[ CAS No. 23735-43-5 ] {[proInfo.proName]}

Name: 23735-43-5|(S)-(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate|95%
Brand: Ambeed
SKU: A185550
Price: 21.0 USD
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Quality Control of [ 23735-43-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 23735-43-5 ]

Product Details of [ 23735-43-5 ]

CAS No. :	23735-43-5	MDL No. :	MFCD00063234
Formula :	C₁₃H₁₈O₅S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SRKDUHUULIWXFT-NSHDSACASA-N
M.W :	286.34	Pubchem ID :	2723760
Synonyms :

Calculated chemistry of [ 23735-43-5 ]

Physicochemical Properties

Num. heavy atoms :	19
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.54
Num. rotatable bonds :	4
Num. H-bond acceptors :	5.0
Num. H-bond donors :	0.0
Molar Refractivity :	69.72
TPSA :	70.21 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.75 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.92
Log Po/w (XLOGP3) :	1.83
Log Po/w (WLOGP) :	2.93
Log Po/w (MLOGP) :	1.58
Log Po/w (SILICOS-IT) :	1.86
Consensus Log Po/w :	2.22

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.74
Solubility :	0.524 mg/ml ; 0.00183 mol/l
Class :	Soluble
Log S (Ali) :	-2.92
Solubility :	0.341 mg/ml ; 0.00119 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.69
Solubility :	0.0579 mg/ml ; 0.000202 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	3.81

Safety of [ 23735-43-5 ]

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 [ 23735-43-5 ]

* 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 [ 23735-43-5 ]
Downstream synthetic route of [ 23735-43-5 ]

[ 23735-43-5 ] Synthesis Path-Upstream 1~12

1
[ 98-59-9 ]
[ 14347-78-5 ]
[ 23735-43-5 ]

Yield	Reaction Conditions	Operation in experiment
98%	at 0 - 20℃;	According to the procedure described for the preparation of (R)-(−)-20a, (R)-(−)-2,2-dimethyl-4-(hydroxymethyl)-1,3-dioxolane (19b) (2.50 g, 18.7 mmol) afforded the right-hand (S)-(+)-3-tosyloxy-1,2-propanediol acetonide 20b (5.23 g, 98percent yield, 99.2percent ee). [α]_D²⁰ +4.5 (c 1.0, EtOH) (lit. [α]_D²⁵ +4.7 (c 1.0, EtOH)).²⁶ The characterization data from IR, NMR and HRMS spectra were identical in all aspects with those of (R)-(−)-20a enantiomer.
87%	With dmap; triethylamine In dichloromethane at 0 - 20℃;	To a solution of(R)-2,2-Dimethyl-1,3-dioxolane-4-methanol 9a (5 g, 37.8 mmol), Et3N (10.5 mL, 75.6 mmol) and DMAP (462 mg, 3.78 mmol) in DCM (20 mL) at 0 °C, was slowly added a solution of p-toluenesulfonic chloride (TsC1) (10.8 g, 56.7 mmol) in DCM. The reaction mixture was warmed to room temperature and stirred overnight. After diluting with water, the reaction mixture was extracted with DCM. The combined organic layers was dried over Na2SO4, filtered, and concentrated. The crude produce was purified by column chromatography on silica gel (eluent: hexanes/EtOAc = 5/1) to give product lOa (9.39 g, 87percent) as colorless liquid. ‘H NMR (400 MHz, CDC13) 7.82 (d, J= 8.4 Hz, 2H), 7.40 (d, J= 8.4 Hz, 2H), 4.30 (tt, J 6.0, 5.1 Hz, 1H), 4.12 —3.91 (m, 3H), 3.79 (ddd, J= 8.8, 5.1, 0.7 Hz, 1H), 2.47 (s, 3H), 1.36 (s, 3H), 1.33 (s, 3H).
84%	at 0℃; for 7 h;	To a solution of (R)-(2,2-dimethyl-l,3-dioxolan-4-yl)methanol LIV (23.1 g, 0.175 mol) in pyridine (150 mL) at 0°C was added tosyl chloride (44.5 g, 0.23 mol) in portions. The mixture was stirred for 7 h at 0°C and was placed in a refrigerator for 18 h. Et₂0 (150 mL) was added and the mixture was washed with 1 N aqueous HC1 (5 x 150 mL). The organic layer was washed with aqueous NaHCCh (150 mL) and water (150 mL). The organic phase was dried over Na₂S04, filtered, concentrated and dried under vacuum. The crude product was purified by column chromatography on silica gel (1 : 1 Et₂0:hexane) to afford (S)-(2,2-dimethyl-l,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate LV (42.1 g, 0.15 mol, 84percent).

Reference： [1] Chemical and Pharmaceutical Bulletin, 1995, vol. 43, # 10, p. 1719 - 1723
[2] Journal of Medicinal Chemistry, 2010, vol. 53, # 8, p. 3198 - 3213
[3] Tetrahedron, 2013, vol. 69, # 5, p. 1634 - 1648
[4] Journal of the American Chemical Society, 1980, vol. 102, # 20, p. 6304 - 6311
[5] Journal of the Chemical Society, Chemical Communications, 1984, # 6, p. 349 - 350
[6] Magnetic Resonance in Chemistry, 1998, vol. 36, # 1, p. 64 - 68
[7] Patent: WO2016/94570, 2016, A1, . Location in patent: Paragraph 00471
[8] Patent: WO2011/143497, 2011, A1, . Location in patent: Page/Page column 50
[9] Tetrahedron: Asymmetry, 1995, vol. 6, # 5, p. 1181 - 1190
[10] European Journal of Organic Chemistry, 2006, # 21, p. 4805 - 4812
[11] Journal of Medicinal Chemistry, 1992, vol. 35, # 23, p. 4415 - 4424
[12] Patent: US5182296, 1993, A,
[13] Chemistry and Biology, 2009, vol. 16, # 1, p. 82 - 92
[14] Patent: US6335366, 2002, B2, . Location in patent: Referential example 6(1)
[15] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 24, p. 6915 - 6919
[16] Journal of Medicinal Chemistry, 2016, vol. 59, # 8, p. 3635 - 3649

2
[ 22323-82-6 ]
[ 98-59-9 ]
[ 23735-43-5 ]

Reference： [1] Journal of Heterocyclic Chemistry, 2004, vol. 41, # 3, p. 311 - 316
[2] Chemical and Pharmaceutical Bulletin, 1991, vol. 39, # 3, p. 607 - 611
[3] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 5, p. 963 - 968

3
[ 15042-01-0 ]
[ 23735-43-5 ]

Reference： [1] Tetrahedron: Asymmetry, 1995, vol. 6, # 5, p. 1181 - 1190
[2] Tetrahedron: Asymmetry, 1995, vol. 6, # 5, p. 1181 - 1190
[3] Journal of the American Chemical Society, 1980, vol. 102, # 20, p. 6304 - 6311

4
[ 22323-80-4 ]
[ 23735-43-5 ]

Reference： [1] Tetrahedron: Asymmetry, 1995, vol. 6, # 5, p. 1181 - 1190
[2] Journal of the American Chemical Society, 1980, vol. 102, # 20, p. 6304 - 6311

5
[ 4306-35-8 ]
[ 23735-43-5 ]

Reference： [1] Journal of the American Chemical Society, 1980, vol. 102, # 20, p. 6304 - 6311

6
[ 50765-70-3 ]
[ 77-76-9 ]
[ 23735-43-5 ]

Reference： [1] Collection of Czechoslovak Chemical Communications, 1993, vol. 58, # 7, p. 1645 - 1667

7
[ 50765-70-3 ]
[ 67-64-1 ]
[ 23735-43-5 ]

Reference： [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 18, p. 2395 - 2398

8
[ 40519-00-4 ]
[ 23735-43-5 ]

Reference： [1] Collection of Czechoslovak Chemical Communications, 1993, vol. 58, # 7, p. 1645 - 1667

9
[ 119970-97-7 ]
[ 23735-43-5 ]

Reference： [1] Collection of Czechoslovak Chemical Communications, 1993, vol. 58, # 7, p. 1645 - 1667

10
[ 51704-66-6 ]
[ 23735-43-5 ]

Reference： [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 18, p. 2395 - 2398

11
[ 141656-36-2 ]
[ 23735-43-5 ]

Reference： [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 18, p. 2395 - 2398

12
[ 141656-30-6 ]
[ 23735-43-5 ]

Reference： [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 18, p. 2395 - 2398

[ 23735-43-5 ] Synthesis Path-Downstream 1~88

2
[ 67795-40-8 ]
[ 23735-43-5 ]
[ 912576-59-1 ]

Reference： [1]Nucleosides, nucleotides and nucleic acids,2005,vol. 24,p. 1265 - 1276

3
[ 55023-35-3 ]
[ 23735-43-5 ]
4-[[(S)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]-7,9-dimethylpyrido[3',2':4,5]thieno[3,2-d]pyrimidine [ No CAS ]
[ 912576-60-4 ]

Reference： [1]Nucleosides, nucleotides and nucleic acids,2005,vol. 24,p. 1265 - 1276

4
[ 249937-13-1 ]
[ 23735-43-5 ]
[ 1044590-54-6 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1562 - 1575
[2]Organic and Biomolecular Chemistry,2016,vol. 14,p. 947 - 956

5
[ 23735-43-5 ]
[ 10387-40-3 ]
[ 120200-02-4 ]

Reference： [1]European Journal of Organic Chemistry,2006,p. 4805 - 4812

6
4-[6-(3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-N-[(3R)-piperidin-3-yl]pyrimidin-2-amine trishydrochloride [ No CAS ]
[ 23735-43-5 ]
N-((3R)-1-([(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl)piperidin-3-yl)-4-[6-(3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]pyrimidin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With tetra-(n-butyl)ammonium iodide; potassium carbonate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 130℃; for 5h;	Example 9: Preparation of (2R)-3-r(3RV3-((4-[6-f3-hvdroxyphenyl)imidazof2,l- bl [ 1 ,31thiazol-5-yl")pyrimidin-2-vU amino)piperidin- 1 -ylipropane- 1 ,2-diol9a: Preparation of N-((3lambda)-l-[(4i?)-2s2-dimethyl-l,3-dioxolan-4-yl]methyl}piperidin-3- yl)-4-[6-(3-methoxyphenyl)imidazo[2,l-b][l,3]thiazol-5-yl]pyrimidin-2-amineThe 4-[6-(3-methoxyphenyl)imidazo[2,l-b][l,3]thiazol-5-yl]-N-[(5i?)-piperidin-3- yl]-pyrimidin~2-arnine hydrochloride (310 mg, 0.7 mmol) was dissolved in DMF (15 ml) and was treated successively with Hunig's base (240 uL, 1.4 mmol), potassium carbonate (192 mg, 0.7 mmol) and terabutylammonium iodide (26 mg, 0.07 mmol). The mixture was <n="64"/>heated to 13O0C and the [(4S)-2,2-dimethyl-l,3-dioxolan-4-yl]rnethyl 4-tnethyl- benzenesulfonate (0.2 g, 0.7 mmol) was added in three portions. The mixture was kept at 13O0C for 5 hours, at which point no more starting material appears by HPLC. The volatiles were removed in vacuo and the residue was taken up in ether (100 ml). The organic phase was washed with water (2 X 20 ml) and with an aqueous sodium chloride solution (20 ml). The organic phase was dried over sodium sulfate and concentrated in vacuo, giving a yellow oil. The product was purified by flash chromatography (5:4:0.5 hexanes / EtOAc3 MeOH), affording the title compound as an off-white solid (231 mg, 64%). M.p. = 73-75 C.400 MHz 1H NMR (DMSO-d6) delta: 8.71 (br. s, IH), 8.07 (d, J= 5.1 Hz, IH), 7.42 (d, J= 4.4 Hz, IH), 7.36 (t, J = 7.9 Hz, IH), 7.19-7.11 (m, 2H), 7.04-6.92 (m, 2H), 6.36 (d, J= 5.1 Hz, IH), 4.19 (quintet, J= 6.2 Hz, IH), 3.99 (dd, J= 8.1, 6.2 Hz, IH), 3.96-3.87 (m, IH), 3.77 (s, 3H), 3.52 (t, J= 7.5 Hz* IH), 3.15 (beta, 2H), 3.05 (d, J= 9.9 Hz, IH), 2.69 (d, J= 10.3 Hz, IH), 2.15 (t, J= 9.4 Hz, IH), 2.04 (t, J= 9.5 Hz, IH), 1.90- 1.82 (m, IH), 1.75-1.65 (m, IH), 1.59-1.48 (m, IH), 1.40-1.25 (m, IH), 1.29 (s, 3H), 1.21 (s, 3H). LCMS: 521 [M+H].

Reference： [1]Patent: WO2007/123892,2007,A2 .Location in patent: Page/Page column 61-62

7
[ 1003567-09-6 ]
[ 23735-43-5 ]
5-chloro-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}-4-[4-methoxybenzyl]oxy-N-methylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95.6%	With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 3h;	Step 4: 5-Chloro-2[(4R)-2,2-dimethyl-l,3-dioxolan-4-yl]methoxy}-4-[(4- methoxybenzylJoxy-N-methybenzamide; A slurry of 5-chloro-2-hydroxy-4-[(4-methoxybenzyl)oxy]-N-methylbenzamide (3.2 g), D- alpha,beta-isoprpylidenglycerol-gamma-tosylate (2.9 g) and cesium carbonate (3.6 g) in DMF (10 ml) was heated to 100 0C for 3 h. The mixture was extracted between ethyl acetate (200 ml) and water (100 ml). The organic layer was washed 3 times with water (100 ml), dried and removed in vacuo yielding 4.2 g (95.6 %) of the subtitled compound as a white solid. 1H-NMR (acetone-d6, 400 MHz): delta 8.11 (s, IH), 7.45 (d, J=8.9, 2H), 7.01 (s, IH), 6.97 (d, J=8.8, 2H)5 5.23 (s, 2H), 4.66-4.60 (m, IH)5 4.64-4.43 (m, IH)5 4.24-4.01 (m, 3H)5 3.81 (s5 3H)5 2.87 (d, J=4.6, 3H)5 1.44 (s, 3H)5 1.36 (s5 3H); APCI-MS: m/z 436 (MH+).

Reference： [1]Patent: WO2008/10765,2008,A1 .Location in patent: Page/Page column 62

8
[ 23735-43-5 ]
1,3-bis[(4S)-2,2-dimethyl-1,3-dioxolan-4-ylmethylthio]propanone O-benzyloxime [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2006,p. 4805 - 4812

9
[ 23735-43-5 ]
[ 120200-00-2 ]

Reference： [1]European Journal of Organic Chemistry,2006,p. 4805 - 4812
[2]Journal of Heterocyclic Chemistry,1997,vol. 34,p. 909 - 915

10
[ 23735-43-5 ]
[ 143393-27-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1457 - 1461
[2]Journal of Medicinal Chemistry,1993,vol. 36,p. 2235 - 2237

11
[ 23735-43-5 ]
(2R,4S)-trans-2-(2-(4-chlorophenyl)ethyl)-2-(imidazol-1-yl)methyl-4-(4-aminophenylthio)methyl-1,3-dioxolane [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1457 - 1461
[2]Journal of Medicinal Chemistry,1993,vol. 36,p. 2235 - 2237

12
[ 23735-43-5 ]
(+/-)-cis-2-(2-(4-chlorophenyl)ethyl)-2-(imidazol-1-yl)methyl-4-(3-aminophenylthio)methyl-1,3-dioxolane [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1457 - 1461

13
[ 23735-43-5 ]
3-{(2R,4S)-2-[2-(4-Chloro-phenyl)-ethyl]-2-imidazol-1-ylmethyl-[1,3]dioxolan-4-ylmethylsulfanyl}-phenylamine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1457 - 1461

14
[ 23735-43-5 ]
2-{(2S,4S)-2-[2-(4-Chloro-phenyl)-ethyl]-2-imidazol-1-ylmethyl-[1,3]dioxolan-4-ylmethylsulfanyl}-phenylamine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1457 - 1461

15
[ 23735-43-5 ]
2-{(2R,4S)-2-[2-(4-Chloro-phenyl)-ethyl]-2-imidazol-1-ylmethyl-[1,3]dioxolan-4-ylmethylsulfanyl}-phenylamine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1457 - 1461

16
[ 23735-43-5 ]
[ 499136-63-9 ]

Reference： [1]Angewandte Chemie - International Edition,2003,vol. 42,p. 208 - 211

17
[ 23735-43-5 ]
Toluene-4-sulfonic acid (S)-8-tert-butyl-1,4-dioxa-spiro[4.5]dec-2-ylmethyl ester [ No CAS ]

Reference： [1]Magnetic Resonance in Chemistry,1998,vol. 36,p. 64 - 68

18
(R)-1-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl)-butane-1,2,3,4-tetraol [ No CAS ]
[ 23735-43-5 ]

Reference： [1]Tetrahedron Asymmetry,1995,vol. 6,p. 1181 - 1190

19
Sodium; (R)-4-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-2,3,4-trihydroxy-butyrate [ No CAS ]
[ 23735-43-5 ]

Reference： [1]Tetrahedron Asymmetry,1995,vol. 6,p. 1181 - 1190

20
[ 22323-80-4 ]
[ 23735-43-5 ]

Reference： [1]Tetrahedron Asymmetry,1995,vol. 6,p. 1181 - 1190
[2]Journal of the American Chemical Society,1980,vol. 102,p. 6304 - 6311

21
[ 15042-01-0 ]
[ 23735-43-5 ]

Reference： [1]Tetrahedron Asymmetry,1995,vol. 6,p. 1181 - 1190
[2]Tetrahedron Asymmetry,1995,vol. 6,p. 1181 - 1190
[3]Journal of the American Chemical Society,1980,vol. 102,p. 6304 - 6311

22
[ 23735-43-5 ]
[ 22195-47-7 ]

Reference： [1]Tetrahedron Asymmetry,1995,vol. 6,p. 1181 - 1190

23
[ 23735-43-5 ]
[ 168427-92-7 ]

Reference： [1]Helvetica Chimica Acta,1995,vol. 78,p. 486 - 504

24
[ 23735-43-5 ]
1-[(2R,3R,4R,5R)-4-(2,4-Dichloro-benzyloxy)-5-(2,4-dichloro-benzyloxymethyl)-3-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-tetrahydro-furan-2-yl]-3-hydroxymethyl-5-methyl-1H-pyrimidine-2,4-dione [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1995,vol. 78,p. 486 - 504

25
[ 23735-43-5 ]
1-[(2R,3R,4R,5R)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-3-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-4-hydroxy-tetrahydro-furan-2-yl]-5-methyl-1H-pyrimidine-2,4-dione [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1995,vol. 78,p. 486 - 504

26
[ 23735-43-5 ]
Diisopropyl-phosphoramidous acid (2R,3R,4R,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 2-cyano-ethyl ester [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1995,vol. 78,p. 486 - 504

27
[ 23735-43-5 ]
[ 168428-01-1 ]

Reference： [1]Helvetica Chimica Acta,1995,vol. 78,p. 486 - 504

28
[ 23735-43-5 ]
[ 91575-89-2 ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1984,p. 349 - 350

29
[ 40519-00-4 ]
[ 23735-43-5 ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1993,vol. 58,p. 1645 - 1667

30
[ 119970-97-7 ]
[ 23735-43-5 ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1993,vol. 58,p. 1645 - 1667

31
[ 23735-43-5 ]
[ 144042-74-0 ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 4415 - 4424

32
[ 51704-66-6 ]
[ 23735-43-5 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1992,p. 2395 - 2398

33
[ 141656-36-2 ]
[ 23735-43-5 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1992,p. 2395 - 2398

34
[ 141656-30-6 ]
[ 23735-43-5 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1992,p. 2395 - 2398

35
[ 23735-43-5 ]
[ 144256-12-2 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1992,vol. 40,p. 1462 - 1469

36
[ 23735-43-5 ]
[ 133242-30-5 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1992,vol. 40,p. 1462 - 1469

37
[ 4306-35-8 ]
[ 23735-43-5 ]

Reference： [1]Journal of the American Chemical Society,1980,vol. 102,p. 6304 - 6311

38
[ 23735-43-5 ]
[ 126455-77-4 ]

Reference： [1]Tetrahedron Letters,1991,vol. 32,p. 2821 - 2824

39
[ 23735-43-5 ]
[ 135304-59-5 ]

Reference： [1]Tetrahedron Letters,1991,vol. 32,p. 2821 - 2824

40
[ 23735-43-5 ]
[ 135304-60-8 ]

Reference： [1]Tetrahedron Letters,1991,vol. 32,p. 2821 - 2824

41
[ 865235-92-3 ]
[ 23735-43-5 ]
1-(4-{1-[4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyloxy)-3-methyl-phenyl]-1-ethyl-propyl}-2-methyl-phenyl)-3-ethyl-pentyl-1-yn-3-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With sodium hydroxide; In DMF (N,N-dimethyl-formamide); at 60℃; for 11h;	To a solution of 4- {1-ethyl-1- [4- (3-ethyl-3-hydroxy-pent-1-ynyl)-3-methyl- phenyl]-propyl}-2-methyl-phenol (compound prepared in Example 1- (4)) (250 mg, 0.660 mmol) in anhydrous DMF (6.6 ml) were added NaOH (40 mg, 0.99 mmol) and toluene-4-sulfonic acid (S)-2, 2-dimethyl- [1, 3] dioxolan-4- ylmethyl ester (214 mg, 0.792 mmol) and the mixture was stirred at 60 degrees C for 11 h. The mixture was poured into saturated NH4CI aq. and the products were extracted with EtOAc. The extacts were washed with brine, dried over MgS04, filtered and concentrated under reduced pressure. The obtained residue was purified by Silica gel chromatography (EtOAc: n- Hexane=1: 10) to give the title compound (177 mg, 56%) as a white solid. 1H-NMR (300MHz, CDCl3) : 0.59 (t, 6H), 1.11 (t, 6H), 1.40 (s, 3H), 1.46 (s, 3H), 1.70-1. 83 (m, 4H), 2.04 (q, 4H), 2.14 (s, 3H), 2.37 (s, 3H), 3.89-3. 99 (m, 2H), 4.04-4. 19 (m, 3H), 4.42-4. 50 (m, 1H), 6.68 (d, 1H), 6.84 (s, 1H), 6.90 (d, 2H), 6.99 (s, 1 H), 7.27 (d, 1 H).

Reference： [1]Patent: WO2005/87700,2005,A2 .Location in patent: Page/Page column 227-228

42
[ 865235-93-4 ]
[ 23735-43-5 ]
(E)-1-(4-{1-[4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyloxy)-3-methyl-phenyl]-1-ethyl-propyl}-2-methyl-phenyl)-3-ethyl-pentyl-1-en-3-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 100℃; for 14h;	To a solution of 4-{1-ethyl-1- [4- ( (E)-3-ethyl-3-hydroxy-pent-1-enyl)-3- methyl-phenyl]-propyl}-2-methyl-phenol (compound prepared in Example 1- (5) ) (150 mg, 0.394 mmol) in anhydrous DMF (6.6 ml) were added K2CO3 (136 mg, 0.985 mmol) and toluene-4-sulfonic acid (S)-2, 2-dimethyl- [1,3] dioxolan-4-ylmethyl ester (169 mg, 0.591 mmol) and the mixture was stirred at 100 degrees C for 14 h. The mixture was poured into saturated NH4CI aq. and the products were extracted with EtOAc. The extacts were washed with brine, dried over MgS04, filtered and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (EtOAc: n-Hexane=1: 7) to give the title compound (170 mg, 88%). 'H-NMR (300MHz, CDCl3) : 0.61 (t, 6H), 0.92 (t, 6H), 1.40 (s, 3H), 1.46 (s, 3H), 1.63 (q, 4H), 2.04 (q, 4H), 2.16 (s, 3H), 2.31 (s, 3H), 3. 89-4. 16 (m, 4H), 4.48 (m, 1 H), 6.00 (d, 1 H), 6.68 (d, 1 H), 6.74 (s, 1 H), 6.91-6. 97 (m, 4H), 7.29 (d, 1H).

Reference： [1]Patent: WO2005/87700,2005,A2 .Location in patent: Page/Page column 229

43
[ 865236-23-3 ]
[ 23735-43-5 ]
C₂₉H₄₀O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 100℃;	To a solution of 3- {4- [1-ethyl-1- (4-hydroxy-3-methyl-phenyl)-propyl]-2- methyl-phenyl}-propionic acid methyl ester (compound prepared in Example 18- (2)) (320 mg, 0.90 mmol) in anhydrous DMF (9 ml) at room temperature under nitrogen atmosphere were added K2CO3 (248 mg, 1.80 mmol) and (S)-toluene-4-sulfonic acid 2, 2-dimethyl- [1, 3] dioxolan-4-ylmethyl ester (309 mg, 1.08 mmol). After stirring overnight at 100 degrees C, the reaction mixture was diluted with ethyl acetate, washed with sat. NH4CI, water and brine, and dried over MgS04. The solution was concentrated under reduced pressure and the obtained residue was dissolved in methanol (9 ml). To the solution was added concentrated HCI with 4drops and the mixture was stirred at room temperature for 30 min. The mixture was concentrated under reduced pressure and the obtained residue was purified by silica-gel chromatography (hexane/EtOAc=7: 1) to give the title compound (187 mg, 0.43 mmol, 48%). 1H NMR (CDCI3) : 6.99-6. 83 (m, 5H), 6.69 (d, 1H), 4.10 (m, 1H), 4.03 (dd, 2H), 3.82 (m, 2H), 3.67 (s, 3H), 2.89 (dt, 2H), 2.57 (dt, 2H), 2.25 (s, 3H), 2.16 (s, 3H), 2.04 (q, 4H), 0.59 (t, 6H).

Reference： [1]Patent: WO2005/87700,2005,A2 .Location in patent: Page/Page column 230-231

44
[ 335318-13-3 ]
[ 23735-43-5 ]
C₂₅H₂₅ClN₄O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 16h;	Example 8 This example illustrates the preparation of 3-(2-chlorophenyl)-1-[(2S)-2,3-dihydroxyethyl]-7-isopropylamino-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one A mixture of 1.0 g (2.6 mmol) of 7-benzylthio-3-(2-chlorophenyl)-3,4-dihydro-pyrimido[4,5-d]pyrimidin-2(1H)-one, 1.5 g (5.2 mmol) L-alpha,beta-isopropylidene glycerol-gamma-tosylate and 1.44 g (10.4 mmol) of potassium carbonate was stirred in DMF (20 mL) and heated at 80 C. under nitrogen atmosphere. After 16 hours, the reaction mixture was cooled to room temperature, poured in to a brine solution, extracted with ethyl acetate and dried over sodium sulfate. The solution was concentrated under vacuum, purified by flash chromatography (eluding with 40% EtOAc/Hexane) to give 1.1 g of the isopropylidene ketal adduct as an oil. (mass spec. MH+=496).

Reference： [1]Patent: US6642241,2003,B1 .Location in patent: Page/Page column 15-16

45
[ 23735-43-5 ]
[ 23788-74-1 ]
[ 396090-71-4 ]

Yield	Reaction Conditions	Operation in experiment
		Following the procedure described above, but substituting (R)-2,2-dimethyl-1,3-dioxolan-4-ylmethyl p-tosylate with (S)-2,2-dimethyl-1,3-dioxolan-4-ylmethyl p-tosylate gave 3-(1 -methylindol-3-yl)-4-[3-((S)-2,2-dimethyl-1,3-dioxolan-4-ylmethyloxy)phenyl]- 1H-pyrrole-2,5-dione.

Reference： [1]Patent: US2002/52397,2002,A1

46
[ 23735-43-5 ]
4-(3'-chloro-4'-fluoroanilino)-6-[(4R)-2,2-dimethyl-1,3-dioxolan-4-ylmethoxy]-7-methoxyquinazoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%		EXAMPLE 6 Using an analogous procedure to that described in Example 1,4-(3'-chloro-4'-fluoroanilino)-6-hydroxy-7-methoxyquinazoline was reacted with (4S)-2,2-dimethyl-4-(4-toluenesulphonyloxymethyl)-1,3-dioxolane to give 4-(3'-chloro-4'-fluoroanilino)-6-[(4R)-2,2-dimethyl-1,3-dioxolan-4-ylmethoxy]-7-methoxyquinazoline in 57% yield; NMR Spectrum: 1.35 (s, 3H), 1.42 (s, 3H), 3.85 (m, 1H), 3.96 (s, 3H), 4.2 (m, 3H), 4.55 (m, 1H), 7.21 (s, 1H), 7.44 (t, 1H), 7.8 (m, 2H), 8.12 (m, 1H), 8.5 (s, 1H), Elemental Analysis: Found C, 58.1; H, 4.6; N, 9.5; C21 H21 ClFN3 O4 requires C, 58.1; H, 4.9; N, 9.7%.

Reference： [1]Patent: US5770603,1998,A

47
[ 312306-35-7 ]
[ 23735-43-5 ]
[ 952665-39-3 ]

Yield	Reaction Conditions	Operation in experiment
66%	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 44h;	To a stirred solution of (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (1.58 g, 5.50 mmol) in anhydrous DMF (10 mL) under nitrogen gas was added 2-tert-butyl-5-nitro-1H-indole (1.00 g, 4.58 mmol) followed by Cs2CO3 (2.99 g, 9.16 mol). The mixture was stirred and heated at 80 C. under nitrogen gas. After 20 hours, 50% conversion was observed by LCMS. The reaction mixture was re-treated with Cs2CO3 (2.99 g, 9.16 mol) and (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (1.58 g, 5.50 mmol) and heated at 80 C. for 24 hours. The reaction mixture was cooled to room temperature. The solids were filtered and washed with ethyl acetate and hexane (1:1). The layers were separated and the organic layer washed with water (2×10 mL) and brine (2×10 mL). The organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane/hexane=1.5/1) to give (R)-2-tert-butyl-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-nitro-1H-indole (1.0 g, 66%). 1H NMR (400 MHz, CDCl3) delta 8.48 (d, J=2.2 Hz, 1H), 8.08 (dd, J=2.2, 9.1 Hz, 1H), 7.49 (d, J=9.1 Hz, 1H), 6.00 (s, 1H), 4.52-4.45 (m, 3H), 4.12 (dd, J=6.0, 8.6 Hz, 1H), 3.78 (dd, J=6.0, 8.6 Hz, 1H), 1.53 (s, 3H), 1.51 (s, 9H), 1.33 (s, 3H).

Reference： [1]Patent: US2007/244159,2007,A1 .Location in patent: Page/Page column 158-159

48
[ 107516-75-6 ]
[ 23735-43-5 ]
[ 916454-36-9 ]

Yield	Reaction Conditions	Operation in experiment
93%		Example 5 Synthesis of (R)-3-aminomethyl-1-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole-7-carboxylic acid pyridin-3-ylamide A mixture of K2CO3 (1.06 g, 7.65 mmol) and 1H-indole-2,6-dicarboxylic acid diethyl ester (1.0 g, 3.8 mmol) in DMF (15 mL) was stirred at room temperature for 0.5 h. Then toluene-4-sulfonic acid (S)-2,2-dimethyl-[1,3]dioxolan-4-yl methyl ester (1.20 g, 4.2 mmol) in DMF (5 mL) was added. The reaction mixture was warmed to 100 C. and kept at this temperature overnight. The reaction was concentrated and the residues were extracted with EtOAc several times. The combined organic extracts were washed with brine, dried over MgSO4 and concentrated. Purification by silica gel chromatography gave 1.34 g of 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-indole-2,6-dicarboxylic acid diethyl ester as white solid, yield 93%. ESI-MS m/z 376.42 [M+H]+.

Reference： [1]Patent: US2006/276453,2006,A1 .Location in patent: Page/Page column 35-36
[2]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 1994 - 1999

49
[ 82362-50-3 ]
[ 23735-43-5 ]
[ 143327-63-3 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; butan-1-ol; for 8h;Heating / reflux;	I.I Synthesis of QC-47 (2lambda,45)-l-{2-[2-(4-Chlorophenyl)ethyl]-4-fluoromethyl-[l ,3]dioxolan-2-ylmethyl}-lH- imidazole hydrochloride (QC-47) was prepared according to the synthetic scheme shown in Figure 1, wherein the reaction steps (a) - (h) are briefly as follows: (a) Mg, diethyl ether, reflux, 15 min: (b) (+/-)-epichlorohydrin, diethyl ether, reflux, 2 h; (c) imidazole, NaH, DMF, 70-80 0C, 4.5 h; (d) Swern oxidation; (e) /?-TsOH-H?O, toluene, n-butanol, reflux 8 h; (f) separate diastereomers (silica gel, EtOAc); (g) Bu4NF, THF, reflux 18.5 h; (h) 37% aq HCl, 2-propanol, rt

Reference： [1]Patent: WO2008/151437,2008,A1 .Location in patent: Page/Page column 34; sheet 1/36

50
[ 249937-13-1 ]
[ 23735-43-5 ]
C₂₅H₃₀FN₃O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 3745 - 3748

51
[ 31166-44-6 ]
[ 23735-43-5 ]
[ 1143519-92-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In toluene; at 127℃; for 20h;	Example 48 rac-[(4S,5R)-2-(6-tert-Butyl-4-ethoxy-pyhdin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5- dimethyl-4,5-dihydro-imidazol-1 -yl]-[4-((S)-2,3-dihydroxy-propyl)-piperazin-1 -yl]- methanone <n="71"/>(S)-(+)-2,2-Dimethyl-1 ,3-dioxolan-4-ylmethyl p-toluenesulfonate (286 mg, 1.0 mmol, Aldrich) and piperazine-1-carboxylic acid benzyl ester (235 mg, 1.1 mmol, Aldhch) were combined with potassium carbonate (148 g, 1.1 mmol) in dry toluene (6 ml_) in a 10 mL pressure vessel. This was well stirred and heated to 127 0C for 20 h. The reaction was cooled, diluted with ethyl ether (20 mL) and 20 mL of water. The organics were washed with water, brine, dried (MgSO4) and evaporated to give 4-(S)-(-)-(2,2-dimethyl-[1 ,3]dioxolan-4-ylmethyl)- piperazine-1 -carboxylic acid benzyl ester as a heavy oil which was purified by flash column chromatography (silica gel, eluting with 3% thethylamine and 1 :1 ethyl acetate:hexane to ethyl acetate). LR-MS: 334 [(IvRH)+].4-(S)-(-)-(2,2- dimethyl-[1 ,3]dioxolan-4-ylmethyl)-piperazine-1 -carboxylic acid benzyl ester (220 mg, 0.65 mmol) was dissolved in 20 mL of ethanol and 10% palladium on carbon (50 mg, Aldrich). The mixture was hydrogenated in a Parr reactor at 40 psi for 18 h. The reaction mixture was filtered through Celite and evaporated to give an oil. The oil was mostly dissolved in hexane, treated with Norite, filtered and crystallized from cold hexane to give 1-(S)-(-)-(2,2-dimethyl-[1 ,3]dioxolan-4- ylmethyl)-piperazine. LR-MS: 200 [(M+H)+].

Reference： [1]Patent: WO2009/47161,2009,A1 .Location in patent: Page/Page column 69; 70

52
[ 1155773-94-6 ]
[ 23735-43-5 ]
[ 1155773-16-2 ]
[ 1155773-96-8 ]

Yield	Reaction Conditions	Operation in experiment
14%; 30%	With lithium hexamethyldisilazane; In tetrahydrofuran; N,N-dimethyl-formamide; at 200℃; for 0.5h;Microwave irradiation;	As depicted in Scheme 23 above, a 5 mL microwave reactor vial equipped with a stir bar was charged with ER-819930 (110 mg, 0.000238 mol), DMF (1.5 mL), ((4S)-2,2-dimethyl-l,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (205 mg, 0.000715 mol) and 1.00 M of lithium hexamethyldisilazide in tetrahydrofuran (520 muL, 0.00052 mol). The reactor vial was heated by microwave irradiation at 200C for 15 min. More ((4S)-2,2-dimethyl-l,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (157 mg, 0.000548 mol) and 1.00 M of lithium hexamethyldisilazide in tetrahydrofuran (477 muL, 0.000477 mol) were added, and reaction mixture was heated by microwave irradiation at 200C for another 15 min. Purification by preparative reverse phase HPLC provided acetonide ER-819993 (40 mg, 30%) and diol material (18 mg, 14%) as 1 :1 mixtures of diastereomers. Separation of diastereomeric diols by chiral HPLC on Chiralpac AS column eluting with heptane-isopropanol (9:1) afforded the first eluting diastereomer ER-819788 (5.0 mg) and the second eluting diastereomer ER-819789 (5.2 mg). Absolute stereochemistry was assigned tentatively based on analogy in chiral HPLC retention time with ER-819762/ER- 819763 pair of enantiomers.

Reference： [1]Patent: WO2009/64274,2009,A1 .Location in patent: Page/Page column 28

53
[ 1155773-94-6 ]
[ 23735-43-5 ]
[ 1155773-19-5 ]
[ 1155773-20-8 ]

Yield	Reaction Conditions	Operation in experiment
		As depicted in Scheme 69 above, a 5 mL microwave reactor vial equipped with a stir bar was charged with ER-819930 (110 mg, 0.000238 mol), DMF (1.5 mL), ((4S)-2,2-dimethyl-l,3-dioxolan-4-yl)methyl 4- methylbenzenesulfonate (205 mg, 0.000715 mol) and 1.00 M of lithium hexamethyldisilazide in tetrahydrofuran (520 muL, 0.00052 mol). The reactor vial was heated by microwave irradiation at 2000C for 15 min. More ((4S)-2,2-dimethyl-l,3-dioxolan-4-yl)methyl 4- methylbenzenesulfonate (157 mg, 0.000548 mol) and 1.00 M of lithium hexamethyldisilazide in tetrahydrofuran (477 muL, 0.000477 mol) were added, and reaction mixture was heated by microwave irradiation at 200C for another 15 min. Purification by preparative reverse phase HPLC provided acetonide ER-819993 (40 mg, 30%) and diol material (18 mg, 14%) as 1 :1 mixtures of diastereomers. Separation of diastereomeric diols by chiral HPLC on Chiralpac AS column eluting with heptane-isopropanol (9:1) afforded the first eluting diastereomer ER- 819788 (5.0 mg) and the second eluting diastereomer ER-819789 (5.2 mg). Absolute stereochemistry was assigned tentatively based on analogy in chiral HPLC retention time with ER-819762/ER-819763 pair of enantiomers. (BMS-231, 249).

Reference： [1]Patent: WO2009/70305,2009,A1 .Location in patent: Page/Page column 103

54
[ 26621-44-3 ]
[ 23735-43-5 ]
[ 1191453-79-8 ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 6h;Product distribution / selectivity;	A solution of 3-nitro-1H-pyrazole (prepared as in Example 5, 12.0 g, 106 mmol) in N,N-dimethylformamide (150 mL) was treated with para-toluenesulfonic acid (S)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl ester (25.5 g, 89.0 mmol), and potassium carbonate (24.5 g, 178 mmol). The reaction mixture was heated to 90 C. for 6 h under nitrogen. After this time, the reaction mixture was diluted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, rinsed and concentrated in vacuo. Purification by ISCO flash chromatography (128 g, 5-30% ethyl acetate/hexanes) afforded 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-3-nitro-1H-pyrazole (14.5 g, 73%) as a light yellow oil.
73%	With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 6h;Inert atmosphere;	A solution of 3-nitro-1H-pyrazole (Intermediate 2, 12.0 g, 106 mmol) in N,N-dimethylformamide (150 mL) was treated with para-toluenesulfonic acid (S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester (25.5 g, 89.0 mmol), and potassium carbonate (24.5 g, 178 mmol). The reaction mixture was heated to 90 C. for 6 h under nitrogen. After this time, the reaction mixture was diluted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, rinsed and concentrated in vacuo. Silica gel column chromatography (ISCO 120 g, 5-30% ethyl acetate/hexanes) afforded 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-3-nitro-1H-pyrazole (14.5 g, 73%) as a light yellow oil; ESI-LRMS m/e calcd for C9H13N3O4 [M+H+] 228, found 228 [M+H+].

Reference： [1]Patent: US2009/264445,2009,A1 .Location in patent: Page/Page column 49
[2]Patent: US2009/264434,2009,A1 .Location in patent: Page/Page column 26; 42

55
[ 55041-27-5 ]
[ 23735-43-5 ]
[ 865239-03-8 ]

Yield	Reaction Conditions	Operation in experiment
42.6%		To a solution of 3,3-bis [4-hydroxy-3-methylphenyl] pentane (1 g, 3.52 mmol) in DMSO (9 ml) was added t-BuOK (379 mg, 3.38 mmol) at room temperature under N2 atmosphere. After 5min., (S)- (+)-2, 2-dimethyl 1, 3-dioxolan-4-yl-methyl- p-toluenesulfonate (796 mg, 2.78 mmol) was added and the reaction mixture was stirred at 60 degrees C for 12 h. Then the reaction mixture was poured into sat. NH4CI and the products were extracted with EtOAc. The extracts were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The obtained residue was chromatographed on silica gel with n- Hexane: Acetone (20: 1) to give the title compound (472 mg, 42.6%) as a white amorphous. 'H-NMR (300MHz, CDCI3) : 7.00-6. 80 (m, 4H), 6.80-6. 60 (m, 2H), 4.90 (s, 1 H), 4.55-4. 45 (m, 1H), 4.20-3. 90 (m, 4H), 2.10, 2.20 (S, 6H), 2.10-1. 90 (m, 4H), 1.49 (s, 3H), 1.48 (s, 3H), 0.60 (t, 6H).

Reference： [1]Patent: WO2005/87700,2005,A2 .Location in patent: Page/Page column 340-341

56
[ 919482-40-9 ]
[ 23735-43-5 ]
[ 919482-43-2 ]

Yield	Reaction Conditions	Operation in experiment
		Example 5 Preparation of 1-[(2R)-2,3-dihydroxypropyl]-3-{1-[(1R, 3S, 4S)-spiro[bicyclo-[2.2.1]heptane-2,1'-cyclopropan]-3-ylmethyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-One hydrochloride 1) 1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3-{1-[(1R, 3S, 4S)-spiro[bicyclo[2.2.1]heptane-2,1'-cyclopropan]-3-ylmethyl]piperidin4-yl}-1,3-dihydro-2H-benzimidazol-2-One 3-{1-[(1R, 3S, 4S)-spiro[bicyclo[2.2.1]heptane-2,1'-cyclopropan]-3-ylmethyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one (1.47 g) as obtained in 4) of Example 3 was dissolved in dimethylformamide (25 mL), and to which 60-72% sodium hydride (an oil dispersion) (418 mg) was added at room temperature and stirred for 15 minutes. To the resulting reaction liquid, a [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 4-methylbenzenesulfonate (2.39 g) solution in dimethylformamide (5 mL) was added at room temperature, and stirred at 80 C. for 5 hours. The reaction liquid was cooled to room temperature, to which phosphate buffer (pH 6.5) was added, followed by extraction with ethyl acetate. The extract was washed with water, dried over anhydrous sodium sulfate, removed of the solvent by distillation and the resulting residue was purified on silica gel column chromatography (hexane/ethyl acetate=9/1-1/1) to provide 1.80 g of the title compound as a colorless, oily substance.

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 4091 - 4094
[2]Patent: US2007/15792,2007,A1 .Location in patent: Page/Page column 14

57
[ 1245252-94-1 ]
[ 23735-43-5 ]
[ 1207361-27-0 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; sodium iodide; In N,N-dimethyl-formamide; at 110℃; for 22h;	Example 225; [00174] Synthesis of l-(4-(7-(((R)-2,2-dimethyl-l,3-dioxolan-4-yl)methyl)-4-((S)-3- methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea (jz): A solution of (S)-l-ethyl-3-(4-(4-(3-methylmorpholino)-5, 6,7, 8-tetrahydropyrido[3,4- d]pyrimidin-2-yl)phenyl)urea hydrochloride (jk) (270 mg, 0.69 mmol), (S)-(2,2-dimethyl-l,3- dioxolan-4-yl)methyl 4-methylbenzenesulfonate (377 mg, 132 mmol), sodium iodide (104 mg, 0.69 mmol), DIPEA (0.48 mL, 2.8 mmol), and DMF (1.0 mL) was heated at 110 0C for 22 h. The mixture was partitioned between ethyl acetate and sat. NaHCCb . The phases were separated, and the aqueous layer extracted with ethyl acetate (2x). The combined organic phases were dried over Na2SO4, filtered and concentrated onto Celite, and the residue chromatographed: ISCO 12 g column 0-20% IPA in DCM to afford 228 mg (64%) of the title compound jz as an off-white solid: LC-MS: m/z = +511 (M+H)+.

Reference： [1]Patent: WO2010/14939,2010,A1 .Location in patent: Page/Page column 215-216

58
[ 1152311-77-7 ]
[ 23735-43-5 ]
[ 1152311-87-9 ]
[ 1152311-88-0 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 46h;Inert atmosphere;	Cesium carbonate (8.23 g, 25.3 mmol) was added to a mixture of benzyl 2-(6-fluoro- 5-nitro-lH-indol-2-yl)-2-methylpropanoate (3.0 g, 8.4 mmol) and (S)-(2,2-dimethyl-l,3- dioxolan-4-yl)methyl 4-methylbenzenesulfonate (7.23 g, 25.3 mmol) in DMF (17 mL). The reaction was stirred at 80 C for 46 hours under nitrogen atmosphere. The mixture was then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude product, a viscous brown oil which contains both of the products shown above, was taken directly to the next step without further purification. (R)-Benzyl 2-(l-((2,2- dimethyl-l,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-lH-indol-2-yl)-2-methylpropanoate, ESI- MS m/z calc. 470.2, found 471.5 (M+l)+. Retention time 2.20 minutes. ((S)-2,2-Dimethyl-l,3- dioxolan-4-yl)methyl 2-(l-(((R)-2,2-dimethyl-l,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-lH- indol-2-yl)-2-methylpropanoate, ESI-MS m/z calc. 494.5, found 495.7 (M+l)+. Retention time 2.01 minutes.
	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 46h;Inert atmosphere;	Cesium carbonate (8.23 g, 25.3 mmol) was added to a mixture of benzyl 2-(6- fluoro-5-nitro-lH-indol-2-yl)-2-methylpropanoate (3.0 g, 8.4 mmol) and (S)-(2,2- dimethyl-l,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (7.23 g, 25.3 mmol) in DMF (N,N-dimethylformamide) (17 mL). The reaction was stirred at 80 C for 46 hours under a nitrogen atmosphere. The mixture was then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over MgS04, filtered and concentrated. The crude product, a viscous brown oil which contains both of the products shown above, was taken directly to the next step without further purification. (R)-Benzyl 2-(l- ((2,2-dimethyl-l,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-lH-indol-2-yl)-2- methylpropanoate, ESI-MS m/z calc. 470.2, found 471.5 (M+l)+. Retention time 2.20 minutes. ((S)-2,2-Dimethyl-l,3-dioxolan-4-yl)methyl 2-(l-(((R)-2,2-dimethy 1-1,3 - dioxolan-4-yl)methyl)-6-fluoro-5-nitro-lH-indol-2-yl)-2-methylpropanoate, ESI-MS m/z calc. 494.5, found 495.7 (M+l)+. Retention time 2.01 minutes.
	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 46h;Inert atmosphere;	Cesium carbonate (8.23 g, 25.3 mmol) was added to a mixture of benzyl 2-(6- fluoro-5-nitro-1H-indol-2-yl)-2-methylpropanoate (3.0 g, 8.4 mmol) and (S)-(2,2- dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (7.23 g, 25.3 mmol) in DMF (N,N-dimethylformamide) (17 mL). The reaction was stirred at 80 C for 46 hours under a nitrogen atmosphere. The mixture was then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude product, a viscous brown oil which contains both of the products shown above, was taken directly to the next step without further purification. (R)-Benzyl 2-(1- ((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1H-indol-2-yl)-2- methylpropanoate, ESI-MS m/z calc.470.2, found 471.5 (M+1)+. Retention time 2.20 minutes. ((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)methyl 2-(1-(((R)-2,2-dimethyl-1,3- dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1H-indol-2-yl)-2-methylpropanoate, ESI-MS m/z calc.494.5, found 495.7 (M+1)+. Retention time 2.01 minutes.

	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 46h;Inert atmosphere;	Cesium carbonate (8.23 g, 25.3 mmol) was added to a mixture of benzyl 2-(6-fluoro-5-nitro-1H-indol-2-yl)-2-methylpropanoate (3.0 g, 8.4 mmol) and (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (7.23 g, 25.3 mmol) in DMF (17 mL). The reaction was stirred at 80 C. for 46 hours under a nitrogen atmosphere. The mixture was then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude product, a viscous brown oil which contains both of the products shown above, was taken directly to the next step without further purification. (R)-Benzyl 2-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1H-indol-2-yl)-2-methylpropanoate, ESI-MS m/z calc. 470.2, found 471.5 (M+1)-. Retention time 2.20 minutes. ((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)methyl 2-(1 -(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1H-indol-2-yl)-2-methylpropanoate, ESI-MS m/z calc. 494.5, found 495.7 (M+1)+. Retention time 2.01 minutes.
	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 46h;Inert atmosphere;	j00315J Cesium carbonate (8.23 g, 25.3 mmol) was added to a mixture of benzyl 2-(6- fluoro-5 -nitro- 1 H-indol-2-yl)-2-methylpropanoate (3.0 g, 8.4 mmol) and (S)-(2,2- dimethyl- 1,3 -dioxolan-4-yl)methyl 4-methylbenzenesulfonate (7.23 g, 25.3 mmol) in DMF (17 mL). The reaction was stirred at 80 C for 46 hours under a nitrogen atmosphere. The mixture was then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude product, a viscous brown oil which contains both of the products shown above, was taken directly to the next step without further purification. (R)-B enzyl 2-( 1 -((2,2-dimethyl- 1,3 -dioxolan-4- yl)methyl)-6-fluoro-5 -nitro- 1 H-indol-2-yl)-2-methylpropanoate, ESI-MS m/z calc. 470.2, found 471.5 (M+1)t Retention time 2.20 minutes. ((S)-2,2-Dimethyl-1,3-dioxolan-4- yl)methyl 2-( 1 -(((R)-2,2-dimethyl- 1,3 -dioxolan-4-yl)methyl)-6-fluoro-5 -nitro- 1 H-indol-2- yl)-2-methylpropanoate, ESI-MS m/z calc. 494.5, found 495.7 (M+1). Retention time 2.01 minutes.
7.23 g	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 46h;Inert atmosphere;	Cesium carbonate (8.23 g, 25.3 mmol) was added to a mixture of benzyl 2-(6- fluoro-5-nitro-lH-indol-2-yl)-2-methylpropanoate (3.0 g, 8.4 mmol) and (S)-(2,2- dimethyl-l,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (7.23 g, 25.3 mmol) in DMF (17 mL). The reaction was stirred at 80 C for 46 hours under a nitrogen atmosphere. The mixture was then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over MgS04, filtered and concentrated. The crude product, a viscous brown oil which contains both of the products shown above, was taken directly to the next step without further purification. (R)-Benzyl 2-(l-((2,2-dimethyl-l,3-dioxolan-4- yl)methyl)-6-fluoro-5-nitro-lH-indol-2-yl)-2-methylpropanoate , ESI-MS m/z calc. 470.2, found 471.5 (M+l)+. Retention time 2.20 minutes. ((S)-2,2-Dimethyl-l,3-dioxolan-4- yl)methyl 2-(l-(((R)-2,2-dimethyl-l,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-lH-indol-2- yl)-2-methylpropanoate, ESI-MS m/z calc. 494.5, found 495.7 (M+l)+. Retention time 2.01 minutes.
	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 46h;Inert atmosphere;	Cesium carbonate (8.23 g, 25.3 mmol) was added to a mixture of benzyl 2-(6- fluoro-5-nitro- lH-indol-2-yl)-2-methylpropanoate (3.0 g, 8.4 mmol) and (S)-(2,2- dimethyl- l,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (7.23 g, 25.3 mmol) in DMF (17 mL). The reaction was stirred at 80 C for 46 hours under a nitrogen atmosphere. The mixture was then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over MgS04, filtered and concentrated. The crude product, a viscous brown oil which contains both of the products shown above, was taken directly to the next step without further purification. (R)-Benzyl 2-(l-((2,2-dimethyl- l,3- dioxolan-4-yl)methyl)-6-fluoro-5-nitro-lH-indol-2-yl)-2-methylpropanoate, ESI-MS m/z calc. 470.2, found 471.5 (M+l)+. Retention time 2.20 minutes. ((S)-2,2-Dimethyl- l,3- dioxolan-4-yl)methyl 2-(l-(((R)-2,2-dimethyl- l,3-dioxolan-4-yl)methyl)-6-fluoro-5- nitro- lH-indol-2-yl)-2-methylpropanoate, ESI-MS m/z calc. 494.5, found 495.7 (M+l)+. Retention time 2.01 minutes.
	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 46h;Inert atmosphere;	Cesium carbonate (8.23 g, 25.3 mmol) was added to a mixture of benzyl 2-(6- fluoro-5-nitro-lH-indol-2-yl)-2-methylpropanoate (3.0 g, 8.4 mmol) and (S)-(2,2- dimethyl-l,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (7.23 g, 25.3 mmol) in DMF (17 mL). The reaction was stirred at 80 C for 46 hours under a nitrogen (1104) atmosphere. The mixture was then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over MgS04, filtered and concentrated. The crude product, a viscous brown oil which contains both of the products shown above, was taken directly to the next step without further purification. (R)-Benzyl 2-(l-((2,2-dimethyl-l,3-dioxolan-4- yl)methyl)-6-fluoro-5-nitro-lH-indol-2-yl)-2-methylpropanoate, ESI-MS m/z calc. 470.2, found 471.5 (M+l)+. Retention time 2.20 minutes. ((S)-2,2-Dimethyl-l,3-dioxolan-4- yl)methyl 2-(l-(((R)-2,2-dimethyl-l,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-lH-indol-2- yl)-2-methylpropanoate, ESI-MS m/z calc. 494.5, found 495.7 (M+l)+. Retention time 2.01 minutes.
	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 46h;Inert atmosphere;	Cesium carbonate (8.23 g, 25.3 mmol) was added to a mixture of benzyl 2- (6-fluoro-5-nitro-lH-indol-2-yl)-2-methylpropanoate (3.0 g, 8.4 mmol) and (S)-(2,2- dimethyl-l,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (7.23 g, 25.3 mmol) in DMF (N,N-dimethylformamide) (17 mL). The reaction was stirred at 80 C for 46 hours under a nitrogen atmosphere. The mixture was then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over MgS04, filtered and concentrated. The crude product, a viscous brown oil which contains both of the products shown above, was taken directly to the next step without further purification. (R)-Benzyl 2-(l -((2,2- dimethyl- l,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-lH-indol-2-yl)-2- methylpropanoate, ESI-MS m/z calc. 470.2, found 471.5 (M+l)+. Retention time 2.20 minutes. ((S)-2, 2-Dimethyl- l,3-dioxolan-4-yl)methyl 2-(l-(((R)-2, 2-dimethyl- 1,3- dioxolan-4-yl)methyl)-6-fluoro-5-nitro-lH-indol-2-yl)-2-methylpropanoate, ESI-MS m/z calc. 494.5, found 495.7 (M+l)+. Retention time 2.01 minutes.
	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 46h;Inert atmosphere;	Cesium carbonate (8.23 g, 25.3 mmol) was added to a mixture of benzyl 2-(6-fluoro-5-nitro-1 H-indol-2-yl)-2- methylpropanoate (3.0 g, 8.4 mmol) and (S)-(2,2-dimethyl- 1 ,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (7.23 g, 25.3 mmol) in DMF (N,N-dimethylformamide) (17 mE). The reaction was stirred at 80 C. for 46 hours under a nitrogen atmosphere. The mixture was then partitionedbetween ethyl acetate and watet The aqueous layer was extracted with ethyl acetate. The combined ethyl acetatelayers were washed with brine, dried over Mg504, filteredand concentrated. The crude product, a viscous brown oilwhich contains both of the products shown above, was takendirectly to the next step without further purification. (R)l3enzyl 2-(1 -((2,2-dimethyl- 1 ,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1 H-indol-2-yl)-2-methylpropanoate, ESI-MSmlz calc. 470.2, found 471.5 (M+1). Retention time 2.20minutes. ((S)-2,2-Dimethyl- 1 ,3-dioxolan-4-yl)methyl 2-(1 -(((R)-2,2-dimethyl- 1 ,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1 H-indol-2-yl)-2-methylpropanoate, ESI-MS mlz calc.494.5, found 495.7 (M+1). Retention time 2.01 minutes.
	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 46h;Inert atmosphere;	Cesium carbonate (8.23 g, 25.3 mmol) was added to a mixture of benzyl 2-(6- fluoro-5-nitro-lH-indol-2-yl)-2-methylpropanoate (3.0 g, 8.4 mmol) and (S)-(2,2- dimethyl-l,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (7.23 g, 25.3 mmol) in DMF (N,N-dimethylformamide) (17 mL). The reaction was stirred at 80 C for 46 hours under a nitrogen atmosphere. The mixture was then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over MgS04, filtered and concentrated. The crude product, a viscous brown oil which contains both of the products shown above, was taken directly to the next step without further purification. (R)-Benzyl 2-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1H-indol-2-yl)-2-methylpropanoate, ESI-MS m/z calc. 470.2, found 471.5 (M+l)+. Retention time 2.20 minutes. ((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)methyl 2-(1-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1H-indol-2-yl)-2-methylpropanoate, ESI-MS m/z calc. 494.5, found 495.7 (M+l)+. Retention time 2.01 minutes.
	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 46h;Inert atmosphere;	Cesium carbonate (8.23 g, 25.3 mmol) was added to a mixture of benzyl 2-(6-fluoro-5-nitro-1H-indol-2-yl)-2-methylpropanoate (3.0 g, 8.4 mmol) and (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (7.23 g, 25.3 mmol) in DMF (N,N-dimethylformamide) (17 mL). The reaction was stirred at 80 C. for 46 hours under a nitrogen atmosphere. The mixture was then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude product, a viscous brown oil which contains both of the products shown above, was taken directly to the next step without further purification. (R)-Benzyl 2-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1H-indol-2-yl)-2-methylpropanoate, ESI-MS m/z calc. 470.2, found 471.5 (M+1)+. Retention time 2.20 minutes. ((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)methyl 2-(1-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1H-indol-2-yl)-2-methylpropanoate, ESI-MS m/z calc. 494.5, found 495.7 (M+1)+. Retention time 2.01 minutes.

Reference： [1]Patent: WO2010/53471,2010,A1 .Location in patent: Page/Page column 68
[2]Patent: WO2018/64632,2018,A1 .Location in patent: Paragraph 00198; 00199; 00200
[3]Patent: WO2018/107100,2018,A1 .Location in patent: Paragraph 00217-00219
[4]Patent: US2018/280349,2018,A1 .Location in patent: Paragraph 0088-0089
[5]Patent: WO2019/10092,2019,A1 .Location in patent: Paragraph 00312; 00313; 00314; 00315
[6]Patent: WO2019/18353,2019,A1 .Location in patent: Paragraph 00140
[7]Patent: WO2019/18395,2019,A1 .Location in patent: Paragraph 00171
[8]Patent: WO2018/227049,2018,A1 .Location in patent: Paragraph 00189-00191
[9]Patent: WO2019/113089,2019,A1 .Location in patent: Paragraph 00238
[10]Patent: US2019/119253,2019,A1 .Location in patent: Paragraph 0506; 0507
[11]Patent: WO2019/191620,2019,A1 .Location in patent: Paragraph 00419
[12]Patent: US2019/240197,2019,A1 .Location in patent: Paragraph 0565; 0566

59
[ 1152311-79-9 ]
[ 23735-43-5 ]
[ 1152311-80-2 ]
[ 1152311-74-4 ]
[ 1152312-03-2 ]
[ 1152311-82-4 ]
[ 1152311-81-3 ]

Yield	Reaction Conditions	Operation in experiment
48%	With caesium carbonate; In N,N-dimethyl-formamide; at 90℃; for 24h;	To a solution of 2-(4-(tert-butyldimethylsilyloxy)-2-methylbutan-2-yl)-6-fluoro-5- nitro-lH-indole (1.9 g, 5.0 mmol) and (S)-(2,2-dimethyl-l,3-dioxolan-4-yl)methyl 4- methylbenzenesulfonate (2.86 g, 10.0 mmol) in DMF (10 mL) was added Cs2CO3 (4.88 g, 15.0 mmol). The mixture was heated at 90 0C for 24 hours. The reaction was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine and dried over MgSO4. After the removal of solvent, the residue was purified by column chromatography (10-50% ethyl acetate - hexane) to afford 6- fluoro-l,l-dimethyl-7-nitro-2,3-dihydro-lH-pyrrolo[l,2-a]indole (600 mg, 48%). ESI-MS m/z calc. 248.1, found 249.2 (M+l)+. Retention time 2.00 minutes; 2-(4-(((R)-2,2-dimethyl-l,3- dioxolan-4-yl)methoxy)-2-methylbutan-2-yl)-l-(((R)-2,2-dimethyl-l,3-dioxolan-4-yl)methyl)-6- fluoro-5-nitro-lH-indole (270 mg, containing some (R)-2-(4-((2,2-dimethyl-l,3-dioxolan-4- yl)methoxy)-2-methylbutan-2-yl)-6-fluoro-5-nitro-lH-indole). ESI-MS /n/z calc. 494.2 and 380.2, found 495.4 and 381.4 (M+l)+. Retention time 2.12 and 1.92 minutes; (R)-3-(l-((2,2- dimethyl-l,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-lH-indol-2-yl)-3-methylbutan-l-ol (1.0 g, containing some 3-(6-fluoro-5-nitro-lH-indol-2-yl)-3-methylbutan-l-ol). ESI-MS m/z calc. 380.2 and 266.1, found 381.2 and 267.2 (M+l)+. Retention time 1.74 and 1.48 minutes.

Reference： [1]Patent: WO2010/53471,2010,A1 .Location in patent: Page/Page column 62-63

60
[ 42058-59-3 ]
[ 23735-43-5 ]
methyl 3-((R)-2,2-dimethyl-1,3-dioxolan-4-ylmethyloxy)phenylacetate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1693 - 1696

61
[ 67385-09-5 ]
[ 23735-43-5 ]
[ 1221430-02-9 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 3198 - 3213

62
[ 919482-35-2 ]
[ 23735-43-5 ]
[ 919482-36-3 ]

Yield	Reaction Conditions	Operation in experiment
		5) 1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3-{1-[(4S)-spiro-[2.5]-oct-4-ylmethyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-One 3-{1-[(4S)-spiro[2.5]oct-4-ylmethyl]piperidin-4-yl}-1.3-dihydro-2H-benzimidazol-2-one (2.94 g) was dissolved in dimethylformamide (60 mL), and to which 60-72% sodium hydride (oil dispersion) (706.6 mg) was added at room temperature and stirred for 30 minutes. To the reaction liquid, [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 4-methylbenzene-sulfonate (7.25 g) was added and stirred at 80 C. for 7 hours. After cooling the reaction liquid to room temperature, water was added, followed by extraction with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, removed of the solvent by distillation and the resulting residue was purified on silica gel column chromatography (hexane/ethyl acetate=2/1-1/2) to provide 3.43 g of the title compound as a pale yellow, oily substance.

Reference： [1]Patent: US2007/15792,2007,A1 .Location in patent: Page/Page column 12

63
[ 919482-30-7 ]
[ 23735-43-5 ]
1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3-{1-[(6S)-spiro[4.5]-dec-6-ylmethylpiperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one [ No CAS ]
1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3-{1-[(6R)-spiro[4.5]-dec-6-ylmethylpiperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		2) 1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3-[1-(spiro[4.5]-dec-6-ylmethyl)piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-One The compound (90 mg) as obtained in 1) was dissolved in dimethylformamide (3 mL), and to the solution 60-72% sodium hydride (oil dispersion) (20 mg) was added at room temperature, followed by 30 minutes' stirring. After addition of [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 4-methylbenzene-sulfonate (140 mg) and potassium iodide (20 mg), the reaction liquid was stirred at 60 C. for 14 hours. The reaction liquid was cooled to room temperature, to which 1M aqueous sodium hydroxide solution was added, followed by extraction with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, removed of the solvent by distillation, and the resulting residue was purified on silica gel column chromatography (hexane/ethyl acetate=5/1-2/1) to provide 100.2 mg of the title compound as a pale yellow, oily substance. 3) 1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3-{1-[(6S or 6R)-spiro[4.5]-dec-6-ylmethyl)piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-One The two kinds of diastereomers of the compound (100.2 mg) as obtained in 2) were separated using CHIRALPAK AD (Daicel Co., Ltd.; 2 cm×25 cm, hexane/2-propanol/diethylamine=6/1/0.007), to provide as the first eluate 44.1 mg of (6S or 6R) body of the title compound.

Reference： [1]Patent: US2007/15792,2007,A1 .Location in patent: Page/Page column 11

64
[ 1304788-38-2 ]
[ 23735-43-5 ]
[ 1304788-39-3 ]

Reference： [1]Heterocycles,2011,vol. 82,p. 1669 - 1674

65
[ 1304788-44-0 ]
[ 23735-43-5 ]
[ 1304788-45-1 ]

Reference： [1]Heterocycles,2011,vol. 82,p. 1669 - 1674

66
[ 174274-85-2 ]
[ 23735-43-5 ]
[ 952665-39-3 ]

Yield	Reaction Conditions	Operation in experiment
66%	With caesium carbonate; In N,N-dimethyl-formamide;	(R)-2-tert-Butyl-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-nitro-1H-indole To a stirred solution of (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (1.58 g, 5.50 mmol) in anhydrous DMF (10 mL) under nitrogen gas was added 2-tert-butyl-5-nitro-1H-indole (1.00 g, 4.58 mmol) followed by Cs2CO3 (2.99 g, 9.16 mol). The mixture was stirred and heated at 80 C. under nitrogen gas. After 20 hours, 50% conversion was observed by LCMS. The reaction mixture was re-treated with Cs2CO3 (2.99 g, 9.16 mol) and (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (1.58 g, 5.50 mmol) and heated at 80 C. for 24 hours. The reaction mixture was cooled to room temperature. The solids were filtered and washed with ethyl acetate and hexane (1:1). The layers were separated and the organic layer was washed with water (210 mL) and brine (210 mL). The organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane/hexane=1.5/1) to give (R)-2-tert-butyl-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-nitro-1H-indole (1.0 g, 66%). 1H NMR (400 MHz, CDCl3) delta 8.48 (d, J=2.2 Hz, 1H), 8.08 (dd, J=2.2, 9.1 Hz, 1H), 7.49 (d, J=9.1 Hz, 1H), 6.00 (s, 1H), 4.52-4.45 (m, 3H), 4.12 (dd, J=6.0, 8.6 Hz, 1H), 3.78 (dd, J=6.0, 8.6 Hz, 1H), 1.53 (s, 3H), 1.51 (s, 9H), 1.33 (s, 3H).
66%	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 44h;Inert atmosphere;	To a stirred solution of (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (1.58 g, 5.50 mmol) in anhydrous DMF (10 mL) under nitrogen gas was added 2-tert-butyl-5-nitro-1H-indole (1.00 g, 4.58 mmol) followed by Cs2CO3 (2.99 g, 9.16 mol). The mixture was stirred and heated at 80 C. under nitrogen gas. After 20 hours, 50% conversion was observed by LCMS. The reaction mixture was re-treated with Cs2CO3 (2.99 g, 9.16 mol) and (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (1.58 g, 5.50 mmol) and heated at 80 C. for 24 hours. The reaction mixture was cooled to room temperature. The solids were filtered and washed with ethyl acetate and hexane (1:1). The layers were separated and the organic layer was washed with water (210 mL) and brine (210 mL). The organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane/hexane=1.5/1) to give (R)-2-tert-butyl-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-nitro-1H-indole (1.0 g, 66%). 1H NMR (400 MHz, CDCl3) delta 8.48 (d, J=2.2 Hz, 1H), 8.08 (dd, J=2.2, 9.1 Hz, 1H), 7.49 (d, J=9.1 Hz, 1H), 6.00 (s, 1H), 4.52-4.45 (m, 3H), 4.12 (dd, J=6.0, 8.6 Hz, 1H), 3.78 (dd, J=6.0, 8.6 Hz, 1H), 1.53 (s, 3H), 1.51 (s, 9H), 1.33 (s, 3H).

Reference： [1]Patent: US2011/98311,2011,A1
[2]Patent: US2015/231142,2015,A1 .Location in patent: Paragraph 1839

67
[ 23735-43-5 ]
[ 1350322-86-9 ]

Reference： [1]Patent: US2011/281888,2011,A1

68
[ 23735-43-5 ]
[ 1350324-59-2 ]

Reference： [1]Patent: US2011/281888,2011,A1

69
[ 23735-43-5 ]
[ 1350324-60-5 ]

Reference： [1]Patent: US2011/281888,2011,A1

70
[ 3469-69-0 ]
[ 23735-43-5 ]
[ 1350324-61-6 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2h;	1-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]methyl}-4-iodo-1H-pyrazole A mixture of 4-iodopyrazole (1.00 g, 5.16 mmol), ((4S)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (1.624 g, 5.671 mmol), Cs2CO3 (2.52 g, 7.73 mmol) and DMF (5 mL, 60 mmol) was heated to 100 C. for 2 h. The solution was extracted with EtOAc, and washed with water (2*). The organic layer was concentrated in vacuo and purified via column chromatography, eluting with 2-10% EtOAc/hexanes. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): delta=1.34 (d, J=8.8 Hz, 6H), 3.76 (dd, J=8.6, 6.1 Hz, 1H), 4.08 (dd, J=8.6, 6.3 Hz, 1H), 4.23-4.37 (m, 2H), 4.39-4.46 (m, 1H), 7.50-7.55 (m, 1H), 7.77 (s, 1H). MS (ES+): m/z=309.01 (100) [MH+]. HPLC: tR=1.34 min (polar-3 min, UPLC-ACQUITY).

Reference： [1]Patent: US2011/281888,2011,A1 .Location in patent: Page/Page column 63

71
[ 1350324-13-8 ]
[ 23735-43-5 ]
[ 1350324-02-5 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 23h;	tert-Butyl 5-bromo-3-[(1S)-1-(2-chloro-6-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine-1-carboxylate To a suspension of tert-butyl 5-bromo-3-[(1S)-1-(2-chloro-3-fluoro-6-hydroxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (84.5 mg, 0.180 mmol) and potassium carbonate (104.5 mg, 0.7561 mmol) in DMF (3 mL), ((4S)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (103.6 mg, 0.3618 mmol) in DMF (2 mL) was added and the reaction mixture was heated to 60 C. for a total of 23 h. EtOAc was added to dilute the reaction mixture and a standard aqueous workup was performed. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude was adsorbed onto a pre-filled silica gel loading cartridge [RediSepRf 5 gram] and purified using the Teledyne/ISCO system [RediSepRf 12 g Gold Silica], eluting with a 5-20% EtOAc:heptane solvent system. Fractions containing product were combined and concentrated in vacuo. The material obtained was dissolved in MeOH, passed through a syringe filter, and purified a second time by MDP, under acidic conditions (formic acid). Fractions containing product were pooled together and concentrated in vacuo, affording the title material as a clear and colorless film. 1H NMR (400 MHz, CDCl3): delta=8.43 (d, J=2.3 Hz, 1H), 7.53 (s, 1H), 7.53 (s, 1H), 7.02 (dd, J=9.1, 8.3 Hz, 1H), 6.70 (dd, J=9.1, 4.0 Hz, 1H), 4.92 (q, J=7.0 Hz, 1H), 4.31 (quint, J=5.7 Hz, 1H), 3.97 (dd, J=8.3, 6.6 Hz, 1H), 3.91 (dd, J=9.0, 5.9 Hz, 1H), 3.65 (br s, 1H), 3.46 (br s, 1H), 1.76 (d, J=7.1 Hz, 3H), 1.69 (s, 9H), 1.36 (d, J=5.3 Hz, 6H). MS (ES+): m/z 605.30/606.98/608.99 (23/61/9) [MH++Na]. HPLC: tR 4.15 min (ZQ3, nonpolar-5min).

Reference： [1]Patent: US2011/281888,2011,A1 .Location in patent: Page/Page column 53-54

72
[ 23735-43-5 ]
C₂₇H₃₀ClFN₄O₃ [ No CAS ]

Reference： [1]Patent: US2011/281888,2011,A1

73
[ 23735-43-5 ]
C₂₆H₂₅ClF₄N₄O₃ [ No CAS ]

Reference： [1]Patent: US2011/281888,2011,A1

74
[ 23735-43-5 ]
C₃₂H₃₆ClF₃N₄O₅ [ No CAS ]

Reference： [1]Patent: US2011/281888,2011,A1

75
[ 23735-43-5 ]
C₂₆H₂₆ClF₃N₄O₃ [ No CAS ]

Reference： [1]Patent: US2011/281888,2011,A1

76
[ 2033-45-6 ]
[ 23735-43-5 ]
[ 1350322-87-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;18-crown-6 ether; In N,N-dimethyl-formamide; at 70℃;	1-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]methyl}-4-iodo-3,5-dimethyl-1H-pyrazole A mixture of 3,5-dimethyl-4-iodopyrazole (200.0 mg, 0.9008 mmol), ((4S)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (515.9 mg, 1.802 mmol), K2CO3 (136.9 mg, 0.9909 mmol), 1,4,7,10,13,16-hexaoxacyclooctadecane (23.81 mg, 0.09008 mmol) and DMF (4 mL, 50 mmol) was heated to 70 C. overnight. The material was extracted in EtOAc, and washed with water (3*). The organic layer was dry-loaded onto silica gel for column chromatography, eluting with 20-30% EtOAc/hexanes. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid.

Reference： [1]Patent: US2011/281888,2011,A1 .Location in patent: Page/Page column 30

77
[ 19968-17-3 ]
[ 23735-43-5 ]
[ 1350323-39-5 ]
[ 1350323-38-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 2h;	4-Bromo-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-5-(trifluoromethyl)-1H-pyrazole and 4-bromo-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3-(trifluoromethyl)-1H-pyrazole; A mixture of 4-bromo-3-trifluoromethyl-1H-pyrazole (400.0 mg, 1.861 mmol), toluene-4-sulfonic acid (S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester (799.2 mg, 2.791 mmol), K2CO3 (400.0 mg, 2.894 mmol) and DMF (6 mL, 80 mmol) was heated to 90 C. for 2 h. The material was extracted with EtOAc, washing with water (3×). The organic layer was dry-loaded onto silica gel, and purified via column chromatography, eluting with 10-30% EtOAc/heptane. The fractions containing each pure product were concentrated in vacuo to afford the title compounds as clear oils. 3-Trifluoromethyl isomer: 1H NMR (400 MHz, CD3OD): delta=1.31 (s, 3H), 1.34 (s, 3H), 3.78 (dd, J=8.6, 5.8 Hz, 1H), 4.10 (dd, J=8.8, 6.6 Hz, 1H), 4.22-4.31 (m, 1H), 4.36 (dd, J=14.1, 4.0 Hz, 1H), 4.41-4.49 (m, 1H), 7.92 (s, 1H). MS (ES+): m/z=329.01/331.01 (100/100) [MH+]. HPLC: tR=1.59 min (polar-3 min, UPLC-ACQUITY). 5-Trifluoromethyl isomer: MS (ES+): m/z=329.01/331.01 (100/100) [MH+]. HPLC: tR=1.62 min (polar-3 min, UPLC-ACQUITY).

Reference： [1]Patent: US2011/281888,2011,A1 .Location in patent: Page/Page column 39

78
[ 23735-43-5 ]
[ 1346507-98-9 ]

Reference： [1]Patent: WO2011/143497,2011,A1

79
[ 23735-43-5 ]
[ 1346507-99-0 ]

Reference： [1]Patent: WO2011/143497,2011,A1

80
[ 23735-43-5 ]
[ 1346508-00-6 ]

Reference： [1]Patent: WO2011/143497,2011,A1

81
[ 23735-43-5 ]
[ 1346508-01-7 ]

Reference： [1]Patent: WO2011/143497,2011,A1

82
[ 1346507-84-3 ]
[ 23735-43-5 ]
[ 1346507-97-8 ]

Yield	Reaction Conditions	Operation in experiment
83%		To a solution of compound XC (32.40 g, 0.03 mol) in DMF (400 mL) were added K2C03 (20.7 g, 0.15 mol) and Et4NI (23.0 g, 0.09 mol). After stirring for 20 min at room temperature, the mixture was treated with (S)-(2,2-dimefhyl-l,3-dioxolan-4- yl)methyl 4-methylbenzenesulfonate LV (17.6 g, 0.061 mol). The mixture was heated at 85C for 24 h. The solvent was evaporated under reduced pressure. The residue was treated with water (200 mL) and the mixture was extracted with EtOAc (2 x 200 mL). The organic phase was washed with 5% aqueous NaCl, dried over Na2SC>4, filtered and concentrated. The crude product was purified by column chromatography on silica gel (100% hexane?l:2 hexane/EtOAc) to yield benzyl (lR,2S,3S,4R,5S)-2-((2R,3R,4R,5R)-3,5-dihydroxy-5- methyl-4-(N-methy-ieri-butoxycarbonylamino)tetrahydro-2H-pyran-2-yloxy)-4-((2R,3R,6S)- 6-((N-(((R)-2,2-dimethyl-l,3-dioxolan-4-yl)methyl)-2-nitrophenylsulfonamido)methyl)-3- ieri-butoxycarbonylaminotetrahydro-2H-pyran-2-yloxy)-3-hydroxy-5-ieri-butoxycarbonyl aminocyclohexylcarbamate C (32.27 g, 0.027 mole, 83% yield).

Reference： [1]Patent: WO2011/143497,2011,A1 .Location in patent: Page/Page column 76

83
[ 1221486-48-1 ]
[ 23735-43-5 ]
[ 1353948-59-0 ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 24h;Inert atmosphere;	EXAMPLE 14 2-Chloro-7-(S-1,2-isopropylideneglycer-3-yl)-10,11-dihydrodibenzo[a,d]cyclohepten-5-one (13a) The preparation of the title compound is carried out by method E. Yield: 89% C21H21ClO4 (Mr=372.85) MS m/z (%): 374/372 (15/43, M+), 359/357 (6/17), 299/297 (26/76), 273/271 (5/13), 260/258 (4/10), 194 (11), 178 (24), 165 (37), 145 (24), 115 (46), 101 (100), 73 (16), 59 (16). 1H-NMR (DMSO-d6) delta in ppm: 1.29 (s, 3H, -CH3), 1.34 (s, 3H, -CH3), 3.06 (s, 4H, -CH2-CH2-), 3.73-3.80 (m, 1H, -OCH2-), 4.03-4.12 (m, 3H, -CH2O-, -OCH2-), 4.37-4.42 (m, 1H, -CH-), 7.13 (d, 1H, J=8.3, C8-H), 7.27 (d, 1H, J=8.4, C9-H), 7.39-7.47 (m, 3H, C1-H, C3-H, C6-H), 7.85 (d, 1H, J=8.3, C4-H). 13C-NMR (DMSO-d6) delta in ppm: 25.8 (-CH3), 26.9 (-CH3), 33.3 (C11), 34.4 (C10), 66.0 (-OCH2-), 69.3 (-CH2O-), 74.0 (-CH-), 115.0 (C6), 120.3 (C8), 127.0 (C3), 129.5 (C1), 131.6 (C9), 132.6 (C4), 135.1 (C4a), 136.9 (C5a), 137.5 (C9a), 138.6 (C2), 144.8 (C11a), 157.3 (C7), 193.2 (C5). General Method EFor the preparation of 2-chloro-7-(S-1,2-isopropylideneglycer-3-yl)-10,11-dihydrodibenzo[a,d]cyclohepten-5-one, 0.57 mmol of 2-chloro-7-hydroxy-10,11-dihydrodibenzo[a,d]cyclohepten-5-one is dissolved in 10 ml of anhydrous DMF, and 0.82 mmol of the corresponding alpha,beta-isopropylideneglycerol gamma-tosylate and 1.65 mmol of K2CO3 are added. The reaction mixture is stirred at 80 C. under an argon atmosphere for 24 h. The reaction mixture is cooled to room temperature dissolved in 50 ml of water and extracted with diethyl ether and the organic phase is concentrated in vacuo. The product is obtained in the form of a pale yellow oil.

Reference： [1]Patent: US2012/115862,2012,A1 .Location in patent: Page/Page column 14; 16

84
[ 1221486-48-1 ]
[ 23735-43-5 ]
[ 1383443-39-7 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 5868 - 5877

85
[ 1221486-58-3 ]
[ 23735-43-5 ]
[ 1383443-42-2 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 5868 - 5877

86
[ 1221486-58-3 ]
[ 23735-43-5 ]
[ 1383443-36-4 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 5868 - 5877

87
[ 17800-45-2 ]
[ 23735-43-5 ]
C₂₀H₂₃NO₃S [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 7558 - 7561

88
[ 98-17-9 ]
[ 23735-43-5 ]
(R)-(-)-2,2-dimethyl-4-(3-trifluoromethylphenoxy)methyl-1,3-dioxolane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%		In the same manner as described for the preparation of (S)-(+)-21a (Method A), the tosylate (S)-(+)-20b (5.0 g, 17.5 mmol) afforded the acetonide (R)-(-)-21b (4.13 g, 86% yield, 99.2% ee). [alpha]D20 -7.4 (c 0.5, EtOH). The characterization data from IR, NMR and HRMS spectra were identical in all aspects with those of (S)-(+)-21a enantiomer.

Reference： [1]Tetrahedron,2013,vol. 69,p. 1634 - 1648

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Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 23735-43-5 ] {[proInfo.proName]}

Quality Control of [ 23735-43-5 ]

Related Doc. of [ 23735-43-5 ]

Product Details of [ 23735-43-5 ]

Calculated chemistry of [ 23735-43-5 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 23735-43-5 ]

Application In Synthesis of [ 23735-43-5 ]

[ 23735-43-5 ] Synthesis Path-Upstream 1~12

[ 23735-43-5 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 23735-43-5 ]

Aryls

Sulfonates

Related Parent Nucleus of [ 23735-43-5 ]

Aliphatic Heterocycles

Dioxolanes

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 23735-43-5 ]

Related Parent Nucleus of
[ 23735-43-5 ]