Dimethylformamide → 2-Pyridinyl-carbamic acid 4-[6-(5-isopropyl-pyridine-2-sulfonylamino)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yloxy]-but-2-ynyl ester

HRID 2085100Notes

Reaction equation

HRID 2085100 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1C(N=[N+]=[N-])=O.[CH:12]([C:15]1[CH:16]=[CH:17][C:18]([S:21]([NH:24][C:25]2[C:30]([O:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[O:38][CH3:39])=[C:29]([O:40][CH2:41][C:42]#[C:43][CH2:44][OH:45])[N:28]=[C:27]([C:46]3[CH:51]=[CH:50][N:49]=[CH:48][CH:47]=3)[N:26]=2)(=[O:23])=[O:22])=[N:19][CH:20]=1)([CH3:14])[CH3:13].C[N:53]([CH:55]=[O:56])C>CN(C1C=CN=CC=1)C.C(Cl)(Cl)Cl.C(OCC)(=O)C>[CH:12]([C:15]1[CH:16]=[CH:17][C:18]([S:21]([NH:24][C:25]2[N:26]=[C:27]([C:46]3[CH:47]=[CH:48][N:49]=[CH:50][CH:51]=3)[N:28]=[C:29]([O:40][CH2:41][C:42]#[C:43][CH2:44][O:45][C:55](=[O:56])[NH:53][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[C:30]=2[O:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[O:38][CH3:39])(=[O:22])=[O:23])=[N:19][CH:20]=1)([CH3:14])[CH3:13]

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 5110493Pyridine-2-carbonyl azideHCID 101443345-Isopropyl-pyridine-2-sulfonic acid [6-(4-hydroxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-amide

Product 1

HCID 101901082-Pyridinyl-carbamic acid 4-[6-(5-isopropyl-pyridine-2-sulfonylamino)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yloxy]-but-2-ynyl ester

Reagents, catalysts & solvents 3

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

Conditions

Temperature
75 °C

Procedure

A solution of 50 mg of 2-picolinic acid azide (prepared from 2-picolinic acid according to Chem. Pharm. Bull. 25 (1977) 1651-1657) and 10 mg of DMAP in 8 ml of chloroform was stirred for 1 h at 75° C. 50 mg of 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide (Example 1g) followed by 3 ml of DMF was added and the resulting clear solution was stirred for 16 h at 75° C. The mixture was diluted with 75 ml of ethyl acetate and washed with 50 ml of 10% aqueous citric acid followed by 50 ml of water. The organic layer was evaporated and the crude product was purified by chromatography on prep. tlc-plates with dichlormethane:methanol 10:1 to give 41 mg of 2-pyridinyl-carbamic acid 4-[6-(5-isopropyl-pyridine-2-sulfonylamino)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yloxy]-but-2-ynyl ester as a white solid. LC-MS: tR=4.74 min, [M+1]+=682.47, [M−1]−=680.41.

Workup

  1. additionwas added
  2. washwashed with 50 ml of 10% aqueous citric acid
  3. customThe organic layer was evaporated
  4. customthe crude product was purified by chromatography on prep

Sources & evidence

ORD record
ord-41ca85dc82794152a2325d98862ca05c
Source dataset
uspto-grants-2004_04
Patent number
US06720322B2

Reaction notes

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