Diisopropylethylamine → (2R)-1-oxo-1-(1-(phenylsulfonyl)-4-(tetrahydro-2H-pyran-3-ylamino)-1H-pyrrolo[2,3-b]pyridin-5-ylamino)propan-2-yl acetate

HRID 1257659Notes

Reaction equation

HRID 1257659 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([NH2:26])[C:18]([NH:19][CH:20]4[CH2:25][CH2:24][CH2:23][O:22][CH2:21]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([C@:30]([CH3:35])([OH:34])[C:31]([OH:33])=O)(=O)C.CN(C([O:43]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N([CH2:67][CH3:68])C(C)C)(C)C>ClCCl>[C:67]([O:34][C@H:30]([CH3:35])[C:31](=[O:33])[NH:26][C:17]1[C:18]([NH:19][CH:20]2[CH2:25][CH2:24][CH2:23][O:22][CH2:21]2)=[C:13]2[CH:12]=[CH:11][N:10]([S:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)(=[O:8])=[O:9])[C:14]2=[N:15][CH:16]=1)(=[O:43])[CH3:68]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 440878(2S)-2-hydroxy-2-methyl-3-oxobutanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673439541-(phenylsulfonyl)-N4-(tetrahydro-2H-pyran-3-yl)-1H-pyrrolo[2,3-b]pyridine-4,5-diamine

Product 1

HCID 67323050(2R)-1-oxo-1-(1-(phenylsulfonyl)-4-(tetrahydro-2H-pyran-3-ylamino)-1H-pyrrolo[2,3-b]pyridin-5-ylamino)propan-2-yl acetateYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(phenylsulfonyl)-N4-(tetrahydro-2H-pyran-3-yl)-1H-pyrrolo[2,3-b]pyridine-4,5-diamine (1.1 g, 3.0 mmol) in dichloromethane (DCM) (18 mL) was treated with acetyl-D-lactic acid (530 mg, 4.0 mmol), 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (HATU) (1.24 g, 3.25 mmol) and N,N-diisopropylethylamine (1.13 mL, 6.5 mmol) at room temperature for 20 h. The mixture was then washed with 10% NaHCO3 in water, dried with MgSO4, filtered and concentrated. Purification by flash chromatography (40 to 100% Ethyl acetate in Heptane) afforded 830 mg (58%) of (2R)-1-oxo-1-(1-(phenylsulfonyl)-4-(tetrahydro-2H-pyran-3-ylamino)-1H-pyrrolo[2,3-b]pyridin-5-ylamino)propan-2-yl acetate. LCMS (Method E, ESI): RT=1.37 min, m+H=487.2; 1H NMR (400 MHz, CDCl3) δ 8.13 (d, J=7.8 Hz, 2H), 7.92 (d, J=34.9 Hz, 1H), 7.66-7.38 (m, 5H), 6.61 (t, J=14.7 Hz, 1H), 5.13 (p, J=6.9 Hz, 1H), 4.94 (t, J=7.6 Hz, 1H), 3.93 (d, J=11.5 Hz, 2H), 3.71 (dt, J=13.3, 6.5 Hz, 3H), 3.57 (s, 1H), 3.50-3.29 (m, 1H), 3.17 (q, J=7.4 Hz, 2H), 2.17 (t, J=14.0 Hz, 3H), 1.61 (t, J=13.7 Hz, 5H).

Workup

  1. washThe mixture was then washed with 10% NaHCO3 in water
  2. dry with materialdried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash chromatography (40 to 100% Ethyl acetate in Heptane)

Sources & evidence

ORD record
ord-7314cf06005a4302932730aa9efe8cc5
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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