Ammonium Chloride → HCID 135921523, compound

HRID 2189232Notes

Reaction equation

HRID 2189232 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:35])=[C:6]([C:8]2[N:17]=[C:16]([NH:18][C@@H:19]3[CH2:23]B(C(OC(C)(C)C)=O)[C@@H:21](C(OC)=O)[CH2:20]3)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:7]=1.[Cl-].[NH4+:37]>C(OCC)C.C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:35])=[C:6]([C:8]2[N:17]=[C:16]([NH:18][C@H:19]3[CH2:20][C@H:21]([C:5]([OH:35])([CH3:6])[CH3:4])[NH:37][CH2:23]3)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:7]=1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 136337396HCID 136337396, compound

Product 1

HCID 135921523HCID 135921523, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A Grignard solution of MeMgl (0.270 mL, 3M in diethyl ether, 0.810 mmol) was added to a solution of (2R,4R)-1-tert-butyl 2-methyl 4-(2-(5-fluoro-2-hydroxyphenyl)quinazolin-4-ylamino)borolane-1,2-dicarboxylate (0.039 g, 0.081 mmol, prepared as described in Synthesis 89-A) in THF (1 mL) and the solution refluxed for 10 h. Saturated aqueous ammonium chloride (20 mL) was added and the aqueous phase extracted with ethyl acetate (3×20 mL). Organic phases were combined, dried (MgSO4) and concentrated. The resulting crude Boc-protected amine was stirred with 4M HCl in dioxane (6 mL) for 1 h. The mixture was concentrated and the crude purified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g), eluting with methanol and then 1 M ammonia in methanol. Further purification by silica column chromatography (3 cm plug of silica), eluting with 20% methanol in dichloromethane, gave the title compound as a solid (0.012 g, 31%).

Workup

  1. temperaturethe solution refluxed for 10 h
  2. extractionthe aqueous phase extracted with ethyl acetate (3×20 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. concentrationThe mixture was concentrated
  6. customthe crude purified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g)
  7. washeluting with methanol
  8. customFurther purification by silica column chromatography (3 cm plug of silica)
  9. washeluting with 20% methanol in dichloromethane

Sources & evidence

ORD record
ord-76e0386898af49abac7153cd9769e83a
Source dataset
uspto-grants-2012_12
Patent number
US08324226B2

Reaction notes

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