Carbonate Ion → HCID 178462351, compound

HRID 591955Notes

Reaction equation

HRID 591955 reaction equation
[Cl:1][C:2]1[C:3]([NH:22][C@@H:23]2[C@@H:28]3[CH2:29][C@@H:25]([CH:26]=[CH:27]3)[C@@H:24]2[C:30]([NH2:32])=[O:31])=[C:4]2[N:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH:16]4[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]4)[CH:15]=3)[NH:8][C:5]2=[N:6][CH:7]=1.[CH2:33]1[O:36][C@@H:34]1[CH3:35].C(=O)([O-])[O-]>CO>[Cl:1][C:2]1[C:3]([NH:22][C@@H:23]2[C@@H:28]3[CH2:29][C@@H:25]([CH:26]=[CH:27]3)[C@@H:24]2[C:30]([NH2:32])=[O:31])=[C:4]2[N:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH:16]4[CH2:21][CH2:20][N:19]([CH2:33][C@H:34]([OH:36])[CH3:35])[CH2:18][CH2:17]4)[CH:15]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 19660Carbonate IonHCID 146261(R)-1,2-EpoxypropaneHCID 178514006HCID 178514006, compound

Product 1

HCID 178462351HCID 178462351, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(1S,2S,3R,4R)-3-[6-Chloro-2-(1-piperidin-4-yl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine-7-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (Compound LVII above) (100 mg, 0.2 mmol) was combined with (R)-(−)-propylene oxide (25.6 mg, 0.442 mmol) and MP-Carbonate (140 mg, 0.442 mmol) in methanol (10 mL) and stirred in a sealed tube overnight. The product was filtered and the filtrate concentrated to afford a solid which was purified via reverse phase chromatography (Gilson) to afford following extractive neutralization of fractions and concentration the title compound as a white solid. 1H NMR (d-chloroform): 14.01 (br s, 1H), 7.92 (s, 1H), 7.83 (s, 1H), 7.69 (s, 1H), 7.13 (br s, 1H), 6.83 (s, 1H), 6.37 (1, 2H), 6.15 (d, J=9 Hz, 1H), 5.25 (t, J=9 Hz, 1H), 4.26 (m, 1H), 3.89 (m, 1H), 3.22 (d, J=10 Hz, 1H), 3.11 (s, 1H), 2.99 (d, J=10 Hz, 1H), 2.86 (s, 1H), 2.81 (m, 2H), 2.66-2.13 (m, 7H), 2.03 (m, 2H), 1.61 (d, J=10 Hz, 1H), 1.22 (d, J=7 Hz, 3H). MS: 510.9 (M+H). HPLC retention time: 1.59 minutes (G Method).

Workup

  1. filtrationThe product was filtered
  2. concentrationthe filtrate concentrated
  3. customto afford a solid which
  4. customwas purified via reverse phase chromatography (Gilson)
  5. customto afford
  6. concentrationneutralization of fractions and concentration the title compound as a white solid

Sources & evidence

ORD record
ord-ff7f4df71a3449bea2b401c969664496
Source dataset
uspto-grants-2016_01
Patent number
US09238656B2

Reaction notes

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