Ammonia → N-((S)-1-amino-1-oxopropan-2-yl)-6-((S)-1,2-dihydroxyethyl)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamide

HRID 2276819Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2276819
[OH:1][C@@H:2]([C:5]1[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)[N:8]=[C:7]([C:25]([NH:27][C@@H:28]([CH3:33])[C:29]([O:31]C)=O)=[O:26])[CH:6]=1)[CH2:3][OH:4].[NH3:34]>CO>[NH2:34][C:29](=[O:31])[C@@H:28]([NH:27][C:25]([C:7]1[CH:6]=[C:5]([C@H:2]([OH:1])[CH2:3][OH:4])[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)=[CH:13][CH:12]=2)[N:8]=1)=[O:26])[CH3:33]

Komponenten

4

Edukt 2

HCID 222AmmoniaHCID 71572320(S)-methyl 2-(6-((S)-1,2-dihydroxyethyl)-2-(4-(4-fluorophenoxy)phenyl) pyrimidine-4-carboxamido)propanoate

Produkt 1

HCID 71572210N-((S)-1-amino-1-oxopropan-2-yl)-6-((S)-1,2-dihydroxyethyl)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamideAusbeute 87 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel2×

Versuchsvorschrift

To (S)-methyl 2-(6-((S)-1,2-dihydroxyethyl)-2-(4-(4-fluorophenoxy)phenyl) pyrimidine-4-carboxamido)propanoate (0.120 g, 0.263 mmol) was added MeOH (2.5 mL) and 7M NH3 in MeOH (2.5 mL, 17.5 mmol). The reaction was sealed, stirred overnight then evaporated in vacuo. MeOH was added and the reaction mixture evaporated again in vacuo. The resulting solid was triturated with 4 mL 20% EtOAc/hexanes, filtered, and rinsed once with 2 mL 20% EtOAc/hexanes. The material was dried under vacuum to give N-((S)-1-amino-1-oxopropan-2-yl)-6-((S)-1,2-dihydroxyethyl)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamide (Compound Example No. 16) as a pale peach-colored powder (0.099 g, 0.23 mmol. 87% yield). 1H NMR (400 MHz, DMSO-d6): 8.99 (1 H, d, J=7.7 Hz), 8.55 (2 H, d, J=9.0 Hz), 8.01 (1 H, s), 7.60 (1 H, s), 7.33-7.25 (2 H, m), 7.24-7.17 (3 H, m), 7.14 (2 H, d, J=8.8 Hz), 5.83 (1 H, d, J=5.3 Hz), 4.83 (1 H, t, J=5.9 Hz), 4.70 (1 H, q, J=3.9 Hz), 4.50 (1 H, p, J=7.2 Hz), 3.84-3.77 (1 H, m), 3.71-3.63 (1 H, m), 1.41 (3 H, d, J=7.0 Hz); LC/MS: m/z=441.2 [M+H]+.

Aufarbeitung

  1. customThe reaction was sealed
  2. customthen evaporated in vacuo
  3. additionMeOH was added
  4. customthe reaction mixture evaporated again in vacuo
  5. customThe resulting solid was triturated with 4 mL 20% EtOAc/hexanes
  6. filtrationfiltered
  7. washrinsed once with 2 mL 20% EtOAc/hexanes
  8. customThe material was dried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-3af9332b890c4277a4dc8817e005473f
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09133131B2

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