Trifluoroacetic acid → (S)-ethyl 2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(ethyl)amino)acetate

HRID 2207066

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:52]=[CH:51][C:40]([CH2:41][N:42]([CH2:49][CH3:50])[CH2:43][C:44]([O:46][CH2:47][CH3:48])=[O:45])=[CH:39][C:38]=2[O:53][CH3:54])=[C:19]([CH3:55])[N:18]=1>C(#N)CC>[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:52]=[CH:51][C:40]([CH2:41][N:42]([CH2:49][CH3:50])[CH2:43][C:44]([O:46][CH2:47][CH3:48])=[O:45])=[CH:39][C:38]=2[O:53][CH3:54])=[C:19]([CH3:55])[N:18]=1

Participants

Conditions

Temperature: 120 °C

Procedure

Trifluoroacetic acid (0.066 mL) was added to a mixture of (S)-3-aminohexan-1-ol (300 mg) and the product from step (vii) (490 mg) in propionitrile (5 mL). The mixture was heated at 120° C. for 16 h and cooled to RT. The solvent was removed by evaporation. The residue was purified by flash column chromatography on amino silica gel to afford the sub-title compound (330 mg) as a colourless gum; 1H NMR (CDCl3); 6.94 (1H, s), 6.88 (1H, d), 6.79 (1H, d), 4.66 (1H, d), 4.58 (2H, br s), 4.13 (2H, q), 4.11-4.06 (1H, m), 3.88 (3H, s), 3.70 (2H, s), 3.66 (2H, s), 3.42 (1H, ddd), 3.28-3.20 (3H, m), 2.65 (2H, q), 2.34 (3H, s), 1.82-1.74 (1H, m), 1.45-1.33 (1H, m), 1.26-1.21 (5H, m), 1.07-1.02 (5H, m), 0.73 (3H, t).

Workup

temperaturecooled to RT
customThe solvent was removed by evaporation
customThe residue was purified by flash column chromatography on amino silica gel

Sources & evidence

ORD record: ord-6076f5c99b58431e8e2112e690ccc276
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09376398B2

Linked notes

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