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[ CAS No. 6017-21-6 ] {[proInfo.proName]}

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Chemical Structure| 6017-21-6
Chemical Structure| 6017-21-6
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Product Details of [ 6017-21-6 ]

CAS No. :6017-21-6 MDL No. :MFCD00524838
Formula : C9H6N4 Boiling Point : -
Linear Structure Formula :- InChI Key :KLMBASWITNCMTF-UHFFFAOYSA-N
M.W : 170.17 Pubchem ID :22347
Synonyms :

Calculated chemistry of [ 6017-21-6 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.11
Num. rotatable bonds : 2
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 45.93
TPSA : 72.3 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.44 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.65
Log Po/w (XLOGP3) : 2.67
Log Po/w (WLOGP) : 2.19
Log Po/w (MLOGP) : 0.35
Log Po/w (SILICOS-IT) : 2.01
Consensus Log Po/w : 1.77

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.79
Solubility : 0.278 mg/ml ; 0.00163 mol/l
Class : Soluble
Log S (Ali) : -3.84
Solubility : 0.0246 mg/ml ; 0.000144 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.71
Solubility : 0.333 mg/ml ; 0.00195 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 1.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.28

Safety of [ 6017-21-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 6017-21-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 6017-21-6 ]

[ 6017-21-6 ] Synthesis Path-Downstream   1~69

  • 1
  • [ 6017-21-6 ]
  • [ 124-42-5 ]
  • [ 5473-05-2 ]
YieldReaction ConditionsOperation in experiment
29% With sodium ethanolate In ethanol 1.5 h, reflux, then RT.;
  • 2
  • [ 6017-21-6 ]
  • [ 6313-33-3 ]
  • [ 54288-02-7 ]
YieldReaction ConditionsOperation in experiment
45% With sodium ethanolate In ethanol 1.5 h, reflux, then RT.;
  • 3
  • [ 6017-21-6 ]
  • [ 3599-89-1 ]
  • [ 100121-19-5 ]
  • 4
  • [ 64-18-6 ]
  • [ 6017-21-6 ]
  • [ 5098-15-7 ]
YieldReaction ConditionsOperation in experiment
With zinc
  • 5
  • [ 10432-44-7 ]
  • [ 100-34-5 ]
  • [ 6017-21-6 ]
  • 6
  • [ 62737-71-7 ]
  • [ 100-34-5 ]
  • [ 6017-21-6 ]
YieldReaction ConditionsOperation in experiment
With sodium acetate In ethanol
  • 7
  • [ 6017-21-6 ]
  • 4-amidinopyridine hydrochloride [ No CAS ]
  • [ 93794-47-9 ]
YieldReaction ConditionsOperation in experiment
85% With sodium methylate In ethanol for 3h; Heating;
  • 8
  • [ 6017-21-6 ]
  • [ 75-04-7 ]
  • [ 60100-09-6 ]
  • [ 89073-91-6 ]
YieldReaction ConditionsOperation in experiment
33% With hydrogenchloride at 150℃; for 5h;
  • 9
  • [ 6017-21-6 ]
  • [ 75-04-7 ]
  • [ 60100-09-6 ]
  • [ 89073-92-7 ]
YieldReaction ConditionsOperation in experiment
40% With hydrogenchloride at 150℃; for 5h;
  • 10
  • [ 6017-21-6 ]
  • [ 60100-09-6 ]
  • [ 74-89-5 ]
  • [ 83366-39-6 ]
YieldReaction ConditionsOperation in experiment
28% With hydrogenchloride at 150℃; for 5h;
  • 11
  • [ 6017-21-6 ]
  • [ 60100-09-6 ]
  • [ 74-89-5 ]
  • [ 83366-42-1 ]
YieldReaction ConditionsOperation in experiment
63% With hydrogenchloride at 150℃; for 5h;
  • 12
  • [ 100-34-5 ]
  • [ 109-77-3 ]
  • [ 6017-21-6 ]
YieldReaction ConditionsOperation in experiment
95.1% With potassium dihydrogenphosphate In water for 2h; 3 Example 3 The saturated aqueous solution of sodium acetate in Example 1, 1) was replaced with a saturated aqueous solution of potassium phosphate, and the other charge ratio and operation method were changed to obtain 147 g of pale yellow solid 2-phenylazomalononitrile, yield 95.1% (calculated as malondialdehyde).;_1) Synthesis of 2-phenylazomalononitrile (Formula 4a);_250 g of concentrated hydrochloric acid and 600 mL of water were added to a 2000 mL four-necked reaction flask, cooled to below 10 ° C, 96 g of aniline (formula 2a) was added dropwise, cooled to 0 ° C, controlled at 0 to 5 ° C. A solution of sodium nitrite (73.5 g) was added dropwise over 1 hour, and the solution of the diazonium salt (formula 3a) was formed by incubation at 5 ° C for 1 h. Add malononitrile 60g, stirring for half an hour to dissolve and clarify, add sodium acetate saturated aqueous solution, adjust the solution pH. The reaction was carried out for 2 hours, filtered, washed with water and the cake was dried and recrystallized to give 142.7 g of pale yellow solid 2-phenylazomalononitrile (Formula 4a) in a yield of 92.3%.
With sodium ethanolate
  • 13
  • [ 123-39-7 ]
  • [ 6017-21-6 ]
  • [ 83366-39-6 ]
  • [ 83366-42-1 ]
YieldReaction ConditionsOperation in experiment
1: 3% 2: 50% With ammonia at 150℃; for 5h;
  • 14
  • [ 627-45-2 ]
  • [ 6017-21-6 ]
  • [ 89073-91-6 ]
YieldReaction ConditionsOperation in experiment
64% With ammonia at 150℃; for 5h;
  • 15
  • H2NC(NH)(CH2)4C(NH)NH2 [ No CAS ]
  • [ 6017-21-6 ]
  • 1,4-bis<4,6-diamino-5-(phenylazo)pyrimidin-2-yl>butane [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With sodium In butan-1-ol for 4h; Heating;
  • 16
  • [ 6017-21-6 ]
  • [ 1670-14-0 ]
  • [ 101352-53-8 ]
YieldReaction ConditionsOperation in experiment
48% With sodium ethanolate In ethanol 1.5 h, reflux, then RT.;
  • 17
  • [ 6017-21-6 ]
  • [ 97961-53-0 ]
  • [ 97961-54-1 ]
YieldReaction ConditionsOperation in experiment
64% With sodium In butan-1-ol for 4h; Heating;
  • 18
  • [ 6017-21-6 ]
  • [ 116612-50-1 ]
  • [ 116612-51-2 ]
YieldReaction ConditionsOperation in experiment
With sodium butanolate In butan-1-ol Heating; Yield given;
  • 19
  • [ 6017-21-6 ]
  • Azacycloundec-2-ylideneamine [ No CAS ]
  • 15-Phenylazo-2,13,16-triaza-bicyclo[10.3.1]hexadeca-1(16),12,14-trien-14-ylamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium butanolate In butan-1-ol Heating; Yield given;
  • 20
  • [ 6017-21-6 ]
  • [ 94343-49-4 ]
  • 17-Phenylazo-2,15,18-triaza-bicyclo[12.3.1]octadeca-1(18),14,16-trien-16-ylamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium butanolate In butan-1-ol Heating; Yield given;
  • 21
  • [ 6017-21-6 ]
  • [ 94051-87-3 ]
YieldReaction ConditionsOperation in experiment
60% With hydroxylamine hydrochloride; sodium methylate In methanol
YieldReaction ConditionsOperation in experiment
Katal. Hydrier. in Gegenwart v. Formamid/NH3;
YieldReaction ConditionsOperation in experiment
Malononitril, Benzoldiazonium-chlorid;
  • 25
  • [ 6017-21-6 ]
  • [ 256376-68-8 ]
  • [ 370879-49-5 ]
YieldReaction ConditionsOperation in experiment
73% With sodium methylate In N,N-dimethyl-formamide at 110℃; for 12h;
  • 26
  • [ 6017-21-6 ]
  • [ 94051-88-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 60 percent / NH2OH*HCl, NaOCH3 / methanol 2: methanol / 15 h
  • 27
  • [ 6017-21-6 ]
  • [ 36848-19-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 48 percent / NaOEt / ethanol / 1.5 h, reflux, then RT. 2: 58 percent / NBS, NaOH / 0.25 h / 40 °C
  • 28
  • [ 6017-21-6 ]
  • [ 102712-31-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 45 percent / NaOEt / ethanol / 1.5 h, reflux, then RT. 2: 32 percent / NBS, NaOH / 0.25 h / 40 °C
  • 29
  • [ 6017-21-6 ]
  • [ 102712-32-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 29 percent / NaOEt / ethanol / 1.5 h, reflux, then RT. 2: 52 percent / NBS, NaOH / 0.25 h / 40 °C
  • 30
  • [ 6017-21-6 ]
  • [ 83366-42-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 28 percent / HCl / 5 h / 150 °C 2: 52 percent / dimethylformamide / 2 h / Ambient temperature 3: 94 percent / 50percent (CH3)2NH/MeOH / 24 h / Ambient temperature
Multi-step reaction with 3 steps 1: 50 percent / NH3 / 5 h / 150 °C 2: 52 percent / dimethylformamide / 2 h / Ambient temperature 3: 94 percent / 50percent (CH3)2NH/MeOH / 24 h / Ambient temperature
  • 31
  • [ 6017-21-6 ]
  • [ 89073-87-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 28 percent / HCl / 5 h / 150 °C 2: 3 percent / diphenyl ether; various solvent(s) / 2 h / Heating
Multi-step reaction with 2 steps 1: 50 percent / NH3 / 5 h / 150 °C 2: 3 percent / diphenyl ether; various solvent(s) / 2 h / Heating
  • 32
  • [ 6017-21-6 ]
  • [ 89073-86-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 28 percent / HCl / 5 h / 150 °C 2: 52 percent / dimethylformamide / 2 h / Ambient temperature
Multi-step reaction with 2 steps 1: 50 percent / NH3 / 5 h / 150 °C 2: 52 percent / dimethylformamide / 2 h / Ambient temperature
  • 33
  • [ 6017-21-6 ]
  • [ 1173726-60-7 ]
  • [ 1261068-02-3 ]
YieldReaction ConditionsOperation in experiment
80% With triethylamine In ethanol for 7h; Reflux;
  • 34
  • [ 6017-21-6 ]
  • [ 1173726-58-3 ]
  • [ 1261067-89-3 ]
YieldReaction ConditionsOperation in experiment
89% With triethylamine In ethanol for 7h; Reflux;
  • 35
  • [ 6017-21-6 ]
  • [ 1316194-27-0 ]
  • [ 1316194-29-2 ]
YieldReaction ConditionsOperation in experiment
87% With acetic acid for 0.0333333h; Microwave irradiation;
  • 36
  • [ 6017-21-6 ]
  • [ 1316194-28-1 ]
  • [ 1316194-37-2 ]
YieldReaction ConditionsOperation in experiment
81% With acetic acid for 0.0333333h; Microwave irradiation;
  • 37
  • [ 62-53-3 ]
  • [ 109-77-3 ]
  • [ 6017-21-6 ]
YieldReaction ConditionsOperation in experiment
97% Stage #1: aniline With hydrogenchloride; acetic acid; sodium nitrite In water at 0 - 10℃; for 2h; Stage #2: malononitrile In water for 0.5h; Stage #3: With sodium acetate In water for 2h; 1.1 1) Synthesis of 2-phenylazo-malononitrile (Formula 4a) 200g of concentrated hydrochloric acid was added 2000mL four reaction flask, 50 mL glacial acetic acid and 600mL of water, cooled to 10 , aniline was added dropwise 96g (Formula. 2A), further cooled to 0 deg.] C, temperature 0 ~ 5 , dropwise The solution of sodium nitrate was dissolved in a solution of sodium nitrate (180 mL in water) for about 1 hour. After completion of the drop, the solution was incubated at 5 ° C for 1 h to form a diazonium salt (Formula 3a) solution. Adding 60 g of malononitrile,After stirring for half an hour to dissolve,A saturated aqueous solution of sodium acetate was added dropwise,Adjust the reaction solution pH,The reaction was carried out for 2 hours, filtered, washed with water and the cake was dried and recrystallized to give 150 g of a pale yellow solid 2-phenylazo-malononitrile (Formula 4a) in a yield of 97% Mp 134 to 136 ° C.
96.8% With hydrogenchloride; sodium acetate; sodium nitrite In ethanol; water at 0 - 5℃; for 0.25h; 1.A A: Phenylazopropanedinitrile Weigh 4.66g (50mmol) of aniline into a 250mL two-mouth flask, ice bath for a while, slowly add 8.5mL of concentrated hydrochloric acid, try to keep the temperature at 0 ~ 5 °C; drops, until the temperature is stable, slowly add 4.55g (66mmol) sodium nitrite and 8mL aqueous solution, stirring 15min; then slowly added 8.04g of sodium acetate and 20mL aqueous solution;Stir until the temperature is stable, add 5.19 g of propylene dinibutrate and 6 mL of ethanol solution, resulting in a large number of bright yellow solids, add 80mL of water, continue to react for 1h. TLC monitoring, suction filtration, the filter cake was washed with an appropriate amount of water, and dried to give 8.24 g of a bright yellow solid with a yield of 96.8%.
92% Stage #1: aniline With water; sodium nitrite at 20℃; Stage #2: malononitrile at 20℃; General procedure for synthesis of azo compounds General procedure: The as-synthesized aryl diazonium salt was added to activecompound (1 mmol) and the mixture was ground at roomtemperature for appropriate time; the color of the reactionwill change [for the preparation of salt of 2-hydroxynaphthalene-1,4-dione and naphthol, we mixed 1 mmol from theformer compounds with 0.8 mL water and NaOH (0.1 g,2.5 mmol) in the other vessel and then added to the aryldiazonium salts]. After completion of the reaction (TLC),the mixture was washed by distilled water (50 mL) and thenano-CuFe2O4-SO3H was separated using an external magnet.The solid products were filtrate and washed with EtOH.The most of the product were recrystallized from appropriatesolvents and gave corresponding products in highyields. Some of them need purification with short columnchromatography. CAUTION: Although aryldiazoium ferrite sulfate saltsare stable in the dry state, and we did not experience anyproblems, the operation needs to be conducted carefully,especially when they are subjected to grinding.
88% Stage #1: aniline With hydrogenchloride; sodium nitrite In water for 0.5h; Cooling with ice; Stage #2: malononitrile With sodium acetate In water at 0℃; for 2h; 28.A Step A: N-phenyicarbonohydrazonoyi dicyanide To an ice-cold solution of the aniline (5.0 g, 53.7 mmol) in H20 (5 mL) were successively addeddropwise 37% aq HC1 (11 equiv) and sodium nitrite (370 g, 53.7 mrnoi). The mixture was stirred for30 mm and then added dropwise to a solution of Malononitrile (5.32 g, 81 mrnoi) and sodium acetate(137 g, 1664 rnmoi) in 1120 (8.5 rnL)with continuous stirring at 0 °C After 2 h, the insoluble hydrazone was collected by filtration and washed with 1-120. The precipitate was dissolved in EtOAc and washed with brine. The organic layer was dried (Na2SO4) and concentrated under vacuum to give crude which was purified by Flash chromatography to provided N-phenylcarbonohydrazonoyldicyanide (8 g, 47.0 mmoi, 88 %),
82% Stage #1: aniline With hydrogenchloride; sodium nitrite In water at 0 - 5℃; for 0.5h; Stage #2: malononitrile With sodium acetate In ethanol; water for 1.5h; 14 Synthesis of Compound (5) In three flask, aniline (46.6g, 0.50mol, 1eq), ice was added concentrated hydrochloric acid was added dropwise with stirring (85mL). Drop was completed, additional small amount of ice. Maintaining the temperature 0-5 , solution of sodium nitrite (29.0g, 0.42moll, 0.8eq) in water (50mL) was added. Dropping was completed, stirring was continued for 30 minutes. After addition of sodium acetate (51.0g, 0.62mol, 1.2eq) in water (100 mL), stirred 30 minutes, then was added malononitrile (33.0g, 0.50mol, 1eq) in ethanol (25mL) was added, and the reaction was stirred for 1 hour. After completion of the reaction, suction filtration, the filter cake was washed with distilled water, and dried to give a yellow solid (70.2g), Yield: 82.0%
78% Stage #1: aniline With hydrogenchloride; sodium nitrite In water at 0 - 5℃; Stage #2: malononitrile With sodium acetate In ethanol; water at 0 - 5℃; for 1.5h;
60% Stage #1: aniline With hydrogenchloride; sodium nitrite In water at 0 - 5℃; for 0.166667h; Stage #2: malononitrile With sodium acetate In ethanol; water at 0 - 5℃; for 0.5h;
Stage #1: aniline With hydrogenchloride; sodium nitrite Stage #2: malononitrile
Stage #1: aniline With hydrogenchloride In water at 0℃; Stage #2: With sodium nitrite In water at 0 - 5℃; Stage #3: malononitrile With sodium acetate In ethanol; water at 0℃; 10A Example 10A 2-[5-Fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3 -yl]-5-[(E)-phenyldiazenyl]pyrimidine-4,6-diamine With stirring, 3.85 g (41.34 mmol) of aniline were added to water (40 ml) and conc. hydrochloric acid (7.07 ml), and this mixture was cooled to 0° C. A solution of 2.85 g (41.34 mmol) of sodium nitrite in water (21 ml) was then added dropwise at between 0° C. and 5° C., followed by stirring at 0° C. for 15 min. Thereafter, at 0° C., a solution of 4.28 g (52.25 mmol) of sodium acetate in water (19 ml) was added rapidly dropwise, and then, with thorough stirring, a solution of 2.73 g (41.34 mmol) of malononitrile in ethanol (10 ml) was added dropwise. After 2 h at 0° C., the resulting precipitate was isolated by filtration with suction and washed three times with water (50 ml each time) and with petroleum ether (50 ml). The residue, still moist, was dissolved in DMF (46 ml) and added dropwise at precisely 85° C. to a solution of 9.5 g (33.07 mmol) of 5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3, 4-b]pyridine-3-carboximidamide acetate (Example 9A) in DMF (46 ml) and triethylamine (5.76 ml). The mixture was then stirred at 100° C. for 4 h and left to cool to RT overnight. The mixture was poured into water (480 ml) and subjected to extractive stirring at RT for 1 h. After the precipitate had been isolated by filtration with suction, it was washed twice with water (100 ml each time) and twice with methanol (50 ml each time) and then dried under a high vacuum. Yield: 9.6 g (59% of theory) LC-MS (method 2): Rt=1.21 min MS (ESIpos): m/z=458 (M+H)+

  • 38
  • [ 6017-21-6 ]
  • [ 128462-44-2 ]
  • [ 1239368-79-6 ]
YieldReaction ConditionsOperation in experiment
72% With hydrogenchloride In ethanol; water for 10h; Reflux;
  • 39
  • [ 6017-21-6 ]
  • [ 1334527-89-7 ]
  • [ 1334527-35-3 ]
YieldReaction ConditionsOperation in experiment
51% With sodium methylate at 100℃; Capped vessel; 3.C.1 Carboximidamide 10 was dissolved in toluene (or DMF) and charged with NaOMe (1-2 eq). 2-(Phenyldiazenyl)malononitrile 13 (1.1 eq) was added, and the reaction vessel was then capped and heated at 100 °C until > 90% complete by LC/MS analysis. Reaction was then diluted with DCM and extracted with NH4C1 (cone, aq). The aqueous portion was then extracted an addition two times with DCM. The organic portions were then combined, dried (Na2S04), filtered, and concentrated. The crude oil was purified by either reverse phase, preparative HPLC or by normal phase chromatography and a methanol/DCM gradient to give desired pyrimidine 14. Compound 1-34 was synthesized as an orange solid (51% yield from the corresponding carboximidamide) following General Procedure C.1H NMR (400 MHz, DMSO d6) δ 8.34 (bs, 2H), 7.95-7.93 (m, 2H), 7.51-7.10 (m, 9H), 5.29 (s, 2H), 2.83 (t, 2H), 2.62 (t, 2H), 2.48-2.45 (m, 2H) ppm.
  • 40
  • [ 6017-21-6 ]
  • [ 1376572-44-9 ]
  • C24H19FN8S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium methylate In N,N-dimethyl-formamide at 110℃; 3.C-I.1 Example 3: General Procedure C-IX5 X4[00321] Step 1, Pyrimidine Formation: Carboximidamide XI was dissolved in DMF (or ethanol) and charged withNaOMe (1-2 eq). 2-(Phenyldiazenyl)malononitrile (1.1 eq) was added, and the reaction vessel was then capped and heated at 110 °C until > 90% complete by LC/MS analysis. The reaction mixture was then diluted with DCM and extracted with NH4CI (cone, aq). The aqueous portion was then extracted an additional two times with DCM. The organic portions were then combined, dried (Na2S04), filtered, and concentrated. The crude solid was purified by either precipitation or normal phase chromatography using an appropriate methanol/DCM gradient to give desired pyrimidine X2.Compound 1-71[00325] This compound was synthesized as an orange solid (22% yield over 3 steps) following General Procedure C-I using the 3-thiophenyl-derived carboximidamide as the key starting unit in Step 1 and methyl chloroformate as the electrophile in the acylation step. 1HNMR (400 MHz, CDC13) δ 7.34 (dd, 1H), 7.23-7.16 (m, 1H), 7.21 (dd, 1H), 7.11-6.97 (m, 4H), 6.76 (ddd, 1H), 6.47 (bs, 1H), 5.53 (s, 2H), 5.16 (bs, 4H), 3.74 (s, 3H) ppm.
  • 41
  • [ 6017-21-6 ]
  • C17H15FN4 [ No CAS ]
  • C26H21FN8 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium methylate In N,N-dimethyl-formamide at 110℃; 6.C-II.1 Example 6: General Procedure C-IIX5 X4[00338] Step 1, Pyrimidine Formation: Carboximidamide XI (prepared according to General Procedure B) was dissolved in DMF (or ethanol) and charged with NaOMe (1-2 eq). 2-(Phenyldiazenyl)malononitrile (1.1 eq) was added, and the reaction vessel was then capped and heated at 110 °C until > 90% complete by LC/MS analysis. The reaction mixture was then diluted with DCM and extracted with NH CI (cone, aq). The aqueous portion was then extracted an additional two times with DCM. The organic portions were then combined, dried (Na2S04), filtered, and concentrated. The crude solid was purified by either precipitation or normal phase chromatography using an appropriate methanol/DCM gradient to give desired pyrirnidine X2.Compound 1-83[00343] This compound was synthesized as a yellow solid (2.5 % yield over 4 steps - cyclization reaction was 100%) following General Procedures F and C-II using acetophenone en route to the required ethyl l-(2-fluorobenzyl)-5 -phenyl- lH-pyrazole-3-carboxylate starting unit. 1H NMR (400 MHz, CDC13): δ 7.42-7.20 (m, 5H), 7.20-7.15 (m, IH), 7.05-6.90 (m, 2H), 7.02 (s, IH), 6.84-6.76 (m, IH), 5.52 (s, 2H), 5.45 (bs, IH), 5.04 (bs, 4H), 3.77 (s, 3H) ppm.
  • 42
  • [ 6017-21-6 ]
  • [ 1350653-28-9 ]
  • [ 1350653-29-0 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In N,N-dimethyl-formamide at 100℃; for 4h; 10A Example 10A 2-[5-Fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3 -yl]-5-[(E)-phenyldiazenyl]pyrimidine-4,6-diamine With stirring, 3.85 g (41.34 mmol) of aniline were added to water (40 ml) and conc. hydrochloric acid (7.07 ml), and this mixture was cooled to 0° C. A solution of 2.85 g (41.34 mmol) of sodium nitrite in water (21 ml) was then added dropwise at between 0° C. and 5° C., followed by stirring at 0° C. for 15 min. Thereafter, at 0° C., a solution of 4.28 g (52.25 mmol) of sodium acetate in water (19 ml) was added rapidly dropwise, and then, with thorough stirring, a solution of 2.73 g (41.34 mmol) of malononitrile in ethanol (10 ml) was added dropwise. After 2 h at 0° C., the resulting precipitate was isolated by filtration with suction and washed three times with water (50 ml each time) and with petroleum ether (50 ml). The residue, still moist, was dissolved in DMF (46 ml) and added dropwise at precisely 85° C. to a solution of 9.5 g (33.07 mmol) of 5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3, 4-b]pyridine-3-carboximidamide acetate (Example 9A) in DMF (46 ml) and triethylamine (5.76 ml). The mixture was then stirred at 100° C. for 4 h and left to cool to RT overnight. The mixture was poured into water (480 ml) and subjected to extractive stirring at RT for 1 h. After the precipitate had been isolated by filtration with suction, it was washed twice with water (100 ml each time) and twice with methanol (50 ml each time) and then dried under a high vacuum. Yield: 9.6 g (59% of theory) LC-MS (method 2): Rt=1.21 min MS (ESIpos): m/z=458 (M+H)+
  • 43
  • [ 6017-21-6 ]
  • [ 1375183-37-1 ]
  • [ 1375183-38-2 ]
YieldReaction ConditionsOperation in experiment
99% With pyridine; 1,8-diazabicyclo[5.4.0]undec-7-ene In ethanol at 110℃; for 26h; sealed tube; 9.1 Compound 1-57 and Intermediate-7; Step 1:; A suspension of l-(2-fluorobenzyl)-5-(thiazol-2-yl)-lH-l,2,4-triazole-3-carboximidamide (Intermediate-6, 0.38 mmol) and 2-(phenyldiazenyl)malononitrile (1 equiv) in ethanol (6 mL) in a sealed tube was heated at 1 10°C for 2h. The reaction was cone, to afford 2-(l-(2- fluorobenzyl)-5-(thiazol-2-yl)-lH-l,2,4-triazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6- diamine as an orange solid (>99% yield).
  • 44
  • [ 6017-21-6 ]
  • CH4(15)N2*ClH [ No CAS ]
  • C10H10N4(15)N2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium butanolate In butan-1-ol for 4h; Reflux;
  • 45
  • [ 62-53-3 ]
  • [ 6017-21-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium nitrite; hydrogenchloride / water / 0 - 5 °C 2: sodium ethanolate
Multi-step reaction with 2 steps 1: hydrogenchloride; sodium nitrite / water / 1 h / 0 - 5 °C 2: potassium dihydrogenphosphate / water / 2 h
  • 46
  • [ 6017-21-6 ]
  • C37H54N6O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: hydrazine hydrate; pyridine 2: chloroform / 24 h
  • 47
  • [ 6017-21-6 ]
  • C14H12FN5*C2H4O2 [ No CAS ]
  • [ 428854-23-3 ]
YieldReaction ConditionsOperation in experiment
90.1% With sodium methylate In N,N-dimethyl-formamide at 110℃; for 16h; 15 Synthesis of Compound (6) in three flask was added N, N- dimethylformamide (50 mL) was added compound 19 (3.3g, 0.010mol, 1.0eq), sodium methoxide was added under stirring (1.1g, 0.020mol, 2.0eq). Were added compound 5 (1.9g, 0.011mol, 1.1eq), the reaction temperature was raised to 110 16 hours. After completion of the reaction, concentrated under reduced pressure, the residue was added water to complete precipitation. Suction filtered, the filter cake washed with ethanol to give a red-brown solid (4.0 g of), a yield of 90.1%.
  • 48
  • [ 6017-21-6 ]
  • 4-(thiazol-2-yldiazenyl)-1H-pyrazole-3,5-diamine [ No CAS ]
  • 6-(phenyldiazenyl)-3-(thiazol-2-yldiazenyl)pyrazolo[1,5-a]pyrimidine-2,5,7-triamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine In ethanol for 8h; Reflux;
  • 49
  • [ 6017-21-6 ]
  • 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamide hydrochloride [ No CAS ]
  • [ 370879-49-5 ]
YieldReaction ConditionsOperation in experiment
97.4% With sodium methylate In 1,4-dioxane at 100℃; for 1h; 1 Example 1: Preparation of LA-1 To 500ml four-necked flask was added dioxane 200ml,With stirring, LA-A (200.0 g, 0.65 mol,1.0eq),LA-B (110.0 g, 0.65 mol, 1.0 eq),Sodium methoxide (70.0 g, 1.3 mol, 2.0 eq),Warming to about 100 ,Slowly return,The reaction was stirred for 1.0 h.After the reaction,The reaction mixture was gradually cooled to room temperature with stirring,Continue stirring in an ice bath for 2.0 h.The reaction was suction filtered.Suction filtration,The cake is dried at 50 ° C for 12-16h.Obtained brick red solid LA-1: 27.97g (yield 97.4%, liquid phase purity 99.53%, melting point> 250 ° C)
84.6% With sodium methylate In N,N-dimethyl-formamide at 110℃; for 12h; 1a A, to the 500ml reaction flask by adding 50.0g (0.16πο1) 1- (2-fluorobenzyl) -1H-pyrazolo [3,4-b] pyridine-3-carboxamidine hydrochloride, 27.2 g (0.16 mol) Benzimidazole malononitrile, 8.6 g (0.16 mol) Sodium methoxide 350ml DMF, stirred at 110 ° C for 12 h, cooled to 25 ° C, filtered to obtain a solid which was washed with 250 ml of ethanol for 10 min, Filtering the solid, repeating the washing step 2 times to obtain a solid, After drying in a 85 ° C oven for 5 h, To give 60.7 g of compound m, Yield was 84.6%
  • 50
  • [ 6017-21-6 ]
  • 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamide hydrochloride [ No CAS ]
  • [ 428854-23-3 ]
YieldReaction ConditionsOperation in experiment
95% With sodium methylate In toluene at 120℃; 1.1 The present embodiment relates to a method for synthesizing a high purity levocizine comprising the steps of: Step one, in the 2L three bottles,1- (2-fluorobenzyl) -1HH-pyrazolo [3,4-b] pyridine-3-carboxamidine hydrochloride (Compound 1, 94.5 g, 0.31 mol)1.2 L of toluene, followed by the addition of sodium methoxide (17 g, 0.31 mol)Phenyl azo malononitrile(Compound 2,252.5 g, 0.31 mol),Heated to 120 ° C reflux, TLC detection reaction is completed, cooled to room temperature, suction filter, filter cake washed once with toluene, and then water beating solid, suction filter, drying intermediates to get compound 3 (129g, 0 · 29mo 1,Yield 95%Content of 99%),
  • 51
  • [ 6017-21-6 ]
  • [ 1040724-73-9 ]
  • 2-(1H-indol-3-yl)-6-(phenyldiazenyl)pyrazolo[1,5-a]pyrimidine-5,7-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With pyridine In ethanol for 14h; Reflux;
  • 52
  • [ 6017-21-6 ]
  • [ 60100-09-6 ]
  • 4,6-diamino-5-(phenylazo)pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With ammonia at 145 - 150℃; for 2h; Autoclave; 1.2 2) Synthesis of 3,5-diamino-4-phenylazo pyrimidine (Formula 5a) Add 1200 mL formamide and 150g 2- phenylazo malononitrile (formula 4a) in 2000mL autoclave, the reaction system was evacuated into ammonia, all valves closed and heated to 145 ~ 150 incubated for 2 hours , the end of the reaction, was cooled to room temperature, drained ammonia, filtered, and the filter cake was rinsed with water, drained to give a brown solid after 3,5-diamino-4-yl phenylazo pyrimidine (formula 5a).
With ammonia at 145 - 150℃; for 2h; Autoclave; 1.2 2) Synthesis of 4,6-diamino-5-(phenylazo)pyrimidine (Formula 5a) In a 2000 mL autoclave, 1200 mL of formamide and 150 g of 2-phenylazomalononitrile (Formula 4a) were added and the reaction system was evacuated and passed through liquid ammonia. All valves were closed and heated to 145 to 150 ° C for 2 hours. The reaction is finished, the temperature is cooled to 25 to 15 ° C, the ammonia is removed, filtered, and the filter cake is rinsed with water and dried to obtain a brown solid 4,6-diamino-5-(phenylazo)pyrimidine (Formula 5a).
  • 53
  • [ 6017-21-6 ]
  • 1-(thiophen-2-yl)methyl-1H-pyrazolo[3,4-b]pyridine-3-carboxamidine [ No CAS ]
  • 2-[1-(thiophen-2-yl)methyl-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(E)phenyldiazenyl]-4,6-pyrimidinediamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
82.4% In N,N-dimethyl-formamide at 110℃; for 12h; Inert atmosphere; 1.G G: 2-[1-(thiophen-2-yl)methyl-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(E)phenyldiazenyl]- 4,6-pyrimidinediamine Weigh 3.5 g (13.6 mmol) of the product obtained in Step F and 2.34 g (13.75 mmol of the product of Step A, dissolved in 80 mL of DMF and reacted under N2 protection at 110° C. for 12 h. TLC monitoring, the reaction was complete, cooling, concentration under reduced pressure, suction filtration, The filter cake is washed with an appropriate amount of water and then washed with a small amount of ethanol to obtain an orange solid. The filtrate is added with an appropriate amount of water until no more solids are precipitated. The filter cake is filtered, and the filter cake is washed with a suitable amount of water and then washed with a small amount of ethanol to obtain an orange solid. A total of 4.79 g of a product was obtained with a yield of 82.4%.
  • 54
  • [ 6017-21-6 ]
  • 1-(5-methylpyridin-3-yl)methyl-1H-pyrazolo[3,4-b]pyridine-3-carboxamidine [ No CAS ]
  • 2-[1-(5-methylpyridin-3-yl)methyl-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(E)phenyldiazenyl]-4,6-pyrimidinediamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
71.2% In N,N-dimethyl-formamide at 110℃; for 12h; Inert atmosphere; 2.D D: 2-[1-(5-methylpyridin-3-yl)methyl-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(E)phenyldiazoalkenyl]-4,6-pyrimidinediamine Weigh 3.9 g (22.92 mmol) of the product of Example 2 Step C and 6 g (22.53 mmol) of phenyldiazomalononitrile in 120 mL of DMF. The reaction was carried out at about 110° C. for 12 h under N 2 protection. TLC was monitored and the basic reaction was completed. Vacuum filtration, the filter cake was washed with an appropriate amount of water, and an appropriate amount of water was added to the filtrate until solid was no longer produced. The solid was filtered by suction and the filter cake was washed with 10% ethanol and dried to obtain 7 g of orange solid, yield 71.2%.
  • 55
  • [ 6017-21-6 ]
  • 1-(2-fluoropyridine 3-yl)methyl-1H-pyrazolo[3,4-b]pyridine-3-carboxamidine [ No CAS ]
  • 2-[1-(2-fluoropyridin-3-yl)methyl-1H-pyrazolo[3,4-b]pyridine-3-yl]-5-[(E)phenyldiazenyl]-4,6-pyrimidine diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
88.8% In N,N-dimethyl-formamide at 110℃; for 0.5h; 14.F F: 2-[1-(2-fluoropyridin-3-yl)methyl-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(E)phenyldiazene -4,6-pyrimidinediamine 5.5 g (20.35 mmol) of the product from Example E and 3.5 g (20.5676 mmol) of phenylazolopropanedinitrile are weighed and dissolved in 110 mL of DMF. The reaction is carried out in a microwave reactor at 110° C. for 30 min with a power of 50 W. TLC monitoring, the reaction is complete, cooling, suction filtration, filter cake washed with the right amount of water to obtain a bright yellow solid, the filtrate was added an appropriate amount of water until no solid precipitated, suction filtration, the filter cake was washed with a small amount of 10% ethanol to give a yellow solid , Drying, a total yield of 7.96g, yield 88.8%.
  • 56
  • [ 6017-21-6 ]
  • 1-(benzo[d][1,3]dioxo-4-ylmethyl)-5-fluoro-1H-pyrazolo[3,4-b]pyridine-3-carboxamidine [ No CAS ]
  • 2-(1-(benzo[d][1,3]dioxo-4-ylmethyl)-5-fluoro-1H-pyrazolo[3,4-b]pyridin-3-yl)-5-(phenylazo)pyrimidine-4,6-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In N,N-dimethyl-formamide at 85 - 100℃; for 4h; Inert atmosphere; 21.5 Step 5)2-(1-(benzo[d][1,3]dioxo-4-ylmethyl)-5-fluoro-1H-pyrazolo[3,4-b]pyridin-3-yl)-5-(phenylazo)pyrimidine-4,6-diamine 1-(Benzo[d][1,3]dioxo-4-ylmethyl)-5-fluoro-1H-pyrazolo[3,4-b]pyridine-3-carboxamidine (1.17 g, 3.73mmol)Dissolved in N,N-dimethylformamide (50 mL), triethylamine (0.80 mL, 5.8 mmol).Heated to 85 ° C under nitrogen protection,Phenylazomalononitrile (960 mg, 5.64 mmol) was then added.The temperature was further raised to 100 ° C and stirred for 4 hours.After cooling to room temperature, the resulting reaction solution was directly subjected to the next reaction without further purification.
  • 57
  • [ 6017-21-6 ]
  • 5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxamidine [ No CAS ]
  • 2-(5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-5-(phenylazo)pyrimidine-4,6-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With triethylamine In N,N-dimethyl-formamide at 85 - 100℃; for 4h; 1 step 1)2-(5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-5-(phenylazo)pyrimidine-4,6 -diamine 5-Fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxamidine (3.0 g, 10.0 mmol) was weighed out.In a 250 ml flask, N,N-dimethylformamide (30.0 mL) was added thereto.And triethylamine (2.0 mL, 14.0 mmol), warmed to 85 ° C,Phenylazomalononitrile (2.2 g, 13 mmol) was added, and the mixture was heated to 100 ° C for 4 hours.Cool to room temperature, let stand overnight, add water (150 mL), stir for 1 hour, filter,The filter cake was washed sequentially with water (20 mL) and methanol (20 mL).Drying in vacuo gave a yellow solid (4.0 g, 84.0%)
  • 58
  • [ 6017-21-6 ]
  • 5-fluoro-1-(2-fluorobenzyl)-1H-indazole-3-carboximidamide [ No CAS ]
  • 2-(5-fluoro-1-(2-fluorobenzyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide at 100℃; 63.5 Step 5: 2-(5-fluoro-1-(2-fluorobenzyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine 5-Fluoro-1-(2-fluorobenzyl)-IH-indazole-3-carboximidamide (3.14 g, 11.0 mmol) andbenzeneazomalononitrile (2.24 g, 13.2 mmol) were added into N,N-dimethylformamide (30.00mL ). The mixture was stirred at 100 oc overnight. The mixture was cooled to rt, and the reactionmixture was concentrated on a rotary evaporator to give the crude product which was used in thenext step without further purification.MS (ESI, pos.ion) m/z: 457.1 (M+1).
  • 59
  • [ 6017-21-6 ]
  • 5,7-difluoro-1-(pyridin-3-ylmethyl)-1H-indazole-3-carboximidamide [ No CAS ]
  • 2-(5,7-difluoro-1-(pyridin-3-ylmethyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In N,N-dimethyl-formamide at 85 - 100℃; for 5h; Inert atmosphere; 3.4 Step 4: 2-( 5, 7 -difluoro-1-(pyridin-3-ylmethyl)-1H -indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine 5, 7-Difluoro-1-(pyridin-3-ylmethyl)-1H-indazole-3-carboximidamide (1.0 g, 3.5 mmol)was dissolved in N,N-dimethylformamide (50 mL), then triethylamine (0.80 mL, 5.8 mmol) wasadded into the mixture. The resulting mixture was heated to 85 oc under nitrogen protection, and to the mixture was added benzeneazomalononitrile (900 mg, 5.30 mmol). After the addition, themixture was heated to 100 oc and stirred for 5 hours. The mixture was cooled to roomtemperature and used directly in the next group without further purification.MS (ESI, pos. ion) m/z: 458.1 (M+ 1).
  • 60
  • [ 6017-21-6 ]
  • 6-fluoro-1-(2-fluorobenzyl)-1H-indazole-3-carboximidamide [ No CAS ]
  • 2-(6-fluoro-1-(2-fluorobenzyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In N,N-dimethyl-formamide at 85 - 100℃; 5.6 Step 6: 2-( 6-fluoro-1-(2-fluorobenzyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine 6-Fluoro-1-(2-fluorobenzyl)-1H-indazole-3-carboximidamide (602 mg, 2.10 mmol)was dissolved in N,N-dimethylformamide (2.5 mL), then triethylamine (0.35 mL, 2.5 mmol) wasadded into the mixture. The resulting mixture was heated to 85 °C, and to the flask was addeddropwise slowly a solution of benzeneazomalononitrile (447.7 mg, 2.63 mmol) inN,N-dimethylformamide (2.5 mL). After the addition, the mixture was heated to 100 oc andstirred for 4 h. The mixture was cooled to room temperature and stirred overnight. The mixturewas used directly in the next group without further purification.MS (ESI, pos. ion) m/z: 457.3 (M+ 1).
  • 61
  • [ 6017-21-6 ]
  • 6-fluoro-1-(pyridin-3-ylmethyl)-1H-indazole-3-carboximidamide [ No CAS ]
  • 2-(6-fluoro-1-(pyridin-3-ylmethyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With triethylamine at 85 - 100℃; for 5h; Inert atmosphere; 7.4 Step 4: 2-( 6-fluoro-1-(pyridin-3-ylmethyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine 6-Fluoro-1-(pyridin-3-ylmethyl)-1H-indazole-3-carboximidamide (1.40 g, 5.20 mmol)was dissolved in N,N-dimethylformamide (20 mL), then triethylamine (1.1 mL, 7.9 mmol) wasadded into the mixture. The resulting mixture was heated to 85 oc under nitrogen protection, andto the mixture was added benzeneazomalononitrile (1.2 g, 7.1 mmol). After the addition, themixture was heated to 100 oc and stirred for 5 h. The mixture was warmed to room temperature,and water (20 mL) was added into the mixture. The resulting mixture was stirred at rt for 1 hour.Then there was a white solid precipitate out, and the mixture was filtered by suction. The filtercake was washed with water (50 mL x 2) and ethanol (50 mL x 2), and then dried in oven to givea claybank solid (1.10 g, 48.0%).MS (ESI, pos. ion) m/z: 440.1 (M+ 1).
  • 62
  • [ 6017-21-6 ]
  • 7-fluoro-1-(2-fluorobenzyl)-1H-indazole-3-carboximidamide [ No CAS ]
  • 2-(7-fluoro-1-(2-fluorobenzyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% With triethylamine In N,N-dimethyl-formamide at 85 - 100℃; 10.6 Step 6: 2-(7-fluoro-1-(2-fluorobenzyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine 7-Fluoro-1-(2-fluorobenzyl)-1H-indazole-3-carboximidamide (6.8 g, 24 mmol) wasdissolved in N,N-dimethylformamide (15 mL), then triethylamine (4.1 mL, 29 mmol) was addedinto the mixture. The resulting mixture was heated to 85 °C, and to the mixture was added asolution ofbenzeneazomalononitrile (5.1 g, 30 mmol) in N,N-dimethylformamide (15 mL). Afterthe addition, the mixture was heated to 100 oc and stirred for 4 h, then the mixture was stirred atrt overnight. To the reaction mixture was added water (1.0 L), and the resulting mixture wasstirred for 1 hour at room temperature. Then the mixture was filtered by suction through aBuchner funnel. The filter cake were washed with water (100 mL x 2) and methanol (50 mL x 2)and dried to give a yellow solid (10.5 g, 96.0%).MS (ESI, pos.ion) m/z: 457 (M+ 1).
  • 63
  • [ 6017-21-6 ]
  • 7-fluoro-1-(pyridin-3-ylmethyl)-1H-indazole-3-carboximidamide [ No CAS ]
  • 2-(7-fluoro-1-(pyridin-3-ylmethyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In N,N-dimethyl-formamide at 85 - 100℃; 19.4 Step 4: 2-(7-fluoro-1-(pyridin-3-ylmethyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine 7-Fluoro-1-(pyridin-3-ylmethyl)-1H-indazole-3-carboximidamide (2.99 g, 11.1 mmol)was placed in a 250 mL flask, then N,N-dimethylformamide (40 mL) and triethylamine (1.9 mL,14.0 mmol) were added into the mixture. The resulting mixture was heated to 85 °C, and to theflask was added dropwise slowly a solution of benzeneazomalononitrile (2.54 g, 14.9 mmol) inN,N-dimethylformamide (40 mL). After the addition, the mixture was heated to 100 oc andstirred for 4 h. The mixture was cooled to rt and stirred overnight, which was used in the nextstep without further purification.MS (ESI, pos. ion) m/z: 440.1 (M+ 1).
  • 64
  • [ 6017-21-6 ]
  • 7-fluoro-1-(pyridin-2-ylmethyl)-1H-indazole-3-carboximidamide [ No CAS ]
  • 2-(7-fluoro-1-(pyridin-2-ylmethyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In N,N-dimethyl-formamide at 85 - 100℃; for 5h; Inert atmosphere; 21.4 Step 4: 2-(7-fluoro-1-(pyridin-2-ylmethyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine 7-Fluoro-1-(pyridin-2-ylmethyl)-1H-indazole-3-carboximidamide (650 mg, 2.41 mmol)was dissolved in N,N-dimethylformamide (50 mL), then triethylamine (0.50 mL, 3.6 mmol) wasadded into the mixture. The resulting mixture was heated to 85 oc under nitrogen protection, andto the mixture was added benzeneazomalononitrile (620 mg, 3.64 mmol). After the addition, themixture was heated to 100 oc and stirred for 5 h. The mixture was used directly in the next groupwithout further purification.MS (ESI, pos.ion) m/z: 440.1 [M+1(
  • 65
  • [ 6017-21-6 ]
  • 7-fluoro-1-(pyridin-4-ylmethyl)-1H-indazole-3-carboximidamide [ No CAS ]
  • 2-(7-fluoro-1-(pyridin-4-ylmethyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In N,N-dimethyl-formamide at 85 - 100℃; for 4h; Inert atmosphere; 23.4 Step 4: 2-(7-fluoro-1-(pyridin-4-ylmethyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine 7-Fluoro-1-(pyridin-4-ylmethyl)-1H-indazole-3-carboximidamide(1.71 g, 6.35 mmol)was dissolved in N,N-dimethylformamide (50 mL), then triethylamine (1.32 mL, 9.50 mmol)was added into the mixture. The resulting mixture was heated to 85 oc under nitrogen protection,and to the mixture was added benzeneazomalononitrile (1.62 g, 9.52 mmol). After the addition,the mixture was heated to 100 oc and stirred for 4 h. The reaction was stopped, and the reactionmixture was used directly in the next step without further purification.MS (ESI, pos. ion) m/z: 440.3 (M+ 1).
  • 66
  • [ 6017-21-6 ]
  • 5,7-difluoro-1-(2-fluorobenzyl)-1H-indazole-3-carboximidamide [ No CAS ]
  • 2-(5,7-difluoro-1-(2-fluorobenzyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% With triethylamine In N,N-dimethyl-formamide at 85 - 100℃; 1.6 Step 6: 2-(5, 7-difluoro-1-(2-fluorobenzyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine 5,7-Difluoro-1-(2-fluorobenzyl)-1H-indazole-3-carboximidamide (2.6 g, 8.5 mmol)was dissolved in N,N-dimethylformamide (50 mL), then triethylamine (1.5 mL, 11 mmol) wasadded into the mixture. The resulting mixture was heated to 85 °C, and to the mixture was addeda solution of benzeneazomalononitrile (1.8 g, 11 mmol) in N,N-dimethylformamide (50 mL).After the addition, the mixture was heated to 100 oc and stirred for 4 h. Then the reactionmixture was stirred at room temperature overnight. To the reaction mixture was added water(300 mL), and the resulting mixture was stirred for 1 hour at room temperature to precipitate outthe solid. Then the mixture was filtered by suction through a Buchner funnel. The filter cake waswashed with water (50 mL x 2) and methanol (50 mL x 2) to give a yellow solid (4.0 g, 98.0%).MS (ESI, pos.ion) m/z: 475.4 (M+ 1).
  • 67
  • [ 6017-21-6 ]
  • 7-fluoro-1-(pyrimidin-5-ylmethyl)-1H-indazole-3-carboximidamide [ No CAS ]
  • 2-(7-fluoro-1-(pyrimidin-5-ylmethyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In N,N-dimethyl-formamide at 85 - 100℃; for 5h; Inert atmosphere; 33.4 Step 4: 2-(7-fluoro-1-(pyrimidin-5-ylmethyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine 7-Fluoro-1-(pyrimidin-5-ylmethyl)-1H-indazole-3-carboximidamide (1.72 g, 6.36mmol) was dissolved in N,N-dimethylformamide (80 mL), then triethylamine (3.1 mL, 22 mmol)was added into the mixture. The resulting mixture was heated to 85 oc under nitrogen protection,and to the mixture was added benzeneazomalononitrile (2.17 g, 12.8 mmol). The mixture washeated to 100 oc and stirred for 5 h. The reaction mixture was cooled to room temperature andused directly in the next step without further purification.MS (ESI, pos.ion) m/z: 441.1 (M+1).
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