Dichloromethane → HCID 118207704, compound

HRID 2205622Notes

Reaction equation

HRID 2205622 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[CH2:26][C@@H:25]3[CH2:27][C@H:22]2[CH2:23][N:24]3C(OC(C)(C)C)=O)[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].[C@H:22]12[CH2:27][C@H:25]([NH:24][CH2:23]1)[CH2:26][N:21]2[C:12]1[CH:13]=[C:14]2[N:19]([CH3:20])[CH:18]=[CH:17][C:15]2=[N:16][C:11]=1[C@@H:9]([NH:8][C:6]1[C:5]([C:35]#[N:36])=[C:4]([CH3:37])[N:3]=[C:2]([NH2:1])[N:7]=1)[CH3:10]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 118214758HCID 118214758, compound

Product 2

HCID 313Hydrochloric AcidHCID 118207704HCID 118207704, compoundYield 78%

Procedure

To a 100 mL pear flask was added tert-butyl (1S,4S)-5-(5-((S)-1-((2-amino-5-cyano-6-methylpyrimidin-4-yl)amino)ethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (220 mg, 0.44 mmol) in dichloromethane (4.5 mL) to give a solution. To this solution was added TFA (1.5 mL). The mixture was stirred at room temperature for 30 minutes. 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 lyophilized to give an HCl salt of the title compound as a yellow-green solid (160 mg, 78%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.67 (d, J=7.07 Hz, 3H), 2.00 (d, J=10.61 Hz, 1H), 2.33 (br s, 1H), 2.43 (s, 3H), 3.09-3.25 (m, 1H), 3.45 (d, J=10.11 Hz, 2H), 3.96-4.06 (m, 4H), 4.10-4.18 (m, 1H), 4.49 (br s, 1H), 5.95 (quin, J=6.88 Hz, 1H), 6.78 (d, J=2.27 Hz, 1H), 7.76 (br s, 1H), 8.03 (br s, 1H), 8.25 (br s, 1H), 8.63 (br s, 1H), 9.08 (br s, 1H), 9.78 (br s, 1H), 10.19 (br s, 1H); ESI-MS m/z [M+H]+ calc'd for C21H25N9, 404. found 404.

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-82f5a110753b4f588db9df2404694bfe
Source dataset
uspto-grants-2016_06
Patent number
US09371321B2

Reaction notes

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