Trifluoroacetic acid → HCID 90409377, compound

HRID 589116Notes

Reaction equation

HRID 589116 reaction equation
COC1C=C(OC)C=CC=1C[NH:6][CH2:7][C:8]1[CH:9]=[C:10]([C:27]2[C:28]([CH3:33])=[N:29][O:30][C:31]=2[CH3:32])[C:11]2[O:16][CH2:15][C@H:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[N:13]3[C:23](=[O:26])[NH:24][C:25]=1[C:12]=23.[F:40][C:41]([F:46])([F:45])[C:42]([OH:44])=[O:43]>O>[F:40][C:41]([F:46])([F:45])[C:42]([OH:44])=[O:43].[F:40][C:41]([F:46])([F:45])[C:42]([OH:44])=[O:43].[NH2:6][CH2:7][C:8]1[CH:9]=[C:10]([C:27]2[C:28]([CH3:33])=[N:29][O:30][C:31]=2[CH3:32])[C:11]2[O:16][CH2:15][C@H:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[N:13]3[C:23](=[O:26])[NH:24][C:25]=1[C:12]=23

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90409700HCID 90409700, compound

Product 1

HCID 90409377HCID 90409377, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of (4S)-9-{[(2,4-dimethoxybenzyl)amino]methyl}-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one (70.0 mg, 0.133 mmol) in trifluoroacetic acid (5 mL) and water (30 μL) was heated in the microwave at 120° C. for 10 min. The reaction mixture was concentrated to give a crude residue. Purification via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at flow rate of 60 mL/min) gave the desired product (66 mg, 82%) as a single enantiomer. 1H NMR (300 MHz, DMSO-d6) δ 11.28 (s, 1H), 8.48 (d, J=4.4 Hz, 1H), 8.18 (br s, 2H), 7.80 (ddd, J=7.7, 7.7, 1.7 Hz, 1H), 7.32 (dd, J=7.1, 5.0 Hz, 1H), 7.19 (d, J=7.9 Hz, 1H), 6.94 (s, 1H), 5.59 (s, 1H), 4.89-4.73 (m, 1H), 4.44 (dd, J=11.5, 3.0 Hz, 1H), 4.13 (d, J=5.5 Hz, 2H), 2.24 (s, 3H), 2.07 (s, 3H); LCMS calculated for C20H20N5O3 (M+H)+: m/z=378.2. found: 378.0.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto give a crude residue
  3. customPurification via preparative LCMS (XBridge C18 column
  4. washeluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-2a6f9535a038457f95e213ee88ee86dc
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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