[ CAS No. 35980-77-9 ] {[proInfo.proName]}

Name: 35980-77-9|2-Morpholinopyridin-4-amine|98%
Brand: Ambeed
SKU: A112966
Price: 55.0 USD
Availability: InStock
Rating: 97 (30 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 35980-77-9

Structure of 35980-77-9 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 35980-77-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 35980-77-9 ]

SDS Specification

Alternatived Products of [ 35980-77-9 ]

Product Details of [ 35980-77-9 ]

CAS No. :	35980-77-9	MDL No. :	MFCD02945666
Formula :	C₉H₁₃N₃O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZSXQDGMZXKOADT-UHFFFAOYSA-N
M.W :	179.22	Pubchem ID :	23818810
Synonyms :

Calculated chemistry of [ 35980-77-9 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.44
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	54.37
TPSA :	51.38 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.22 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.43
Log Po/w (XLOGP3) :	0.25
Log Po/w (WLOGP) :	0.13
Log Po/w (MLOGP) :	0.08
Log Po/w (SILICOS-IT) :	0.73
Consensus Log Po/w :	0.52

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.38
Solubility :	7.4 mg/ml ; 0.0413 mol/l
Class :	Very soluble
Log S (Ali) :	-0.89
Solubility :	23.1 mg/ml ; 0.129 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.85
Solubility :	2.53 mg/ml ; 0.0141 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.13

Safety of [ 35980-77-9 ]

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 [ 35980-77-9 ]

* 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 [ 35980-77-9 ]
Downstream synthetic route of [ 35980-77-9 ]

[ 35980-77-9 ] Synthesis Path-Upstream 1~5

1
[ 110-91-8 ]
[ 14432-12-3 ]
[ 35980-77-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	at 200℃; for 1 h; microwave	A suspension of 26a (5.Og, 38.9mmol) in moφholine (13mL) was heated under microwave condition at 200⁰C for Ih. After being cooled to room temperature, precipitate appeared in the mixture. Ether (45mL) was added and the suspension was stirred for lOmin before being filtered. The filter cake was washed with ether and dried to afford 26b (6.61 g, 95percent).
87%	at 200℃; for 0.5 h; Irradiation	a) 2-Morpholin-4-yl-pyridin-4-ylamine A stirred mixture of 45.8 g (356 mmol) 4-amino-2-chloropyridine in 124 ml morpholine was heated at 200° C. for 30 min in a microwave oven. The resulting yellow solution was then cooled to room temperature whereupon crystals appeared. 400 ml ether was then added and the suspension stirred for 10 minutes before being filtered. The filter cake was washed with ether and dried to afford 92.9 g of crystalline material (87percent yield of desired product) which ¹H NMR analysis revealed to comprise 60 wt percent 2-morpholin-4-yl-pyridin-4-ylamine and 40 wt percent morpholine.
1 g	at 170℃; for 16 h;	A neat mixture of 2-chloropyridin-4-amine (1.0 g, 7.81 mmol) in morpholine (1 ml) was heated at 170°C for 16 h. The resulting mixture was poured into water (10 ml) and extracted with EtOAc (4 x 10 ml). The collected organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure yielding 2-morpholinopyridin-4-amine (1.0 g, 5.5 mmol). This material was used directly for the next step without further purification. LCMS: Method C, 0.64 mi MS: ES+180.21.

Reference： [1] Patent: WO2008/88881, 2008, A1, . Location in patent: Page/Page column 51
[2] Angewandte Chemie - International Edition, 2018, vol. 57, # 34, p. 11035 - 11039[3] Angew. Chem., 2018, vol. 130, # 34, p. 11201 - 11205,5
[4] Patent: US2005/65151, 2005, A1, . Location in patent: Page/Page column 6; 14
[5] Patent: WO2017/93718, 2017, A1, . Location in patent: Page/Page column 64

2
[ 848144-27-4 ]
[ 35980-77-9 ]

Reference： [1] Patent: WO2012/3283, 2012, A1, . Location in patent: Page/Page column 154

3
[ 23056-36-2 ]
[ 35980-77-9 ]

Reference： [1] Patent: WO2012/3283, 2012, A1,

4
[ 35981-62-5 ]
[ 35980-77-9 ]

Reference： [1] Pharmaceutical Chemistry Journal, 1972, vol. 6, # 3, p. 146 - 149[2] Khimiko-Farmatsevticheskii Zhurnal, 1972, vol. 6, # 3, p. 18 - 21

5
[ 14432-16-7 ]
[ 35980-77-9 ]

Reference： [1] Pharmaceutical Chemistry Journal, 1972, vol. 6, # 3, p. 146 - 149[2] Khimiko-Farmatsevticheskii Zhurnal, 1972, vol. 6, # 3, p. 18 - 21

[ 35980-77-9 ] Synthesis Path-Downstream 1~51

1
[ 151-56-4 ]
[ 35980-77-9 ]
[ 36265-14-2 ]

Reference： [1]Pharmaceutical Chemistry Journal,1972,vol. 6,p. 146 - 149
Khimiko-Farmatsevticheskii Zhurnal,1972,vol. 6,p. 18 - 21

2
[ 35981-62-5 ]
[ 35980-77-9 ]

Reference： [1]Pharmaceutical Chemistry Journal,1972,vol. 6,p. 146 - 149
Khimiko-Farmatsevticheskii Zhurnal,1972,vol. 6,p. 18 - 21

3
[ 14432-16-7 ]
[ 35980-77-9 ]

Reference： [1]Pharmaceutical Chemistry Journal,1972,vol. 6,p. 146 - 149
Khimiko-Farmatsevticheskii Zhurnal,1972,vol. 6,p. 18 - 21

4
[ 110-91-8 ]
[ 14432-12-3 ]
[ 35980-77-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	at 200℃; for 1h;microwave;	A suspension of 26a (5.Og, 38.9mmol) in mophiholine (13mL) was heated under microwave condition at 2000C for Ih. After being cooled to room temperature, precipitate appeared in the mixture. Ether (45mL) was added and the suspension was stirred for lOmin before being filtered. The filter cake was washed with ether and dried to afford 26b (6.61 g, 95%).
87%	at 200℃; for 0.5h;Irradiation;	a) 2-Morpholin-4-yl-pyridin-4-ylamine A stirred mixture of 45.8 g (356 mmol) 4-amino-2-chloropyridine in 124 ml morpholine was heated at 200 C. for 30 min in a microwave oven. The resulting yellow solution was then cooled to room temperature whereupon crystals appeared. 400 ml ether was then added and the suspension stirred for 10 minutes before being filtered. The filter cake was washed with ether and dried to afford 92.9 g of crystalline material (87% yield of desired product) which 1H NMR analysis revealed to comprise 60 wt % 2-morpholin-4-yl-pyridin-4-ylamine and 40 wt % morpholine.
1 g	In neat (no solvent); at 170℃; for 16h;	A neat mixture of 2-chloropyridin-4-amine (1.0 g, 7.81 mmol) in morpholine (1 ml) was heated at 170C for 16 h. The resulting mixture was poured into water (10 ml) and extracted with EtOAc (4 x 10 ml). The collected organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure yielding 2-morpholinopyridin-4-amine (1.0 g, 5.5 mmol). This material was used directly for the next step without further purification. LCMS: Method C, 0.64 mi MS: ES+180.21.

Reference： [1]Patent: WO2008/88881,2008,A1 .Location in patent: Page/Page column 51
[2]Angewandte Chemie - International Edition,2018,vol. 57,p. 11035 - 11039
Angew. Chem.,2018,vol. 130,p. 11201 - 11205,5
[3]Patent: US2005/65151,2005,A1 .Location in patent: Page/Page column 6; 14
[4]Patent: WO2017/93718,2017,A1 .Location in patent: Page/Page column 64

5
[ 35980-77-9 ]
[ 848579-81-7 ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium acetate; Iodine monochloride; In acetic acid; at 10 - 15℃; for 1h;	To a stirred solution of 92.8 g (311 mmol, 60 wt % purity) <strong>[35980-77-9]2-morpholin-4-yl-pyridin-4-ylamine</strong> in 1000 ml glacial acetic acid was added 76.5 g (932 mmol) sodium acetate and the mixture was then cooled to 15 C. in an ice-bath. A solution of 50.4 g (311 mmol) iodine monochloride in 200 ml glacial acetic acid was then added dropwise at a rate such that the reaction temperature remained at 10-15 C. After 40 min the addition was complete. The reaction mixture was then stirred for a further 20 min before being poured onto 1000 ml water. The mixture was concentrated in vacuo and the residue partitioned between THF/ethyl acetate (1:1) and saturated brine. 5 N aqueous sodium hydroxide solution was added until the aqueous phase was pH 14, whereupon some product precipitated. The crystals were collected by filtration to afford 16.9 g (18%) 5-iodo-<strong>[35980-77-9]2-morpholin-4-yl-pyridin-4-ylamine</strong> as a yellow crystalline solid. The mother liquid phases were separated and the organic phase dried over sodium sulfate and concentrated in vacuo. The residue was triturated in ether and the resulting crystals collected by filtration to afford a further 47.2 g (50%) of 5-iodo-<strong>[35980-77-9]2-morpholin-4-yl-pyridin-4-ylamine</strong> as a yellow crystalline solid. The mother liquor was concentrated in vacuo and the residue was purified by flash chromatography (1/1-1/2 heptane/ethyl acetate) to afford a further 9.4 g (10%) 5-iodo-<strong>[35980-77-9]2-morpholin-4-yl-pyridin-4-ylamine</strong> as a yellow crystalline solid. Meanwhile, the aqueous phase from the initial aqueous extraction was left to stand for 2 days whereupon crystals deposited. These crystals were collected by filtration to afford a further 5.2 g (5%) 5-iodo-<strong>[35980-77-9]2-morpholin-4-yl-pyridin-4-ylamine</strong> as a yellow crystalline solid. ES-MS m/e (%): 306 (M+H+, 100).
	With iodine; sodium carbonate; potassium iodide; In water; for 2h;Reflux;	A solution of KI (33.34 g, 200.9 mmol) and iodine (31.4 g, 123.9 mmol) in water (500.0 mL) was added to a solution of <strong>[35980-77-9]2-morpholinopyridin-4-amine</strong> (30.0 g, 167.4 mmol) and sodium carbonate (10.4 g, 98.8 mmol) in water (250.0 mL) at reflux. The reaction mixture was stirred for 2 h at refiux. After cooling to rt, the reaction mixture was quenched by the addition of 20% sodium thiosulfate solution. The separated solid was filtered and dried under vacuum to afford a pale yellow colored solid as 5-iodo-<strong>[35980-77-9]2-morpholinopyridin-4-amine</strong>. 1H NMR (400MHz, DMSO-de) delta 7.97 (s, 1H), 6.04 (s, 1H), 5.80 (s, 2H), delta 3.64 (t, J= 9.6 Hz, 4H), 3.24 (t, J= 9.6 Hz, 4H).

Reference： [1]Patent: US2005/65151,2005,A1 .Location in patent: Page/Page column 6; 14
[2]Patent: WO2012/3283,2012,A1 .Location in patent: Page/Page column 154

6
[ 35980-77-9 ]
[ 1104376-13-7 ]
[ 1104375-86-1 ]

Yield	Reaction Conditions	Operation in experiment
		-(2-Chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-N-methyl-1H-indazol-4-amine (304 mg, 0.80 mmol) the corresponding aminoheteroaryl (0.80 mmol), 1,8-diazabicyclo-[5.4.0]-undec-7-ene (0.239 mL, 1.60 mmol), bis(dibenzylideneacetone)palladium(0) (69 mg, 0.12 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (139 mg, 0.24 mmol) were suspended in dioxane (5 mL) and sealed into a microwave tube. The reaction mixture was degassed, purged with nitrogen and heated at 120 C. overnight in an oil bath. The reaction mixture was allowed to cool to room temperature, filtered off and washed with dichloromethane. The filtrate was concentrated to dryness. The residue was dissolved in a solution of 20% water in trifluoroacetic acid (5 mL) and the reaction was heated to 75 C. for 24 hours. The mixture was concentrated to dryness, taken up in methanol (2.5 mL)-toluene (2.5 mL) and concentrated to dryness. The residue was dissolved in DMF (1 mL), neutralized with 7N methanolic ammonia, and purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml/minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford the desired product.

Reference： [1]Patent: US2009/23719,2009,A1 .Location in patent: Page/Page column 17

7
6-chloro-4-morpholin-4-yl-pyridin-2-amine [ No CAS ]
[ 35980-77-9 ]

Yield	Reaction Conditions	Operation in experiment
56%		A suspension of 2-chloro-6-morpholinopyridine-4-amine (567 mg, 2.65 mmol, see note e) and 10% palladium on charcoal (57 mg) in ethyl acetate (8 mL) - ethanol (1.6 mL) was hydrogenated under 1 atm at at room temperature for 5 hours. N,N-Diisopropylethylamine (0.55 mL) was added. The mixture was filtered and the filtrate was concentrated to dryness. The residue was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate and concentrated to afford 2- morpholinopyridin-4-amine (265 mg, 56%) as a white solid. NMR Spectrum: (DMSOd6) 3.37-3.43(m, 4 H), 3.69-3.76(m, 4 H), 6.03(d, 1 H), 6.32(dd, 1 H), 7.53(bs, 2 H), 7.62(d, 1 H); Mass spectrum: MH+ 180

Reference： [1]Patent: US2009/23719,2009,A1 .Location in patent: Page/Page column 18

8
[ 35980-77-9 ]
[ 1040377-12-5 ]