Hydrochloric Acid → HCID 71727134, compound

HRID 1774172Notes

Reaction equation

HRID 1774172 reaction equation
Cl.[Si]([O:9][CH2:10][C@@H:11]([N:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][N:29]=[C:28]([NH:32][C@H:33]3[CH2:38][CH2:37][O:36][CH2:35][C@H:34]3[F:39])[N:27]=2)=[CH:22][C:21]1=[O:40])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([F:19])[CH:13]=1)(C(C)(C)C)(C)C>O1CCOCC1.CO>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([C@H:11]([N:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][N:29]=[C:28]([NH:32][C@H:33]4[CH2:38][CH2:37][O:36][CH2:35][C@H:34]4[F:39])[N:27]=3)=[CH:22][C:21]2=[O:40])[CH2:10][OH:9])=[CH:13][C:14]=1[F:19]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86731990HCID 86731990, compound

Product 1

HCID 71727134HCID 71727134, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A 4.0M solution of hydrogen chloride (18.6 mL, 74.5 mmol) in dioxane was slowly added to a cold (0° C.) solution of 1-((S)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-((3S,4S)-3-fluorotetrahydro-2H-pyran-4-ylamino)pyrimidin-4-yl)pyridin-2(1H)-one (8.6 g, 14.9 mmol) in MeOH (40 mL), and the mixture was stirred for 1 hour. The reaction mixture was concentrated, and the residue was taken up in saturated NaHCO3 and extracted with ethyl acetate (2×). The organic layer was dried, filtered and concentrated. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (1:4) to give 1-((S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-(((3S,4S)-3-fluorotetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one as a solid (4.58 g, 66%; 97% e.e. by chiral HPLC (Chiral Tech, column OD-H, 4.6 mm×250 mm, 5u, 30% ethanol/70% hexanes, 1 mL/minute)). 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J=5.0 Hz, 1H), 7.41 (m, 2H), 7.21-7.09 (m, 3H), 6.89 (d, J=5.0 Hz, 1H), 6.76 (d, J=7.0 Hz, 1H), 6.20 (m, 1H), 5.55 (d, J=8.2 Hz, 1H), 4.75 (d, J=50 Hz, 1H), 4.38-4.18 (m, 4H), 4.05 (m, 1H), 3.69-3.53 (m, 2H), 3.12 (br, s, 1H), 2.08-1.84 (m, 2H); m/z (APCI-pos) M+1=463.1, 465.0.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. extractionextracted with ethyl acetate (2×)
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography
  7. washeluting with hexanes/ethyl acetate (1:4)

Sources & evidence

ORD record
ord-aa5017d7949e463abf90bf34f34fb2c0
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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