[ CAS No. 115093-90-8 ] {[proInfo.proName]}

Name: 115093-90-8|4,5-Dichloro-7H-pyrrolo[2,3-d]pyrimidine|98%
Brand: Ambeed
SKU: A260048
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Quality Control of [ 115093-90-8 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 115093-90-8 ]

CAS No. :	115093-90-8	MDL No. :	MFCD09999173
Formula :	C₆H₃Cl₂N₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VFTPONHUNNOSKG-UHFFFAOYSA-N
M.W :	188.01	Pubchem ID :	11106092
Synonyms :

Calculated chemistry of [ 115093-90-8 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	43.91
TPSA :	41.57 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) :	-5.85 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.56
Log Po/w (XLOGP3) :	2.25
Log Po/w (WLOGP) :	2.26
Log Po/w (MLOGP) :	1.38
Log Po/w (SILICOS-IT) :	2.85
Consensus Log Po/w :	2.06

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.03
Solubility :	0.176 mg/ml ; 0.000936 mol/l
Class :	Soluble
Log S (Ali) :	-2.76
Solubility :	0.327 mg/ml ; 0.00174 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.77
Solubility :	0.0318 mg/ml ; 0.000169 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.46

Safety of [ 115093-90-8 ]

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 [ 115093-90-8 ]

* 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 [ 115093-90-8 ]
Downstream synthetic route of [ 115093-90-8 ]

[ 115093-90-8 ] Synthesis Path-Upstream 1~3

1
[ 3680-69-1 ]
[ 115093-90-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	With N-chloro-succinimide In N,N-dimethyl-formamide at 20℃; for 72 h;	General procedure: To a solution of readily available 3a (20mmol) in N, N-dimethylformamide (DMF) (15mL) was added NCS/NBS (21mmol) and the reaction mixture was stirred at room temperature for 72h. Then ice water (150mL) was poured into the mixture, the precipitate was filtered, washed with water (3×100mL), and dried to give 3b and 3c.
95%	With N-chloro-succinimide In N,N-dimethyl-formamide at 20℃; for 12 h;	Dissolve 4-chloro-pyrrolo[2,3-d]pyrimidine (20 mmol) in DMF (6 mL), add NBS or NCS (21 mmol) in portions on ice bath, react at room temperature for 12 h, and pour the reaction mixture into 80 mL of ice. In the water, a large number of off-white solids precipitated and were filtered. The filter cake was washed with 15 mL of water and dried to give Intermediate 2. 4,5-dichloro-pyrrolo[2,3-d]pyrimidine (2a) Gray solid, yield 95percent
88%	With N-chloro-succinimide In dichloromethane for 72 h; Heating / reflux	3H, m), 2.4 (3H, s), 1.31 (3H, J=6.8 Hz, d); MS (ES+) [M+H]⁺=455.6.15. Example 15(S)-N-(3-bromophenyl)-4-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N'-cyano-2-methylpiperazine-1-carboximidamide A. Preparation of 4,5-dichloro-7H-pyrrolo[2,3-d]pyrimidine: 4-Chloro-pyrrolo[2,3-d]pyrimidine (0.5 g, 3.26 mmol) was suspended in anhydrous CH₂Cl₂(25 ml), and N-chlorosuccinimide (0.87 g, 6.52 mmol) was added. The reaction mixture was refluxed for 3 days, then cooled to room temperature. The white solid was collected by filtration to give 5-dichloro-7H-pyrrolo[2,3-d]pyrimidine (0.54 g, 2.9 mmol, 88percent).¹H NMR (CD₃OD): δ 8.57 (1H, s), 7.60 (1H, s); MS (ES+) [M+H]⁺=188.

80%	With N-chloro-succinimide In dichloromethane at 20℃; for 6 h; Heating / reflux	PREPARATION 7; 4,5-dichloro-7H-pyrrolor2,3-dlpyrimidineN-Chlorosuccinimide (4.78 g, 35.81 mmol) was added portionwise to a stirred suspension of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (5g, 32.56 mmol) in DCM, dry (125ml) at room temperature. The resulting suspension was stirred for 1 hour then heated to reflux for 5 hours, then allowed to cool down and left to stir at room temperature overnight. The reaction mixture was evaporated and suspended in water (50 mL). The suspension was filtered giving crude product as a grey solid. The solid was suspended in hot methnol and filtered. The solid was then suspended in hot ethyl acetate and filtered to give 4,5- dichloro-7H-pyrrolo[2,3-d]pyrimidine (4.87 g, 80 percent) as a grey solid. IH NMR (400.13 MHz, DMSO-d6) δ 7.91 (IH, s), 8.64 (IH, s), 12.87 (IH, s) MS m/e MH⁺ 188
80%	With N-chloro-succinimide In dichloromethane at 20℃; Heating / reflux	PREPARATION I4,5-dichloro-7H-pyrrolor2,3-dlpyrimidine; N-Chlorosuccinimide (4.78 g, 35.81 mmol) was added portionwise to a stirred suspension of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (5g, 32.56 mmol) in DCM, dry (125ml) at room temperature. The resulting suspension was stirred for 1 hour then heated to reflux for 5 hours, then allowed to cool down and left to stir at room temperature overnight. The reaction mixture was evaporated and suspended in water (50 mL). The suspension was filtered giving crude product as a grey solid. The solid was suspended in hot methnol and filtered. The solid was then suspended in hot ethyl acetate and filtered to give 4,5- dichloro-7H-pyrrolo[2,3-d]pyrimidine (4.87 g, 80 percent) as a grey solid. IH NMR (400.13 MHz, DMSO-d6) δ 7.91 (IH, s), 8.64 (IH, s), 12.87 (IH, s) MS m/e MH⁺ 188
72%	With N-chloro-succinimide In dichloromethane at 20℃; for 18 h;	METHOD I 4,5-Dichloro-7H-pyrrolo[2,3-d]pyrimidine 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine (154 mg, 1.0 mmol) was suspended in 6.0 mL of dry dichloromethane in a flame-dried flask and to this mixture was added N-chlorosuccinimide (147 mg, 1.1 mmol) in one portion. The resulting mixture stirred at room temperature for 18 h, at which time the solvent was removed under reduced pressure. The residue was triturated with water and isolated by filtration to afford 137 mg (72percent) of the title compound as a gray solid, mp 224-227° C.(dec). LRMS: 188 (M+1).

Reference： [1] Synthesis, 2011, # 9, p. 1442 - 1446
[2] Archiv der Pharmazie, 2016, vol. 349, # 5, p. 356 - 362
[3] European Journal of Medicinal Chemistry, 2017, vol. 138, p. 543 - 551
[4] Patent: CN107556318, 2018, A, . Location in patent: Paragraph 0101-0105
[5] Journal of Medicinal Chemistry, 1988, vol. 31, # 11, p. 2086 - 2092
[6] Patent: US2009/42893, 2009, A1, . Location in patent: Page/Page column 13
[7] Helvetica Chimica Acta, 1994, vol. 77, # 4, p. 897 - 903
[8] Patent: WO2008/75109, 2008, A1, . Location in patent: Page/Page column 115
[9] Patent: WO2008/75110, 2008, A1, . Location in patent: Page/Page column 107
[10] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 5, p. 2052 - 2062
[11] Patent: US6635762, 2003, B1, . Location in patent: Page/Page column 25
[12] Patent: US2009/264450, 2009, A1, . Location in patent: Page/Page column 7
[13] Patent: WO2012/80735, 2012, A1, . Location in patent: Page/Page column 11; 43
[14] Patent: WO2015/143712, 2015, A1, . Location in patent: Page/Page column 50; 51

2
[ 1618-36-6 ]
[ 115093-90-8 ]

Yield	Reaction Conditions	Operation in experiment
83%	With N-chloro-succinimide In dichloromethane at 43℃; for 8 h;	A. Preparation of 4,5-dichloro-7H-pyrrolo[2,3-d]pyrimidine; Following the procedure in Pdulo, J. S.; Saxena, N. K.; Nassiri, M. R.; Turk, S. R.; Drach, J. C.; Townsend, L. B. J. Med. Chem. 31:2086 (1988), 4-chloro-5-methyl-7H-pyrrolo[2,3-d]pyrimidine (Example 1A, 20. g, 0.13 mol) was suspended in anhydrous dichloromethane (500 mL), followed by addition of N-chlorosuccinimide (20.8 g, 0.160 mol). The reaction mixture was refluxed at 43° C. for 8 hours. The reaction was cooled down, and the white solid was filtered, washed with dichloromethane (300 mL), and dried to give 4,5-dichloro-7H-pyrrolo[2,3-d]pyrimidine (20 g, 83percent)

Reference： [1] Patent: US2006/189638, 2006, A1, . Location in patent: Page/Page column 10

3
[ 128-09-6 ]
[ 3680-69-1 ]
[ 115093-90-8 ]

Reference： [1] Journal of Medicinal Chemistry, 2009, vol. 52, # 21, p. 6515 - 6518

[ 115093-90-8 ] Synthesis Path-Downstream 1~87

1
[ 115093-90-8 ]
[ 74564-16-2 ]
[ 123148-80-1 ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 1984 - 1992

2
[ 115093-90-8 ]
[ 81777-40-4 ]
[ 115093-84-0 ]

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 2086 - 2092

3
[ 115093-90-8 ]
[ 4330-21-6 ]
[ 157666-30-3 ]

Yield	Reaction Conditions	Operation in experiment
		Step 2: Synthesis of (2R,35,5R)-5-(4,5-dichloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(((4-methylbenzoyl)oxy)methyl)tetrahydrofuran-3-yl 4-methylbenzoateTo a suspension of NaH (60% dispersion in mineral oil, 0.538 g, 13.46 mmol) in anhydrous ACN (100 ml) under argon atmosphere in a 250 ml three necked round-bottom flask, was added <strong>[115093-90-8]4,<strong>[115093-90-8]5-dichloro-7H-pyrrolo[2,3-d]pyrimidine</strong></strong> (2.3 g, 12.23 mmol) in portions and the mixture was stirred at ambient temperature for 30 minutes. The cloudy mixture became clear and then

Reference： [1]Helvetica Chimica Acta,1994,vol. 77,p. 897 - 903
[2]Helvetica Chimica Acta,1999,vol. 82,p. 12 - 18
[3]Patent: WO2015/143712,2015,A1 .Location in patent: Page/Page column 50; 51

4
[ 3680-69-1 ]
[ 115093-90-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 20℃; for 72h;	General procedure: To a solution of readily available 3a (20mmol) in N, N-dimethylformamide (DMF) (15mL) was added NCS/NBS (21mmol) and the reaction mixture was stirred at room temperature for 72h. Then ice water (150mL) was poured into the mixture, the precipitate was filtered, washed with water (3×100mL), and dried to give 3b and 3c.
95%	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 20℃; for 12h;	Dissolve 4-chloro-pyrrolo[2,3-d]pyrimidine (20 mmol) in DMF (6 mL), add NBS or NCS (21 mmol) in portions on ice bath, react at room temperature for 12 h, and pour the reaction mixture into 80 mL of ice. In the water, a large number of off-white solids precipitated and were filtered. The filter cake was washed with 15 mL of water and dried to give Intermediate 2. 4,5-dichloro-pyrrolo[2,3-d]pyrimidine (2a) Gray solid, yield 95%
88%	With N-chloro-succinimide; In dichloromethane; for 72h;Heating / reflux;	3H, m), 2.4 (3H, s), 1.31 (3H, J=6.8 Hz, d); MS (ES+) [M+H]+=455.6.15. Example 15(S)-N-(3-bromophenyl)-4-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N'-cyano-2-methylpiperazine-1-carboximidamide A. Preparation of 4,5-dichloro-7H-pyrrolo[2,3-d]pyrimidine: 4-Chloro-pyrrolo[2,3-d]pyrimidine (0.5 g, 3.26 mmol) was suspended in anhydrous CH2Cl2 (25 ml), and N-chlorosuccinimide (0.87 g, 6.52 mmol) was added. The reaction mixture was refluxed for 3 days, then cooled to room temperature. The white solid was collected by filtration to give 5-dichloro-7H-pyrrolo[2,3-d]pyrimidine (0.54 g, 2.9 mmol, 88%).1H NMR (CD3OD): delta 8.57 (1H, s), 7.60 (1H, s); MS (ES+) [M+H]+=188.

80%	With N-chloro-succinimide; In dichloromethane; at 20℃; for 6h;Heating / reflux;	PREPARATION 7; 4,5-dichloro-7H-pyrrolor2,3-dlpyrimidineN-Chlorosuccinimide (4.78 g, 35.81 mmol) was added portionwise to a stirred suspension of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (5g, 32.56 mmol) in DCM, dry (125ml) at room temperature. The resulting suspension was stirred for 1 hour then heated to reflux for 5 hours, then allowed to cool down and left to stir at room temperature overnight. The reaction mixture was evaporated and suspended in water (50 mL). The suspension was filtered giving crude product as a grey solid. The solid was suspended in hot methnol and filtered. The solid was then suspended in hot ethyl acetate and filtered to give 4,5- dichloro-7H-pyrrolo[2,3-d]pyrimidine (4.87 g, 80 %) as a grey solid. IH NMR (400.13 MHz, DMSO-d6) delta 7.91 (IH, s), 8.64 (IH, s), 12.87 (IH, s) MS m/e MH+ 188
80%	With N-chloro-succinimide; In dichloromethane; at 20℃;Heating / reflux;	PREPARATION I4,5-dichloro-7H-pyrrolor2,3-dlpyrimidine; N-Chlorosuccinimide (4.78 g, 35.81 mmol) was added portionwise to a stirred suspension of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (5g, 32.56 mmol) in DCM, dry (125ml) at room temperature. The resulting suspension was stirred for 1 hour then heated to reflux for 5 hours, then allowed to cool down and left to stir at room temperature overnight. The reaction mixture was evaporated and suspended in water (50 mL). The suspension was filtered giving crude product as a grey solid. The solid was suspended in hot methnol and filtered. The solid was then suspended in hot ethyl acetate and filtered to give 4,5- dichloro-7H-pyrrolo[2,3-d]pyrimidine (4.87 g, 80 %) as a grey solid. IH NMR (400.13 MHz, DMSO-d6) delta 7.91 (IH, s), 8.64 (IH, s), 12.87 (IH, s) MS m/e MH+ 188
72%	With N-chloro-succinimide; In dichloromethane; at 20℃; for 18h;	METHOD I 4,5-Dichloro-7H-pyrrolo[2,3-d]pyrimidine 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine (154 mg, 1.0 mmol) was suspended in 6.0 mL of dry dichloromethane in a flame-dried flask and to this mixture was added N-chlorosuccinimide (147 mg, 1.1 mmol) in one portion. The resulting mixture stirred at room temperature for 18 h, at which time the solvent was removed under reduced pressure. The residue was triturated with water and isolated by filtration to afford 137 mg (72%) of the title compound as a gray solid, mp 224-227 C.(dec). LRMS: 188 (M+1).
	With N-chloro-succinimide; In dichloromethane; for 18h;Reflux;	C. Preparation of 4,5-dichloro-7H-pyrrolo[2,3-d]pyrimidine. To a solution of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (154 mg, 1.0 mmol) in CH2Cl2 (6 mL) was added NCS (134 mg, 1.0 mmol). The reaction mixture was refluxed for 18 hours, filtered, and concentrated under vacuum to give the title compound, which was carried on crude. MS (ES+) [M+H]+=189.
	With N-chloro-succinimide; In dichloromethane; at 20 - 60℃; for 38h;	4-cUoro-lH-pyrrolo[2,3-d]pyrirddine( lg, 6.5mmol, commercially available from e.g. Sigma- Aldrich, Apollo or Alfa Aesar) was dissolved in DCM ( 30ml) and then NCS (1.04g, 7.8mmol) was added . The reaction mixture was stirred at room temperature for 16 hours, and then heated at 60C for 22 hours. After cooling a light yellow solid was obtained by filtration of the desired product in 1.2g. LCMS [MH+] 188.0 (at) 1.42 min ( 5 min run)
	With N-chloro-succinimide; In dichloromethane; at 40℃; for 16h;Inert atmosphere;	Step l:Synthesis of 4,5-dichloro-7H-pyrrolo[2,3-d]pyrimidineTo a mixture of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (2.5 g, 16.28 mmol) in dry DCM (100 mL) was added NCS (4.35 g, 32.6 mmol) at 25 C. The resulting mixture was stirred for 16 hours at 40 C under argon atmosphere. When the 4-chloro-7H-pyrrolo[2,3-d]pyrimidine was consumed, the mixture was filtered directly without cooling. The solid was collected, washed with DCM (20 ml), dried under vacuum to give 4,5-dichloro-7H-pyrrolo[2,3-d]pyrimidine as a solid. LC-MS: (ES, /// r): 188.01 [M+H]+. H- MR: (300MHz, d6-OMSO, ppm): delta 12.90 (br, 1H), 8.65 (s, 1H), 7.93 (d, J= 2.7Hz, 1H).
1.08 g	With N-chloro-succinimide; In dichloromethane; for 72h;Reflux;	To a solution of 4-chloro-7H-pyrrolo[2,3-djpyrimidine (2.0 g, 13.04 mmol) in DCM (80 mL) was added N-chlorosuccinimide (1.7 g, 13.04 mmol). The reaction mixture was refluxed 3 days. The reaction mixture was dissolved in water and extracted with EtOAc (3 x 50 mL). Combined organic layers were dried over Mg504, filtered and evaporated to afford 4,5-dichloro-7H-pyrrolo[2,3- djpyrimidine (1.08 g). LCMS: MW (calcd): 186.97; MS (ES, m/z): 187.98 (M+H).

Reference： [1]Synthesis,2011,p. 1442 - 1446
[2]Archiv der Pharmazie,2016,vol. 349,p. 356 - 362
[3]European Journal of Medicinal Chemistry,2017,vol. 138,p. 543 - 551
[4]Patent: CN107556318,2018,A .Location in patent: Paragraph 0101-0105
[5]Journal of Medicinal Chemistry,1988,vol. 31,p. 2086 - 2092
[6]Patent: US2009/42893,2009,A1 .Location in patent: Page/Page column 13
[7]Helvetica Chimica Acta,1994,vol. 77,p. 897 - 903
[8]Patent: WO2008/75109,2008,A1 .Location in patent: Page/Page column 115
[9]Patent: WO2008/75110,2008,A1 .Location in patent: Page/Page column 107
[10]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 2052 - 2062
[11]Patent: US6635762,2003,B1 .Location in patent: Page/Page column 25
[12]Patent: US2009/264450,2009,A1 .Location in patent: Page/Page column 7
[13]Patent: WO2012/80735,2012,A1 .Location in patent: Page/Page column 11; 43
[14]Patent: WO2015/143712,2015,A1 .Location in patent: Page/Page column 50; 51
[15]Patent: WO2019/12284,2019,A1 .Location in patent: Paragraph 0165
[16]Bioorganic and medicinal chemistry letters,2020,vol. 30

5
[ 496-15-1 ]
[ 115093-90-8 ]
5-chloro-4-(2,3-dihydro-indol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]

Reference： [1]Tetrahedron Letters,2006,vol. 47,p. 4149 - 4151

6
[ 115093-90-8 ]
[ 177-11-7 ]
C₂₀H₂₇N₅O₄ [ No CAS ]

Reference： [1]Tetrahedron Letters,2006,vol. 47,p. 4149 - 4151

7
[ 10416-59-8 ]
[ 115093-90-8 ]
C₉H₁₁Cl₂N₃Si [ No CAS ]

Reference： [1]Tetrahedron,2007,vol. 63,p. 9850 - 9861

8
[ 115093-90-8 ]
[ 952429-08-2 ]

Reference： [1]Tetrahedron,2007,vol. 63,p. 9850 - 9861

9
[ 115093-90-8 ]
[ 952429-09-3 ]

Reference： [1]Tetrahedron,2007,vol. 63,p. 9850 - 9861

10
[ 115093-90-8 ]
[ 952429-15-1 ]

Reference： [1]Tetrahedron,2007,vol. 63,p. 9850 - 9861
[2]European Journal of Medicinal Chemistry,2020,vol. 188

11
[ 115093-90-8 ]
5-chloro-3,7-dihydro-7-(β-D-ribofuranosyl)-4H-pyrrolo[2,3-d]pyrimidin-4-one [ No CAS ]

Reference： [1]Tetrahedron,2007,vol. 63,p. 9850 - 9861
[2]European Journal of Medicinal Chemistry,2020,vol. 188

12
[ 115093-90-8 ]
4-amino-5-chloro-7-(β-L-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]

Reference： [1]Tetrahedron,2007,vol. 63,p. 9850 - 9861

13
[ 115093-90-8 ]
4-amino-5-chloro-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]

Reference： [1]Tetrahedron,2007,vol. 63,p. 9850 - 9861

14
[ 115093-90-8 ]
4,5-bis-(2,3-dihydro-indol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]

Reference： [1]Tetrahedron Letters,2006,vol. 47,p. 4149 - 4151

15
[ 115093-90-8 ]
[ 157666-36-9 ]

Reference： [1]Helvetica Chimica Acta,1999,vol. 82,p. 12 - 18
[2]Helvetica Chimica Acta,1994,vol. 77,p. 897 - 903

16
[ 115093-90-8 ]
[ 220870-00-8 ]

Reference： [1]Helvetica Chimica Acta,1999,vol. 82,p. 12 - 18

17
[ 115093-90-8 ]
[ 157666-28-9 ]

Reference： [1]Helvetica Chimica Acta,1994,vol. 77,p. 897 - 903

18
[ 115093-90-8 ]
[ 115093-87-3 ]

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 2086 - 2092

19
[ 115093-90-8 ]
[ 115093-93-1 ]

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 2086 - 2092

20
[ 115093-90-8 ]
[ 115093-91-9 ]

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 2086 - 2092

21
[ 115093-90-8 ]
[ 115093-96-4 ]

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 2086 - 2092

22
[ 115093-90-8 ]
[ 123148-85-6 ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 1984 - 1992

23
[ 115093-90-8 ]
[ 123148-89-0 ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 1984 - 1992

24
[ 115093-90-8 ]
[ 123148-93-6 ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 1984 - 1992

25
[ 115093-90-8 ]
[ 123148-96-9 ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 1984 - 1992

26
[ 907182-16-5 ]
[ 115093-90-8 ]
[3-(4-Fluoro-phenoxy)-phenyl]-[1-(5-chloro-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-piperidin-4-ylmethyl]-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With triethylamine; In isopropyl alcohol; at 85℃; for 22h;	C. Preparation of [3-(4-Fluoro-phenoxy)-phenyl]-[1-(5-chloro-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-piperidin-4-ylmethyl]-amine dihydrochloride salt A suspension of [3-(4-Fluoro-phenoxy)-phenyl]-piperidin-4-ylmethyl-amine (4.5 g, 0.015 mol) and <strong>[115093-90-8]4,<strong>[115093-90-8]5-dichloro-7H-pyrrolo[2,3-d]pyrimidine</strong></strong> (2.82 g, 0.015 mol) in i-PrOH (300 mL) was placed in a round-bottomed flask. Following addition of triethylamine (3 g, 0.030 mol), the reaction mixture was then heated at 85 C. for 22 hours with stirring. The whole solution became clear after half an hour. After the reaction was complete as determined by LC/MS, the resulting mixture was allowed to cool to room temperature. The precipitated solid was isolated from the reaction mixture by filtration on a Buechner funnel and washed with water (10 mL) and then cold methanol (10 mL), dried under vacuum overnight to provide [3-(4-Fluoro-phenoxy)-phenyl]-[1-(5-chloro-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-piperidin-4-ylmethyl]-amine (4.5 g, 66%). The mother liqueur was allowed to stand overnight, an additional amount of product was isolated (0.6 g, 76%). The solid was suspended in 1 N HCl (20 mL) and strried at room temperature for an hour.

Reference： [1]Patent: US2006/189638,2006,A1 .Location in patent: Page/Page column 10

27
[ 1618-36-6 ]
[ 115093-90-8 ]

Yield	Reaction Conditions	Operation in experiment
83%	With N-chloro-succinimide; In dichloromethane; at 43℃; for 8h;	A. Preparation of 4,5-dichloro-7H-pyrrolo[2,3-d]pyrimidine; Following the procedure in Pdulo, J. S.; Saxena, N. K.; Nassiri, M. R.; Turk, S. R.; Drach, J. C.; Townsend, L. B. J. Med. Chem. 31:2086 (1988), 4-chloro-5-methyl-7H-pyrrolo[2,3-d]pyrimidine (Example 1A, 20. g, 0.13 mol) was suspended in anhydrous dichloromethane (500 mL), followed by addition of N-chlorosuccinimide (20.8 g, 0.160 mol). The reaction mixture was refluxed at 43 C. for 8 hours. The reaction was cooled down, and the white solid was filtered, washed with dichloromethane (300 mL), and dried to give 4,5-dichloro-7H-pyrrolo[2,3-d]pyrimidine (20 g, 83%)

Reference： [1]Patent: US2006/189638,2006,A1 .Location in patent: Page/Page column 10

28
[ 110-89-4 ]
[ 115093-90-8 ]
5-chloro-4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%		METHOD J 5-Chloro-4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine The product from Method I (57 mg, 0.3 mmol) was suspended in 3:0 mL of tert-butanol and to this solution was added piperidine (90 muL, 0.9 mmol) and the resulting system heated at reflux for 1 hour. The reaction mixture was cooled to room temperature and water was added (4.0 mL). The solution was adjusted to pH 1 with 1 N HCl and then washed with ether. The aqueous layer was removed and adjusted to pH 12 with 2 N NaOH. The solution was then extracted 2*15 mL with dichloromethane and the combined organics washed with water then brine and dried over MgSO4. Evaporation of solvent afforded 45 mg of a yellow solid that was purified by silica-gel chromatography (3:1 ethyl acetate/hexanes) to yield 23 mg (32%) of the title compound as a light yellow solid. Mp 170-172 C. 1H NMR (400 MHz, CDCl3)delta: 1.67-1.74 (m, 6H), 3.65-3.67 (m, 4H), 7.10 (s, 1H), 8.31 (s, 1H), LRMS: 237 (M+1).

Reference： [1]Patent: US6635762,2003,B1 .Location in patent: Page/Page column 25

Yield	Reaction Conditions	Operation in experiment
137 mg (72%)		METHOD R 4,5-Dichloro-7H-pyrrolo[2,3-d]pyrimidine 4-Chloro-7H-pyrrolo[2,3d]pyrimidine (154 mg, 1.0 mmol) was suspended in 6.0 mL of dry dichloromethane in a flame-dried flask and to this mixture was added N-chlorosuccinimide (147 mg, 1.1 mmol) in one portion. The resulting mixture stirred at room temperature for 18 h, at which time the solvent was removed under reduced pressure. The residue was triturated with water and isolated by filtration to afford 137 mg (72%) of the title compound as a gray solid, mp 224-227 C.(dec). LRMS: 188 (M+1).

30
[ 1035389-33-3 ]
[ 115093-90-8 ]
[ 1035386-82-3 ]

Yield	Reaction Conditions	Operation in experiment
33.5%		45B. (4-(lH-benzord1imidazol-2-yl)-l-(5-chloro-7H-pyrrolor2.3-d1pyrimidin-4- yl)piperidin-4-yl)methanamineN-Ethyldiisopropylamine (0.132 ml, 0.76 mmol) was added to 4,5-dichloro-7H- pyrrolo[2,3-d]pyrimidine (119 mg, 0.63 mmol) (Preparation 7) and 1-(4-(1H- benzo[d]imidazol-2-yl)piperidin-4-yl)-N-(diphenylmethylene)methanamine (250mg, 0.63 mmol) in butan-1-ol (4 ml). The resulting solution was stirred at 110 0C for 2 hours.Hydrogen chloride 6N in isopropanol (1.056 ml, 6.34 mmol) and water (1 ml) were added and the reaction was heated for a further 10 minutes. The crude product was purified by ion exchange chromatography, using an SCX column. The product was eluted from the column using 7M NH3/MeOH and product containing fractions were evaporated to dryness. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5mu silica, 19 mm diameter, 100 mm length), using decreasingly polar <n="148"/>mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford (4-(lH-benzo[d]imidazol-2-yl)-l- (5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl)methanamine (81 mg, 33.5 %) as a white solid. 1U NMR (400.13 MHz, DMSO-d6) delta 1.86 - 1.93 (2H, m), 2.44-2.52 (2H, d), 2.82 (2H, s),3.21 (2H, s), 4.03 - 4.06 (2H, m), 7.12 - 7.15 (2H, m), 7.45 (IH, s), 7.51 - 7.54 (2H, m),8.22 (IH, s)MS m/e MH+ 382

Reference： [1]Patent: WO2008/75109,2008,A1 .Location in patent: Page/Page column 145-146

31
[ 1035346-17-8 ]
[ 115093-90-8 ]
(1-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)piperidin-4-yl)methanamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33.4%		EXAMPLE 29(l-(5-Chloro-7H-pyrrolor2.3-d1pyrimidin-4-yl)-4-(3-(l-methyl-lH-pyrazol-4- yl)phenyl)piperidin-4-yl)methanamine; N-Ethyldiisopropylamine (0.120 ml, 0.69 mmol) was added to 4,5-dichloro-7H- pyrrolo[2,3-d]pyrimidine (108 mg, 0.58 mmol) (Preparation I) and N- (diphenylmethylene)- 1 -(4-(3-( 1 -methyl- 1 H-pyrazol-4-yl)phenyl)piperidin-4- yl)methanamine (250mg, 0.58 mmol) (Example 28D) in butan-1-ol (4 ml). The resulting solution was stirred at 110 0C for 2 hours. Hydrogen chloride 6N in isopropanol (0.959 ml, 5.75 mmol) and water (1 ml) were added and heating continued for 10 minutes. The crude product was purified by ion exchange chromatography, using an SCX column. The product was eluted from the column using 7M NH3/MeOH and product containing fractions were evaporated to dryness. The crude product was purified by preparative HPLC (Waters XBridge Prep Cl 8 OBD column, 5mu silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford (l-(5- chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-(3-(l -methyl- lH-pyrazo 1-4- yl)phenyl)piperidin-4-yl)methanamine (81 mg, 33.4 %) as a white solid. IH NMR (400.13 MHz, DMSO-d6) delta 1.98 - 2.01 (2H, m), 2.26 (2H, s), 2.72 (2H, s), 3.87 (5H, s), 7.24 (IH, s), 7.35 (IH, t), 7.40 - 7.42 (IH, m), 7.45 (IH, s), 7.56 (IH, s), 7.87 - 7.88 (IH, m), 8.17 (IH, s), 8.21 (IH, s) <n="154"/>MS m/e MH+ 422

Reference： [1]Patent: WO2008/75110,2008,A1 .Location in patent: Page/Page column 151

32
[ 115093-90-8 ]
[ 6882-74-2 ]
[ 1041703-83-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 3359 - 3363

33
[ 115093-90-8 ]
[ 6219-58-5 ]
[ 1041703-73-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 3359 - 3363

34
[ 115093-90-8 ]
[ 167484-18-6 ]
[ 908283-43-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 3359 - 3363

35
[ 115093-90-8 ]
[ 163226-45-7 ]
C₃₄H₂₉Cl₂N₃O₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 206 - 213

36
[ 1192189-21-1 ]
[ 115093-90-8 ]
[ 1192189-19-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In isopropyl alcohol; at 130℃; for 0.5h;Microwave irradiation;	D. Preparation of 1-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-(4-fluorophenoxy)phenyl)-4-methylpiperidine-4-carboxamide. N-(3-(4-Fluorophenoxy)phenyl)-4-methylpiperidine-4-carboxamide from step B (50 mg, 0.13 mmol), <strong>[115093-90-8]4,<strong>[115093-90-8]5-dichloro-7H-pyrrolo[2,3-d]pyrimidine</strong></strong> from step C (19 mg, 0.1 mmol), and triethylamine (0.04 mL, 0.3 mmol) were combined in isopropanol (1 mL) and heated at 130 C. for 30 minutes under microwave conditions. The product was isolated by prep HPLC to give the title compound. 1H NMR (CD3OD): delta 8.22 (s, 1H), 7.30-7.35 (m, 4H), 7.03-7.14 (m, 4H), 6.73-6.76 (m, 1H), 3.96-4.02 (m, 2H), 3.44-3.51 (m, 2H), 2.35-2.38 (m, 2H), 1.74-1.81 (m, 2H), 1.38 (s, 3H); MS (ES+) [M+H]+=480.

Reference： [1]Patent: US2009/264450,2009,A1 .Location in patent: Page/Page column 7

37
[ 128-09-6 ]
[ 3680-69-1 ]
[ 115093-90-8 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 6515 - 6518

38
[ 115093-90-8 ]
[ 169447-70-5 ]
[ 76-05-1 ]
C₁₁H₁₄ClN₅ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 6515 - 6518

39
(R)-N-((3-aminopyrrolidin-3-yl)methyl)-2,4-difluorobenzamide [ No CAS ]
[ 115093-90-8 ]
(S)-N-((3-amino-1-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl)methyl)-2,4-difluorobenzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 4615 - 4622

40
C₁₂H₁₆FN₃O [ No CAS ]
[ 115093-90-8 ]
[ 1004990-33-3 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 4615 - 4622

41
[ 1004992-38-4 ]
[ 115093-90-8 ]
(S)-N-((3-amino-1-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl)methyl)-4-chlorobenzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 4615 - 4622

42
[ 115093-90-8 ]
[ 41107-17-9 ]

Reference： [1]Synthesis,2011,p. 1442 - 1446

43
[ 115093-90-8 ]
4-amino-5-bromo-7-(5-deoxy-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]

Reference： [1]Synthesis,2011,p. 1442 - 1446

44
[ 115093-90-8 ]
[ 27821-07-4 ]
[ 1323111-55-2 ]

Reference： [1]Synthesis,2011,p. 1442 - 1446

45
[ 1154161-03-1 ]
[ 115093-90-8 ]
3-[(5-chloro-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-N-methyl-4-(4-morpholinyl)benzenesulfonamide hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	In isopropyl alcohol; at 80℃; for 18h;	EXAMPLE 1 193-[(5-chloro-1 H-pyrrolo[2,3-c/]pyrimidin-4-yl)amino]-/V-methyl-4-(4- morpholinyl)benzenesulfonamide hydrochlorideA mixture of 3-amino-/V-methyl-4-(4-morpholinyl)benzenesulfonamide (0.141 g, 0.519 mmol) isopropanol (1 mL) was treated with <strong>[115093-90-8]4,<strong>[115093-90-8]5-dichloro-7H-pyrrolo[2,3-d]pyrimidine</strong></strong> (0.075 g, 0.399 mmol) and heated at 80 C overnight. After 18 h, the reaction mixture was cooled to rt and the solid collected by filtration, washed with MeOH, and dried to afford the title compound (0.107 g, 58%) as a pale gray solid.

Reference： [1]Patent: WO2011/149827,2011,A1 .Location in patent: Page/Page column 163

46
((2R,3R,4R)-3-(benzoyloxy)-4-fluoro-5-hydroxy-4-methyltetrahydrofuran-2-yl)methyl benzoate [ No CAS ]
[ 115093-90-8 ]
C₂₆H₂₀Cl₂FN₃O₅ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 7094 - 7098

47
[ 115093-90-8 ]
[ 1365626-36-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 2052 - 2062

48
[ 115093-90-8 ]
[ 100-39-0 ]
[ 1380310-92-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 2052 - 2062

49
[ 115093-90-8 ]
[ 1372611-13-6 ]

Reference： [1]Collection of Czechoslovak Chemical Communications,2011,vol. 76,p. 1413 - 1431

50
[ 115093-90-8 ]
[ 1372611-15-8 ]

Reference： [1]Collection of Czechoslovak Chemical Communications,2011,vol. 76,p. 1413 - 1431

51
[ 115093-90-8 ]
(2S/R,3R,4R,5R)-5-((benzoyloxy)methyl)-3-methyltetrahydrofuran-2,3,4-triyltribenzoate [ No CAS ]
[ 1372611-11-4 ]

Reference： [1]Collection of Czechoslovak Chemical Communications,2011,vol. 76,p. 1413 - 1431

52
[ 115093-90-8 ]
[ 98-09-9 ]
[ 1383343-39-2 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 4,5-dicWoro H-pyrrolo[2,3-JJpyrimidine D39 (lg) in DMF ( 20ml) at 0C was added sodium hydride (60% w/w in mineral oil, 255mg, 6.4mmol) and the mixture stirred for 20 mins. Phenylsulfonyl chloride (1.3 lg, 7.4mmol) was the added dropwise and the reaction mixture was kept in a cool bath for 15 hours. The mixture was poured into water (40ml), and the precipitate was filtered, washed with water and Et20, dried in a vacuum to give the desired product D40 in 1.62g as an ashen solid. LCMS [MuEta+] 329.9 (at) 1.77min ( 5 min run)

Reference： [1]Patent: WO2012/80735,2012,A1 .Location in patent: Page/Page column 11; 43

53
[ 115093-90-8 ]
[ 1383342-15-1 ]

Reference： [1]Patent: WO2012/80735,2012,A1

54
[ 115093-90-8 ]
[ 1383343-42-7 ]

Reference： [1]Patent: WO2012/80735,2012,A1

55
3-(4-amino-1H-pyrazol-1-yl)-N-(6-methylpyridin-3-yl)benzamide [ No CAS ]
[ 115093-90-8 ]
3-(4-((5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-1H-pyrazol-1-yl)-N-(6-methylpyridin-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tert-butyl alcohol; at 90℃; for 12h;	General procedure: The <strong>[115093-90-8]4,<strong>[115093-90-8]5-dichloro-7H-pyrrolo[2,3-d]pyrimidine</strong></strong> (0.11 mmol) was added to 3-(4- amino-i H-pyrazol -1 -yl)-N-(6-methylpyridin-3 -yl)benzamide (0.1 mmol) in tBuOH (1.0 mL) and stirred at 90 C for 12 h. The solvent was evaporated and the residue was purified by reverse-phase preparative HPLC to give the product.Procedures in Scheme 4 were utilized to synthesize this compound. LC-MS: 445(M+H).

Reference： [1]Patent: WO2015/84936,2015,A1 .Location in patent: Page/Page column 55; 56

56
(3R,5S)-tert-butyl 3-amino-5-((tert-butyldimethylsilyl)oxy)piperidine-1-carboxylate [ No CAS ]
[ 115093-90-8 ]
(3S,5R)-tert-butyl 3-((tert-butyldimethylsilyl)oxy)-5-((5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 80 - 90℃; for 40h;	Step 1. (3S,5R)-tert-Butyl 3-((tert-butyldimethylsilyl)oxy)-5-((5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidine-1-carboxylate. A mixture of (3R,5S)-tert-butyl 3-amino-5-((tert-butyldimethylsilyl)-oxy)piperidine-1-carboxylate (200 mg, 0.61 mmol), <strong>[115093-90-8]4,<strong>[115093-90-8]5-dichloro-7H-pyrrolo[2,3-d]pyrimidine</strong></strong> (136 mg, 0.73 mmol) and DIPEA (156 mg, 1.21 mmol) in n-BuOH (5 mL) was heated to 80 C. for 20 hours. LC-MS showed about 60% <strong>[115093-90-8]4,<strong>[115093-90-8]5-dichloro-7H-pyrrolo[2,3-d]pyrimidine</strong></strong> was remaining. 200 mg of (3R,5S)-tert-butyl 3-amino-5-((tert-butyldimethylsilyl)oxy)piperidine-1-carboxylate was added, and the reaction mixture was heated to 90 C. for 20 hours. The reaction mixture was evaporated to dryness to give crude material, which after chromatography (silica, DCM/MeOH, 100:0-90:10) gave (3S,5R)-tert-butyl 3-((tert-butyldimethylsilyl)oxy)-5-((5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidine-1-carboxylate (290 mg, 83%) as a yellow solid. LC/MS (M+H) 482.1

Reference： [1]Patent: US2015/158864,2015,A1 .Location in patent: Paragraph 0591

57
[ 76513-69-4 ]
[ 115093-90-8 ]
C₁₂H₁₇Cl₂N₃OSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: Step 1. Halide monomers (300 mumol) were dissolved anhydrous DMF (10 ml/mmol, 3 ml) under argon atmosphere. NaH (60% suspension in mineral oil, 2 equiv, 600 mumol, 30 mg) was added at 0 C. to each reaction vial. Each reaction vial was stirred at 0 C. for 30 min. SEM chloride (2 equiv, 600 mumol, 106 muL) was added dropwise to the reaction mixture and stirring was continued at 25 C. for 16 hrs. Completion of reaction was monitored by LCMS/TLC and solvents were stripped off using thermo explorer (1 hr, 5 torr, and 45 C.). The residue was purified by column chromatography using 5-10% ethyl acetate-hexane as eluent. For each monomer yield was around 75-80%.

Reference： [1]Patent: US2015/158864,2015,A1 .Location in patent: Paragraph 0261; 0262

58
[ 115093-90-8 ]
(R)-1-(3-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)prop-2-en-1-one [ No CAS ]

Reference： [1]Patent: US2015/158864,2015,A1

59
[ 115093-90-8 ]
C₂₂H₃₆ClN₅O₃Si [ No CAS ]

Reference： [1]Patent: US2015/158864,2015,A1

60
[ 115093-90-8 ]
C₁₂H₁₆ClN₅O [ No CAS ]

Reference： [1]Patent: US2015/158864,2015,A1

61
[ 115093-90-8 ]
C₁₁H₁₄ClN₅ [ No CAS ]

Reference： [1]Patent: US2015/158864,2015,A1

62
[ 115093-90-8 ]
3-amino-N-methylbenzenesulfonamide [ No CAS ]
3-[(5-chloro-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-N-methylbenzenesulfonamide hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 7431 - 7448

63
[ 115093-90-8 ]
[ 57260-71-6 ]
4-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 110℃; for 16h;	General procedure: To a solution of 3a-3c (3.2mmol) and N, N-diisopropylethylamine (DIEA) (4.8mmol) in DMF (3mL) was added N-Boc-piperazine (3.6mmol), the resulting mixture was heated at 110C for 16h. The reaction mixture was poured into ice water (30mL) and extracted with ethyl acetate (3×30mL), the combined organic layers were washed with brine (2×30mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography with petroleum ether/ethylacetate (1: 3) to obtain 4a-4c.

Reference： [1]Archiv der Pharmazie,2016,vol. 349,p. 356 - 362
[2]European Journal of Medicinal Chemistry,2017,vol. 138,p. 543 - 551

64
[ 367-27-1 ]
[ 115093-90-8 ]
[ 1613479-25-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 3199 - 3203

65
C₆H₄ClN₃O [ No CAS ]
[ 115093-90-8 ]

Yield	Reaction Conditions	Operation in experiment
	With trichlorophosphate; In acetonitrile; at 110℃; for 0.0833333h;Microwave irradiation;	General procedure: A solution of 6,7-dimethoxyisoquinolin-1(2H)-one(200 mg, 0.97 mmol), phosphoryl trichloride (0.268 mL, 2.92 mmol) inacetonitrile (5 mL) was stirred at 110 C for 5 minutes under microwaveirradiation. The reaction was quenched with a saturated aqueous sodium bicarbonatesolution and stirred at ambient temperature for 1 h. It was filtered throughcelite and washed with ethyl acetate. The filtrate was concentrated to dryness.The crude material was purified by flash chromatography, eluting with heptanesand ethyl acetate (1:0 to 0:1) to give the desired product as a gum (99 mg,45.4 %).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 3199 - 3203

66
1-O-acetyl-2,3,5-tri-O-benzoyl-3-C-ethyl-α,β-D-ribofuranose [ No CAS ]
[ 115093-90-8 ]
4,5-dichloro-N7-(3′-C-ethyl-2′,3′,5′-tri-O-benzoyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.471 g		General procedure: In a flame-dried 2-neck round bottom flask, equipped with a stir bar was added the appropriate heterocycle (1.1 eq.) under argon. Then, anhydrous MeCN (7.5mL/mmol SM) was added, followed by BSA (1.2 eq.). The resulting suspension was stirred at ambient temperature for approximately 10min; after which a clear solution was obtained. Then, glycosyl donor, 18 [15] (1 eq.) was added in one portion, immediately followed by TMSOTf (1.25 eq.). The resulting solution was stirred at ambient temperature for another 15min, and then transferred to a pre-heated oil bath at 80C. Heating was continued until TLC analysis showed full consumption of the starting material (?2-3h), after which the mixture was cooled to ambient temperature. EA was added, and the mixture poured into a sat. aq. NaHCO3 solution. The layers were separated and the water layer extracted twice more with EA. The organic layers were combined, dried over Na2SO4, filtered and evaporated till dryness. The residue was purified by column chromatography 15% EA/Hexanes.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 157,p. 248 - 267

67
[ 115093-90-8 ]
[ 151965-56-9 ]
6,7-dichloro-9-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}-7-deazapurine [ No CAS ]

Reference： [1]ChemMedChem,2018,vol. 13,p. 1779 - 1796

68
[ 115093-90-8 ]
9-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}-7-chloro-7-deazaadenine [ No CAS ]

Reference： [1]ChemMedChem,2018,vol. 13,p. 1779 - 1796

69
[ 115093-90-8 ]
9-[2-(phosphorylmethoxy)ethyl]-7-chloro-7-deazaadenine bis(L-phenylalanine isopropyl ester) [ No CAS ]

Reference： [1]ChemMedChem,2018,vol. 13,p. 1779 - 1796

70
[ 115093-90-8 ]
C₁₅H₂₈ClN₄O₄PSi₂ [ No CAS ]

Reference： [1]ChemMedChem,2018,vol. 13,p. 1779 - 1796

71
[ 115093-90-8 ]
[ 73874-95-0 ]
tert-butyl N-[1-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.42 g	With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 20℃; for 72h;	Tert-butyl N-(4-piperidyl)carbamate (895.3 mg, 4.47 mmol) and 4,5-dichloro-7H-pyrrolo[2,3- djpyrimidine (1080 mg, 5.36 mmol) were dissolved in NMP (8 ml) and DIPEA (2.33 ml, 13.4 mmol) was added dropwise. The reaction mixture was stirred at room temperature 3 days. The mixture was dissolved in water and extracted with EtOAc (3 x l5mL). Combined organic layers were dried and concentrated to afford the cmde product which was recrystallized with acetonitrile to afford tert-butyl N-(5 -chloro-7H-pyrrolo [2,3 -djpyrimidin-4-yl)carbamate(1.42 g). LCMS: MW (calcd): 351.15; MS (ES, m/z): 352.22 (M+H).

Reference： [1]Patent: WO2019/12284,2019,A1 .Location in patent: Paragraph 0166

72
[ 115093-90-8 ]
[ 2365-48-2 ]
C₉H₈ClN₃O₂S [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry letters,2020,vol. 30

73
[ 115093-90-8 ]
C₈H₆ClN₃O₂S [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry letters,2020,vol. 30

74
[ 115093-90-8 ]
4-ethoxy-5-chloro-N7-(β-D-ribofuranosyl)-pyrrolo[2,3-d]pyrimidine [ No CAS ]