Water → 8-(7-methyl-2-(propylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-ol

HRID 530091Notes

Reaction equation

[CH2:1]([NH:4][C:5]1[N:6]=[C:7](Cl)[C:8]2[CH:13]=[CH:12][N:11]([CH3:14])[C:9]=2[N:10]=1)[CH2:2][CH3:3].CCN(C(C)C)C(C)C.Cl.[CH:26]12[NH:33][CH:30]([CH2:31][CH2:32]1)[CH2:29][CH:28]([OH:34])[CH2:27]2.O>C(O)CCC>[CH3:14][N:11]1[C:9]2[N:10]=[C:5]([NH:4][CH2:1][CH2:2][CH3:3])[N:6]=[C:7]([N:33]3[CH:26]4[CH2:32][CH2:31][CH:30]3[CH2:29][CH:28]([OH:34])[CH2:27]4)[C:8]=2[CH:13]=[CH:12]1

Participants

Conditions

Temperature: 125 °C

Procedure

To a solution of 2-(n-propyl)amino-4-chloro-7-methyl-pyrrolo[2,3-d]pyrimidine (CXXIV) (1.0 g, 4.5 mmol) in n-butanol (10 mL) were added DIPEA (1.0 g, 7.8 mmol) and 8-aza-bicyclo[3.2.1]octan-3-ol hydrochloride (1.1 g, 6.7 mmol). The mixture was stirred at 125° C. for 16 h. After cooling to room temperature, water (20 mL) was added, and the mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with water and then with a brine solution, and dried over anhydrous Na2SO4. The solvents were removed in vacuo and the resultant residue was purified by flash column chromatography (pet ether/EtOAc=6/1) to yield 8-(7-methyl-2-(propylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-ol (CLIV) (800 mg, 57% yield) as a yellow solid. LCMS (ESI) m/z=316 (M+H)+.

Workup

temperatureAfter cooling to room temperature
extractionthe mixture was extracted with EtOAc (3×50 mL)
washThe combined organic layers were washed with water
dry with materialwith a brine solution, and dried over anhydrous Na2SO4
customThe solvents were removed in vacuo
customthe resultant residue was purified by flash column chromatography (pet ether/EtOAc=6/1)

Sources & evidence

ORD record: ord-ea1d0434364042bdbd58fe17afbe07aa
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09351972B2

Reaction notes

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