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

HRID 1042269Notes

Reaction equation

HRID 1042269 reaction equation
[N:1]1[C:6]2[NH:7][CH:8]=[CH:9][C:5]=2[C:4]([C:10]2[C:11]([NH:16][C:17]3[C:26]([CH3:27])=[CH:25][CH:24]=[C:23]4[C:18]=3[CH:19]=[CH:20][NH:21][C:22]4=O)=[N:12][CH:13]=[CH:14][CH:15]=2)=[N:3][CH:2]=1.P(Cl)(Cl)([Cl:31])=O>>[N:1]1[C:6]2[NH:7][CH:8]=[CH:9][C:5]=2[C:4]([C:10]2[C:11]([NH:16][C:17]3[C:18]4[CH:19]=[CH:20][N:21]=[C:22]([Cl:31])[C:23]=4[CH:24]=[CH:25][C:26]=3[CH3:27])=[N:12][CH:13]=[CH:14][CH:15]=2)=[N:3][CH:2]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 596273715-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1(2H)-one

Product 1

HCID 59627376N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amineYield 67.3%

Procedure

5-(3-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1(2H)-one (750 mg, 2036 μmol) was suspended in phosphorous oxychloride (9.5 mL, 10.2 mmol). The reaction vessel was flushed with N2 and sealed. The reaction was heated in an oil bath for 5 h. The excess reagent was removed in vacuo. The residue was azeotroped with toluene times and then put under high vacuum overnight. The residue was suspended with 50 g of ice. The suspension was neutralized with NaHCO3 (aq., sat.). The resulting mixture was extracted with DCM. The DCM solution was concentrated in vacuo and the residue was purified via flash column on silica (Hexane:EtOAc gradient of 50-10%) 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 (530 mg, 67% yield). MS (ESI, pos. ion) m/z: 387 [M+H]+

Workup

  1. customThe reaction vessel was flushed with N2
  2. customsealed
  3. temperatureThe reaction was heated in an oil bath for 5 h
  4. customThe excess reagent was removed in vacuo
  5. customThe residue was azeotroped with toluene times
  6. customput under high vacuum overnight
  7. extractionThe resulting mixture was extracted with DCM
  8. concentrationThe DCM solution was concentrated in vacuo
  9. customthe residue was purified via flash column on silica (Hexane:EtOAc gradient of 50-10%)

Sources & evidence

ORD record
ord-e3100cf83e314e539dea424865e7c4ac
Source dataset
uspto-grants-2013_10
Patent number
US08557830B2

Reaction notes

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