Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[CH:2]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-:14])=[O:13])[CH:7]=1)[C:3](=O)[CH3:4].[C:15]([NH:18][C:19]([NH2:21])=[S:20])(=[O:17])[CH3:16]>C(O)C>[CH3:4][C:3]1[N:21]=[C:19]([NH:18][C:15](=[O:17])[CH3:16])[S:20][C:2]=1[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-:14])=[O:13])[CH:7]=1
Reactant: CC(=O)C(Br)c1cccc([N+](=O)[O-])c1
Reactant: CC(=O)NC(N)=S
Solvent: CCO
Product: CC(=O)Nc1nc(C)c(-c2cccc([N+](=O)[O-])c2)s1
Temperature: 70 °C
Reaction time: 2 h
Yield: 52 %

Procedure:
A mixture of 1-bromo-1-(3-nitro-phenyl)-propan-2-one (Example 49a) (0.5 g, 1.94 mmol) and N-acetylthiourea (0.23 g, 1.94 mmol) in ethanol (10 ml) is stirred at 70° C. for 2 hours. After cooling the reaction to room temperature, the precipitated product is removed by filtration and dried under vacuum to give the titled compound (0.28 g).
Reaction SMILES: [I-:1].[I-].[I-].[CH2:4]([N:7]([C:11]1[CH:12]=[CH:13][C:14]2[C:23]([CH:24]=1)=[S+:22][C:21]1[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=1)[N:15]=2)[CH2:8][CH2:9][CH3:10])[CH2:5][CH3:6].C(N([C:32]1[CH:33]=[CH:34][C:35]2C(C=1)=[S+]C1[C:37](=[CH:38][CH:39]=[CH:40]C=1)[N:36]=2)CCC)CC.C(N(C1C=CC2C(C=1)=[S+]C1C(=CC=CC=1)N=2)CCC)CC.C(NCCCC)CCC>>[I-:1].[CH2:35]([N:36]([C:19]1[CH:18]=[CH:17][C:16]2[C:21]([CH:20]=1)=[S+:22][C:23]1[C:14](=[CH:13][CH:12]=[C:11]([N:7]([CH2:8][CH2:9][CH3:10])[CH2:4][CH2:5][CH3:6])[CH:24]=1)[N:15]=2)[CH2:37][CH2:38][CH2:39][CH3:40])[CH2:34][CH2:33][CH3:32]
Reactant: CCCN(CCC)c1ccc2nc3ccccc3[s+]c2c1
Agent: [I-]
Solvent: CCCCNCCCC
Product: CCCCN(CCCC)c1ccc2nc3ccc(N(CCC)CCC)cc3[s+]c2c1

Procedure:
This compound was obtained following isolation of 3-(N,N-dipropylamino)-phenothiazin-5-ium triiodide and subsequent treatment with dibutylamine. Precipitation from dichloromethane by addition of diethyl ether yielded purple lustrous crystals. Mass spectrometry: C26H38N3OS requires m/z=424; found m/z=424 (I− not detected by mass spectrometry).
Reaction SMILES: [OH-].[Na+].[CH3:3][N:4]1[C:9](=[O:10])[C:8]2[C:11]([C:14]([O:16]CC)=[O:15])=[CH:12][S:13][C:7]=2[N:6]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:5]1=[O:23].O>CO.O1CCCC1>[CH3:3][N:4]1[C:9](=[O:10])[C:8]2[C:11]([C:14]([OH:16])=[O:15])=[CH:12][S:13][C:7]=2[N:6]([CH2:19][CH:20]([CH3:21])[CH3:22])[C:5]1=[O:23]
Reactant: CCOC(=O)c1csc2c1c(=O)n(C)c(=O)n2CC(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)Cn1c(=O)n(C)c(=O)c2c(C(=O)O)csc21
Reaction time: 6 h
Yield: 92.6 %

Procedure:
2M Sodium hydroxide solution (30 ml) was added to a solution of ethyl 1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxylate (16.13 g) in methanol (25 ml) and tetrahydrofuran (50 ml). After 6 hours, further 2M sodium hydroxide solution (30 ml) was added. After a further 2 hours, water (500 ml) was added and the mixture was extracted with ether (250 ml). The aqueous layer extracts were acidified with concentrated hydrochloric acid and extracted with ethyl acetate (3×250 ml). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was redissolved in tetrahydrofuran (100 ml) and evaporated to give the subtitle compound (13.58 g) as a solid.
Reaction SMILES: [NH2:1][CH2:2][C@H:3]([NH:9][C:10]([CH2:12][NH:13][C:14]([C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[NH:26][C:27]([N:29]1[CH2:32][CH2:31][CH2:30]1)=[O:28])=[O:15])=[O:11])[C@@H:4]([OH:8])[CH2:5][CH2:6][CH3:7].[CH3:33][C:34]([CH3:38])([CH3:37])[CH:35]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[CH3:33][C:34]([CH3:38])([CH3:37])[CH2:35][NH:1][CH2:2][C@H:3]([NH:9][C:10]([CH2:12][NH:13][C:14]([C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[NH:26][C:27]([N:29]1[CH2:32][CH2:31][CH2:30]1)=[O:28])=[O:15])=[O:11])[C@@H:4]([OH:8])[CH2:5][CH2:6][CH3:7]
Reactant: CC(C)(C)C=O
Reactant: CCC[C@H](O)[C@H](CN)NC(=O)CNC(=O)c1cc(C(F)(F)F)ccc1NC(=O)N1CCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(Cl)Cl
Product: CCC[C@H](O)[C@H](CNCC(C)(C)C)NC(=O)CNC(=O)c1cc(C(F)(F)F)ccc1NC(=O)N1CCC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 51.9 %

Procedure:
Azetidine-1-carboxylic acid (1S,2S)-(2-{[(1-aminomethyl-2-hydroxy-pentylcarbamoyl)-methyl]-carbamoyl}-4-trifluoromethyl-phenyl)-amide (165 mg, 0.35 mmol, see procedure 1b) was dissolved in dichloroethane (4 mL). The resultant solution was charged sequentially with trimethylacetaldehyde (20.5 mg, 0.2 mmol) and sodium triacetoxyborohydride (148 mg, 0.7 mmol), stirred for 3 h at RT, quenched with sat. NaHCO3, and extracted twice with EtOAc. The organic extracts were combined, washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by reverse-phase HPLC to afford the title compound (55 mg) as a white powder after lyopholization. MS found: (M+H)+=530.5.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[O:9][C:8]([CH3:14])([CH3:13])[CH2:7][C:6]2=[O:15])#[CH:2].I[C:17]1[CH:27]=[CH:26][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][CH:18]=1>CCN(CC)CC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:14][C:8]1([CH3:13])[CH2:7][C:6](=[O:15])[C:5]2[C:10](=[CH:11][CH:12]=[C:3]([C:1]#[C:2][C:17]3[CH:27]=[CH:26][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][CH:18]=3)[CH:4]=2)[O:9]1
Reactant: CCOC(=O)c1ccc(I)cc1
Reactant: C#Cc1ccc2c(c1)C(=O)CC(C)(C)O2
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Product: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(=O)CC(C)(C)O3)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 50.3 %

Procedure:
A solution of 6-ethynyl-2,2-dimethylchroman-4-one (Compound 262, 2.60 g, 13.0 mmol) and ethyl 4-iodobenzoate (3.6 g, 13.0 mmol) in 50.0 mL Et3N was purged with argon for 15 minutes. To this solution was added bis(triphenylphosphine)-palladium(II) chloride (1.82 g, 2.6 mmol) and copper(I) iodide (496 mg, 2.6 mmol). After sparging for an additional 10 minutes with argon, the solution was stirred overnight at room temperature. The reaction mixture was filtered through a pad of Celite using an Et2O wash. Concentration of the filtrate under reduced pressure, followed by column chromatography (2-5% EtOAc-hexanes) of the residual solid afforded 2.28 g (50%) the title compound as an orange solid. 1H NMR (300 MHz, CDCl3) δ: 8.06 (1H, d, J=2.2 Hz), 8.02 (2H, d, J=8.5 Hz), 2.61 (1H, dd, J=2.2, 8.6 Hz), 7.55 (2H, d, J=8.5 Hz), 6.93 (1H, d, J=8.6 Hz), 4.39 (2H, q, J=7.1 Hz), 2.75 (3H, s), 1.48 (6H, s), 1.41 (t, J=7.1 Hz).
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][S:7][C:8]2[C:9](=[O:17])[N:10]([CH2:14][CH2:15][CH3:16])[CH:11]=[CH:12][N:13]=2)=[CH:4][CH:3]=1.[Na].[OH:21]OS([O-])=O.[K+].[OH2:27]>O1CCCC1>[Cl:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][S:7]([C:8]2[C:9](=[O:17])[N:10]([CH2:14][CH2:15][CH3:16])[CH:11]=[CH:12][N:13]=2)(=[O:21])=[O:27])=[CH:4][CH:3]=1
Reactant: O=S([O-])OO
Reactant: CCCn1ccnc(SCc2ccc(Cl)cc2)c1=O
Reactant: O
Agent: [K+]
Agent: [Na]
Solvent: C1CCOC1
Product: CCCn1ccnc(S(=O)(=O)Cc2ccc(Cl)cc2)c1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 23 %

Procedure:
To 360 mg (1.17 mM) of 3-[(4-chlorobenzyl)thio]-1-propylpyrazin-2(1H)-one and 107.7 mg (1.28 mM) of sodium hydrogenocarbonate in 2 ml of tetrahydrofurane were added 2.9 g (4.7 mM) of oxone in 2 ml of water. The reaction mixture was stirred for 3 h at room temperature. Water was added and the aqueous layer was extracted with ethyle acetate. The organic layer was separated and washed with water, dried on anhydrous sodium sulfate and evaporated under vacuum. The residue was taken up in diisopropyle oxide, filtered and washed with diisopropyle oxide, to give 90 mg of 3-[(4-chlorobenzyl)sulfonyl]-1-propylpyrazin-2(1H)-one. Yield: 23%.
Reaction SMILES: CS([C:5]1[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[CH:8]=[C:7]([C:21]([F:24])([F:23])[F:22])[N:6]=1)(=O)=O.[NH2:25][CH2:26][C:27]1[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=1>CC#N>[CH3:20][S:17]([C:14]1[CH:15]=[CH:16][C:11]([C:9]2[CH:8]=[C:7]([C:21]([F:24])([F:23])[F:22])[N:6]=[C:5]([NH:25][CH2:26][C:27]3[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=3)[N:10]=2)=[CH:12][CH:13]=1)(=[O:19])=[O:18]
Reactant: CS(=O)(=O)c1ccc(-c2cc(C(F)(F)F)nc(S(C)(=O)=O)n2)cc1
Reactant: NCc1cccnc1
Solvent: CC#N
Product: CS(=O)(=O)c1ccc(-c2cc(C(F)(F)F)nc(NCc3cccnc3)n2)cc1
Yield: 94.2 %

Procedure:
To a stirred solution of 2-(methylsulfonyl)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)pyrimidine (0.10 g, 0.26 mmol) in MeCN (3 ml) was added 3-(aminomethyl)-pyridine (169 mg, 6 eq) and the resultant solution heated under reflux for 3 h. The cooled reaction mixture was concentrated in vacuo and the resulting oil purified by SPE chromatography with chloroform then chloroform:methanol (50:1) as eluant. This gave the title compound as a yellow solid (100 mg, 93%).
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][CH2:13][C@@H:14]([NH2:16])[CH3:15])[N:5]=[C:4]([CH3:17])[C:3]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19].[OH:23][CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:36]=[CH:35][C:31]([C:32](O)=[O:33])=[CH:30][C:29]=1[O:37][CH3:38]>>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][CH2:13][C@@H:14]([NH:16][C:32](=[O:33])[C:31]2[CH:35]=[CH:36][C:28]([O:27][CH2:26][CH2:25][CH2:24][OH:23])=[C:29]([O:37][CH3:38])[CH:30]=2)[CH3:15])[N:5]=[C:4]([CH3:17])[C:3]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19]
Reactant: COc1cc(C(=O)O)ccc1OCCCO
Reactant: CCOC(=O)c1c(C)nc2cccc(OC[C@H](C)N)c2c1N
Product: CCOC(=O)c1c(C)nc2cccc(OC[C@H](C)NC(=O)c3ccc(OCCCO)c(OC)c3)c2c1N

Procedure:
Prepared as in Example 24a from (S)-ethyl 4-amino-5-(2-aminopropoxy)-2-methylquinoline-3-carboxylate (Example 26b) and 4-(3-hydroxypropoxy)-3-methoxybenzoic acid (Baraldi, P. G. et al. J. Med. Chem. 1999, 42, 5131) as a brown solid. MS 512 (MH+).
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][N: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(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][N: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][CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]2)=[CH:18][CH:17]=1
Reactant: COc1cc2ncnc(Oc3ccc(N)cc3)c2cc1OC
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: OCC1CCCCC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1cc2ncnc(Oc3ccc(NC(=O)OCC4CCCCC4)cc3)c2cc1OC
Yield: 82.9 %

Procedure:
4-[(6,7-Dimethoxy-4-quinazolinyl)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, cyclohexylmethanol (30 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 (61 mg, yield 70%).
Reaction SMILES: CN(C=O)C.[CH2:6]([C:9]1[C:17]2[O:16][N:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[C:13]=2[CH:12]=[CH:11][C:10]=1[O:22][CH2:23][CH2:24][CH2:25]Br)[CH2:7][CH3:8].[NH:27]1[CH2:31][CH2:30][NH:29][C:28]1=[O:32]>C(OCC)(=O)C>[CH2:6]([C:9]1[C:17]2[O:16][N:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[C:13]=2[CH:12]=[CH:11][C:10]=1[O:22][CH2:23][CH2:24][CH2:25][N:27]1[CH2:31][CH2:30][NH:29][C:28]1=[O:32])[CH2:7][CH3:8]
Reactant: CCCc1c(OCCCBr)ccc2c(C(F)(F)F)noc12
Reactant: O=C1NCCN1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCCc1c(OCCCN2CCNC2=O)ccc2c(C(F)(F)F)noc12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a DMF solution (5 mL) of 7-propyl-3-(trifluoromethyl)-6-(3-bromopropyloxy)-1,2-benzisoxazole as prepared in Example 7 (322 mg, 0.88 mmol), was added 2-imidazolidinone (320 mg, 3.52 mmol) and CsCO3 (320 mg, 0.97 mmol) then stirred at room temperature overnight. After aqueous work-up and silica gel chromatography (hexanes: 70% ethyl acetate), the title compound was obtained.
Reaction SMILES: [C:1]1(=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:8]([CH2:10][C:11]([O:13]CC)=O)#[N:9].[C:16]([CH2:18][C:19]([NH2:21])=[O:20])#[N:17].C(N(CC)CC)C>CO>[C:16]([CH:18]1[C:1]2([CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[CH:10]([C:8]#[N:9])[C:11](=[O:13])[NH:21][C:19]1=[O:20])#[N:17]
Reactant: CCOC(=O)CC#N
Reactant: N#CCC(N)=O
Reactant: O=C1CCCCC1
Solvent: CO
Solvent: CCN(CC)CC
Product: N#CC1C(=O)NC(=O)C(C#N)C12CCCCC2
Yield: 88 %

Procedure:
98 g (1 mol) of cyclohexanone, 113 g (1 mol) of ethyl cyanoacetate, 84 g (1 mol) of cyanoacetamide, and 100 ml of methanol were mixed in a reaction flask. 101 g (1 mol) of triethylamine was added dropwise under stirring, and the reaction mixture was stirred for 8 hours with the temperature controlled within the range of 25° C. to 30° C., and then was cooled and filtered. The filter cake was suspended in water, and the suspension was adjusted to pH 2-3 with concentrated hydrochloric acid while stirring. The suspension was filtered, washed with water, and dried to provide 1,5-dicyano-2,4-dioxo-3-azaspiro[5,5]-undecane. Yield: 88%, melting point: 202 to 210° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=O)[NH:10][C:11]3[C:19]=2[CH:18]=[C:17]2[C:13](=[C:14]([C:21]4[CH:26]=[CH:25][C:24]([Br:27])=[CH:23][CH:22]=4)[C:15](=[O:20])[NH:16]2)[CH:12]=3)=[CH:4][CH:3]=1.CN(C)C=O.[C:34](=[O:37])([O-])[O-].[K+].[K+].Br[CH2:41][CH:42]([CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH3:48]>CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:34](=[O:37])[N:10]([CH2:9][CH:8]([CH2:5][CH2:4][CH2:3][CH2:2][CH2:7][CH3:6])[CH2:19][CH2:18][CH2:17][CH2:13][CH2:14][CH2:21][CH2:22][CH3:23])[C:11]3[C:19]=2[CH:18]=[C:17]2[C:13](=[C:14]([C:21]4[CH:22]=[CH:23][C:24]([Br:27])=[CH:25][CH:26]=4)[C:15](=[O:20])[N:16]2[CH2:41][CH:42]([CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH:12]=3)=[CH:6][CH:7]=1
Reactant: O=C1Nc2cc3c(cc2=C1c1ccc(Br)cc1)NC(=O)C=3c1ccc(Br)cc1
Reactant: O=C([O-])[O-]
Reactant: CCCCCCCCC(CBr)CCCCCC
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CO
Product: CCCCCCCCC(CCCCCC)CN1C(=O)C(c2ccc(Br)cc2)=c2cc3c(cc21)=C(c1ccc(Br)cc1)C(=O)N3CC(CCCCCC)CCCCCCCC
Temperature: 90 °C
Yield: 106.8 %

Procedure:
3,7-Bis-(4-bromo-phenyl)-1H,5H-pyrrolo[2,3-f]indole-2,6-dione (1.500 g, 3.023 mmol) (1.3) is dissolved into anhydrous dimethylformamide (60 cm3) and then potassium carbonate (4.178 g, 30.23 mmol) and 7-bromomethyl-pentadecane (2.308 g, 7.558 mmol) are added. The resulting mixture is heated to 90° C. for 21 hours before been cooling down, poured into methanol (400 cm3), filtered and washed with water (200 cm3) to recover the pure product (1.525 g, Yield: 53%). NMR (1H, 300 MHz, CDCl3): δ 7.61 (d, J=8.7 Hz, 4H), 7.57 (d, J=8.6 Hz, 4H), 6.29 (s, 2H), 3.50 (d, J=7.3 Hz, 4H), 1.76 (m, 2H), 1.28 (m, 48H), 0.86 (t, J=7.1 Hz, 12H)
Reaction SMILES: Br[C:2]1[C:11]([NH:12][C:13](=[O:26])[C:14](=[O:25])[CH2:15][C:16]([CH3:24])([C:18]2C=CC=C[CH:19]=2)[CH3:17])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][O:5][C:6]2=O.NC1C=C2C(=CC=1)C(=O)[O:32]C2.CC(C)(C=C)CC(=O)C(O)=O>>[CH3:17][C:16]([CH3:24])([CH:18]=[CH2:19])[CH2:15][C:14](=[O:25])[C:13]([NH:12][C:11]1[CH:2]=[C:3]2[C:8]([CH2:6][O:5][C:4]2=[O:32])=[CH:9][CH:10]=1)=[O:26]
Reactant: CC(C)(CC(=O)C(=O)Nc1ccc2c(c1Br)COC2=O)c1ccccc1
Reactant: Nc1ccc2c(c1)COC2=O
Agent: C=CC(C)(C)CC(=O)C(=O)O
Product: C=CC(C)(C)CC(=O)C(=O)Nc1ccc2c(c1)C(=O)OC2

Procedure:
was obtained analogously to the process that is described for 4-bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide from 5-aminophthalide and 4,4-dimethyl-2-oxo-5-hexenoic acid, melting point 103-104° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[CH2:6][CH2:5][C:4]([CH3:8])([CH3:7])[CH:3]1[OH:9].[H-].[Na+].C1OCCOCCOCCOCCOCCOC1.[N+:31]([C:34]([CH3:36])=[CH2:35])([O-:33])=[O:32]>C(#N)C.O1CCCC1>[N+:31]([CH:34]([CH3:36])[CH2:35][O:9][CH:3]1[C:4]([CH3:8])([CH3:7])[CH2:5][CH2:6][C:2]1([CH3:10])[CH3:1])([O-:33])=[O:32]
Reactant: CC1(C)CCC(C)(C)C1O
Reactant: C=C(C)[N+](=O)[O-]
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC#N
Product: CC(COC1C(C)(C)CCC1(C)C)[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2,2,5,5-Tetramethyl-1-cyclopentanol is added to a dry flask under argon at 0° C. Dry tetrahydrofuran is added with a syringe. Sodium hydride (60% dispersion in oil) is added quickly in one portion and the contents of the flask are stirred for one hour at room temperature. A 10 mM solution of 18-crown-6-ether in acetonitrile is added with a syringe and the flask cooled to 0° C. A tetrahydrofuran solution of 2-nitropropene is added with vigorous stirring over a 10 minute period. After completion of the reaction as judged by thin layer chromatography, it is quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic layer is dried over MgSO4 and evaporated to yield 1-(2-nitropropoxy)-2,2,5,5-tetramethylcyclopentane.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH3:14])[C@@H:9]([CH3:13])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15]([O:19][C:20]([NH:22]O)=[O:21])([CH3:18])([CH3:17])[CH3:16]>>[C:1]([O:5][C:6]([N:8]([CH3:14])[C@@H:9]([CH3:13])[C:10]([O:12][NH:22][C:20]([O:19][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:21])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)NO
Reactant: C[C@@H](C(=O)O)N(C)C(=O)OC(C)(C)C
Product: C[C@@H](C(=O)ONC(=O)OC(C)(C)C)N(C)C(=O)OC(C)(C)C

Procedure:
[(tert-Butoxy)carbonyl]amino (2S)-2-{[(tert-butoxy)carbonyl](methyl)amino}-propanoate is prepared from (2S)-2-{[(tert-butoxy)carbonyl](methyl)amino}propanoic acid and N-tert-butoxycarbonyl hydroxylamine according to Scheme 6. (0.96 g, 61%), The compound exists as rotomers and is reported as such. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.73-7.89 (1H, m), 4.61-5.04 (1H, m), 2.86-2.96 (3H, m), 1.41-1.53 (21H, m).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[C:5]=1[C:6](Cl)=[O:7])[CH3:2].[NH2:28][C:29]1[CH:30]=[CH:31][C:32]([N+:39]([O-:41])=[O:40])=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1.C(N(CC)CC)C>ClCCl>[CH2:1]([O:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[C:5]=1[C:6]([NH:28][C:29]1[CH:30]=[CH:31][C:32]([N+:39]([O-:41])=[O:40])=[C:33]([C:35]([F:36])([F:37])[F:38])[CH:34]=1)=[O:7])[CH3:2]
Reactant: Nc1ccc([N+](=O)[O-])c(C(F)(F)F)c1
Reactant: CCCCCCCCCCCCCCCc1cccc(OCC)c1C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCCCCc1cccc(OCC)c1C(=O)Nc1ccc([N+](=O)[O-])c(C(F)(F)F)c1

Procedure:
2-ethoxy-6-pentadecyl-benzoyl chloride was condensed with 5-Amino-2-nitrobenzotrifluoride in dichloromethane in presence of triethylamine as acid scavenger to yield 2-Ethoxy-N-(4-nitro-3-trifluromethyl-phenyl)-6-pentadecyl-benzamide. The reaction mixture was then concentrated in vacuo and the residue was extracted into ethyl acetate. The ethyl acetate layer was washed with water and with cold aqueous hydrochloric acid, then dried over sodium sulphate and finally concentrated in vacuo. The residue obtained was chromatographed over silica gel to afford the desired product.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:13]=[CH:12][C:10]([NH2:11])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.Cl[C:15]1[C:16](=[O:34])[N:17]([CH2:27][C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[C:18](=[O:26])[C:19]=1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.O>CC#N>[N:4]1([C:7]2[CH:13]=[CH:12][C:10]([NH:11][C:15]3[C:16](=[O:34])[N:17]([CH2:27][C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)[C:18](=[O:26])[C:19]=3[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2][O:1][CH2:6][CH2:5]1
Reactant: O=C1C(Cl)=C(c2ccccc2)C(=O)N1Cc1cccnc1
Reactant: Nc1ccc(N2CCOCC2)cc1
Solvent: O
Solvent: CC#N
Product: O=C1C(Nc2ccc(N3CCOCC3)cc2)=C(c2ccccc2)C(=O)N1Cc1cccnc1
Temperature: 130 °C
Yield: 27 %

Procedure:
4-Morpholinoaniline (0.94 mmol, 178 mg) dissolved in dry CH3CN (2 mL) was added to crude 3-chloro-4-phenyl-1-(pyridin-3-ylmethyl)-1H-pyrrole-2,5-dione (0.47 mmol, 140 mg) and the reaction mixture was subjected to microwave heating single node 130° C. for 10 min. 0.3 mL water was added and the reaction mixture was purified using HPLC (57% 0.1M ammonium acetate buffer: 43% CH3CN→100% CH3CN, 20 mL/min) to give 56 mg (27%) of the title compound. 1H NMR (400 MHz, CD3CN) δ 8.63 (d, 1H), 8.51 (dd, 1H), 7.81-7.73 (m, 1H), 7.36-7.31 (m, 1H), 7.16-7.11 (m,1H), 7.10-7.04 (m, 2H), 6.99-6.93 (m, 2H), 6.69-6.64 (m, 2H), 6.59-6.53 (m, 2H), 4.75 (s, 2H), 3.74 (t, J=4.8 Hz, 4H), 2.97 (t, J=4.8 Hz, 4H).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]=O)=[CH:9][C:4]=2[CH:3]=[CH:2]1.[C:12]([Si:16]([CH3:31])([CH3:30])[O:17][CH2:18][CH2:19]OC1C=CC(I)=CC=1C=O)(C)(C)C.C[Si]([NH:36][Si](C)(C)C)(C)C.C([Li])CCC.C[Si](Cl)(C)C.C(N(CC)CC)C.C(Cl)(=O)C>>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]=[N:36][C:18]([O:17][Si:16]([CH3:31])([CH3:30])[CH3:12])=[CH2:19])=[CH:9][C:4]=2[CH:3]=[CH:2]1
Reactant: O=Cc1ccc2occc2c1
Reactant: CC(C)(C)[Si](C)(C)OCCOc1ccc(I)cc1C=O
Reactant: C[Si](C)(C)N[Si](C)(C)C
Agent: C[Si](C)(C)Cl
Agent: [Li]CCCC
Solvent: CC(=O)Cl
Solvent: CCN(CC)CC
Product: C=C(N=Cc1ccc2occc2c1)O[Si](C)(C)C

Procedure:
In a manner similar to the method described in example 190b, 1-benzofuran-5-carbaldehyde (1.2 g, 10 mmol) (Maybr-INT) was used as the starting material in place of 2-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-5-iodo-benzaldehyde to react with 1,1,3,3,3-hexamethyldisilazane (1.6 g, 10 mmol), n-butyllithium (2.5 M, 4 mL, 10 mmol), trimethylsilyl chloride (1.1 g, 10 mmol), triethylamine (1.36 g, 13.6 mmol) and acetyl chloride (1 g, 13.6 mmol) to give crude 1-(1-benzofuran-5-yl)-3-trimethylsilyoxy-2-aza-1,3-butadiene as a yellow gum and used for the next step without further purification.
Reaction SMILES: [F:1][C:2]([F:28])([F:27])[C:3]1[CH:4]=[C:5]([CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=1)[CH2:6][N:7]1[C:11]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[C:10]([CH2:18]O)[N:9]=[N:8]1.Cl.Cl.[OH:31][NH2:32].O>CS(C)=O>[F:1][C:2]([F:28])([F:27])[C:3]1[CH:4]=[C:5]([CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=1)[CH2:6][N:7]1[C:11]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[C:10]([CH:18]=[N:32][OH:31])[N:9]=[N:8]1
Reactant: OCc1nnn(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c1-c1cccnc1
Reactant: NO
Agent: Cl
Solvent: CS(C)=O
Solvent: O
Product: ON=Cc1nnn(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c1-c1cccnc1
Reaction time: 6 h

Procedure:
Add 3 eq sulfur trioxide pyridine complex (Aldrich) to a solution of [1-(3,5-bis-trifluoromethyl-benzyl)-5-pyridin-3-yl-1H-[1,2,3]triazol-4-yl]-methanol in DMSO, then add 10 eq TEA. Stir for 6 hours, pour into 15 ml 1N HCl and extract with EtOAc (2×20 ml). Remove solvent and dissolve the crude aldehyde in MeOH. Add 1.5 eq of hydroxyl amine hydrochloride and stir for 6 hours. Pour into 50 ml water and extract with EtOAc. Purify via radial chromatography 1:1 hexanes:EtOAc to give the title compound. MS (IS) 416.1 (M+1). Rf=0.16 (1:1 hexanes:EtOAc).