[ CAS No. 1034924-06-5 ] {[proInfo.proName]}

Name: 1034924-06-5|(2-Methylpyrimidin-5-yl)boronic acid|96%
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SKU: A120798
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Quality Control of [ 1034924-06-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 1034924-06-5 ]

CAS No. :	1034924-06-5	MDL No. :	MFCD07375144
Formula :	C₅H₇BN₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BTJLWJOEZRVRNL-UHFFFAOYSA-N
M.W :	137.93	Pubchem ID :	45787274
Synonyms :

Calculated chemistry of [ 1034924-06-5 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.2
Num. rotatable bonds :	1
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	36.82
TPSA :	66.24 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) :	-7.49 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	-0.49
Log Po/w (WLOGP) :	-1.54
Log Po/w (MLOGP) :	-1.84
Log Po/w (SILICOS-IT) :	-1.19
Consensus Log Po/w :	-1.01

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.76
Solubility :	23.7 mg/ml ; 0.172 mol/l
Class :	Very soluble
Log S (Ali) :	-0.43
Solubility :	50.8 mg/ml ; 0.368 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.9
Solubility :	17.3 mg/ml ; 0.126 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.87

Safety of [ 1034924-06-5 ]

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 [ 1034924-06-5 ]

* 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.

Upstream synthesis route of [ 1034924-06-5 ]
Downstream synthetic route of [ 1034924-06-5 ]

[ 1034924-06-5 ] Synthesis Path-Upstream 1~1

1
[ 7752-78-5 ]
[ 1034924-06-5 ]

Reference： [1] Patent: WO2014/75392, 2014, A1, . Location in patent: Page/Page column 66; 67
[2] Patent: WO2017/166104, 2017, A1, . Location in patent: Page/Page column 57-58

[ 1034924-06-5 ] Synthesis Path-Downstream 1~88

1
[ 1072854-55-7 ]
[ 1034924-06-5 ]
[ 1072855-06-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 5618 - 5624

2
[ 1034924-06-5 ]
[ 1420618-39-8 ]
[ 1420619-03-9 ]

Yield	Reaction Conditions	Operation in experiment
	With 2-dicyclohexylphosphino-2?,6?-di-i-propoxy-1,1?-biphenyl; palladium diacetate; sodium carbonate; In 1,4-dioxane; at 125℃; for 3h;Microwave irradiation; Sealed tube; Inert atmosphere;	Compound 1-41 was prepared from compound 1-2 according to the following coupling procedures:[00773] Compound 1-2 (230 umol), boronic acid (690 umol, 3 eq.), sodium carbonate (1.15 mmol, 5 eq.),RuPhos (70 muetaiotaomicron?, 0.30 eq.), and palladium diacetate (35 umol, 0.15 eq.) were combined in a 2 mL microwave- reaction tube with a stir bar which was sealed with a septum. The atmosphere was purged three times with vacuum, backfilling with dry argon, then 1,4-dioxane (1.6 mL) and water (0.4 mL) were added. The reaction was subjected to microwave heating at 125 °C for 3h. The reaction mixture was diluted with DCM (ca. 30 mL), treated with silica gel (ca. 1 g) and concentrated; flash chromatography of this residue (on 15 g silica gel, eluting with a MeOH/DCM or EtOAc/hexanes gradient as required, approx. 750 mL total eluent) gave the product 1-41 as a light-yellow to off- white powder. ESI-MS m/z: 485.8 [M+H]+.

Reference： [1]Patent: WO2013/12915,2013,A1 .Location in patent: Paragraph 00772-00773

3
[ 1198319-60-6 ]
[ 1034924-06-5 ]
[ 1470082-12-2 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 8834 - 8848

4
[ 1034924-06-5 ]
[ 1494218-39-1 ]
[ 1494218-40-4 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 9586 - 9600

5
[ 1034924-06-5 ]
[ 1403396-19-9 ]
[ 1403396-97-3 ]

Yield	Reaction Conditions	Operation in experiment
	With 1,1'-bis(diphenylphosphino)ferrocene-palladium(ii)dichloride-chloroform adduct; potassium carbonate; In 1,4-dioxane; water; at 90℃; for 3h;	The compound (2.34 g, 6.59 mmol) obtained in Example 16-2), <strong>[1034924-06-5](2-methylpyrimidin-5-yl)boronic acid</strong> (1.00 g, 7.25 mmol), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride-dichloromethane complex (0.54 g, 0.66 mmol), and potassium carbonate (2.73 g, 19.76 mmol) were dissolved in a mixed solvent of 1,4-dioxane (20 mL) and water (10 mL), and the mixture was stirred at 90°C for 3 h. The reaction mixture was cooled to room temperature and then diluted with ethyl acetate (150 mL). The organic layer was washed with saturated aqueous sodium hydrogencarbonate and saturated sodium chloride solution and then dried with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane = 50:50 to 100:0). The obtained partially purified product was dissolved in methanol (5 mL). 4 N hydrochloric acid-dioxane (2.39 mL) was added to the solution, and the mixture was stirred at room temperature for 2 h. The solvent was distilled off, and the residue was separated into organic and aqueous layers with methylene chloride (150 mL) and saturated aqueous sodium hydrogencarbonate (50 mL). The organic layer was washed with saturated sodium chloride solution and then dried with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain the title compound (591 mg, yield: 82percent) as a white solid. 1H-NMR (CDCl3) delta: 1.13 (2H, dd, J = 7.4, 3.5 Hz), 1.67 (2H, dd, J = 7.8, 3.5 Hz), 2.80 (3H, s), 7.48-7.61 (4H, m), 8.84 (2H, s)

Reference： [1]Patent: EP2700643,2014,A1 .Location in patent: Paragraph 0417

6
[ 1034924-06-5 ]
[ 1610703-69-9 ]
[ 1610703-67-7 ]

Yield	Reaction Conditions	Operation in experiment
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 90℃;Inert atmosphere;	Into a 5-L 4-neck round-bottom flask purged and maintained with an inert atmosphere ofnitrogen was placed a solution of 6-chloro-9-ethyl-8-iodo-9H-purine (242 g, 784 mmol), <strong>[1034924-06-5](2-methylpyrimidin-5-yl)boronic acid</strong> (108 g, 783 mmol), potassium carbonate (162 g, 1.17 mol) and Pd(dppf)C12-DCM (32 g, 39 mmol) in dioxane (2.4 L) and water (480 mL). The resulting solution was stirred overnight at 90°C. The reaction mixture was cooled to room temperature, then extracted with 2 x 1.5 L of ethyl acetate. The organic extracts were combined, dried over anhydrous magnesium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with petroleum ether/dichloromethane/ethyl acetate (5:1:1) providing 6-chloro-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purine (Intermediate IV). ?H NMR (300 MHz, CDC13) 9.12 (s, 2 H), 8.80 (s, 1 H), 4.46 (q, J= 7.2 Hz, 2 H), 2.89 (s, 3 H), 1.57-1.51 (t, J 7.2 Hz, 3 H). MS (El) Calc?d for C,2H12N6C1 [M+H], 275; found, 275.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 90℃;Inert atmosphere;	Into a 5-L 4-neck round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 6-chloro-9-ethyl-8-iodo-9H-purine (242 g, 784 mmol) , <strong>[1034924-06-5](2-methylpyrimidin-5-yl)boronic acid</strong> (108 g, 783 mmol), potassium carbonate (162 g, 1.17 mol) and Pd(dppf)Cl2-DCM (32 g, 39 mmol) in dioxane (2.4 L) and water (480 mL). The resulting solution was stirred overnight at 90 . The reaction mixture was cooled to room temperature, then extracted with 2 x 1.5 L of EtOAc. The organic extracts were combined, dried (MgSO4) and concentrated under vacuum. The residue was purified by chromatography on SiO2(5: 1: 1 petroleum ether/DCM/EtOAc) providing 6-chloro-9-ethyl-8- (2-methylpyrimidin-5-yl) -9H-purine (Intermediate I) .1H NMR (300 MHz, CDCl3) delta 9.12 (s, 2 H) , 8.80 (s, 1 H) , 4.46 (q, J 7.2 Hz, 2 H) , 2.89 (s, 3 H) , 1.57-1.51 (t, J 7.2 Hz, 3 H) . MS (EI) calc?d for C12H12N6Cl [M+H]+, 275 found, 275.

Reference： [1]Patent: WO2014/75392,2014,A1 .Location in patent: Page/Page column 66; 67; 68
[2]Patent: WO2017/166104,2017,A1 .Location in patent: Page/Page column 57-58

7
[ 7752-78-5 ]
[ 1034924-06-5 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; Triisopropyl borate; In tetrahydrofuran; toluene; at -78℃; for 1h;Inert atmosphere;	Into a 1 0-L 4-neck round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 5-bromo-2-iodopyrimidine (590 g, 2.07 mol) in THE (3 L). This was followed by dropwise addition of 1 M solution of dimethyl zinc (3.11 L, 3.11 mol) with stirring at 0°C. To this was added Pd(PPh3)4 (120 g, 104 mmol). The resulting solution was stirred for 3 h at 0°C, then quenched by the addition of 600 mL of aqueous NH4C1. The resultingsolution was extracted with 2 x 1.5 L of ethyl acetate. The organic extracts were combined, dried over anhydrous magnesium sulfate and concentrated under vacuum. The residue was applied onto a silica gel colunm and eluted with ethyl acetate/petroleum ether (1:50) to provide <strong>[7752-78-5]5-bromo-2-methylpyrimidine</strong>. Into a 1 0-L 4-neck round-bottom flask purged and maintained with an inert atmosphereof nitrogen was placed a solution of <strong>[7752-78-5]5-bromo-2-methylpyrimidine</strong> (184 g, 1.06 mol) and B(iPrO) 3 (240 g, 1.28 mol) in THE/toluene (3/3 L). This was followed by the dropwise addition of a 2.5 M solution of n-BuLi (510 mL, 1.28 mol) with stirring at -78°C. The resulting solution was stirred for 1 hat -78°C, then quenched by the addition of 200 nit of aqueous NH4CI. The organic phase was dried and concentrated under vacuum. The aqueous phase was adjusted to pH4 with AcOH. The solid was collected by filtration and dried in an oven under reduced pressure providing (2-methylpyrimidin-5 -yl)boronic acid.
	With n-butyllithium; Triisopropyl borate; In tetrahydrofuran; toluene; at -78℃; for 1h;Inert atmosphere;	Into a 10-L 4-neck round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of <strong>[7752-78-5]5-bromo-2-methylpyrimidine</strong> (184 g, 1.06 mol) and B (i-PrO)3(240 g, 1.28 mol) in THF/toluene (3/3 L) . This was followed by the dropwise addition of a 2.5 M solution of n-BuLi (510 mL, 1.28 mol) with stirring at -78 . The resulting solution was stirred for 1 h at -78 , then quenched by the addition of 200 mL of aqueous NH4Cl. The organic phase was dried and concentrated under vacuum. The aqueous phase was adjusted to pH 4 with AcOH. The solid was collected by filtration and dried in an oven under reduced pressure providing (2-methylpyrimidin-5-yl) boronic acid.

Reference： [1]Patent: WO2014/75392,2014,A1 .Location in patent: Page/Page column 66; 67
[2]Patent: WO2017/166104,2017,A1 .Location in patent: Page/Page column 57-58

8
[ 1034924-06-5 ]
[ 1610720-03-0 ]

Reference： [1]Patent: WO2014/75392,2014,A1

9
[ 1034924-06-5 ]
6-[1-(cyclopropylcarbonyl)-4-fluoropyrrolidin-3-yl]oxy}-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purine [ No CAS ]

Reference： [1]Patent: WO2014/75392,2014,A1

10
[ 1034924-06-5 ]
[ 1610723-00-6 ]

Reference： [1]Patent: WO2014/75392,2014,A1

11
[ 1034924-06-5 ]
[ 1610714-46-9 ]

Reference： [1]Patent: WO2014/75392,2014,A1

12
[ 1034924-06-5 ]
[ 1610714-47-0 ]

Reference： [1]Patent: WO2014/75392,2014,A1

13
[ 1034924-06-5 ]
[ 1610715-08-6 ]
[ 1610715-07-5 ]

Reference： [1]Patent: WO2014/75392,2014,A1

14
[ 1034924-06-5 ]
C₁₆H₁₈FN₇O*ClH [ No CAS ]

Reference： [1]Patent: WO2014/75392,2014,A1

15
[ 1034924-06-5 ]
[ 1610715-13-3 ]
[ 1610715-12-2 ]

Reference： [1]Patent: WO2014/75392,2014,A1

16
[ 1034924-06-5 ]
[ 1610714-48-1 ]

Reference： [1]Patent: WO2014/75392,2014,A1

17
[ 1034924-06-5 ]
[ 1610715-09-7 ]

Reference： [1]Patent: WO2014/75392,2014,A1

18
[ 1034924-06-5 ]
[ 1610715-11-1 ]

Reference： [1]Patent: WO2014/75392,2014,A1

19
[ 1034924-06-5 ]
(3S,4S)-tert-butyl 3-[9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-yl]oxy}-4-fluoropyrrolidine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2014/75392,2014,A1

20
[ 1034924-06-5 ]
[ 1610714-52-7 ]

Reference： [1]Patent: WO2014/75392,2014,A1

21
[ 1034924-06-5 ]
[ 1610714-53-8 ]

Reference： [1]Patent: WO2014/75392,2014,A1

22
[ 1034924-06-5 ]
[ 1621585-55-4 ]
[ 1621585-88-3 ]

Yield	Reaction Conditions	Operation in experiment
84%	With bis-triphenylphosphine-palladium(II) chloride; caesium carbonate; In tetrahydrofuran; at 65℃; for 18.0833h;	Step 1. Synthesis of N-[(4aR,8aS)-8a-(2,4-difluorophenyl)-6-(2-methylpyrimidin-5-yl)-4,4a,8,8a-tetrahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C76) A mixture of C30 (60 mg, 0.11 mmol), <strong>[1034924-06-5]2-methylpyrimidine-5-boronic acid</strong> (30.9 mg, 0.224 mmol), bis(triphenylphosphine)palladium(II) dichloride (4.3 mg, 6.0 mumol) and tetrahydrofuran (5 mL) was sparged with argon for 5 minutes, followed by addition of aqueous cesium carbonate solution (2 M, 280 muL). The reaction mixture was stirred at 65° C. for 18 hours and then concentrated in vacuo; the residue was diluted with water (15 mL) and extracted with ethyl acetate (3*20 mL). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel chromatography (Gradient: 30percent to 100percent ethyl acetate in heptane) afforded the product as a white solid. Yield: 44 mg, 92 mumol, 84percent. 1H NMR (400 MHz, CD3OD) delta 8.88 (d, J=1.4 Hz, 2H), 8.00 (br d, J=6.7 Hz, 2H), 7.56-7.62 (m, 1H), 7.50-7.53 (m, 1H), 7.40-7.44 (m, 2H), 7.07-7.12 (m, 2H), 5.66 (br s, 1H), 4.79 (d, J=11 Hz, 1H), 4.34 (br d, J=10.8 Hz, 1H), 3.73 (br s, 1H), 2.93-3.05 (m, 2H), 2.67 (s, 3H)

Reference： [1]Patent: US2014/228356,2014,A1 .Location in patent: Paragraph 0290; 0291

23
[ 1034924-06-5 ]
6-chloro-1,3,3-trimethyl-1,3-dihydro-pyrrolo[3,2-c]pyridin-2-one [ No CAS ]
1,3,3-trimethyl-6-(2-methylpyrimidin-5-yl)pyrrolo[3,2-c]pyridin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30 mg	With dicyclohexyl-(2?,4?,6?-triisopropyl-3,6-dimethoxy-[1,1?-biphenyl]-2-yl)phosphine; sodium t-butanolate; In 1,4-dioxane; at 110℃; for 1h;Inert atmosphere; Sealed tube; Microwave irradiation;	Example 108 1,3,3-trimethyl-6-(2-methylpyrimidin-5-yl)pyrrolo[3,2-c]pyridin-2-one A mixture of 6-chloro- 1,3,3 -trimethyl- 1,3 -dihydro-pyrrolo[3 ,2-clpyridin-2-one (example 83a)(0.1 g, 0.475 mmol), <strong>[1034924-06-5]2-methylpyrimidine-5-boronic acid</strong> (0.078 g, 0.57 mmol) and NaOtBu(0.068 g, 0.7 12 mmol) in dioxane (2.0 ml) in a microwave vessel was sparged with argon for 15 minutes. Then Brettphos (0.019, 0.024 mmol) was added to the reaction mixture and sparging was continued for 15 minutes. The vial was sealed and the reaction mixture was irradiated to 110C for 1 hour. The reaction mixture was filtered through celite and the filtrate was concentrated in vacuo. The crude material was purified by preparative reversed phase HPLC over aX Terra Prep RPC18 250 x 19 mm 10 t column using acetonitrile/ 5 mM aqueous ammonium acetate solution as eluent. The title compound was obtained as off white solid (30 mg) MS ESI (m/z): 268.8 [(M+H)i.

Reference： [1]Patent: WO2014/202493,2014,A1 .Location in patent: Page/Page column 101; 102

24
[ 1034924-06-5 ]
(4S)-7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide [ No CAS ]
(9S)-5-(2-methylpyrimidin-5-yl)-N-(pyrazin-2-yl)-1,6,8-triazatricyclo[7.2.1.0^2,7]dodeca-2⁽⁷⁾,3,5-triene-8-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49.5%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; water; at 100℃; for 6h;Inert atmosphere;	Tripotassium phosphate (804 mg, 3.79 mmol) was added to a stirred solution of (4S)-7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide (600 mg, 1.894 mmol), <strong>[1034924-06-5](2-methylpyrimidin-5-yl)boronic acid</strong> (314 mg, 2.273 mmol) in 1,4-dioxane (12 mL) and water (2.000 mL). The reaction mixture was degassed for 15 min X-phos (90 mg, 0.189 mmol), and Pd2(dba)3 (87 mg, 0.095 mmol) were added. The reaction mixture was further degassed for 15 min, and was stirred at 100 C. for 6 hr. The reaction mixture was cooled to 28 C. and was partitioned between water (30 mL) and EtOAc (70 mL). Organic layer was separated and was dried over anhydrous Na2SO4, filtered. The filtrate was evaporated to get crude (TLC eluent: 5% MeOH in CHCl3: Rf=0.2; UV active). The crude compound was purified by 100-200 silica gel by eluting 20% MeOH in ethyl acetate to afford (4S)-7-(2-methylpyrimidin-5-yl)-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide (353 mg, 0.938 mmol, 49.5% yield) as pale yellow solid, LCMS (m/z): 375.19 [M+H]+. 1H NMR (CDCl3, 400 MHz): delta 13.57 (s, 1H), 9.53 (d, J=1.5 Hz, 1H), 9.33 (s, 2H), 8.38 (d, J=1.6 Hz, 1H), 8.30 (s, 1H), 7.66 (d, J=8.0 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H), 5.71 (dd, J=5.9, 3.2 Hz, 1H), 3.41-3.11 (m, 3H), 3.04 (dd, J=12.1, 3.3 Hz, 1H), 2.84 (s, 3H), 2.36 (dddd, J=14.0, 9.9, 6.1, 4.1 Hz, 1H), 2.11 (d, J=7.1 Hz, 1H).
49.5%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; water; at 100℃; for 6h;	Tripotassium phosphate (804 mg, 3.79 mmol) was added to a stirred solution of (4S)-7- chloro-N-(pyrazin-2-yl)-3,4-dihydro-l,4-methanopyrido[2,3-^][l,4]diazepine-5(2H)- carboxamide (600 mg, 1.894 mmol), <strong>[1034924-06-5](2-methylpyrimidin-5-yl)boronic acid</strong> (314 mg, 2.273 mmol) in 1,4-dioxane (12 mL) and water (2.000 mL). The reaction mixture was degassed for 15 min X-phos (90 mg, 0.189 mmol), and Pd2(dba)3 (87 mg, 0.095 mmol) were added. The reaction mixture was further degassed for 15 min, and was stirred at 100 C for 6 hr. The reaction mixture was cooled to 28 C and was partitioned between water (30 mL) and EtOAc (70 mL). Organic layer was separated and was dried over anhydrous Na2S04, filtered. The filtrate was evaporated to get crude (TLC eluent: 5% MeOH in CHC13: R/ = 0.2; UV active). The crude compound was purified by 100-200 silica gel by eluting 20% MeOH in ethyl acetate to afford (45)-7-(2-methylpyrimidin-5-yl)-N-(pyrazin-2-yl)-3,4- dihydro-l,4-methanopyrido[2,3-^][l,4]diazepine-5(2H)-carboxamide (353 mg, 0.938 mmol, 49.5 % yield) as pale yellow solid, LCMS (m/z): 375.19 [M+H]+.1H NMR (CDC13, 400 MHz): delta 13.57 (s, 1H), 9.53 (d, J = 1.5 Hz, 1H), 9.33 (s, 2H), 8.38 (d, J = 1.6 Hz, 1H), 8.30 (s, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H), 5.71 (dd, J= 5.9, 3.2 Hz, 1H), 3.41 - 3.11 (m, 3H), 3.04 (dd, J= 12.1, 3.3 Hz, 1H), 2.84 (s, 3H), 2.36 (dddd, J= 14.0, 9.9, 6.1, 4.1 Hz, 1H), 2.11 (d, J= 7.1 Hz, 1H).

Reference： [1]Patent: US2015/152108,2015,A1 .Location in patent: Paragraph 1199; 1200; 1201
[2]Patent: WO2016/79709,2016,A1 .Location in patent: Page/Page column 457

25
[ 1034924-06-5 ]
tert-butyl 2-(3-carbamoyl-5-chloro-1H-pyrazolo[3,4-d]thiazol-1-yl)acetate [ No CAS ]
tert-butyl 2-(3-carbamoyl-5-(2-methylpyrimidin-5-yl)-1H-pyrazolo[3,4-d]thiazol-1-yl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38.4%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃; for 4h;Inert atmosphere;	To a mixture of compound S11 (300 mg, 0.84 mmol) and K2CO3(292 mg, 2.1 mmol) in dioxane/H2O (10 mL, 9:1) was added <strong>[1034924-06-5]2-methylpyrimidin-5-ylboronic acid</strong> (138 mg, 1 mmol.) and Pd(PPh3)4(100 mg, 0.08 mmol). The reaction was degassed under N2for three times and stirred at 90 C. for 4 hrs under N2atmosphere. After cooling, the mixture was diluted with saturated aq. NaHCO3(10 mL) and extracted with EtOAc (20 mL×2). The combined organic phases were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluted with DCM: MeOH=50:1 to 20:1) to give the title compound (121 mg, 38.4% yield) as white solid. LC/MS (ESI) m/z: 375 (M+H)+
38.4%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃; for 4h;Inert atmosphere;	To a mixture of scheme 6-9 compound S12 (300 mg, 0.84 mmol) and K2CO3 (292 mg, 2.1 mmol) in dioxane/H2O (10 mL, 9:1) was added <strong>[1034924-06-5]2-methylpyrimidin-5-ylboronic acid</strong> (138 mg, 1 mmol.) and Pd(PPh3)4 (100 mg, 0.08 mmol). The reaction was degassed under N2 three times and stirred at 90 oC for 4 h under N2 atmosphere. After cooling, the mixture was diluted with saturated aqeuous NaHCO3 (10 mL) and extracted with EtOAc (20 mL x 2). The combined organic phases were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluted with DCM: MeOH=50: 1 to 20: 1) to afford the title compound (121 mg, 38.4 % yield) as a white solid. LC/MS (ESI) m/z: 375 (M+H)+.

Reference： [1]Patent: WO2017/35353,2017,A1 .Location in patent: Paragraph 0738
[2]Patent: WO2017/35409,2017,A1 .Location in patent: Paragraph 0674

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[ 1110641-70-7 ]
[ 1034924-06-5 ]
(S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(2-methylpyrimidin-5-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 3649 - 3657

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[ 1034924-06-5 ]
5-(9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-yl)-3-isobutyl-3-methyl-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one [ No CAS ]