Hydrochloric Acid → HCID 71040791, compound

HRID 1626124Notes

Reaction equation

HRID 1626124 reaction equation
C(OC(=O)[NH:7][C:8]1[O:9][CH2:10][C:11]([F:35])([F:34])[C@:12]([C:15]2[CH:20]=[C:19]([NH:21][CH:22]3[C:30]4[N:29]=[CH:28][C:27]([C:31]#[N:32])=[CH:26][C:25]=4[CH2:24][CH2:23]3)[CH:18]=[CH:17][C:16]=2[F:33])([CH3:14])[N:13]=1)(C)(C)C.Cl.C(=O)(O)[O-].[Na+]>>[NH2:7][C:8]1[O:9][CH2:10][C:11]([F:34])([F:35])[C@:12]([C:15]2[CH:20]=[C:19]([NH:21][CH:22]3[C:30]4[N:29]=[CH:28][C:27]([C:31]#[N:32])=[CH:26][C:25]=4[CH2:24][CH2:23]3)[CH:18]=[CH:17][C:16]=2[F:33])([CH3:14])[N:13]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 131731670HCID 131731670, compound

Product 1

HCID 71040791HCID 71040791, compoundYield 14%

Procedure

A solution of {(R)-4-[5-((RS)-3-cyano-6,7-dihydro-5H-[1]pyrindin-7-ylamino)-2-fluoro-phenyl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl}-carbamic acid tert-butyl ester (110 mg, 219 μmol) in hydrochloric acid (4M in dioxane; 1.65 ml, 6.58 mmol) was stirred at room temperature and the progress of reaction was followed on TLC. After completion, the mixture was poured into an aqueous saturated solution of sodium bicarbonate, then extracted with ethyl acetate. The combined organic layers were dried over sodium sulphate and the solvent removed leaving a yellow solid. The crude material was purified by flash chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 0:100 as the eluent. The (RS)-7-[3-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-4-fluoro-phenylamino]-6,7-dihydro-5H-[1]pyrindine-3-carbonitrile (12 mg, 14% yield) was obtained as a mixture of epimers and as a yellow solid. MS (ISP): m/z=402.4 [M+H]+.

Workup

  1. customthe progress of reaction
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulphate
  4. customthe solvent removed
  5. customleaving a yellow solid
  6. customThe crude material was purified by flash chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 0:100 as the eluent

Sources & evidence

ORD record
ord-7c8613da2e2f406e825d13a51e4a298c
Source dataset
uspto-grants-2014_07
Patent number
US08785436B2

Reaction notes

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