1,8-Diazabicyclo(5.4.0)undec-7-ene → Ethyl sulfamic acid-[6-chloro-5-(o-methoxy-phenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide

HRID 10255Notes

Reaction equation

HRID 10255 reaction equation
[NH2:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][CH3:16])=[C:6]([Cl:17])[N:5]=[C:4]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)[N:3]=1.C1CCN2C(=NCCC2)CC1.[CH2:35]([NH:37][S:38](Cl)(=[O:40])=[O:39])[CH3:36]>C1COCC1.C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:17][C:6]1[N:5]=[C:4]([C:18]2[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=2)[N:3]=[C:2]([NH:1][S:38](=[O:40])(=[O:39])[NH:37][CH2:35][CH3:36])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH3:16]

Participants

7

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 11040810Ethylsulfamoyl chlorideHCID 219795734-Amino-6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)pyrimidine

Product 1

HCID 21979572Ethyl sulfamic acid-[6-chloro-5-(o-methoxy-phenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-Amino-6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidine (100 mg) was dissolved in THF (5 ml) and DCM (5 ml). DBU (46 mg) and DMAP (37 mg) were added followed by the addition of ethyl-sulfamoylchloride (prepared from ethylamine hydrochloride and sulfuryl chloride). The mixture was stirred for 12 h at r.t. The solvent was evaporated. Water and a 10% solution of citric acid were added followed by extraction with EtOAc and DCM. The combined organic layers were dried over sodium sulfate and the solvent was evaporated under reduced pressure. After purification of the residue by chromatography over silicagel with EtOAc/methanol/ammonia=4:1:0.5, ethyl sulfamic acid-[6-chloro-5-(o-methoxy-phenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide (10 mg) was obtained. tR=4.31 min, (LC); [M+H]+=436.14 (ES+).

Workup

  1. customThe solvent was evaporated
  2. additionWater and a 10% solution of citric acid were added
  3. extractionfollowed by extraction with EtOAc and DCM
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customAfter purification of the residue by chromatography over silicagel with EtOAc/methanol/ammonia=4:1:0.5

Sources & evidence

ORD record
ord-8747ffbddac545759a82510b3d14071c
Source dataset
uspto-grants-2006_08
Patent number
US07094781B2

Reaction notes

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