Sodium Hydroxide → (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-(1,2-dimethyl-3-oxo-2,3-dihydro-1H-indazol-6-yl)pyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetic acid

HRID 879369Notes

Reaction equation

[C:1]([O:5][C@@H:6]([C:12]1[C:38]([CH3:39])=[CH:37][C:15]2[N:16]=[C:17]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([C:25]4[CH:33]=[C:32]5[C:28]([C:29](=[O:36])[N:30]([CH3:35])[N:31]5[CH3:34])=[CH:27][CH:26]=4)[CH:20]=3)[S:18][C:14]=2[C:13]=1[C:40]1[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][CH:41]=1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>C1COCC1.CO>[C:1]([O:5][C@@H:6]([C:12]1[C:38]([CH3:39])=[CH:37][C:15]2[N:16]=[C:17]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([C:25]4[CH:33]=[C:32]5[C:28]([C:29](=[O:36])[N:30]([CH3:35])[N:31]5[CH3:34])=[CH:27][CH:26]=4)[CH:20]=3)[S:18][C:14]=2[C:13]=1[C:40]1[CH:41]=[CH:42][C:43]([Cl:46])=[CH:44][CH:45]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 50 °C

Procedure

To a stirred solution of (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-(1,2-dimethyl-3-oxo-2,3-dihydro-1H-indazol-6-yl)pyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate (9.4 mg, 0.014 mmol) in THF (0.5 mL) and methanol (0.5 mL) was added 1N NaOH solution (0.5 mL, excess). The reaction mixture was stirred at 50° C. for 2 h and then purified by reverse phase HPLC, eluting by 0-100% acetonitrile in H2O with 0.1% TFA to give the desired product. LCMS-ESI+ (m/z): [M+H]+ calcd for C34H32ClN4O4S: 627.2; found: 627.2. 1H NMR (400 MHz, CD3OD) δ 8.75 (d, J=5.2 Hz, 1H), 8.49 (s, 1H), 8.06 (s, 1H), 7.96 (dd, J=5.2, 1.2 Hz, 1H), 7.90 (s, 1H), 7.85 (q, J=8.4 Hz, 2H), 7.70-7.67 (m, 1H), 7.61-7.56 (m, 3H), 5.27 (s, 1H), 3.51 (s, 3H), 3.47 (s, 3H), 2.62 (s, 3H), 0.98 (s, 9H).

Workup

custompurified by reverse phase HPLC
washeluting by 0-100% acetonitrile in H2O with 0.1% TFA

Sources & evidence

ORD record: ord-9bbda6bfc4f2438f825030a0a4020d76
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987250B2

Reaction notes

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