Hydrochloric Acid → HCID 59864752, compound

HRID 889607Notes

Reaction equation

HRID 889607 reaction equation
C([O:8][C:9](=[O:53])[CH2:10][CH2:11][N:12]([CH2:43][C:44]1[O:45][C:46]2[CH:52]=[CH:51][CH:50]=[CH:49][C:47]=2[CH:48]=1)[S:13]([C:16]1[CH:21]=[CH:20][C:19]([C@H:22]([C:29](=[O:42])[NH:30][C:31]2[S:32][C:33]3[C:38]([N:39]=2)=[CH:37][CH:36]=[C:35]([O:40][CH3:41])[N:34]=3)[CH2:23][CH:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)=[CH:18][CH:17]=1)(=[O:15])=[O:14])C1C=CC=CC=1.[OH-].[Na+].Cl>C1COCC1.O>[O:45]1[C:46]2[CH:52]=[CH:51][CH:50]=[CH:49][C:47]=2[CH:48]=[C:44]1[CH2:43][N:12]([S:13]([C:16]1[CH:21]=[CH:20][C:19]([C@H:22]([C:29](=[O:42])[NH:30][C:31]2[S:32][C:33]3[C:38]([N:39]=2)=[CH:37][CH:36]=[C:35]([O:40][CH3:41])[N:34]=3)[CH2:23][CH:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)=[CH:18][CH:17]=1)(=[O:14])=[O:15])[CH2:11][CH2:10][C:9]([OH:53])=[O:8]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 86625467HCID 86625467, compound

Product 1

HCID 59864752HCID 59864752, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

The title I compound, 3-(benzofuran-2-ylmethyl-{4-[(R)-2-cyclopentyl-1-(5-methoxy-thiazolo[5,4-b]pyridin-2-ylcarbamoyl)-ethyl]-benzenesulfonyl}-amino)-propionic acid benzyl ester (280 mg, 0.372 mmol) is dissolved in THF. To this is added a solution of sodium hydroxide (22 mg, 0.558 mmol) in water. The reaction is stirred at RT overnight. LC/MS indicates ˜80% reaction completion and, therefore, more sodium hydroxide (10 mg, 0.250 mmol) is added. After 2 h of stirring at RT, the reaction is acidified to pH 1 with concentrated hydrochloric acid, then concentrated to remove solvent. The residue is diluted with ethyl acetate and water. The organic layer is separated, dried over anhydrous sodium sulfate, filtered, and concentrated to afford the crude product as a yellow foam. Purification by preparative HPLC affords 3-(benzofuran-2-ylmethyl-{4-[(R)-2-cyclopentyl-1-(5-methoxy-thiazolo[5,4-b]pyridin-2-ylcarbamoyl)-ethyl]-benzenesulfonyl}-amino)-propionic acid as a white solid: 1H NMR (400 MHz, DMSO-D6) δ 1.4 (m, 2 H) 1.6 (m, 3 H) 1.7 (m, 3 H) 2.1 (m, 1H) 3.35 (m, 1 H) 3.9 (s, 3 H) 4.0 (m, 1 H) 4.6 (s, 2 H) 6.7 (s, 1 H) 6.9 (d, J=8.8 Hz, 1 H) 7.1 (m, 2 H) 7.3 (m, 2 H) 7.5 (dt, J=4.3, 2.1 Hz, 1 H) 7.6 (d, J=8.3 Hz, 2 H) 7.8 (d, J=8.6 Hz, 2 H) 8.0 (d, J=8.8 Hz, 1 H) 12.7 (s, 1 H); LC/MS 663.5 (M+1), 661.5 (M−1). EC50 in primary enzyme assay 0.22 μM.

Workup

  1. custom˜80% reaction completion
  2. stirringAfter 2 h of stirring at RT
  3. concentrationconcentrated
  4. customto remove solvent
  5. additionThe residue is diluted with ethyl acetate and water
  6. customThe organic layer is separated
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford the crude product as a yellow foam
  11. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-bae7e03bd1e5449ea58c596768b170d0
Source dataset
uspto-grants-2012_08
Patent number
US08252931B2

Reaction notes

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