Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9]([C@@H:11]2[CH2:15][C@H:14]([O:16][CH3:17])[CH2:13][N:12]2C(OCC2C=CC=CC=2)=O)=[O:10])=[CH:4][CH:3]=1.[H][H]>[Pd].CO>[F:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9]([C@@H:11]2[CH2:15][C@H:14]([O:16][CH3:17])[CH2:13][NH:12]2)=[O:10])=[CH:4][CH:3]=1
Reactant: CO[C@H]1C[C@@H](C(=O)Nc2ccc(F)nc2)N(C(=O)OCc2ccccc2)C1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CO[C@@H]1CN[C@H](C(=O)Nc2ccc(F)nc2)C1
Yield: 93.3 %

Procedure:
To a stirred suspension of palladium on carbon (10%, 80 mg) in methanol (100 mL) was added a solution of (2S,4S)-benzyl 4-methoxy-2-(pyrazin-2-ylcarbamoyl)pyrrolidine-1-carboxylate 62A (400 mg, 1.12 mmol) in methanol (100 mL) under nitrogen. The suspension was hydrogenated with a hydrogen balloon atmosphere overnight. The resulting suspension was filtered through a pad of celite and washed with methanol. Concentration of the filtrate gave the product as an oil (250 mg, 100%) which was used without purification in the next step. LC/MS [M+H]+: 240; Ret time (Method F): 0.91 min.
Reaction SMILES: F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[O:25]1[C:30]2([CH2:35][CH2:34][N:33]([CH2:36][C:37]3[CH:38]=[C:39]([CH2:44][CH2:45][OH:46])[CH:40]=[C:41]([F:43])[CH:42]=3)[CH2:32][CH2:31]2)[CH2:29][NH:28][CH2:27][CH2:26]1.[CH:47]1([C:52]2[S:53][CH:54]=[C:55]([C:57](O)=[O:58])[N:56]=2)[CH2:51][CH2:50][CH2:49][CH2:48]1.C(N(CC)CC)C>CN(C=O)C>[CH:47]1([C:52]2[S:53][CH:54]=[C:55]([C:57]([N:28]3[CH2:29][C:30]4([CH2:35][CH2:34][N:33]([CH2:36][C:37]5[CH:38]=[C:39]([CH2:44][CH2:45][OH:46])[CH:40]=[C:41]([F:43])[CH:42]=5)[CH2:32][CH2:31]4)[O:25][CH2:26][CH2:27]3)=[O:58])[N:56]=2)[CH2:48][CH2:49][CH2:50][CH2:51]1
Reactant: OCCc1cc(F)cc(CN2CCC3(CC2)CNCCO3)c1
Reactant: O=C(O)c1csc(C2CCCC2)n1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: O=C(c1csc(C2CCCC2)n1)N1CCOC2(CCN(Cc3cc(F)cc(CCO)c3)CC2)C1
Reaction time: 0.5 h

Procedure:
O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.33 g) was added to a solution of 2-(3-(1-oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-5-fluorophenyl)ethanol (example 55, step c) (0.21 g), 2-cyclopentylthiazole-4-carboxylic acid (example 59, step d) (0.13 g) and triethylamine (0.38 mL) in DMF (7 mL) and the resulting yellow solution was stirred for 30 min. The mixture was partitioned between ethyl acetate and brine (100 mL), the organic phase was washed with brine (2×100 mL), dried over sodium sulphate, filtered and the solvent evaporated. The resulting gum was purified by silica gel chromatography eluting with 47.5:47.5:5 isohexane:ethyl acetate:triethylamine to 95:5 ethyl acetate:triethylamine gradient. The fractions containing product were combined, toluene (200 mL) was added and the solvent evaporated under reduced pressure to give the subtitled compound as a clear gum. Yield 0.19 g.
Reaction SMILES: B(Cl)(Cl)Cl.[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]([CH2:17][O:18]CC)[O:15][CH:16]=2)=[CH:8][CH:7]=1>ClCCl>[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[N:13]=[C:14]([CH2:17][OH:18])[O:15][CH:16]=2)=[CH:10][CH:11]=1
Reactant: CCOCc1nc(-c2ccc(Cl)cc2)co1
Agent: ClB(Cl)Cl
Solvent: ClCCl
Product: OCc1nc(-c2ccc(Cl)cc2)co1
Temperature: 25 °C
Reaction time: 2 h
Yield: 82.8 %

Procedure:
181 ml of a 1M solution of boron trichloride in dichloromethane was added dropwise to a stirred solution of 21.5 g (90.5 mmol) of 4-(4-chlorophenyl)-2-ethoxymethyl-oxazole in 100 ml of dichloromethane. The temperature of the mixture was held below 10° C. during the addition by cooling with ice. After completion of the addition the mixture was stirred at room temperature for 2 hours and then poured on to 500 ml of ice/water. The dichloromethane phase was separated and the aqueous phase was extracted with 100 ml of dichloromethane. The combined dichloromethane extracts were washed with saturated sodium hydrogen carbonate solution, dried over sodium sulphate, filtered and evaporated. Recrystallization of the residue from toluene yielded 15.7 g (83%) of 4-(4-chlorophenyl)-2-oxazolemethanol of melting point 68°-71.5° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([O:10][CH3:11])[N:3]=1.[CH2:12]([Li])[CH2:13][CH2:14]C.CC1(C)CCCC(C)(C)N1>>[CH2:14]([C:7]1[C:2]([Cl:1])=[N:3][C:4]([O:10][CH3:11])=[N:5][C:6]=1[O:8][CH3:9])[CH:13]=[CH2:12]
Reactant: [Li]CCCC
Reactant: COc1cc(Cl)nc(OC)n1
Agent: CC1(C)CCCC(C)(C)N1
Product: C=CCc1c(Cl)nc(OC)nc1OC

Procedure:
Synthesis of 2,4-dichloro-7-aryl-6,7-dihydro-5H-cyclopenta[d]pyrimidines 33 could also be performed according to the pathway described on Scheme 12. 4-Chloro-2,6-dimethoxypyrimidine 40 could be deprotonated with a strong base, such as n-butyllithium or 2,2,6,6-tetramethylpiperidine, and quenched with allyl bromide to give 5-allyl-4-chloro-2,6-dimethoxypyrimidine 41. Nencka, R.; Votruba, I.; H{hacek over (r)}ebabecký, H.; Jansa, P.; Tlou{hacek over (s)}t' ova, E.; Horská, K.; Masojídková, M.; Holý, A. J. Med. Chem. 2007, 50, 6016-6023. The latter compound can react with α-styrylborinic acids in the presence of a palladium catalyst, such as tetrakis(triphenylphosphine)palladium, to provide compounds of formula 42 which can undergo ring closure olefin metathesis under Grubbs conditions to form 2,4-dimethoxy-7-aryl-5H-cyclopenta[d]pyrimidines 43. Grubbs, R. H. Handbook of Metathesis, 2003, First Edition, Wiley-VCH. The double bond in compounds 43 can be reduced to give 2,4-dimethoxy-7-aryl-6,7-dihydro-5H-cyclopenta[d]pyrimidines 44, which upon acid-catalyzed hydrolysis, followed by chlorination with phosphorus oxychloride afford intermediates 33.
Reaction SMILES: [N:1]1[C:2]([C:6]2[CH:11]=[N:10][CH:9]=[CH:8][N:7]=2)=[N:3][CH2:4][CH:5]=1.[H-].[Na+].Cl[CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20]>CN(C=O)C>[CH3:20][Si:19]([CH3:22])([CH3:21])[CH2:18][CH2:17][O:16][CH2:15][N:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[CH:11]=[N:10][CH:9]=[CH:8][N:7]=1
Reactant: C1=NC(c2cnccn2)=NC1
Reactant: C[Si](C)(C)CCOCCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C[Si](C)(C)CCOCn1ccnc1-c1cnccn1
Temperature: 40 °C
Reaction time: 2 h
Yield: 62.4 %

Procedure:
To a solution of 2-(4H-imidazol-2-yl)pyrazine (0.75 g, 5.1 mmol) in DMF (7 mL) was added sodium hydride (60% dispersion in oil, 0.42 g, 10.3 mmol) and the reaction stirred at 40° C. for 2 hours. [2-(chloromethoxy)ethyl](trimethyl)silane (1.71 g, 10.3 mmol) was added and the reaction was stirred at 40° C. for a further 3 hours The reaction mixture was partitioned between EtOAc and water and the layers separated. The aqueous layers was extracted with EtOAc (×2) and the combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified using column chromatography (gradient 20-60% EtOAc in hexane) to give the title compound (0.88 g, yellow oil). 1H NMR (400 MHz, CDCl3) δ ppm: 9.47 (d, J=1.0 Hz, 1 H), 8.36-8.59 (m, 2 H), 7.26-7.28 (m, 1 H), 7.24 (d, J=1.3 Hz, 1 H), 5.96-6.00 (m, 2 H), 3.53-3.61 (m, 2 H), 0.86-0.94 (m, 2 H), −0.10-−0.05 (m, 9 H).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1.[Cl:13][C:14]1[CH:22]=[CH:21][C:17]([C:18](Cl)=[O:19])=[CH:16][CH:15]=1>C(Cl)Cl>[Cl:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([NH:1][CH2:2][C:3]2[CH:4]=[CH:5][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:11][CH:12]=2)=[O:19])=[CH:16][CH:15]=1
Reactant: COC(=O)c1ccc(CN)cc1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Solvent: ClCCl
Product: COC(=O)c1ccc(CNC(=O)c2ccc(Cl)cc2)cc1
Reaction time: 12 h
Yield: 57.3 %

Procedure:
To a stirred solution of methyl 4-(aminomethyl)benzoate (75 g, 0.46 mol) and TEA (315 mL, 2.27 mol) in anhydrous DCM (1.5 L) was added a solution of freshly prepared 4-chloro benzoyl chloride (0.91 mol) in DCM (400 mL). The resulting mixture was allowed to stir for 12 hrs. The reaction was quenched with a 10% aqueous solution of sodium hydrogenocarbonate. The organic layer was washed with a 1.5N HCl solution and water. After drying over MgSO4 and evaporation of the solvent in vacuo, a solid was obtained. Recrystallization form MeOH gave the title compound (80 g) in a 60% yield as a white powder.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([N:8]([CH2:14][O:15][CH3:16])[C:9]2[S:10][CH:11]=[CH:12][N:13]=2)[N:5]=[C:4]([CH2:17][OH:18])[CH:3]=1.N1C=CN=C1.[Si:24](Cl)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]>CN(C)C=O.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH2:17][O:18][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[N:5]=[C:6]([N:8]([CH2:14][O:15][CH3:16])[C:9]2[S:10][CH:11]=[CH:12][N:13]=2)[CH:7]=1
Reactant: COCN(c1cc(Br)cc(CO)n1)c1nccs1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COCN(c1cc(Br)cc(CO[Si](C)(C)C(C)(C)C)n1)c1nccs1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
18.5 g of (4-bromo-6-((methoxymethyl)(1,3-thiazol-2-yl)amino)pyridin-2-yl)-methanol was dissolved in 110 mL of dimethylformamide and 9.64 g of imidazole was added thereto. Under cooling with an ice bath, 10.2 g of tert-butyldimethylsilyl chloride was added thereto followed by stirring at room temperature for 3 hours. The reaction solution was diluted with ethyl acetate and washed with water and brine. The resulting organic layer was dried over magnesium sulfate and filtered, and the filtrate was concentrated. The resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=9/1 to 4/1) to give the title compound.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[C:13]([NH:16][C:17]1[CH:44]=[CH:43][C:20]([C:21]([O:23][C:24]2[C:29]([F:30])=[C:28]([F:31])[C:27]([F:32])=[C:26]([NH:33][C:34](=[O:39])[C:35]([CH3:38])([CH3:37])[CH3:36])[C:25]=2[C:40](=[O:42])[CH3:41])=O)=[CH:19][C:18]=1[F:45])(=[O:15])[CH3:14].[Cl-].[NH4+]>O1CCCC1.CCCCCC>[C:13]([NH:16][C:17]1[CH:44]=[CH:43][C:20]([C:21]2[O:23][C:24]3[C:29]([F:30])=[C:28]([F:31])[C:27]([F:32])=[C:26]([NH:33][C:34](=[O:39])[C:35]([CH3:38])([CH3:36])[CH3:37])[C:25]=3[C:40](=[O:42])[CH:41]=2)=[CH:19][C:18]=1[F:45])(=[O:15])[CH3:14]
Reactant: CC(=O)Nc1ccc(C(=O)Oc2c(F)c(F)c(F)c(NC(=O)C(C)(C)C)c2C(C)=O)cc1F
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CC(=O)Nc1ccc(-c2cc(=O)c3c(NC(=O)C(C)(C)C)c(F)c(F)c(F)c3o2)cc1F
Temperature: -78 °C
Reaction time: 2 h
Yield: 40.9 %

Procedure:
0.83 mL (5.9 mmol) of diisopropylamine was dissolved in 10 mL of tetrahydrofuran under argon atmosphere, 3.5 mL of a 1.6 M solution of n-butyl lithium in n-hexane was added dropwise under ice-cooling and the solution was cooled to -78 ° C. To this solution was added a solution of 838 mg (1.79 mmol) of the above 2-acetyl-4,5,6-trifluoro-3-pivaloylaminophenyl 4-acetylamino-3-fluorobenzoate in 20 mL of tetrahydrofuran was added dropwise and the mixture was stirred for 2 hours while the temperature of the mixture was gradually raised to 0° C. An aqueous solution of ammonium chloride was added to the reaction solution, the mixture was extracted twice with ethyl acetate, the organic layer was washed once with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilied off under reduced pressure, the residue was dissolved in 24 mL of ethanol, 6 mL of concentrated hydrochloric acid was added and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction solution and the precipitated crystals were collected by filtration to give 330 mg of 2-(4-acetylamino-3-fluorophenyl)-6,7,8-trifluoro-5-pivaloylamino-4H-1-benzopyran-4-one (yield: 77%).
Reaction SMILES: [F:1][C:2]([F:29])([S:25](F)(=[O:27])=[O:26])[C:3]([F:24])([F:23])[C:4]([F:22])([F:21])[C:5]([F:20])([F:19])[C:6]([F:18])([F:17])[C:7]([F:16])([F:15])[C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10].C(N(CC)CC)C.[CH2:37]([NH2:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>O>[CH2:37]([NH:44][S:25]([C:2]([F:1])([F:29])[C:3]([F:23])([F:24])[C:4]([F:22])([F:21])[C:5]([F:19])([F:20])[C:6]([F:18])([F:17])[C:7]([F:15])([F:16])[C:8]([F:13])([F:14])[C:9]([F:10])([F:12])[F:11])(=[O:26])=[O:27])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1
Reactant: NCc1ccccc1
Reactant: O=S(=O)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Solvent: O
Solvent: CCN(CC)CC
Product: O=S(=O)(NCc1ccccc1)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F

Procedure:
50.21 g (100.0 mmol) of perfluorooctanesulfonyl fluoride is added in drops to a mixture of 10.62 g (105.0 mmol) of triethylamine and 10.72 g (100.0 mmol) of benzylamine at 80° C. while being stirred vigorously. It is stirred for 2 days at 80° C., the reaction mixture is mixed with 300 ml of water and extracted 3 times with ethyl acetate. The combined organic extracts are dried on sodium sulfate, filtered and concentrated by evaporation. The residue is chromatographed on silica gel (mobile solvent: dichloromethane/methanol=4/1).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:11][C:12]1[C:20]2[C:19]3[CH2:21][NH:22][CH2:23][CH2:24][C:18]=3[NH:17][C:16]=2[N:15]=[CH:14][CH:13]=1.CCN(C(C)C)C(C)C.[CH:34]1([C:38](Cl)=[O:39])[CH2:37][CH2:36][CH2:35]1>ClCCCl>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:11][C:12]1[C:20]2[C:19]3[CH2:21][N:22]([C:38]([CH:34]4[CH2:37][CH2:36][CH2:35]4)=[O:39])[CH2:23][CH2:24][C:18]=3[NH:17][C:16]=2[N:15]=[CH:14][CH:13]=1
Reactant: Clc1ccc2c(c1Nc1ccnc3[nH]c4c(c13)CNCC4)OCO2
Reactant: O=C(Cl)C1CCC1
Solvent: ClCCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C(C1CCC1)N1CCc2[nH]c3nccc(Nc4c(Cl)ccc5c4OCO5)c3c2C1
Temperature: 25 °C
Yield: 30 %

Procedure:
(5-Chloro-benzo[1,3]dioxol-4-yl)-(6,7,8,9-tetrahydro-5H-dipyrido[2,3-b;3′,4′-d]pyrrol-4-yl)-amine (100 mg, 0.29 mmol) and DIEA (0.15 mL, 0.88 mmol) were dissolved in 1,2-dichloroethane (2 mL) and stirred at room temperature. Cyclobutanecarbonyl chloride (0.04 mL, 0.35 mmol) was added dropwise, and the reaction was stirred for 1 h at room temperature. The reaction was concentrated. The crude material was dissolved in DMSO (3 mL) and filtered. The filtrate was purified directly via prep-LC-MS to provide 69 (37 mg, 30% yield) as a white fluffy solid. LC-MS (M+H=425, obsd.=425).
Reaction SMILES: Br[C:2]1[C:3]([C:24]#[N:25])=[CH:4][CH:5]=[C:6]2[C:14]=1[NH:13][C:12]1[C:11]([CH3:16])([CH3:15])[C:10]3[CH:17]=[C:18]([O:21][CH3:22])[CH:19]=[CH:20][C:9]=3[C:8](=[O:23])[C:7]2=1.[N-:26]=[N+]=[N-].[Na+].CN[C@H]1CCCC[C@@H]1NC.O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+].[OH-].[Na+]>C(O)C.[Cu](I)I.O>[NH2:26][C:2]1[C:3]([C:24]#[N:25])=[CH:4][CH:5]=[C:6]2[C:14]=1[NH:13][C:12]1[C:11]([CH3:16])([CH3:15])[C:10]3[CH:17]=[C:18]([O:21][CH3:22])[CH:19]=[CH:20][C:9]=3[C:8](=[O:23])[C:7]2=1
Reactant: [N-]=[N+]=[N-]
Reactant: COc1ccc2c(c1)C(C)(C)c1[nH]c3c(Br)c(C#N)ccc3c1C2=O
Agent: I[Cu]I
Agent: CN[C@H]1CCCC[C@@H]1NC
Agent: O=C1O[C@H]([C@@H](O)CO)C([O-])=C1O
Solvent: CCO
Solvent: O
Product: COc1ccc2c(c1)C(C)(C)c1[nH]c3c(N)c(C#N)ccc3c1C2=O
Yield: 26.7 %

Procedure:
Under nitrogen atmosphere, 4-bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U5, 25.0 mg, 63.25 μmol), copper iodide (2.41 mg, 12.65 μmol), sodium azide (20.6 mg, 316.3 μmol), (1S,2S)—N,N′-dimethyl-cyclohexane-1,2-diamine (2.70 mg, 18.98 μmol), and sodium ascorbate (1.25 mg, 6.325 μmol) were dissolved in ethanol (0.70 mL) and water (0.30 mL) and the mixture was stirred at 100° C. for 2 hr. The reaction solution was poured into aqueous solution of sodium hydroxide (1 M), extracted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (methanol/dichloromethane) to obtain the title compound (5.6 mg, 27%).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[NH:9]1[CH:13]=[CH:12][N:11]=[CH:10]1>O1CCCC1>[Cl:1][C:2]1[N:7]=[C:6]([N:9]2[CH:13]=[CH:12][N:11]=[CH:10]2)[CH:5]=[CH:4][N:3]=1
Reactant: c1c[nH]cn1
Reactant: Clc1ccnc(Cl)n1
Solvent: C1CCOC1
Product: Clc1nccc(-n2ccnc2)n1
Yield: 101.9 %

Procedure:
In anhydrous tetrahydrofuran, 680 mg of 2,4-dichloropyrimidine was substituted with 680 mg of imidazole. The reaction mixture was then treated according to the procedure of Example 5 to yield 840 mg of the 2-chloro-4-(1-imidazolyl)pyrimidine, recrystallized from a mixture of n-hexane and ethyl acetate, having a melting point of 127.5°-128° C.
Reaction SMILES: [NH2:1][C:2]1[S:6][N:5]=[C:4]([CH3:7])[C:3]=1[C:8]#[N:9].[N:10]([O-])=[O:11].[Na+].O>C(O)=O.N([O-])=O.[Na+]>[C:8]([C:3]1[C:4]([CH3:7])=[N:5][S:6][C:2]=1[NH:1][N:10]=[O:11])#[N:9]
Reactant: O=N[O-]
Reactant: Cc1nsc(N)c1C#N
Agent: [Na+]
Solvent: O=CO
Solvent: O
Product: Cc1nsc(NN=O)c1C#N
Yield: 51533.2 %

Procedure:
First, 4 g (0.028 mol) of 5-amino-4-cyano-3-methylisothiazole was dissolved in 40 mL of 98% formic acid. While the mixture was stirred, an aqueous sodium nitrite solution (containing 2.1 g (0.03 mmol) of sodium nitrite in 6 mL of water) was added dropwise at 0° C. or less. After completion of dropwise addition, the mixture was continuously stirred at 0° C. further for one hour. To the solution, 100 mL of water was added to precipitate crystals, which were collected by filtration and washed with ice cold water. The crystals were dried in the air at room temperature overnight to obtain 2.6 g (56% in yield) of 4-cyano-3-methyl-5-nitrosoaminoisothiazole. To 2 g (0.012 mol) of the obtained nitrosoaminoisothiazole, 20 mL of methanol was added, stirred while heating to an inner temperature of 55 to 60° C. for one hour and cooled to room temperature to precipitate crystals, which were collected by filtration. The crystals were recrystallized from methanol to obtain 0.66 g (41% in yield) of triazene dissociative direct dye D-34.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][OH:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[F:12][C:13]1[C:18](F)=[CH:17][C:16]([NH2:20])=[C:15]([N+:21]([O-:23])=[O:22])[CH:14]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O.C(OCC)(=O)C>[F:12][C:13]1[C:18]([O:9][CH2:8][CH2:7][N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[CH:17][C:16]([NH2:20])=[C:15]([N+:21]([O-:23])=[O:22])[CH:14]=1
Reactant: OCCN1CCCCC1
Reactant: Nc1cc(F)c(F)cc1[N+](=O)[O-]
Agent: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Nc1cc(OCCN2CCCCC2)c(F)cc1[N+](=O)[O-]
Temperature: 22 °C
Reaction time: 2 h
Yield: 54.5 %

Procedure:
A solution of 1.11 g of 2-piperidin-1-ylethanol in 20 mL of N,N-dimethylformamide (DMF) is cooled to 0° C. with an ice bath. 689 mg of sodium hydride (60% in suspension in oil) are added in small portions. The suspension obtained is added dropwise to a suspension containing 500 mg of 4,5-difluoro-2-nitrophenylamine and 724 mg of sodium bicarbonate in 15 mL of DMF. The reaction medium is stirred at ambient temperature (22° C.) for 2 hours and then heated at 90° C. for 1 hour. The solvent is concentrated to dryness, then the reaction crude is taken up in 30 mL of ethyl acetate and the organic phase is washed with 2×30 mL of distilled water and 1×30 mL of a saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate and the solvent is evaporated off under vacuum in a rotary evaporator. The crude is triturated in ethyl ether and the solid is filtered through sintered glass and rinsed with ethyl ether. 443 mg of 4-fluoro-2-nitro-5-(2-piperidin-1-ylethoxy)-phenylamine in the form of a red solid are isolated. 1H NMR (300 MHz, DMSO-d6, δ in ppm): 1.37 (m, 2H); 1.48 (m, 4H); 2.43 (m, 4H); 2.69 (t, J=6.5 Hz, 2H); 4.13 (t, J=6.5 Hz, 2H); 6.65 (d, J=8.0 Hz, 1H); 7.48 (broad s, 2H); 7.75 (d, J=12.0 Hz, 1H).
Reaction SMILES: [P:1]([O-:32])([O:28][CH2:29][CH2:30]Br)([O:3][C@@H:4]1[CH2:9][CH2:8][CH2:7][O:6][C@H:5]1[CH2:10][O:11][CH2:12][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])=[O:2].[N:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>>[P:1]([O-:32])([O:28][CH2:29][CH2:30][N+:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([O:3][C@@H:4]1[CH2:9][CH2:8][CH2:7][O:6][C@H:5]1[CH2:10][O:11][CH2:12][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])=[O:2]
Reactant: CCCCCCCCCCCCCCCCOC[C@@H]1OCCC[C@H]1OP(=O)([O-])OCCBr
Reactant: c1ccncc1
Product: CCCCCCCCCCCCCCCCOC[C@@H]1OCCC[C@H]1OP(=O)([O-])OCC[n+]1ccccc1
Temperature: 80 °C
Reaction time: 20 h

Procedure:
1.512 g of dl-trans-2-hexadecyloxymethyltetrahydropyran-3-yl 2-bromoethyl phosphate (prepared as described in the first half of Example 1) was dissolved in 20 ml of pyridine, and the resulting solution was heated, with stirring, at 80° C. for 20 hours. The mixture was then cooled and the pyridine was removed by distillation under reduced pressure. The residue was subjected to column chromatography through 45 g of silica gel. The fraction eluted with a 60:35:5 by volume mixture of methylene chloride, methanol and water gave 1.422 g of the title compound as a white powder, melting at 123°-129° C.
Reaction SMILES: Br[C:2]1[C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[N:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1>>[S:8]1[CH:9]=[CH:10][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([C:14]3[CH:15]=[CH:16][N:11]=[CH:12][CH:13]=3)[C:7]1=2
Reactant: OB(O)c1ccncc1
Reactant: Brc1cccc2ccsc12
Product: c1cc(-c2ccncc2)c2sccc2c1

Procedure:
This compound was prepared in analogy to the procedure described in Example 16i) starting from 7-bromo-benzo[b]thiophene (Focus synthesis, CAS:1423-61-6) using 4-pyridineboronic acid as reagent to obtain 4-benzo[b]thiophen-7-yl-pyridine as a grey solid. MS (ISP): m/e 212.1 (M+H)+
Reaction SMILES: [C:1]([OH:4])(=[O:3])[CH3:2].CN(C=O)C.C([O-])(=O)C.[Na+].Br[CH2:16][C:17]([C:19]1[N:20]=[CH:21][C:22]([NH:25][C:26](=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28])=[N:23][CH:24]=1)=[O:18]>C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>[CH3:28][C:27]([CH3:30])([CH3:29])[C:26]([NH:25][C:22]1[N:23]=[CH:24][C:19]([C:17](=[O:18])[CH2:16][O:3][C:1](=[O:4])[CH3:2])=[N:20][CH:21]=1)=[O:31]
Reactant: CC(=O)O
Reactant: CC(C)(C)C(=O)Nc1cnc(C(=O)CBr)cn1
Agent: CC(=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(=O)OCC(=O)c1cnc(NC(=O)C(C)(C)C)cn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.9 %

Procedure:
A 500 mL round bottomed flask equipped with a magnetic stirrer, addition funnel, thermocouple probe and nitrogen inlet/outlet was charged with 4.40 mL (76.86 mmol) of acetic acid, 140 mL of DMF and 7.000 g (85.33 mmol) of sodium acetate. Then, 23.30 g (77.62 mmol) of the compound obtained in step 5 was added portionwise over 45 min. After stirring at room temperature for an additional 1 h, HPLC analysis indicated complete reaction. The reaction mixture was diluted with 350 mL of ethyl acetate and 100 mL of saturated sodium bicarbonate was added with stirring. The organic layer was separated, washed with 3×100 mL of water and concentrated at 30° C./60 mmHg to a volume of ca. 60 mL. The resulting slurry was diluted with 200 mL of heptane, concentrated at 30° C./60 mmHg to a volume of ca. 150 mL, and stirred at 50° C. for 30 min. After cooling to room temperature, the solid was collected by filtration, washed with 40 mL of 10% ethyl acetate in heptane and dried by suction, then under reduced pressure (house vacuum) for 24 h, to give 19.52 g (90.0% yield) of the title compound as an off-white solid; 98.81% pure as determined by HPLC analysis (same conditions as in step 4, retention time 6.78 min).