Dimethylamine, hydrochloride → (R)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N,N-dimethylpyrrolidine-2-carboxamide

HRID 1485310Notes

Reaction equation

HRID 1485310 reaction equation
[CH:1]([C:4]1[NH:8][N:7]=[C:6]([NH:9][C:10]2[C:11]3[CH2:26][CH2:25][CH2:24][C:12]=3[N:13]=[C:14]([N:16]3[CH2:20][CH2:19][CH2:18][CH:17]3[C:21]([OH:23])=O)[N:15]=2)[CH:5]=1)([CH3:3])[CH3:2].Cl.[CH3:28][NH:29][CH3:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[CH:1]([C:4]1[NH:8][N:7]=[C:6]([NH:9][C:10]2[C:11]3[CH2:26][CH2:25][CH2:24][C:12]=3[N:13]=[C:14]([N:16]3[CH2:20][CH2:19][CH2:18][C@@H:17]3[C:21]([N:29]([CH3:30])[CH3:28])=[O:23])[N:15]=2)[CH:5]=1)([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 10473Dimethylamine, hydrochlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867236291-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxylic acid

Product 1

HCID 86723650(R)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N,N-dimethylpyrrolidine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxylic acid (300 mg, 0.842 mmol) in DMF (5 mL) was added dimethyl amine hydrochloride (343 mg, 4.213 mmol), HATU (320 mg, 0.842 mmol), diisopropylethylamine (163 mg, 1.263 mmol) and the reaction mixture was stirred at RT for 16 h. The progress of reaction was monitored by LCMS. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (3×30 mL). The organic layer was washed with water (8×40 mL) and dried over anhydrous sodium sulfate. Removal of solvent under reduced pressure gave a crude product which was purified by reverse phase HPLC followed by chiral HPLC to afford (R)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N,N-dimethylpyrrolidine-2-carboxamide, and its (S) enantiomer. 1H NMR (400 MHz, CD3OD, freebase) δ (ppm): 1.28 (d, 6H), 1.90-2.18 (m, 5H), 2.30-2.42 (m, 1H), 2.62-3.08 (m, 4H), 2.76 (s, 3H), 2.82-2.30 (m, 1H), 2.98 (s, 3H), 3.61-3.91 (m, 2H), 5.01 (d, 1H), 6.00 (brs, 1H).

Workup

  1. customThe progress of reaction
  2. extractionextracted with EtOAc (3×30 mL)
  3. washThe organic layer was washed with water (8×40 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customRemoval of solvent under reduced pressure
  6. customgave a crude product which
  7. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-bb4855ed0aa544118abaa3dd008716c2
Source dataset
uspto-grants-2016_08
Patent number
US09422267B2

Reaction notes

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