Sodium Hydroxide → (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)pyridin-4-yl)benzo[d]thiazol-6-yl)acetic acid

HRID 879363Notes

Reaction equation

HRID 879363 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:24]=[CH:23][N:22]=[C:21]([C:25]4[CH:34]=[N:33][C:32]5[NH:31][C:30](=[O:35])[CH2:29][O:28][C:27]=5[CH:26]=4)[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].[OH-].[Na+]>C1COCC1.CO>[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:24]=[CH:23][N:22]=[C:21]([C:25]4[CH:34]=[N:33][C:32]5[NH:31][C:30](=[O:35])[CH2:29][O:28][C:27]=5[CH:26]=4)[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

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86700167(S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)pyridin-4-yl)benzo[d]thiazol-6-yl)acetate

Product 1

HCID 86700169(S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)pyridin-4-yl)benzo[d]thiazol-6-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)pyridin-4-yl)benzo[d]thiazol-6-yl)acetate (17.1 mg, 0.027 mmol) in THF (1.1 mL) and methanol (1.1 mL) was added 1N NaOH solution (0.8 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 (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)pyridin-4-yl)benzo[d]thiazol-6-yl)acetic acid. LCMS-ESI+ (m/z): [M+H]+ calcd for C32H28ClN4O5S: 615.2; found: 615.2. 1H NMR (400 MHz, CD3OD) δ 8.74 (d, J=4.8 Hz, 1H), 8.61 (d, J=2.0 Hz, 1H), 8.43 (s, 1H), 7.99 (d, J=2.0 Hz, 1H), 7.94 (s, 1H), 7.91 (dd, J=5.2, 1.6 Hz, 1H), 7.71-7.68 (m, 1H), 7.62-7.59 (m, 3H), 5.28 (s, 1H), 4.72 (s, 2H), 2.63 (s, 3H), 0.97 (s, 9H).

Workup

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

Sources & evidence

ORD record
ord-ed233b7f250449d295fef7cc4bd7ea24
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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