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

HRID 1848037Notes

Reaction equation

HRID 1848037 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.[NH2:24][C@@H:25]1[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]1[OH:31].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:24][C@@H:25]5[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]5[OH:31])[O:18][C:14]=4[CH:13]=3)[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 735777(1R,2R)-2-AminocyclohexanolHCID 866810496-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylsulfinyl)benzo[d]oxazole

Product 1

HCID 71549859(1R,2R)-2-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanolYield 38%

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 this Example, (1R,2R)-(−)-2-aminocyclohexanol (88 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)-2-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol (64 mg, 38%) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 8.66 (s, 1H), 8.49 (d, J=2.0 Hz, 1H), 8.38 (d, J=1.7 Hz, 1H), 7.81 (d, J=7.6 Hz, 1H), 7.39 (s, 1H), 7.10-7.16 (m, 2H), 5.48 (s, 2H), 4.69 (d, J=4.2 Hz, 1H), 3.30-3.40 (m, 2H), 1.83-1.97 (m, 2H), 1.57-1.67 (m, 2H), 1.15-1.30 (m, 4H). LCMS (ESI) m/z 442 and 444 (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-cf9b394f12a04eb792ef8e16197627ef
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

Loading…