Home Cart 0 Sign in  
X

[ CAS No. 74290-65-6 ]

{[proInfo.proName]} ,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 74290-65-6
Chemical Structure| 74290-65-6
Chemical Structure| 74290-65-6
Structure of 74290-65-6 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Bulk Inquiry Add To Cart

Quality Control of [ 74290-65-6 ]

Related Doc. of [ 74290-65-6 ]

Alternatived Products of [ 74290-65-6 ]

Product Details of [ 74290-65-6 ]

CAS No. :74290-65-6 MDL No. :MFCD09750037
Formula : C5H6BrN3 Boiling Point : -
Linear Structure Formula :- InChI Key :VQNGEHYFPRPIGF-UHFFFAOYSA-N
M.W :188.03 g/mol Pubchem ID :9899043
Synonyms :

Calculated chemistry of [ 74290-65-6 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.2
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 39.1
TPSA : 51.8 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.84 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.44
Log Po/w (XLOGP3) : 0.86
Log Po/w (WLOGP) : 1.14
Log Po/w (MLOGP) : 0.11
Log Po/w (SILICOS-IT) : 1.34
Consensus Log Po/w : 0.98

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.04
Solubility : 1.71 mg/ml ; 0.0091 mol/l
Class : Soluble
Log S (Ali) : -1.53
Solubility : 5.53 mg/ml ; 0.0294 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.54
Solubility : 0.549 mg/ml ; 0.00292 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.25

Safety of [ 74290-65-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 74290-65-6 ]

* 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.

  • Upstream synthesis route of [ 74290-65-6 ]
  • Downstream synthetic route of [ 74290-65-6 ]

[ 74290-65-6 ] Synthesis Path-Upstream   1~7

  • 1
  • [ 74290-65-6 ]
  • [ 5521-58-4 ]
Reference: [1] Journal of Heterocyclic Chemistry, 1980, vol. 17, p. 143 - 147
  • 2
  • [ 74290-65-6 ]
  • [ 89464-87-9 ]
YieldReaction ConditionsOperation in experiment
75% With sodium methylate; sodium In methanol; water (i)
2-Amino-3-bromo-5-methylpyrazine (0.374 g) was added to a freshly prepared solution of sodium methoxide in methanol (made by addition of sodium (0.115 g) to methanol (6 ml)).
The reaction was heated under reflux for 18 hours, cooled to ambient temperature and the solvent removed by evaporation.
Water (5 ml) was added to the residue and extracted with dichloromethane (3*20 ml).
The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation.
The residue was purified by chromatography on silica gel, eluding with dichloromethane to give 2-amino-3-methoxy-5-methylpyrazine as a white crystalline solid (0.208 g, 75percent), m.p. 67°-69° C.; mass spectrum (+ve CI): 140 (M+H)+.
75% With sodium methylate; sodium In methanol; water (b)
2-Amino-3-bromo-5-methylpyrazine (0.374 g) was added to a freshly prepared solution of sodium methoxide in methanol (made by addition of sodium (0.115 g) to methanol (6 ml)).
The reaction was heated under reflux for 18 hours, cooled to ambient temperature and the solvent removed by evaporation.
Water (5 ml) was added to the residue and extracted with dichloromethane (3*20 ml).
The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation.
The residue was purified by chromatography on silica gel, eluding with dichloromethane to give 2-amino-3-methoxy-5-methylpyrazine as a white crystalline solid (0.208 g, 75percent), m.p. 67°-69° C.; mass spectrum (+ve CI): 140 (M+H)+.
75% With sodium methylate; sodium In methanol; water (ii)
2-Amino-3-bromo-5-methylpyrazine (0.374 g) was added to a freshly prepared solution of sodium methoxide in methanol (made by addition of sodium (0.115 g) to methanol (6 ml).
The reaction mixture was heated under reflux for 18 hours, cooled to ambient temperature and the solvent removed by evaporation.
Water (5 ml) was added to the residue and extracted with dichloromethane (3*20 ml).
The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation.
The residue was purified by chromatography on silica gel, eluding with dichloromethane to give 2-amino-3-methoxy-5-methylpyrazine as a white crystalline solid (0.208 g, 75percent), m.p. 67°-69° C.; mass spectrum (+ve CI): 140 (M+H)+.
Reference: [1] Patent: US5861401, 1999, A,
[2] Patent: US5866568, 1999, A,
[3] Patent: US5668137, 1997, A,
  • 3
  • [ 67-56-1 ]
  • [ 124-41-4 ]
  • [ 74290-65-6 ]
  • [ 89464-87-9 ]
YieldReaction ConditionsOperation in experiment
92% at 30 - 100℃; for 6 h; Inert atmosphere [00791] To a mixture of 3-bromo-5-methyl-pyrazin-2-amine (31 g, 164.87 mmol) in MeOH (150 mL) was added NaOMe (14 g, 263.79 mmol) in one portion at 30 °C under N2. The mixture was stirred at 100 °C for 6 hrs. The mixture was concentrated under reduced pressure and the resulting residue was dissolved in water (100 mL). The mixture was extracted with EtOAc and the combined organic layers were washed with brine (20 mL), dried with Na2S04, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (to afford 3-methoxy-5-methyl-pyrazin-2-amine (21 g, 92percent yield) as a white solid. 1H MR (400 MHz, CDCh-d) δ ppm 7.39 (s, 1H) 4.59 (br s, 2 H) 3.97 (s, 3 H) 2.29 (s, 3 H)
Reference: [1] Patent: WO2018/136265, 2018, A1, . Location in patent: Paragraph 00791
  • 4
  • [ 124-41-4 ]
  • [ 74290-65-6 ]
  • [ 89464-87-9 ]
Reference: [1] Journal of Medicinal Chemistry, 1997, vol. 40, # 6, p. 996 - 1004
  • 5
  • [ 5521-58-4 ]
  • [ 74290-65-6 ]
YieldReaction ConditionsOperation in experiment
88% With pyridine; bromine In dichloromethane at 20℃; To a solution of 5-methylpyrazin-2-amine (5.00g, 45.8 mmol) and pyridine (4.35g,55.0 mmol) in DCM (250 mL) was added bromine (8.80 g, 55.0 mmol). The mixture was stirredat rt overnight. To the reaction mixture was added water (150 mL), and the resulting mixture waspartitioned. The organic layer was washed with saturated brine (100 mL), dried over anhydroussodium sulfate and filtered. The filtrate was concentrated in vacuo to give the title compound asa yellow solid (7.64 g, 88 percent).MS (ESI, pos. ion) m/z: 190.2 [M+Ht;1H NMR (400 MHz, CDCh) 8 (ppm): 7.83 (s, lH), 4.93 (s, 2H), 2.41 (s, 3H).
69% With N-Bromosuccinimide In dichloromethane at 0 - 30℃; for 1 h; Inert atmosphere [00790] To a mixture of 5-methylpyrazin-2-amine (10 g, 92 mmol) in DCM (300 mL) was added BS (16 g, 91.63 mmol) in one portion at 0 °C under N2. The mixture was stirred at 30 °C for 1 hr. The resulting mixture was poured into saturated aq. Na2S03 (100 mL) and the aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine, dried with Na2S04, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to afford 3-bromo-5-methyl-pyrazin-2-amine (12 g, 69percent yield,) as a light yellow solid. MR (400 MHz, CDCh-d) δ ppm 7.82 (s, 1H) 4.79 - 5.03 (m, 2 H) 2.39 (s, 3 H).
65% With N-Bromosuccinimide In dichloromethane at 0 - 20℃; for 12 h; Step 1.
3-Bromo-5-methylpyrazin-2-amine.
To a cooled, 0° C., solution of 5-methylpyrazin-2-amine (5.00 g, 0.05 mol) in DCM (230 mL) was added 1-bromopyrrolidine-2,5-dione (8.97 g, 0.05 mol) all at once.
The reaction mixture was allowed to warm to room temperature and stirred for 12 h.
The reaction was quenched with 1 N sodium thiosulfate (50 mL), the layers were separated and the organic phase was extracted with water (2*50 mL).
The combined organic layers were dried (Na2SO4), and the solvent was removed under reduced pressure.
Purification (FCC, SiO2, 0-50percent, EtOAc/hexanes) afforded the title compound as a yellow solid (8.61 g, 65percent).
[M+H]=188.9/190.11
56.4% With pyridine; bromine In chloroform for 0.5 h; To a suspension of 5-methylpyrazin-2-amine (1.09g, 10 mmol) in chloroform (100 mL) was added pyridine(0.85 ml., 10.5 mmol). The mixture was stirred in a foilwrappedflask fitted with an addition funnel, and a solution ofbromine (0.54 ml., 10.5 mmol) in chloroform (10 mL) wasadded dropwise over 10 min. The mixture was allowed toreact an additional 20 minutes after addition was completeand then poured into a separatory funnel containing 10 mLwater. The phases were separated and the organics washedagain with water, dried over sodium sulfate, filtered and concentratedin vacuo. The resulting red oil was purified by silicagel chromatography with 12-100percent EtOAc/hexanes. Themajor UV active peak was collected to give 3-bromo-5-methylpyrazin-2-amine (1.06 g, 5.64 mmol, 56.4percent yield) as a cream-colored solid.

Reference: [1] Patent: WO2018/108125, 2018, A1, . Location in patent: Paragraph 00511
[2] Patent: WO2018/136265, 2018, A1, . Location in patent: Paragraph 00790
[3] Patent: US2014/275531, 2014, A1, . Location in patent: Paragraph 0353
[4] Patent: JP5714745, 2015, B2, . Location in patent: Paragraph 0687; 0688
[5] Patent: US5866568, 1999, A,
[6] Patent: US5668137, 1997, A,
  • 6
  • [ 5521-58-4 ]
  • [ 74290-65-6 ]
  • [ 74290-68-9 ]
YieldReaction ConditionsOperation in experiment
50%
Stage #1: With hydrogen bromide; acetic acid In chloroform at 50℃; for 0.5 h; Darkness
Stage #2: With bromine In chloroform at 55℃; for 21 h;
Stage #3: With sodium carbonate In chloroform; water
A solution of HBr/CH3CO2H (360 g (260 mL), 1.50 mol, 33percent HBr in CH3CO2H) in anhydrous CHCl3 (300 mL) was added over 15 min to a solution of 5-methylpyrazin-2-amine 15 (42 g, 0.38 mmol) in CHCl3 (1 L). The reaction flask was wrapped in aluminum foil and heated to 50 °C for 30 min in the dark whereupon a solution of Br2 (68 g, 0.42 mmol) in CHCl3 (500 mL) was added dropwise over 3 h during which time the internal temperature of the reaction never exceeded 55 °C. After 18 h at 55 °C the solvent was evaporated under reduced pressure. The crude mixture was diluted with water (200 mL) and the pH was adjusted to pH=9 by the addition of solid Na2CO3. The suspension was filtered under vacuum and the filtrate was extracted with EtOAc (1 L.x.5). The combined organic extracts were concentrated under reduced pressure and purified by flash silica gel chromatography eluting with petroleum ether/EtOAc (5:1-->1:1) to give compound 6-bromo-5-methylpyrazin-2-amine 17a (36 g, 50percent) as a light orange solid; mp 154-157 °C; IR (KBr): 3315, 3188, 1744, 1638, 1575, 1482, 1375, 1308, 1051 cm-1; 1H NMR (400 MHz, CDCl3): δ=7.84 (s, 1H), 4.55 (br s, 2H), 2.52 (s, 3H); 13C NMR (100 MHz, CDCl3): δ=152.2, 141.8, 138.4, 129.2, 22.2; HRMS-ESI: calcd for C5H7BrN3 (M+H)+: 187.9823 and 189.9803; found: 187.9816 and 189.9796. An analytical sample of 3-bromo-5-methylpyrazin-2-amine (17b) was also isolated for spectroscopic analysis; mp 56-57 °C. 1H NMR (400 MHz, CDCl3): δ=7.80 (s, 1H), 4.95 (br s, 2H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3): δ=150.6, 142.8, 139.9, 125.2, 19.7; HRMS-ESI: calcd for C5H7BrN3 (M+H)+: 187.9823 and 189.9803; found: 187.9817 and 189.9796.
Reference: [1] Journal of Heterocyclic Chemistry, 1980, vol. 17, p. 143 - 147
[2] Tetrahedron, 2011, vol. 67, # 47, p. 9063 - 9066
  • 7
  • [ 5521-58-4 ]
  • [ 74290-65-6 ]
  • [ 74290-68-9 ]
YieldReaction ConditionsOperation in experiment
50%
Stage #1: With hydrogen bromide; acetic acid In chloroform at 50℃; for 0.5 h; Darkness
Stage #2: With bromine In chloroform at 55℃; for 21 h;
Stage #3: With sodium carbonate In chloroform; water
A solution of HBr/CH3CO2H (360 g (260 mL), 1.50 mol, 33percent HBr in CH3CO2H) in anhydrous CHCl3 (300 mL) was added over 15 min to a solution of 5-methylpyrazin-2-amine 15 (42 g, 0.38 mmol) in CHCl3 (1 L). The reaction flask was wrapped in aluminum foil and heated to 50 °C for 30 min in the dark whereupon a solution of Br2 (68 g, 0.42 mmol) in CHCl3 (500 mL) was added dropwise over 3 h during which time the internal temperature of the reaction never exceeded 55 °C. After 18 h at 55 °C the solvent was evaporated under reduced pressure. The crude mixture was diluted with water (200 mL) and the pH was adjusted to pH=9 by the addition of solid Na2CO3. The suspension was filtered under vacuum and the filtrate was extracted with EtOAc (1 L.x.5). The combined organic extracts were concentrated under reduced pressure and purified by flash silica gel chromatography eluting with petroleum ether/EtOAc (5:1-->1:1) to give compound 6-bromo-5-methylpyrazin-2-amine 17a (36 g, 50percent) as a light orange solid; mp 154-157 °C; IR (KBr): 3315, 3188, 1744, 1638, 1575, 1482, 1375, 1308, 1051 cm-1; 1H NMR (400 MHz, CDCl3): δ=7.84 (s, 1H), 4.55 (br s, 2H), 2.52 (s, 3H); 13C NMR (100 MHz, CDCl3): δ=152.2, 141.8, 138.4, 129.2, 22.2; HRMS-ESI: calcd for C5H7BrN3 (M+H)+: 187.9823 and 189.9803; found: 187.9816 and 189.9796. An analytical sample of 3-bromo-5-methylpyrazin-2-amine (17b) was also isolated for spectroscopic analysis; mp 56-57 °C. 1H NMR (400 MHz, CDCl3): δ=7.80 (s, 1H), 4.95 (br s, 2H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3): δ=150.6, 142.8, 139.9, 125.2, 19.7; HRMS-ESI: calcd for C5H7BrN3 (M+H)+: 187.9823 and 189.9803; found: 187.9817 and 189.9796.
Reference: [1] Journal of Heterocyclic Chemistry, 1980, vol. 17, p. 143 - 147
[2] Tetrahedron, 2011, vol. 67, # 47, p. 9063 - 9066
Historical Records

Related Functional Groups of
[ 74290-65-6 ]

Bromides

Chemical Structure| 914452-71-4

[ 914452-71-4 ]

2-Bromo-6-methylpyrazine

Similarity: 0.80

Chemical Structure| 21943-12-4

[ 21943-12-4 ]

2-Amino-3-bromopyrazine

Similarity: 0.80

Chemical Structure| 111454-68-3

[ 111454-68-3 ]

5-Bromo-2,3-dimethylpyrazine

Similarity: 0.77

Chemical Structure| 74290-66-7

[ 74290-66-7 ]

3,5-Dibromo-6-methylpyrazin-2-amine

Similarity: 0.76

Chemical Structure| 859064-02-1

[ 859064-02-1 ]

2-Bromo-6-cyanopyrazine

Similarity: 0.71

Amines

Chemical Structure| 21943-12-4

[ 21943-12-4 ]

2-Amino-3-bromopyrazine

Similarity: 0.80

Chemical Structure| 74290-66-7

[ 74290-66-7 ]

3,5-Dibromo-6-methylpyrazin-2-amine

Similarity: 0.76

Chemical Structure| 5521-58-4

[ 5521-58-4 ]

5-Methylpyrazin-2-amine

Similarity: 0.74

Chemical Structure| 5521-56-2

[ 5521-56-2 ]

6-Methylpyrazin-2-amine

Similarity: 0.72

Chemical Structure| 6294-70-8

[ 6294-70-8 ]

5,6-Dimethylpyrazin-2-amine

Similarity: 0.69

Related Parent Nucleus of
[ 74290-65-6 ]

Pyrazines

Chemical Structure| 914452-71-4

[ 914452-71-4 ]

2-Bromo-6-methylpyrazine

Similarity: 0.80

Chemical Structure| 21943-12-4

[ 21943-12-4 ]

2-Amino-3-bromopyrazine

Similarity: 0.80

Chemical Structure| 111454-68-3

[ 111454-68-3 ]

5-Bromo-2,3-dimethylpyrazine

Similarity: 0.77

Chemical Structure| 74290-66-7

[ 74290-66-7 ]

3,5-Dibromo-6-methylpyrazin-2-amine

Similarity: 0.76

Chemical Structure| 5521-58-4

[ 5521-58-4 ]

5-Methylpyrazin-2-amine

Similarity: 0.74