N,N-Diethyl-2-propanamine → (+/-)-N-(3-(hydroxymethyl)-1-(pyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-yl)-5-isopropylpyrimidine-2-carboxamide

HRID 1755267Notes

Reaction equation

HRID 1755267 reaction equation
Cl.[NH2:2][C:3]1([CH2:17][OH:18])[CH2:7][CH2:6][N:5]([C:8]2[C:9]3[N:10]([CH:14]=[CH:15][CH:16]=3)[CH:11]=[CH:12][N:13]=2)[CH2:4]1.[CH:19]([C:22]1[CH:23]=[N:24][C:25]([C:28](O)=[O:29])=[N:26][CH:27]=1)([CH3:21])[CH3:20].C(N(CC)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.C(OCC)(=O)C>[OH:18][CH2:17][C:3]1([NH:2][C:28]([C:25]2[N:24]=[CH:23][C:22]([CH:19]([CH3:21])[CH3:20])=[CH:27][N:26]=2)=[O:29])[CH2:7][CH2:6][N:5]([C:8]2[C:9]3[N:10]([CH:14]=[CH:15][CH:16]=3)[CH:11]=[CH:12][N:13]=2)[CH2:4]1

Participants

7

Reactant 4

HCID 521913N,N-Diethyl-2-propanamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 839144005-Isopropylpyrimidine-2-carboxylic acidHCID 86720543(+/-)-(3-Amino-1-(pyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-yl)methanol hydrochloride salt

Product 1

HCID 86720542(+/-)-N-(3-(hydroxymethyl)-1-(pyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-yl)-5-isopropylpyrimidine-2-carboxamideYield 32.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of (±)-(3-amino-1-(pyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-yl)methanol hydrochloride salt (62 mg, 0.2 mmol) and 5-isopropylpyrimidine-2-carboxylic acid (40 mg, 0.22 mmol) in DMF (5 mL) was added diethylisopropyl amine (650 mg, 5 mmol), followed by HATU (76 mg, 0.2 mmol). The resulting solution was stirred at room temperature for 1 h. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous solutions of KH2PO4 and NaHCO3, followed by brine. The organic layer was concentrated in vacuo and the residue purified by reverse phase HPLC (acetonitrile-H2O with 0.1% TFA as eluent) to give 25 mg of the title compound (32% yield) as a white solid.

Workup

  1. washwashed with saturated aqueous solutions of KH2PO4 and NaHCO3
  2. concentrationThe organic layer was concentrated in vacuo
  3. customthe residue purified by reverse phase HPLC (acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-def7478e224b47e48fa639f2e61c74be
Source dataset
uspto-grants-2015_10
Patent number
US09169261B2

Reaction notes

Loading…