2-Aminothiazole → HCID 86723661, compound

HRID 1485320Notes

Reaction equation

HRID 1485320 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[NH2:6].C([Mg]Cl)(C)C.[CH:12]([C:15]1[NH:19][N:18]=[C:17]([NH:20][C:21]2[C:22]3[CH2:38][CH2:37][CH2:36][C:23]=3[N:24]=[C:25]([N:27]3[CH2:31][CH2:30][CH2:29][C@H:28]3[C:32](OC)=[O:33])[N:26]=2)[CH:16]=1)([CH3:14])[CH3:13]>C1COCC1>[CH:12]([C:15]1[NH:19][N:18]=[C:17]([NH:20][C:21]2[C:22]3[CH2:38][CH2:37][CH2:36][C:23]=3[N:24]=[C:25]([N:27]3[CH2:31][CH2:30][CH2:29][C@H:28]3[C:32]([NH:6][C:2]3[S:1][CH:5]=[CH:4][N:3]=3)=[O:33])[N:26]=2)[CH:16]=1)([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 21552-AminothiazoleHCID 86723662HCID 86723662, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 86723661HCID 86723661, compoundYield 50.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of thiazol-2-amine (1.08 g, 10.8 mmol) in THF (12 mL) was added isopropyl magnesium chloride (5.4 mL, 10.8 mmol) dropwise at 0° C. The reaction mixture was stirred at the same temperature for 20 min., followed by dropwise addition of solution of methyl (2S)-1-[4-[(5-isopropyl-1H-pyrazol-3-yl)amino]-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl]pyrrolidine-2-carboxylate (1 g, 2.702 mmol) in THF (5 mL). The reaction mixture was stirred at RT for 2 h. The progress of reaction was monitored by LCMS. The reaction mixture was quenched with a saturated solution of ammonium chloride (200 mL) and extracted with EtOAc (2×200 mL). The organic layer was washed with water (2×200 mL) followed by brine (200 mL) and dried over anhydrous sodium sulfate and concentrated under vacuum to obtain a crude product, which was recrystallized in diethyl ether (50 mL) to afford (2S)-1-[4-[(5-isopropyl-1H-pyrazol-3-yl)amino]-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl]-N-thiazol-2-yl-pyrrolidine-2-carboxamide (600 mg). 1H NMR (400 MHz, CDCl3) δ (ppm): 1.30 (d, 6H), 2.00-2.22 (m, 5H), 2.50-2.70 (m, 3H), 2.80-3.05 (m, 3H), 3.61-3.80 (m, 2H), 4.85 (d, 1H), 6.28 (brs, 1H), 6.93 (d, 1H), 6.99 (brs, 1H), 7.40 (d, 1H). The other enantiomer is prepared using chiral (R) starting material.

Workup

  1. stirringThe reaction mixture was stirred at RT for 2 h
  2. customThe progress of reaction
  3. customThe reaction mixture was quenched with a saturated solution of ammonium chloride (200 mL)
  4. extractionextracted with EtOAc (2×200 mL)
  5. washThe organic layer was washed with water (2×200 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customto obtain a crude product, which
  9. customwas recrystallized in diethyl ether (50 mL)

Sources & evidence

ORD record
ord-7d2fc16a5269476a8bd9034ad4332927
Source dataset
uspto-grants-2016_08
Patent number
US09422267B2

Reaction notes

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