Hydrochloric Acid → 5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(4-piperidinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 1909986Notes

Reaction equation

HRID 1909986 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][CH:19]=3)[N:16]([C:20](=[O:29])[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[CH:23]=3)[CH2:15][CH2:14]4)=[CH:9][N:8]([CH:30]3[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]3)[C:4]=2[N:5]=[CH:6][N:7]=1.Cl>O1CCOCC1>[CH3:28][C:24]1[CH:23]=[C:22]([CH2:21][C:20]([N:16]2[C:17]3[C:13](=[CH:12][C:11]([C:10]4[C:3]5[C:2]([NH2:1])=[N:7][CH:6]=[N:5][C:4]=5[N:8]([CH:30]5[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]5)[CH:9]=4)=[CH:19][CH:18]=3)[CH2:14][CH2:15]2)=[O:29])[CH:27]=[CH:26][CH:25]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 668238551,1-dimethylethyl 4-(4-amino-5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-piperidinecarboxylate

Product 1

HCID 668236435-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(4-piperidinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 99.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
50 °C

Procedure

To 1,1-dimethylethyl 4-(4-amino-5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-piperidinecarboxylate (230 mg, 0.406 mmol) were added 1,4-Dioxane and 4N HCl in dioxane (4 mL, 16.00 mmol). The mixture was allowed to stir overnight at 50° C. The reaction was concentrated. The solid was sonicated with 1:1 Hexane:DCM and the solid was isolated by filtration to isolate 5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(4-piperidinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (188 mg, 80% yield) as a white solid as the trihydrochloride salt. LC-MS (ES) m/z=467.4 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) δ 8.38 (s, 1H), 8.29 (d, J=8.34 Hz, 1H), 7.61 (s, 1H), 7.41 (s, 1H), 7.35 (dd, J=1.77, 8.34 Hz, 1H), 7.22-7.28 (m, 1H), 7.18 (s, 1H), 7.13 (t, J=7.33 Hz, 2H), 5.07-5.18 (m, 1H), 4.25 (t, J=8.46 Hz, 2H), 3.90 (s, 2H), 3.68 (s, 2H), 3.61-3.67 (m, 2H), 3.25-3.31 (m, 3H), 2.41-2.54 (m, 2H), 2.36 (s, 3H), 2.34 (br. s., 2H).

Workup

  1. concentrationThe reaction was concentrated
  2. customThe solid was sonicated with 1:1 Hexane
  3. customDCM and the solid was isolated by filtration

Sources & evidence

ORD record
ord-b1249d4a8f2a431ba7ac453c43d3fe1d
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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