Hydrochloric Acid → (2S)-N-(5-chloropyridin-2-yl)-3-(2-hydroxyethoxy)-2-(3-o-tolyl-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)propanamide

HRID 1098044Notes

Reaction equation

HRID 1098044 reaction equation
Cl.[Si]([O:19][CH2:20][CH2:21][O:22][CH2:23][C@H:24]([O:35][C:36]1[C:37]2[N:44]=[N:43][N:42]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=3[CH3:51])[C:38]=2[N:39]=[CH:40][N:41]=1)[C:25]([NH:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][N:29]=1)=[O:26])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>CO>[Cl:34][C:31]1[CH:32]=[CH:33][C:28]([NH:27][C:25](=[O:26])[C@@H:24]([O:35][C:36]2[C:37]3[N:44]=[N:43][N:42]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=4[CH3:51])[C:38]=3[N:39]=[CH:40][N:41]=2)[CH2:23][O:22][CH2:21][CH2:20][OH:19])=[N:29][CH:30]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 57504545(2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-chloropyridin-2-yl)-2-(3-o-tolyl-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)propanamide

Product 1

HCID 57504426(2S)-N-(5-chloropyridin-2-yl)-3-(2-hydroxyethoxy)-2-(3-o-tolyl-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)propanamideYield 49.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Hydrochloric acid (10%, 1 mL) was added dropwise to (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-chloropyridin-2-yl)-2-(3-o-tolyl-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)propanamide (Intermediate AP7) (250 mg, 0.35 mmol) in methanol (20.00 mL) at room temperature. The resulting solution was stirred for 4 hours. Most of the methanol was evaporated and the remaining aq. soln was diluted with saturated NH4Cl and extracted with EtOAc (2×30 mL). The organic layers were combined, dried (MgSO4) and evaporated to give crude product. The crude product was purified by flash silica chromatography, eluting with 0 to 100% EtOAc in isohexane to afford the product (81 mg, 48.8%). 1H NMR (400 MHz, CDCl3) δ2.20 (s, 3H), 2.60-2.66 (m, 1H), 3.73-3.83 (m, 4H), 4.20-4.32 (m, 2H), 6.15 (t, 1H), 7.41-7.54 (m, 4H), 8.17-8.21 (m, 1H), 8.23-8.25 (m, 1H), 8.70 (s, 1H), 9.20 (s, 1H), OH not observed; m/z (ESI+) (M+H)+=470.43; HPLC tR=2.25 min

Workup

  1. customMost of the methanol was evaporated
  2. additionthe remaining aq. soln was diluted with saturated NH4Cl
  3. extractionextracted with EtOAc (2×30 mL)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customto give crude product
  7. customThe crude product was purified by flash silica chromatography
  8. washeluting with 0 to 100% EtOAc in isohexane

Sources & evidence

ORD record
ord-66bbe8c6d906404583bd3635c862624c
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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