Diisopropylethylamine → (1R,2R)-1-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]oxazol-2-yl)amino)-2,3-dihydro-1H-inden-2-ol

HRID 1848038Notes

Reaction equation

HRID 1848038 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:23]=[CH:22][C:15]4[N:16]=[C:17](S(C)=O)[O:18][C:14]=4[CH:13]=3)[C:5]2=[N:6][CH:7]=1.[CH2:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C@@H:26]([NH2:33])[C@@H:25]1[OH:34].CCN(C(C)C)C(C)C>CC(N(C)C)=O>[Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:23]=[CH:22][C:15]4[N:16]=[C:17]([NH:33][C@@H:26]5[C:27]6[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=6)[CH2:24][C@H:25]5[OH:34])[O:18][C:14]=4[CH:13]=3)[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 69311541-Amino-2-indanol, trans-(-)-HCID 866810496-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylsulfinyl)benzo[d]oxazole

Product 1

HCID 89498725(1R,2R)-1-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]oxazol-2-yl)amino)-2,3-dihydro-1H-inden-2-olYield 22%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

A stirred mixture of 6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylsulfinyl)benzo[d]oxazole (150 mg, 0.384 mmol) from Step 3 of Example 61, (1R,2R)-(−)-trans-1-amino-2-indanol (114 mg, 0.768 mmol), and DIEA (99 mg, 0.768 mmol) in anhydrous DMA (3 mL) in a sealed vial was heated in a Biotage microwave synthesizer at 120° C. for 30 min. After the reaction mixture was cooled to rt, it was purified directly by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C-18 column as the stationary phase to afford (1R,2R)-1-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]oxazol-2-yl)amino)-2,3-dihydro-1H-inden-2-ol (40 mg, 22%) as a white solid. 1H NMR (499 MHz, DMSO-d6) δ 8.68 (s, 1H), 8.49 (d, J=2.0 Hz, 1H), 8.36-8.44 (m, 2H), 7.45 (s, 1H), 7.12-7.24 (m, 6H), 5.51 (s, 2H), 5.47 (d, J=5.2 Hz, 1H), 5.01 (t, J=7.6 Hz, 1H), 4.34 (m, 1H), 3.15 (dd, J=7.1, 15.5 Hz, 1H), 2.73 (dd, J=7.6, 15.5 Hz, 1H). LCMS (ESI) m/z 476 and 478 (M+H)+.

Workup

  1. temperatureAfter the reaction mixture was cooled to rt
  2. customit was purified directly by reverse-phase
  3. additiona mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C-18 column as the stationary phase

Sources & evidence

ORD record
ord-b29ab31820c442cf85c1e2df39743e14
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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