Trifluoroacetic acid → HCID 59616623, compound

HRID 1471034Notes

Reaction equation

HRID 1471034 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C@H:15]([C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([C@@H:25]4[CH2:29][CH2:28][CH2:27][N:26]4[C:30](=[O:40])[C@@H:31]([NH:35][C:36]([O:38][CH3:39])=[O:37])[CH:32]([CH3:34])[CH3:33])=[O:24])=[CH:18][CH:17]=3)[CH2:14][CH2:13][C@H:12]2[C:41]2[CH:46]=[CH:45][C:44]([NH:47][C:48]([C@@H:50]3[CH2:54][CH2:53][CH2:52][N:51]3[C:55](OC(C)(C)C)=[O:56])=[O:49])=[CH:43][CH:42]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:62](O)(C(F)(F)F)=[O:63].[C:69]([O:73][C:74]([N:76]1[CH2:80][CH2:79][CH2:78][C@H]1C(O)=O)=[O:75])(C)(C)C>C(Cl)Cl>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C@H:15]([C:16]3[CH:17]=[CH:18][C:19]([NH:22][C:23]([C@@H:25]4[CH2:29][CH2:28][CH2:27][N:26]4[C:30](=[O:40])[C@@H:31]([NH:35][C:36]([O:38][CH3:39])=[O:37])[CH:32]([CH3:34])[CH3:33])=[O:24])=[CH:20][CH:21]=3)[CH2:14][CH2:13][C@H:12]2[C:41]2[CH:42]=[CH:43][C:44]([NH:47][C:48]([C@@H:50]3[CH2:54][CH2:53][CH2:52][N:51]3[C:55](=[O:56])[C@@H:80]([NH:76][C:74](=[O:75])[O:73][CH3:69])[C@H:79]([O:63][CH3:62])[CH3:78])=[O:49])=[CH:45][CH:46]=2)=[CH:7][CH:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 67238076HCID 67238076, compound

Product 1

HCID 59616623HCID 59616623, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of the product from Example 189A (30 mg, 0.036 mmol) in a 1:1 mixture of CH2Cl2:TFA (0.4 mL) was stirred at rt for 45 min. The mixture was concentrated in vacuo, and the residue was partitioned between saturated aq. NaHCO3 and EtOAc (2×). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to give a solid. The solid was subjected to the procedure described in Example 189A (27 mg), substituting (2S,3R)-3-methoxy-2-(methoxycarbonylamino)butanoic acid for (S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid, to give the title compound (17 mg, 52%). 1H NMR (400 MHz, DMSO-D6) δ ppm 0.85-0.97 (m, 6H), 1.08-1.19 (m, 12H), 1.60-1.66 (m, 2H), 1.80-2.05 (m, 8H), 2.08-2.20 (m, 2H), 3.25 (s, 3H), 3.42-3.50 (m, 2H), 3.52 (s, 3H), 3.53 (s, 3H), 3.58-3.72 (m, 2H), 3.76-3.87 (m, 2H), 3.98-4.06 (m, 1H), 4.26 (t, J=7.81 Hz, 1H), 4.38-4.46 (m, 2H), 5.15 (d, J=6.40 Hz, 2H), 6.17 (d, J=8.78 Hz, 2H), 6.94 (d, J=8.89 Hz, 2H), 7.13 (d, J=8.24 Hz, 4H), 7.32 (t, J=8.84 Hz, 2H), 7.49 (dd, J=8.57, 2.06 Hz, 4H), 9.96 (d, J=15.51 Hz, 2H). MS (ESI) m/z 910.6 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue was partitioned between saturated aq. NaHCO3 and EtOAc (2×)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a solid

Sources & evidence

ORD record
ord-f714d210c3aa409da1c0a28ef0c81e62
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Reaction notes

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