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

HRID 1910006Notes

Reaction equation

HRID 1910006 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:30])[CH2:21][C:22]3[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=3[F:29])[CH2:15][CH2:14]4)=[CH:9][N:8]([CH:31]3[CH2:36][CH2:35][N:34](C(OC(C)(C)C)=O)[CH2:33][CH2:32]3)[C:4]=2[N:5]=[CH:6][N:7]=1.Cl.C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl>O1CCOCC1>[F:29][C:23]1[CH:24]=[CH:25][C:26]([F:28])=[CH:27][C:22]=1[CH2:21][C:20]([N:16]1[C:17]2[C:13](=[CH:12][C:11]([C:10]3[C:3]4[C:2]([NH2:1])=[N:7][CH:6]=[N:5][C:4]=4[N:8]([CH:31]4[CH2:32][CH2:33][NH:34][CH2:35][CH2:36]4)[CH:9]=3)=[CH:19][CH:18]=2)[CH2:14][CH2:15]1)=[O:30]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 668236061,1-dimethylethyl 4-(4-amino-5-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-piperidinecarboxylate

Product 1

HCID 668236445-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(4-piperidinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 82%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To 1,1-dimethylethyl 4-(4-amino-5-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-piperidinecarboxylate (180 mg, 0.306 mmol) was added HCl (4 mL, 16.00 mmol) 4M in dioxane. The reaction was let stir at room temp overnight. The reaction was concentrated then diluted with diethyl ether and filtered to isolate 5-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(4-piperidinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (140 mg, 0.249 mmol, 82% yield) as a light yellow solid as the dihydrochloride salt. LC/MS (ES) m/z=489.0 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) δ 8.39 (s, 1H), 8.24 (d, J=8.34 Hz, 1H), 7.61 (s, 1H), 7.44 (s, 1H), 7.32-7.37 (m, 1H), 7.04-7.20 (m, 3H), 5.08-5.18 (m, 1H), 4.36 (t, J=8.46 Hz, 2H), 3.99 (s, 2H), 3.68 (s, 3H), 3.65 (d, J=13.89 Hz, 2H), 3.36-3.40 (m, 2H), 2.41-2.53 (m, 2H), 2.37 (d, 2H).

Workup

  1. concentrationThe reaction was concentrated
  2. additionthen diluted with diethyl ether
  3. filtrationfiltered

Sources & evidence

ORD record
ord-39d3a88f0d8342a3bb72973e02ba3698
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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