Trifluoroacetic acid → HCID 178439372, compound

HRID 1485315Notes

Reaction equation

HRID 1485315 reaction equation
[CH:1]([C:4]1[CH:8]=[C:7]([NH:9][C:10]2[C:11]3[CH2:38][CH2:37][CH2:36][C:12]=3[N:13]=[C:14]([N:16]3[CH2:20][CH2:19][CH2:18][CH:17]3[C:21]([NH:23][C@H:24]3[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25]3)=[O:22])[N:15]=2)[NH:6][N:5]=1)([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:1]([C:4]1[CH:8]=[C:7]([NH:9][C:10]2[C:11]3[CH2:38][CH2:37][CH2:36][C:12]=3[N:13]=[C:14]([N:16]3[CH2:20][CH2:19][CH2:18][C@@H:17]3[C:21]([NH:23][C@H:24]3[CH2:28][CH2:27][NH:26][CH2:25]3)=[O:22])[N:15]=2)[NH:6][N:5]=1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178439370HCID 178439370, compound

Product 1

HCID 178439372HCID 178439372, compoundYield 7.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (3S)-tert-butyl 3-(1-(4-(3-isopropyl-1H-pyrazol-5-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamido)pyrrolidine-1-carboxylate (350 mg, 0.667 mmol) in DCM (3.5 mL) was added TFA (0.15 ml, 2.003 mmol) dropwise under nitrogen atmosphere at 0° C. The resultant mixture was stirred at RT for 16 h. The reaction mixture was concentrated under reduced pressure. The crude obtained was purified by reverse phase HPLC. The stereoisomers obtained were separated by chiral HPLC to afford 21 mg of (R)-1-(4-(3-isopropyl-1H-pyrazol-5-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N—((S)-pyrrolidin-3-yl)pyrrolidine-2-carboxamide. 1H NMR (400 MHz, CDCl3) δ (ppm) 1.30 (d, 6H), 1.94-2.15 (m, 6H), 2.60-2.77 (m, 4H), 2.79-3.10 (m, 6H), 3.58-3.66 (m, 1H), 3.70-3.80 (m, 1H), 4.05-4.13 (m, 1H), 4.58 (dd, 1H), 6.38 (s, 1H), 6.79 (s, 1H). The other diastereomers were prepared using appropriate chiral starting materials.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customThe crude obtained
  3. customwas purified by reverse phase HPLC
  4. customThe stereoisomers obtained
  5. customwere separated by chiral HPLC

Sources & evidence

ORD record
ord-4cd9481ef025463391d3c372a1c36c2a
Source dataset
uspto-grants-2016_08
Patent number
US09422267B2

Reaction notes

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