Trifluoroacetic acid → (R)-2-((S)-2-(4-(tert-butyl)benzamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanamido)propanoic acid

HRID 1775864Notes

Reaction equation

HRID 1775864 reaction equation
[C:1]([C:5]1[CH:53]=[CH:52][C:8]([C:9]([NH:11][C@@H:12]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]3[N:37]=[CH:36][C:35]([C:38]4[CH:43]=[CH:42][C:41]([O:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH3:51])=[CH:40][CH:39]=4)=[CH:34][N:33]=3)=[CH:28][CH:27]=2)[C:13]([NH:15][C@H:16]([CH3:24])[C:17]([O:19]C(C)(C)C)=[O:18])=[O:14])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl.C1(C)C=CC=CC=1>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:9]([NH:11][C@@H:12]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]3[N:37]=[CH:36][C:35]([C:38]4[CH:39]=[CH:40][C:41]([O:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH3:51])=[CH:42][CH:43]=4)=[CH:34][N:33]=3)=[CH:28][CH:27]=2)[C:13]([NH:15][C@H:16]([CH3:24])[C:17]([OH:19])=[O:18])=[O:14])=[O:10])=[CH:52][CH:53]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 117741141(R)-tert-butyl 2-((S)-2-(4-(tert-butyl)benzamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanamido)propanoate

Product 1

HCID 86582530(R)-2-((S)-2-(4-(tert-butyl)benzamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanamido)propanoic acidYield 68%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

Prepared using General Procedure 8. To a stirred solution of (R)-tert-butyl 2-((S)-2-(4-(tert-butyl)benzamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanamido)propanoate (120 mg, 0.166 mmol) in DCM (4 mL) was added TFA (3 mL) and stirred for 2 h. The reaction mixture was diluted with toluene (15 mL) and solvent removed. DMSO (3 mL) was added and the solution was sonicated. This solution was added to vigorously stirring water (30 mL) and the white solid was isolated by filtration and washed with additional ACN (10 mL). The material was dried under high vacuum for 24 h to afford 75 mg (66%) of (R)-2-((S)-2-(4-(tert-butyl)benzamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanamido)propanoic acid Compound 398 as a white powder. LCMS-ESI (m/z) calculated for C40H48N4O5: 664.4. found 665.0 [M+H]+, tR=12.33 min (Method 10). The chiral purity was calculated at >99% e.e. (Chiral Method). 1H NMR (400 MHz, DMSO-d6) δ 12.64 (s, 1H), 9.15 (s, 2H), 8.52 (d, J=8.7 Hz, 1H), 8.45 (d, J=7.4 Hz, 1H), 8.35-8.20 (m, 2H), 7.85-7.68 (m, 4H), 7.56-7.50 (m, 2H), 7.49-7.39 (m, 2H), 7.14-7.03 (m, 2H), 4.93-4.80 (m, 1H), 4.38-4.17 (m, 1H), 4.03 (t, J=6.5 Hz, 2H), 3.22-3.12 (m, 1H), 3.12-3.02 (m, 1H), 1.81-1.67 (m, 2H), 1.53-1.24 (m, 20H), 0.95-0.80 (m, 3H).

Workup

  1. customPrepared
  2. customremoved
  3. additionDMSO (3 mL) was added
  4. customthe solution was sonicated
  5. additionThis solution was added to vigorously stirring water (30 mL)
  6. customthe white solid was isolated by filtration
  7. washwashed with additional ACN (10 mL)
  8. customThe material was dried under high vacuum for 24 h

Sources & evidence

ORD record
ord-ed9084dca2ca474da7877ba0ebfafa3c
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

Loading…