Tert-Butylamine → 1-(Tert-butylamino)isoquinoline-7-carboxylic acid

HRID 537201Notes

Reaction equation

HRID 537201 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([OH:14])=[O:13])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+].[C:92]([NH2:96])([CH3:95])([CH3:94])[CH3:93].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>O1CCOCC1>[C:92]([NH:96][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([OH:14])=[O:13])[CH:10]=2)[CH:5]=[CH:4][N:3]=1)([CH3:95])([CH3:94])[CH3:93]

Participants

8

Reactant 6

HCID 6385Tert-ButylamineHCID 2733832Lithium HexamethyldisilazideHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 211924911-Chloroisoquinoline-7-carboxylic acidHCID 23676156Sodium t-butoxideHCID 25112535Brettphos

Product 1

HCID 674915901-(Tert-butylamino)isoquinoline-7-carboxylic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a suspension of 1-chloroisoquinoline-7-carboxylic acid (100 mg, 0.482 mmol), RuPhos (6.5 mg, 0.014 mmol), BrettPhos (11.2 mg, 0.014 mmol) and sodium tert-butoxide (70.2 mg, 0.723 mmol) in dioxane (0.5 mL) was added t-butylamine (0.254 mL, 2.41 mmol). The vessel was sealed and mixture was heated to 110° C. and stirred overnight. The reaction was cooled down to room temperature and lithium bistrimethylsilylamide (0.136 mL, 0.723 mmol) was added. The reaction mixture was heated to 110° C. and left stirring overnight. The reaction mixture was cooled down to room temperature and filtered through celite and rinsed with methanol. The filtrate was concentrated under reduced pressure and 1N aqueous sodium hydroxide (1 mL) was added. Partitioned between ethyl acetate and a mixture of water and 1N aqueous sodium hydroxide. The layers were separated and the aqueous layer was acidified to pH 4. The aqueous layer was extracted into ethyl acetate. The extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure to obtain 1-(tert-butylamino)isoquinoline-7-carboxylic acid.

Workup

  1. customThe vessel was sealed
  2. temperatureThe reaction was cooled down to room temperature
  3. temperatureThe reaction mixture was heated to 110° C.
  4. waitleft
  5. stirringstirring overnight
  6. temperatureThe reaction mixture was cooled down to room temperature
  7. filtrationfiltered through celite
  8. washrinsed with methanol
  9. concentrationThe filtrate was concentrated under reduced pressure and 1N aqueous sodium hydroxide (1 mL)
  10. additionwas added
  11. customPartitioned between ethyl acetate
  12. additiona mixture of water and 1N aqueous sodium hydroxide
  13. customThe layers were separated
  14. extractionThe aqueous layer was extracted into ethyl acetate
  15. dry with materialThe extracts were dried over magnesium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-716204317dc247519610999be8679a0f
Source dataset
uspto-grants-2014_10
Patent number
US08859773B2

Reaction notes

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