Hydrochloric Acid → Rodatristat Ethyl

HRID 1499280Notes

Reaction equation

HRID 1499280 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:32][CH2:31][C:11]3([CH2:15][N:14](C(OCC4C=CC=CC=4)=O)[C@H:13]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:12]3)[CH2:10][CH2:9]2)[CH:5]=[C:4]([O:33][C@H:34]([C:39]2[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][C:40]=2[C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:35]([F:38])([F:37])[F:36])[N:3]=1.[Si](I)(C)(C)C.Cl>C(#N)C.C(OCC)C>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:32][CH2:31][C:11]3([CH2:15][NH:14][C@H:13]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:12]3)[CH2:10][CH2:9]2)[CH:5]=[C:4]([O:33][C@H:34]([C:39]2[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][C:40]=2[C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:35]([F:38])([F:37])[F:36])[N:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 85247Trimethylsilyl iodideHCID 117952718(S)-2-benzyl 3-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1'-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate

Product 1

HCID 92045025Rodatristat Ethyl

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of (S)-2-benzyl 3-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate (from Step 3, Example 34c, 315 mg, 0.43 mmol) in acetonitrile (300 mL) was added TMSI (0.13 mL, 0.9 mmol) [Method B]. The reaction mixture was then warmed to RT for an additional 30-40 min, then cooled to 0-5° C., and 2 M HCl in diethyl ether (0.5 mL) was added. The reaction mixture was the allowed to warm RT and then concentrated in vacuo. Normal phase silica gel chromatography provide the title compound as an off-white solid.

Workup

  1. temperaturecooled to 0-5° C.
  2. temperatureto warm RT
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8105ce9db82a4bab93185188bb29d34d
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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