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Diisopropylethylamine → HCID 59605375, compound

HRID 1945990
Notes
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Reaction equation

HRID 1945990 reaction equation
[CH3:1][N:2]1[C:10]([CH2:11][N:12]2[CH2:15][CH:14]([CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[CH2:13]2)=[N:9][C:8]2[C:3]1=[N:4][C:5]([NH:28][C:29]1[C:30]([NH2:35])=[CH:31][CH:32]=[CH:33][CH:34]=1)=[N:6][C:7]=2[N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.[F:36][C:37]([F:42])([CH3:41])[C:38](O)=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:36][C:37]([C:41]1[N:28]([C:5]2[N:4]=[C:3]3[C:8]([N:9]=[C:10]([CH2:11][N:12]4[CH2:13][CH:14]([CH:16]5[CH2:21][CH2:20][O:19][CH2:18][CH2:17]5)[CH2:15]4)[N:2]3[CH3:1])=[C:7]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[N:6]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[N:35]=1)([F:42])[CH3:38]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27828252,2-Difluoropropionic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59605532HCID 59605532, compound

Product 1

HCID 59605375HCID 59605375, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of N-{9-methyl-6-morpholin-4-yl-8-[3-(tetrahydropyran-4-yl)azetidin-1-ylmethyl]-9H-purin-2-yl}benzene-1,2-diamine (0.234 g, 0.49 mmol) and 2,2-difluoropropionic acid (0.057 g, 0.51 mmol) and DIPEA (0.185 mL, 1.08 mL) in DMF (14 mL) was added HATU (0.223 g, 0.59 mmol) and the reaction mixture was stirred at room temperature for 24 h. The reaction mixture was concentrated in vacuo and the residue purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 7.5:92.5). The solution was concentrated in vacuo, the residue was diluted in acetic acid (30 mL) and the reaction mixture was stirred at 90° C. for 18 h. The reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography (Si—PPC, MeOH:DCM, 0:100 to 7.5:92.5) followed by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 95:5 to 2:98) to give 468 as a white solid (0.063 g, 24%). LCMS (Method I): RT=3.34 min, [M+H]+ 553.3. 1H NMR (400 MHz, DMSO-d6): δ 7.84-7.82 (m, 1 H); 7.75-7.72 (m, 1 H); 7.42-7.36 (m, 2 H); 4.58 (dd, J=7.85, 6.0 Hz, 2 H); 4.40-4.00 (m, 4 H); 4.32 (t, J=6.0 Hz, 2 H); 3.78 (s, 3 H); 3.77 (s, 2 H); 3.77-3.73 (m, 4 H); 2.85 (d, J=11.1 Hz, 2 H); 2.68-2.66 (m, 1 H); 2.26 (t, J=19.02 Hz, 3H); 2.09 (t, J=11.1 Hz, 2 H); 1.57 (d, J=12.5 Hz, 3 H); 1.03 (d, J=12.5 Hz, 2 H)

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 7.5:92.5)
  3. concentrationThe solution was concentrated in vacuo
  4. additionthe residue was diluted in acetic acid (30 mL)
  5. stirringthe reaction mixture was stirred at 90° C. for 18 h
  6. concentrationThe reaction mixture was concentrated in vacuo
  7. customthe residue was purified by flash chromatography (Si—PPC, MeOH:DCM, 0:100 to 7.5:92.5)

Sources & evidence

ORD record
ord-42cb865b71574f23939c174858588e46
Source dataset
uspto-grants-2013_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08394796B2

Reaction notes

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