Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:15]1[CH:45]=[CH:44][C:18]([O:19][CH2:20][CH:21]([OH:43])[CH2:22][O:23][C:24]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:17][CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[H-].[Na+].I[CH3:49]>CN(C)C=O>[CH3:49][O:43][CH:21]([CH2:22][O:23][C:24]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[CH2:20][O:19][C:18]1[CH:17]=[CH:16][C:15]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])=[CH:45][CH:44]=1
Reactant: CI
Reactant: CCCCCCCCCCCCCCc1ccc(OCC(O)COC(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCc1ccc(OCC(COC(c2ccccc2)(c2ccccc2)c2ccccc2)OC)cc1
Reaction time: 2 h
Yield: 98.1 %

Procedure:
To a solution of about 558 mg of 1-(4-tetradecylphenoxy)-3-(triphenylmethoxy)-2-propanol in about 5 ml of dry dimethylformamide was added a prewashed suspension of about 66 mg of sodium hydride in about 2 ml of dimethylformamide followed by about 157 mg of iodomethane. The mixture was stirred under argon for about 2 hours, quenched slowly with water and extracted twice with ether:hexane (about 1:1). The extracts were combined, dried, and the solvents evaporated, giving about 560 mg of the desired title compound.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:49]2[CH:54]=[CH:53][C:52]([OH:55])=[CH:51][CH:50]=2)[CH2:9][NH:10][C:11]2[N:19]=[C:18](N3CC[C@@H](NC(NCC4C=CC=C(O)C=4)=O)C3)[N:17]=[C:16]3[C:12]=2[N:13]=[CH:14][N:15]3[C@@H:37]2[CH2:41][C@H:40]([NH:42]C(=O)CO)[C@@H:39]([OH:47])[C@H:38]2[OH:48])=[CH:4][CH:3]=1.[ClH:56]>CO.O1CCOCC1>[NH2:42][C@H:40]1[CH2:41][C@@H:37]([N:15]2[CH:14]=[N:13][C:12]3[C:16]2=[N:17][C:18]([Cl:56])=[N:19][C:11]=3[NH:10][CH2:9][CH:8]([C:49]2[CH:54]=[CH:53][C:52]([OH:55])=[CH:51][CH:50]=2)[C:5]2[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=2)[C@H:38]([OH:48])[C@@H:39]1[OH:47]
Reactant: O=C(CO)N[C@H]1C[C@@H](n2cnc3c(NCC(c4ccc(O)cc4)c4ccc(O)cc4)nc(N4CC[C@@H](NC(=O)NCc5cccc(O)c5)C4)nc32)[C@H](O)[C@@H]1O
Reactant: Cl
Solvent: CO
Solvent: C1COCCO1
Product: N[C@H]1C[C@@H](n2cnc3c(NCC(c4ccc(O)cc4)c4ccc(O)cc4)nc(Cl)nc32)[C@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of Example 7 step 1 (3.45 g, 5.80 mmol) in methanol (7 ml) is treated with 4M HCl in dioxane (3 ml) and the reaction mixture is stirred at room temperature overnight. The solvent is removed in vacuo and the residue is partitioned between saturated sodium bicarbonate solution and DCM. The organic portion is separated, dried (MgSO4) and concentrated in vacuo to afford the title compound.
Reaction SMILES: C[O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[N:5]=1.[OH-].[Na+].Cl>C(O)C>[CH3:11][O:10][C:7]1[CH:8]=[CH:9][C:4]([C:3]([OH:23])=[O:2])=[N:5][C:6]=1[O:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:21])([F:22])[F:20])[CH:14]=1
Reactant: COC(=O)c1ccc(OC)c(Oc2cccc(C(F)(F)F)c2)n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COc1ccc(C(=O)O)nc1Oc1cccc(C(F)(F)F)c1
Temperature: 70 °C
Reaction time: 1.5 h

Procedure:
5-methoxy-6-[3-(trifluoromethyl)phenoxy] picolinic acid methyl ester (0.7 g, 0.0021 mol) was dissolved in 2.8 ml of ethyl alcohol. One milliliter of an aqueous solution of sodium hydroxide (0.102 g, 0.0021×1.2 mol) was added to the obtained solution. The resultant mixture was heated and stirred at 70° C. for 1.5 hours. After cooling, the obtained reaction solution was mixed with 2 ml of concentrated hydrochloric acid, thereby precipitating solids. The precipitated solids were filtered out from the solution, washed with water, and then dried.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][N:13]=[C:14]([C:17]([OH:19])=[O:18])[CH2:15][CH3:16])[CH2:9][N:8]=[C:7]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:6]=2[CH:26]=1.[N+](=[CH2:29])=[N-]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][N:13]=[C:14]([C:17]([O:19][CH3:29])=[O:18])[CH2:15][CH3:16])[CH2:9][N:8]=[C:7]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:6]=2[CH:26]=1
Reactant: CCC(=NNC1=Nc2ccc(Cl)cc2C(c2ccccc2)=NC1)C(=O)O
Reactant: C=[N+]=[N-]
Product: CCC(=NNC1=Nc2ccc(Cl)cc2C(c2ccccc2)=NC1)C(=O)OC

Procedure:
In the manner given in Example 10, 7-chloro-2-[(1-carboxypropylidene)hydrazino]-5-phenyl-3H-1,4-benzodiazepine is treated with etheral diazomethane to give 7-chloro-2-[[1-(methoxycarbonyl)propylidene]hydrazino]-5-phenyl-3H-1,4-benzodiazepine.
Reaction SMILES: B(F)(F)F.CCOCC.O[CH:11]([CH3:29])[CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[C:25](=[O:26])[C:24]2[N:23]([CH3:27])[CH:22]=[N:21][C:20]=2[N:19]([CH3:28])[C:17]1=[O:18].C[Si]([N:34]=[N+]=[N-])(C)C.C(OP(OCC)OCC)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CCCCC.O>[NH2:34][CH:11]([CH3:29])[CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[C:25](=[O:26])[C:24]2[N:23]([CH3:27])[CH:22]=[N:21][C:20]=2[N:19]([CH3:28])[C:17]1=[O:18]
Reactant: CC(O)CCCCn1c(=O)c2c(ncn2C)n(C)c1=O
Reactant: C[Si](C)(C)N=[N+]=[N-]
Agent: CCOP(OCC)OCC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: FB(F)F
Solvent: CCOCC
Solvent: O
Solvent: CCCCC
Product: CC(N)CCCCn1c(=O)c2c(ncn2C)n(C)c1=O
Reaction time: 6 h
Yield: 50 %

Procedure:
The method described in Koziara and Zwierzak, Tetrahedron Letters 28:6513-6516,1987 was followed to make CT1520. Briefly, boron trifluoride etherate (0.06 mol) was added dropwise at 10°-30° C. to a stirred solution of 1-(5-hydroxyhexyl)-3,7-dimethylxanthine (0.05 mol) and trimethylsilylazide (0.06 mol) in pentane (50 ml). After 24 hours at room temperature the mixture was poured into 100 mls of water. The organic phase was separated, washed with a 10% solution of sodium bicarbonate, and dried over sodium sulfate. The solution of the azide in pentane was stirred at 25°-30° C., and 0.05 mol of triethylphosphite was added. Stirring was continued for 6 hours, and the solution was left at this temperature for 72 hours. Solvent was evaporated off and the iminophosphorane was dissolved in ethanol (15 mls) and treated with p-toluenesulfonic acid monohydrate (0.05 mol) and water (0.05 mol). The mixture was refluxed for eight hours, evaporated and the residue diluted with 100 mls of ether. The tosyl salt of the amine was precipitated out and was recovered by filtration. Then, 30% aqueous ammonium hydroxide (20 mls) was added to the crystals and the free amine was extracted into dichloromethane (3×15 mls), dried over sodium sulfate and the solvent evaporated to yield the free amine as a viscous oil, 0.7 g with a 50% yield.
Reaction SMILES: C([SiH](CC)CC)C.FC(F)(F)C(O)=O.[CH2:15]([O:22][C:23](=[O:47])[CH2:24][CH:25]([NH:30][C:31](=[O:46])[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH:39]=[CH:40][C:41]1[CH:45]=[CH:44][S:43][CH:42]=1)[CH2:26][N:27]([CH3:29])[CH3:28])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[CH2:15]([O:22][C:23](=[O:47])[CH2:24][CH:25]([NH:30][C:31](=[O:46])[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][C:41]1[CH:45]=[CH:44][S:43][CH:42]=1)[CH2:26][N:27]([CH3:28])[CH3:29])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: CN(C)CC(CC(=O)OCc1ccccc1)NC(=O)CCCCCCCC=Cc1ccsc1
Agent: CC[SiH](CC)CC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: Cc1ccccc1
Product: CN(C)CC(CC(=O)OCc1ccccc1)NC(=O)CCCCCCCCCc1ccsc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 111.8 %

Procedure:
Triethylsilane (0.23 mL, 1.43 mmol) and trifluoroacetic acid (0.21 mL, 2.9 mmol) were added to a solution of 4-dimethylamino-3-(10-thiophen-3-yl-dec-9-enoylamino)-butyric acid benzyl ester (67 mg, 0.14 mmol) in toluene (8 mL). The reaction mixture was stirred at room temperature for 12 hours after which time the solution was added to cold saturated aq. sodium bicarbonate solution. The aqueous phase was separated and extracted twice with dichloromethane. The combined organics were dried over magnesium sulfate, filtered and concentrated in vacuo to afford 4-dimethylamino-3-(10-thiophen-3-yl-decanoylamino)-butyric acid benzyl ester (74 mg), m/e=473.3 ([M+H]+).
Reaction SMILES: [CH2:1]([OH:23])[C@H:2]1[O:7][C@H:6]([O:8][C@:9]2([CH2:18][OH:19])[O:13][C@H:12](CO)[C@@H:11]([OH:16])[C@@H:10]2[OH:17])[C@H:5]([OH:20])[C@@H:4]([OH:21])[C@@H:3]1[OH:22].[C:24]([O-])(=[O:26])C.[N+](C1C([N+]([O-])=O)=C(O)C(=CC=1)C([O-])=O)([O-])=O.[Na+]>>[CH2:1]([OH:23])[C@H:2]1[O:7][C@H:6]([O:8][C@H:9]2[C@H:10]([OH:17])[C@@H:11]([OH:16])[C@H:12]([OH:13])[O:19][C@@H:18]2[CH2:24][OH:26])[C@H:5]([OH:20])[C@@H:4]([OH:21])[C@@H:3]1[OH:22]
Reactant: CC(=O)[O-]
Reactant: OC[C@H]1O[C@@](CO)(O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O)[C@@H]1O
Agent: O=C([O-])c1ccc([N+](=O)[O-])c([N+](=O)[O-])c1O
Agent: [Na+]
Product: 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

Procedure:
The fourth test is practised on 0.1 to 0.4 mg of dry yeast matter which are placed in the presence of saccharose at a final concentration of 0.1 Molar, in a test tube in a buffered medium with acetate buffer at pH 4.7, placed in a water bath at 30° C. At the end of 5 minutes, the saccharose inversion reaction is blocked by the addition of the reactant with sodium dinitrosalicylate which serves to determine reducing sugars formed, by colorimetric reaction.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@@H:13]([CH2:14][OH:15])[CH2:12][O:11][C@@H:10]([CH2:16][CH2:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.O>CS(C)=O.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[C@@H:13]([CH:14]=[O:15])[CH2:12][O:11][C@@H:10]([CH2:16][CH2:17][CH:18]2[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1C[C@H](CCC2CCCCC2)OC[C@@H]1CO
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1C[C@H](CCC2CCCCC2)OC[C@@H]1C=O
Temperature: 10 °C
Reaction time: 0.5 h

Procedure:
Dissolve 2-(S)-(2-cyclohexylethyl)-5-(S)-hydroxymethylmorpholine-4-carboxylic acid tert-butyl ester (165 mg, 0.50 mmol) in dimethylsulfoxide (2 mL), and cool to 10° C. Add triethylamine (0.28 mL, 2.02 mmol) followed by pyridine sulfur trioxide complex and stir for 30 min. Dilute with ethyl acetate and pour into cold water. Wash with 5% citric acid (50 mL), saturated aqueous sodium chloride (50 mL) and dry (sodium sulfate), filter and concentrate give the desired compound as an oil which is used without further purification.
Reaction SMILES: [F:1][C:2]1[C:12]([F:13])=[C:11]([F:14])[C:10]([F:15])=[CH:9][C:3]=1[C:4]([CH2:6][C:7]#[N:8])=[O:5].[C:16]([O:19][C:20](=O)C)(=O)C>>[F:1][C:2]1[C:12]([F:13])=[C:11]([F:14])[C:10]([F:15])=[CH:9][C:3]=1[C:4]([C:6](=[CH:16][O:19][CH3:20])[C:7]#[N:8])=[O:5]
Reactant: N#CCC(=O)c1cc(F)c(F)c(F)c1F
Reactant: CC(=O)OC(C)=O
Product: COC=C(C#N)C(=O)c1cc(F)c(F)c(F)c1F
Temperature: 150 °C
Yield: 95.3 %

Procedure:
A mixture of 16 g of 2,3,4,5-tetrafluorobenzoylacetonitrile, 15.6 g of trimethyl o-iformate and 18.8 g of acetic anhydride is heated at 150° C. (bath temperature) for 3 hours. The solvent mixture is distilled off completely under a waterpump vacuum and finally under a high vacuum, at a bath temperature of 120° C. 18.2 g of 2-(2,3,4,5-tetrafluorobenzoyl)-3-methoxy-acrylonitrile are obtained as a dark brown oil.
Reaction SMILES: [C:1]1(C)C=CC=CC=1.[CH2:8]([O:15][C:16]([NH:18][C@H:19]([C:25]([OH:27])=[O:26])[CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(OCC)(=O)C>[CH2:8]([O:15][C:16]([N:18]1[CH:19]([CH2:20][CH2:21][C:22]([OH:24])=[O:23])[C:25](=[O:27])[O:26][CH2:1]1)=[O:17])[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: O=C(O)CC[C@H](NC(=O)OCc1ccccc1)C(=O)O
Reactant: Cc1ccccc1
Agent: C=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOC(C)=O
Solvent: O
Product: O=C(O)CCC1C(=O)OCN1C(=O)OCc1ccccc1
Reaction time: 3 h

Procedure:
To 300 ml of toluene were added 100 g of DL-N-benzyloxycarbonylglutamic acid, 20 g of powdery paraformaldehyde and 4 g of p-toluenesulfonic acid monohydrate, and the resulting mixture was subjected to azeotropic dehydration for 3 hours. Subsequently, the solvent was removed by distillation under reduced pressure, and the oily product thus obtained was dissolved in 200 ml of ethyl acetate, after which the resulting solution was washed with water. The organic layer thus formed was then separated and dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure to obtain oily DL-3-benzyloxycarbonyl-4-(2-carboxyethyl)oxazolidin-5-one. Thus product was dissolved in 250 ml of toluene with heating, and 120 g of n-propylamine was added thereto, after which the resulting mixture was heated under reflux for 3.5 hours. Subsequently, the solvent was removed by distillation under reduced pressure, and the resulting residue was dissolved in 250 ml of ethyl acetate, after which the resulting solution was washed with three 100-ml portions of diluted hydrochloric acid. The resulting organic layer was separated, and the pH thereof was adjusted to 10 with a 3% aqueous sodium hydroxide solution, after which the resulting aqueous layer was separated. The pH of the aqueous layer was adjusted to 6 with diluted hydrochloric acid, and the crystals thus precipitated were collected by filtration to obtain 87 g (yield 76%) of DL-N2 -benzyloxycarbonyl-N1 -n-propyl-α-glutamylamide having a melting point of 132°-135° C.
Reaction SMILES: [C:1]([N:3]1[CH2:8][CH2:7][CH:6]([N:9]([CH:23]2[CH2:25][CH2:24]2)[C:10](=[O:22])[C:11]2[CH:16]=[CH:15][C:14]([C:17]3[O:21][CH:20]=[N:19][CH:18]=3)=[CH:13][CH:12]=2)[CH2:5][CH2:4]1)#[N:2].[CH2:26]([O:28][C:29](=[O:34])[C:30]([NH:32][OH:33])=N)[CH3:27]>>[CH2:26]([O:28][C:29]([C:30]1[N:2]=[C:1]([N:3]2[CH2:4][CH2:5][CH:6]([N:9]([CH:23]3[CH2:25][CH2:24]3)[C:10](=[O:22])[C:11]3[CH:12]=[CH:13][C:14]([C:17]4[O:21][CH:20]=[N:19][CH:18]=4)=[CH:15][CH:16]=3)[CH2:7][CH2:8]2)[O:33][N:32]=1)=[O:34])[CH3:27]
Reactant: N#CN1CCC(N(C(=O)c2ccc(-c3cnco3)cc2)C2CC2)CC1
Reactant: CCOC(=O)C(=N)NO
Product: CCOC(=O)c1noc(N2CCC(N(C(=O)c3ccc(-c4cnco4)cc3)C3CC3)CC2)n1

Procedure:
The title compound is prepared from N-(1-cyano-piperidin-4-yl)-N-cyclopropyl-4-oxazol-5-yl-benzamide and hydroxyamino-imino-acetic acid ethyl ester following a procedure analogous to that described in Example 1. LC (method 3): tR=1.77 min; Mass spectrum (ESI+): m/z=452 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][N+:13]([O-:15])=[O:14])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].I[CH2:17][CH2:18][C:19](=[O:29])[CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH:12]([N+:13]([O-:15])=[O:14])[CH2:17][CH2:18][C:19](=[O:29])[CH2:20][CH2:21][C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: O=C(CCI)CCc1ccc(F)cc1
Reactant: COc1ccc(CC[N+](=O)[O-])cc1OC
Solvent: C1CCOC1
Product: COc1ccc(CC(CCC(=O)CCc2ccc(F)cc2)[N+](=O)[O-])cc1OC
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a solution of 48.5 g (0.23 mole) of 2-(3',4'dimethoxyphenyl)-1-nitroethane in 400 ml of dry tetrahydrofuran was added 96.0 (0.23 mole) of 40% Triton B. The solution was stirred at room temperature for 10 minutes. 66.7 g (0.23 mole) of 1-iodo-5-(4'-fluorophenyl)-3-pentanone in a minimum amount of dry tetrahydrofuran was added dropwise. The mixture was heated at 50° C. for 3 hours, then allowed to stir at room temperature overnight. Solvent was removed in vacuo and the residue taken up in ether and extracted twice with water. The organic layer was dried over anh MgSO4, filtered and concentrated at reduced pressure to obtain a crude oil. The crude material was passed through HPLC to give 79 g purified material.
Reaction SMILES: C(=O)(O)[O-].[Na+].[CH2:6]([N:8]([CH2:32][CH3:33])[C:9]1[CH:14]=[CH:13][C:12]([S:15]([N:18]2[CH2:22][CH:21]([O:23][Si](C(C)(C)C)(C)C)[CH2:20][C:19]2=[S:31])(=[O:17])=[O:16])=[CH:11][CH:10]=1)[CH3:7]>C(Cl)Cl>[CH2:32]([N:8]([CH2:6][CH3:7])[C:9]1[CH:14]=[CH:13][C:12]([S:15]([N:18]2[CH2:22][CH:21]([OH:23])[CH2:20][C:19]2=[S:31])(=[O:16])=[O:17])=[CH:11][CH:10]=1)[CH3:33]
Reactant: CCN(CC)c1ccc(S(=O)(=O)N2CC(O[Si](C)(C)C(C)(C)C)CC2=S)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCN(CC)c1ccc(S(=O)(=O)N2CC(O)CC2=S)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 72.6 %

Procedure:
30 cm3 of sodium bicarbonate is added at -20° C. over one hour to a solution of 1.3 g of 1-[[4-(diethylamino)-phenyl]-sulphonyl]-4-[(1,1-dimethylethyl)-dimethylsilyloxy]-2-pyrrolidine thione obtained above, in 30 cm3 of methylene chloride. The mixture is agitated for 16 hours at ambient temperature, decanted, extracted with methylene chloride, the extracts are dried and evaporated to dryness. After crystallization from a chloroform - hexane mixture, 700 mg of the desired product is obtained. M.p=149-150° C.
Reaction SMILES: FC(F)(F)C([O-])=O.[F:8][C:9]1[CH:10]=[C:11]([CH2:16][C@H:17]([NH3+:54])[C:18](=[O:53])[NH:19][C@H:20]2[CH2:45][O:44][C:43](=[O:46])[C@H:42]3[N:38]([CH2:39][C@H:40]([CH3:47])[CH2:41]3)[C:37](=[O:48])[C@H:36]([CH3:49])[NH:35][C:34](=[O:50])[C@H:33]3[N:28]([CH2:29][CH2:30][CH2:31][CH2:32]3)[C:27](=[O:51])[C@H:26]3[N:22]([CH2:23][CH2:24][CH2:25]3)[C:21]2=[O:52])[CH:12]=[C:13]([F:15])[CH:14]=1.[CH:55]1([CH2:61][CH2:62][C:63](O)=[O:64])[CH2:60][CH2:59][CH2:58][CH2:57][CH2:56]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C>C(#N)C.O.CN(C)C=O>[F:15][C:13]1[CH:12]=[C:11]([CH2:16][C@H:17]([NH:54][C:63](=[O:64])[CH2:62][CH2:61][CH:55]2[CH2:60][CH2:59][CH2:58][CH2:57][CH2:56]2)[C:18](=[O:53])[NH:19][C@H:20]2[CH2:45][O:44][C:43](=[O:46])[C@H:42]3[N:38]([CH2:39][C@H:40]([CH3:47])[CH2:41]3)[C:37](=[O:48])[C@H:36]([CH3:49])[NH:35][C:34](=[O:50])[C@H:33]3[N:28]([CH2:29][CH2:30][CH2:31][CH2:32]3)[C:27](=[O:51])[C@H:26]3[N:22]([CH2:23][CH2:24][CH2:25]3)[C:21]2=[O:52])[CH:10]=[C:9]([F:8])[CH:14]=1
Reactant: O=C(O)CCC1CCCCC1
Reactant: C[C@@H]1C[C@H]2C(=O)OC[C@H](NC(=O)[C@@H]([NH3+])Cc3cc(F)cc(F)c3)C(=O)N3CCC[C@H]3C(=O)N3CCCC[C@H]3C(=O)N[C@@H](C)C(=O)N2C1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C([O-])C(F)(F)F
Solvent: O
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: C[C@@H]1C[C@H]2C(=O)OC[C@H](NC(=O)[C@H](Cc3cc(F)cc(F)c3)NC(=O)CCC3CCCCC3)C(=O)N3CCC[C@H]3C(=O)N3CCCC[C@H]3C(=O)N[C@@H](C)C(=O)N2C1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
100 mg (0.13 mmol) of the compound from example 29A and 22.0 mg (0.14 mmol) of 3-cyclohexylpropionic acid are introduced under argon into anhydrous dimethylformamide (1 ml) at 0° C. and then 54.0 mg (0.14 mmol) of HATU and 0.025 ml (0.14 mmol) of ethyldiisopropylamine are added. After 30 min, a further 0.05 ml (0.29 mmol) of ethyldiisopropylamine are added to the reaction mixture. The reaction mixture is stirred overnight with slow warming to RT. The reaction solution is subjected directly to an RP-HPLC using acetonitrile/water as eluent. In the course of this, 50 mg (49% of th.) of a colorless solid are obtained.
Reaction SMILES: [C:1]([C:3](=[C:7](OCC)[CH2:8][CH3:9])[C:4]([NH2:6])=[O:5])#[N:2].[Cl:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[C:16]([Cl:21])[C:15]=1[NH:22][NH2:23].O>CO>[NH2:2][C:1]1[N:22]([C:15]2[C:14]([Cl:13])=[CH:19][C:18]([Cl:20])=[CH:17][C:16]=2[Cl:21])[N:23]=[C:7]([CH2:8][CH3:9])[C:3]=1[C:4]([NH2:6])=[O:5]
Reactant: NNc1c(Cl)cc(Cl)cc1Cl
Reactant: CCOC(CC)=C(C#N)C(N)=O
Solvent: CO
Solvent: O
Product: CCc1nn(-c2c(Cl)cc(Cl)cc2Cl)c(N)c1C(N)=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 82 %

Procedure:
Part A: To a stirred solution of 320 mg (1.9 mmol) of 2-cyano-3-ethoxypentenamide in 7 mL of MeOH was added 465 mg (2.2 mmol) of 2,4,6-trichlorophenylhydrazine. The solution was stirred 3 h at reflux, treated with 2 mL of water, and allowed to stir an additional 1 h, cooling to RT. The white solid which precipitated was filtered, washed with 2:1 MeOH-water, and air-dried to afford 520 mg (82%) of 5-amino-3-ethyl-1-(2,4,6-trichlorophenyl) pyrazole-4-carboxamide, mp 186-188° C., Mass Spec(CI+): 331.9989(M)+.
Reaction SMILES: [CH3:1][C:2]1([CH3:18])[C@@H:4]([C:5]#[C:6][C:7](=[O:14])[O:8][CH2:9][C:10]([Cl:13])([Cl:12])[Cl:11])[C@H:3]1[C:15]([OH:17])=[O:16].CC1(C)[C@@H](/C=C\C(=O)OCCOC)[C@H]1C(O[CH:35]([CH3:49])[C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([O:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:37]=1)=O.O(C1C=C(C(O)C)C=CC=1)C1C=CC=CC=1>>[CH3:1][C:2]1([CH3:18])[C@@H:4]([C:5]#[C:6][C:7](=[O:14])[O:8][CH2:9][C:10]([Cl:13])([Cl:11])[Cl:12])[C@H:3]1[C:15]([O:17][CH:35]([CH3:49])[C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([O:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:37]=1)=[O:16]
Reactant: COCCOC(=O)/C=C\[C@H]1[C@@H](C(=O)OC(C)c2cccc(Oc3ccccc3)c2)C1(C)C
Reactant: CC1(C)[C@H](C(=O)O)[C@@H]1C#CC(=O)OCC(Cl)(Cl)Cl
Agent: CC(O)c1cccc(Oc2ccccc2)c1
Product: CC(OC(=O)[C@@H]1[C@H](C#CC(=O)OCC(Cl)(Cl)Cl)C1(C)C)c1cccc(Oc2ccccc2)c1

Procedure:
Using the procedure of Step D of Example 9, 6 g of (1R,cis) 2,2-dimethyl-3-[3-oxo-3-(2,2,2-trichloroethoxy)-1-propynyl]-cyclopropane-carboxylic acid and 4.1 g of 1-(R) (3-phenoxyl-phenyl)- ethanol were reacted to obtain after chromatography and elution with an 8-2 mixture of cyclohexaneethyl acetate 4.38 g of (R)α-methoxy-3-phenoxy-benzyl (1R, cis) 2,2-dimthyl-3-[3-oxo-3-(2,2,2-trichloroethoxy)-1-propynyl]-cyclopropane-carboxylate.
Reaction SMILES: [K+].[Br-:2].Br.C([N:11]([CH:30]([CH3:32])[CH3:31])[CH2:12][C:13]([C:15]1[CH:20]=[CH:19][C:18]([NH:21][S:22]([NH:25][C:26]([CH3:29])([CH3:28])[CH3:27])(=[O:24])=[O:23])=[CH:17][CH:16]=1)=[O:14])C1C=CC=CC=1>>[BrH:2].[C:26]([NH:25][S:22]([NH:21][C:18]1[CH:19]=[CH:20][C:15]([CH:13]([OH:14])[CH2:12][NH:11][CH:30]([CH3:31])[CH3:32])=[CH:16][CH:17]=1)(=[O:24])=[O:23])([CH3:29])([CH3:28])[CH3:27]
Reactant: CC(C)N(CC(=O)c1ccc(NS(=O)(=O)NC(C)(C)C)cc1)Cc1ccccc1
Reactant: [Br-]
Agent: Br
Agent: [K+]
Product: CC(C)NCC(O)c1ccc(NS(=O)(=O)NC(C)(C)C)cc1

Procedure:
Infrared (pelletized with KBr): 840, 1145, 1330, 1395, 1520, 1615, 2800, 2980, 3160, 3300 cm-1. Prepared from N-[4-(N-benzyl-N-isopropylglycyl)phenyl]-N'-tert.-butylsulfamide hydrobromide.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH:22]C(=O)OC(C)(C)C)[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)=[C:4]([F:30])[CH:3]=1>Cl.O1CCOCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[CH:10]=2)=[C:4]([F:30])[CH:3]=1
Reactant: CC(C)(C)OC(=O)Nc1cccc(Nc2cc(Nc3ccc(Br)cc3F)ncn2)c1
Agent: Cl
Solvent: C1COCCO1
Product: Nc1cccc(Nc2cc(Nc3ccc(Br)cc3F)ncn2)c1
Reaction time: 3 h
Yield: 100.2 %

Procedure:
A solution of 4-bromo-2-fluoroaniline (701 mg, 3.69 mmol), diisopropylethylamine (0.70 mL, 4.03 mmol), and 4,6-dichloropyrimidine (500 mg, 3.36 mmol) in EtOH (10 mL) was heated in an 85° C. oil bath for 5 d. Flash chromatography (2% MeOH/CHCl3) of the residue gave 380 mg (37%) of N-(4-bromo-2-fluorophenyl)-6-chloropyrimidin-4-amine as a pale yellow solid. MS (m/z): 304, 302. A suspension of N-(4-bromo-2-fluorophenyl)-6-chloropyrimidin-4-amine (0.37 g, 1.22 mmol) and tert-butyl 3-aminophenylcarbamate (0.28 g, 1.35 mmol) in n-BuOH (4 mL) was heated in an oil bath at 120-130° C. for 6 h. The reaction mixture was cooled and concentrated to give 0.68 g of a brown foam. Flash chromatography gave 0.16 g (28%) tert-butyl 3-(6-[4-bromo-2-fluorophenyl]aminopyrimidin-4-yl)aminophenylcarbamate as a white solid. MS (m/z): (M+H) 476, 474. tert-Butyl 3-(6-[4-bromo-2-fluorophenyl]aminopyrimidin-4-yl)aminophenylcarbamate (0.15 g, 0.32 mmol) was taken up in 4M HCl in dioxane (5 mL). After several minutes a white solid began to precipitate. The mixture was allowed to stand for 3 h and was concentrated via rotary evaporation. Saturated aqueous sodium bicarbonate (5 mL) was added and the mixture was sonicated for several minutes. The solid was collected by filtration, was washed with water (5 mL), and was dried overnight under vacuum to give 0.12 g (100%) of 3-[6-(4-bromo-2-fluorophenylamino)-pyrimidin-4-yl-amino]-phenylamine (IR-17) as a white powder. MS (m/z): (M+H) 376, 374.