[ CAS No. 90905-33-2 ] {[proInfo.proName]}

Name: 90905-33-2|2-Methylpyrimidine-5-carbaldehyde|97%
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SKU: A110857
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Quality Control of [ 90905-33-2 ]

COA NMR CNMR HPLC LC-MS

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Product Details of [ 90905-33-2 ]

CAS No. :	90905-33-2	MDL No. :	MFCD07186434
Formula :	C₆H₆N₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	IJBONYUNKRDIFC-UHFFFAOYSA-N
M.W :	122.12	Pubchem ID :	3160970
Synonyms :

Calculated chemistry of [ 90905-33-2 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.17
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	32.39
TPSA :	42.85 Å²

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) :	-7.0 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.12
Log Po/w (XLOGP3) :	0.07
Log Po/w (WLOGP) :	0.6
Log Po/w (MLOGP) :	-0.7
Log Po/w (SILICOS-IT) :	1.48
Consensus Log Po/w :	0.51

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.07
Solubility :	10.4 mg/ml ; 0.0854 mol/l
Class :	Very soluble
Log S (Ali) :	-0.52
Solubility :	36.6 mg/ml ; 0.299 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.94
Solubility :	1.4 mg/ml ; 0.0115 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.07

Safety of [ 90905-33-2 ]

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

Application In Synthesis of [ 90905-33-2 ]

* 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 [ 90905-33-2 ]
Downstream synthetic route of [ 90905-33-2 ]

[ 90905-33-2 ] Synthesis Path-Upstream 1~5

1
[ 90905-33-2 ]
[ 2239-83-0 ]

Yield	Reaction Conditions	Operation in experiment
51%	With sodium tetrahydroborate In methanol at 0 - 15℃; for 3 h;	To a mixture of 2-methylpyrimidine-5-carbaldehyde (8 g, 66 mmol, compound 44b) in MeOH (100 mL) was added NaBH₄ (7.5 g, 197 mmol) at 0 °C, and the resulting reaction mixture was stirred at 15°C for 3 hrs. Then the reaction mixture was quenched by saturated NH₄C1 solution (30 mL), extracted by ethyl acetate (20 mL) three times. The separated organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography to afford (2-methylpyrimidin-5-yl)methanol (4.1 g, 51percent, compound 44c) as a white solid.
39%	at 0 - 20℃; for 1 h;	A solution of 2-methyl-pyrimidine-5-carbaldehyde (5 g, 41 mmol) in MeOH (100 mL) was added NaBH₄(2.3 g, 61.5 mmol) at 0° C. in portions and the resulting mixture was stirred at room temperature for 1 h. The solvent was removed under reduced pressure to give the remains, which was suspended in H₂O (20 mL) and extracted with EtOAc (5×50 ml). The organic layer was dried over Na₂SO₄and concentrated to afford the title compound (2 g, yield: 39percent). ¹H NMR (CDCl₃400 MHz): δ8.64 (s, 2H), 4.72 (s, 2H), 2.73 (s, 3H).

Reference： [1] Patent: WO2016/180695, 2016, A1, . Location in patent: Page/Page column 153
[2] Patent: US2014/107340, 2014, A1, . Location in patent: Paragraph 0121
[3] Patent: US2008/275037, 2008, A1, . Location in patent: Page/Page column 29
[4] Patent: WO2010/33168, 2010, A2, . Location in patent: Page/Page column 80-81

2
[ 124-42-5 ]
[ 90905-33-2 ]

Yield	Reaction Conditions	Operation in experiment
10 g	With sodium In ethanol for 5 h; Reflux	To 500 mL of EtOH was added sodium (12 g, 0.50 mol) in portions at room temperature and the resulting mixture was stirred until the sodium was dissolved completely. To a suspension of the previously prepared salt (60 g, 0.17 mol) and acetamidine hydrochloride (17.4 g, 0.19 mol) in EtOH (2.5 L) was added the above solution at room temperature and the resulting mixture was heated to reflux for 5 h. After filtration, the solvent was removed under reduced pressure to give the remains, which was suspended in H₂O (200 mL) and extracted with DCM (3 mL×100). The organic layer was washed with brine, dried over Na₂SO₄and concentrated. The crude product was purified by column chromatography on silica gel (petroleum ether: EtOAc=5:1 to 2:1) to afford 2-methyl-pyrimidine-5-carbaldehyde (10 g, yield: 50percent). ¹H NMR (CDCl₃400 MHz): δ10.10 (s, 1H), 9.07 (s, 2H), 2.84 (s, 3H)

Reference： [1] Angewandte Chemie - International Edition, 2004, vol. 43, # 16, p. 2099 - 2103
[2] Patent: US2014/107340, 2014, A1, . Location in patent: Paragraph 0120

3
[ 143-37-3 ]
[ 90905-33-2 ]

Reference： [1] Synlett, 2000, # 8, p. 1172 - 1174

4
[ 124-42-5 ]
[ 79-08-3 ]
[ 68-12-2 ]
[ 90905-33-2 ]

Reference： [1] Journal of medicinal chemistry, 2004, vol. 47, # 20, p. 4829 - 4837

5
[ 2009-81-6 ]
[ 124-42-5 ]
[ 90905-33-2 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1991, vol. 28, # 5, p. 1281 - 1285

[ 90905-33-2 ] Synthesis Path-Downstream 1~86

1
[ 2009-81-6 ]
[ 124-42-5 ]
[ 90905-33-2 ]

Reference： [1]Journal of Heterocyclic Chemistry,1991,vol. 28,p. 1281 - 1285

2
[ 625-81-0 ]
[ 90905-33-2 ]
[ 173068-92-3 ]

Reference： [1]Journal of the American Chemical Society,1996,vol. 118,p. 471 - 472

3
[ 625-81-0 ]
[ 90905-33-2 ]
[ 173068-92-3 ]
(R)-2-Methyl-1-(2-methyl-pyrimidin-5-yl)-propan-1-ol [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1998,vol. 120,p. 12157 - 12158
[2]Tetrahedron Asymmetry,1997,vol. 8,p. 1717 - 1719
[3]Journal of the American Chemical Society,1998,vol. 120,p. 12157 - 12158
[4]Tetrahedron Asymmetry,1997,vol. 8,p. 1717 - 1719
[5]Journal of the American Chemical Society,1998,vol. 120,p. 12157 - 12158
[6]Organic Letters,2003,vol. 5,p. 4337 - 4339
[7]Organic Letters,2003,vol. 5,p. 4337 - 4339
[8]Angewandte Chemie - International Edition,2004,vol. 43,p. 2099 - 2103

4
[ 1119-90-0 ]
[ 90905-33-2 ]
(R)-1-(2-Methyl-pyrimidin-5-yl)-pentan-1-ol [ No CAS ]
[ 205518-95-2 ]

Reference： [1]Heterocycles,1997,vol. 46,p. 235 - 240

5
[ 557-20-0 ]
[ 90905-33-2 ]
(R)-1-(2-Methyl-pyrimidin-5-yl)-propan-1-ol [ No CAS ]
(S)-1-(2-Methyl-pyrimidin-5-yl)-propan-1-ol [ No CAS ]

Reference： [1]Heterocycles,1997,vol. 46,p. 235 - 240
[2]Heterocycles,1997,vol. 46,p. 235 - 240

6
[ 14402-93-8 ]
[ 90905-33-2 ]
[ 259856-07-0 ]

Reference： [1]Heterocycles,2000,vol. 52,p. 151 - 158

7
2-dimethylaminomethylene-1,3-bis(dimethylimmonio)propane bistetrafluoroborate [ No CAS ]
[ 143-37-3 ]
[ 90905-33-2 ]

Reference： [1]Synlett,2000,p. 1172 - 1174

8
[ 90905-33-2 ]
[ 227752-03-6 ]
[ 312262-90-1 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide;	Step E 1-(2-Methyl-pyrimidin-5-yl)-7-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-hept-1-en-3-one (1-7) To a solution of 1-6 (5.5 g, 16.2 mmol), <strong>[90905-33-2]5-formyl-2-methylpyrimidine</strong> (1-6a, 1.8 g, 14.7 mmol; for preparation, see J. Heterocyclic Chem., 28, 1281 (1991)) in 40 mL DMF was added K2CO3(4.07 g, 32 mmol). The mixture was stirred at ambient temperature for 15 hr, and concentrated to a paste. The residue was diluted with water, extracted with ethyl acetate, and dried over magnesium sulfate. Following concentration, the residue was chromatographed on silica gel (70 chloroform/25 ethyl acetate/5 methanol) to give 1-7 as a white solid. Rf=0.20 (silica, 70 chloroform/20 ethyl acetate/10 methanol). 1H NMR (400 MHz, CDCl3) delta 8.80 (s, 2H), 7.44 (d, 1H, J=16 Hz), 7.05 (d, 1H, J=7 Hz), 6.81 (d, 1H, J=16 Hz), 6.35 (d, 1H, J=7 Hz), 4.72 (br s, 1H), 3.39 (m, 2H), 2.69 (s, 3H), 2.64 (m, 4H), 2.58 (m, 2H), 1.91 (m, 2H), 1.74 (m, 4H).
	With K2CO3; In N,N-dimethyl-formamide;	Step E 1-(2-Methyl-pyrimidin-5-yl)-7-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-hept-1-en-3-one (1-7) To a solution of 1-6 (5.5 g, 16.2 mmol), <strong>[90905-33-2]5-formyl-2-methylpyrimidine</strong> (1-6a, 1.8 g, 14.7 mmol; for preparation, see J. Heterocyclic Chem., 28, 1281 (1991)) in 40 mL DMF was added K2CO3 (4.07 g, 32 mmol). The mixture was stirred at ambient temperature for 15 hr, and concentrated to a paste. The residue was diluted with water, extracted with ethyl acetate, and dried over magnesium sulfate. Following concentration, the residue was chromatographed on silica gel (70 chloroform/25 ethyl acetate/5 methanol) to give 1-7 as a white solid. Rf=0.20 (silica, 70 chloroform/20 ethyl acetate/10 methanol). 1H NMR (400 MHz, CDCl3) delta8.80(s, 2H), 7.44 (d, 1H, J=16Hz), 7.05 (d, 1H, J=7Hz), 6.81 (d, 1H, J=16Hz), 6.35 (d, 1H, J=7Hz), 4.72 (br s, 1H), 3.39 (m, 2H), 2.69 (s, 3H), 2.64 (m, 4H), 2.58 (m, 2H), 1.91 (m, 2H), 1.74 (m, 4H).

Reference： [1]Journal of medicinal chemistry,2004,vol. 47,p. 4829 - 4837
[2]Patent: US6410526,2002,B1
[3]Patent: US2004/38963,2004,A1

9
[ 124-42-5 ]
[ 79-08-3 ]
[ 68-12-2 ]
[ 90905-33-2 ]

Reference： [1]Journal of medicinal chemistry,2004,vol. 47,p. 4829 - 4837

10
[ 1068-55-9 ]
[ 90905-33-2 ]
2-methyl-1-(2-methyl-5-pyrimidyl)propan-1-ol [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2004,vol. 43,p. 2099 - 2103

11
[ 124-42-5 ]
2-dimethylaminomethylene-1,3-bis(dimethylimmonio)propane bistetrafluoroborate [ No CAS ]
[ 90905-33-2 ]

Yield	Reaction Conditions	Operation in experiment
10 g	With sodium; In ethanol; for 5h;Reflux;	To 500 mL of EtOH was added sodium (12 g, 0.50 mol) in portions at room temperature and the resulting mixture was stirred until the sodium was dissolved completely. To a suspension of the previously prepared salt (60 g, 0.17 mol) and acetamidine hydrochloride (17.4 g, 0.19 mol) in EtOH (2.5 L) was added the above solution at room temperature and the resulting mixture was heated to reflux for 5 h. After filtration, the solvent was removed under reduced pressure to give the remains, which was suspended in H2O (200 mL) and extracted with DCM (3 mL×100). The organic layer was washed with brine, dried over Na2SO4 and concentrated. The crude product was purified by column chromatography on silica gel (petroleum ether: EtOAc=5:1 to 2:1) to afford 2-methyl-pyrimidine-5-carbaldehyde (10 g, yield: 50percent). 1H NMR (CDCl3 400 MHz): delta10.10 (s, 1H), 9.07 (s, 2H), 2.84 (s, 3H)

Reference： [1]Angewandte Chemie - International Edition,2004,vol. 43,p. 2099 - 2103
[2]Patent: US2014/107340,2014,A1 .Location in patent: Paragraph 0120

12
[ 90905-33-2 ]
[ 404869-61-0 ]

Reference： [1]Journal of medicinal chemistry,2004,vol. 47,p. 4829 - 4837

13
[ 90905-33-2 ]
[ 227753-49-3 ]

Reference： [1]Journal of medicinal chemistry,2004,vol. 47,p. 4829 - 4837

14
[ 90905-33-2 ]
[ 404869-65-4 ]

Reference： [1]Journal of medicinal chemistry,2004,vol. 47,p. 4829 - 4837

15
[ 90905-33-2 ]
[ 404869-67-6 ]

Reference： [1]Journal of medicinal chemistry,2004,vol. 47,p. 4829 - 4837

16
[ 90905-33-2 ]
[ 259856-10-5 ]

Reference： [1]Heterocycles,2000,vol. 52,p. 151 - 158

17
[ 312263-25-5 ]
[ 90905-33-2 ]
7-[6-(4-Methoxy-benzylamino)-pyridin-2-yl]-1-(2-methyl-pyrimidin-5-yl)-hept-1-en-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27.7 g (61%)	With sodium hydroxide; In tetrahydrofuran;	Step A 7-[6-(4-Methoxy-benzylamino)-pyridin-2-yl]-1-(2-methyl-pyrimidin-5-yl)-hept-1-en-3-one (16-1) To a solution of 6-7 (42.8 g, 102 mmol) and <strong>[90905-33-2]2-methyl-pyrimidine-5-carbaldehyde</strong> (12.45 g, 102 mmol) in THF (250 mL) at 0° was added 4M NaOH (26.7 mL, 107 mmol) dropwise. After 15 minutes the ice bath was removed and the mixture stirred for an additional 10 minutes. The solution was diluted with water, extracted with ethyl acetate, and dried (Na2SO4). Following concentration, the residue was triturated with ether to give 27.7 g (61percent) of 16-1 as a white solid. 1H NMR (400 MHz, CDCl3) 8.78 (s, 2H), 7.33 (m, 4H), 6.85 (m, 3H), 6.46 (d, J=7.1 Hz, 1H), 6.19 (d, J=8.3 Hz, 1H), 4.80 (br s, 1H), 4.39 (d, J=5.6 Hz, 2H), 3.80 (s, 3H), 2.78 (s, 3H), 2.67 (m, 4H), 1.76 (m, 4H). MS (M++H) 417.0.

Reference： [1]Patent: US2001/53853,2001,A1

18
[ 351447-85-3 ]
[ 90905-33-2 ]
7-(2,3-Dihydro-1H-pyrrolo[2,3-b]pyridin-6-yl)-1-(2-methyl-pyrimidin-5-yl)-hept-1-en-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With potassium carbonate; In N,N-dimethyl-formamide;	Step F 7-(2,3-Dihydro-1H-pyrrolo[2,3-b]pyridin-6-yl)-1-(2-methyl-pyrimidin-5-yl)-hept-1-en-3-one (23-8) To a solution of 23-7 (0.49 g, 1.5 mmol) and <strong>[90905-33-2]2-methyl-pyrimidine-5-carbaldehyde</strong> (0.183 g, 1.5 mmol) in 15 mL DMF was added K2CO3 (0.310 g, 2.25 mmol). The mixture was stirred at ambient temperature for 2 hr and concentrated to a paste. The residue was purified by PCTLC (0-10percent MeOH/CH2Cl2) which provided 0.400 g (83percent yield) of 23-8. 1H NMR (400 MHz, CDCl3) delta 8.79 (s, 2H), 7.42 (d, 1H, J=16.4 Hz), 7.18 (m, 1H), 6.81 (d, 1H, J=16.4 Hz), 6.38 (m, 1H), 4.39 (br s, 1H), 3.60 (m, 2H), 3.02 (m, 2H), 2.77 (s, 3H), 2.70 (d, 2H), 2.62 (d, 2H), 1.74 (m, 4H).

Reference： [1]Patent: US2001/53853,2001,A1

19
[ 351447-90-0 ]
[ 90905-33-2 ]
[8-(2-Methyl-pyrimidin-5-yl)-6-oxo-oct-7-enyl]-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In tetrahydrofuran;	Step B [8-(2-Methyl-pyrimidin-5-yl)-6-oxo-oct-7-enyl]-carbamic acid tert-butyl ester (24-3) A solution of 24-2 (3.13 g, 9.28 mmol), potassium carbonate (1.75 g, 12.6 mmol), and <strong>[90905-33-2]2-methyl-pyrimidine-5-carbaldehyde</strong> (1.04 g, 8.51 mmol) in THF (20 mL) was warmed to 40° C. for 5 h. The mixture was diluted with water and extracted four times with ether. The combined organics were washed with brine and dried (Na2SO4). Purification via silica chromatography (hexane/ethyl acetate) afforded the title compound 24-3 (1.67 g). 1H NMR (CDCl3, 400 MHz) delta 8.80 (s, 2H), 7.46 (d, 1H, J=16.3 Hz), 6.83 (d, 1H, J=16.3 Hz), 4.55 (s, 1H), 3.13 (m, 2H), 2.78 (s, 3H), 2.68 (t, 2H, J=7.3 Hz), 1.71 (m, 2H), 1.53 (m, 2H), 1.44 (s, 9H), 1.38 (m, 2H).

Reference： [1]Patent: US2001/53853,2001,A1

Yield	Reaction Conditions	Operation in experiment
49%		(ii) A suspension of the above perchlorate salt (14.8 g) and acetamidine hydrochloride (4.0 g) in methanol (200 ml) was stirred at 40° C. during the gradual addition of a solution of sodium (1.0 g) in methanol(50 ml). After 3 hours the solution was neutralized with acetic acid and evaporated under reduced pressure. The residue was diluted with water (50 ml) and extracted with chloroform (2*100 ml). The chloroform extracts were dried and evaporated to give 2 -methylpyrimidine-5-carboxaldehyde (2.5 g, 49percent). The product was characterized by proton nuclear magnetic resonance spectroscopy and the spectrum is recorded in Table 2 below. The mono-substituted pyrimidine-5-carboxaldehydes of formula V listed in Table 2 below were prepared from {2-[(dimethylamino)methylene]propanediylidene}bis-[dimethylammonium perchlorate] and the appropriate amidine hydrochloride following the procedure described above for the preparation of 2-methylpyrimidine-5 -carboxaldehyde.

21
[ 625-81-0 ]
[ 90905-33-2 ]
C₅H₅N₂CH(C₃H₇)OZnC₃H₇ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2002,vol. 124,p. 10010 - 10011

22
[ 90905-33-2 ]
[ 2239-83-0 ]

Yield	Reaction Conditions	Operation in experiment
51%	With sodium tetrahydroborate; In methanol; at 0 - 15℃; for 3h;	To a mixture of <strong>[90905-33-2]2-methylpyrimidine-5-carbaldehyde</strong> (8 g, 66 mmol, compound 44b) in MeOH (100 mL) was added NaBH4 (7.5 g, 197 mmol) at 0 °C, and the resulting reaction mixture was stirred at 15°C for 3 hrs. Then the reaction mixture was quenched by saturated NH4C1 solution (30 mL), extracted by ethyl acetate (20 mL) three times. The separated organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography to afford (2-methylpyrimidin-5-yl)methanol (4.1 g, 51percent, compound 44c) as a white solid.
39%	With methanol; sodium tetrahydroborate; at 0 - 20℃; for 1h;	A solution of <strong>[90905-33-2]2-methyl-pyrimidine-5-carbaldehyde</strong> (5 g, 41 mmol) in MeOH (100 mL) was added NaBH4 (2.3 g, 61.5 mmol) at 0° C. in portions and the resulting mixture was stirred at room temperature for 1 h. The solvent was removed under reduced pressure to give the remains, which was suspended in H2O (20 mL) and extracted with EtOAc (5×50 ml). The organic layer was dried over Na2SO4 and concentrated to afford the title compound (2 g, yield: 39percent). 1H NMR (CDCl3 400 MHz): delta8.64 (s, 2H), 4.72 (s, 2H), 2.73 (s, 3H).
	With methanol; sodium tetrahydroborate; at 0℃; for 0.5h;	B) (2-Methylpyrimidin-5-yl)methanolA solution of <strong>[90905-33-2]2-methylpyrimidine-5-carbaldehyde</strong> (6.48 g, 53.1 mmol) in methanol (320 mL) was cooled to 0° C. and treated with sodium tetrahydroborate (2.9 g, 77 mmol). After 30 min, the reaction was treated with H2O (50 mL) and extracted with EtOAc (250 mL.x.15). The organic layers were combined and dried over MgSO4 and concentrated to yield a white solid.

A solution of <strong>[90905-33-2]2-methylpyrimidine-5-carbaldehyde</strong> (7.5 g, 0.058 mol) in methanol (370 mL, 9.1 mol) was cooled to 0 0C and treated with sodium tetrahydroborate (3.4 g, 0.090 mol). After 30 min, the reaction was quenched with eq H2O (200 mL) and extracted with ethyl acetate. The organic layer was dried over MgSO4 and concentrated to give the title compound as a yellow solid.

Reference： [1]Patent: WO2016/180695,2016,A1 .Location in patent: Page/Page column 153
[2]Patent: US2014/107340,2014,A1 .Location in patent: Paragraph 0121
[3]Patent: US2008/275037,2008,A1 .Location in patent: Page/Page column 29
[4]Patent: WO2010/33168,2010,A2 .Location in patent: Page/Page column 80-81

23
[ 75-16-1 ]
[ 90905-33-2 ]
[ 1071435-96-5 ]

Yield	Reaction Conditions	Operation in experiment
		B) 1-(2-methylpyrimidin-5-yl)ethanolTo a stirred solution of <strong>[90905-33-2]2-methylpyrimidine-5-carbaldehyde</strong> (5.00 g, 38.9 mmol) in tetrahydrofuran (85 mL) was slowly added 33 muL of 1.4 M methylmagnesium bromide solution in tetrahydrofuran at 0° C. The mixture was stirred at room temperature for 1 hour and then quenched with water (50 mL) and extracted with EtOAc (3.x.200 mL). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (0-100percent EtOAc/hexane) to afford a colorless oil.
		B) 1 -(2-methylpyrimidin-5-yl)ethanol[00305] To a stirred solution of <strong>[90905-33-2]2-methylpyrimidine-5-carbaldehyde</strong> (5.00 g, 38.9 mmol) in tetrahydrofuran (85 mL) was slowly added 33 mL of 1.4 M methylmagnesium bromide solution in tetrahydrofuran at 0 0C. The mixture was stirred at room temperature for 1 hour and then quenched with water (50 mL) and extracted with EtOAc (3 x 200 mL). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (0-100percent EtOAc/hexane) to afford a colorless oil.

Reference： [1]Patent: US2008/275037,2008,A1 .Location in patent: Page/Page column 30; 31
[2]Patent: WO2008/123963,2008,A1 .Location in patent: Page/Page column 57

24
6-[(3S,4S)-4-methylpyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one hydrogen chloride [ No CAS ]
[ 90905-33-2 ]
[ 1082743-82-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 50℃;	(b) 6-((3S,4S)-4-methyl-1 -f(2-methylpyrimidin-5-vnmethylipyrrolidin-3-yll-1 - ftetrahvdro-2H-pyran-4-yl)-1 ,5-dihvdro-4H-pyrazolof3.4-dipyrimidin-4-oneSi) <n="104"/>To a solution of 6-[(3S,4S)-4-methylpyrrolidin-3-yl]-1-(tetrahydro-2H- pyran-4-yl)-1H-pyra2olo[3,4-d]pyrimidin-4(5H)-one hydrogen chloride (493 mg) in 1,2-dichloroethane (1OmL) was added acetic acid (174 mg), 2- methylpynmidine-5-carbaldehyde (236 mg) and sodium triacetoxy borohydnde (635 mg) The reaction mixture was heated at 50°C overnight The reaction mixture was concentrated onto silica gel and purified by CombiFlash chromatography to provide the title compound (146 mg) 400 MHz 1H NMR (CDCI3) delta 863 (s, 2H), 801 (s, 1H), 482-476 (m, 1H), 412-408 (m, 2H), 368 (d, J = 50 Hz, 3H), 364-354 (m, 2H), 328 (t, J = 83 Hz, 1 H), 304 (d, J =99 Hz, 1H), 289-286 (m, 1H), 271 (s, 3H), 266-262 (m, 1H), 249-227 (m, 3H), 197 (t, J= 79 Hz, 1H), 191-183 (m, 2H), 119 (d, J = 705 Hz, 3H) MS (M+H m/z 4102)

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9045 - 9054
[2]Patent: WO2008/139293,2008,A1 .Location in patent: Page/Page column 102-103

25
[ 90905-33-2 ]
[ 1082743-82-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 50℃;	To a solution of 6-[(3S,4S)-4-methylpyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one hydrogen chloride (493 mg) in 1,2-dichloroethane (10 mL) was added acetic acid (174 mg), <strong>[90905-33-2]2-methylpyrimidine-5-carbaldehyde</strong> (236 mg) and sodium triacetoxy borohydride (635 mg). The reaction mixture was heated at 50° C. overnight. The reaction mixture was concentrated onto silica gel and purified by CombiFlash chromatography to provide the title compound (146 mg). 400 MHz 1H NMR (CDCl3) delta 8.63 (s, 2H), 8.01 (s, 1H), 4.82-4.76 (m, 1H), 4.12-4.08 (m, 2H), 3.68 (d, J=5.0 Hz, 3H), 3.64-3.54 (m, 2H), 3.28 (t, J=8.3 Hz, 1H), 3.04 (d, J=9.9 Hz, 1H), 2.89-2.86 (m, 1H), 2.71 (s, 3H), 2.66-2.62 (m, 1H), 2.49-2.27 (m, 3H), 1.97 (t, J=7.9 Hz, 1H), 1.91-1.83 (m, 2H), 1.19 (d, J=7.05 Hz, 3H). MS: (M+H m/z 410.2).

Reference： [1]Patent: US2009/30003,2009,A1 .Location in patent: Page/Page column 41

26
[ 165825-49-0 ]
[ 90905-33-2 ]
C₂₅H₃₁N₃O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 4578 - 4581

27
[ 1083049-06-2 ]
[ 90905-33-2 ]
C₂₁H₂₇N₇O [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 7946 - 7949

28
[ 1344670-20-7 ]
[ 90905-33-2 ]
C₁₈H₁₅FN₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 6515 - 6518

29
[ 3360-70-1 ]
[ 90905-33-2 ]
C₁₈H₁₆N₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 6515 - 6518

30
[ 1359979-48-8 ]
[ 90905-33-2 ]
[ 1359979-65-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1335 - 1339

31
[ 1365607-11-9 ]
[ 90905-33-2 ]
[ 1365609-22-8 ]

Yield	Reaction Conditions	Operation in experiment
51%	With iron(III) chloride hexahydrate; In N,N-dimethyl-formamide; at 90℃; for 14h;	Example 26: l-{l-[9-Methyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-yl]piperidin-4-yl}- l,3-dihydro-2H-benzimidazol-2-one Compoundl-(l-r9-Methyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-yllpiperidin-4-yl)-1.3-dihvdro- 2H-benzimidazol-2-one[00230] To a solution of l-(l-(5-amino-6-(methylamino)pyrimidin-4-yl)piperidin-4-yl)- lH-benzo[d]imidazol-2(3H)-one (300 mg, 0.88 mmol) in anhydrous DMF (5 mL) were added <strong>[90905-33-2]2-methylpyrimidine-5-carbaldehyde</strong> (108 mg, 0.88 mmol) and Iron (III) chloride hexahydrate (0.88 g, 0.24 mmol). The dark brown solution was heated to 90 °C for 14 hour in an open air vessel. The reaction mixture was cooled to room temperature and poured over ice (5 g). The resulting mixture was extracted with ethyl acetate (50 mL), the organic layer was washed with brine (10 mL), and dried over MgS04. The solution was filtered, and concentrated under reduced pressure. The resulting solids were triturated with 15 mL of diethyl ether (15 mL) for 30 min. The precipitate was collected by vacuum filtration to give 201 mg (51 percent yield) of the title compound. NMR (400MHz, DMSO-d6): 5 10.86 (s, 1H), 9.16 (s, 2H), 8.33 (s, 1H), 7.18 - 7.1 1 (m, 1H), 6.98 - 6.87 (m, 3H), 4.55 (t, lH), 3.86 (s, 3H), 2.71 (s, 3H), 2.34 (dd, 2H), 1.84 (d, 2H); MS (EI) for C23H23N90: 442.3 (MH+).

Reference： [1]Patent: WO2012/37226,2012,A1 .Location in patent: Page/Page column 179-180

32
[ 90905-33-2 ]
[ 1380649-15-9 ]

Yield	Reaction Conditions	Operation in experiment
56%	With hydroxylamine hydrochloride; sodium carbonate; In methanol; water; at 30℃; for 0.5h;	Step-2: 2-Methyl-pyrimidine-5-carbaldehvde oxime:To a mixture of 2-methyl-5-formyl-pyrimidine (180 gm) and hydroxylamine hydrochloride (128 gm) in 50percent v/v aqueous methanol (3600 ml) was added sodium carbonate (94 gm). The reaction mixture was stirred at 30°C for 0.5 h. The resulting suspension was cooled and filtered at -10°C to provide single isomer of title compound in 1 13.5 gm quantity (56percent) as a solid.H'NMR: (DMSO-de) delta 1 1.64 (s, 1H), 8.83 (s, 2H), 8.14 (s, 1H), 2.60 (s, 3H).Further processing of the filtrate such as evaporation and salt removal, provided a mixture of isomers in 51 gm quantity which can be used for the next reaction.

Reference： [1]Patent: WO2012/76989,2012,A1 .Location in patent: Page/Page column 57

33
[ 90905-33-2 ]
[ 1380649-17-1 ]

Reference： [1]Patent: WO2012/76989,2012,A1

34
[ 90905-33-2 ]
[ 1380649-19-3 ]

Reference： [1]Patent: WO2012/76989,2012,A1

35
[ 90905-33-2 ]
[ 1380649-84-2 ]
C₈H₅Br₂N₃O [ No CAS ]

Reference： [1]Patent: WO2012/76989,2012,A1

36
ethanimidamide hydrochloride [ No CAS ]
vinamidinium diperchlorate [ No CAS ]
[ 90905-33-2 ]

Yield	Reaction Conditions	Operation in experiment
52%		Preparation 4: 2-Bromomethyl-5-isoxazol-3-yl-pyrimidine:Step- 1 : 2-Methyl-5-formyl-pyrimidine:To a mixture of vinamidium diperchlorate salt (310 gm, prepared as per procedure described in Collection Czechoslov Chem. Commun. Vol. 30, 1965) and acetamidine hydrochloride (106 gm) in actonitrile (2.5 L) at 30°C was added w/v 50percent aqueous sodium hydroxide (96.8 gm dissolved in 97 ml water) solution drop wise over a period of 2 h under stirring. The suspension was stirred for 3 h and pH of the reaction mixture was adjusted to 7 by addition of acetic acid (~ 147 ml). The solid was filtered and washed with acetonitrile (750 ml). The filtrate was evaporated under vacuum to provide a residue. The residue was stirred with water (750 ml) and the mixture was extracted with dichloromethane (300 ml X 5). The layers were separated and organic layer was evaporated to provide title compound in 52 gm quantity (52percent) as a low melting solid.H'NMR: (DMSO-de) delta 1 1.08 (bs, 1H), 10.08 (s, 1H), 9.09 (s, 2H), 2.69 (s, 3H).

Reference： [1]Patent: WO2012/76989,2012,A1 .Location in patent: Page/Page column 56-57

37
[ 90905-33-2 ]
[ 1071435-92-1 ]

Reference： [1]Patent: WO2008/123963,2008,A1

38
[ 90905-33-2 ]
[ 1071435-93-2 ]

Reference： [1]Patent: WO2008/123963,2008,A1

39
[ 90905-33-2 ]
[ 1071435-98-7 ]

Reference： [1]Patent: WO2008/123963,2008,A1

40
[ 90905-33-2 ]
[ 1071435-99-8 ]

Reference： [1]Patent: WO2008/123963,2008,A1

41
[ 90905-33-2 ]
[ 1071436-37-7 ]

Reference： [1]Patent: WO2008/123963,2008,A1

42
(-)-2-((3,4-trans)-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one [ No CAS ]
[ 90905-33-2 ]
(+)-2-((3,4-trans)-4-methyl-1-((2-methylpyrimidin-5-yl)methyl)pyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%		152. (+)-2- 3,4-trans)-4-methyl-l-g2-methylpyrimidin-5- yl)methyl)pyrrolidin-3-yl)-7-ftetrahvdro-2H-pyran-4-yl)imidazo[5,l- f] ri,2,41triazin-4(3H)-one [1111] To a stirred solution of (-)-2-((3,4-trans)-4-methylpyrrolidin-3-yl)-7- (tetrahydro-2H-pyran-4-yl)imidazo[5,l- J[l,2,4]triazin-4(3H)-one (150 mg, 0.49 mmol) in MeOH (10 mL) was added <strong>[90905-33-2]2-methylpyrimidine-5-carbaldehyde</strong> (78 mg, 0.64 mmol) at room temperature and stirred for 2 h under argon atmosphere. To the resulting solution was added NaCNBH3 (93 mg, 1.48 mmol) and stirring was continued for another 8 h at room temperature. The volatiles were evaporated under reduced pressure. The residue was diluted with water and extracted with CH2C12 (2 x 50 mL). Combined organic layer was dried over sodium sulphate, filtered and concentrated in vacuo to obtain the crude product. The crude material was purified by silica gel column chromatography to afford (+)-2-((3,4-trans)-4-methyl-l-((2- methylpyrimidin-5-yl)methyl)pyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4- yl)imidazo[5,l- J[l,2,4]triazin-4(3H)-one (50 mg, 31percent) as an off-white solid. 1H- NMR (DMSO-d6, 400 MHz): delta 11.52 (bs, 1H), 8.62 (s, 2H), 7.65 (s, 1H), 3.96-3.92 (m, 2H), 3.72-3.67 (m, 1H), 3.62-3.59 (m, 1H), 3.54-3.47 (m, 2H), 3.42-3.38 (m, 1H), 2.94-2.85 (m, 4H), 2.66-2.65 (m, 1H), 2.63 (s, 3H), 2.28-2.24 (m, 1H), 1.89-1.85 (m, 4H), 1.09 (d, 3H); Mass (ESI): 410 [M++l]; LC-MS: 97.36percent; 410.4 (M++l); (column; Eclipse XDB C-18, (150x4.6 mm, 5.0mu); RT 5.74 min. 0.05percent TFA (Aq): ACN; 1.0 ml/min); UPLC (purity): 99percent; (column; Acquity UPLC HSS-T3, 100x2.1 mm, 1.8mu; RT 2.92 min. 0.025percent TFA (Aq): ACN; 0.30 ml/min; Chiral HPLC: 100percent, R, = 15.87 min (Chiralpak IA, 250 x 4.6mm, 5mu; mobile phase (A) 0.1percent DEA in n- Hexane (B) DCM:MeOH (80:20) (A: B : 80:20); flow Rate: 1.00 mL/min); Optical rotation [a]D2°: + 5.0° (c = 0.25, DCM). TLC: 10percent MeOH/DCM (Rf: 0.5).

Reference： [1]Patent: WO2013/142269,2013,A1 .Location in patent: Paragraph 1111

43
[ 4447-60-3 ]
[ 90905-33-2 ]
[ 1600499-21-5 ]

Yield	Reaction Conditions	Operation in experiment
29%	With methanesulfonic acid; potassium carbonate; In isopropyl alcohol; at 20℃; for 23h;	To a mixture of <strong>[90905-33-2]2-methylpyrimidine-5-carbaldehyde</strong> (1.0 g, 8.2 mmol) and triisopropoxymethane (2.3 g, 12 mmol) in isopropanol (15 ml) was added methanesulfonic acid (0.079 g, 0.053 ml, 0.819 mmol). The reaction was stirred at room temperature for 23 hours. Potassium carbonate (1.132 g, 8.19 mmol) was added and the mixture was filtered and the solution was concentrated in vacuo. The crude mixture was purified by flash chromatography to yield 5-(diisopropoxymethyl)-2-methylpyrimidine (536 mg, 29percent) [0357] 1H NMR (500 MHz, CDCl3) delta 8.71 (s, 2H), 5.60 (s, 1H), 3.93 (dt, J=12.3, 6.1 Hz, 2H), 2.74 (s, 3H), 1.21 (dd, J=14.8, 6.1 Hz, 12H)

Reference： [1]Patent: US2014/107340,2014,A1 .Location in patent: Paragraph 0356-0357

44
[ 90905-33-2 ]
[ 504-63-2 ]
[ 1600499-27-1 ]