Hydrochloric Acid → HCID 11517695, compound

HRID 244113Notes

Reaction equation

HRID 244113 reaction equation
C(OC([N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][C:18]2[N:22]3[CH:23]=[CH:24][N:25]=[C:26]([NH2:27])[C:21]3=[C:20]([C:28]3[CH:37]=[C:36]4[C:31]([CH:32]=[CH:33][C:34]([C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)=[N:35]4)=[CH:30][CH:29]=3)[N:19]=2)[CH2:13][CH2:12]1)=O)C1C=CC=CC=1.Cl>>[C:38]1([C:34]2[CH:33]=[CH:32][C:31]3[C:36](=[CH:37][C:28]([C:20]4[N:19]=[C:18]([CH2:17][CH:14]5[CH2:15][CH2:16][NH:11][CH2:12][CH2:13]5)[N:22]5[CH:23]=[CH:24][N:25]=[C:26]([NH2:27])[C:21]=45)=[CH:29][CH:30]=3)[N:35]=2)[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 11555975HCID 11555975, compound

Product 1

HCID 11517695HCID 11517695, compound

Conditions

Temperature
60 °C

Procedure

4-[8-Amino-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-3-ylmethyl]-piperidine-1-carboxylic acid benzyl ester (1.94 g, 3.41 mmol) was mixed with 37% HCl (90.00 mL, 3.96 mol), heated to 60° C. and continued to stir for 5 mins. It was then cooled to rt, washed with ether (2×90 mL) and then with CH2Cl2 (2×90 mL). The aqueous layer was gradually basified with 5N NaOH and extracted with CH2Cl2 (3×50 mL). The combined organic layer was dried with Na2SO4, filtered and concentrated in vacuo. The crude product was purified by a 25 g Jones silica gel (eluted with 10% (7N NH3) in MeOH/EtOAc), affording the desired product; 1H NMR (400 MHz, METHANOL-d) δ 8.38 (1H, d, J=8.68), 8.24 (1H, d, J=0.74 Hz), 8.08 (2H, dd, J=1.55 Hz, J=1.19), 8.00 (2H, m), 7.80 (1H, dd, J=1.68, J=1.70), 7.51 (1H, d, J=5.14), 7.44 (3H, m), 6.99 (1H, d, J=5.10), 2.99 (2H, d, J=12.60), 2.94 (2H, d, J=7.20), 2.55 (2H, t), 2.01 (1H, m), 1.66 (2H, d, J=12.72), 1.29 (2H, m); MS (ES+): m/z 435.12/436.10 (15/5) [MH+]; HPLC: tR=1.71 min (OpenLynx, polar—5 min).

Workup

  1. temperatureIt was then cooled to rt
  2. washwashed with ether (2×90 mL)
  3. extractionextracted with CH2Cl2 (3×50 mL)
  4. dry with materialThe combined organic layer was dried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by a 25 g Jones silica gel (eluted with 10% (7N NH3) in MeOH/EtOAc)

Sources & evidence

ORD record
ord-2100da7c33734251b20b7c227e543067
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

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