Water → HCID 72194378, compound

HRID 879309Notes

Reaction equation

HRID 879309 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[CH:15]=[C:14]([C:16]4[S:17][C:18]5[C:24]([C:25]6[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=6)=[C:23]([C@H:32]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:33]([O:35]C)=[O:34])[C:22]([CH3:42])=[CH:21][C:19]=5[N:20]=4)[CH:13]=[CH:12][N:11]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.O>CO>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[CH:15]=[C:14]([C:16]4[S:17][C:18]5[C:24]([C:25]6[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=6)=[C:23]([C@H:32]([O:37][C:38]([CH3:40])([CH3:39])[CH3:41])[C:33]([OH:35])=[O:34])[C:22]([CH3:42])=[CH:21][C:19]=5[N:20]=4)[CH:13]=[CH:12][N:11]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

4

Reactant 2

HCID 962WaterHCID 86699829HCID 86699829, compound

Product 1

HCID 72194378HCID 72194378, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

The solution of crude (S)-methyl 2-(2-(2-(1H-indazol-5-yl)pyridin-4-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate from the previous reaction was treated directly with LiOH monohydrate (60 mg, 1.42 mmol), H2O (500 μL), and MeOH (500 μL). The reaction was heated to 50° C. for 15 h. The reaction failed to reach completion (LCMS analysis). The reaction was then heated to 100° C. for 30 min and reached completion. The system was cooled to 23° C. and filtered (0.45 micron Teflon® filter). The filtrate was purified directly on a C-18 Gemini column using a Gilson liquid handler (Eluent H2O/CH3CN gradient with both mobile phase components spiked 0.1% v/v with TFA). The title compound was obtained as a mono-trifluoroacetic acid salt. LCMS-ESI+: calc'd for C32H27ClN4O3S: 583.2 and 585.2 (M+H+); Found: 583.3 and 585.3 (M+H+). 1H NMR (400 MHz, CD3OD) δ: 8.78 (d, J=5.5 Hz, 1H), 8.58 (s, 1H), 8.51 (s, 1H), 8.22 (s, 1H), 8.11 (dd, J=8.6, 1.2 Hz, 1H), 8.04 (dd, J=5.4, 1.2 Hz, 1H), 7.99 (s, 1H), 7.74-7.70 (m, 2H), 7.65-7.60 (m, 3H), 5.23 (s, 1H), 2.65 (s, 3H), 0.99 (s, 9H).

Workup

  1. temperatureThe reaction was then heated to 100° C. for 30 min
  2. temperatureThe system was cooled to 23° C.
  3. filtrationfiltered
  4. filtration(0.45 micron Teflon® filter)
  5. customThe filtrate was purified directly on a C-18 Gemini column

Sources & evidence

ORD record
ord-5f6ab780992c4f1f91bbaf902d2782a1
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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