Hydrochloric Acid → HCID 57820111, compound

HRID 1714165Notes

Reaction equation

HRID 1714165 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15](=[O:49])/[CH:16]=[CH:17]/[C:18]1[CH:23]=[CH:22][C:21]([CH:24]([NH:38][C:39]([CH3:48])([CH3:47])[CH2:40][N:41]2[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]2)[C:25](=[O:37])[NH:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=2)=[CH:20][CH:19]=1)(C)(C)C.Cl>CO>[NH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15](=[O:49])/[CH:16]=[CH:17]/[C:18]1[CH:23]=[CH:22][C:21]([CH:24]([NH:38][C:39]([CH3:47])([CH3:48])[CH2:40][N:41]2[CH2:42][CH2:43][CH2:44][CH2:45][CH2:46]2)[C:25](=[O:37])[NH:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:35])([F:36])[F:34])=[CH:29][CH:28]=2)=[CH:20][CH:19]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 57819962HCID 57819962, compound2×

Product 1

HCID 57820111HCID 57820111, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(E)-[2-(3-{4-[(1,1-Dimethyl-2-piperidin-1-yl-ethylamino)-(4-trifluoromethyl-phenylcarbamoyl)-methyl]-phenyl}-acryloylamino)-phenyl]-carbamic acid tert-butyl ester (crude material from Example 15) was treated with 1.25M HCl in methanol (2 mL) at room temperature for 2 hours. The reaction was quenched slowly with solid sodium bicarbonate until the pH was 6-7. The mixture was diluted in acetonitrile with a small amount of dimethylsulfoxide, passed through a 40 μm pipette filter, and then purified by preparative HPLC to obtain 8 mg desired product (12% over two steps). MS: calc'd 594 (MH+) exp 594 (MH+). 1H NMR (CD3OD, 400 MHz) δ 7.81 (d, 2H, J=10.6 Hz), 7.78 (d, 1H, J=15.6 Hz), 7.71 (d, 2H, J=8.2 Hz), 7.64 (d, 2H, J=10.6 Hz), 7.62 (d, 2H, J=8.2 Hz), 7.32 (m, 4H), 6.90 (d, 1H, J=16 Hz), 4.90 (s, 1H), 3.55 (broad m, 2H), 3.17 (broad m, 2H), 3.16 (d, 1H, J=13.6 Hz), 3.01 (d, 1H, J=13.6 Hz), 2.2-1.8 (m, 6H), 1.33 (s, 3H), 1.32 (s, 3H).

Workup

  1. customThe reaction was quenched slowly with solid sodium bicarbonate until the pH was 6-7
  2. additionThe mixture was diluted in acetonitrile with a small amount of dimethylsulfoxide
  3. filtrationfilter
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-13d52d02bfff446799d5db6b61fc05b8
Source dataset
uspto-grants-2010_09
Patent number
US07795315B2

Reaction notes

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