Sulfuric Acid → HCID 86582225, compound

HRID 1775892Notes

Reaction equation

HRID 1775892 reaction equation
[C:1]([C:5]1[S:9][C:8]([C:10]([NH:12][C@@H:13]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]3[N:36]=[CH:35][C:34]([C:37]4[CH:42]=[CH:41][C:40]([O:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])=[CH:39][CH:38]=4)=[CH:33][N:32]=3)=[CH:27][CH:26]=2)[C:14]([N:16]2[CH2:19][CH:18]([C:20]([O:22]C)=[O:21])[CH2:17]2)=[O:15])=[O:11])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].S(=O)(=O)(O)O>C1COCC1.O>[C:1]([C:5]1[S:9][C:8]([C:10]([NH:12][C@@H:13]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]3[N:36]=[CH:35][C:34]([C:37]4[CH:42]=[CH:41][C:40]([O:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])=[CH:39][CH:38]=4)=[CH:33][N:32]=3)=[CH:27][CH:26]=2)[C:14]([N:16]2[CH2:19][CH:18]([C:20]([OH:22])=[O:21])[CH2:17]2)=[O:15])=[O:11])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 1118Sulfuric AcidHCID 117777790HCID 117777790, compound

Product 1

HCID 86582225HCID 86582225, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (S)-methyl 1-(2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)azetidine-3-carboxylate (341 mg, 0.489 mmol) in THF (10 mL) was added sulfuric acid (3 mL of a 5 M aqueous solution, 15 mmol). After 24 h, the mixture was diluted with water (100 mL) and extracted with EA (2×100 mL). The combined organic extracts were washed with brine (50 mL), dried over MgSO4 and solvents evaporated. Column chromatography (AcOH/EA/DCM/iso-hexanes) gave 233 mg (70%) of (S)-1-(2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)azetidine-3-carboxylic acid Compound 635 as a white solid. LCMS-ESI (m/z) calculated for C39H46N4O5S: 682.3; no m/z observed, tR=10.17 min (Method 10). The chiral purity was >98% e.e. (Chiral Method). 1H NMR (400 MHz, DMSO-d6) δ 12.75 (s, 1H), 9.17 (d, J=1.8 Hz, 2H), 8.77 (app dd, J=8.3, 2.7 Hz, 1H), 8.32 (dd, J=8.2, 4.7 Hz, 2H), 7.79 (d, J=8.7 Hz, 2H), 7.70 (d, J=3.9 Hz, 1H), 7.47-7.52 (m, 2H), 7.11-7.07 (m, 2H), 6.93 (app dd, J=3.9, 1.4 Hz, 1H), 4.70-4.63 (m, 1H), 4.43 (t, J=9.0 Hz, 0.5H), 4.30 (dd, J=8.7, 6.0 Hz, 0.5H), 4.21 (t, J=8.9 Hz, 0.5H), 4.15 (dd, J=8.5, 6.3 Hz, 0.5H), 4.08-3.99 (m, 3H), 3.47-3.40 (m, 1H), 3.93-3.87 (m, 1H), 3.15-3.01 (m, 2H), 1.77-1.70 (m, 2H), 1.49-1.16 (m, 17H), 0.88 (t, J=6.8 Hz, 3H).

Workup

  1. extractionextracted with EA (2×100 mL)
  2. washThe combined organic extracts were washed with brine (50 mL)
  3. dry with materialdried over MgSO4 and solvents
  4. customevaporated

Sources & evidence

ORD record
ord-b6024fc39cfd41c8a2cbc4ee38a70117
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

Loading…