Trifluoroacetic acid → (R)-tert-butyl 1-(3-(4-((2-amino-4-((S)-1-hydroxyhexan-3-ylamino)-6-methyl pyrimidin-5-yl)methyl)-3-methoxyphenoxy)propyl)pyrrolidine-2-carboxylate

HRID 2207088Notes

Reaction equation

HRID 2207088 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C@@H:9]([CH2:13][CH2:14][CH3:15])[CH2:10][CH2:11][OH:12].[NH2:16][C:17]1[N:22]=[C:21](OS(C2C(C)=CC(C)=CC=2C)(=O)=O)[C:20]([CH2:36][C:37]2[CH:58]=[CH:57][C:40]([O:41][CH2:42][CH2:43][CH2:44][N:45]3[CH2:49][CH2:48][CH2:47][C@@H:46]3[C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])=[CH:39][C:38]=2[O:59][CH3:60])=[C:19]([CH3:61])[N:18]=1>C(#N)CC.C(OC([O-])=O)(O)=O.[Na+]>[NH2:16][C:17]1[N:22]=[C:21]([NH:8][C@@H:9]([CH2:13][CH2:14][CH3:15])[CH2:10][CH2:11][OH:12])[C:20]([CH2:36][C:37]2[CH:58]=[CH:57][C:40]([O:41][CH2:42][CH2:43][CH2:44][N:45]3[CH2:49][CH2:48][CH2:47][C@@H:46]3[C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])=[CH:39][C:38]=2[O:59][CH3:60])=[C:19]([CH3:61])[N:18]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 11062353(S)-3-aminohexan-1-olHCID 117992770(R)-tert-butyl 1-(3-(4-((2-amino-4-(mesitylsulfonyloxy)-6-methylpyrimidin-5-yl)methyl)-3-methoxyphenoxy)propyl)pyrrolidine-2-carboxylate

Product 1

HCID 117992620(R)-tert-butyl 1-(3-(4-((2-amino-4-((S)-1-hydroxyhexan-3-ylamino)-6-methyl pyrimidin-5-yl)methyl)-3-methoxyphenoxy)propyl)pyrrolidine-2-carboxylateYield 76.8%

Reagents, catalysts & solvents 2

HCID 7854PropionitrileSolventHCID 88008498Sodium hydrogen dicarbonateSolvent

Conditions

Temperature
120 °C

Procedure

Trifluoroacetic acid (0.091 mL) was added to the mixture of (S)-3-aminohexan-1-ol (416 mg) and the product from step (ix) (775 mg) in propionitrile (8 mL). After the mixture was heated at 120° C. for 16 h, the reaction mixture was cooled to RT, diluted with sat. sodium hydrogen dicarbonate and extracted with EtOAc. The combined organic layer was dried and concentrated under reduced pressure. The residue was purified by flash column chromatography on amino silica gel to afford the sub-title compound (520 mg) as a white gum; 1H NMR (CDCl3); 6.81 (1H, d), 6.44 (1H, d), 6.38 (1H, dd), 4.80 (2H, br s), 4.13-4.03 (1H, m), 4.03-3.90 (2H, m), 3.84 (3H, s), 3.59 (2H, s), 3.49-3.37 (1H, m), 3.34-3.22 (1H, m), 3.18-3.08 (1H, m), 3.08-3.00 (1H, m), 2.91-2.80 (1H, m), 2.62-2.49 (1H, m), 2.41-2.30 (1H, m), 2.35 (3H, s), 2.10-1.70 (8H, m), 1.44-1.34 (1H, m), 1.42 (9H, s), 1.28-0.89 (4H, m), 0.75 (3H, t); LC-MS: m/z 573.

Workup

  1. temperaturethe reaction mixture was cooled to RT
  2. extractionextracted with EtOAc
  3. customThe combined organic layer was dried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash column chromatography on amino silica gel

Sources & evidence

ORD record
ord-ff1e3afd535a43c2b14e6611338d74d4
Source dataset
uspto-grants-2016_06
Patent number
US09376398B2

Reaction notes

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