Diisopropylethylamine → HCID 118447873, compound

HRID 1775477Notes

Reaction equation

HRID 1775477 reaction equation
Cl.[CH3:2][C@:3]1([N:8]2[C:12]3[N:13]=[C:14]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)[N:15]=[C:16]([C:17]4[CH:18]=[N:19][C:20]([NH2:23])=[N:21][CH:22]=4)[C:11]=3[CH2:10][CH2:9]2)[CH2:7][CH2:6][NH:5][CH2:4]1.[C:30]([O:34][C:35]([NH:37][C:38]([CH3:43])([CH3:42])[C:39](O)=[O:40])=[O:36])([CH3:33])([CH3:32])[CH3:31].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.C([O-])(O)=O.[Na+]>CN1C(=O)CCC1>[C:30]([O:34][C:35](=[O:36])[NH:37][C:38]([CH3:43])([CH3:42])[C:39]([N:5]1[CH2:6][CH2:7][C@@:3]([N:8]2[C:12]3[N:13]=[C:14]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)[N:15]=[C:16]([C:17]4[CH:18]=[N:19][C:20]([NH2:23])=[N:21][CH:22]=4)[C:11]=3[CH2:10][CH2:9]2)([CH3:2])[CH2:4]1)=[O:40])([CH3:33])([CH3:31])[CH3:32]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118436187HCID 118436187, compound

Product 1

HCID 118447873HCID 118447873, compoundYield 76.7%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a mixture of the product of Example 4, Step 2, 5-{7-[(3S)-3-methylpyrrolidin-3-yl]-2-(morpholin-4-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}pyrimidin-2-amine hydrochloride (˜1.0 g, ˜1.77 mmol), 2-tert-butoxycarbonylamino-2-methyl-propionic acid (504 mg, 2.48 mmol) and DIEA (2.16 mL, 12.4 mmol) in 10 mL NMP, was added HATU (1.0 g, 2.67 mmol). The reaction was covered with foil and stirred at room temperature for 18 h. The reaction mixture was dropped into aqueous NaHCO3 and the resulting precipitate was collected by filtration. The filtrate was extracted with DCM (3 times). The filtrate and solids were combined, washed with brine, dried over MgSO4 and concentrated. The residue was purified by Biotage (40-FM cartridge) using a gradient of 0-10% MeOH/EtOAc as eluent to give the title compound (771 mg, 76%) as a foamy solid. 1H NMR (400 MHz, 80° C., DMSO-d6) δ 8.73 (s, 2 H), 6.71-6.54 (m, 3 H), 4.06-3.83 (m, 2 H), 3.70-3.41 (m, 12 H), 3.08 (t, J=8.1 Hz, 2 H), 2.47-2.35 (m, 1H, partially overlapped with DMSO), 2.10-2.01 (m, 1 H), 1.39-1.28 (m, 18 H). m/z (APCI+) for C28H41CN9O4568.3 (M+H)+.

Workup

  1. filtrationthe resulting precipitate was collected by filtration
  2. extractionThe filtrate was extracted with DCM (3 times)
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by Biotage (40-FM cartridge)

Sources & evidence

ORD record
ord-74a2be7873154ccc82db35d22db325c6
Source dataset
uspto-grants-2016_02
Patent number
US09260439B2

Reaction notes

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