Cyclohexanol → HCID 58504468, compound

HRID 2367624Notes

Reaction equation

HRID 2367624 reaction equation
[CH:1]1([OH:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.ClC(Cl)(O[C:21](=[O:27])OC(Cl)(Cl)Cl)Cl.[NH2:29][C:30]1[N:35]=[C:34]([C:36]2[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[C:38]([F:44])[CH:37]=2)[CH:33]=[C:32]([N:45]2[CH2:50][CH2:49][CH2:48][C@@H:47]([NH2:51])[CH2:46]2)[N:31]=1>C(Cl)Cl>[CH:1]1([O:7][C:21](=[O:27])[NH:51][C@@H:47]2[CH2:48][CH2:49][CH2:50][N:45]([C:32]3[CH:33]=[C:34]([C:36]4[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[C:38]([F:44])[CH:37]=4)[N:35]=[C:30]([NH2:29])[N:31]=3)[CH2:46]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 7966CyclohexanolHCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 58504655HCID 58504655, compound

Product 1

HCID 58504468HCID 58504468, compoundYield 78.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A premixed solution of cyclohexanol (40.7 μl, 0.389 mmol) and Hunig's base (57 uL) in CH2Cl2 (1 mL) was slowly added to a solution of triphosgene (38.5 mg, 0.130 mmol) in CH2Cl2 (1 mL), and the resulting mixture was stirred for 1 hr at room temperature. A premixed solution of 4-{2-amino-6-[(3R)-3-amino-1-piperidinyl]-4-pyrimidinyl}-2-fluorobenzonitrile (125 mg, 0.324 mmol) and Hunig's base (226 uL) in CH2Cl2 (5 mL) was added, and the reaction mixture was stirred at room temperature overnight. The reaction was concentrated, and then loaded on a Biotage SNAP 10 g column and purified with a gradient of 0 to 55% EtOAc in Hexane over 25 minutes to afford the title compound (45 mg) as a light yellow oil. LC-MS (ES) m/z=439 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. concentrationThe reaction was concentrated
  3. custompurified with a gradient of 0 to 55% EtOAc in Hexane over 25 minutes

Sources & evidence

ORD record
ord-c052530f7e524ae4b5ec0c169207e913
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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