Acetonitrile--water (1/1) → (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-1H-pyrazolo[4,3-b]pyridin-6-yl)benzo[d]thiazol-6-yl)acetic acid

HRID 879299Notes

Reaction equation

HRID 879299 reaction equation
[C:1]([O:5][C@@H:6]([C:9]1[C:27]([CH3:28])=[CH:26][C:12]2[N:13]=[C:14]([C:16]3[CH:17]=[C:18]4[N:24]([CH3:25])[N:23]=[CH:22][C:19]4=[N:20][CH:21]=3)[S:15][C:11]=2[C:10]=1[C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)[CH2:7][OH:8])([CH3:4])([CH3:3])[CH3:2].C(#N)C.[OH2:39]>>[C:1]([O:5][C@@H:6]([C:9]1[C:27]([CH3:28])=[CH:26][C:12]2[N:13]=[C:14]([C:16]3[CH:17]=[C:18]4[N:24]([CH3:25])[N:23]=[CH:22][C:19]4=[N:20][CH:21]=3)[S:15][C:11]=2[C:10]=1[C:29]1[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=1)[C:7]([OH:39])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

3

Reactant 2

HCID 18373917Acetonitrile--water (1/1)HCID 86699817(S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-1H-pyrazolo[4,3-b]pyridin-6-yl)benzo[d]thiazol-6-yl)ethanol

Product 1

HCID 72195157(S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-1H-pyrazolo[4,3-b]pyridin-6-yl)benzo[d]thiazol-6-yl)acetic acid

Procedure

To a solution of (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-1H-pyrazolo[4,3-b]pyridin-6-yl)benzo[d]thiazol-6-yl)ethanol (50 mg, 0.099 mmol)in acetonitrile/water (2 mL/0.5 mL) was added CrO3/H5IO6 (0.439M, 1.1 mL, 0.483 mmol) and CrO3 (20 mg, 0.198 mmol). The reaction solution was stirred at room temperature for 1 h and quenched with 5% Na2S2O3 solution. The mixture was extracted with ethyl acetate, washed with water and brine. The organic solution was dried and concentrated to give crude which was purified by reverse phase HPLC, eluting by 5-100% acetonitrile in H2O with 0.1% TFA to give the desired product. LCMS-ESI+: calc'd for C27H25ClN4O3S: 521.14 (M+H+); Found: 521.2 (M+H+), 1H NMR (400 MHz, CD3OD) δ 9.20 (d, J=8 Hz, 1H), 8.67 (s, 1H), 8.24 (s, 1H), 7.88 (s, 1H), 7.71-7.59 (m, 4H), 5.27 (s, 1H), 4.16 (s, 3H), 2.62 (s, 3H), 0.98 (s, 9H).

Workup

  1. customquenched with 5% Na2S2O3 solution
  2. extractionThe mixture was extracted with ethyl acetate
  3. washwashed with water and brine
  4. customThe organic solution was dried
  5. concentrationconcentrated
  6. customto give crude which
  7. customwas purified by reverse phase HPLC
  8. washeluting by 5-100% acetonitrile in H2O with 0.1% TFA

Sources & evidence

ORD record
ord-481da55f2b424678bf1789bf3d315634
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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