Ammonia → HCID 86723648, compound

HRID 1485308Notes

Reaction equation

HRID 1485308 reaction equation
[CH:1]([C:4]1[NH:8][N:7]=[C:6]([NH:9][C:10]2[C:11]3[CH2:27][CH2:26][CH2:25][C:12]=3[N:13]=[C:14]([N:16]3[CH2:20][CH2:19][CH2:18][C@@H:17]3[C:21]([O:23]C)=O)[N:15]=2)[CH:5]=1)([CH3:3])[CH3:2].[NH3:28]>C1COCC1.O>[CH:1]([C:4]1[NH:8][N:7]=[C:6]([NH:9][C:10]2[C:11]3[CH2:27][CH2:26][CH2:25][C:12]=3[N:13]=[C:14]([N:16]3[CH2:20][CH2:19][CH2:18][C@@H:17]3[C:21]([NH2:28])=[O:23])[N:15]=2)[CH:5]=1)([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 222AmmoniaHCID 86723649HCID 86723649, compound

Product 1

HCID 86723648HCID 86723648, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (R)-methyl 1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxylate (500 mg, 1.351 mmol) in THF (10 mL) was added 28% aqueous ammonia (20 mL) and reaction mixture was allowed to stir at 60° C. for 24 h. The progress of reaction was monitored by LCMS. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2×100 mL). The organic layer was separated, dried over anhydrous sodium sulfate and concentrated under vacuum to obtain a crude product which was purified by reverse phase HPLC to afford (R)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide (80 mg). 1H NMR (400 MHz, DMSO-d6, freebase) δ (ppm): 1.22 (d, 6H), 1.81-2.01 (m, 6H), 2.02-2.18 (m, 1H), 2.59-2.70 (m, 4H), 2.86-2.92 (m, 1H), 3.48 (brs, 1H), 3.67 (brs, 1H), 4.35 (d, 1H), 6.43 (brs, 1H), 6.85 (s, 1H), 7.18 (s, 1H), 8.78 (brs, 1H). The other enantiomer was prepared using the (R) chiral starting material.

Workup

  1. customThe progress of reaction
  2. extractionextracted with EtOAc (2×100 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customto obtain a crude product which
  7. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-ef680938de6b408c96bd85bf3f7f6b71
Source dataset
uspto-grants-2016_08
Patent number
US09422267B2

Reaction notes

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