Diisopropylethylamine → 5-nitro-1-(phenylsulfonyl)-N-(tetrahydro-2H-pyran-3-yl)-1H-pyrrolo[2,3-b]pyridin-4-amine

HRID 1257657Notes

Reaction equation

Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][N:5]=[C:4]2[N:11]([S:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)(=[O:16])=[O:15])[CH:12]=[CH:13][C:3]=12.Cl.[O:24]1[CH2:29][CH2:28][CH2:27][CH:26]([NH2:30])[CH2:25]1.C(N(CC)C(C)C)(C)C>C(O)(C)C>[N+:8]([C:7]1[CH:6]=[N:5][C:4]2[N:11]([S:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)(=[O:16])=[O:15])[CH:12]=[CH:13][C:3]=2[C:2]=1[NH:30][CH:26]1[CH2:27][CH2:28][CH2:29][O:24][CH2:25]1)([O-:10])=[O:9]

Participants

Conditions

Temperature: 82 °C

Procedure

A stirred suspension of 4-chloro-5-nitro-1-(phenyl sulfonyl)-1H-pyrrolo[2,3-b]pyridine (11.10 g, 33.0 mmol) in isopropanol (IPA) (100 ml) was treated with tetrahydro-2H-pyran-3-amine hydrochloride (5.0 g, 36.0 mmol) and N,N-diisopropylethylamine (15.0 mL, 84.0 mmol), and stirred at 82° C. for four hours. The mixture was then cooled and left to stand at 5° C. for 2 h. The resulting precipitate was collected by filtration and washed with IPA. Trituration (water) afforded 11.7 g (89%) of 5-nitro-1-(phenylsulfonyl)-N-(tetrahydro-2H-pyran-3-yl)-1H-pyrrolo[2,3-b]pyridin-4-amine. LCMS (Method E, ESI): RT=1.65 min, m+H=403.2; 1H NMR (400 MHz, CDCl3) δ 9.22 (d, J=7.6 Hz, 1H), 9.11 (s, 1H), 8.20 (d, J=8.0 Hz, 2H), 7.69-7.56 (m, 2H), 7.60-7.42 (m, 2H), 6.76 (d, J=4.2 Hz, 1H), 4.14 (ddt, J=10.7, 7.1, 3.5 Hz, 1H), 3.98 (dd, J=11.5, 2.7 Hz, 1H), 3.85-3.62 (m, 2H), 3.58 (dd, J=11.5, 6.4 Hz, 1H), 2.27-2.06 (m, 1H), 1.86 (tdt, J=11.8, 7.5, 3.9 Hz, 2H), 1.79-1.63 (m, 1H).

Workup

temperatureThe mixture was then cooled
waitleft
waitto stand at 5° C. for 2 h
filtrationThe resulting precipitate was collected by filtration
washwashed with IPA

Sources & evidence

ORD record: ord-09a659ee42684d629ffeb6fa561cb4fc
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461328B2

Reaction notes

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