Trifluoroacetic acid → HCID 69597777, compound

HRID 724703Notes

Reaction equation

HRID 724703 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[C:8]([NH:11][C@@H:12]([CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)[C:13]([NH:15][C@@H:16]([CH2:35][C:36]1[CH:41]=[CH:40][C:39]([CH:42]2[S:46](=[O:48])(=[O:47])[N:45](C(C)(C)C)[C:44](=[O:53])[CH2:43]2)=[CH:38][CH:37]=1)[CH2:17][NH:18][CH2:19][CH2:20][CH2:21][CH2:22][O:23][C:24]1[CH:33]=[CH:32][CH:31]=[C:30]([OH:34])[C:25]=1[C:26]([O:28][CH3:29])=[O:27])=[O:14])(=[O:10])[CH3:9].FC(F)(F)C(O)=O>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[C:8]([NH:11][C@@H:12]([CH2:54][C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1)[C:13]([NH:15][C@@H:16]([CH2:35][C:36]1[CH:37]=[CH:38][C:39]([CH:42]2[S:46](=[O:48])(=[O:47])[NH:45][C:44](=[O:53])[CH2:43]2)=[CH:40][CH:41]=1)[CH2:17][NH:18][CH2:19][CH2:20][CH2:21][CH2:22][O:23][C:24]1[CH:33]=[CH:32][CH:31]=[C:30]([OH:34])[C:25]=1[C:26]([O:28][CH3:29])=[O:27])=[O:14])(=[O:10])[CH3:9]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 69597944HCID 69597944, compound

Product 1

HCID 69597777HCID 69597777, compound

Conditions

Temperature
130 °C

Procedure

Methyl 2-[4-((2S)-2-[(2S)-2-(acetylamino)-3-phenylpropanoyl]amino-3-[4-(2-tert-butyl-1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]propylamino)butoxy-]6-hydroxybenzoate trifluoroacetate (salt) was submitted in two batches to deprotection conditions in the a microwave. The first batch (5.1 mg, 0.0061 mmol) was combined with crushed 3 Å molecular sieves (7.9 mg) and trifluoroacetic acid (0.75 mL) and heated at 130° C. 3 times for one minute each time. The second batch (18 mg, 0.021 mmol) was combined with crushed 3 Å molecular sieves (29 mg) and trifluoroacetic acid (2.6 mL) and heated at 130° C. twice for one minute each time. The reactions were combined and filtered through a glass frit. The filtrate was purified on a 50 mm Luna C18 column using a 10–70% acetonitrile in water gradient with 0.05% trifluoroacetic acid at 30 mL per minute over a 30 minute period. The major product was lyophilized to obtain a white solid (12 mg), which was further purified on a 50 mm Luna C18 column using a 0–50% acetonitrile in water gradient with 0.05% trifluoroacetic acid at 30 mL per minute over a 30 minute period. The desired fractions were combined and lyophilized to give a white solid (6 mg, 24%). 1H NMR (400 MHz, CD3OD): δ 7.50 (d, J=8.0 Hz, 2H), 7.30 (m, 6H), 7.17 (m, 2H), 6.55 (dd, J=7.3 Hz, J′=6.5 Hz, 2H), 5.17 (m, 1H), 4.36 (m, 2H), 4.09 (bs, 2H), 3.91 (s, 3H), 3.22–2.83 (m, 9H), 1.92 (m, 7H); LCMS found for C35H43N4O9S (M+H)+: m/z=695.2.

Workup

  1. temperatureheated at 130° C. twice for one minute each time
  2. filtrationfiltered through a glass frit
  3. customThe filtrate was purified on a 50 mm Luna C18 column
  4. customover a 30 minute

Sources & evidence

ORD record
ord-44c1434d26b4456589b22b943b0075d1
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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