HCID 27281524, compound → HCID 68782418, compound

HRID 1968529Notes

Reaction equation

HRID 1968529 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[C@@H:14]3[CH2:15][C@@H:11]([CH:12]=[CH:13]3)[C@@H:10]2[C:16]([NH2:18])=[O:17])[C:5]([Cl:19])=[CH:4][N:3]=1.[NH2:20][C:21]1[CH:22]=[N:23][N:24]([C@H:26]2[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27]2)[CH:25]=1>CC(O)C>[Cl:19][C:5]1[C:6]([NH:8][C@@H:9]2[C@@H:14]3[CH2:15][C@@H:11]([CH:12]=[CH:13]3)[C@@H:10]2[C:16]([NH2:18])=[O:17])=[N:7][C:2]([NH:20][C:21]2[CH:22]=[N:23][N:24]([C@H:26]3[CH2:30][CH2:29][NH:28][CH2:27]3)[CH:25]=2)=[N:3][CH:4]=1

Participants

4

Reactant 2

HCID 27281524HCID 27281524, compoundHCID 57522618HCID 57522618, compound

Product 1

HCID 68782418HCID 68782418, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
85 °C

Procedure

(+)-(1S,2S,3R,4R)-3-(2,5-Dichloropyrimidin-4-ylamino)bicyclo[2.2.1]hept-5-ene-2-carboxamide (75 mg, 0.25 mmol) and (S)-tert-butyl 3-(4-amino-1H-pyrazol-1-yl)pyrrolidine-1-carboxylate (63 mg, 0.25 mmol) were combined with 2-propanol (2.4 ml) in a sealed tube and the mixture was heated to 85° C. for 4 hours. The reaction mixture was concentrated to dryness, then treated with 5 mL TFA and stirred for 15 minutes. The mixture was again concentrated to dryness, the residue was dissolved in CH2Cl2, and the mixture was treated with aqueous saturated NaHCO3. The layers were separated and the aqueous layer was further extracted 3× with ethyl acetate. The extracts were dried (Na2SO4) and concentrated, then purified by flash chromatography yielding the desired product. 1H NMR (300 MHz, DMSO-D6) ppm 1.41 (d, J=7.8 Hz, 1H) 1.92-2.04 (m, 1H) 2.07-2.21 (m, 2H) 2.52-2.56 (m, 1H) 2.71-2.91 (m, 3H) 2.93 (d, J=5.4 Hz, 1H) 2.95-3.03 (m, 1H) 3.12 (dd, J=11.5, 7.12 Hz, 1H) 4.13 (t, J=7.5 Hz, 1H) 4.65-4.77 (m, 1H) 6.25-6.40 (m, 2H) 7.25 (s, 1H) 7.51 (s, 1H) 7.61-7.84 (m, 3H) 7.89 (s, 1H) 9.10 (s, 1H); MS (ESI(+)) m/e 415 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. additiontreated with 5 mL TFA
  3. concentrationThe mixture was again concentrated to dryness
  4. dissolutionthe residue was dissolved in CH2Cl2
  5. additionthe mixture was treated with aqueous saturated NaHCO3
  6. customThe layers were separated
  7. extractionthe aqueous layer was further extracted 3× with ethyl acetate
  8. dry with materialThe extracts were dried (Na2SO4)
  9. concentrationconcentrated
  10. custompurified by flash chromatography

Sources & evidence

ORD record
ord-ccb9a18d2fb6409982de0d4f526f5325
Source dataset
uspto-grants-2013_04
Patent number
US08426408B2

Reaction notes

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