Hydrochloric Acid → HCID 57833256, compound

HRID 729976Notes

Reaction equation

HRID 729976 reaction equation
C(OC([N:8]1[C@H:12]([C:13](O)=[O:14])[CH2:11][O:10]C1(C)C)=O)(C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:51][C:52]1[CH:57]=[CH:56][C:55]([C:58]2[N:63]=[C:62]([NH2:64])[N:61]=[C:60]([NH:65][C:66]3[CH:71]=[CH:70][C:69]([O:72][C:73]4[CH:78]=[CH:77][N:76]=[C:75]([C:79]([F:82])([F:81])[F:80])[CH:74]=4)=[CH:68][CH:67]=3)[CH:59]=2)=[CH:54][CH:53]=1.Cl.C(=O)(O)[O-].[Na+]>CN(C)C(=O)C.CS(C)=O.CCOC(C)=O.CO>[NH2:8][CH:12]([CH2:13][OH:14])[C:11]([NH:51][C:52]1[CH:57]=[CH:56][C:55]([C:58]2[CH:59]=[C:60]([NH:65][C:66]3[CH:71]=[CH:70][C:69]([O:72][C:73]4[CH:78]=[CH:77][N:76]=[C:75]([C:79]([F:81])([F:82])[F:80])[CH:74]=4)=[CH:68][CH:67]=3)[N:61]=[C:62]([NH2:64])[N:63]=2)=[CH:54][CH:53]=1)=[O:10]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 6932187(4S)-3-(tert-Butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidine-4-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57833369HCID 57833369, compound

Product 1

HCID 57833256HCID 57833256, compoundYield 43%

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of (4S)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidine-4-carboxylic acid (0.56 g, 2.3 mmol) in dry N,N-dimethylacetamide (10 mL) was added HATU (0.11 g, 2.87 mmol) and DIEA (0.742 g, 5.75 mmol). After the reaction solution was stirred at rt for 1 h, 6-(4-aminophenyl)-N4-(4-{[2-(trifluoromethyl)pyridin-4-yl]oxy}phenyl)pyrimidine-2,4-diamine (Example 165, 0.84 g, 1.92 mmol) was added. The solution was stirred for an additional 24 h at rt and separated by preparative HPLC to afford a solid intermediate, which was treated with methanol (10 mL) and concentrated HCl (0.5 mL) for 12 h at rt. The resulting mixture was diluted with DMSO and purified by HPLC to give a solid. The solid was stirred with saturated sodium bicarbonate and EtOAc for 2 h. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated to afford 0.433 g (43%) of pure product. 1H NMR (DMSO-d6) δ 9.34 (s, 1H), 8.59 (d, 1H), 7.88 (m, 4H), 7.76 (d, 2H), 7.37 (s, 1H), 7.16 (m, 3H), 6.45 (s, 1H), 6.36 (s, 2H), 4.88 (t, 1H), 3.56 (m, 2H), 3.39 (m, 1H); MS ES 526 (M+H)+calcd 526.

Workup

  1. stirringThe solution was stirred for an additional 24 h at rt
  2. customseparated by preparative HPLC
  3. customto afford a solid intermediate, which
  4. custompurified by HPLC
  5. customto give a solid
  6. customThe organic layer was separated
  7. washwashed with water and brine
  8. dry with materialdried over magnesium sulfate
  9. customevaporated

Sources & evidence

ORD record
ord-6a3948ecbad04e338c0cf285c18a1de0
Source dataset
uspto-grants-2009_09
Patent number
US07582646B2

Reaction notes

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