Pyridine → HCID 117952356, compound

HRID 1499188Notes

Reaction equation

HRID 1499188 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:30][CH2:29][C:11]3([CH2:15][N:14]([C:16]([O:18][CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[O:17])[C@H:13]([C:26]([OH:28])=[O:27])[CH2:12]3)[CH2:10][CH2:9]2)[CH:5]=[C:4]([O:31][C@H:32]([C:37]2[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][C:38]=2[N:44]2[CH:48]=[CH:47][C:46]([CH3:49])=[N:45]2)[C:33]([F:36])([F:35])[F:34])[N:3]=1.[CH:50]1([C:54](Cl)=[O:55])[CH2:53][CH2:52][CH2:51]1.N1C=CC=[CH:59][CH:58]=1>CCOC(C)=O>[Cl:43][C:40]1[CH:41]=[CH:42][C:37]([C@@H:32]([O:31][C:4]2[N:3]=[C:2]([NH:1][C:54]([CH:50]3[CH2:53][CH2:52][CH2:51]3)=[O:55])[N:7]=[C:6]([N:8]3[CH2:30][CH2:29][C:11]4([CH2:15][N:14]([C:16]([O:18][CH2:19][C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=5)=[O:17])[C@H:13]([C:26]([O:28][CH2:58][CH3:59])=[O:27])[CH2:12]4)[CH2:10][CH2:9]3)[CH:5]=2)[C:33]([F:35])([F:34])[F:36])=[C:38]([N:44]2[CH:48]=[CH:47][C:46]([CH3:49])=[N:45]2)[CH:39]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 78705Cyclobutanecarbonyl chlorideHCID 117942156HCID 117942156, compound

Product 1

HCID 117952356HCID 117952356, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-8-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2-((benzyloxy)carbonyl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid (product of Step 3, Example 10m) (300 mg, 0.412 mmol) in pyridine (1.0 mL) was added cyclobutanecarbonyl chloride (54 mg, 0.045 mmol). The reaction mixture was stirred at RT for 3 h, then diluted with EtOAc, and washed with 0.5 N HCl. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. Purification on a 40 g Isco RediSep silica cartridge (EtOAc/heptane) provides (S)-2-benzyl 3-ethyl 8-(6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-2-(cyclobutanecarboxamido) pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate as an off-white solid.

Workup

  1. washwashed with 0.5 N HCl
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification on a 40 g Isco RediSep silica cartridge (EtOAc/heptane)

Sources & evidence

ORD record
ord-181a5fcecd7d43349a037937414109ea
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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