Glycolic Acid → HCID 118272570, compound

HRID 588198Notes

Reaction equation

HRID 588198 reaction equation
[F:1][CH:2]([F:29])[CH2:3][O:4][C:5]1[C:9]2[CH:10]=[N:11][C:12]([NH:14][C:15]([NH:17][C@@H:18]3[C@@H:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:21][NH:20][CH2:19]3)=[O:16])=[CH:13][C:8]=2[NH:7][N:6]=1.NC(N)=O.[C:34](O)(=[O:37])[CH2:35][OH:36].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CC(N(C)C)=O>[F:29][CH:2]([F:1])[CH2:3][O:4][C:5]1[C:9]2[CH:10]=[N:11][C:12]([NH:14][C:15]([NH:17][C@@H:18]3[C@@H:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:21][N:20]([C:35](=[O:36])[CH2:34][OH:37])[CH2:19]3)=[O:16])=[CH:13][C:8]=2[NH:7][N:6]=1

Participants

7

Reactant 5

HCID 757Glycolic AcidHCID 1176UreaHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118271813HCID 118271813, compound

Product 1

HCID 118272570HCID 118272570, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

In a 4 mL, 1 dram vial were added 1-(3-(2,2-difluoroethoxy)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-((3R,4S)-4-phenylpyrrolidin-3-yl)urea: (20 mg, 0.050 mmol, Intermediate 34B), glycolic acid (8 mg, 0.099 mmol), HATU (37.8 mg, 0.099 mmol) and DIEA (0.025 ml, 0.149 mmol) all in DMA (0.5 ml). The solution was shaken at room temperature over night. The solution was analyzed by LC/MS and found to contain the desired compound. The filtered crude solution was directly injected to the Gilson semi-preparative HPLC (0.1% TFA in ACN and Water on a Waters Sunfire C18 ODB, 5 uM, 19 mm×100 mm, Part No. 186002567 column using a gradient of 10%-60% ACN over 12 minutes). The fractions were analyzed by LC/MS and the pure fractions were concentrated to provide 1-(3-(2,2-difluoroethoxy)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-((3R,4S)-1-(2-hydroxyacetyl)-4-phenylpyrrolidin-3-yl)urea (101), was isolated as an off white powder. MS: [M+H]+ m/z 461.

Sources & evidence

ORD record
ord-7b52b1144b4c4d59bf90f824acc0e2da
Source dataset
uspto-grants-2016_01
Patent number
US09226922B2

Reaction notes

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