Dimethylamine → 2-(dimethylamino)-1-(3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)ethanone acetate salt

HRID 1848108Notes

Reaction equation

HRID 1848108 reaction equation
C([O:3][C:4]([C:6]1[CH:7]=[C:8]2[N:14]=[CH:13][N:12]([CH2:15][C:16]3[CH:32]=[CH:31][C:19]4[N:20]=[C:21]([NH:23][C@@H:24]5[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]5[OH:30])[S:22][C:18]=4[CH:17]=3)[C:9]2=[N:10][CH:11]=1)=[CH2:5])C.Br[N:34]1[C:38](=[O:39])CC[C:35]1=O.CNC>CN(C=O)C>[C:25]([OH:30])(=[O:39])[CH3:26].[CH3:35][N:34]([CH3:38])[CH2:3][C:4]([C:6]1[CH:7]=[C:8]2[N:14]=[CH:13][N:12]([CH2:15][C:16]3[CH:32]=[CH:31][C:19]4[N:20]=[C:21]([NH:23][C@@H:24]5[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]5[OH:30])[S:22][C:18]=4[CH:17]=3)[C:9]2=[N:10][CH:11]=1)=[O:5]

Participants

5

Reactant 3

HCID 674DimethylamineHCID 67184N-bromobutanimideHCID 86681083(1R,2R)-2-((6-((6-(1-ethoxyvinyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

Product 1

HCID 866810842-(dimethylamino)-1-(3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)ethanone acetate saltYield 9.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (1R,2R)-2-((6-((6-(1-ethoxyvinyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (90 mg, 0.20 mmol) from the previous step in DMF (2 mL) at 0° C. was added N-bromosuccinimide (36 mg, 0.20 mmol), and the mixture was stirred for 15 min. To the mixture was added dimethylamine (2M in THF, 0.90 mL, 1.80 mmol) and stirring was continued at 0° C. for 5 min. The reaction mixture was 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 2-(dimethylamino)-1-(3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)ethanone acetate salt (5 mg, 5%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.01 (d, J=1.7 Hz, 1H), 8.75 (s, 1H), 8.67 (d, J=1.7 Hz, 1H), 8.03 (d, J=7.5 Hz, 1H), 7.68 (s, 1H), 7.20-7.32 (m, 2H), 5.52 (s, 2H), 4.80 (br s, 1H), 3.78 (s, 2H), 3.51 (br m, 1H), 3.30 (br m, 1H), 2.25 (s, 6H), 2.04 (br m, 1H), 1.82-1.86 (m, 4H), 1.59-1.65 (br m, 2H), 1.10-1.60 (m, 4H); LCMS (ESI) m/z 465 (M+H)+.

Workup

  1. stirringstirring
  2. waitwas continued at 0° C. for 5 min
  3. customThe reaction mixture was purified directly by reverse-phase
  4. 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-f906fe57521d43c9aaebe51e0e7b2751
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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