Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[NH:5][C:4]([CH3:11])([CH3:10])[CH2:3]1.[C:12]([O:20][CH3:21])(=[O:19])[CH2:13][CH2:14][C:15](OC)=[O:16].[NH2-:22].[Li+].CO>C1(C)C(C)=CC=CC=1>[C:12]([O:20][CH:21]1[CH2:7][C:6]([CH3:9])([CH3:8])[NH:22][C:4]([CH3:11])([CH3:10])[CH2:3]1)(=[O:19])[CH2:13][CH2:14][C:15]([O:1][CH:2]1[CH2:3][C:4]([CH3:11])([CH3:10])[NH:5][C:6]([CH3:9])([CH3:8])[CH2:7]1)=[O:16]
Reactant: [NH2-]
Reactant: CC1(C)CC(O)CC(C)(C)N1
Reactant: COC(=O)CCC(=O)OC
Agent: [Li+]
Solvent: CO
Solvent: Cc1ccccc1C
Product: CC1(C)CC(OC(=O)CCC(=O)OC2CC(C)(C)NC(C)(C)C2)CC(C)(C)N1

Procedure:
322.3 g (2.05 mol) of 4-hydroxy-2,2,6,6-tetramethylpiperidine and 146.1 g (1 mol) of dimethyl succinate in 300 ml of xylene are heated to 80° C. 1.2 g of lithium amide are added to the reaction mixture at this temperature, and the temperature is raised to 120°-125° C. A mixture of methanol and xylene is then distilled off slowly under a slow stream of nitrogen. After approx. 10 hours virtually no more methanol distills off, which indicates the end of the transesterification. The contents of the flask are diluted with 500 ml of petroleum ether (boiling range 110°-140° C.) and are washed in the separating funnel while still warm (60°-70° C.) with three times 100 ml of water. The reaction product crystallizes from the organic phase on cooling as colourless crystals. The di-(2,2,6,6-tetramethyl-4-piperidinyl) succinate obtained melts at 118° C.
Reaction SMILES: [C:1]([C:6]1[CH:11]=[C:10]([C:12]([CH2:15][CH3:16])([CH3:14])[CH3:13])[CH:9]=[CH:8][C:7]=1[OH:17])([CH2:4][CH3:5])([CH3:3])[CH3:2].[OH-:18].[K+].CN(C)[CH:22]=[O:23]>C1(C)C=CC=CC=1>[OH:17][C:7]1[C:6]([C:1]([CH2:4][CH3:5])([CH3:3])[CH3:2])=[CH:11][C:10]([C:12]([CH2:15][CH3:16])([CH3:14])[CH3:13])=[CH:9][C:8]=1[C:22]([OH:23])=[O:18]
Reactant: [OH-]
Reactant: CN(C)C=O
Reactant: CCC(C)(C)c1ccc(O)c(C(C)(C)CC)c1
Agent: [K+]
Solvent: Cc1ccccc1
Product: CCC(C)(C)c1cc(C(=O)O)c(O)c(C(C)(C)CC)c1
Yield: 50 %

Procedure:
2,4-di-t-amyl phenol (0.44 m) and KOH (0.5 m) were refluxed in toluene for two hours. Dimethylformamide (100 ml) was added and solvent was removed by distillation until the temperature reached 145°. CO2 was bubbled in and more solvent was removed until the temperature reached 160°. This temperature was maintained for four hours with CO2 passing in and the reaction mixture was worked up to give 2-hydroxy-3,5-di-t-amylbenzoic acid which was esterified to form the methyl ester, which had a boiling point of 127°-129°C at 0.7 mm Hg pressure, in 50% yield. The ester was then converted to the hydrazide by refluxing with hydrazine hydrate in aqueous ethanol. The hydrazide had a melting point of 132°-133°C and the following elemental analysis by weight:
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]3[CH:17]=[CH:16][C:14]([NH2:15])=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1.[CH3:18][N:19]([CH3:29])[C:20]1[CH:28]=[CH:27][C:23]([C:24](Cl)=[O:25])=[CH:22][CH:21]=1.C(Cl)Cl.CCOC(C)=O>N1C=CC=CC=1>[CH3:18][N:19]([CH3:29])[C:20]1[CH:28]=[CH:27][C:23]([C:24]([NH:15][C:14]2[CH:16]=[CH:17][C:11]([C:9]3[N:10]=[C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]4[CH:8]=3)=[CH:12][CH:13]=2)=[O:25])=[CH:22][CH:21]=1
Reactant: CN(C)c1ccc(C(=O)Cl)cc1
Reactant: Nc1ccc(-c2cn3cc(F)ccc3n2)cc1
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CN(C)c1ccc(C(=O)Nc2ccc(-c3cn4cc(F)ccc4n3)cc2)cc1
Yield: 35.8 %

Procedure:
Prepared as described in the Amide Coupling section using 4-(6-fluoroimidazo[1,2-a]pyridin-2-yl)aniline (100 mg, 0.44 mmol) and 4-dimethylaminobenzoyl chloride (81 mg, 0.44 mmol) in dry pyridine (5 ml) to give the title compound (59 mg, 36%) as a pale yellow solid after work-up and flash chromatography (1:1 DCM/EtOAc).
Reaction SMILES: C1N([C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)N=NC=1COCC(N)(COCC1N=NN([C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)C=1)CO.[F:43][C:44]([F:141])([F:140])[C:45]([F:139])([F:138])[C:46]([F:137])([F:136])[C:47]([F:135])([F:134])[C:48]([F:133])([F:132])[C:49]([F:131])([F:130])[C:50]([F:129])([F:128])[C:51]([F:127])([F:126])[CH2:52][CH2:53][CH2:54][CH2:55][O:56][C:57]1[CH:58]=[C:59]([CH:63]=[C:64]([O:96][CH2:97][CH2:98][CH2:99][CH2:100][C:101]([F:125])([F:124])[C:102]([F:123])([F:122])[C:103]([F:121])([F:120])[C:104]([F:119])([F:118])[C:105]([F:117])([F:116])[C:106]([F:115])([F:114])[C:107]([F:113])([F:112])[C:108]([F:111])([F:110])[F:109])[C:65]=1[O:66][CH2:67][CH2:68][CH2:69][CH2:70][C:71]([F:95])([F:94])[C:72]([F:93])([F:92])[C:73]([F:91])([F:90])[C:74]([F:89])([F:88])[C:75]([F:87])([F:86])[C:76]([F:85])([F:84])[C:77]([F:83])([F:82])[C:78]([F:81])([F:80])[F:79])[C:60]([OH:62])=[O:61].[CH:142]1[C:154]2[N:153]([CH2:155][CH2:156][O:157][CH2:158][CH2:159]O)[C:152]3[C:147](=[CH:148][CH:149]=[CH:150][CH:151]=3)[C:146]=2[CH:145]=[CH:144][CH:143]=1>>[CH:151]1[C:152]2[N:153]([CH2:155][CH2:156][O:157][CH2:158][CH2:159][O:61][C:60](=[O:62])[C:59]3[CH:58]=[C:57]([O:56][CH2:55][CH2:54][CH2:53][CH2:52][C:51]([F:126])([F:127])[C:50]([F:128])([F:129])[C:49]([F:130])([F:131])[C:48]([F:132])([F:133])[C:47]([F:134])([F:135])[C:46]([F:136])([F:137])[C:45]([F:138])([F:139])[C:44]([F:140])([F:141])[F:43])[C:65]([O:66][CH2:67][CH2:68][CH2:69][CH2:70][C:71]([F:94])([F:95])[C:72]([F:93])([F:92])[C:73]([F:91])([F:90])[C:74]([F:89])([F:88])[C:75]([F:87])([F:86])[C:76]([F:85])([F:84])[C:77]([F:83])([F:82])[C:78]([F:81])([F:80])[F:79])=[C:64]([O:96][CH2:97][CH2:98][CH2:99][CH2:100][C:101]([F:124])([F:125])[C:102]([F:122])([F:123])[C:103]([F:120])([F:121])[C:104]([F:118])([F:119])[C:105]([F:117])([F:116])[C:106]([F:115])([F:114])[C:107]([F:113])([F:112])[C:108]([F:111])([F:110])[F:109])[CH:63]=3)[C:154]3[C:146](=[CH:145][CH:144]=[CH:143][CH:142]=3)[C:147]=2[CH:148]=[CH:149][CH:150]=1
Reactant: O=C(O)c1cc(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)c(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)c(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)c1
Reactant: OCCOCCn1c2ccccc2c2ccccc21
Agent: NC(CO)(COCc1cn([C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)nn1)COCc1cn([C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)nn1
Product: O=C(OCCOCCn1c2ccccc2c2ccccc21)c1cc(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)c(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)c(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)c1

Procedure:
The synthesis of a mobility donor fluorinated dendron D1 of the present invention is as shown in the Scheme below. D1 is prepared using 3,4,5-tris-(12,12,12,11,11,10,10,9,9,8,8,7,7,6,6,5,5-heptadecafluoro-n-dodecan-1-yloxy)-benzoic acid as a starting material. The intermediate is then reacted with an alcohol of the desired apex moiety, 2-(2-carbazol-9yl-ethoxy)-ethanol, to obtain the compound of the invention.
Reaction SMILES: Cl.[O:2]1[C:6]2[CH2:7][NH:8][CH2:9][CH2:10][C:5]=2[CH:4]=[CH:3]1.[CH2:11]([C:19]1[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=1)[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(CC)CC)C.C(P(=O)(OCC)OCC)#N>CN(C)C=O.O>[CH2:11]([C:19]1[CH:20]=[CH:21][C:22]([C:23]([N:8]2[CH2:9][CH2:10][C:5]3[CH:4]=[CH:3][O:2][C:6]=3[CH2:7]2)=[O:24])=[CH:26][CH:27]=1)[CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: O=C(O)c1ccc(CCc2ccccc2)cc1
Reactant: c1cc2c(o1)CNCC2
Agent: CCOP(=O)(C#N)OCC
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: O=C(c1ccc(CCc2ccccc2)cc1)N1CCc2ccoc2C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 0.552 g (3.458 mmol) of 4,5,6,7-tetrahydrofuro[2,3-c]pyridine hydrochloride, 0.78 g (3.46 mmol) of 4-phenethylbenzoic acid and 1.93 ml (13.8 mmol) of triethylamine in 15 ml of N,N-dimethylformamide, 0.63 ml (4.15 mmol) of diethyl cyanophosphonate was added dropwise, followed by overnight stirring at room temperature. This mixture was poured into water and extracted with diethyl ether 3 times. The combined organic layer was dried over anhydrous sodium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=6/1 to 3/1) to yield 6-(4-phenethylbenzoyl)-4,5,6,7-tetrahydrofuro[2,3-c]pyridine.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH:5]=[O:6].[OH:7][CH2:8][CH:9]([CH3:12])[CH:10]=[O:11]>>[CH2:5]([OH:6])[CH2:4][CH2:3][CH2:2][OH:1].[CH3:12][CH:9]([CH2:10][OH:11])[CH2:8][OH:7]
Reactant: O=CCCCO
Reactant: CC(C=O)CO
Product: CC(CO)CO
Product: OCCCCO

Procedure:
The polyvinyl acetal resins of the invention include 4-hydroxybutanal as an aldehyde component. Pure 4-hydroxybutanal is suitable for the invention, but is obtained only by laborious and costly methods. An economical source of 4-hydroxybutanal is an aqueous aldehyde stream produced commercially when allyl alcohol is hydroformylated in the presence of a rhodium catalyst. The aqueous stream, which typically contains about 5-20 wt. % aldehydes, is obtained by extracting the hydroformylation reaction mixture with water. The aldehyde mixture contains about a 7:1 molar ratio of 4-hydroxybutanal and 3-hydroxy-2-methylpropanal. In the commercial process, the aldehyde stream is hydrogenated to give 1,4-butanediol and 2-methyl-1,3-propanediol. However, the aqueous aldehyde stream is alternatively and advantageously used for the process and compositions of the present invention. The aqueous aldehyde solution used for the invention can have any desired aldehyde concentration.
Reaction SMILES: CO[C:3]([C:5]1[C:14]([OH:15])=[C:13]2[C:8]([CH:9]=[CH:10][C:11](=[O:23])[N:12]2[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:7][N:6]=1)=[O:4].OC(C(F)(F)F)=O.[NH2:31][CH2:32][C:33]([CH3:38])([CH3:37])[C:34]([OH:36])=[O:35].C[O-].[Na+]>CCO.C([O-])(O)=O.[Na+]>[CH2:16]([N:12]1[C:13]2[C:8](=[CH:7][N:6]=[C:5]([C:3]([NH:31][CH2:32][C:33]([CH3:38])([CH3:37])[C:34]([OH:36])=[O:35])=[O:4])[C:14]=2[OH:15])[CH:9]=[CH:10][C:11]1=[O:23])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: COC(=O)c1ncc2ccc(=O)n(Cc3ccccc3)c2c1O
Reactant: CC(C)(CN)C(=O)O
Agent: C[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: CCO
Product: CC(C)(CNC(=O)c1ncc2ccc(=O)n(Cc3ccccc3)c2c1O)C(=O)O
Temperature: 150 °C
Yield: 27.8 %

Procedure:
A mixture of 1-benzyl-8-hydroxy-2-oxo-1,2-dihydro-[1,6]naphthyridine-7-carboxylic acid methyl ester (19 mg, 0.061 mmol), 3-amino-2,2-dimethyl-propionic acid TFA salt (71 mg, 0.31 mmol) and NaOMe (33 mg, 0.61 mmol) in 2 mL of EtOH was heated at 150° C. in a microwave reactor for 6 h. Solvent was evaporated in vacuo, and the residue was partitioned between water and EtOAc. 1 M was added with vigorous stirring until pH about 1. The organic layer was dried over MgSO4 and concentrated in vacuo. The crude product was purified by silica gel chromatography (5-60% EtOAc/hexanes+2% AcOH). The product isolated was then dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 1 with 4 M HCl, and the resulting precipitate was collected by filtration and dried to give 6.7 mg of the title compound. MS: (+) m/z 396.30 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:41]=[CH:40][C:5]2[N:6](CC3C=CC(OC)=CC=3)[C:7](=[O:30])[CH:8]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[Cl:29])[N:9]=[C:10]([C:11]3[CH:21]=[CH:20][C:14]4[NH:15][C:16](=[O:19])[N:17]([CH3:18])[C:13]=4[CH:12]=3)[C:4]=2[CH:3]=1.[Al+3].[Cl-].[Cl-].[Cl-].C(OCC)(=O)C>C1(OC)C=CC=CC=1.ClC(Cl)=C>[Cl:1][C:2]1[CH:41]=[CH:40][C:5]2[NH:6][C:7](=[O:30])[CH:8]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[Cl:29])[N:9]=[C:10]([C:11]3[CH:21]=[CH:20][C:14]4[NH:15][C:16](=[O:19])[N:17]([CH3:18])[C:13]=4[CH:12]=3)[C:4]=2[CH:3]=1
Reactant: COc1ccc(CN2C(=O)C(Cc3ccccc3Cl)N=C(c3ccc4[nH]c(=O)n(C)c4c3)c3cc(Cl)ccc32)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: COc1ccccc1
Solvent: CCOC(C)=O
Solvent: C=C(Cl)Cl
Product: Cn1c(=O)[nH]c2ccc(C3=NC(Cc4ccccc4Cl)C(=O)Nc4ccc(Cl)cc43)cc21
Temperature: 85 °C
Reaction time: 0.5 h
Yield: 59 %

Procedure:
7-Chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-5-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one (0.4 g, 0.68 mmol) was dissolved in 10% anisole in 1,1-dichloroethene (DCE, 3 mL) under nitrogen and AlCl3 (0.455 g, 3.42 mmol) was added in one portion. The resulting orange solution was heated to 85° C. for 1.5 h. The solution was allowed to cool. Ethyl acetate was added followed by ice water. This mixture was stirred for 30 min (turned from yellow to colorless) then partitioned and the organic layer was washed with water then brine. The organic layer was dried over MgSO4, then filtered to give a clear, very pale yellow solution. Silica gel was added and the solvent was removed under reduced pressure. Chromatography on silica gel eluting with 5-50-100% ethyl acetate in hexanes gave 7-chloro-3-(2-chlorobenzyl)-5-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one as a white solid (59% yield).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]1[O:14][CH2:13][CH2:12][O:11]1.[CH:15]([N:18]([CH:21]([CH3:23])C)[CH2:19][CH3:20])(C)C.Cl.[CH:25]1([C:31]([OH:48])([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:32]([O:34][CH2:35][CH:36]2CCNCC2)=[O:33])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1>C(#N)C.ClCCl>[CH:42]1([C:31]([OH:48])([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:32]([O:34][CH2:35][CH:36]2[CH2:20][CH2:19][N:18]([CH2:15][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]3[O:14][CH2:13][CH2:12][O:11]3)[CH2:21][CH2:23]2)=[O:33])[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1
Reactant: O=C(OCC1CCNCC1)C(O)(c1ccccc1)C1CCCCC1
Reactant: BrCCCCCCCCC1OCCO1
Reactant: CCN(C(C)C)C(C)C
Agent: Cl
Solvent: CC#N
Solvent: ClCCl
Product: O=C(OCC1CCN(CCCCCCCCCC2OCCO2)CC1)C(O)(c1ccccc1)C1CCCCC1
Temperature: 60 °C

Procedure:
2-(8-Bromooctyl)-1,3-dioxolane (218 mg, 0.82 mmol) followed by di-isopropylethylamine (361 μL, 2.07 mmol) were added to a solution of piperidin-4-ylmethyl 2-cyclohexyl-2-hydroxy-2-phenylacetate hydrochloride (252 mg, 0.69 mmol) in acetonitrile (4 mL). The reaction mixture was heated at 60° C. for 17 hours. After this time, the reaction was cooled to RT and diluted with dichloromethane. The organic extracts were washed with water, filtered through a hydrophobic frit, and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography eluting with 100% dichloromethane to 40:1 dichloromethane:methanol to afford the title compound that was used without further purification in the next step.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[C:4]([F:12])([F:11])[C:5]([F:10])([F:9])[N:6]=[N+:7]=[N-:8].[CH2:14]([N:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[CH3:15]>CCOCC>[CH3:1][N+:16]([CH2:19][CH3:20])([CH2:17][CH3:18])[CH2:14][CH3:15].[N:6]([C:5]([F:9])([F:10])[C:4]([F:12])([F:11])[C:3]([O-:13])=[O:2])=[N+:7]=[N-:8]
Reactant: CCN(CC)CC
Reactant: COC(=O)C(F)(F)C(F)(F)N=[N+]=[N-]
Solvent: CCOCC
Product: CC[N+](C)(CC)CC
Product: [N-]=[N+]=NC(F)(F)C(F)(F)C(=O)[O-]
Reaction time: 576 h

Procedure:
A mixture of 37.0 g (0.184 mole) of methyl-3-azidotetrafluoropropionate, prepared as in Example 9, 20.2 g (0.20 mole of triethylamine, and 50 ml of ether was stirred at 25°. A second layer slowly formed. The reaction was stopped after 24 days, at which time the second layer was not increasing in volume. Evaporation of volatiles under full pump vacuum left 54.9 g (99% of theory) of methyltriethylammonium 3-azidotetrafluoropropionate as a moist solid. IR(CHCl3): 3020 (sat'd CH), 2170 (N3), 1690 (CO2), and 1250-1100 cm-1 (CF). NMR (DMSO-d6): 1H 3.31 (q, JHH 7 Hz, 6H, CH2), 2.93 (s, 3H, NCH3), and 1.22 ppm (t, JHH 7 Hz, 9H, CH3); 19F -90.8 (t, JFF 6.3 Hz, 2F, CF2N3) and -115.6 ppm (t, JFF 6.3 Hz, 2F, CF2C=O).
Reaction SMILES: [CH2:1]([N:8]([CH3:24])[C:9]1[C:10](=[O:23])[NH:11][C:12]2[C:17]([N:18]=1)=[CH:16][C:15]([C:19]([O:21][CH3:22])=[O:20])=[CH:14][CH:13]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[O:31](S(C(F)(F)F)(=O)=O)[S:32]([C:35]([F:38])([F:37])[F:36])(=O)=[O:33]>ClCCl>[CH2:1]([N:8]([CH3:24])[C:9]1[C:10]([O:23][S:32]([C:35]([F:38])([F:37])[F:36])(=[O:33])=[O:31])=[N:11][C:12]2[C:17]([N:18]=1)=[CH:16][C:15]([C:19]([O:21][CH3:22])=[O:20])=[CH:14][CH:13]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)c1ccc2[nH]c(=O)c(N(C)Cc3ccccc3)nc2c1
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)c1ccc2nc(OS(=O)(=O)C(F)(F)F)c(N(C)Cc3ccccc3)nc2c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of methyl 3-[benzyl(methyl)amino]-2-oxo-1,2-dihydroquinoxaline-6-carboxylate (200 mg, 0.62 mmol) in dichloromethane (30 mL) was added pyridine (196 mg, 2.48 mmol), followed by Tf2O (349 mg, 1.24 mmol) at room temperature. The mixture was stirred overnight at room temperature, then quenched with water (100 mL), extracted with dichloromethane (3×20 mL1), and the organic layers combined and dried over anhydrous magnesium sulfate and concentrated under vacuum to afford methyl 3-(benzyl(methyl)amino)-2-(trifluoromethylsulfonyloxy)quinoxaline-6-carboxylate as a red solid (300 mg, crude).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[O:12][CH2:13][CH3:14])[C:7]#[N:8])[CH3:2].C(N)(=S)C.Cl.CN(C)C=[O:23]>>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[O:12][CH2:13][CH3:14])[C:7]([NH2:8])=[O:23])[CH3:2]
Reactant: CCOc1ccc(C#N)cc1OCC
Reactant: CN(C)C=O
Agent: CC(N)=S
Agent: Cl
Product: CCOc1ccc(C(N)=O)cc1OCC
Temperature: 130 °C

Procedure:
In 120 ml of 10% hydrochloric acid-dimethylformamide were dissolved 29 g of 3,4-diethoxybenzonitrile and 23 g of thioacetamide. The solution was heated at 90° C. for 3 hours and further at 130° C. for 5 hours to conduct a reaction. The reaction mixture was subjected to distillation to remove the solvent. The residue was washed twice with 100 ml of diethyl ether, followed by washing with 100 ml of water. The resulting crystals were collected by filtration and dried to obtain 21.7 g of 3,4-diethoxybenzamide.
Reaction SMILES: C([N:3](CC)CC)C.P(N=[N+]=[N-])(OC1C=CC=CC=1)(OC1C=CC=CC=1)=O.[CH3:27][O:28][C:29]1[C:30]([N+:38]([O-:40])=[O:39])=[C:31]([CH:35]=[CH:36][CH:37]=1)C(O)=O.O>C1(C)C=CC=CC=1>[CH3:27][O:28][C:29]1[C:30]([N+:38]([O-:40])=[O:39])=[C:31]([NH2:3])[CH:35]=[CH:36][CH:37]=1
Reactant: CCN(CC)CC
Reactant: COc1cccc(C(=O)O)c1[N+](=O)[O-]
Agent: [N-]=[N+]=NP(=O)(Oc1ccccc1)Oc1ccccc1
Solvent: O
Solvent: Cc1ccccc1
Product: COc1cccc(N)c1[N+](=O)[O-]
Yield: 35 %

Procedure:
Triethylamine (6.29 mL) and diphenyl azidophosphate (6.66 mL, 30.1 mmol) were added to a suspension of 3-methoxy-2-nitrobenzoic acid (3.00 g, 15.2 mmol) in toluene (50 mL). The reaction mixture was stirred under reflux for 2 hours, water (10 mL) was added and it was stirred overnight under reflux. After evaporation of the solvent, the residue was dissolved in AcOEt and the resulting solution was filtered through celite. The organic phase was washed with saturated solution of NaHCO3, brine, dried over MgSO4, filtered and evaporated. The crude residue was purified by flash chromatography (cyclohexane/AcOEt 4:1) to yield 900 mg (5.35 mmol, 35%) of 3-methoxy-2-nitrophenylamine as a yellow solid.
Reaction SMILES: [S:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][NH:5][C:4]=2[CH:3]=[CH:2]1.C(N(CC)CC)C.[N+:18]([C:21]1[CH:29]=[CH:28][C:24]([C:25](Cl)=[O:26])=[CH:23][CH:22]=1)([O-:20])=[O:19]>ClCCl>[N+:18]([C:21]1[CH:22]=[CH:23][C:24]([C:25]([N:5]2[CH2:6][CH2:7][CH2:8][CH2:9][C:10]3[S:1][CH:2]=[CH:3][C:4]2=3)=[O:26])=[CH:28][CH:29]=1)([O-:20])=[O:19]
Reactant: c1cc2c(s1)CCCCN2
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(c1ccc([N+](=O)[O-])cc1)N1CCCCc2sccc21
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 10.71 g of 5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepine and 19.4 ml of triethylamine in 150 ml of dichloromethane under argon is added in small portions 4 -nitrobenzoyl chloride (exothermic). The mixture is stirred for 3 hours at 25° C. and then washed with water, sodium bicarbonate solution, brine and dried (Na2SO4). The solvent is removed, the residue dried under vacuum and recrystallized by dissolving in hot ethyl acetate and diluting with hexane. Chilling overnight and filtering gives 16 g of light brown crystals, m.p. 141°14 142° C.
Reaction SMILES: C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[NH:8][CH2:9][CH2:10][S:11][C:12]([O:14]C2C=CC([N+]([O-])=O)=CC=2)=O)C=CC=CC=1.[NH:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1>>[O:39]1[CH2:40][CH2:41][N:36]([C:12]([S:11][CH2:10][CH2:9][NH2:8])=[O:14])[CH2:37][CH2:38]1
Reactant: C1COCCN1
Reactant: O=C(Oc1ccc([N+](=O)[O-])cc1)SCCNC(c1ccccc1)(c1ccccc1)c1ccccc1
Product: NCCSC(=O)N1CCOCC1

Procedure:
N-triphenylmethyl-2-paranitrophenoxycarbonylthioethylamine (300 mg) and morpholine (162 μl) were subjected to similar reactions to those described in References 2 and 4 to give 2-morpholinocarbonylthioethylamine (crude formate: 134 mg). The product was dissolved in anhydrous methanol (3 ml). To the reaction solution were added triethylamine (486 μl) and mitomycin A (195 mg: 0.8 molar equivalent). The mixture was treated in a similar manner to that described in Example 1 to obtain Compound 33 (176 mg) in the form of grayish blue powders with a yield of 50%.
Reaction SMILES: [NH2:1][CH2:2][C:3]([CH3:8])([CH3:7])[C:4]([NH2:6])=[O:5].OC1C=CC=CN=1.[C:16]([O:20][C:21](=[O:50])[NH:22][C@H:23]([C@@H:41]1[CH2:45][C@@H:44]([CH:46]([CH3:48])[CH3:47])[C:43](=[O:49])[O:42]1)[CH2:24][N:25]1[CH2:30][C:29](=[O:31])[N:28]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[Cl:38])[CH2:27][C:26]1([CH3:40])[CH3:39])([CH3:19])([CH3:18])[CH3:17]>C(N(CC)CC)C>[C:16]([O:20][C:21](=[O:50])[NH:22][C@@H:23]([CH2:24][N:25]1[CH2:30][C:29](=[O:31])[N:28]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[Cl:38])[CH2:27][C:26]1([CH3:39])[CH3:40])[C@@H:41]([OH:42])[CH2:45][C@H:44]([C:43](=[O:49])[NH:1][CH2:2][C:3]([C:4](=[O:5])[NH2:6])([CH3:8])[CH3:7])[CH:46]([CH3:48])[CH3:47])([CH3:17])([CH3:18])[CH3:19]
Reactant: CC(C)[C@@H]1C[C@@H]([C@H](CN2CC(=O)N(c3ccccc3Cl)CC2(C)C)NC(=O)OC(C)(C)C)OC1=O
Reactant: CC(C)(CN)C(N)=O
Agent: Oc1ccccn1
Solvent: CCN(CC)CC
Product: CC(C)[C@H](C[C@H](O)[C@H](CN1CC(=O)N(c2ccccc2Cl)CC1(C)C)NC(=O)OC(C)(C)C)C(=O)NCC(C)(C)C(N)=O
Temperature: 80 °C
Reaction time: 4 h
Yield: 66.9 %

Procedure:
140 mg of 3-amino-2,2-di(methyl)propionamide obtained in Reference Example 2 (1.21 mmol) and 38 mg of 2-hydroxypyridine (0.40 mmol) were added to a solution of 205 mg of {(S)-2-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl ester obtained in Example (1m) (0.40 mmol) in triethylamine (4 ml), and the mixture was stirred at 80° C. for four hours. The reaction mixture was cooled and then concentrated under reduced pressure and further stirred at 80° C. for 14 hours. The reaction mixture was cooled and then water was added, followed by extraction with methylene chloride. Then, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent: methylene chloride/methanol=40/3) to obtain 167 mg of the title compound (yield: 66%).
Reaction SMILES: [CH2:1]([Br:4])[CH:2]=[CH2:3].C(NCC)C.Br.C([NH3+])C=C.[CH2:15]([N:18]([CH2:21][CH3:22])[CH2:19][CH3:20])[CH:16]=[CH2:17]>CC(C)=O>[Br-:4].[CH2:19]([N+:18]([CH2:21][CH3:22])([CH2:15][CH:16]=[CH2:17])[CH2:1][CH:2]=[CH2:3])[CH3:20]
Reactant: C=CCN(CC)CC
Reactant: C=CCBr
Agent: Br
Agent: C=CC[NH3+]
Solvent: CC(C)=O
Solvent: CCNCC
Product: C=CC[N+](CC)(CC)CC=C
Product: [Br-]
Reaction time: 0.25 h

Procedure:
The diethyidiallylammonium bromide monomer was prepared in two steps. 60.5 Grams (0.5 mol) of allyl bromide were slowly added to 160 grams (2.20 mol) of diethylamine in 100 milliliters of acetone. After about 15 minutes, the solution became cloudy and white crystals of the byproduct, allyl ammonium hydrogen bromide, were formed. The solution containing allyldiethyl amine was filtered, and distilled at 112° C. under nitrogen to purify the material. The allyldiethyl amine was redissolved in 200 milliliters of acetone, and more allyl bromide added slowly. Crystals of the product, diallydiethylammonium bromide, precipitated out immediately. The product was recovered by filtration and washed with several quantities of acetone, and dried under vacuum.