Glycolic Acid → 2-((R)-1-(1-(2-hydroxyacetyl)piperidin-4-yl)ethylamino)-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile

HRID 1853474

Reaction equation

HRID 1853474 reaction equation
C(N(C(C)C)CC)(C)C.FC(F)(F)C(O)=O.[NH:17]1[CH2:22][CH2:21][CH:20]([C@H:23]([NH:25][C:26]2[N:31]=[C:30]([C:32]3[C:40]4[C:35](=[N:36][CH:37]=[C:38]([C:41]([F:44])([F:43])[F:42])[CH:39]=4)[N:34]([S:45]([C:48]4[CH:54]=[CH:53][C:51]([CH3:52])=[CH:50][CH:49]=4)(=[O:47])=[O:46])[CH:33]=3)[C:29]([C:55]#[N:56])=[CH:28][N:27]=2)[CH3:24])[CH2:19][CH2:18]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[C:79](O)(=[O:82])[CH2:80][OH:81]>O1CCCC1>[OH:82][CH2:79][C:80]([N:17]1[CH2:18][CH2:19][CH:20]([C@H:23]([NH:25][C:26]2[N:31]=[C:30]([C:32]3[C:40]4[C:35](=[N:36][CH:37]=[C:38]([C:41]([F:43])([F:44])[F:42])[CH:39]=4)[N:34]([S:45]([C:48]4[CH:49]=[CH:50][C:51]([CH3:52])=[CH:53][CH:54]=4)(=[O:46])=[O:47])[CH:33]=3)[C:29]([C:55]#[N:56])=[CH:28][N:27]=2)[CH3:24])[CH2:21][CH2:22]1)=[O:81]

Participants

6

Reactant 4

HCID 757Glycolic AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 866435932-((R)-1-(piperidin-4-yl)ethylamino)-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile 2,2,2-trifluoroacetate

Product 1

HCID 594146092-((R)-1-(1-(2-hydroxyacetyl)piperidin-4-yl)ethylamino)-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrileYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diisopropylethylamine (179 μl, 1.025 mmol) was added to a mixture of 2-((R)-1-(piperidin-4-yl)ethylamino)-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile 2,2,2-trifluoroacetate (140 mg, 0.205 mmol), TBTU (131.7 mg, 0.14 mmol) and glycolic acid (15.6 mg, 0.205 mmol) in tetrahydrofuran (3 mL). The reaction mixture was stirred at room temperature for 1 hour. The crude mixture was concentrated to dryness and redissolved in ethyl acetate. The organic phase was washed with a saturated solution of sodium bicarbonate and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography to afford the title compound (60 mg, 47% yield). Also obtained was 20 mg (21% yield) of the detosylated compound.

Workup

  1. concentrationThe crude mixture was concentrated to dryness
  2. dissolutionredissolved in ethyl acetate
  3. washThe organic phase was washed with a saturated solution of sodium bicarbonate and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified on silica gel by flash column chromatography

Sources & evidence

ORD record
ord-04e05ebf1186403782ec74a7532cc8ed
Source dataset
uspto-grants-2015_02
Patent number
US08962642B2

Linked notes

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