1187929-04-9|(S)-Morpholine-3-carboxylic acid hydrochloride| Ambeed

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 1187929-04-9 ] Purity: 97% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 1187929-04-9 ]

CAS No. :	1187929-04-9
Formula :	C₅H₁₀ClNO₃
M.W :	167.59
SMILES Code :	O=C([C@H]1NCCOC1)O.[H]Cl
MDL No. :	MFCD06809590
InChI Key :	CWSLARZELUGARZ-WCCKRBBISA-N
Pubchem ID :	42614332

Safety of [ 1187929-04-9 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 1187929-04-9 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	0
Fraction Csp3	0.8
Num. rotatable bonds	1
Num. H-bond acceptors	4.0
Num. H-bond donors	2.0
Molar Refractivity	40.57
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	58.56 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.0
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	-2.43
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	-0.52
Log P_o/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.	-3.07
Log P_o/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	-0.05
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	-1.21

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	0.72
Solubility	875.0 mg/ml ; 5.22 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Highly soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	1.74
Solubility	9220.0 mg/ml ; 55.0 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	0.11
Solubility	217.0 mg/ml ; 1.29 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.	-9.05 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	2.0
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)	2.3

Application In Synthesis of [ 1187929-04-9 ]

* 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.

Downstream synthetic route of [ 1187929-04-9 ]

[ 1187929-04-9 ] Synthesis Path-Downstream 1~35

1
[ 1187929-04-9 ]
[ 28920-43-6 ]
[ 281655-37-6 ]

References: [1]Journal of Biological Chemistry,2010,vol. 285,p. 8976 - 8984.

2
[ 1187929-04-9 ]
[ 1578155-69-7 ]
[ 1578153-27-1 ]

Yield	Reaction Conditions	Operation in experiment
1.01 kg	With 2,2,6,6-tetramethyl-piperidine; In dichloromethane; for 16.0h;Large scale;	The 50 L flask was charged with crude (4R)-6-(bromomethyl)-4-(2-chloro-4-fluoro- phenyl)-2-thiazol-2-yl- 1 ,4-dthydropyrimidine-5-carboxylic acid methyl ester(compound IXa) from last step) in dichloromethane solution, (35)-<strong>[1187929-04-9]morpholine-3-carboxylic acid hydrochloride</strong>salt (1.02 eq, 0.53 kg, 3.14 mol) and 2,2,6,6-tetramethylpiperidine (2.87 eq, 1.24 kg, 8.80 mol) at25C - 28 C. The resulting solution was stirred at 25 C - 28 C for 16 hours.After reaction completion, water (10.0 L) was added to reaction mixture to quench thereaction. The reaction mixture was adjusted to pH = 2.5 using H3P04. After phase separation, the organic phase was washed with acid solution (using H3P04 to adjust pH = 2.5) twice to remove all the TMP. The organic solution was concentrated to dryness in vacuo and the residue was redissolved in MIBK (10.0 L). To the solution was then added MSA (0.78 eq, 0.23 kg, 2.39 mol) slowly in 2 hours. After the addition of MSA, the solution was heated to 40 C - 45 C and stirred for 2 hours. The resulting suspension was cooled to 23 C - 25 C. The reaction mixture was filtered and the collected solid was rinsed with MIBK (1.0 L). The resulting solid was dried invacuum oven at 45 C for 16 hours to afford the MSA salt of Example 3 (1.45 kg).To a 20 L flask was charged with MSA salt of Example 3 (L45 kg, 2.45 mel), EtOAc (15.0 L) and NaHCO3 aqueous solution (10 wt%, L33 kg) at roomtemperature After phase separation, the organic phase was washed with water (3.0 L). The organic solution was concentrated to dryness in vacu.o and the residue was re-dissolved in acetone (1.10 L).The resulting acetone solution was slowly added into water (12,0 L) in 12 hours at 20C -25 C. The resulting suspension was stirred for an additional 72 hours at 20C -25 C. Reaction mixture was filtered and the collected solid was rinsed with water (5.0 L) for 2 times. The resulting solid was dried under vacuum at 55 C for 72 hours until the weight was constant to give 1.01 kg product as light yellow solid. The purity was 99.5%, the yield was 66.6% for 3 steps,and the MS m/e =495.1 [M+H].

References: [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 3352 - 3371.
[2]Patent: WO2016/102438,2016,A1 .Location in patent: Page/Page column 13; 14; 15; 16.

3
[ 1187929-04-9 ]
(R)-4-(2-chlorophenyl)-6-bromomethyl-2-thiazol-2-yl-1,4-dihydropyrimidine-5-carboxylic acid ethyl ester [ No CAS ]
(3S)-4-[[(4S)-4-(4-chlorophenyl)-5-methoxycarbonyl-2-thiazol-2-yl-1,4-dihydropyrimidin-6-yl]methyl]morpholine-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
7.40 g	With 2,2,6,6-tetramethyl-piperidine; In dichloromethane; at 25 - 28℃; for 16.0h;	To the 100 mL flask was charged with (R)-4-(2-chlorophenyl)-6-bromomethyl-2-thiazol- 2-yl-1,4-dthydropyrimidine-5-carboxylic acid ethyl ester (compound IXc, 8.14g, 18.50 mrnol) inDCM solution, (35)-<strong>[1187929-04-9]morpholine-3-carboxylic acid hydrochloride</strong> salt (compound X, 1.50 eq.,4.64 g, 27.70 mmol) and 2,2,6,6-tetramethylpiperidine (5.10 eq, 13.03 g, 94.16 mmoi), The reaction mixture was stirred at 25 C - 28 C for 16 hours. After reaction completion, the reaction mixture was adjusted to pH = 2.5 using H3P04, After phase separation, the organic phase was washed with acid water (using H3P04 to adjust to pH = 2.5) twice to remove all the TMP andconcentrated till dryness in vacuo. The residue was dissolved in EtOAc (30 mL) at 25 C -28 C. To the previous solution was then slowly added n-heptane (50 rnL) while maintain at 25 C -28C. The resulted suspension was stirred for another 0.5 hour at 25 C -28 C. After vacuum filtration, the collected solid was dried in vacuum oven at 55 C for 16 hours until the weight was constant to give 7.40 g product (Example 10) as a yellow solid. The purity was 99.0%, the yieldwas 80.7%, and MS m/e =49 1.3 [M+H] .

References: [1]Patent: WO2016/102438,2016,A1 .Location in patent: Page/Page column 23.

4
[ 1187929-04-9 ]
(R)-6-(bromomethyl)-4-(2-chloro-4-fluorophenyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylic acid ethyl ester [ No CAS ]
[ 1578153-81-7 ]

References: [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 3352 - 3371.
[2]Journal of Medicinal Chemistry,2019.

5
[ 1187929-04-9 ]
C₁₈H₁₆BrClFN₃O₂S [ No CAS ]
(3S)-4-[[4-(2-chloro-4-fluoro-phenyl)-5-propoxycarbonyl-2-thiazol-2-yl-1,4-dihydropyrimidin-6-yl]methyl]morpholine-3-carboxylic acid [ No CAS ]