Diisopropylethylamine → HCID 178492721, compound

HRID 1676613Notes

Reaction equation

HRID 1676613 reaction equation
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(C(C)C)C(C)C)C.Cl.[NH2:43][C@@H:44]1[CH2:49][CH2:48][C@H:47]([OH:50])[CH2:46][CH2:45]1>CN(C)C=O>[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:43][C@H:44]5[CH2:49][CH2:48][C@@H:47]([OH:50])[CH2:46][CH2:45]5)=[O:28])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 252529054-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acidHCID 178479277HCID 178479277, compound

Product 1

HCID 178492721HCID 178492721, compoundYield 67.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 0.08 g (0.18 mmole) of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-22), 0.13 mL (0.72 mmole) of ethyldiisopropyl amine and 0.030 g (0.20 mmole) of cis-4-amino-cyclohexanol hydrochloride in 2.0 mL of dimethylformamide was added 0.085 g (0.2 mmole) of 1-(di-1-pyrrolidinylmethylene)-1H-benzotriazolium 3-oxide hexafluorophosphate. The mixture was stirred at room temperature for 1 hour, then diluted with 10 mL of ice water. The resulting solid was collected by filtration, washed with saturated sodium carbonate and water, and dried under vacuum. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 100:0-90:10) gave 0.066 g of cis-4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(4-hydroxy-cyclohexyl)-3-methoxy-benzamide (I-68) as a white solid.

Workup

  1. filtrationThe resulting solid was collected by filtration
  2. washwashed with saturated sodium carbonate and water
  3. customdried under vacuum
  4. customPurification by silica gel chromatography
  5. washeluting with dichloromethane-methanol (gradient, 100:0-90:10)

Sources & evidence

ORD record
ord-e7eec823a1e7401db7f7dccd72bba23a
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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