Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:9][C@@H:10]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:11]([NH:13][CH2:14][C:15]#[N:16])=[O:12])=[CH:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[CH3:33][N:34]([CH:36]=O)[CH3:35]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:15]([CH2:14][NH:13][C:11](=[O:12])[C@@H:10]([O:9][C@H:8]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:5]1[CH:6]=[CH:7][C:2]([C:2]2[CH:7]=[CH:6][C:33]([N:34]3[CH2:36][CH2:14][NH:13][CH2:11][CH2:35]3)=[CH:4][CH:3]=2)=[CH:3][CH:4]=1)[CH2:17][CH:18]([CH3:20])[CH3:19])#[N:16]
Reactant: CN(C)C=O
Reactant: CC(C)C[C@H](O[C@H](c1ccccc1)c1ccc(Br)cc1)C(=O)NCC#N
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Product: CC(C)C[C@H](O[C@H](c1ccccc1)c1ccc(-c2ccc(N3CCNCC3)cc2)cc1)C(=O)NCC#N
Temperature: 85 °C

Procedure:
(2S)-2-{[(R)-(4-bromophenyl)(phenyl)methyl]oxy}-N-(cyanomethyl)-4-methylpentanamide (1 g, 2.41 mmol) 1-[4-(dihydroxyboryl)phenyl]piperazin-4-ium chloride (642 mg, 2.65 mmol), PdCl2(dppf) (88 mg, 0.120 mmol) and 2M Na2CO3 (4.8 ml, 9.63 mmol) were dissolved in 25 ml DMF, the solution was degassed 3 times and heated for 10 h @ 85° C. The solution was cooled, poured into 125 ml NaHCO3 (sat.) and the product extracted with 3×25 ml ethyl acetate. The combined organic layers were then washed with 4× water, then dried with Na2SO4. The product was then purified on silica gel (5% MeOH/5% NH4OH/90% DCM).
Reaction SMILES: [Mg].II.[CH3:4][C:5]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:6]=1Cl.[C:13]([C:17]1[CH:22]=[CH:21][C:20](Br)=[CH:19][CH:18]=1)([CH3:16])([CH3:15])[CH3:14].Cl>O1CCCC1.BrCCBr.[Ni](Cl)Cl>[C:13]([C:17]1[CH:22]=[CH:21][C:20]([C:6]2[CH:7]=[CH:8][CH:9]=[C:10]([CH3:11])[C:5]=2[CH3:4])=[CH:19][CH:18]=1)([CH3:16])([CH3:15])[CH3:14]
Reactant: Cc1cccc(Cl)c1C
Reactant: CC(C)(C)c1ccc(Br)cc1
Agent: Cl[Ni]Cl
Agent: Cl
Agent: II
Solvent: BrCCBr
Solvent: C1CCOC1
Product: Cc1cccc(-c2ccc(C(C)(C)C)cc2)c1C
Temperature: 25 °C
Reaction time: 2 h

Procedure:
23.8 g (1.1 eq.) of magnesium (for Grignard reactions from Aldrich) were suspended in 95 ml of tetrahydrofuran (THF) and activated by addition of a small amount of iodine. 62.7 g (0.45 mol) of 2,3-dimethylchlorobenzene were subsequently added. To start the Grignard reaction, a few drops of 1,2-dibromoethane were carefully added. After the reaction had been started successfully, the remaining 62.7 g (0.45 mol) of 2,3-dimethylchlorobenzene diluted with 380 ml of THF were added dropwise at such a rate that the reaction solution boiled gently. The reaction mixture was subsequently refluxed until the magnesium had mostly reacted (2 hours). After the reaction mixture had cooled to room temperature, a further 95 ml of THF were added to the viscous mixture. 190.0 g (0.89 mol) of p-tert-butylbromobenzene diluted with 190 ml of THF were placed in a further reaction flask. 1.0 g (1 mol %) of nickel(II) chloride was added thereto, followed by careful addition of the Grignard solution. The temperature rose briefly to 80° C. The reaction mixture was stirred at 50–55° C. for 2 hours. After cooling to room temperature, 190 ml of 2 molar hydrochloric acid were carefully added. The aqueous phase was extracted with diethyl ether (3×200 ml), the combined organic phases were dried over magnesium sulfate and the solvent was removed under reduced pressure. The residue was recrystallized from boiling ethanol and two crystal fractions were obtained (1st fraction: 139.3 g, 100% according to GC/2nd fraction: 20.5 g, 96.2% according to GC). Combined yield: 159.8 g (0.67 mol/75%). 1H NMR (400 MHz, CDCl3): δ=7.41 (“d”, 2H, aromatic), 7.21 (“d”<2H, aromat.), 7.14–7.07 (m, 3H, aromat.), 2.33 (s, 3H, CH3), 2.16 (s, 3H, CH3), 1.36 (s, 9H, tert-butyl) ppm.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17]([C:19]3[N:20]=[CH:21][N:22]([CH:24]([CH3:26])[CH3:25])[CH:23]=3)[S:18][C:11]=12)[NH2:5].FC1C=CC=CC=1NC(=O)CC(O)=O.[CH3:41][O:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[NH:49][C:50](=[O:55])[CH2:51][C:52](O)=[O:53]>>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:52](=[O:53])[CH2:51][C:50]([NH:49][C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2[O:42][CH3:41])=[O:55])[CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17]([C:19]3[N:20]=[CH:21][N:22]([CH:24]([CH3:26])[CH3:25])[CH:23]=3)[S:18][C:11]=12
Reactant: CC(C)n1cnc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1
Reactant: COc1ccccc1NC(=O)CC(=O)O
Agent: O=C(O)CC(=O)Nc1ccccc1F
Product: COc1ccccc1NC(=O)CC(=O)Nc1ccc(Oc2ccnc3cc(-c4cn(C(C)C)cn4)sc23)c(F)c1

Procedure:
Title compound 126 (scheme 36) was obtained similarly to the compound 122 (example 45, scheme 36) starting from the amine 125 and replacing the acid 29 with the acid 27. 1H NMR (DMSO-d6). δ (ppm): 10.58 (s, 1H), 9.64 (s, 1H), 8.43 (d, J=5.6 Hz, 1H), 8.07 (dd, J=1.6 and 7.2 Hz, 1H), 8.05 (d, J=1.2 Hz, 1H), 7.87 (dd, J=2.4 and 12.8 Hz, 1H), 7.84 (d, J=1.2 Hz, 1H), 7.67 (s, 1H), 7.49 (t, J=8.8 Hz, 1H), 7.43 (dd, J=1.6 and 8.8 Hz, 1H), 7.12-7.04 (m, 2H), 6.92 (ddd, J=2.4, 7.2 and 8.8 Hz, 1H), 6.58 (d, J=5.6 Hz, 1H), 4.48 (quin, J=6.4 Hz, 1H), 3.86 (s, 3H), 3.64 (s, 2H), 1.46 (d, J=6.8 Hz, 6H). MS (m/z): 559.2 (M+H).
Reaction SMILES: Cl.C1([CH:8]([CH:12]2[CH2:17][CH2:16][N:15](C3C=CC(NC(C4C=CC=CC=4C4C=CC(C(F)(F)F)=CC=4)=O)=CC=3)[CH2:14][CH2:13]2)[C:9]([OH:11])=[O:10])C=CC=CC=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.OCC(OC)=O>C(Cl)Cl.O>[NH:15]1[CH2:16][CH2:17][CH:12]([CH2:8][C:9]([OH:11])=[O:10])[CH2:13][CH2:14]1
Reactant: O=C(Nc1ccc(N2CCC(C(C(=O)O)c3ccccc3)CC2)cc1)c1ccccc1-c1ccc(C(F)(F)F)cc1
Agent: COC(=O)CO
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: O=C(O)CC1CCNCC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of intermediate (24) (0.000084 mol), PyBOP (0.00017 mol) and triethylamine (0.5 ml) in DCM (5 ml) was stirred for 60 minutes at room temperature. Methyl hydroxyacetate (0.0001 mol) was added and the reaction mixture was stirred for 3 hours at 40° C., then over the weekend at room temperature. Water (2 ml) was added. The mixture was stirred for 15 minutes, then filtered through Extrelut™ and the organic filtrate was evaporated. The residue was purified by HPLC. The product fractions were collected and the solvent was evaporated, yielding 4-piperidineacetic acid, α-phenyl-1-[4-[[[4′-(trifluoromethyl)[1,1′-biphenyl]-2-yl]carbonyl]amino]-phenyl]-, 2-methoxy-2-oxoethyl ester (compound 20).
Reaction SMILES: [CH3:1][C:2]1[C:7]([I:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[C:13](=[O:14])[NH:12][N:11]=[N:10]1.[C:15](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH3:1][C:2]1[C:7]([I:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[C:13](=[O:14])[N:12]([CH3:15])[N:11]=[N:10]1
Reactant: Cc1c(I)cccc1-n1nn[nH]c1=O
Reactant: O=C([O-])[O-]
Agent: O=C([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: COS(=O)(=O)OC
Product: Cc1c(I)cccc1-n1nnn(C)c1=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of the above-mentioned 1-(2-methyl-3-iodophenyl)-1,4-dihydrotetrazole-5-one, potassium carbonate 17.40 g, dimethyl sulfate 5.78 g and N,N-dimethylformamide 150 mL was stirred at 25° C. for one hour. To the reaction mixtures was added aqueous saturated sodium bicarbonate solution and the mixtures were extracted with ethyl acetate. The organic layers were washed with aqueous saturated sodium bicarbonate solution and were dried over anhydrous sodium sulfate. The resulting mixtures were concentrated under reduced pressure to give 1-(2-methyl-3-iodophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (hereinafter, referred to as “Intermediate (PRI-P)”) 8.10 g.
Reaction SMILES: [N:1]([CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[NH:9][C:10]([CH3:34])=[C:11]([C:30]([O:32][CH3:33])=[O:31])[CH:12]([C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=2)[C:13]=1[C:14]([O:16]CCC#N)=[O:15])=[N+:2]=[N-:3].[OH-].[K+]>CC(C)=O>[N:1]([CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[NH:9][C:10]([CH3:34])=[C:11]([C:30]([O:32][CH3:33])=[O:31])[CH:12]([C:21]2[CH:22]=[CH:23][C:24]([N+:27]([O-:29])=[O:28])=[CH:25][CH:26]=2)[C:13]=1[C:14]([OH:16])=[O:15])=[N+:2]=[N-:3]
Reactant: COC(=O)C1=C(C)NC(CCCCN=[N+]=[N-])=C(C(=O)OCCC#N)C1c1ccc([N+](=O)[O-])cc1
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)=O
Product: COC(=O)C1=C(C)NC(CCCCN=[N+]=[N-])=C(C(=O)O)C1c1ccc([N+](=O)[O-])cc1
Yield: 61.2 %

Procedure:
A solution of 2-(4-azidobutyl)-3-(2-cyanoethoxy)carbonyl-1,4-dihydro-5-methoxycarbonyl-6-methyl-4-(4-nitrophenyl)pyridine (1.38 g, 2.95 mmol) in 10 ml acetone was treated with 15 ml 1N KOH solution at 0° C. for 1 hr. The acetone was removed in vacuo and the aqueous layer was acidified to pH=3 by 2N hydrochloric acid, the resulting yellow precipitate was collected by filtration, washed with 10 ml of cold water and dried in vacuo to yield 750 mg (61% yield) of 2-(4-azidobutyl)-1,4-dihydro-5-methoxycarbonyl-6-methyl-4-(4-nitrophenyl) pyridine-3-carboxylic acid as a yellow powder.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[C:16]([CH3:40])=[C:17]([CH3:39])[C:18]4[O:22][C:21]([CH3:24])([CH3:23])[CH:20]([O:25][CH2:26][C:27]5[CH:36]=[CH:35][C:30]([C:31]([O:33]C)=[O:32])=[CH:29][CH:28]=5)[C:19]=4[C:37]=3[CH3:38])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.C1COCC1.[OH-].[Na+].Cl>CO>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:10][CH2:11][N:12]([C:15]3[C:16]([CH3:40])=[C:17]([CH3:39])[C:18]4[O:22][C:21]([CH3:24])([CH3:23])[CH:20]([O:25][CH2:26][C:27]5[CH:28]=[CH:29][C:30]([C:31]([OH:33])=[O:32])=[CH:35][CH:36]=5)[C:19]=4[C:37]=3[CH3:38])[CH2:13][CH2:14]2)=[CH:7][CH:8]=1
Reactant: COC(=O)c1ccc(COC2c3c(C)c(N4CCN(c5ccc(OC)cc5)CC4)c(C)c(C)c3OC2(C)C)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: COc1ccc(N2CCN(c3c(C)c(C)c4c(c3C)C(OCc3ccc(C(=O)O)cc3)C(C)(C)O4)CC2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 74.2 %

Procedure:
To a solution of methyl 4-(((5-(4-[4-methoxyphenyl]piperazin-1-yl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-yl)oxy)methyl)benzoate (0.18 g, 0.33 mmol) obtained in Example 135 in methanol (1 mL)-THF (1 ml) was added 1N sodium hydroxide (0.5 mL). The mixture was stirred at room temperature for 16 hours. The reaction mixture was acidified with 1 N hydrochloric acid and extracted with ethyl acetate. The organic extract was washed with water and saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. The residue was recrystallized from hexane-ethyl acetate to obtain 0.13 g (yield 75%) of the title compound. mp. 162–163° C.
Reaction SMILES: C(N(CC)CC)C.[Br:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1.[Cl:16][C:17]1[CH:18]=[C:19]([CH2:23][CH2:24][C:25](O)=[O:26])[CH:20]=[CH:21][CH:22]=1.CCN=C=NCCCN(C)C.C([O-])(O)=O.[Na+]>C(Cl)Cl.O>[Br:8][C:9]1[CH:15]=[CH:14][C:12]([NH:13][C:25](=[O:26])[CH2:24][CH2:23][C:19]2[CH:20]=[CH:21][CH:22]=[C:17]([Cl:16])[CH:18]=2)=[CH:11][CH:10]=1
Reactant: Nc1ccc(Br)cc1
Reactant: O=C(O)CCc1cccc(Cl)c1
Agent: CCN=C=NCCCN(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: O=C(CCc1cccc(Cl)c1)Nc1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
Triethylamine (1.01 mL, 7.27 mmol) was added slowly to a mixture of 4-bromoaniline (0.500 g, 2.91 mmol), 3-(3-chlorophenyl)propanoic acid (0.643 g, 2.91 mmol), and EDCI (0.669 g, 3.49 mmol) in CH2Cl2 (20 mL). The mixture was stirred at room temperature for 48 hours and saturated aqueous NaHCO3 was added. Water (50 mL) was added followed by additional CH2Cl2. The mixture as stirred for 10 minutes and layers were separated. The CH2Cl2 layer was dried over Na2SO4, then filtered. The solvent was removed under reduced pressure and the residual oil chromatographed (CH2Cl2/EtOAc) to provide the title compound as a white fluffy solid.
Reaction SMILES: [O:1]=[CH:2][C:3]1[CH:11]=[CH:10][C:8]([OH:9])=[C:5]([O:6][CH3:7])[CH:4]=1.[C:12](=O)([O-])[O-].[K+].[K+].C(=O)([O-])[O-].P(OC)(OC)(OC)=O>O.CN(C)C=O>[CH:2](=[O:1])[C:3]1[CH:11]=[CH:10][C:8]([O:9][CH3:12])=[C:5]([O:6][CH3:7])[CH:4]=1
Reactant: O=C([O-])[O-]
Reactant: COc1cc(C=O)ccc1O
Agent: [K+]
Solvent: COP(=O)(OC)OC
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(C=O)cc1OC
Temperature: 100 °C
Yield: 96.6 %

Procedure:
In a three-neck flask (capacity 100 ml) equipped with a mechanical stirrer and reflux condenser, 20 ml of dimethylformamide (anhydrous), 5.00 g (0.033 mol) of vanillin and 5.00 g (0.036 mol) of anhydrous potassium carbonate were placed and the mixture was heated under a nitrogen atmosphere to 100° C. The mixture was a clear to amber solution of vanillin with carbonate in suspension. To this mixture was added 5.00 ml (0.043 mol) of trimethyl phosphate over about 5 minutes while maintaining the reaction temperature below 125° C. The mixture was maintained at about 80° C. for one hour and then cooled to 40° C. The mixture was poured into 200 ml water and extracted two times with 50 ml of methylene chloride. The methylene chloride extracts were washed twice with 100 ml of water. The combined extracts were dried over anhydrous potassium carbonate, filtered, and concentrated to give 5.3 g (95%) of veratraldehyde as a pale oil.
Reaction SMILES: Cl.[C:2]([O:6][C:7](=[O:10])[CH2:8][NH2:9])([CH3:5])([CH3:4])[CH3:3].[N+:11]([C:14]1[CH:19]=[CH:18][C:17](F)=[CH:16][CH:15]=1)([O-:13])=[O:12].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[C:2]([O:6][C:7](=[O:10])[CH2:8][NH:9][C:17]1[CH:18]=[CH:19][C:14]([N+:11]([O-:13])=[O:12])=[CH:15][CH:16]=1)([CH3:5])([CH3:4])[CH3:3]
Reactant: CC(C)(C)OC(=O)CN
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CC(C)(C)OC(=O)CNc1ccc([N+](=O)[O-])cc1
Temperature: 90 °C
Yield: 81.3 %

Procedure:
A mixture of glycine tert-butyl ester hydrochloride (3.35 g, 20 mmol), 4-nitrofluorobenzene (2.82 g, 20 mmol) and potassium carbonate (4.2 g, 30 mmol) in DMSO (15 mL) was heated at 90° C. for 22 hr. The reaction mixture was allowed to cool to room temperature and then poured onto crushed ice. The precipitated yellow solid was filtered, washed with water and dried (Na2SO4) to give N-(4-nitrophenyl)glycine tert-butyl ester (4.1 g, 81%).
Reaction SMILES: [C:1]([CH2:5][OH:6])([F:4])([F:3])[F:2].[N+:7]([O-:10])([OH:9])=[O:8].[O:11]=O>>[N+:7]([O-:10])([OH:9])=[O:8].[C:5]([OH:11])([C:1]([F:4])([F:3])[F:2])=[O:6]
Reactant: O=O
Reactant: OCC(F)(F)F
Solvent: O=[N+]([O-])O
Product: O=C(O)C(F)(F)F

Procedure:
CF3CH2OH (200.00 g, 2.00 moles), 55% nitric acid (114.55 g, 1.00 mole) and FeCl2.nH2O (0.0020 g) were placed into the autoclave used in Example 1. The mixture was heated with stirring in the same manner as in Example 1. 3.0 hours after the start of heating, the reaction temperature rose to 125° C. and the reaction pressure increased to 0.75 MPa. From that time, oxygen was fed into the gas phase in the same manner as in Example 1, whereby the reaction pressure was controlled at 0.75 MPa. 6.0 hours after the start of heating, complete consumption of the starting fluoroalkyl alcohol was confirmed by gas chromatography to confirm the completion of the reaction [CF3CH2OH conversion: 100.0 g.c. %; CF3COOH selectivity: 98.5 g.c. % or higher]. The same procedure as in Example 1 was followed, thus giving an aqueous nitric acid solution of CF3COOH (361.18 g, a material balance of 99.43 mass %).
Reaction SMILES: [C:1]([C:5]1[CH:31]=[CH:30][C:8]([C:9]([NH:11][C:12]2[CH:28]=[C:27]([NH2:29])[CH:26]=[CH:25][C:13]=2[C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)=[O:15])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl[C:33]([O:35][CH2:36][CH3:37])=[O:34]>>[C:1]([C:5]1[CH:31]=[CH:30][C:8]([C:9]([NH:11][C:12]2[CH:28]=[C:27]([NH:29][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH:26]=[CH:25][C:13]=2[C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)=[O:15])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)Cl
Reactant: COc1ccc(NC(=O)c2ccc(N)cc2NC(=O)c2ccc(C(C)(C)C)cc2)cc1
Product: CCOC(=O)Nc1ccc(C(=O)Nc2ccc(OC)cc2)c(NC(=O)c2ccc(C(C)(C)C)cc2)c1
Yield: 55 %

Procedure:
Using the procedure described in Example 59, Part E, 2-(4-tert-butylbenzoylamino)-4-amino-N-(4-methoxyphenyl)benzamide was reacted with ethyl chloroformate (0.52 mmol) to yield 129 mg (55%) of the title compound as a solid.
Reaction SMILES: C(=O)(O)N.[N:5]1[N:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]2=[C:7]([C:14](OC)=[O:15])[CH:6]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[N:5]1[N:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]2=[C:7]([CH2:14][OH:15])[CH:6]=1
Reactant: COC(=O)c1cnn2ccccc12
Agent: NC(=O)O
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Product: OCc1cnn2ccccc12

Procedure:
A solution of methyl pyrazolo[1,5-a]pyridine-3-carboxylate carbamate (1) (400 mg, 2.10 mmol) in THF (4 mL) was added LiAlH4 (159 mg, 4.20 mmol) at room temperature for 1 h. The reaction mixture was concentrated and 10 mL sat. aq. NaHCO3 was added, extracted with EA (3×10 mL). The organic phase was dried with anhydrous Na2SO4, filtered and concentrated. The residue was purified by Prep-TLC TLC using PE/EtOAc=2/1 to give title compound as oil.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][CH2:9][OH:10])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:11]1([CH3:21])[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[N:1]1([CH2:7][CH2:8][CH2:9][O:10][S:17]([C:14]2[CH:15]=[CH:16][C:11]([CH3:21])=[CH:12][CH:13]=2)(=[O:19])=[O:18])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1
Reactant: OCCCN1CCOCC1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OCCCN2CCOCC2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 73.5 %

Procedure:
To a mixture of 0.145 g (1 mmole) of 3-morpholin-4-yl-propan-1-ol and 5 mL of pyridine was added 0.001 g of 4-dimethylaminopyridine and 0.210 g (1.1 mmole) of p-toluenesulphonyl chloride. The mixture was stirred at ambient temperature overnight and then concentrated under reduced pressure. The residue was taken up in 10 mL of dichloromethane and washed once with 5 mL of saturated sodium bicarbonate, twice with 5 mL of water, and then brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 0.22 g of toluene-4-sulfonic acid 3-morpholin-4-yl-propyl ester as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([O:14][CH2:15][CH:16]=[C:17]([Cl:19])[Cl:18])[CH:5]=[C:6]([Cl:13])[C:7]=1[O:8][CH2:9][CH2:10][CH2:11][NH2:12].C(N(CC)CC)C.[Cl:27][C:28]1[CH:36]=[CH:35][C:31]([C:32](Cl)=[O:33])=[CH:30][CH:29]=1>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([O:14][CH2:15][CH:16]=[C:17]([Cl:19])[Cl:18])[CH:5]=[C:6]([Cl:13])[C:7]=1[O:8][CH2:9][CH2:10][CH2:11][NH:12][C:32](=[O:33])[C:31]1[CH:35]=[CH:36][C:28]([Cl:27])=[CH:29][CH:30]=1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Reactant: NCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(NCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl)c1ccc(Cl)cc1
Yield: 71.4 %

Procedure:
To a solution of 0.21 g of 3,5-dichloro-4-(3-aminopropyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene and 0.07 g of triethylamine dissolved in 5 ml of dichloromethane was added dropwise a solution of 0.11 g of 4-chlorobenzoyl chloride dissolved in 5 ml of dichloromethane, while stirring under ice cooling. After stirring at room temperature for 6 hours, the reaction mixture was washed with water and then concentrated to give a residue. The residue was subjected to silica gel chromatography, which afforded 0.21 g of 3,5-dichloro-4-(3-(4-chlorobenzamido)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene (71% yield), m.p., 95.1° C.
Reaction SMILES: [Br:1][CH:2]([CH2:6][CH3:7])[C:3](Br)=[O:4].Cl.[CH2:9]([O:16][NH2:17])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>CCOC(C)=O>[Br:1][CH:2]([CH2:6][CH3:7])[C:3]([NH:17][O:16][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:4]
Reactant: CCC(Br)C(=O)Br
Reactant: NOCc1ccccc1
Agent: Cl
Solvent: CCOC(C)=O
Product: CCC(Br)C(=O)NOCc1ccccc1
Yield: 72 %

Procedure:
Prepared in 72% yield (4.71 g, 17.3 mmol) from the reaction of 2-bromobutyryl bromide (5.0 g, 24 mmol) with O-benzylhydroxylamine, hydrochloride via general procedure A. Rf=0.49 (3:1, hexanes:EtOAc); mp=99.3-101.6° C.; 1H-NMR (500 MHz, CDCl3): δ 8.92 (br s, 1H), 7.52-7.31 (m, 5H), 4.93 (s, 2H), 4.12 (app q, J=7.2 Hz 1H), 2.02-1.94 (m, 2H), and 1.00 (t, J=7.0 Hz, 3H); 13C-NMR (126 MHz, CDCl3): δ 166.6, 134.8, 129.5, 129.0, 128.7, 78.4, 48.8, 28.8, and 11.8; FT-IR (neat) 3112, 2963, 2933, 2874, 1695, 1668 (s), 1528, 1496, 1454, 1364, 1177, 1089, 1023 cm-1. HRMS calculated for C11H15BrNO [M+H]+, 256.0332; found 256.0329.
Reaction SMILES: [N:1]1([C:10]([O:12][CH2:13][CH:14]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]3[C:15]2=[CH:16][CH:17]=[CH:18][CH:19]=3)=[O:11])[CH2:9][C@@H:7]([OH:8])[CH2:6][C@@H:2]1[C:3](O)=[O:4].[NH2:27][CH2:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30].ON1C=CC=CC1=O.F[B-](F)(F)F.C(C(=NOC(N(C)C)=[N+](C)C)C(OCC)=O)#N.C(N(C(C)C)CC)(C)C>C(#N)C.CN(C=O)C>[N:1]1([C:10]([O:12][CH2:13][CH:14]2[C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:21]3[C:26]2=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:11])[CH2:9][C@@H:7]([OH:8])[CH2:6][C@@H:2]1[C:3]([NH:27][CH2:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:4]
Reactant: O=C(O)[C@H]1C[C@H](O)CN1C(=O)OCC1c2ccccc2-c2ccccc21
Reactant: CC(C)(C)OC(=O)CN
Agent: CCOC(=O)C(C#N)=NOC(N(C)C)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: O=c1ccccn1O
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)CNC(=O)[C@H]1C[C@H](O)CN1C(=O)OCC1c2ccccc2-c2ccccc21
Reaction time: 1 h

Procedure:
1.4 g of Fmoc-D-Hyp-OH are dissolved in 25 ml of dry acetonitrile and then 1.05 g of H-Gly-OtBu and 0.445 g of N-hydroxypyridone are added. Then 1.31 g of O-[(cyano(ethoxycarbonyl)methylidene)amino]-1,1,3,3-tetramethyluronium tetrafluoroborate (TOTU) are introduced in/portions within 10 minutes, as well as 1.03 ml of diisopropylethylamine in 15 ml of DMF dropwise over the course of 15 minutes. After 1 h, the mixture is concentrated, the residue is taken up in ethyl acetate and extraction with sodium chloride solution is carried out. The organic phase is dried over sodium sulfate and evaporated to dryness. The remaining oil is taken up in a little ether and added dropwise to petroleum ether while stirring. The flocculent precipitate is filtered off with suction and dried in vacuo.