(Diethylamino)sulfur trifluoride → (R)-N-(cyclohex-2-en-1-yl)-6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-amine

HRID 1848216Notes

Reaction equation

HRID 1848216 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:28]=[CH:27][C:15]4[N:16]=[C:17]([NH:19][C@@H:20]5[CH2:25][CH2:24][CH2:23][CH2:22][C@@H:21]5O)[S:18][C:14]=4[CH:13]=3)[C:5]2=[N:6][CH:7]=1.C(N(S(F)(F)F)CC)C>C(Cl)Cl>[C@@H:20]1([NH:19][C:17]2[S:18][C:14]3[CH:13]=[C:12]([CH2:11][N:8]4[C:5]5=[N:6][CH:7]=[C:2]([F:1])[CH:3]=[C:4]5[N:10]=[CH:9]4)[CH:28]=[CH:27][C:15]=3[N:16]=2)[CH2:25][CH2:24][CH2:23][CH:22]=[CH:21]1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluoride2×HCID 86681159(1S,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

Product 1

HCID 86681194(R)-N-(cyclohex-2-en-1-yl)-6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-amineYield 3.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred mixture of (1R,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (156 mg, 0.4 mmol) from Example 162 in CH2Cl2 (10 mL) at −78° C. under argon was added diethylaminosulfur trifluoride (63 μL, 0.5 mmol). After stirring the mixture for 3 h, additional diethylaminosulfur trifluoride (63 μL, 0.5 mmol) was added. After the mixture was stirred for a further 3 h, it was poured over ice. Additional CH2Cl2 (50 mL) was added and the mixture was stirred until the ice was melted. The layers were separated and the organic layer was washed with brine (50 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase to afford (R)—N-(cyclohex-2-en-1-yl)-6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-amine (5 mg, 3%) as a white powder. 1H NMR (500 MHz, DMSO-d6) δ 8.67 (s, 1H), 8.41 (s, 1H), 8.03-8.13 (m, 2H), 7.68 (s, 1H), 7.32 (d, J=8.3 Hz, 1H), 7.24 (dd, J=1.3, 8.3 Hz, 1H), 5.83 (m, 1H), 5.72 (m, 1H), 5.48 (s, 2H), 4.40 (br s, 1H), 1.95-2.03 (m, 2H), 1.90 (m, 1H), 1.70 (m, 1H), 1.54-1.62 (m, 2H); LCMS (ESI) m/z 380 (M+H)+.

Workup

  1. stirringAfter the mixture was stirred for a further 3 h
  2. additionit was poured over ice
  3. customThe layers were separated
  4. washthe organic layer was washed with brine (50 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by reverse-phase preparative HPLC
  9. additiona mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase

Sources & evidence

ORD record
ord-437fcaa3b71145c09d445612be4412c9
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

Loading…