Sodium Hydroxide → HCID 118318875, compound

HRID 921224Notes

Reaction equation

HRID 921224 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:38]([CH3:39])=[N:37][C:36]2=[CH:40][C:33]3=[N:34][N:35]2[C:13]=1[N:14]1[CH2:46][CH2:45][C:17]([CH3:47])([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]2[CH:25]=[C:26]([F:44])[CH:27]=[CH:28][C:29]=2[CH2:30][N:31]([CH:41]2[CH2:43][CH2:42]2)[CH2:32]3)[CH2:16][CH2:15]1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CCO>[C:1]([O:5][C@@H:6]([C:12]1[C:38]([CH3:39])=[N:37][C:36]2=[CH:40][C:33]3=[N:34][N:35]2[C:13]=1[N:14]1[CH2:15][CH2:16][C:17]([CH3:47])([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]2[CH:25]=[C:26]([F:44])[CH:27]=[CH:28][C:29]=2[CH2:30][N:31]([CH:41]2[CH2:43][CH2:42]2)[CH2:32]3)[CH2:45][CH2:46]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 118318872HCID 118318872, compound

Product 1

HCID 118318875HCID 118318875, compoundYield 74.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of ethyl (2S)-2-(tert-butoxy)-2-{11-cyclopropyl-16-fluoro-4,25-dimethyl-24-oxa-1,5,7,8,11-pentaazapentacyclo[23.2.2.16,9.02,7.013,18]triaconta-2,4,6(30),8,13(18),14,16-heptaen-3-yl}acetate (35 mg, 0.054 mmol) and NaOH (2.154 mg, 0.054 mmol) in EtOH (3 mL) was refluxed for 2 h. It was then cooled to rt and purified by preparative HPLC to isolate (2S)-2-(tert-butoxy)-2-{11-cyclopropyl-16-fluoro-4,25-dimethyl-24-oxa-1,5,7,8,11-pentaazapentacyclo[23.2.2.16,9.02,7.013,18]triaconta-2,4,6(30),8,13(18),14,16-heptaen-3-yl}acetic acid (25.2 mg, 0.040 mmol, 73.7% yield) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 7.18 (t, J=7.2 Hz, 1H), 6.98 (d, J=9.9 Hz, 1H), 6.85 (t, J=7.7 Hz, 1H), 6.43 (s, 1H), 5.75 (s, 1H), 4.39 (t, J=11.9 Hz, 1H), 3.89 (d, J=9.9 Hz, 1H), 3.65-3.54 (m, 2H), 3.30 (d, J=15.0 Hz, 2H), 3.17 (s, 2H), 2.87-2.77 (m, 1H), 2.73-2.63 (m, 2H), 2.51-2.45 (m, 4H), 1.89-1.42 (m, 11H), 1.16 (br. s., 12H), 0.33 (br. s., 1H), 0.24 (br. s., 1H), 0.13 (br. s., 1H), −0.06 (br. s., 1H). LCMS (M+1)=622.3.

Workup

  1. temperaturewas refluxed for 2 h
  2. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-4dc9bed5147c4ba3bc46d03731862df7
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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