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[ CAS No. 945950-37-8 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 945950-37-8
Chemical Structure| 945950-37-8
Chemical Structure| 945950-37-8
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Product Details of [ 945950-37-8 ]

CAS No. :945950-37-8 MDL No. :MFCD13619883
Formula : C7H7N3 Boiling Point : -
Linear Structure Formula :- InChI Key :QWIAHMVNMONKCU-UHFFFAOYSA-N
M.W : 133.15 Pubchem ID :51341959
Synonyms :

Calculated chemistry of [ 945950-37-8 ]

Physicochemical Properties

Num. heavy atoms : 10
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.14
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 38.85
TPSA : 41.57 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.36 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.4
Log Po/w (XLOGP3) : 1.06
Log Po/w (WLOGP) : 1.27
Log Po/w (MLOGP) : 0.51
Log Po/w (SILICOS-IT) : 2.03
Consensus Log Po/w : 1.25

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.0
Solubility : 1.33 mg/ml ; 0.01 mol/l
Class : Very soluble
Log S (Ali) : -1.52
Solubility : 3.98 mg/ml ; 0.0299 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.89
Solubility : 0.171 mg/ml ; 0.00129 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.25

Safety of [ 945950-37-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H320-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 945950-37-8 ]

* 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.

  • Downstream synthetic route of [ 945950-37-8 ]

[ 945950-37-8 ] Synthesis Path-Downstream   1~76

  • 1
  • 4-chloro-1H-pyrrolo[2,3-d]pyrimidine [ No CAS ]
  • iron(III) acetylacetonate [ No CAS ]
  • [ 945950-37-8 ]
YieldReaction ConditionsOperation in experiment
69% With magnesium chloride; In tetrahydrofuran; at 20℃; for 8h; Example 31; [(1S,2S,4R)-2-Hydroxy-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentyl]methyl sulfamate (Compound I-46); Step a: 4-Methyl-7H-pyrrolo[2,3-d]pyrimidine; A 3.00 M solution of magnesium chloride in THF (13.0 mL, 39.0 mmol) was added dropwise to a stirred solution of 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (2.50 g, 16.3 mmol) and ferric acetylacetonate (700. mg 1.98 mmol) in THF (30.0 mL) under an atmosphere of argon. The resulting reaction mixture was stirred at rt for 8 h. The mixture was poured onto a mixture of ice (100 mL) and ammonium chloride (1.00 g) and the mixture was extracted with chloroform. Volatiles were removed in vacuo, and C-18 column chromatography eluting with a gradient of 0 to 60% AcCN in water with 0.1% AA afforded the title compound (1.50 g, 69%). LC/MS: Rt=0.94 min, ES+ 134 (AA standard).
  • 2
  • [ 918523-58-7 ]
  • [ 945950-37-8 ]
  • [ 1195071-58-9 ]
YieldReaction ConditionsOperation in experiment
To <strong>[945950-37-8]4-methyl-7H-pyrrolo[2,3-d]pyrimidine</strong> (42, 0.192 g, 1.44 mmol), propane-1-sulfonic acid (2,4-difluoro-3-formyl-phenyl)-amide (9, 0.456 g, 1.73 mmol), potassium hydroxide (0.263 g, 4.69 mmol) and 1.0 mL of methanol were added to provide a solution. The reaction was allowed to stir at room temperature for 30 hours, then quenched with water and adjusted to pH~5 with acetic acid and sodium bicarbonate and extracted with ethyl acetate and saturated sodium chloride. The organic layer was washed with water and brine, dried with magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluding with ethyl acetate and hexane with 4% acetic acid. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as an off-white solid (P-0055, 215 mg). 1H-NMR(dmso-d6) showed it contains about >80% of the desired compound, used in the next step without further purification. MS(ESI) [M+H-]+=397.1.
  • 3
  • [ 75-16-1 ]
  • [ 3680-69-1 ]
  • [ 945950-37-8 ]
YieldReaction ConditionsOperation in experiment
84.2% Step 1: 4-methyl-7H-pyrrolo[2,3-d]pyrimidine 150 g of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine and 5.72 g of Pd(bppf)Cl2 were added to 1.5 L of tetrahydrofuran, stirred at room temperature for 0.5 hour, and then cooled down to below 0 C. To the resulting mixture was slowly added dropwise 850 mL of methylmagnesium bromide (3M dissolved in ether). After the addition was completed, the temperature was raised to 6065 C., and the resulting mixture reacted under reflux for 2 hours. Then, the temperature was lowered to below 0 C., and the reaction was quenched by slowly adding dropwise concentrated hydrochloric acid. After the addition was completed, 650 mL of purified water was added to the resulting mixture and stirred for 15 minutes, the phases were separated and the organic phase was discarded. The aqueous phase was adjusted to pH 6 with NaHCO3 and then suction-filtered, the filter cake was washed with 455 mL of purified water, and the filtrate was collected and extracted three times with 1.05 L of ethyl acetate, and then the organic phase was concentrated to obtain 4-methyl-7H-pyrrolo[2,3-d]pyrimidine (109.5 g, 84.2%). 1H-NMR (500 MHz, DMSO-d6): delta=12.00 (bs, 1H), 8.61 (s, 1H), 7.47 (d, J=3.6 Hz, 1H), 6.62 (d, J=3.5 Hz, 1H), 2.64 (d, J=1.6 Hz, 3H); MS (ES): 134.07 (M+H+).
(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In diethyl ether; toluene; at 20 - 60℃;Inert atmosphere; Into a round bottom flask the catalyst PdCl2(dppf), under an atmosphere of nitrogen, was placed with 15 mL of toluene along with a stir bar. A suspension of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (1, 1.47 g, 9.57 mmol) in 15 mL of toluene was added at room temperature. After stirring for 10 minutes, methylmagnesium bromide (17.00 mL, 3.00 M in ether, 51.00 mmol) was added dropwise. The solution turned from orange to yellow, and was slowly heated to 60 C. and stirred for 3 hrs at 60 C. and then overnight at room temperature. The resulting dark orange reaction mixture was quenched with 1 N hydrochloric acid and adjusted to pH~5, then extracted with ethyl acetate and water saturated with sodium chloride. The organic layer was washed with water and brine, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluding with ethyl acetate and hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as a yellow solid (42, 202 mg). 1H-NMR(dmso-d6) was consistent with the desired compound. MS(ESI) [M+H+]+=134.3.
Step 1a-Preparation of 4-methyl-7H-pyrrolo[2,3-d]pyrimidine (15)To 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (9, 5.03 g, 32.8 mmol) in 100 mL of toluene, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) 1:1 complex with dichloromethane (0.627 g, 0.328 mmol) is added under an atmosphere of nitrogen. After stirring for 10 minutes, methylmagnesium bromide (62.9 mL, 3.00 M in ether, 189 mmol) is added slowly. The reaction is heated at 55 C. overnight, then cooled to -70 to -80 C. and quenched by adding ammonium chloride dropwise. Then 1N hydrochloric acid is added and the pH is adjusted to 7-8 with the addition of saturated sodium bicarbonate. This is extracted 3× with ethyl acetate. The combined organic layer is washed with saturated ammonium chloride and brine, then dried with magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with ethyl acetate and dichloromethane, then methanol and dichloromethane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound as a tan solid (15). MS (ESI) [M+H+]+=134. This is reacted similarly to steps 2 and 3 of Scheme 4 to provide the desired compound 16.
Step 1 - Preparation of 4-methyl-7H-pyrrolo[2,3-d]pyrimidine (7):[0215] Into a round bottom flask the catalyst [1,1 '-bis(diphenylphosphino)ferrocene]dichloropalladium(II), 1 : 1 complex with dichloromethane (70.0 mg, 0.09 mmol), is placed under nitrogen with 15 mL of toluene along with a stir bar. A suspension of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (1, 1.47 g, 9.57 mmol) in 15 mL of toluene is added at room temperature. After stirring for 10 minutes, methylmagnesium bromide (17.00 mL, 3.00 M in ether, 51.00 mmol) is added dropwise. The solution is slowly heated to 60 C and stirred for 3 hrs at 60 C, then overnight at room temperature. The resulting dark orange reaction mixture is quenched with 1 N hydrochloric acid and adjusted to pH ~5, then extracted with ethyl acetate and water saturated with sodium chloride. The organic layer is washed with water and brine, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography eluting with ethyl acetate and hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound as a yellow solid (8, 202 mg). 1H-NMR(dmso-d6) is consistent with the desired compound. MS(ESI)[M+H+]+ = 134.3.
To 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (17, 5.03 g, 32.8 mmol) in 100 mL of toluene, [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium(II) 1:1 complex with dichloromethane (0.627 g, 0.328 mmol) was added under nitrogen. After stirring for 10 minutes, methylmagnesium bromide (62.9 mL, 3.00 M in ether, 189 mmol) was added slowly. The reaction was heated at 55 C. overnight, then cooled to -70 to -80 C. and quenched by adding ammonium chloride dropwise. Then 1N hydrochloric acid was added and the pH was adjusted to 7-8 with addition of saturated sodium bicarbonate. This was extracted 3× with ethyl acetate. The combined organic layer was washed with saturated ammonium chloride and brine, then dried with magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with ethyl acetate and dichloromethane, then methanol and dichloromethane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as a tan solid (18). MS (ESI) [M+H?]?=134.

  • 4
  • [ 945950-37-8 ]
  • [ 1415220-34-6 ]
  • 5
  • [ 945950-37-8 ]
  • [ 1415220-35-7 ]
  • 6
  • [ 945950-37-8 ]
  • [ 1303426-83-6 ]
YieldReaction ConditionsOperation in experiment
0.94 g With N-iodo-succinimide; In dichloromethane; at 20℃; for 0.75h; To <strong>[945950-37-8]4-methyl-7H-pyrrolo[2,3-d]pyrimidine</strong> (18, 0.634 g, 4.76 mmol) in 50 mL of dichloromethane, N-iodosuccinimide (1.3 g, 5.7 mmol) was added and the reaction stirred at room temperature for 45 minutes. The reaction was concentrated under vacuum, then ethyl acetate was added and washed with 1 N aqueous sodium thiosulfate. The organic layer was dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with 20-100% ethyl acetate in hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (19, 0.94 g). MS (ESI) [M+H+]+=260.26.
1.69 g With N-iodo-succinimide; In dichloromethane; at 20℃; for 2h; Suspended in 30mL of DCM was 4-methyl -7H- pyrrolo [2,3-d] pyrimidine (1g, 7.51mmol) was added N- iodosuccinimide (1.86g, 8.26mmol).It was stirred at room temperature for 2 hours the reaction mixture.The volatiles were removed in vacuo.Of anhydrous ethyl acetate and 50% saturated NaHCO3The residue obtained was extracted.With water and the organic layer was washed with brine, dried (MgSO4), Filtered and the volatiles removed in vacuo.The residue was suspended in acetonitrile and sonicated for 45 minutes.The solid was collected by filtration to give 5-iodo-4-methyl--7H- pyrrolo [2,3-d] pyrimidine (1.69 g).
  • 7
  • [ 945950-37-8 ]
  • [ 1415220-38-0 ]
  • 8
  • [ 945950-37-8 ]
  • [ 1415220-39-1 ]
  • 9
  • [ 945950-37-8 ]
  • [ 1415220-40-4 ]
  • 10
  • [ 945950-37-8 ]
  • [ 1415220-41-5 ]
  • 11
  • [ 945950-37-8 ]
  • [ 1415220-42-6 ]
  • 12
  • [ 945950-37-8 ]
  • C35H32ClN3O3 [ No CAS ]
  • 13
  • [ 945950-37-8 ]
  • C35H32BrN3O3 [ No CAS ]
  • 14
  • [ 945950-37-8 ]
  • C35H32IN3O3 [ No CAS ]
  • 15
  • [ 945950-37-8 ]
  • [ 1415220-49-3 ]
  • 16
  • [ 945950-37-8 ]
  • [ 163226-45-7 ]
  • [ 1415220-36-8 ]
  • 17
  • [ 945950-37-8 ]
  • [ 163226-45-7 ]
  • [ 1415220-48-2 ]
YieldReaction ConditionsOperation in experiment
75% With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 2h;Inert atmosphere; General procedure: To a mixture of appropriate 3a-e (1.5 mmol), 1 (1.57 mmol) and Ph3P (3.75 mmol) in THF was added DIAD (3.75 mmol) dropwise at 0 C under nitrogen and stirring continued at rt. Completion of reaction was analyzed by TLC, solvent evaporated under reduced pressure and crude was purified by column chromatography on silica gel by eluting up to 30 % ethyl acetate in hexane to give couple products in more than 80 % yield. The deprotection was carried out by heating at 60 C in 10 % HCl in MeOH. After completion (monitored by TLC), the reaction mixture was neutralized by NaHCO3 and purified by silica gel chromatography (10% methanol in DCM) to get 6a-e in 70-85% yield.
  • 18
  • [ 75-24-1 ]
  • [ 3680-69-1 ]
  • [ 945950-37-8 ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; toluene;Reflux; To a previously degassed solution of 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine (418mg, 2.72mmol) and palladium tetrakis (157mg, 0.14mmol) in THF (27mL) was added a solution of trimethylaluminium (2.72mL, 5.44mmol, 2M in toluene). After refluxing overnight, the mixture was cooled to 0C and quenched by slow addition of saturated aqueous ammonium chloride. The medium was diluted with EtOAc. The mixture was filtered and the filtrate was decanted. The organic layer was washed with brine, filtered and concentrated under vacuum to afford impure title compound (338mg). LC/MS (ES+): (0290) 134.1 (M+l).
  • 19
  • [ 945950-37-8 ]
  • [ 1309432-09-4 ]
  • 20
  • [ 945950-37-8 ]
  • [ 1254567-73-1 ]
  • [ 1309432-10-7 ]
YieldReaction ConditionsOperation in experiment
Step 1 - Preparation of 2-methyl-propane-l-sulfonic acid {2,4-difluoro-3-fhydroxy-(4-methyl-7H- pyrrolof 2, 3-d] pyrimidin- 5 -yl) -methyl] -phenyl} -amide (77):[0259] In a round bottom flask, <strong>[945950-37-8]4-methyl-7H-pyrrolo[2,3-d]pyrimidine</strong> (7, 97.0 mg, 0.728 mmol) is combined with 2-methyl-propane-l-sulfonic acid (2,4-difluoro-3-formyl-phenyl)-amide (62, 202 mg, 0.728 mmol), potassium hydroxide (204 mg, 3.64 mmol) and 1.4 mL of methanol. The reaction is stirred at room temperature for 7 hours. The reaction is neutralized with 0.1 N aqueous hydrochloric acid and extracted 3x with ethyl acetate. The combined organic layer is washed with brine, dried with sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with ethyl acetate and dichloromethane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (77, 113 mg). MS (ESI) [M- H+]- = 409.2.
  • 21
  • [ 945950-37-8 ]
  • [ 1303427-22-6 ]
  • 22
  • [ 945950-37-8 ]
  • C30H37N3O3Si [ No CAS ]
  • 23
  • [ 945950-37-8 ]
  • C34H41N5O4Si [ No CAS ]
  • 24
  • [ 945950-37-8 ]
  • C41H54N6O6Si [ No CAS ]
  • 25
  • [ 945950-37-8 ]
  • C34H40N6O3Si [ No CAS ]
  • 26
  • [ 945950-37-8 ]
  • C28H26N6O2 [ No CAS ]
  • 27
  • [ 945950-37-8 ]
  • [ 76513-69-4 ]
  • 4-methyl-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
25% a- Synhtesis of Int. 402: A sol. of <strong>[945950-37-8]4-methyl-7H-pyrrazolo[2,3-d]pyrimidine</strong> (3.11 g, 23.4 mmol) in DMF (40 mL) was cooled to 0C and treated with NaH 60% (1.40 g, 35.0 mmol). The r.m. was stirred at 0C for 2h then 2-(trimethylsilyl)ethoxymethyl chloride (4.96 mL, 28.0 mmol) was added. The r.m. was stirred at r.t. for 2h and diluted in EtOAc. The organic layer was washed with water and brine (twice), dried over MgS04 and evaporated in vacuo to give brown oil. The oil was purified by prep. LC (irregular SiOH 15-40 muiotaeta, 80g, Grace, mobile phase gradient: from DCM 100% to DCM 96%, MeOH 4%). The desired fractions were collected and solvent evaporated until dryness to give 3.53 g. The residue was purified by prep. LC (irregular SiOH 15-40 muiotaeta, 80g, Grace, mobile phase gradient: from DCM 100% to DCM 96%, MeOH 4%). The pure fractions were collected and solvent evaporated until dryness to give 1.56 g of Int. 402 as a brown oil (25%).
85 mg Sodium hydride (36mg, 0.90mmol, 60% w/w) was added to a cooled (0C) solution of impure 4-Methyl-7H-pyrrolo[2,3-d]pyrimidine (80mg, 0.6mmol) in DMF (3mL). After stirring at 0C for lOmin, 2-(trimethylsilyl)ethoxymethyl chloride (120mg, 0.72mmol) was added. The mixture was slowly allowed to stir at room temperature for 2h. The mixture was carefully quenched by addition of saturated aqueous ammonium chloride. The aqueous layer was extracted with EtOAc (three times). The combined organic layer was washed with brine, dried over sodium sulphate, filtered and concentrated under reduced pressure. Purification of the residue by chromatography on silica (cHex/EtOAc) afforded the title compound (85mg, 53%). LC/MS (ES+): 264.3 (M+l).
  • 28
  • [ 945950-37-8 ]
  • 5-iodo-4-methyl-7-(p-tolylsulfonyl)pyrrolo[2,3-d]pyrimidine [ No CAS ]
  • 29
  • [ 945950-37-8 ]
  • 5-[[3-[[ethyl(methyl)amino sulfonyl]amino]-2-fluoro-phenyl]hydroxymethyl]-4-methyl-7-(p-tolylsulfonyl)pyrrolo[2,3-d]pyrimidine [ No CAS ]
  • 30
  • [ 945950-37-8 ]
  • 5-[3-[[ethyl(meth)sulfamoyl]amino]-2-fluoro-benzoyl]-4-methyl-7-(p-tolylsulfonyl)pyrrolo[2,3-d]pyrimidine [ No CAS ]
  • 31
  • [ 945950-37-8 ]
  • 5-[3-[[ethyl(methyl)sulfamoyl]amino]-2-fluorobenzoylamino]-4-methyl-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]
  • 32
  • [ 945950-37-8 ]
  • (3aR,4R,6S,6aR)-2,2-dimethyl-6-phenyltetrahydrofuro[3,4-d][1,3]dioxol-4-ol [ No CAS ]
  • (2R,3R,4S,5S)-2-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-phenyltetrahydrofuran-3,4-diol [ No CAS ]
  • 33
  • [ 945950-37-8 ]
  • (3aR,4R,6S,6aR)-2,2-dimethyl-6-phenyltetrahydrofuro[3,4-d][1,3]dioxol-4-ol [ No CAS ]
  • 7-((3aR,4R,6S,6aR)-2,2-dimethyl-6-phenyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
124 mg To a solution of (3aR,4R,65,6aR)-2,2-dimethyl-6- phenyltetrahydrothro[3,4-d] [1 ,3]dioxol-4-ol (11-5) (250 mg, 1.06 mmol) in toluene (15 mE) was added 154 tE CC14. The reaction was cooled in a dry ice/acetone bath (.---50 C.), then tris-(dimethylamino) phosphine (264 mg, 1.38 mmol) in 2 mE toluene was added drop-wise over 10 mm. The internal reaction temperature rose to 35 C. during addition and the clear solution changed to light yellow. The reaction was taken out of the cold bath and the temperature was maintained between - 15C. and 0C. for 1 h. The reaction was quenched with ice cold brine (3 mE) and the layers were separated. The organic phase was dried over Mg504 and filtered then added to a pre-stirred mixture of 4-methyl-7H-pyrrolo[2,3-d]pyri- midine (V-i) (141 mg, 1.06 mmol) intoluene (15 mE), solid KOH (89 mg, 1.59 mmol), tris-(3,6-dioxaheptyl)-amine (144 mg, 0.423 mmol). The reaction mixture was stirred at rt for 40 h then quenched with saturated NH4C1 solution (25 mE) and extracted with DCM (2x30 mE). The combined organic extracts were dried (Mg504), filtered and concentrated. The crude residue was purified by ISCO 40 g Si column with 0-50% EtOAc/Hep to provide 124 mg a white solid U-6. ?H NMR (400 MHz, CHEOROFORM-d) oe ppm 8.88 (s, 1H) 7.29-7.45 (m, 6H) 6.70 (d, J=2.93 Hz, 1H) 6.23 (s, 1H) 5.79 (d, J=5.62 Hz, 1H) 5.44 (d, J=3.55 Hz, 1H) 5.28-5.34 (m, 1H) 2.82-2.93 (m, 3H) 1.57 (s, 3H) 1.38 (s, 3H).
  • 34
  • [ 945950-37-8 ]
  • (3aR,4R,6R,6aR)-6-(4-fluorobenzyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-ol [ No CAS ]
  • (2R,3S,4R,5R)-2-(4-fluorobenzyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrofuran-3,4-diol [ No CAS ]
  • 35
  • [ 945950-37-8 ]
  • (3aR,4R,6R,6aR)-6-(4-fluorobenzyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-ol [ No CAS ]
  • (3aR,4R,6R,6aR)-4-chloro-6-(4-fluorobenzyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole [ No CAS ]
  • 7-((3aR,4R,6R,6aR)-6-(4-fluorobenzyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
120 mg To an oven dried reaction vial, equipped with a magnetic stirbar and cooled under a stream of argon, was added pyrrolopyrimidine v-i (75.0 mg, 0.56 mmol), potassium hydroxide (70.7 mg, 1.26 mmol), toluene (2.3 mE), acetonitrile (0.38 mE) and TDA-1 (0.11 mE, 0.34 mmol). The solution was stirred for 30 minutes at room temperature at which point the crude solution of chloride YY-5 was added to the vial. The reaction was stirred at room temperature for 24 hours. The reaction was quenched with sat. NH4C1 aq. and transferred to a separatory funnel with EtOAc. The product was extracted with 3 portions EtOAc and the combined organic phases were dried (Mg504), filtered, and concentrated under vacuum. The crude residue was purified via flash column chromatography (12 g 5i02, Isco, 100% Hept. to 100% EtOAc, 9 mE fractions) to afford the title compound YY-6 (120 mg, 55% over 2 steps) as a yellow gum. ECMS [M+H]384; ?H NMR (400 MHz, CHEOROFORM-d) oe ppm 8.87 (s, 1H), 7.04-7.18 (m, 2H), 6.88-7.03 (m, 2H), 6.72 (br.s, 1H), 6.25 (d, J=2.57 Hz, 1H), 5.15-5.29 (m, 1H), 4.86 (dd, J=6.30, 4.46 Hz, 1H), 4.34-4.47 (m, 1H), 2.83-3.12 (m, 5H), 1.62 (s, 3H), 1.37 (s, 3H).
  • 36
  • [ 544-97-8 ]
  • [ 3680-69-1 ]
  • [ 945950-37-8 ]
YieldReaction ConditionsOperation in experiment
561 mg With tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; toluene; at 60 - 80℃; for 40h;Inert atmosphere; A suspension of 4-chloro-7H-pyrrolo[2,3-d]pyri- midine (1.54 g, 10 mmol) and Pd(PPh3)4(ii6 mg, 0.100 mmol) in THF (10.0 mE, iM) was vacuum purged with N2. Then a solution of dimethylzinc (3.82 g, 40.0 mmol, 20.0 mE, 2M in toluene) was added and the mixture was vacuum flushed with N2 and then heated to 60 C. for 16 h. ECMSAPC1(+) showed .-i:i mixture of starting material to product. The reaction was heated to 80 C. for another 24 h, in which ECMS showed a 2: 1 mixture of product to starting material. The reaction mixture was cooled in an ice-water bath then quenched with saturated NaHCO3 (aq) and extracted with EtOAc. The EtOAc was washed with brine, dried with Mg504, filter and concentrated to an oil. The crude material was purified by ISCO-Rf on a 24 g column eluting with 0-100% EtOAc-Heptane to give compound V-1 (561 mg, 42%). ECMS [M+i] 134; ?HNMR (400 MHz, CDC13) oe ppm8.94 (s, iH), 7.42 (d, J=3.4 Hz, iH), 6.68 (d, J=3.4 Hz, iH),2.87 (s, 3H)
  • 37
  • 5-bromo-2-[(4-methoxyphenyl)methyl]isoindolin-1-one [ No CAS ]
  • [ 945950-37-8 ]
  • 5-(4-methyl-7H-pyrrolo [2, 3-d] pyrimidin-7-yl)isoindolin-1-one [ No CAS ]
  • 38
  • 5-bromo-2-[(4-methoxyphenyl)methyl]isoindolin-1-one [ No CAS ]
  • [ 945950-37-8 ]
  • 2-(4-methoxybenzyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)isoindolin-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
47% With potassium phosphate; copper(l) iodide; (±)-trans-1,2-diaminocyclohexane; In 1,4-dioxane; at 90℃; for 16h;Inert atmosphere; Procedure C: A solution of <strong>[945950-37-8]4-methyl-7H-pyrrolo[2,3-d]pyrimidine</strong> (1, 0.4 g, 3.0 mmol), 5-bromo-2-(4-methoxybenzyl) isoindolin-1-one (2, 1.0 g, 4.5 mmol) and potassium phosphate (1.91 g, 9.0 mmol) in 1, 4-dioxane (15 ml) was degassed with nitrogen for 10 min. Copper (I) iodide (0.28 g, 1.5 mmol) and trans-1, 2-diaminocyclohexane (0.17 g, 1.5 mmol) were added and the reaction was refluxed at 90 C. for 16 h. Progress of the reaction was monitored by TLC. After completion, solvent was removed under reduced pressure. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The organic layer was separated, dried over sodium sulphate, filtered and concentrated under reduced pressure to afford 2-(4-methoxybenzyl)-5-(4-methyl-7H-pyrrolo [2, 3-d] pyrimidin-7-yl) isoindolin-1-one (3) as a yellow solid. Yield: 0.55 g, 47%; MS (ESI) m/z 385.12[M+1]+
  • 39
  • [ 945950-37-8 ]
  • 7-((1R,4S)-4-(4-fluorophenoxy)cyclopent-2-en-1-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]
  • 40
  • [ 945950-37-8 ]
  • (1S,2S,3S,5R)-3-(4-fluorophenoxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol [ No CAS ]
  • 41
  • [ 945950-37-8 ]
  • tert-butyl 8-(((1S,4R)-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-2-en-1-yl)oxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate [ No CAS ]
  • 42
  • [ 945950-37-8 ]
  • tert-butyl 8-(((1S,2S,3S,4R)-2,3-dihydroxy-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentyl)oxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate [ No CAS ]
  • 43
  • [ 945950-37-8 ]
  • (1S,2S,3R,5S)-3-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-((1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)cyclopentane-1,2-diol [ No CAS ]
  • 44
  • [ 945950-37-8 ]
  • 2-(4,5-dichloro-2-(((1S,4R)-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-2-en-1-yl)oxy)benzyl)isoindoline-1,3-dione [ No CAS ]
  • 45
  • [ 945950-37-8 ]
  • 2-(4,5-dichloro-2-(((1S,2S,3S,4R)-2,3-dihydroxy-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentyl)oxy)benzyl)isoindoline-1,3-dione [ No CAS ]
  • 46
  • [ 945950-37-8 ]
  • (1S,2S,3S,5R)-3-(2-(aminomethyl)-4,5-dichlorophenoxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol [ No CAS ]
  • 47
  • [ 945950-37-8 ]
  • (1S,4R)-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-2-en-1-ol [ No CAS ]
  • 48
  • [ 945950-37-8 ]
  • tert-butyl 4-(((1S,4R)-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-2-en-1-yl)oxy)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-carboxylate [ No CAS ]
  • 49
  • [ 945950-37-8 ]
  • tert-butyl 8-(((1S,4R)-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-2-en-1-yl)oxy)-3,4-dihydro-2,7-naphthyridine-2(1H)-carboxylate [ No CAS ]
  • 50
  • [ 945950-37-8 ]
  • 5-chloro-2-(((1S,4R)-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-2-en-1-yl)oxy)benzonitrile [ No CAS ]
  • 51
  • [ 945950-37-8 ]
  • 5-chloro-2-(((1S,2S,3S,4R)-2,3-dihydroxy-4-(4-methyl-7H-pyrrole[2,3-d]pyrimidin-7-yl)cyclopentyl)oxy)benzonitrile [ No CAS ]
  • 52
  • [ 945950-37-8 ]
  • (1S,2S,3S,5R)-3-(2-(aminomethyl)-4-chlorophenoxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol [ No CAS ]
  • 53
  • [ 945950-37-8 ]
  • tert-butyl 5-fluoro-4-methyl-8-(((1S,4R)-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-2-en-1-yl)oxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate [ No CAS ]
  • 54
  • [ 945950-37-8 ]
  • tert-butyl 8-(((1S,2S,3S,4R)-2,3-dihydroxy-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentyl)oxy)-5-fluoro-4-methyl-3,4-dihydroisoquinoline-2(1H)-carboxylate [ No CAS ]
  • 55
  • [ 945950-37-8 ]
  • (1S,2S,3S,5R)-3-((5-fluoro-4-methyl-1,2,3,4-tetrahydroisoquinoline-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol hydrochloride [ No CAS ]
  • 56
  • [ 945950-37-8 ]
  • tert-butyl 6-(difluoromethyl)-5-fluoro-8-(((1S,4R)-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-2-en-1-yl)oxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate [ No CAS ]
  • 57
  • [ 945950-37-8 ]
  • tert-butyl 6-(difluoromethyl)-8-(((1S,2S,3S,4R)-2,3-dihydroxy-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentyl)oxy)-5-fluoro-3,4-dihydroisoquinoline-2(1H)-carboxylate [ No CAS ]
  • 58
  • [ 945950-37-8 ]
  • (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol [ No CAS ]
  • 59
  • [ 890122-43-7 ]
  • [ 945950-37-8 ]
  • tert-butyl ((1S,4R)-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-2-en-1-yl)carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; N,N?-(1S,2S)-cyclohexane-1,2-diylbis[2-(diphenylphosphino)-1-naphthamide]; caesium carbonate; In 1,2-dichloro-ethane; at 20℃; for 48.5h;Inert atmosphere; Cooling; Vial A:To an oven-dried reaction vial equipped with a magnetic stir bar and cooled under a stream of argon, was added Para(benzylideneacetone)dipalladium(0) chloroform adduct (78.7 mg, 0.0760 mmol) and (S,S)- DACH-naphthyltrozol ligand (MFCD02684552) (180 mg, 0.228 mmol). The vial was vacuum purged with argon under dynamic vacuum and DCE (7.5 mL) that had been argon sparged for 30 minutes was added. The solution was stirred at room temperature for 30 minutes, at which time a bright orange solution of the spliced catalyst was obtained.At this stage, vial B is prepared.Vial B:<strong>[945950-37-8]4-methyl-7H-pyrrolo[2,3-d]pyrimidine</strong> (HG-1) was added to an oven-dried reaction vial equipped with a magnetic stir bar and cooled under argon flow(506 mg, 3.8 mmol),((1R,3S)-cyclopent-4-en-1,3-diyl)-di-tert-butyl dicarbonate(BB-1) (prepared as reported in J. Am. Chem. Soc. 2006, 128, 6054-6055) (1.37 g, 4.56 mmol) and cesium carbonate (1.36 g, 4.18 mmol).The vial was vacuum purged with argon under dynamic vacuum and addition of DCE (7.5 mL) that had been sparged with argon for 30 minutes followed by addition of the contents of vial A to the vial via a gas tight syringe. The reaction was stirred at room temperature under argon for 48 hours.The reaction was transferred to a separatory funnel with DCM. The solution was washed with 2 portions of water and 1 portion of saline. A small amount of 1 M HCl was used to deplete the emulsion in the last wash. The organic phase was dried (MgSO4), filtered and concentrated in vacuo.The crude residue was purified via flash column chromatography (40 g SiO2, Isco, 100% heptane to 100% EtOAc, 20 mL eluent) to provide compound BB-2 as a brown gum (814 mg, 68%, >99% ee), which cures on standing
  • 60
  • [ 945950-37-8 ]
  • 2,6-difluoro-N-(2-fluoro-3-(2-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetyl)phenyl)benzenesulfonamide [ No CAS ]
  • 61
  • [ 945950-37-8 ]
  • N-(3-(2-(tert-butyl)-5-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide [ No CAS ]
  • 62
  • [ 945950-37-8 ]
  • N-(3-(2-(tert-butyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide [ No CAS ]
  • 63
  • [ 945950-37-8 ]
  • sodium (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropionate [ No CAS ]
  • 64
  • [ 945950-37-8 ]
  • (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropionamide [ No CAS ]
  • 66
  • [ 945950-37-8 ]
  • (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropionic acid [ No CAS ]
  • 67
  • [ 945950-37-8 ]
  • C17H18ClN5O [ No CAS ]
  • 68
  • [ 945950-37-8 ]
  • [ 68-12-2 ]
  • 3-hydroxy-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acrylaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
60.2% With trichlorophosphate; In 1,4-dioxane; at 0 - 80℃; for 3h; 91.6 g of <strong>[945950-37-8]4-methyl-7H-pyrrolo[2,3-d]pyrimidine</strong> was added to a mixed solvent of 230 mL of DMF and 460 mL of dioxane and cooled down to below 0 C., and then 190 mL of phosphorus oxychloride was added dropwise thereto under stirring, and the temperature of the solution was kept to be lower than 20 C. After the addition was completed, the resulting mixture was heated to 80 C. and stirred to react for 3 hours, and then concentrated under reduced pressure to remove dioxane and DMF. To the residue was added 920 mL of tetrahydrofuran, and the pH was adjusted to 10?12 with 25% aqueous NaOH solution. After the addition was completed, the resulting mixture was heated to 60 C. and stirred to react for 2 hours. Then, the mixture was adjusted to pH 6-7 with concentrated hydrochloric acid, cooled, stirred and crystallized for 2 hours, and then suction-filtered to obtain a filter cake. The filter cake was dried at 60 C. to obtain 3-hydroxy-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acrylaldehyde (78.3 g, 60.2%). 1H-NMR (500 MHz, DMSO-d6): delta=13.51 (bs, 1H), 12.04 (bs, 1H), 9.49 (s, 2H), 8.72 (s, 1H), 7.47 (dd, J=46.2, 3.7 Hz, 2H); MS (ES): 190.06 (M+H+).
  • 69
  • [ 945950-37-8 ]
  • (2R,6S,6aS)-6-((triphenylsilyl)oxy)-1,2,4,5,6,6a-hexahydropentalen-2-yl acetate [ No CAS ]
  • 4-methyl-7-((2R,6S,6aS)-6-((triphenylsilyl)oxy)-1,2,4,5,6,6a-hexahydropentalen-2-yl)-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Step 7: To a flask containing allyl paHadiurn(H) chloride dirner (1.66 g, 4.45 mrnoi), dppf (6.36g, 11.1 rnmol). 4-methyl-7H-pyrrolo[2,3-dipvrimidine (4.44 g, 33.4 mmol). and potassium lertbutoxide (3.74 g, 33.4 mmoi) was added THF (100 mE) under an atmosphere of argon . The solution was stirred at room temperature for 10 minutes. Then, a solution of(2R,6S,6aS)-6- ((triphenylsilyl)oxy}-1,2,4,5,6,6a-hexahydropentalen-2-yl acetate (9.8 g, 22 mmol) in THF (10() mE) was added, and the reaction was heated to 40 C overnight. The reaction was then cooled toroom temperature, filtered through Celite. and concentrated under reduced pressure. Theresidue was subjected to column chromatography on silica (10-50% EtOAc/hexanes) to afford 4-methvl-7-((2R,6S,6a5)-6-((triphenyisiiyi)oxy)-i,2.4,5,6,6a-hexahydropentaien-2-yi)-7H-pvrroio[2,3-d]pyrimidine. MS: 514 (M-1-i). ?H NMR (600 MHz, CDCI,) 3 8.75 (s, 1H), 7.65 -7.58 (m, 6H), 7.43 -- 7.38 (in, 3H), 7.38 --- 7.31 (m, 6H), 7.05 (d, J= 3.7 Hz, IH), 6.54 (d, J = 3.6Hz, 1H), 6.15 (s, 1H), 5.23 --- 5.19 (m, IH), 3.99 (q, J == 7.9Hz. 11-1). 3.17 --- 3.11 (mn, IH), 2.78 (s,311), 2.63 -2.58 (in. 1FI). 2.49- 2.42 (m, 111), 2.29-2.22 (in. 1FI). 2.20- 2.12 (m, 211), 1.22-1.15 (in, IH).
  • 70
  • [ 945950-37-8 ]
  • (3R,3aS,6aR)-6-((3-bromo-2-((4-methoxybenzyl)amino)quinolin-7-yl)methyl)hexahydro-2H-cyclopenta[b]furan-2,3,3a-triol [ No CAS ]
  • (2R,3R,3aS,6aR)-6-((3-bromo-2-((4-methoxybenzyl)amino)quinolin-7-yl)methyl)-2-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)hexahydro-3aH-cyclopenta[b]furan-3,3a-diol [ No CAS ]
YieldReaction ConditionsOperation in experiment
Sten 6: To a stirred solution of (3R,3aS,6aR)-6.-((3-bromo-2-((4-methoxvbenzvl)amino)quinoiin-7-vi)nelhyi)hexahydro-211.-cyciopenta[h]furan-2,3,3a.-trioi (250 rng, 0.486 mmoi) in dry MeCN(9 rnL) was added tributviphosphine (176 ing, 0.869 rnmoi), followed by (E)-diazene-J.2-divlhis(piperi din-i -ylmethanone) (206 111g. 0815 mrnoi) at room temperature. The reactionmixture was stirred at room temperature for I h. and the solution was used directly in the nextstep without characterization; Step 7: To a stirred solution of 4-methyF-7I-Ipyrro1o [2, 3dj pyrimidine (129 mg, 0.970 mniol) in dry DMF (6 mL) was added sodium hydride (60% dispersion in mineral oil) (58.2 111g. 1.46 mmoi) at 0 C. The suspension was stirred at room temperature for 30 minutes, The suspensionwas transferred to the solution from the previous step containing the epoxide intermediate via syringe, and the resulting mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with saturated aqueous ammonium chloride (30 mL) and extracted with EtOAc (40 mL 3). The combined organic layers were washed with brine (40 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure.The residue was purified by Preparative TLC (MeOH/DCM) to afford (2R,3R,3aS,6aR)-6-(3- bromo-2(rnethoxyhenzyi)amino)quinolin-7-yl)methvi)-2-?4-methyi7H-pyrroio[2,3- d]pyrirnidinT-yi)hexahydro-3aWcyclopenta[hfuran-3, 3a-diol. MS: 630/632 (M+ 1/M+3). ?H NMR (40() M1-lz, DMSO-d6) oe 8.69 (s, 11-1), 8.32 (d, J= 6.0 Hz, IH), 8.02 (s, 1H), 7.54 (d, J= 8.2 Hz, 1H), 7.33 (d, J= 8.4 Hz, 2H), 7.14 -7.04 (rn, 3H), 6.91 -6.80 (m, 4H), 6.03(d, J 8.1Hz, 1H), 5.30 (d, J= 7.0 Hz, 1H), 5.12 (s, 1H), -4.61 (d, J= 6.2 Hz, 2H), 4.22 (t. J 7.6 Hz, 1H),4.04 (d, J == 6.6 Hz. 11-1), 3.72 (s, 31-1), 2.83 (dd, J: 13.7, 7.2 Hz, 11-1), 2.69(s. 31-1). 2.65 (s, 11-1),2,37 -2.22 (m, 11:1), 1.99- 1.93 (mn, 1H). 1,55 (d, J= 6.5 Flz. 2H).
  • 71
  • [ 945950-37-8 ]
  • (3R,3aS,6aR)-6-((2-amino-3-chloroquinolin-7-yl)methyl)hexahydro-2H-cyclopenta[b]furan-2,3,3a-triol [ No CAS ]
  • (2R,3R,3aS,6S,6aR)-6-((2-amino-3-chloroquinolin-7-yl)methyl)-2-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)hexahydro-2H-cyclopenta[b]furan-3,3a-diol [ No CAS ]
YieldReaction ConditionsOperation in experiment
Step 3: To a stirred solution of(3R,3aS,6aR)-6-((2-amino-3-chioroquinolin-7- vi)methyi)hexahvdro-2H-cyciopenta[b]furan-2,3,3a-triol (60 mg, 0171 mmol) in thy MeCN (1 mL) under argon was added (E)diazene-1,2diylbis(piperidin-LyImethanone) (64.7 mg, 0257 mmol) in MeCN (0.5 rnL) dropwise at () C. This was followed by the addition of tribulyiphosphine (0.068 n1., 0274 mmoi) in MeCN (C.5 mL) dropwise al 0 C. The resulting solution was stirred al 31) C for -i iv Separately, to a stirred solution of 4-methyi7Hpyrroio[2,3djpyrimidine (43.3 mg, 0.325 mmol) in dry DMF (1 inL) was added Na[1 (1231 mg.60% in mineral oil. 0308 mmol) at room temperature. The suspension was stirred at room temperature for 30 minutes, then the suspension was transferred to the solution originally containing the triol via syringe. The resulting reaction mixture was stirred at room temperature for 1 iv The reaction was quenched with water (10 mL) and extracted with EtOAc (2 x 10 mL).The combined organic layers were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by reverse phase column chromatography (ACN/water with 10 mM NI-{4HC03 modifier) to afford (2R,3 R.3aS,6S.6aR)-6- ((2-amino-3-chioroquinohn-7-yi)mnethyI)-2-(4-mnethyl7Wpyrrolo[2,3-djpyrimi din-7- vi)hexahydro-2H-cyciopenta[b]furan3.3adioi as a solid. MS: 466 (M + 1). ?H-NMR (400 MHz.DMSOd6) oe 8.69 (s, IH), 8.12 (s, IH), 7.88 (d, J = 3.6 Hz, IH), 7.54 (d, J = 8.0 Hz, 1H), 7.28 (s,1H), 7.08 (dd, J == 8.4, 1.6 Hz, 1H), 6.82 (d, J == 3.6 Hz, 11-1), 6.64 (br s, 2H), 600 (d, J 8.4 Hz,1H), 5.31 (d, J = 6.8 Hz, 1H), 5.12 (s, 1H), 4.22 (t, J = 8.0 Hz, 1H). 400 (d, J = 6.0 Hz, 1H), 285279 (m, 1H), 2.69 (s, 3H), 2.65 2.60 (in, IH). 2.33 --- 225 (m, 1H), 1.98 1.93 (in, IH). 1.80167 (m, 2H), 1.58 1.51 (m, IH).
  • 72
  • [ 945950-37-8 ]
  • (3R,3aS,6aR)-6-((2-amino-3-fluoroquinolin-7-yl)methyl)hexahydro-2H-cyclopenta[b]furan-2,3,3a-triol [ No CAS ]
  • (2R,3R,3aS,6S,6aR)-6-((2-amino-3-fluoroquinolin-7-yl)methyl)-2-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)hexahydro-2H-cyclopenta[b]furan-3,3a-diol [ No CAS ]
YieldReaction ConditionsOperation in experiment
Step 3: To a stirred solution of (3R,3aS,6aR}-6-((2-ainino-3-fiuoroquinolin-7- yl)methvi)hexahydro-2H-cyclopenta[b]furan-2,3,3a-trioi (0.067 g. 0.2 mmoi) in dry MeCN (3 rnL) was added trihutyiphosphine (0.077 g, 0.38 rnmol), followed by (E)-diazene-1,2- diylbis(piperidin-1-yimethanone) (0.091 g, 0.36 minol) at room temperature. The reactionmixture was stirred at room temperature for 1 h. Separately, to a stirred solution of 4-rnethyl-7H- pvrroio[2,3-d]pyrimidine (0.053 g, 0.400 mmoi) in dry DMF (2 mE) was added NaH (0.024 g, 60% in mineral oil, 0.600 mmoi) at 0 The suspension was stirred at room temperature for 30 minutes. The suspension was then transferred to the solution originally containing the triol via syringe. The resulting reaction was stirred at room temperature for 2 Ii The reaction mixture wasthen quenched with saturated ammonium chloride (30 mE) and extracted with EtOAc (40 mL x3). The combined organic layers were washed with brine (40 mE), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative TEC (1: 1 DCMIMeOH). The product was further purified by reverse phase column chromatography (ACN/water with 5 mM NH4HCO3 modifier) to afford(2R,3R,3aS,6S,6aR)-6-((2-ainino-3-fiuoroquinolin-7-yl)methyi}-2-(4-methyi-71-1-pyrrolo[2,3- d]pyrimidin-7-yi)hexalwdro-2H-cyclopenta[h]finan-3,3a-diol as a solid, MS: 450 (M + 1). ?HNMR (400 MHz, DMSO-d6) d 8.69 (s, 1H), 7.87 (d, 3 = 4.0 Hz, 1H), 7.74 (d, J = 11.6 Hz, IH), 7.52 (d, J 8.0 Hz, IH), 7.28 (s, 1H), 7.07 (d, 3:::: 8.0 Hz, 11-1), 6.82 (d, J =: 3.6 Hz, 1K), 6.66 (br s, 2H), 6.01 (d. J 8.0 Hz. 1H). 5.31 (d, J 7.2 FIz. 1K). 5,12 (s. 1K). 4,22 (d, J 7.6 FIz. il-i). 401 (d, J = 6.0 Hz, 1H), 2.84 - 2.79 (rn, 1H), 2.69 (5, 3H), 2.67 2.59 (in. IH), 2.28 2.22 (rn,1H), 1.98 1.94 (in. 11-1). 1.76 - 1.69 (rn, 2H), 1.58 1.53 (in. 1Ff).
  • 73
  • [ 945950-37-8 ]
  • (3R,3aS,6aR)-6-((2-amino-3-bromoquinolin-7-yl)methyl)tetrahydrofuro[3,4-b]furan-2,3,3a(4H)-triol [ No CAS ]
  • (2R,3R,3aS,6S,6aR)-6-((2-amino-3-bromoquinolin-7-yl)methyl)-2-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrofuro[3,4-b]furan-3,3a(4H)-diol [ No CAS ]
YieldReaction ConditionsOperation in experiment
Step 10: To a vial containing (3R,3aS,6S,6aR)-6-(2-amino-3-bromoquinolin-7- yi)methyi)tetrahydrofuro[3,4-b]furan-2,3,3a(H)-trioi (20 mg, 0.050 mmol) in anhydrous acetonitrile (750 lii) was added 1,1 -(azodicarbonyi)dipiperidine (19 mg, 0.076 mmoi) followed by tri-n-butyiphosphine (20 .ti, 0.08 mmoi) at room temperature. The mixture was stirred for I h. in a separate oven-dried vial containing 4-methyl-7H-pyrroio[2,3-d]pyrimidine (13 mg, 0.10mmol) dissolved in dn? DMF (250 iii) was added NaH (4.0 mg, 0.10 mmoi). This mixture was stirred for 3() minutes at room temperature and was then added to the mixture described before originally containing the trioL The final reaction mixture was then stirred at room temperature overnight. The reaction mixture was purified by Prep-HPLC (MeCN/water with 0.1% TFA modifier) directly to afford two isomers: (2R.3R,3aS,6S,6aR)-6-((2-amino-3-hromoquinoiin-7-diol as a TFA salt, MS: 512/514 (M + 1/M + 3). ?H NMR (600 MHz, DMSO-d6) oe 8.96 (s, 1H),8.80 (s, 1H), 8.00 (s, 1H), 7.77 (d, J = 8.3 Hz, 1H), 7.55 (s, 1H), 7.41 (cl, J = 8.2 Hz, IH), 7.07 (s,1H), 6.25 (d, J == 8.0 1-Iz, 1H), 4.37 (d. J == 8.() Hz, IFI), 4.32 4.30 (m, 11-1), 4.14 - 4.08 (in, IFI),3.99 -3.95 (m, IH), 3.42 -3.36 (m, IH), 3.08 - 3.03 (m. 2H). 282 (s. 3H) and(2R,3R,3aS,6R,6aR)-6-((2-amino-3-bromoquinoiin-7-yi)methyl)-2-(4-methyl -7H-pyrroio[2,3- dpyrimidin-7-yi)tetra1wdrofuro[3,4-b]furan-3,3a(4H)-dio1 as aTFA salt. (MS: 512/5 14 (M -FI?M - 3). ?H NMR (600 MHz, DMSO-do) oe 8.85 (s. IH), 8.75 (s. IFI), 7.92 (s, IH), 7.77 (d. J 8.1 Hz, 1H), 7.54 (s, 1H), 7.38 (d, J = 7.8 Hz, IH), 6.97 (s, IH), 6.21 (d, J = 7.6 Hz, 1H), 4.46 (d. J = 7.6 Hz, 1H), 4.32 4.25 (in, IH), 4.23 --- 4.20 (m, 1H), 3.99 -3.97 (m, 1H), 3.88 3.86 (in,1H), 3.13 --- 3.04 (in, 21-1). 2.76 (s. 3H).
  • 74
  • [ 945950-37-8 ]
  • (3R,3aS,6R,6aR)-6-(benzyloxy)hexahydro-2H-cyclopenta[b]furan-2,3,3a-triol [ No CAS ]
  • (2R,3R,3aS,6R,6aR)-6-(benzyloxy)-2-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)hexahydro-2H-cyclopenta[b]furan-3,3a-diol [ No CAS ]
YieldReaction ConditionsOperation in experiment
Step 4: To a stirred mixture of (3i?,3aS',6i?,6ai?)-6-(benzyloxy)hexahydro-2 /- cyclopenta[6]furan-2,3,3a-triol (1.7 g, 6.4 mmol) in dry acetonitrile (100 mL) was added tributylphosphine (2.55 mi, 10 mmol) under argon atmosphere, followed by (E)-diazene-l ,2- diylbis(piperidin- 1 -ylmethanone) (2.4 g, 9.6 mmol) at room temperature. The resulting mixture was stirred at room temperature for 30 min. The resulting epoxide containing solution was used directly without any further processing. A separate round bottom flask was charged with a solution of 4-methyl-7i/-pyrrolo[2,3-d]pyrimidine (1.7 g, 13 mmol) in dry DMF (25 mL). To this ws added sodium hydride (60 wt.% dispersed in mineral oil) (0.77 g, 19 mmol) at 0 C under argon atmosphere. The suspension was stirred at room temperature for 30 min, and then it was transferred to the previous obtained epoxide containing solution by means of a syringe. The resulting mixture was stirred at room temperature for 1 h. The reaction was quenched by the addition of saturated aqueous ammonium chloride (100 mL) and extracted with EtOAc (3 c 100 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The residue ws purified by reverse-phase column chromatography on C18 (0-95 % 5 mM aq.NH4HCO3/ACN) to give (2i?,3i?,3a5',6A5,6ai?)-6-(benzyloxy)-2-(4-methyi-7//-pyrrolo[2,3- ol]pyrimidin-7-yl)hexahydro-2i/-eyclopenta[h]furan-3,3a-diol. MS: 382(M+1). M i-f R (300 MHz, l)lSO- /.) d 8.69 (s, 1H), 7.74 (d, J= 3.6 Hz, 1H), 7.36 - 7.25 (m, 5H), 6.73 (d, J= 3.9 Hz, 1H), 6.16 (d, J = 8.4 Hz, 1H), 5.41 (d, J = 6.9 Hz, 1H), 5.24 (s, 1H), 4.55 - 4.50 (m, 2H),4 27 - 4 19 (m, 21 1). 3.92 - 3.86 (m, i l l ). 2 67 (s, 31 1 ). 2 02 - 1 98 (m, 31 1). 1.60 - 1.52 (ra, i l l ).
  • 75
  • [ 945950-37-8 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: anhydrous sodium perchlorate
Multi-step reaction with 3 steps 1.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 1.2: 21.5 h / 20 - 50 °C 2.1: ethanol; water monomer / 20 °C 3.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 4 steps 1.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 1.2: 21.5 h / 20 - 50 °C 2.1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 3.1: N,N-dimethyl-formamide / 22 h / 20 °C 4.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 4 steps 1.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 1.2: 21.5 h / 20 - 50 °C 2.1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 3.1: ethanol / 5 h / 20 °C 4.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C

  • 76
  • [ 945950-37-8 ]
  • [ 1334298-90-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: oxalyl dichloride / 0.25 h / 50 °C 1.2: 21.5 h / 20 - 50 °C 2.1: sodium perchlorate / water / 2 h / 20 - 25 °C 3.1: ethanol / 16 h / 20 °C
Multi-step reaction with 5 steps 1.1: oxalyl dichloride / 0.25 h / 50 °C 1.2: 21.5 h / 20 - 50 °C 2.1: sodium perchlorate / water / 2 h / 20 - 25 °C 3.1: ethanol / 4 h / 20 °C 4.1: hydrogenchloride / water; isopropyl alcohol; dichloromethane / Reflux 5.1: triethylamine / dichloromethane / 0.5 h / 20 °C 5.2: 2.08 h / 26 °C
Multi-step reaction with 3 steps 1.1: oxalyl dichloride / 15 min / 20 - 50 °C 1.2: 21.5 h / 20 - 50 °C 2.1: sodium perchlorate / water / 12 h / 20 - 25 °C 3.1: ethanol / 16 h / 20 °C
Multi-step reaction with 5 steps 1.1: oxalyl dichloride / 15 min / 20 - 50 °C 1.2: 21.5 h / 20 - 50 °C 2.1: sodium perchlorate / water / 12 h / 20 - 25 °C 3.1: ethanol / 4 h / 20 °C 4.1: hydrogenchloride / water; isopropyl alcohol; dichloromethane / Reflux 5.1: triethylamine / dichloromethane / 30 min / 20 °C 5.2: 125 min / 26 °C

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