Diisopropylethylamine → 2-(2,2,2-Trifluoro-1,1-dimethyl-ethyl)-5,6,7,8-tetrahydro-Quinoline-6-carboxylic acid (7,8-dihydro-5H-pyrano[4,3-b]pyridin-3-yl)-amide

HRID 1697474Notes

Reaction equation

[N:1]1[CH:6]=[C:5]([NH2:7])[CH:4]=[C:3]2[CH2:8][O:9][CH2:10][CH2:11][C:2]=12.[F:12][C:13]([F:31])([F:30])[C:14]([C:17]1[CH:26]=[CH:25][C:24]2[CH2:23][C@@H:22]([C:27](O)=[O:28])[CH2:21][CH2:20][C:19]=2[N:18]=1)([CH3:16])[CH3:15].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[N:1]1[CH:6]=[C:5]([NH:7][C:27]([CH:22]2[CH2:21][CH2:20][C:19]3[N:18]=[C:17]([C:14]([CH3:16])([CH3:15])[C:13]([F:31])([F:30])[F:12])[CH:26]=[CH:25][C:24]=3[CH2:23]2)=[O:28])[CH:4]=[C:3]2[CH2:8][O:9][CH2:10][CH2:11][C:2]=12

Participants

Conditions

Temperature: 60 °C

Procedure

To a mixture of 7,8-dihydro-5H-pyrano[4,3-b]pyridin-3-ylamine (36 mg, 0.24 mmol), (S)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (38 mg, 0.13 mmol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (136 mg, 0.36 mmol) in DMF (1 mL), N,N-diisopropylethylamine (0.1 mL, 0.6 mmol) was added and the reaction was heated at 60° C. for 16 hours. The crude was purified by semi-preparative HPLC (55-75 gradient) to give the titled amide (41 mg, 74%). m/z=420.2 (M+1)+. HPLC: 10.31 min. NMR (400 MHz; d6-DMSO) δ 10.21 (s, 1H), 8.51 (d, 1H, J=2.5 Hz), 7.82 (d, 1H, J=2.3 Hz), 7.56 (d, 1H, J=8.1 Hz), 7.37 (d, 1H, J=8.1 Hz), 4.68 (s, 2H), 3.95 (t, 2H, J=5.9 Hz), 2.97-2.80 (m, 7H), 2.19-2.14 (m, 1H), 1.95-1.85 (m, 1H).

Workup

additionwas added
customThe crude was purified by semi-preparative HPLC (55-75 gradient)

Sources & evidence

ORD record: ord-4232f359c74d4a34810bebbae070d118
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163901B2

Reaction notes

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