Acetonitrile → (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(1-methyl-1H-indazol-5-yl)pyridin-4-yl)benzo[d]thiazol-6-yl)acetic acid

HRID 879304Notes

Reaction equation

HRID 879304 reaction equation
[I:1]([OH:5])(=[O:4])(=[O:3])=[O:2].[O-2:6].[O-2].[O-2].[Cr+6:9].[C:10]([O:14][C@@H:15]([C:18]1[C:42]([CH3:43])=[CH:41][C:21]2[N:22]=[C:23]([C:25]3[CH:30]=[CH:29][N:28]=[C:27](C4C=C5C(C=NN5C)=CC=4)[CH:26]=3)[S:24][C:20]=2[C:19]=1[C:44]1[CH:49]=[CH:48][C:47]([Cl:50])=[CH:46][CH:45]=1)[CH2:16][OH:17])([CH3:13])([CH3:12])[CH3:11].[C:51](#[N:53])[CH3:52]>>[I:1]([OH:5])(=[O:4])(=[O:3])=[O:2].[O-2:14].[O-2:6].[O-2:2].[Cr+6:9].[C:10]([O:14][C@@H:15]([C:18]1[C:42]([CH3:43])=[CH:41][C:21]2[N:22]=[C:23]([C:25]3[CH:30]=[CH:29][N:28]=[C:27]([C:18]4[CH:15]=[C:52]5[C:21](=[CH:20][CH:19]=4)[N:22]([CH3:23])[N:53]=[CH:51]5)[CH:26]=3)[S:24][C:20]=2[C:19]=1[C:44]1[CH:45]=[CH:46][C:47]([Cl:50])=[CH:48][CH:49]=1)[C:16]([OH:6])=[O:17])([CH3:13])([CH3:12])[CH3:11]

Participants

6

Reactant 4

HCID 6342Acetonitrile2×HCID 65185Metaperiodic acidHCID 10219390chromium (VI) trioxideHCID 86699820(S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(1-methyl-1H-indazol-6-yl)pyridin-4-yl)benzo[d]thiazol-6-yl)ethanol

Product 2

HCID 72194376(S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(1-methyl-1H-indazol-5-yl)pyridin-4-yl)benzo[d]thiazol-6-yl)acetic acidHCID 131721976Periodic acid chromium trioxide

Procedure

A stock solution of periodic acid/chromium trioxide was prepared according to WO 99/52850 by dissolving periodic acid (11.4 g, 50.0 mmol) and chromium trioxide (23 mg, 1.2 mol %) in wet acetonitrile (0.75% H2O) to a volume of 114 mL. This stock solution (0.6 mL) was added to a solution of (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(1-methyl-1H-indazol-6-yl)pyridin-4-yl)benzo[d]thiazol-6-yl)ethanol (25 mg, 0.049 mmol) in ACN (3 mL) at room temperature and stirred for one hour. The reaction mixture was quenched with saturated Na2SO3 solution and extracted with EtOAc. The organic layer was dried (MgSO4), filtered, concentrated and purified by reverse phase HPLC (H2O/ACN+0.1% TFA) to give the desired product after lyophilization. LCMS-ESI+: calc'd for C33H30ClN4O3S: 597.2 (M+H+); found: 597.2, 599.2. 1H NMR (400 MHz, CD3OD) δ 8.72 (d, J=5.3 Hz, 1H), 8.46 (s, 1H), 8.43 (s, 1H), 8.14-8.08 (m, 2H), 7.94-7.87 (m, 2H), 7.73-7.63 (m, 2H), 7.61-7.54 (m, 3H), 5.26 (s, 1H), 4.10 (s, 3H), 2.63 (s, 3H), 0.97 (s, 9H).

Workup

  1. customThe reaction mixture was quenched with saturated Na2SO3 solution
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by reverse phase HPLC (H2O/ACN+0.1% TFA)

Sources & evidence

ORD record
ord-69782d9eb0224192989f90de5124682d
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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