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

HRID 537201ノート

反応式

HRID 537201 の反応式
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]

参加物

8

反応物 6

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-716204317dc247519610999be8679a0f
出典データセット
uspto-grants-2014_10
特許番号
US08859773B2

反応ノート

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