Diisopropylethylamine → (S)-N-((R)-1-(2-fluoro-5-methyl-4-(methylsulfonamido)phenyl)ethyl)-6-(trifluoromethyl)-2,3-dihydrobenzo[b][1,4]dioxine-2-carboxamide

HRID 1690799Notes

Reaction equation

Cl.[NH2:2][C@@H:3]([C:5]1[C:10]([F:11])=[CH:9][C:8]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])=[C:7]([CH3:17])[CH:6]=1)[CH3:4].[F:18][C:19]([F:34])([F:33])[C:20]1[CH:32]=[CH:31][C:23]2[O:24][C@H:25]([C:28](O)=[O:29])[CH2:26][O:27][C:22]=2[CH:21]=1.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)C=O>[F:11][C:10]1[CH:9]=[C:8]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[C:7]([CH3:17])=[CH:6][C:5]=1[C@H:3]([NH:2][C:28]([C@H:25]1[O:24][C:23]2[CH:31]=[CH:32][C:20]([C:19]([F:34])([F:18])[F:33])=[CH:21][C:22]=2[O:27][CH2:26]1)=[O:29])[CH3:4]

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of (R)—N-(4-(1-aminoethyl)-5-fluoro-2-methylphenyl)methanesulfonamide hydrochloride (48 mg, 0.17 mmol) in N,N-dimethylformamide (3 mL) was stirred for 5 mins. (S)-6-trifluoromethyl-2,3-dihydrobenzo[b][1,4]dioxine-2-carboxylic acid (40 mg, 0.1 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (200 mg, 0.4 mmol) and N,N-diisopropylethylamine (50 μL, 0.3 mmol) was added and the reaction was stirred at 50° C. overnight. Purification by HPLC afforded the final compound. m/z=477.1 (M+H)+. 1H NMR (400 MHz; DMSO-d6) δ 9.16 (s, 1H), 8.66 (t, 1H, J=8.3 Hz), 7.38 (d, 1H, J=2.2 Hz), 7.28-7.21 (m, 2H), 7.05-7.01 (m, 1H), 6.88 (d, 1H, J=8.5 Hz), 5.17-5.08 (m, 1H), 5.04-5.01 (m, 1H), 4.45-4.41 (m, 1H) 4.37-4.31 (m, 1H), 2.99 (s, 3H), 2.09 (s, 3H), 1.37 (d, 3H, J=6.9 Hz).

Workup

customPurification by HPLC

Sources & evidence

ORD record: ord-219264d6a8514eacbbc946a8ef6a4e9a
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08153651B2

Reaction notes

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