Lithium Hexamethyldisilazide → N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amine

HRID 1042270

Reaction equation

HRID 1042270 reaction equation
F[C:2]1[C:7]([C:8]2[C:9]3[CH:16]=[CH:15][NH:14][C:10]=3[N:11]=[CH:12][N:13]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[Cl:17][C:18]1[C:27]2[CH:26]=[CH:25][C:24]([CH3:28])=[C:23]([NH2:29])[C:22]=2[CH:21]=[CH:20][N:19]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[N:11]1[C:10]2[NH:14][CH:15]=[CH:16][C:9]=2[C:8]([C:7]2[C:2]([NH:29][C:23]3[C:22]4[CH:21]=[CH:20][N:19]=[C:18]([Cl:17])[C:27]=4[CH:26]=[CH:25][C:24]=3[CH3:28])=[N:3][CH:4]=[CH:5][CH:6]=2)=[N:13][CH:12]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 59627370HCID 59627370, compoundHCID 596273751-Chloro-6-methylisoquinolin-5-amine

Product 1

HCID 59627376N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amineYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22 °C

Procedure

A mixture of 4-(2-fluoropyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (2.17 g, 10.1 mmol) and 1-chloro-6-methylisoquinolin-5-amine (1.95 g, 10.1 mmol) in THF (4 mL) was sonicated for 3 min until throughly mixed. Lithium bis(trimethylsilyl)amide (7.63 g, 45.6 mmol) (1 N in THF from Aldrich) was added in a stream and the resulting dark brown solution was stirred at 22° C. for 4 h. The reaction was quenched with NaHCO3 (aq., sat.) while cooled in an ice bath. The reaction mixture was then partitioned between EtOAc and NaHCO3 (aq., sat). The aqueous layer was washed with EtOAc twice. The organic layers were combined and concentrated in vacuo. The light brown solid residue was triturated with EtOAc (˜50 mL) to give a yellow solid. This solid was collected by filtration and washed with EtOAc twice and then dried in a vacuum oven (45° C.) over the weekend to give N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amine as a yellow solid (2.85 g, 73% yield). MS (ESI, pos. ion) m/z: 387 [M+H]+

Workup

  1. customwas sonicated for 3 min
  2. additionuntil throughly mixed
  3. customThe reaction was quenched with NaHCO3 (aq., sat.)
  4. temperaturewhile cooled in an ice bath
  5. customThe reaction mixture was then partitioned between EtOAc and NaHCO3 (aq., sat)
  6. washThe aqueous layer was washed with EtOAc twice
  7. concentrationconcentrated in vacuo
  8. customThe light brown solid residue was triturated with EtOAc (˜50 mL)
  9. customto give a yellow solid
  10. filtrationThis solid was collected by filtration
  11. washwashed with EtOAc twice
  12. customdried in a vacuum oven (45° C.) over the weekend

Sources & evidence

ORD record
ord-f4bc954ff6e34216b22f4b38b2c0bbc1
Source dataset
uspto-grants-2013_10
Patent number
US08557830B2

Linked notes

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