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Structure of 120747-85-5

Chemical Structure| 120747-85-5

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Product Details of [ 120747-85-5 ]

CAS No. :120747-85-5
Formula : C5H7N3O
M.W : 125.13
SMILES Code : OCC1=CN=C(N)N=C1
MDL No. :MFCD09991890
InChI Key :NUGGQZDIPXLGQW-UHFFFAOYSA-N
Pubchem ID :21615172

Safety of [ 120747-85-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 120747-85-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.2
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 32.56
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

72.03 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.94
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

-1.03
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

-0.59
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

-1.16
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

0.06
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.36

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-0.39
Solubility 50.5 mg/ml ; 0.403 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

0.01
Solubility 127.0 mg/ml ; 1.01 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-1.08
Solubility 10.4 mg/ml ; 0.0832 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-7.79 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.29

Application In Synthesis of [ 120747-85-5 ]

* 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 [ 120747-85-5 ]

[ 120747-85-5 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 120747-85-5 ]
  • [ 769083-57-0 ]
YieldReaction ConditionsOperation in experiment
52% Step 2: A slurry of 69 (31 g, 0.25 mol) in [CH2CI2] (500 ml) was cooled to [0 C] and slowly treated with SOC2 (55ml, 0.74 mol over 30 min). The reaction was then stirred overnight at [20 C.] The material was concentrated, slurried in acetone, and then filtered. The resulting beige solid Preparation 7 was dried overnight in vacuo (38.4g, 52%, HCI salt).
  • 2
  • [ 120747-84-4 ]
  • [ 120747-85-5 ]
YieldReaction ConditionsOperation in experiment
67% With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 3h; To a stirred solution of 2-aminopyrimidine-5-carbaldehyde (15, 500 mg, 4.06 mmol) in methanol (6 mL) was added sodium borohydride (200 mg, 5.28 mmol) in portions at 000. The resulting solution was slowly warmed to room temperature and was further stirred for 3 hours. After completion (monitored by TLC, 5% MeOH in DCM, Rf 0.3), thereaction mixture was quenched by addition of saturated aqueous NH4CI solution and the resulting reaction mixture was concentrated under vacuo. The residue was directly loaded over a short column of silica gel (100-200 mesh) and eluted with gradient elution of 100% DCM to 7.5% MeOH in DCM. Concentration of fractions containing desired product afforded (2-aminopyrimidin-5-yl)methanol (16) as a light yellow solid. Yield: 340mg (67%). 1H NMR (400 MHz, DMSO-d6) O 8.16 (5, 2H), 6.50 (brs, 2H), 4.99 (t, 1H),4.26 (d, 2H). GCMS [mlz]: 125.0
62% With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 4.33h; A solution of aldehyde (50 g, 0.41 mol) [see, for example, WO 0232893] in MeOH (300 mL) was cooled to 0 C. and carefully treated with NaBH4 (20 g, 0.53 mol in 6 batches) over 20 minutes. The reaction was then allowed to warm to 20 C. and was stirred for 4 hours. The mixture was again cooled to 0 C., carefully quenched with saturated aqueous NH4Cl, and concentrated. Flash chromatography (5-10% 7N NH3-MeOH/CH2Cl2) provided the primary alcohol (31 g, 62%) as a light yellow solid.
62% With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 260h; A solution of aldehyde (50 g, 0.41 mol) [WO 0232893] in MeOH (300 mL) was cooled to 0 C and carefully treated with NaBH4 (20g, 0.53 mol in 6 batches) over 20 minutes. The reaction was then allowed to warm to 20 C and was stirred for 4 hours. The mixture was again cooled to 0 C, carefully quenched with saturated aqueous NH4CI, and concentrated. Flash chromatography (5- 10% 7N NH3-MeOH/CH2CI2) provided the primary alcohol (31g, 62%) as a light yellow solid
62% Step 1: A solution of 68 (50 g, 0.41 mol) in CH30H (300 ml) was cooled to [0 C] and carefully treated with NaBH4 (20g, 0.53 mol in 6 batches) over 20 min. The reaction was then allowed to warm to 20 [C] and was stirred for 4 h. The mixture was again cooled to 0 [C,] carefully quenched with saturated aqueous [NH4CI,] and concentrated. Flash chromatography (5-10% 7N [NH3-CH3OH/CH2CI2)] provided 69 (31g, 62%) as a light yellow solid.
With sodium tetrahydroborate; In methanol; water; N,N-dimethyl-formamide; Example 85 (2-Amino-pyrimidin-5-yl)-methanol A solution of 2-Amino-pyrimidine-5-carbaldehyde (500 mg) in DMF:water:MeOH (4:1:1, 30 mL) was treated with NaBH4 (200 mg, excess) and stirred at RT for 30 minutes. The product could not be extracted into organics so the solvents were removed and the crude product was used directly in the subsequent reaction. MS 126 (M+H+).

  • 3
  • [ 120747-85-5 ]
  • [ 120747-86-6 ]
YieldReaction ConditionsOperation in experiment
52% With thionyl chloride; In dichloromethane; at 0 - 20℃; A slurry of alcohol (31 g, 0.25 mol) from Preparative Example 400, Step A in CH2Cl2 (500 mL) was cooled to 0 C. and slowly treated with SOCl2 (55 mL, 0.74 mol over 30 minutes). The reaction was then stirred overnight at 20 C. The material was concentrated, slurried in acetone, and then filtered. The resulting beige solid was dried overnight in vacuo (38.4 g, 52%, HCl salt).
52% With thionyl chloride; In dichloromethane; at 0 - 20℃; A slurry of alcohol (31 g, 0.25 mol) from Preparative Example 216, Step A in CH2CI2 (500 mL) was cooled to 0 C and slowly treated with SOCI2 (55mL, 0.74 mol over 30 minutes). The reaction was then stirred overnight at 20 C. The material was concentrated, slurried in acetone, and then filtered. The resulting beige solid was dried overnight in vacuo (38.4g, 52%, HCI salt).
With thionyl chloride; In dichloromethane; at 0 - 20℃; for 16h; To a stirred suspension of 130 (500 mg, 4 mmol) in DCM (10 mL) was added SOd2 (1 mL) drop wise atO C. After completion of the addition, the reaction mixture was allowed to RTforl6 h. The reaction mixture was concentrated under reduced pressure to get 290 mg of crude 131 as HCI salt. The crude compound was as such taken for next step without any further purification. To a stirred solution of 6-003 (582 mg, 2 mmol) in DMF (10 mL) was added 131 (290 mg, crude, 2 mmol) and K2C03 (828 mg,6 mmol) at RT. The reaction mixture was irradiated under microwave at 80 C for 1 h. The progress of the reaction was monitored by TLC. The solvent was removed under reduced pressure to get the crude material. The crude compound was purified by Grace Purification system [C-18 column with 0.01 % HCOOH in water and acetonitrile] to afford 500 mg of crude 6-225. The crude compound was purified by prep. HPLC purification to get 6-225 (60 mg, 4 % two steps) as a white solid. 1H NMR (400 MHz,DMSO-d6): O 9.03 (brs, 1 H), 8.53 (brd, J = 7.8 Hz, 1H), 8.31 (s, 2H), 7.35- 7.30 (d, J = 7.3 Hz, 1H),7.23 (d, J= 7.3 Hz, 1H), 7.09-6.84 (m, 2H), 5.13-4.85 (m, 4H), 4.37-4.22 (m, 1H), 2.43 (s, 3H), 2.11(qd, J = 13.3, 6.3 Hz, 1 H), 0.92 (d, J = 6.8 Hz, 3H), 0.90 (d, J = 6.8 Hz, 3HLC-MS: m/z 399.22 [M+H].HPLC purity: 94.03% (220 nm) and chiral HPLC purity is 98.99% (229 nm).
  • 4
  • [ 120747-85-5 ]
  • [ 1046816-75-4 ]
YieldReaction ConditionsOperation in experiment
In hydrogenchloride; (2-Chloro-pyrimidin-5-yl)-methanol A solution of <strong>[120747-85-5](2-Amino-pyrimidin-5-yl)-methanol</strong> (400 mL, 3.2 mmol) was dissolved in HCl (aq. 3M, 20 mL) and treated with NaNO2 (aq. 1N, 20 mL). The reaction was stirred at 0° C. for 18 hours. The mixture was basified with K2CO3 (aq.) then extracted with DCM (3*50 mL). The organics were washed with more K2CO3 (aq.) and the organics concentrated to give the pure product as needles.
  • 5
  • [ 120747-85-5 ]
  • 5-(chloromethyl)pyrimidin-2-amine hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With thionyl chloride; In dichloromethane; at 20℃; for 16h; To a stirred solution of <strong>[120747-85-5](2-aminopyrimidin-5-yl)methanol</strong> (16, 340 mg, 2.72 mmol) in DCM (5 mL) was added thionyl chloride (0.6 mL, 8.16 mmol) at 0C. The resulting solution was slowly warmed to room temperature and was stirred for 16 hours. After complete consumption of compound 16 (monitored by TLC, 5% MeOH in DCM, Rf 0.3), the reaction mixture was concentrated under vacuo. The residue was triturated with acetone to afford the hydrochloride salt of 5-(chloromethyl)pyrimidin-2-amine (17) as an off-white solid. Yield: 340 mg (70%).1H NMR (400 MHz, DMSO-d6) O 8.57 (5, 2H), 7.90 (brs, 3H), 4.71 (5, 2H).
YieldReaction ConditionsOperation in experiment
30% With methanol; sodium tetrahydroborate; at 0 - 20℃; for 2h; General procedure: To a solution of aldehyde in the indicated solvent is added sodium borohydride at 0 C. After stirring at room temperature for 2 hours, water is added and the mixture is concentrated.Following Procedure C using crude 4 (1.0 g, 6.35 mmol), MeOH, and sodium borohy dride (360 mg, 9.55 mmol), then quench with water (1 mL) and purify with silica gel column chromatography (MeOH:DCM := 1 :50) to give AS as a solid (650 mg, 65% yield). (MS: [M+H]+ 160.1)
  • 7
  • [ 120747-85-5 ]
  • C10H15N3O3 [ No CAS ]
  • 8
  • [ 120747-85-5 ]
  • C10H14ClN3O2 [ No CAS ]
  • 9
  • [ 120747-85-5 ]
  • C19H21BrFN3O6 [ No CAS ]
  • 10
  • [ 120747-85-5 ]
  • [ 24424-99-5 ]
  • C20H31N3O7 [ No CAS ]
YieldReaction ConditionsOperation in experiment
10% With dmap; triethylamine; In tetrahydrofuran; at 20℃; To a solution of A13 (2.0 g, 15.9 rnrnoi), TEA (6.47 g, 63.9 rnmoi), and DMAP (1.95 rnrnol) in THF (30 rnL) is added di-tert-butyl dicarbonate (12.2 g, 55.9 rnmol). After stirring at room temperature overnight, the mixture is concentrated and dissolved in EA (100 mL), washed th HC1 solution (0.5 M, 30 rnL) and brine (30 rnL). dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography (EA:PE 1:5) to give 74 as a white solid (680 mg, 10% yield). (MS:[M+H] 4262)
  • 11
  • [ 120747-85-5 ]
  • (2-aminopyrimidin-5-yl)methyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate [ No CAS ]
 

Historical Records

Technical Information

Categories

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[ 120747-85-5 ]

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