tert-Butanol → tert-butyl {(3S)-1-[5-[(tert-butoxycarbonyl)amino]-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]piperidin-3-yl}carbamate

HRID 1499483Notes

Reaction equation

HRID 1499483 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[C:20](C(O)=O)=[CH:19][N:18]=[C:17]3[N:24]([CH2:27][C:28]4[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=4)[N:25]=[CH:26][C:16]=23)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC(OP([O:48][C:49]2C=CC=CC=2)(N=[N+]=[N-])=O)=CC=1.CC[N:57](C(C)C)C(C)C.[C:64]([OH:68])([CH3:67])([CH3:66])[CH3:65]>>[C:64]([O:68][C:49]([NH:57][C:20]1[C:15]([N:11]2[CH2:12][CH2:13][CH2:14][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH2:10]2)=[C:16]2[CH:26]=[N:25][N:24]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)[C:17]2=[N:18][CH:19]=1)=[O:48])([CH3:67])([CH3:66])[CH3:65]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 123414Diphenylphosphoryl azideHCID 867267164-{(3S)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid

Product 1

HCID 86726718tert-butyl {(3S)-1-[5-[(tert-butoxycarbonyl)amino]-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]piperidin-3-yl}carbamateYield 44%

Procedure

A mixture of 4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (1.0 g, 2.1 mmol), diphenylphosphonic azide (0.58 mL, 2.7 mmol) and DIPEA (0.72 mL, 4.2 mmol) in tert-butyl alcohol (20 mL) heated under reflux overnight. The solution was then evaporated under reduced pressure. The resulting residue was dissolved in DCM, washed with 1 M aq. NaOH and brine, then dried over Na2SO4 and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using CombiFlash® apparatus, eluting with 0 to 50% EtOAc/hexanes, to give the sub-title compound as a brown oil (0.50 g, 44%). LCMS calc. for C29H41N6O5 (M+H)+: m/z=553.3. Found: 553.2.

Workup

  1. temperatureheated
  2. temperatureunder reflux overnight
  3. customThe solution was then evaporated under reduced pressure
  4. dissolutionThe resulting residue was dissolved in DCM
  5. washwashed with 1 M aq. NaOH and brine
  6. dry with materialdried over Na2SO4
  7. customevaporated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel using CombiFlash® apparatus
  9. washeluting with 0 to 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-1659ebc1913e4e928f5684c0e2a11810
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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