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

HRID 1848068Notes

Reaction equation

HRID 1848068 reaction equation
[Br:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:11][C:12]3[CH:23]=[CH:22][C:15]4[N:16]=[C:17](S(C)=O)[S:18][C:14]=4[CH:13]=3)[CH:9]=[N:10][C:5]2=[CH:4][CH:3]=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[N:7]=[C:6]2[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])[S:18][C:14]=4[CH:13]=3)[CH:9]=[N:10][C:5]2=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 69311541-Amino-2-indanol, trans-(-)-2×HCID 866810546-((5-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylsulfinyl)benzo[d]thiazole

Product 1

HCID 71550845(1R,2R)-1-((6-((5-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)-2,3-dihydro-1H-inden-2-olYield 15%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
140 °C

Procedure

A stirred mixture of 6-((5-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylsulfinyl)benzo[d]thiazole (130 mg, 0.332 mmol) from Step 4 of Example 78, (1R,2R)-(−)-trans-1-amino-2-indanol (198 mg, 1.33 mmol), and DIEA (214 mg, 1.66 mmol) in anhydrous DMA (2 mL) in a sealed reaction vessel was heated in a Biotage microwave synthesizer at 140° C. for 1.5 h. LCMS indicated that the reaction was incomplete. Additional (1R,2R)-(−)-trans-1-amino-2-indanol (50 mg, 0.335 mmol) was added, and the mixture was heated in a Biotage microwave synthesizer at 140° C. for a further 45 min. The reaction mixture was cooled to rt and purified directly by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase to afford (1R,2R)-1-((6-((5-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)-2,3-dihydro-1H-inden-2-ol (24 mg, 15%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.62 (s, 1H), 8.47 (d, J=7.9 Hz, 1H), 8.08 (d, J=8.3 Hz, 1H), 7.69 (s, 1H), 7.49 (d, J=8.3 Hz, 1H), 7.37 (d, J=8.3 Hz, 1H), 7.11-7.28 (m, 5H), 5.45-5.54 (m, 3H), 5.18 (t, J=7.1 Hz, 1H), 4.24-4.35 (m, 1H), 3.16 (dd, J=6.9, 15.5 Hz, 1H), 2.74 (dd, J=7.1, 15.5 Hz, 1H). LCMS (ESI) m/z 492 and 494 (M+H)+.

Workup

  1. customin a sealed reaction vessel
  2. temperaturethe mixture was heated in a Biotage microwave synthesizer at 140° C. for a further 45 min
  3. temperatureThe reaction mixture was cooled to rt
  4. custompurified directly by reverse-phase
  5. additiona mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase

Sources & evidence

ORD record
ord-1f4ef5a9031b4e9cbc77cbe9318cc041
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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