2,6-Lutidine → HCID 178455361, compound

HRID 1257682Notes

Reaction equation

HRID 1257682 reaction equation
[NH2:1][C:2]1[C:3]([NH:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([OH:27])[CH2:23][CH2:22]2)=[C:4]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:5]2=[N:6][CH:7]=1.N1C(C)=CC=CC=1C.O([Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45])S(C(F)(F)F)(=O)=O>C(Cl)Cl>[C:14]1([S:11]([N:8]2[C:5]3=[N:6][CH:7]=[C:2]([NH2:1])[C:3]([NH:20][C@H:21]4[CH2:22][CH2:23][C@H:24]([O:27][Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45])[CH2:25][CH2:26]4)=[C:4]3[CH:10]=[CH:9]2)(=[O:13])=[O:12])[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 178507999HCID 178507999, compound

Product 1

HCID 178455361HCID 178455361, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Trans 4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclohexanol (5.00 g, 13.0 mmol) was dissolved in DCM (50 mL) and 2,6-lutidine (6.0 mL, 51.8 mmol) was added. The mixture was cooled to 0° C. and tert-butyldimethylsilyl triflate (8.90 mL, 38.9 mmol) was added dropwise. The mixture was allowed to return to room temperature and stirred for 16 h. The mixture was concentrated under vacuum, then the residue was dissolved in methanol (10 mL). This mixture was stirred at room temperature for 90 min, then concentrated. The residue was suspended in water and extracted with DCM (×3). The combined organic extracts were washed sequentially with 10% aqueous citric acid, saturated aqueous NaHCO3 and brine, then dried (Na2SO4) and concentrated under vacuum. Purification by column chromatography on silica gel (gradient: DCM to 25% ethyl acetate in DCM) gave 3.09 g (48%) of trans 1-benzenesulfonyl-N*4*-[4-(tert-butyl-dimethyl-silanyloxy)-cyclohexyl]-1H-pyrrolo[2,3-b]pyridine-4,5-diamine. LCMS (Method B, ESI): RT=3.99 min, m+H=501.1; NMR (400 MHz, CDCl3) δ: 8.14 (d, 2H), 7.84 (s, 1H), 7.54 (m, 1H), 7.45 (m, 3H), 6.55 (d, 1H), 3.70 (m, 2H), 2.35-1.85 (m, 6H), 1.46 (m, 2H), 1.30 (m, 2H), 0.89 (s, 9H), 0.06 (s, 6H).

Workup

  1. customto return to room temperature
  2. concentrationThe mixture was concentrated under vacuum
  3. dissolutionthe residue was dissolved in methanol (10 mL)
  4. stirringThis mixture was stirred at room temperature for 90 min
  5. concentrationconcentrated
  6. extractionextracted with DCM (×3)
  7. washThe combined organic extracts were washed sequentially with 10% aqueous citric acid, saturated aqueous NaHCO3 and brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated under vacuum
  10. customPurification by column chromatography on silica gel (gradient: DCM to 25% ethyl acetate in DCM)

Sources & evidence

ORD record
ord-8c168169a69947d3b81c735c62109ad6
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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