[ CAS No. 188978-71-4 ]

Name: 188978-71-4|(1-((2-(Trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)boronic acid|95%
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Quality Control of [ 188978-71-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 188978-71-4 ]

Product Details of [ 188978-71-4 ]

CAS No. :	188978-71-4	MDL No. :	MFCD11855854
Formula :	C₉H₁₉BN₂O₃Si	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	UEDFWLZMMDKEDO-UHFFFAOYSA-N
M.W :	242.16 g/mol	Pubchem ID :	21874652
Synonyms :

Calculated chemistry of [ 188978-71-4 ]

Physicochemical Properties

Num. heavy atoms :	16
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.67
Num. rotatable bonds :	6
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	66.3
TPSA :	67.51 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.89 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.25
Log Po/w (WLOGP) :	-0.28
Log Po/w (MLOGP) :	-0.43
Log Po/w (SILICOS-IT) :	-2.44
Consensus Log Po/w :	-0.38

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.96
Solubility :	2.63 mg/ml ; 0.0109 mol/l
Class :	Very soluble
Log S (Ali) :	-2.27
Solubility :	1.31 mg/ml ; 0.00542 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.53
Solubility :	7.18 mg/ml ; 0.0296 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.3

Safety of [ 188978-71-4 ]

Signal Word:	Warning	Class:
Precautionary Statements:	P264-P280-P302+P352-P305+P351+P338-P332+P313-P337+P313-P362	UN#:
Hazard Statements:	H315-H319	Packing Group:
GHS Pictogram:

Application In Synthesis of [ 188978-71-4 ]

* 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 [ 188978-71-4 ]

[ 188978-71-4 ] Synthesis Path-Downstream 1~38

1
[ 188978-71-4 ]
[ CAS Unavailable ]
[ 1053360-47-6 ]

Yield	Reaction Conditions	Operation in experiment
75%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In tetrahydrofuran; water for 48h; Heating;

Reference： [1]Han, Qi; Chang, Chong-Hwan; Li, Renhua; Ru, Yu; Jadhav, Prabhakar K.; Lam, Patrick Y. S. [Journal of Medicinal Chemistry, 1998, vol. 41, # 12, p. 2019 - 2028]

2
[ 188978-71-4 ]
[ 188978-69-0 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In tetrahydrofuran; water for 48h; Heating;

Reference： [1]Han, Qi; Chang, Chong-Hwan; Li, Renhua; Ru, Yu; Jadhav, Prabhakar K.; Lam, Patrick Y. S. [Journal of Medicinal Chemistry, 1998, vol. 41, # 12, p. 2019 - 2028]

3
[ 845655-23-4 ]
[ 188978-71-4 ]
[ 845655-24-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate In tetrahydrofuran; dichloromethane; water for 18h; Heating / reflux;	45 (2S)-1-[(2R)-4-Benzoyl-2-methyl-piperazin-1-yl]-2-{8-[2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazol-3-yl]-quinolin-5-yloxy}-propan-1-one Preparation 45 (2S)-1-[(2R)-4-Benzoyl-2-methyl-piperazin-1-yl]-2-{8-[2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazol-3-yl]-quinolin-5-yloxy}-propan-1-one Tetrakis(triphenylphosphine)palladium(0)(6 mg, cat), 1-[[(2-(trimethylsilyl)ethoxy]methyl]pyrazolyl-5-boronic acid [(50 mg, 0.1 mmol), J. Med. Chem. 41 2019-2028; 1998] and sodium carbonate (175 mg, 1.6 mmol) in water (0.5 mL) were added to the compound of Preparation 44 (50 mg, 0.1 mmol) in tetrahydrofuran (2 mL) and the mixture was heated under reflux for 18 hours. The reaction mixture was then evaporated under reduced pressure and the residue was dissolved in dichloromethane and washed with water (5 mL) and brine (2*5 mL). The organic phase was dried over magnesium sulfate and concentrated in vacuo to give an orange oil. The oil was purified by column chromatography on silica gel, eluding with dichloromethane:methanol, 99:1 to 96:4 to afford the title compound as a yellow solid. LRMS (APCI+): m/z [M+H]+ 600

Reference： [1]Current Patent Assignee: PFIZER INC - US2005/43300, 2005, A1 Location in patent: Page/Page column 41

4
[ 188978-71-4 ]
[ 232277-25-7 ]
[ 232276-98-1 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran	1 N-[4-(5-Pyrazolyl)-2,6-dichlorobenzoyl)-4-(2,6-dimethoxyphenyl)-L-phenylalanine 1) N-(4-Bromo-2,6-dichlorobenzoyl)-4-(2,6-dimethoxyphenyl)-L-phenylalanine methyl ester (0.240 g) was coupled with 1-[[2-(trimethylsilyl)ethoxy]methyl]-5-pyrazoleboronic acid (0.343 g) in THF (10 mL) as described in Example 7-2) to give N-[4-[1-[[2-(trimethylsilyl)ethoxy]methyl ]-5-pyrazolyl]-2,6-dichlorobenzoyl]-4-(2,6-dimethoxyphenyl)-L-phenylalanine methyl ester (0.277 g). ESMS: m/z 684 (MH+) and 682 (M-H)-.

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - US6521666, 2003, B1

5
[ 75053-81-5 ]
[ 188978-71-4 ]
[ 1419211-52-1 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(5-bromo-pyridin-2-yloxy)-phenol; (1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)boronic acid With sodium carbonate In 1,2-dimethoxyethane for 0.5h; Inert atmosphere; Stage #2: With tetrakis(triphenylphosphine) palladium⁽⁰⁾ at 100℃; for 16h;	Preparation of 4-{5- [2-(2-trimethylsilanyl-ethoxymethyl)-211-pyrazol-3-yl]- pyridin-2- yloxy}-phenol (F) Preparation of 4-{5-[2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazol-3-yl]- pyridin-2- yloxyj-phenol (F) A suspension of Intermediate E (6.0 g, 23 mmol) and l-(2-trimethylsilanyl-ethoxymethyl)- 1H-pyrazole-5-boronic acid (SM-2) (6.6g, 27 mmol) in a mixture of DME (60 mL) and 2N aqueous Na2CC>3 (33 mL) is sparged with Argon for 30 minutes. The mixture is treated with tetrakis(triphenylphosphine)palladium(0) (2.6 g, 2 mmol) and heated to 100°C for 16 hours. The solution is cooled, poured into water/EtOAc, and the organic layer is collected. The aqueous layer is extracted twice with EtOAc, and the combined organic layers are washed with brine, dried over Na2S04, filtered and concentrated. The residue is purified on Si02 (EtOAc/heptanes) to provide F.Preparation of 4-{5-[2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazol-3-yl]- pyridin-2- yloxyj-phenol (F) A suspension of Intermediate E (6.0 g, 23 mmol) and l-(2-trimethylsilanyl-ethoxymethyl)- 1H-pyrazole-5-boronic acid (SM-2) (6.6g, 27 mmol) in a mixture of DME (60 mL) and 2N aqueous Na2CC>3 (33 mL) is sparged with Argon for 30 minutes. The mixture is treated with tetrakis(triphenylphosphine)palladium(0) (2.6 g, 2 mmol) and heated to 100°C for 16 hours. The solution is cooled, poured into water/EtOAc, and the organic layer is collected. The aqueous layer is extracted twice with EtOAc, and the combined organic layers are washed with brine, dried over Na2S04, filtered and concentrated. The residue is purified on Si02 (EtOAc/heptanes) to provide F.

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2013/12844, 2013, A1 Location in patent: Page/Page column 38; 39

6
[ 1446346-73-1 ]
[ 188978-71-4 ]
[ 1446346-74-2 ]

Yield	Reaction Conditions	Operation in experiment
38%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium carbonate In N,N-dimethyl-formamide at 125℃; for 0.5h; Microwave irradiation;	50.5 [02451 To a mixture of 5-((3-chloroisoquinolin-4-yl)methoxy)-2-methoxyisonicotinaldehyde(18 mg, 0.05 mmol, 1 equiv), 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-ylboronic acid(20 mg, 0.08 mmol, 1.5 equiv), Pd(PPh3)4 (12 mg, 0.01 mmol, 0.2 equiv), K2C03 (30 mg, 0.22mmol, 4 equiv) in a 5 mL microwave tube were added DMF (2 mL). The mixture was heated 30mm at 125 °C in a microwave reactor. The solid was filtered off and the filtrate was concentrated to dryness. The crude was purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 2-methoxy-5-((3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)isoquinolin-4-yl)methoxy)isonicotinaldehyde (10 mg, 38%) as a white solid. LRMS (M+H+)m/z 491.1.
38%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium carbonate In N,N-dimethyl-formamide at 125℃; for 0.5h;	50.5 Step 5 ;To a mixture of 5-((3-chloroisoquinolin-4-yl)methoxy)-2-methoxyisonicotinaldehyde (18 mg, 0.05 mmol, 1 equiv), 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-ylboronic acid (20 mg, 0.08 mmol, 1.5 equiv), Pd(PPh3)4 (12 mg, 0.01 mmol, 0.2 equiv), K2CO3 (30 mg, 0.22 mmol, 4 equiv) in a 5 mL microwave tube were added DMF (2 mL). The mixture was heated 30 min at 125° C. in a microwave reactor. The solid was filtered off and the filtrate was concentrated to dryness. The crude was purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 2-methoxy-5-((3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)isoquinolin-4-yl)methoxy)isonicotinaldehyde (10 mg, 38%) as a white solid. LRMS (M+H+) m/z 491.1.

Reference： [1]Current Patent Assignee: PFIZER INC; UNIVERSITY OF CALIFORNIA - WO2013/102145, 2013, A1 Location in patent: Paragraph 0245
[2]Current Patent Assignee: PFIZER INC; UNIVERSITY OF CALIFORNIA - US2015/344483, 2015, A1 Location in patent: Paragraph 0468; 0469

7
[ 1446344-52-0 ]
[ 188978-71-4 ]
[ 1446344-60-0 ]

Yield	Reaction Conditions	Operation in experiment
79%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium carbonate In 1,4-dioxane; water at 90℃; for 2h;	14.4 [01861 5-((2-bromopyridin-3-yl)methoxy)-2-methoxyisonicotinaldehyde (258 mg, 0.8 mmol, 1equiv), 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-ylboronic acid (233 mg, 0.96 mmol,1.2 equiv), Pd(PPh3)4 (92 mg, 0.08 mmol, 0.1 equiv), K2C03 (331 mg, 2.4 mmol, 3 equiv) in around bottom flask were added dioxane (8 mL) and water (2 mL). The mixture was heated 2 h at90 °C, cooled, filtered, and concentrated. The crude was purified on silica gel using a mixture ofEtOAc and hexanes as eluent to give 2-methoxy-5-((2-( 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 Hpyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde (208 mg, 79%) as a white solid. 1H NMR (400 MHz; CDC13) 6 = 10.54 (s, 1 H), 8.85 (d, 1 H), 8.18 (d, 1 H) 8.03 (s, 1 H), 7.73 (d, 1 H), 7.56 (dd, 1 H), 7.21 (s, 1 H), 6.60 (d, 1H), 5.79 (s, 2 H), 5.27 (s, 2 H), 4.01 (s, 3 H), 3.65 (t, 2 H),0.88 (t, 2 H), 0.05 (s, 9 H). LRMS (M+H+) m/z 441.2.
79%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium carbonate In 1,4-dioxane; water at 90℃; for 2h;	14.4 Step 4 ;5-((2-bromopyridin-3-yl)methoxy)-2-methoxyisonicotinaldehyde (258 mg, 0.8 mmol, 1 equiv), 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-ylboronic acid (233 mg, 0.96 mmol, 1.2 equiv), Pd(PPh3)4 (92 mg, 0.08 mmol, 0.1 equiv), K2CO3 (331 mg, 2.4 mmol, 3 equiv) in a round bottom flask were added dioxane (8 mL) and water (2 mL). The mixture was heated 2 h at 90° C., cooled, filtered, and concentrated. The crude was purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 2-methoxy-5-((2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde (208 mg, 79%) as a white solid. 1H NMR (400 MHz; CDCl3) δ=10.54 (s, 1H), 8.85 (d, 1H), 8.18 (d, 1H) 8.03 (s, 1H), 7.73 (d, 1H), 7.56 (dd, 1H), 7.21 (s, 1H), 6.60 (d, 1H), 5.79 (s, 2H), 5.27 (s, 2H), 4.01 (s, 3H), 3.65 (t, 2H), 0.88 (t, 2H), 0.05 (s, 9H). LRMS (M+H+) m/z 441.2.

Reference： [1]Current Patent Assignee: PFIZER INC; UNIVERSITY OF CALIFORNIA - WO2013/102145, 2013, A1 Location in patent: Paragraph 0185
[2]Current Patent Assignee: PFIZER INC; UNIVERSITY OF CALIFORNIA - US2015/344483, 2015, A1 Location in patent: Paragraph 0385; 0386

8
[ 188978-71-4 ]
[ 1541187-97-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / tetrahydrofuran / 0.28 h / 76 °C / Inert atmosphere 2: potassium carbonate / dimethyl sulfoxide / 16 h / 130 °C
	Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / water; tetrahydrofuran / 16 h / 76 °C / Inert atmosphere 2: potassium carbonate / dimethyl sulfoxide / 130 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2014/14874, 2014, A1
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2015/9611, 2015, A1

9
[ 188978-71-4 ]
[ 1541189-22-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / tetrahydrofuran / 0.28 h / 76 °C / Inert atmosphere 2: potassium carbonate / dimethyl sulfoxide / 16 h / 130 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 2 h / 0 - 20 °C