(S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-6-yl)benzo[d]thiazol-6-yl)acetate → (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-3-(1-methylpiperidin-4-yl)-1H-indazol-6-yl)benzo[d]thiazol-6-yl)acetic acid

HRID 879492Notes

Reaction equation

HRID 879492 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:37]([CH3:38])=[CH:36][C:15]2[N:16]=[C:17]([C:19]3[CH:27]=[C:26]4[C:22]([C:23]([C:29]5[CH2:30][CH2:31][N:32]([CH3:35])[CH2:33][CH:34]=5)=[N:24][N:25]4[CH3:28])=[CH:21][CH:20]=3)[S:18][C:14]=2[C:13]=1[C:39]1[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][CH:40]=1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2]>[Rh].CCO>[C:1]([O:5][C@@H:6]([C:12]1[C:37]([CH3:38])=[CH:36][C:15]2[N:16]=[C:17]([C:19]3[CH:27]=[C:26]4[C:22]([C:23]([CH:29]5[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]5)=[N:24][N:25]4[CH3:28])=[CH:21][CH:20]=3)[S:18][C:14]=2[C:13]=1[C:39]1[CH:40]=[CH:41][C:42]([Cl:45])=[CH:43][CH:44]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 86700307(S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-6-yl)benzo[d]thiazol-6-yl)acetate

Product 1

HCID 86700309(S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-3-(1-methylpiperidin-4-yl)-1H-indazol-6-yl)benzo[d]thiazol-6-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 23948RhodiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
23 °C

Procedure

A flask was charged with 5% w/w Rh/Al2O3 (20 mg, 9.6 μmol), (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-6-yl)benzo[d]thiazol-6-yl)acetate (22.3 mg), and EtOH (absolute, 2 mL). The reaction was evacuated (vacuum) and backfilled from a balloon of H2, then stirred vigorously at 23° C. for 2.5 h. At this point, the reaction was treated with THF (1 mL), and 5 M aq NaOH (1 mL), then heated to 100° C. for 30 min. The reaction was cooled to 23° C., and filtered (0.45 micron teflon syringe filter). The filtrate 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 C34H37ClN4O3S: 617.2, 619.2 (M+H+); Found: 617.4, 619.2 (M+H+). 1H NMR (400 MHz, CD3OD): δ 8.22 (s, 1H), 7.98-7.78 (m, 3H), 7.71 (d, J=8.4 Hz, 1H), 7.65-7.57 (m, 3H), 5.28 (s, 1H), 4.13 (s, 0.5 H, minor diastereomer), 4.09 (s, 2.5 H, major diastereomer), 3.73-3.60 (m, 2H), 3.54-3.37 (m, 2H), 3.29-3.18 (m, 2H), 2.97 (s, 2.5H, major diastereomer), 2.94 (s, 0.5H, minor diastereomer), 2.64 (s, 3H), 2.45-2.31 (m, 2H), 2.28-2.06 (m 1H), 0.99 (s, 9H).

Workup

  1. customThe reaction was evacuated (vacuum)
  2. additionAt this point, the reaction was treated with THF (1 mL), and 5 M aq NaOH (1 mL)
  3. temperatureheated to 100° C. for 30 min
  4. temperatureThe reaction was cooled to 23° C.
  5. filtrationfiltered
  6. filtration(0.45 micron teflon syringe filter)
  7. customThe filtrate was purified by reverse phase HPLC
  8. washeluting by 5-100% acetonitrile in H2O with 0.1% TFA

Sources & evidence

ORD record
ord-b38d22abb5f74ea78b15715c92a2c45f
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

Loading…