HCID 178521019, compound → HCID 178479695, compound

HRID 931220Notes

Reaction equation

HRID 931220 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][N:5]([C:7]2([C:10]3[NH:31][C:13]4=[N:14][C:15]([N:18]5[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24]([N:26]6[CH2:30][CH2:29][CH2:28][CH2:27]6)=[O:25])[CH2:19]5)=[CH:16][CH:17]=[C:12]4[N:11]=3)[CH2:9][CH2:8]2)[CH:6]=1>CC(C)=O>[ClH:1].[Cl:1][C:2]1[CH:3]=[N:4][N:5]([C:7]2([C:10]3[NH:31][C:13]4=[N:14][C:15]([N:18]5[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24]([N:26]6[CH2:27][CH2:28][CH2:29][CH2:30]6)=[O:25])[CH2:19]5)=[CH:16][CH:17]=[C:12]4[N:11]=3)[CH2:9][CH2:8]2)[CH:6]=1

Participants

3

Reactant 1

HCID 178521019HCID 178521019, compound

Product 1

HCID 178479695HCID 178479695, compound

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
40 °C

Procedure

(R)-(1-(2-(1-(4-Chloro-1H-pyrazol-1-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone (140 mg, Example 109-A) was dissolved in 0.5 mL acetone at 22° C. A one molar equivalent of concentrated (36% in water) HCl was added, drop wise, to the rapidly stirred solution. The sample immediately turned cloudy. Sample was warmed to 40° C. and an additional acetone (0.5 mL) was added. After about 30 minutes, the sample was cooled (˜1° C./min) to 22° C. White, opaque solids formed. The sample was vacuum filtered and the solids were collected/dried at room temperature (˜22° C.) to afford (R)-(1-(2-(1-(4-Chloro-1H-pyrazol-1-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone hydrochloride. 1H NMR (400 MHz, DMSO-d6) δ 1.43-2.01 (m, 12H), 2.60 (t, 1H), 2.92-3.10 (m, 2H), 3.29 (t, 2H), 3.38-3.46 (m, 1H), 3.46-3.56 (m, 1H), 4.26 (d, 1H), 4.32 (d, 1H), 7.04 (d, 1H), 7.72 (s, 1H), 7.82 (d, 1H), 8.32 (s, 1H).

Workup

  1. concentrationA one molar equivalent of concentrated (36% in water) HCl
  2. additionwas added
  3. additionan additional acetone (0.5 mL) was added
  4. temperaturethe sample was cooled (˜1° C./min) to 22° C
  5. customWhite, opaque solids formed
  6. filtrationfiltered
  7. customthe solids were collected/dried at room temperature (˜22° C.)

Sources & evidence

ORD record
ord-f2605c58e973491f80364ea961706968
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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