolved with 80 ml of carbon tetrachloride and 10 ml of pyridine and then cooled, 1.7 g of (B) was added to this solution with stirring under ice-cooled condition and the mixture was allowed to stand overnight to precipitate crystals. Following separation of produced crystals and reduction of solvents, the residue was purified by passing through a silica-gel column to obtain crude crystals of (A). Crude (A) was recrystallized with ethyl acetate. Purified (A) was smectic liquid crystal compound having SC* phase. The phase transition points of (A) were shown in table 4. (A) showed a large spontaneous polarization up to 109 nC/cm2 by Sawyer-Tower method described in example 1. When applied a voltage with a square wave to (A), electro-photo-effects of clear contrast and high speed response were observed.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH2:10][CH:11]=C.[F-].[Cs+].Cl.[C:16](OCC)(=O)C>C(N(CC)C1C=CC=CC=1)C>[CH3:1][O:2][C:3]1[C:4]2[O:9][C:10]([CH3:11])=[CH:16][C:5]=2[CH:6]=[CH:7][CH:8]=1
Reactant: C=CCOc1ccccc1OC
Reactant: CCOC(C)=O
Agent: Cl
Agent: [Cs+]
Agent: [F-]
Solvent: CCN(CC)c1ccccc1
Product: COc1cccc2cc(C)oc12
Temperature: 217.5 °C

Procedure:
To a well stirred solution of 1-methoxy-2-(2-propenyloxy)benzene (from step 1) (13.0 g, 80.24 mmol) in N,N-diethyl aniline (130 mL) was added cesium fluoride (15.85 g, 104 mmol) and the mixture was heated to 215-220° C. for 4-5 hours. Reaction mixture was cooled to room temperature and 10% aqueous HCl solution (1.0 lit) was added followed by addition of ethyl acetate (300 mL). The mixture was the filtered through Celite bed. The organic layer was separated and washed with water (2×100 mL) and dried over anhydrous sodium sulfate. Removal of solvent under vacuo gave crude product (11.0 g) as dark brown oil. It was then purified through silica gel column using petroleum ether: ethyl acetate (9:1) as an eluent to afford the product as pale yellow oil (4.6 g).
Reaction SMILES: [O:1]([CH:9]1[CH2:13][C:12](=[O:14])[C:11]([S:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[CH:10]1)[Si](C(C)(C)C)(C)C.C(=O)(O)[O-].[Na+]>C(O)(=O)C.O.O1CCCC1>[OH:1][CH:9]1[CH2:13][C:12](=[O:14])[C:11]([S:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[CH:10]1
Reactant: CCCCCCCCSC1=CC(O[Si](C)(C)C(C)(C)C)CC1=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: O
Product: CCCCCCCCSC1=CC(O)CC1=O
Yield: 78.5 %

Procedure:
4-t-Butyldimethylsiloxy-2-n-octylthiocyclopent-2-en-1-one (90 mg) was dissolved in 5 ml of a mixture of acetic acid, water and tetrahydrofuran in a ratio of 3:1:1, and reacted at room temperature for 48 hours. The reaction mixture was neutralized with sodium bicarbonate, and extracted with ethyl acetate. The extract was treated by conventional methods, and chromatographed on a thin layer plate with cyclohexane/ethyl acetate (4/6) to afford 48 mg of 4-hydroxy-2-n-octylthiocyclopent-2-en-1-one in a yield of 84% showing a single spot. The resulting product had the following characteristics.