[ CAS No. 305790-48-1 ] {[proInfo.proName]}

Name: 305790-48-1|6-Bromo-1-methyl-1H-benzo[d]imidazol-2(3H)-one|95%
Brand: Ambeed
SKU: A103029
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Quality Control of [ 305790-48-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 305790-48-1 ]

SDS Specification

Alternatived Products of [ 305790-48-1 ]

Product Details of [ 305790-48-1 ]

CAS No. :	305790-48-1	MDL No. :	MFCD09759338
Formula :	C₈H₇BrN₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WQXHBMNNVRGWHF-UHFFFAOYSA-N
M.W :	227.06	Pubchem ID :	9815982
Synonyms :

Calculated chemistry of [ 305790-48-1 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.12
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	51.52
TPSA :	37.79 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.66 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.93
Log Po/w (XLOGP3) :	1.44
Log Po/w (WLOGP) :	1.63
Log Po/w (MLOGP) :	1.9
Log Po/w (SILICOS-IT) :	2.22
Consensus Log Po/w :	1.83

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.71
Solubility :	0.443 mg/ml ; 0.00195 mol/l
Class :	Soluble
Log S (Ali) :	-1.84
Solubility :	3.29 mg/ml ; 0.0145 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-3.24
Solubility :	0.131 mg/ml ; 0.000575 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.62

Safety of [ 305790-48-1 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 305790-48-1 ]

* 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 [ 305790-48-1 ]
Downstream synthetic route of [ 305790-48-1 ]

[ 305790-48-1 ] Synthesis Path-Upstream 1~7

1
[ 305790-47-0 ]
[ 305790-48-1 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 20, p. 2747 - 2750
[2] Patent: US6380235, 2002, B1,
[3] Patent: US6423699, 2002, B1,
[4] Patent: EP1719761, 2006, A1, . Location in patent: Page/Page column 28

2
[ 77-78-1 ]
[ 161468-56-0 ]
[ 305790-48-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	at 20℃; for 18 h;	[00338] 6-Bromo-l-methyl-lH-benzo[d]imidazol-2(3H)-one: tert-Butyl 5- bromo-2-oxo-2,3-dihydrobenzo[d]imidazole-l-carboxylate (12 g, 38 mmol) (Puwen Zhang, et. al., Bioorganic Medicinal Chemistry Letters 1 1 (2001) 2747-2750 hereby incoporated by reference) and anhydrous disodium carbonate (3.2 niL, 77 mmol) were mixed in 200 mL THF. To this mixture was added dimethyl sulfate (15 mL, 153 mmol). The mixture was stirred at room temperature for 18 hours. The solvent was evaporated. The residue was dissolved in EtOAc and washed with brine and dried over sodium <n="159"/>sulfate. The solvent was evaporated. The residue was taken up in MeOH (50 mL) and allowed to stand 18 hours. The solvent was evaporated, and the residue was triturated from MeOH (25 mL) to provide the product as a white solid (8.7 g, 100 percent). LCMS (API- ES) m/z: 227, 229 (M+H*).

Reference： [1] Patent: WO2009/11880, 2009, A2, . Location in patent: Page/Page column 157-158

3
[ 32315-10-9 ]
[ 93933-49-4 ]
[ 305790-48-1 ]

Yield	Reaction Conditions	Operation in experiment
24%	Stage #1: for 18 h; Reflux Stage #2: With hydrogenchloride In water for 12 h;	To a solution of2-amino-4-bromobenzenethiol (500 mg,2.50 mmol)in acetic acid (25mL)was added triphosgene (490 mg,1.70 mmol). The mixture was heated at reflux for 18 h.After cooling to room temperature,the solution was partially concentrated under reducedpressure,water was added,and the resulting precipitate was removed via filtration,and washedwith aqueous NaOH (1M). The filtrate was acidified with aqueous HCl (2 N)to pH 2,and placed in a refrigerator for 12 h. The resulting precipitate was filtered,washed with water,anddried under reduced pressure to give the title compound (133 mg,24percent)as a while powder thatrequired no further purification. 1H NMR (400 MHz,DMSO-d6)8 10.97 (s,1H),7.33 (d,J = 1.9Hz,1H),7.13 (dd,J = 8.2,1.9 Hz,1H),6.91 (d,J = 8.2 Hz,1H),3.26 (s,3H)

Reference： [1] Patent: WO2017/205536, 2017, A2, . Location in patent: Page/Page column 89

4
[ 337915-79-4 ]
[ 530-62-1 ]
[ 305790-48-1 ]

Reference： [1] Patent: WO2012/21382, 2012, A1, . Location in patent: Page/Page column 30
[2] Patent: WO2016/57834, 2016, A1, . Location in patent: Paragraph 000821; 000875

5
[ 161468-56-0 ]
[ 305790-48-1 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 20, p. 2747 - 2750

6
[ 321-23-3 ]
[ 305790-48-1 ]

Reference： [1] Patent: WO2012/21382, 2012, A1,
[2] Patent: WO2016/57834, 2016, A1,

7
[ 302800-13-1 ]
[ 305790-48-1 ]

Reference： [1] Patent: WO2012/21382, 2012, A1,
[2] Patent: WO2016/57834, 2016, A1,

[ 305790-48-1 ] Synthesis Path-Downstream 1~88

1
[ 161468-56-0 ]
[ 305790-48-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 2747 - 2750

2
[ 13331-27-6 ]
[ 305790-48-1 ]
1-Methyl-6-(3-nitro-phenyl)-1,3-dihydro-benzoimidazol-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 7 1-Methyl-6-(3-nitro-phenyl)-1,3-dihydro-benzoimidazol-2-one Prepared from 1-methyl-6-bromo-1,3-dihydro-benzoimidazol-2-one and 3-nitro-phenyl boronic acid in the same fashion as that of Example 5. White solid: mp 264-265 C.; 1H-NMR (DMSO-d6) delta11.0 (s, 1H), 8.47 (t, 1H, J=1.5 Hz), 8.19-8.15 (m, 2H), 7.75 (t, 1H, J=8.25 Hz), 7.58 (d, 1H, J=1.5 Hz), 7.43 (dd, 1H, J=8.25, 1.5 Hz), 7.1 (d, 1H, J=8.25 Hz), 3.37 (s, 3H); MS (ES) m/z 268([M-H]-, 50%); Anal. Calc. For C14H11N3O3: C, 62.45; H, 4.12; N, 15.61. Found: C, 61.48; H, 4.36; N, 14.75.
		EXAMPLE 7 1-Methyl-6-(3-nitro-phenyl)-1,3-dihydro-benzoimidazol-2-one Prepared from 1-methyl-6-bromo-1,3-dihydro-benzoimidazol-2-one and 3-nitro-phenyl boronic acid in the same fashion as that of Example 5. White solid: mp 264-265 C.; 1H-NMR (DMSO-d6) delta 11.0 (s, 1H), 8.47 (t, 1H, J=1.5 Hz), 8.19-8.15 (m, 2H), 7.75 (t, 1H, J=8.25 Hz), 7.58 (d, 1H, J=1.5 Hz), 7.43 (dd, 1H, J=8.25, 1.5 Hz), 7.1 (d, 1H, J=8.25 Hz), 3.37 (s, 3H); MS (ES) m/z 268([M-H]-, 50%); Anal. Calc. For C14H11N3O3: C, 62.45, H, 4.12, N, 15.61. Found: C, 61.48, H, 4.36 N, 14.75.

Reference： [1]Patent: US6380235,2002,B1
[2]Patent: US6423699,2002,B1

3
[ 63503-60-6 ]
[ 305790-48-1 ]
6-(3-chloro-phenyl)-1-methyl-1,3-dihydro-benzoimidazol-2-one [ No CAS ]
[ 305790-49-2 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 8 6-(3-chloro-phenyl)-1-methyl-1,3-dihydro-benzoimidazol-2-one Prepared from 1-methyl-6-bromo-1,3-dihydro-benzoimidazol-2-one and 3-chloro-phenyl boronic acid in the same fashion as that of Example 5. mp 219-220 C.; 1H-NMR (DMSO-d6) delta11.0 (s, 1H), 7.75 (bs, 1H), 7.65 (dd, 1H, J=7.5, 1.76 Hz), 7.49-7.44 (m, 2H), 7.39-7.32 (m, 2H), 7.06 (d, 1H, J=7.94 Hz), 3.35 (s, 3H); MS (ES) m/z 259([M+H]+, 100%); Anal. Calc. For C14H11ClN2O: C, 65; H, 4.29; N, 10.83. Found: C, 64.44; H, 4.36; N, 10.6.
		EXAMPLE 8 6-(3-chloro-phenyl)-1-methyl-1,3-dihydro-benzoimidazol-2-one Prepared from 1-methyl-6-bromo-1,3-dihydro-benzoimidazol-2-one and 3-chloro-phenyl boronic acid in the same fashion as that of Example 5. mp 219-220 C.; 1H-NMR (DMSO-d6) delta 11.0 (s, 1H), 7.75 (bs, 1H), 7.65 (dd, 1H, J=7.5, 1.76 Hz), 7.49-7.44 (m, 2H), 7.39-7.32 (m, 2H), 7.06 (d, 1H, J=7.94 Hz), 3.35 (s, 3H), MS (ES) m/z 259([M+H]+, 100%); Anal. Calc. For C14H11ClN2O: C, 65, H, 4.29, N, 10.83. Found: C, 64.44, H, 4.36 N, 10.6.

Reference： [1]Patent: US6380235,2002,B1
[2]Patent: US6423699,2002,B1

4
[ 73183-34-3 ]
[ 305790-48-1 ]
[ 944805-83-8 ]

Yield	Reaction Conditions	Operation in experiment
59%	With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 80℃; for 30.0167h;	[00339] l-Methyl-6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH- benzo[d]imidazol-2(3H)-one: Potassium acetate (6.4 g, 65 mmol), bis(pinacolato)diboron (6.1 g, 24 mmol), and 6-bromo-l-methyl-lH-benzo[d]imidazol-2(3H)-one (4.94 g, 22 mmol) were mixed in 20 mL DMSO, and the mixture was degassed with nitrogen bubbling for 1 minute. To this mixture was added Pd(dppf)Cl2 (0.80 g, 1.1 mmol). The mixture was heated at 8O0C for 20 hours. The mixture was partitioned between 200 mL diethyl ether and 20 mL saturated ammonium chloride. The ether solution was washed with the saturated aqueous ammonium chloride (4 x), dried over sodium sulfate and evaporated. The residue was crystallized from MeOH. The mother liquor was purified by chromatography on silica gel (30 % EtOAc in hexane). The recovered material was combined to provide the product as a white solid (3.5 g, 59 %). LCMS (API-ES) m/z: 275 (M+lT).

Reference： [1]Patent: WO2009/11880,2009,A2 .Location in patent: Page/Page column 157-158

5
[ 77-78-1 ]
[ 161468-56-0 ]
[ 305790-48-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	In tetrahydrofuran; at 20℃; for 18h;	[00338] 6-Bromo-l-methyl-lH-benzo[d]imidazol-2(3H)-one: tert-Butyl 5- bromo-2-oxo-2,3-dihydrobenzo[d]imidazole-l-carboxylate (12 g, 38 mmol) (Puwen Zhang, et. al., Bioorganic & Medicinal Chemistry Letters 1 1 (2001) 2747-2750 hereby incoporated by reference) and anhydrous disodium carbonate (3.2 niL, 77 mmol) were mixed in 200 mL THF. To this mixture was added dimethyl sulfate (15 mL, 153 mmol). The mixture was stirred at room temperature for 18 hours. The solvent was evaporated. The residue was dissolved in EtOAc and washed with brine and dried over sodium <n="159"/>sulfate. The solvent was evaporated. The residue was taken up in MeOH (50 mL) and allowed to stand 18 hours. The solvent was evaporated, and the residue was triturated from MeOH (25 mL) to provide the product as a white solid (8.7 g, 100 %). LCMS (API- ES) m/z: 227, 229 (M+H*).

Reference： [1]Patent: WO2009/11880,2009,A2 .Location in patent: Page/Page column 157-158

6
[ 15501-33-4 ]
[ 305790-48-1 ]
[ 1359761-03-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In N,N-dimethyl-formamide; at 175℃; for 0.333333h;Microwave irradiation;	5-bromo~l-(2,2-diraethylpropyl)-3-raethyl-l,3-dihydro-2H»benziraidazol-2~one (1-5)A solution of 6-bromo-l -methyl- 1, 3 -dihydro-2H-benzimidazol-2-one (1-4, 500 mg, 2.20 mmol) in DMF (10 ml) was treated with Sodium hydride (176 mg, 4.40 mmol, 2.0 eq) followed by the l-Iodo-2,2-Dimethylpropane (585 muEpsilon, 4.40 mmol, 2.0 eq). The reaction was irradiated at 175 deg C for 20 min in a microwave. The reaction was complete by LC/MS, so it was partitioned between EtOAc (2x125 ml) and water (150 ml). The combined organic layers were dried over Na SO4 and concentrated. The crude maroon-orange oil was purified via flash column chromatography (Si02: 100% Hex to 60:40 Hex:EtOAc), affording the title compound, 5-bromo-l-(2,2-dimethylpropyl)-3-methyl-l,3-dihydro-2H-benzimidazol-2-one (1-5), as a yellow solid with >95% purity. 'HNMR (600 MHz, CDC13) delta 7.18 (dd, 1H, J= Hz), 7.10 (s, H), 6.88 (d, IH, J- Hz), 3.63 (s, 2H), 3.40 (s, 3H), 1.02 (s, 9H). LRMS m/z: Calc'd for C7H7Br 202 (M.+H) 232.1, found 232.8.

Reference： [1]Patent: WO2012/21382,2012,A1 .Location in patent: Page/Page column 30-31

7
[ 321-23-3 ]
[ 305790-48-1 ]

Reference： [1]Patent: WO2012/21382,2012,A1
[2]Patent: WO2016/57834,2016,A1
[3]Patent: WO2019/60693,2019,A1
[4]Patent: WO2019/60742,2019,A1
[5]Patent: US2019/192668,2019,A1
[6]Patent: WO2020/10210,2020,A1

8
[ 302800-13-1 ]
[ 305790-48-1 ]

9
[ 305790-48-1 ]
[ 1359757-39-3 ]

Reference： [1]Patent: WO2012/21382,2012,A1

10
[ 305790-48-1 ]
[ 1359759-14-0 ]

Reference： [1]Patent: WO2012/21382,2012,A1

11
[ 305790-48-1 ]
[ 1359759-42-4 ]

Reference： [1]Patent: WO2012/21382,2012,A1

12
[ 305790-48-1 ]
[ 1359759-81-1 ]

Reference： [1]Patent: WO2012/21382,2012,A1

13
[ 305790-48-1 ]
[ 1359759-86-6 ]

Reference： [1]Patent: WO2012/21382,2012,A1

14
[ 305790-48-1 ]
[ 1359761-06-0 ]

Reference： [1]Patent: WO2012/21382,2012,A1

15
[ 305790-48-1 ]
[ 1359759-96-8 ]

Reference： [1]Patent: WO2012/21382,2012,A1

16
[ 305790-48-1 ]
[ 1359759-10-6 ]

Reference： [1]Patent: WO2012/21382,2012,A1

17
[ 305790-48-1 ]
6-bromo-2-chloro-1-methyl-1H-benzo[d]imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With trichlorophosphate; at 110℃; for 18h;	[000822j A stirred solution of compound 2 (0.1 g, 1 eq) in POC13 (3 mL) was heated at 110C for 18 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was slowly basified to pH 8 using saturated sodium bicarbonate solution and extracted with ethyl acetate (2 X 25 mL). Combined organic extracts were washed with brine and dried over anhydrous sodium sulfate and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel 100-200 mesh using 50% EtOAc-hexane to afford the title compound 3. LCMS (mlz): 244.95 (M + 1).

Reference： [1]Patent: WO2016/57834,2016,A1 .Location in patent: Paragraph 000822

18
[ 305790-48-1 ]
C₁₂H₁₄BrN₃ [ No CAS ]

Reference： [1]Patent: WO2016/57834,2016,A1

19
[ 75-03-6 ]
[ 305790-48-1 ]
5-bromo-1-ethyl-3-methyl-benzimidazol-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%		To a solution of <strong>[305790-48-1]5-bromo-3-methyl-1H-benzimidazol-2-one</strong> (30 mg,0.132 mmol)in DMF (1.2 mL)was added NaH (60% in mineral oil,11.6 mg,0.291 mmol). The resultingmixture was stirred at room temperature for 10 min,and then iodoethane (21.1 J.L,0.26 mmol)was added. The reaction mixture was stirred for an additional 4 h,and then water (20 mL)wasadded and the mixture was extracted with EtOAc (20 mL x 3). The combined organic layerswere washed with brine (20 mL),dried over anhydrous Na2S04 and then concentrated in under reduced pressure. The crude residue was purified by reverse phase preparative HPLC(acetonitrile 20-60% I 0.1 %ammonium hydroxide in water)to give the title compound (20.0mg,59%). 1HNMR (400 MHz,DMSO-d6)8 1HNMR (400 MHz,DMSO-d6)8 7.44-7.39 (m,1H),7.22 (dd,J = 8.3,1.9 Hz,1H),7.16 (dd,J = 8.3,0.4 Hz,1H),3.86 (q,J = 7.2 Hz,2H),3.32 (s,3H),1.18 (t,J= 7.2 Hz,3H). LCMS MIZ (M+H)255.

Reference： [1]Patent: WO2017/205536,2017,A2 .Location in patent: Page/Page column 90

20
[ 32315-10-9 ]
[ 93933-49-4 ]
[ 305790-48-1 ]

Yield	Reaction Conditions	Operation in experiment
24%		To a solution of2-amino-4-bromobenzenethiol (500 mg,2.50 mmol)in acetic acid (25mL)was added triphosgene (490 mg,1.70 mmol). The mixture was heated at reflux for 18 h.After cooling to room temperature,the solution was partially concentrated under reducedpressure,water was added,and the resulting precipitate was removed via filtration,and washedwith aqueous NaOH (1M). The filtrate was acidified with aqueous HCl (2 N)to pH 2,and placed in a refrigerator for 12 h. The resulting precipitate was filtered,washed with water,anddried under reduced pressure to give the title compound (133 mg,24%)as a while powder thatrequired no further purification. 1H NMR (400 MHz,DMSO-d6)8 10.97 (s,1H),7.33 (d,J = 1.9Hz,1H),7.13 (dd,J = 8.2,1.9 Hz,1H),6.91 (d,J = 8.2 Hz,1H),3.26 (s,3H)

Reference： [1]Patent: WO2017/205536,2017,A2 .Location in patent: Page/Page column 89

21
[ 305790-48-1 ]
tert-butyl N-[2-[2-([3-[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-5-yl]prop-2-yn-1-yl]oxy)ethoxy]ethyl]carbamate [ No CAS ]

Reference： [1]Patent: WO2019/60742,2019,A1
[2]Patent: US2019/192668,2019,A1

22
[ 305790-48-1 ]
tert-butyl N-[2-(2-[3-[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-5-yl]propoxy]ethoxy)ethyl]carbamate [ No CAS ]

Reference： [1]Patent: WO2019/60742,2019,A1
[2]Patent: US2019/192668,2019,A1

23
[ 305790-48-1 ]
3-(5-(3-(2-(2-aminoethoxy)ethoxy)propyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione trifluoroacetate [ No CAS ]

Reference： [1]Patent: WO2019/60742,2019,A1

24
[ 305790-48-1 ]
2-((S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-N-(2-(2-(3-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)propoxy)ethoxy)ethyl)acetamide [ No CAS ]

Reference： [1]Patent: WO2019/60742,2019,A1

25
3-bromo-1-[(4-methoxyphenyl)methyl]piperidine-2,6-dione [ No CAS ]
[ 305790-48-1 ]
3-(5-bromo-3-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)-1-[(4-methoxyphenyl)methyl]piperidine-2,6-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%		A stirred solution of <strong>[305790-48-1]6-bromo-1-methyl-2,3-dihydro-1H-1,3-benzodiazol-2-one</strong> (8.27 g, 36.42 mmol) in THF (180 mL) was treated with t-BuOK (5.70 g, 50.99 mmol) at 0 oC for 1 h under nitrogen atmosphere followed by the addition of 3-bromo-1-[(4- methoxyphenyl)methyl]piperidine-2,6-dione (11.4 g, 36.42 mmol). The resulting mixture was stirred for 16 h at room temperature under nitrogen atmosphere. The reaction was quenched with sat. NH4Cl (200 mL) at 0 oC. The resulting mixture was extracted with EtOAc (2 x 300 mL). The combined organic layers was washed with brine (200 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with 50% ethyl acetate in dichloromethane to afford 3-(5- bromo-3-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)-1-[(4- methoxyphenyl)methyl]piperidine-2,6-dione (8 g, 48%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) d 7.48 (d, J = 1.8 Hz, 1H), 7.29-7.08 (m, 3H), 7.01 (d, J = 8.0 Hz, 1H), 6.86 (d, J = 8.5 Hz, 2H), 5.54 (dd, J = 13.0, 5.3 Hz, 1H), 4.79 (q, J = 14.3 Hz, 2H), 3.73 (s, 3H), 3.35 (s, 3H), 3.12-2.98 (m, 1H), 2.86-2.66 (m, 2H), 2.12-2.02 (m, 1H). LC/MS (ESI, m/z): [(M + 1)]+ = 458.06, 460.06.
45.8%		6-Bromo-l-methyl-l,3-dihydro-2H-benzo[d]imidazol-2-one (4.0 g, 17.7 mmol) was dissolved in THF, the mixture was cooled to 0 C. t-BuOK (2.38 g, 21.2 mmol) was added to the mixture, the mixture was stirred about at 0 C for 30 min, 3-bromo-l-(4- methoxybenzyl)piperidine-2,6-dione (8.26 g, 26.5 mmol) was added, the mixture was stirred at room temperature overnight. The solvent was evaporated, the crude was purified by column chromatography on silica gel (EtOAc : DCM = 1 : 1) to give 3-(5-bromo-3-methyl-2-oxo-2,3- dihydro-lH-benzo[d]imidazol-l-yl)-l-(4-methoxybenzyl)piperidine-2,6-dione (3.7 g, yield: 45.8%) as a yellow solid. MR (400 MHz, CDCb) delta 7.37-7.34 (m, 2 H), 7.14 (d, J= 2.1 Hz 1 H), 7.06 (dd, J= 8.2, 1.8 Hz, 1 H) ,6.84-6.81 (m, 2 H), 6.34 (d, J= 8.4 Hz , 1 H), 5.18 (dd, J= 13.3, 5.5 Hz , 1 H), 4.96 (s, 2 H), 3.80 (s, 3 H), 3.41 (s, 3 H), 3.01 (ddd, J= 17.5, 4.4, 2.6 Hz, 1 H), 2.87- 2.78 (m, 1 H), 2.56 (ddd, J = 26.8, 13.4, 4.5 Hz, 1 H), 2.20-2.14 (m, 1 H); LC/MS (ESI, m/z): [M+l]+ = 458.3.
37%		To a solution of <strong>[305790-48-1]6-bromo-1-methyl-1H-benzo[d]imidazol-2(3H)-one</strong> (5.0 g, 22.1 mmol) in THF was added t-BuOK (2.48 g, 22.1 mmol) at 0 C. The mixture was stirred at at 0 C for 30 min, then 3-bromo-1-(4-methoxybenzyl) piperidine-2,6-dione(6.9 g, 22.1 mmol) was added and the reaction mixture was stirred at room temperature overnight. Then the mixture was concentrated and the residue was purified by column chromatography on silica gel (EtOAc : DCM = 1 : 1) to give the product 3-(5-bromo-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)- 1-(4-methoxybenzyl)piperidine-2,6-dione (3.7 g, yield 37 %). NMR (400 MHz, DMSO-d6) delta 7.48-7.47 (d, J = 2.0 Hz, 1H), 7.21-7.16 (m, 3H), 7.02-6.99 (d, J = 8.4 Hz, 1H), 6.87-6.84 (m, 2H), 5.55-5.51 (dd, Ji = 6.4 Hz, J2= 14.2 Hz, 1H), 4.84-4.73 (q, J= 14.4 Hz, 2H), 3.72 (s, 3H), 3.34 (s, 3H), 3.08-3.00 (m, 1H), 2.84-2.67 (m, 2H), 2.09-2.04 (m , 1H). LC-MS (ESI+): m/z 459.4 (M+H)+.

Reference： [1]Patent: WO2020/10210,2020,A1 .Location in patent: Paragraph 00695
[2]Patent: WO2019/60693,2019,A1 .Location in patent: Paragraph 00307-00308
[3]Patent: WO2019/60742,2019,A1 .Location in patent: Paragraph 00374; 00381; 003823

26
[ 305790-48-1 ]
3-(3-methyl-5-(3-methyl-1H-pyrazol-5-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

27
[ 305790-48-1 ]
3-(3-methyl-5-(2-methyl-1H-imidazol-5-yl)-2-oxo-2.3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

28
[ 305790-48-1 ]
3-(3-methyl-2-oxo-5-((trimethylsilyl)ethynyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

29
[ 305790-48-1 ]
3-(5-ethynyl-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

30
[ 305790-48-1 ]
tert-butyl (2-(2-(2-(2-(4-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)ethyl)carbamate [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

31
[ 305790-48-1 ]
tert-butyl (15-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-3,6,9,12-tetraoxapentadec-14-yn-1-yl)carbamate [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

32
[ 305790-48-1 ]
tert-butyl (15-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-3,6,9,12-tetraoxapentadecyl)carbamate [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

33
[ 305790-48-1 ]
1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

34
[ 305790-48-1 ]
1-(1-(4-methoxybenzyl)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

35
[ 305790-48-1 ]
3-(5-(aminomethyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)-1-(4-methoxybenzyl)piperidine-2,6-dione hydrochloride [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

36
[ 305790-48-1 ]
3-(3,5-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

37
[ 305790-48-1 ]
1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1
[2]Patent: US2019/192668,2019,A1

38
[ 305790-48-1 ]
3-(5-bromo-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1
[2]Patent: US2019/192668,2019,A1
[3]Patent: WO2020/10210,2020,A1

39
[ 305790-48-1 ]
3-(5-(aminomethyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione acetate [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

40
[ 305790-48-1 ]
N-((1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)methyl)acetamide [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

41
[ 305790-48-1 ]
methyl 1-(1-(4-methoxybenzyl)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carboxylate [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

42
[ 305790-48-1 ]
1-(1-(4-methoxybenzyl)-2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

43
[ 305790-48-1 ]
1-(1-(4-methoxybenzyl)-2,6-dioxopiperidin-3-yl)-N,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

44
[ 305790-48-1 ]
1-(2,6-dioxopiperidin-3-yl)-N,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

45
[ 305790-48-1 ]
1-((1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)methyl)-3-ethylurea [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

46
[ 305790-48-1 ]
1-((1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)methyl)urea [ No CAS ]

Reference： [1]Patent: WO2019/60693,2019,A1

47
[ 67-56-1 ]
[ 201230-82-2 ]
[ 305790-48-1 ]
[ 1301214-75-4 ]

Yield	Reaction Conditions	Operation in experiment
76.9%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine; In N,N-dimethyl-formamide; at 130℃; under 3040.2 Torr; for 17h;	A mixture of 6-bromo-l-methyl-l,3-dihydro-2H-benzo[d]imidazol-2-one (10.0 g, 44.2 mmol), l, -Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (3.6 g, 4.42 mmol), TEA (9.0 g, 88.5 mmol) in MeOH (200 mL) and DMF (10 mL) was sparged with carbon monoxide for about 10 min, placed under 4 atm carbon monoxide atmosphere, and heated to 130 C for 17 hours. The reaction mixture was cooled down to room temperature, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (PE: EA = 2: 1 ) to give product (7.0 g, 76.9%) as a yellow solid. NMR (400 MHz, DMSO-d6) S 1 1.27 (s, 1 H), 7.77 - 7.53 (m, 2 H), 7.07 (d, J = 8.1 Hz, 1 H), 3.84 (s, 3 H), 3.33 (s, 3 H); LC/MS (ESI, m/z): [M +1]+ = 207.1.

Reference： [1]Patent: WO2019/60693,2019,A1 .Location in patent: Paragraph 00346-00347

48
[ 6482-24-2 ]
[ 305790-48-1 ]
5-bromo-1-(2-methoxyethyl)-3-methylbenzoimidazol-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2h;	General procedure: Step 8-4. 5-Bromo-1-[(3R)-oxolan-3-yl]indazole (Compound 80 To a DMF (3.8 mL) solution of 5-bromo-1H-indazole (Compound 6j, 300 mg, 1.52 mmol) was added cesium carbonate (992 mg, 3.05 mmol) and Compound 8e (369 mg, 1.52 mmol) obtained in Step 8-3, and the mixture was stirred at 100 C. for 2 h. After cooling to room temperature, water was added to the reaction solution and extraction was performed using ethyl acetate. The organic layer was washed with water, and the solvent was removed by evaporation under reduced pressure. The resulting product was purified by silica gel column chromatography (ethyl acetate/hexane=1:1) to obtain the titled Compound 8f (198 mg, yield 49%) as a colorless oil-like product. LC/MS mass spectrometry: m/z 267 ([M+H]+).

Reference： [1]Patent: US2019/225604,2019,A1 .Location in patent: Paragraph 0410; 0414-0417; 0548-0551

49
[ 57260-71-6 ]
[ 305790-48-1 ]
tert-butyl 4-(3-methyl-2-oxo-1H-benzimidazol-5-yl)piperazine-1-carboxylate [ No CAS ]