Diisopropylethylamine → HCID 178492711, compound

HRID 1676839Notes

Reaction equation

HRID 1676839 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:27])=[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.[CH:42]1([CH2:45][N:46]2[CH2:51][CH2:50][N:49]([CH:52]3[CH2:57][CH2:56][CH:55]([NH2:58])[CH2:54][CH2:53]3)[CH2:48][CH2:47]2)[CH2:44][CH2:43]1>CN(C)C=O>[CH:1]1([N:6]2[CH2:12][C:11]([F:13])([F:14])[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:58][C@H:55]5[CH2:54][CH2:53][C@@H:52]([N:49]6[CH2:48][CH2:47][N:46]([CH2:45][CH:42]7[CH2:43][CH2:44]7)[CH2:51][CH2:50]6)[CH2:57][CH2:56]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.[CH:1]1([N:6]2[CH2:12][C:11]([F:13])([F:14])[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:58][C@H:55]5[CH2:56][CH2:57][C@H:52]([N:49]6[CH2:50][CH2:51][N:46]([CH2:45][CH:42]7[CH2:43][CH2:44]7)[CH2:47][CH2:48]6)[CH2:53][CH2:54]5)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 11586738trans-4-(4-(Cyclopropylmethyl)piperazin-1-yl)cyclohexanamineHCID 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 acid

Product 2

HCID 178492711HCID 178492711, compoundHCID 178492712HCID 178492712, compound

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), 0.19 mL (1.1 mmole) of ethyldiisopropyl amine and 0.068 mg (0.20 mmole) of the cis/trans mixture of 4-(4-cyclopropylmethyl-piperazin-1-yl)-cyclohexylamine with trihydrochloride in 2.0 mL of dimethylformamide was added 0.085 g (0.20 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, 100:0-70:30) gave 0.026 g 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)-N-[cis-4-(4-cyclopropylmethyl-piperazin-1-yl)-cyclohexyl]-3-methoxy-benzamide (I-299) (Rf: 0.56 in dichloromethane:methanol 7:3) as a white solid, and 0.063 g 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)-N-[trans-4-(4-cyclopropylmethyl-piperazin-1-yl)-cyclohexyl]-3-methoxy-benzamide (I-300) (Rf: 0.44 in dichloromethane:methanol 7:3) 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, 100:0-70:30)

Sources & evidence

ORD record
ord-8861a5f01b5f431e83e282232397f45c
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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