Trifluoroacetic acid methylene chloride → (2S,4S,5S)-4-amino-6-(2,2-dimethylhexanamido)-5-hydroxy-2-isopropyl-1-(1-(3-methoxypropyl)-1H-indazol-6-yl)hexyl acetate

HRID 660400Notes

Reaction equation

HRID 660400 reaction equation
[C:1]([O:4][CH:5]([C:36]1[CH:44]=[C:43]2[C:39]([CH:40]=[N:41][N:42]2[CH2:45][CH2:46][CH2:47][O:48][CH3:49])=[CH:38][CH:37]=1)[C@H:6]([CH:33]([CH3:35])[CH3:34])[CH2:7][C@H:8]1[C@H:12]([CH2:13][NH:14][C:15](=[O:23])[C:16]([CH3:22])([CH3:21])[CH2:17][CH2:18][CH2:19][CH3:20])[O:11]C(C)(C)[N:9]1C(OC(C)(C)C)=O)(=[O:3])[CH3:2].C(O)(C(F)(F)F)=O.C(Cl)Cl>>[C:1]([O:4][CH:5]([C:36]1[CH:44]=[C:43]2[C:39]([CH:40]=[N:41][N:42]2[CH2:45][CH2:46][CH2:47][O:48][CH3:49])=[CH:38][CH:37]=1)[C@H:6]([CH:33]([CH3:34])[CH3:35])[CH2:7][C@H:8]([NH2:9])[C@@H:12]([OH:11])[CH2:13][NH:14][C:15](=[O:23])[C:16]([CH3:22])([CH3:21])[CH2:17][CH2:18][CH2:19][CH3:20])(=[O:3])[CH3:2]

Participants

3

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 59630996(4S,5S)-tert-butyl 4-((S)-2-(acetoxy(1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutyl)-5-((2,2-dimethylhexanamido)methyl)-2,2-dimethyloxazolidine-3-carboxylate

Product 1

HCID 59630982(2S,4S,5S)-4-amino-6-(2,2-dimethylhexanamido)-5-hydroxy-2-isopropyl-1-(1-(3-methoxypropyl)-1H-indazol-6-yl)hexyl acetateYield 61%

Procedure

(4S,5S)-tert-butyl 4-((S)-2-(acetoxy(1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutyl)-5-((2,2-dimethylhexanamido)methyl)-2,2-dimethyloxazolidine-3-carboxylate (25 mg, 0.036 mmol) was dissolved 20% TFA/CH2Cl2 (6 mL) at 0° C. and the stirred for 2 h. The solvent was removed in vacuo and the residue was purified by preparative HPLC to give (2S,4S,5S)-4-amino-6-(2,2-dimethylhexanamido)-5-hydroxy-2-isopropyl-1-(1-(3-methoxypropyl)-1H-indazol-6-yl)hexyl acetate (12 mg, 52%). 1H NMR (400 MHz, CD3OD): 0.84-1.00 (m, 9H), 1.11-1.32 (m, 10H), 1.58 (m, 3H), 1.95 (m, 1H), 2.14 (m, 6H), 3.12 (m, 2H), 3.45 (m, 1H), 3.83 (m, 1H), 4.50 (m, 2H), 5.91 (m, 1H), 7.12 (m, 1H), 7.53 (m, 1H), 7.75 (t, 3H), 8.04 (m, 1H). MS: 644 (M++1).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-ec6818e06f66421f8f1f9f5954670b23
Source dataset
uspto-grants-2011_12
Patent number
US08084485B2

Reaction notes

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