Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[O:15][C:14]([NH2:16])=[N:13][N:12]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.[F:17][C:18]([F:41])([F:40])[C:19]1[CH:39]=[CH:38][C:22]([CH2:23][C@H:24]2[CH2:28]OS(=O)(=O)[N:25]2[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])=[CH:21][CH:20]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[O:15][C:14]([NH:16][CH2:28][C@@H:24]([NH:25][C:31](=[O:32])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:23][C:22]4[CH:38]=[CH:39][C:19]([C:18]([F:41])([F:40])[F:17])=[CH:20][CH:21]=4)=[N:13][N:12]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1
Reactant: CC(C)(C)OC(=O)N1[C@@H](Cc2ccc(C(F)(F)F)cc2)COS1(=O)=O
Reactant: Nc1nnc(-c2ccc3cnccc3c2)o1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N[C@H](CNc1nnc(-c2ccc3cnccc3c2)o1)Cc1ccc(C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 20 %

Procedure:
5-(Isoquinolin-6-yl)-1,3,4-oxadiazol-2-amine (0.083 g, 0.39 mmol) was mixed with (S)-tert-Butyl 4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate-2,2-dioxide (0.15 g, 0.39 mmol) and Cs2CO3 (0.381 g, 1.17 mmol) in 2 mL DMF. The mixture was stirred at room temperature for 3 hours, then at 60° C. for 1 hour. After removing the DMF at a reduced pressure, the remaining residue was treated with 1N HCl for 30 minutes. It was then partitioned between EtOAc and saturated aqueous ammonium chloride. The EtOAc solution was washed twice with saturated aqueous ammonium chloride and dried over sodium sulfate. After removing the EtOAc, the remaining residue was subjected to a silica gel column using 70% EtOAc in hexane as the eluant. A white solid was obtained as the desired product (0.040 g, 20%). LCMS (API-ES) m/z (%): 514.0 (100%, M++H).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.C(NC(C)C)(C)C.[C:35]1([CH2:41][C:42]([O:44][CH3:45])=[O:43])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[Cl-].[NH4+]>C1COCC1>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13](=[O:15])[CH:41]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:42]([O:44][CH3:45])=[O:43])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)NCCCCC(=O)O
Reactant: COC(=O)Cc1ccccc1
Agent: O=C(n1ccnc1)n1ccnc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: COC(=O)C(C(=O)CCCCNC(=O)OC(C)(C)C)c1ccccc1
Yield: 95.7 %

Procedure:
The target compound was prepared as a pale yellow oil in an amount 7.7 g at a yield of 95.7% in the same manner as in Example 1 except that 5.0 g (23 mmol) of 5-(N-t-butoxycarbonylamino)pentanoic acid instead of 5-(N-benzyloxycarbonylamino)pentanoic acid was dissolved in 25 ml of THF and 4.1 g (25.3 mmol) of CDI was added; 9.05 ml (69 mmol) of diisopropylamine and 25 ml of THF were added and 42 ml (69 mmol) of 1.63N BA solution was added dropwise; 10.4 g (69 mmol) of methyl phenylacetate was dissolved in 25 ml of THF; and 30 ml of saturated aqueous ammonium chloride solution was added to the reaction solution, the reaction was terminated, 50 g of 4N hydrochloric acid was added, and 100 ml of ethyl acetate was further added. The analytical results on the target compound are given below.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:13][CH2:12][NH:11][C:10]2=[CH:14][N+:15]([O-:17])=[O:16])=[CH:4][N:3]=1.[CH:18](=[O:23])[CH2:19][CH2:20][CH:21]=O.Cl>C(#N)C>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([CH2:8][N:9]2[C:10]3=[C:14]([N+:15]([O-:17])=[O:16])[CH:21]4[O:23][CH:18]([N:11]3[CH2:12][CH2:13]2)[CH2:19][CH2:20]4)=[CH:6][CH:7]=1
Reactant: O=[N+]([O-])C=C1NCCN1Cc1ccc(Cl)nc1
Reactant: O=CCCC=O
Agent: Cl
Solvent: CC#N
Product: O=[N+]([O-])C1=C2N(Cc3ccc(Cl)nc3)CCN2C2CCC1O2
Temperature: 25 °C
Yield: 71 %

Procedure:
To a 50 ml round bottom flask was added 1.27 g (0.005 mol) 2-chloro-5-((2-(nitromethylene)imidazolidin-1-yl)methyl)pyridine, 30 ml dry acetonitrile, 0.860 g (0.01 mol) succinaldehyde and catalytic concentrated HCl. The reaction was stirred at r.t. and monitored by TLC. After completion, the mixture was evaporated to remove solvent and purified by column chromatography to afford final product as faint yellow powder with 71% yield.
Reaction SMILES: S(OC(C)C#C)([C:4]1[CH:10]=CC(C)=[CH:6][CH:5]=1)(=O)=O.[CH3:16][C:17]1[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[C:18]=1[NH2:19]>>[CH3:6][CH:5]([NH:19][C:18]1[C:20]([CH3:24])=[CH:21][CH:22]=[CH:23][C:17]=1[CH3:16])[C:4]#[CH:10]
Reactant: Cc1cccc(C)c1N
Reactant: C#CC(C)OS(=O)(=O)c1ccc(C)cc1
Product: C#CC(C)Nc1c(C)cccc1C
Temperature: 0 °C

Procedure:
22.4 g of 1-butyn-3-ol tosylate in 26 g of 2,6-dimethylaniline are stirred at 110° C. for 3 hours. The mixture is then poured into ice-water, extracted with ethyl acetate, dried over sodium sulfate and filtered. The solvent is distilled off to yield N-(1-methyl-2-propynyl)-2,6-xylidine; b.p. 68°-72° C./0.05 Torr; m.p. 32°-33° C.
Reaction SMILES: [N:1]1([S:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=2)(=[O:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29]1[N:30]=[C:31]([NH2:34])[S:32][CH:33]=1>>[N:1]1([S:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH:34][C:31]3[S:32][CH:33]=[C:29]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=4)[N:30]=3)=[O:20])=[CH:16][CH:15]=2)(=[O:12])=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1
Reactant: Nc1nc(-c2ccccn2)cs1
Reactant: O=C(O)c1ccc(S(=O)(=O)N2CCCc3ccccc32)cc1
Product: O=C(Nc1nc(-c2ccccn2)cs1)c1ccc(S(=O)(=O)N2CCCc3ccccc32)cc1

Procedure:
4-(3,4-dihydroquinolin-1(2H)-ylsulfonyl)benzoic acid (1) (400 mg, 1.26 mmol) was treated with 4-(pyridin-2-yl)thiazol-2-amine (290 mg, 1.64 mmol) using method C. The residue was purified using flash chromatography eluting with 50-100% EtOAc in hexanes to give 4-(3,4-dihydroquinolin-1(2H)-ylsulfonyl)-N-(4-(pyridin-2-yl)thiazol-2-yl)benzamide as an off-white solid. Yield: 235 mg (39%). 1H-NMR: 8.63-8.60 (m, 1H), 8.21 (d, J=8.5 Hz, 2H), 8.00 (d, J=8.0 Hz, 7.93-7.88 (m, 2H), 7.76 (d, J=8.5 Hz, 2H), 7.61 (d, J=8.0 Hz, 1H), 7.35 (ddd, J=7.5, 5.0, 1.0 Hz, 1H), 7.24-7.19 (m, 1H), 7.14-7.08 (m, 2H), 3.84-3.79 (m, 2H), 2.93 (t, J=8.5 Hz, 2H). 2.45 (t, J=6.5 Hz, 2H), 1.66-1.58 (m, 2H).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][C:5]1[S:9][C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:7][C:6]=1[C:16](Cl)=[O:17].CCN(C(C)C)C(C)C.[N:28]1[C:36]2[C:31](=[N:32][CH:33]=[CH:34][CH:35]=2)[S:30][C:29]=1[C:37]1[CH:43]=[CH:42][CH:41]=[CH:40][C:38]=1[NH2:39]>CC#N>[Cl:1][CH2:2][CH2:3][CH2:4][C:5]1[S:9][C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:7][C:6]=1[C:16]([NH:39][C:38]1[CH:40]=[CH:41][CH:42]=[CH:43][C:37]=1[C:29]1[S:30][C:31]2[C:36]([N:28]=1)=[CH:35][CH:34]=[CH:33][N:32]=2)=[O:17]
Reactant: O=C(Cl)c1nc(-c2ccccc2)sc1CCCCl
Reactant: Nc1ccccc1-c1nc2cccnc2s1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: O=C(Nc1ccccc1-c1nc2cccnc2s1)c1nc(-c2ccccc2)sc1CCCCl
Reaction time: 16 h
Yield: 26 %

Procedure:
A suspension of 5-(3-chloropropyl)-2-phenylthiazole-4-carbonyl chloride (906 mg, 3.2 mmol), DIPEA (1.1 mL, 6.4 mmol), and 2-(thiazolo[5,4-b]pyridin-2-yl)aniline b (585 mg, 2.6 mmol) in CH3CN (12 mL) was stirred for 16 h. The resulting ppt was collected by filtration, rinsed with CH3CN and dried. The crude product was purified by MPLC eluting with DCM/MeOH (0-5% gradient) to give 5-(3-chloropropyl)-2-phenyl-N-(2-(thiazolo[5,4-b]pyridin-2-yl)phenyl)thiazole-4-carboxamide (316 mg, 26% yield).
Reaction SMILES: [OH:1][C@@H:2]([C@H:4]1[C:10](=[O:11])[N:9]2[C@@H:5]1[C@@H:6]([CH3:54])[C:7]([S:25][C@@H:26]1[CH2:30][N:29]([C:31]([O:33][CH2:34][C:35]3[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=3)=[O:32])[C@H:28]([CH2:44][N:45]3[CH2:50][CH2:49][CH2:48][N:47]4[N:51]=[CH:52][CH:53]=[C:46]34)[CH2:27]1)=[C:8]2[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=1)=[O:13])[CH3:3].[CH3:55][I:56]>CC(C)=O.O1CCCC1>[I-:56].[OH:1][C@@H:2]([C@H:4]1[C:10](=[O:11])[N:9]2[C@@H:5]1[C@@H:6]([CH3:54])[C:7]([S:25][C@@H:26]1[CH2:30][N:29]([C:31]([O:33][CH2:34][C:35]3[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=3)=[O:32])[C@H:28]([CH2:44][NH+:45]3[CH2:50][CH2:49][CH2:48][N:47]4[N:51]([CH3:55])[CH2:52][CH:53]=[C:46]34)[CH2:27]1)=[C:8]2[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=1)=[O:13])[CH3:3]
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](CN4CCCn5nccc54)N(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)[C@H](C)[C@H]12
Reactant: CI
Solvent: CC(C)=O
Solvent: C1CCOC1
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](C[NH+]4CCCN5C4=CCN5C)N(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)[C@H](C)[C@H]12
Product: [I-]
Reaction time: 8 h

Procedure:
To a solution of 4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(2S,4S)-1-(4-nitrobenzyloxycarbonyl) -2-{4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-4yl}methylpyrrolidin-4-yl]thio-7-oxo-1-azabicyclo[3.2.0]-hept-2-ene-2-carboxylate (0.78 g) in a mixture of acetone (8 ml) and tetrahydrofuran (16 ml) was added methyl iodide (0.64 ml) with stirring and the mixture was allowed to stand at ambient temperature overnight. The reaction mixture was evaporated in vacuo to give 4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(2S,4S)-1-(4-nitro benzyloxycarbonyl)-2-{1-methyl-4,5,6,7-tetrahydro-4-pyrazolo [1,5-a]primidinio}methylpyrrolidin-4yl]thio-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate iodide (0.88 g).
Reaction SMILES: [CH2:1](Br)[CH:2]=[CH2:3].C([Mg]Br)(C)C.[CH:10](=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.Cl>C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C.C(OCC)C>[C:11]1([CH:10]([OH:17])[CH2:3][CH:2]=[CH2:1])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: C=CCBr
Reactant: O=Cc1ccccc1
Agent: CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C
Agent: CC(C)[Mg]Br
Agent: Cl
Solvent: CCOCC
Product: C=CCC(O)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 93.5 %

Procedure:
To 0.30 ml (1.0 mmol) of tetraisopropoxytitanium and 5 ml of ethyl ether solution containing allyl bromide (1.0 mmol) was added dropwise at −50° C. 1.67 ml of 1.2M ethyl ether solution containing isopropylmagnesium bromide (2.0 mmol). Upon stirring at −50° C. to −40° C. for 1 hour, the reaction liquid turned from yellow into brown. To the reaction liquid was added 0.071 ml (0.7 mmol) of benzaldehyde at −45° C. to −40° C. The temperature was raised to −10° C. to 0° C. over 30 minutes. With 5 ml of 1N hydrochloric acid added, the solution was heated to room temperature and separated into layers. The organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate. After drying with anhydrous magnesium sulfate, the solution was freed of solvent by vacuum distillation. The residues were purified by silica gel chromatography. Thus there was obtained 97 mg of 1-phenyl-3-buten-1-ol (94% yields based on benzaldehyde).
Reaction SMILES: [O:1]1[CH:6]=[CH:5][CH2:4][CH2:3][CH2:2]1.[CH2:7]([OH:10])[CH2:8][OH:9].C(Cl)Cl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[O:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]1[CH:7]([OH:10])[CH2:8][OH:9]
Reactant: OCCO
Reactant: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: O
Product: OCC(O)C1CCCCO1
Temperature: 25 °C
Reaction time: 2 h
Yield: 33.2 %

Procedure:
Dihydropyran (18.25 mL, 200 mmol) was added dropwise to a cold (0° ) mixture of ethylene glycol (55.92 mL, 1 mol) in 500 mL CH2Cl2 containing 3.8 g (20 mmol) of dissolved p-toluene sulfonic acid monohydrate over 2 hrs. The mixture was allowed to stir for an additional 2 hrs at this temperature, and then was allowed to warm to rt. Stirring continued for 2 days, after which the mixture was poured into a separating funnel and allowed to separate. The lower organic layer was removed and saved, and the upper layer was extracted with 100 mL CH2Cl2. The combined CH2Cl2 layers were washed six times with 100 mL portions of sat'd NaCl, and dried over Na2SO4. The solution was filtered and reduced, and the residue was purified by chromatography with the same silica as above. The column was eluted isocratically with 3:2 EtOAc:hexane which contained 1% triethylamine (TEA). Fractions which contained pure product, rf 0.5 (using the same TLC system as above) were pooled and evaporated to give 9.7 g (33% yield) of a colorless oil. 1H NMR (300 mHz, CDCl3, PPM) 5.6-5.5, m, 1H. 4.0-3.9, m, 1H. 4.8-4.65, m, 4H. 3.6-3.5, m, 1H. 1.9-1.7, m, 2H. 1.65-1.5, m, 4H.
Reaction SMILES: [CH3:1][O:2][CH2:3][C@@H:4]1[O:8][C:7](=[O:9])[N:6]([C:10]2[CH:15]=[CH:14][C:13]([C@H:16]3[CH2:21][CH2:20][C@H:19]([O:22][CH2:23][S:24][CH3:25])[CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5]1.I([O-])(=O)(=O)=[O:27].[Na+]>CO.O>[CH3:25][S:24]([CH2:23][O:22][C@H:19]1[CH2:20][CH2:21][C@H:16]([C:13]2[CH:12]=[CH:11][C:10]([N:6]3[CH2:5][C@H:4]([CH2:3][O:2][CH3:1])[O:8][C:7]3=[O:9])=[CH:15][CH:14]=2)[CH2:17][CH2:18]1)=[O:27]
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: COC[C@H]1CN(c2ccc([C@H]3CC[C@H](OCSC)CC3)cc2)C(=O)O1
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COC[C@H]1CN(c2ccc([C@H]3CC[C@H](OCS(C)=O)CC3)cc2)C(=O)O1
Reaction time: 19 h

Procedure:
10.7 g (29.28 mmol) of (R)-5-methoxymethyl-3-[4-(trans-4-methylsulfanylmethoxy-cyclohexyl)-phenyl]-oxazolidin-2-one were dissolved in 500 ml of methanol, cooled to 0° and treated dropwise while stirring during 90 minutes with a solution of 4.7 g (22.0 mmol) of sodium periodate in 150 ml of water. The reaction mixture was stirred in a cold storage chamber at 4°-5° for 19 hours. Thereafter, it was diluted with 1 l of water and extracted with methylene chloride. The organic phase was washed with water, dried over sodium sulfate and filtered. The filtrate was filtered through a 400 g silica gel 60 pad and washed in succession and separately with ethyl acetate (800 ml), methanol (1 l) and tetrahydrofuran (800 ml). 3.16 g of educt remained behind after evaporation of the ethyl acetate eluate. After evaporation the methanol and tetrahydrofuran eluates gave 8.11 g of (R)-3-[4-(trans-4-methanesulfinylmethoxy-cyclohexyl)-phenyl]-5-methoxymethyl-oxazolidin-2-one (S-oxide R:S=1:1 diastereomer mixture) as a yellow oil, b.p. 205°/0.02 mbar, [α]D =-32.2° (c=1.0%, DMSO).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=O)=[CH:11][C:10]=1[O:17][CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:19]([CH2:21][C:22]([O:24][CH3:25])=[O:23])#[N:20]>N1CCCCC1>[CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=[C:21]([C:19]#[N:20])[C:22]([O:24][CH3:25])=[O:23])=[CH:11][C:10]=1[O:17][CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)CC#N
Reactant: COc1cc(C=O)ccc1OCc1ccccc1
Solvent: C1CCNCC1
Product: COC(=O)C(C#N)=Cc1ccc(OCc2ccccc2)c(OC)c1

Procedure:
A mixture of 4-(benzyloxy)-3-methoxybenzaldehyde (1.21 g, 0.005 mol), methyl cyanoacetate (0.50 g, 0.005 mol) methanol (10.0 mL) and piperidine (5 drops) is heated and stirred at reflux for 1 hour and cooled. The product, 3-(4-benzyloxy-3-methoxyphenyl)-2-cyano-2-propenoate is collected by filtration, washed with methanol and dried in air. The yield is 1.50 g (93%) of product having an absorption maximum at 364 nm in methylene chloride solution. The identity of the product is supported by mass spectrometry.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.Cl[C:24](Cl)([O:26][C:27](=[O:33])OC(Cl)(Cl)Cl)Cl.[CH:35]1([CH2:41]CO)[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(N(CC)CC)C.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:27](=[O:33])[O:26][CH2:24][CH2:41][CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]2)=[CH:18][CH:17]=1
Reactant: OCCC1CCCCC1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: COc1cc2nccc(Oc3ccc(NC(=O)OCCC4CCCCC4)cc3)c2cc1OC
Yield: 82.9 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-cyclohexyl-1-ethanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (63 mg, yield 76%).
Reaction SMILES: [CH3:1][Si:2]([CH3:9])([CH3:8])/[CH:3]=[CH:4]\[CH:5]([OH:7])[CH3:6].CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O.[Cr](O)(O)(=O)=O.S(=O)(=O)(O)O>O.CC(C)=O>[CH3:1][Si:2]([CH3:9])([CH3:8])/[CH:3]=[CH:4]/[C:5](=[O:7])[CH3:6]
Reactant: CC(O)/C=C\[Si](C)(C)C
Agent: O=[Cr](=O)(O)O
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)=O
Solvent: O
Product: CC(=O)/C=C/[Si](C)(C)C
Reaction time: 18 h

Procedure:
A solution of 174.6 parts by weight of cis-4-(trimethylsilyl)-3-buten-2-ol (III) in 2000 parts by volume of acetone is chilled to -10° C. and treated slowly with an excess (350 parts by volume) of Jones Reagent (a solution of chromic acid and sulfuric acid in water) while keeping the internal temperature below 10° C. The resulting precipitate is allowed to settle and the supernatant is decanted and concentrated on a rotary evaporator at 25° C. to remove much of the acetone. The precipitate is dissolved in water and the solution is extracted with ethyl ether. The ether extract is added to the acetone residue and the combined solutions are washed with water, then with 5% aqueous hydrochloric acid, and again with water. The ether extract is then dried over sodium sulfate and the ether removed by vacuum distillation. The residue is taken up in 500 parts by volume of isopropanol and 20 parts by volume of concentrated aqueous hydrochloric acid is added. The mixture is stored at room temperature for 18 hours then diluted with 1000 parts by volume of benzene and washed repeatedly with water. The washes are extracted with 500 parts by volume of benzene and dried over sodium sulfate to yield trans-4-(trimethylsilyl)-3-buten-2-one (IV) which has a boiling point of 165°-169° C. and is represented by the following structural formula ##STR10##
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[C:6]([C:9]([F:12])([F:11])[F:10])[C:5]([F:13])=[C:4]([F:14])[C:3]=1[N:15]1[C:19]([NH:20][C:21]([CH2:23][OH:24])=[O:22])=[C:18]([N+:25]([O-:27])=[O:26])[CH:17]=[N:16]1.C(N(CC)CC)C.[CH3:35][NH:36][S:37](Cl)(=[O:39])=[O:38]>C(Cl)Cl>[F:1][C:2]1[C:7]([F:8])=[C:6]([C:9]([F:12])([F:11])[F:10])[C:5]([F:13])=[C:4]([F:14])[C:3]=1[N:15]1[C:19]([NH:20][C:21]([CH2:23][O:24][S:37]([NH:36][CH3:35])(=[O:39])=[O:38])=[O:22])=[C:18]([N+:25]([O-:27])=[O:26])[CH:17]=[N:16]1
Reactant: O=C(CO)Nc1c([N+](=O)[O-])cnn1-c1c(F)c(F)c(C(F)(F)F)c(F)c1F
Reactant: CNS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CNS(=O)(=O)OCC(=O)Nc1c([N+](=O)[O-])cnn1-c1c(F)c(F)c(C(F)(F)F)c(F)c1F
Temperature: 25 °C
Reaction time: 4 h
Yield: 11.8 %

Procedure:
A stirred solution of 0.48 gram (0.0012 mole) of 1-(2,3,5,6-tetrafluoro-4-trifluoromethylphenyl)-5-hydroxymethylcarbonylamino-4-nitropyrazole and 0.27 gram (0.0027 mole) of triethylamine in 28.5 mL of methylene chloride was cooled in an ice-water bath. Methylaminosulfonyl chloride (0.55 gram, 0.0043 mole) was added dropwise, and the mixture was allowed to warm to room temperature and stir for four hours. The reaction mixture was filtered to remove a salt that had formed. The filtrate was extracted in succession with water, dilute hydrochloric acid, a saturated, aqueous sodium bicarbonate solution, and water. The organic phase was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure, leaving a brown oil. This oil was purified by column chromatography on silica gel, which was eluted with ethyl acetate: n-heptane (1:1) to yield an oil. This oil crystallized in methylene chloride and n-heptane to yield 0.07 gram of 1-(2,3,5,6-tetrafluoro-4-trifluoromethylphenyl)-5-methylaminosulfonyloxymethylcarbonylamino -4-nitropyrazole as an ivory-colored solid (Compound 21 of Table 1). The nmr spectrum was consistent with the proposed structure.
Reaction SMILES: [CH3:1][C:2]1([CH3:11])[CH2:7][CH:6]([C:8](O)=[O:9])[CH2:5][CH2:4][O:3]1.C(Cl)(=O)C([Cl:15])=O>C(Cl)Cl.CN(C=O)C>[CH3:1][C:2]1([CH3:11])[CH2:7][CH:6]([C:8]([Cl:15])=[O:9])[CH2:5][CH2:4][O:3]1
Reactant: CC1(C)CC(C(=O)O)CCO1
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC1(C)CC(C(=O)Cl)CCO1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 2,2-dimethyltetrahydro-2H-pyran-4-carboxylic acid (530 mg, 3.35 mmol) in 10 mL of DCM at 0° C. was added 1 drop of DMF followed by oxalyl chloride (0.33 mL, 3.69 mmol) and the reaction stirred at RT for 3 hrs. The reaction was then concentrated and used with out further purification.
Reaction SMILES: CS([C:4]1[N:9]=[C:8]([C:10]2[C:11]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([N+:25]([O-:27])=[O:26])[CH:20]=3)=[N:12][N:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=23)[CH:7]=[CH:6][N:5]=1)=O.[O:28]1[C:33]2[CH:34]=[CH:35][C:36]([NH2:38])=[CH:37][C:32]=2[O:31][CH2:30][CH2:29]1>C(O)C.Cl.C(Cl)Cl>[O:28]1[C:33]2[CH:34]=[CH:35][C:36]([NH:38][C:4]3[N:9]=[C:8]([C:10]4[C:11]([C:19]5[CH:24]=[CH:23][CH:22]=[C:21]([N+:25]([O-:27])=[O:26])[CH:20]=5)=[N:12][N:13]5[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=45)[CH:7]=[CH:6][N:5]=3)=[CH:37][C:32]=2[O:31][CH2:30][CH2:29]1
Reactant: CS(=O)c1nccc(-c2c(-c3cccc([N+](=O)[O-])c3)nn3ccccc23)n1
Reactant: Nc1ccc2c(c1)OCCO2
Agent: Cl
Solvent: CCO
Solvent: ClCCl
Product: O=[N+]([O-])c1cccc(-c2nn3ccccc3c2-c2ccnc(Nc3ccc4c(c3)OCCO4)n2)c1
Temperature: 160 °C
Yield: 67 %

Procedure:
To a solution of 3-[2-(methylsulfinyl)-4-pyrimidinyl]-2-(3-nitrophenyl)pyrazolo[1,5-a]pyridine (1.32 g, 3.49 mmol) in ethanol (4.0 mL) is added 1,4-benzodioxan-6-amine (0.56 mL, 4.54 mmol) and conc. HCl (3 drops). The dark mixture is heated in a microwave apparatus at 160° C. for 20 min. The mixture is monitored, and heated for an additional 10 min. The mixture is diluted with DCM and concentrated to a brown foam. The crude material is purified by silica gel chromatography (30-50% EtOAc/hexanes) to give the desired product (1.09 g). 1H NMR (400 MHz, d6-DMSO) δ 9.36 (s, 1H), 8.88 (d, 1H, J=6.8), 8.45 (s, 1H), 8.28-8.31 (m, 3H), 8.01-8.03 (m, 1H), 7.72 (t, 1H, J=8.0), 7.47-7.51 (m, 1H), 7.13-7.18 (m, 2H), 6.97-6.95 (m, 1H), 6.63-6.65 (m, 2H), 4.14 (m, 1H), 7.13-7.18 (m, 2H), 6.95-6.97 (m, 1H), 6.63-6.65 (m, 2H), 4.14 (s, 4H).