Cyclohexyl isocyanate → HCID 10283168, compound

HRID 2085101Notes

Reaction equation

HRID 2085101 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([NH:11][C:12]2[C:17]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[O:25][CH3:26])=[C:16]([O:27][CH2:28][C:29]#[C:30][CH2:31][OH:32])[N:15]=[C:14]([C:33]3[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=3)[N:13]=2)(=[O:10])=[O:9])=[N:6][CH:7]=1.[CH:39]1([N:45]=[C:46]=[O:47])[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]1>CN(C1C=CN=CC=1)C.C(Cl)(Cl)Cl.CN(C=O)C.C(OCC)(=O)C>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([NH:11][C:12]2[N:13]=[C:14]([C:33]3[CH:34]=[CH:35][N:36]=[CH:37][CH:38]=3)[N:15]=[C:16]([O:27][CH2:28][C:29]#[C:30][CH2:31][O:32][C:46](=[O:47])[NH:45][CH:39]3[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]3)[C:17]=2[O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[O:25][CH3:26])(=[O:10])=[O:9])=[N:6][CH:7]=1

Participants

7

Reactant 2

HCID 18502Cyclohexyl isocyanateHCID 10302118HCID 10302118, compound

Product 1

HCID 10283168HCID 10283168, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Under argon, a suspension of 50 mg of 5-methyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide (Example 3), 10 mg of DMAP and 25 μl of cyclohexylisocyanate in 4 ml of chloroform and 3 ml of DMF was stirred for 72 h at 70° C. The mixture was diluted with 50 ml of ethyl acetate and washed with 50 ml of 10% aqueous citric acid and 2×25 mlf of water. The organic phase was dried over MgSO4 and evaporated. The crude product was purified by column chromatography on silica gel eluting with a gradient of hexane:ethyl acetate 1:1 to ethyl acetate, then with DCM containing 4% of methanol to give 38 mg of cyclohexylcarbamic acid 4-[6-(5-methylpyridine-2-sulfonylamino)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yloxy]-but-2-ynyl ester as a beige foam. LC-MS: tR=4.89 min, [M+1]+=659.33, [M−1]−=657.25.

Workup

  1. washwashed with 50 ml of 10% aqueous citric acid and 2×25 mlf of water
  2. dry with materialThe organic phase was dried over MgSO4
  3. customevaporated
  4. customThe crude product was purified by column chromatography on silica gel eluting with a gradient of hexane:ethyl acetate 1:1 to ethyl acetate

Sources & evidence

ORD record
ord-fc5e00acec8e424f9f4d1dff4952a438
Source dataset
uspto-grants-2004_04
Patent number
US06720322B2

Reaction notes

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