Dichloromethane → 2-Amino-4-methyl-6-((S)-1-(1-methyl-6-((S)-3-(methylamino)pyrrolidin-1-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethylamino)pyrimidine-5-carbonitrile

HRID 2205617Notes

Reaction equation

HRID 2205617 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:16]=[C:15]3[CH:17]=[CH:18][N:19]([CH3:20])[C:14]3=[CH:13][C:12]=2[N:21]2[CH2:25][CH2:24][C@H:23]([N:26](C)[C:27](=O)OC(C)(C)C)[CH2:22]2)[CH3:10])[C:5]([C:35]#[N:36])=[C:4]([CH3:37])[N:3]=1.C(O)(C(F)(F)F)=O.[Cl:45]CCl>>[ClH:45].[NH2:1][C:2]1[N:3]=[C:4]([CH3:37])[C:5]([C:35]#[N:36])=[C:6]([NH:8][C@H:9]([C:11]2[N:16]=[C:15]3[CH:17]=[CH:18][N:19]([CH3:20])[C:14]3=[CH:13][C:12]=2[N:21]2[CH2:25][CH2:24][C@H:23]([NH:26][CH3:27])[CH2:22]2)[CH3:10])[N:7]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 118214739tert-Butyl ((S)-1-(5-((S)-1-((2-amino-5-cyano-6-methylpyrimidin-4-yl)amino)ethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)pyrrolidin-3-yl)(methyl)carbamate

Product 2

HCID 313Hydrochloric AcidHCID 1182077992-Amino-4-methyl-6-((S)-1-(1-methyl-6-((S)-3-(methylamino)pyrrolidin-1-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethylamino)pyrimidine-5-carbonitrileYield 84%

Procedure

To a 25 mL pear flask was added tert-butyl ((S)-1-(5-((S)-1-((2-amino-5-cyano-6-methylpyrimidin-4-yl)amino)ethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)pyrrolidin-3-yl)(methyl)carbamate (61 mg, 0.121 mmol) in dichloromethane (0.8 mL) to give a solution. To this solution was added TFA (0.27 mL), and the mixture was stirred at room temperature for 18 hours. All the volatiles were removed in vacuo, and the residue was re-suspended in toluene and concentrated to remove residual TFA. The residue was then diluted in ACN and water (total of about 90 mL), followed by the addition of 2 N HCl (4 mL). The mixture was then lyophilized to give an HCl salt of the title compound as a yellow-green solid (41 mg, 84%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.66 (d, J=6.82 Hz, 2H), 2.17 (td, J=12.69, 7.20 Hz, 1H), 2.31-2.45 (m, 3H), 2.61 (s, 2H), 3.20-3.39 (m, 2H), 3.46 (br s, 1H), 3.57 (br s, 1H), 3.95 (s, 3H), 5.91 (t, J=6.95 Hz, 1H), 6.79 (br s, 1H), 7.68 (br s, 1H), 8.03 (br s, 1H), 8.48 (br s, 1H), 8.77 (br s, 1H), 9.32-9.50 (m, 1H), 9.60-9.82 (m, 1H); ESI-MS m/z [M+H]+ calc'd for C21H27N9, 406. found 406.

Workup

  1. customto give a solution
  2. customAll the volatiles were removed in vacuo
  3. concentrationconcentrated
  4. customto remove residual TFA
  5. additionThe residue was then diluted in ACN
  6. additionwater (total of about 90 mL), followed by the addition of 2 N HCl (4 mL)

Sources & evidence

ORD record
ord-f4a7f2d4be6949d8b14b8be5190da671
Source dataset
uspto-grants-2016_06
Patent number
US09371321B2

Reaction notes

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