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

HRID 1848032Notes

Reaction equation

HRID 1848032 reaction equation
[N:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]([CH2:10][C:11]2[CH:22]=[CH:21][C:14]3[N:15]=[C:16](S(C)=O)[O:17][C:13]=3[CH:12]=2)[CH:2]=1.[CH2:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C@@H:25]([NH2:32])[C@@H:24]1[OH:33].CCN(C(C)C)C(C)C>CC(N(C)C)=O>[N:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]([CH2:10][C:11]2[CH:22]=[CH:21][C:14]3[N:15]=[C:16]([NH:32][C@@H:25]4[C:26]5[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=5)[CH2:23][C@H:24]4[OH:33])[O:17][C:13]=3[CH:12]=2)[CH:2]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 69311541-Amino-2-indanol, trans-(-)-HCID 866810466-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylsulfinyl)benzo[d]oxazole

Product 1

HCID 71549861(1R,2R)-1-((6-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]oxazol-2-yl)amino)-2,3-dihydro-1H-inden-2-olYield 26%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

A stirred mixture of 6-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylthio)benzo[d]oxazole (108 mg, 0.346 mmol) from Step 5 of Example 56, (1R,2R)-(−)-trans-1-amino-2-indanol (104 mg, 0.698 mmol), and DIEA (90 mg, 0.698 mmol) in anhydrous DMA (1.5 mL) was sealed and heated in a Biotage microwave synthesizer at 120° C. for 30 min. The reaction mixture was cooled to rt and 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-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]oxazol-2-yl)amino)-2,3-dihydro-1H-inden-2-ol (35 mg, 26%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.62 (s, 1H), 8.36-8.45 (m, 2H), 8.09 (dd, J=1.3, 8.1 Hz, 1H), 7.47 (s, 1H), 7.29 (dd, J=4.7, 8.1 Hz, 1H), 7.12-7.25 (m, 6H), 5.52 (s, 2H), 5.47 (d, J=5.1 Hz, 1H), 5.02 (m, 1H), 4.34 (m, 1H), 3.15 (dd, J=7.2, 15.6 Hz, 1H), 2.73 (dd, J=7.6, 15.4 Hz, 1H). LCMS (ESI) m/z 398 (M+H)+.

Workup

  1. customwas sealed
  2. temperatureThe reaction mixture was cooled to rt
  3. custompurified directly by reverse-phase
  4. 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-12caa150f6cc41ddb3432d30727c0f2a
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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