Diisopropylethylamine → HCID 178492713, compound

HRID 1676840

Reaction equation

HRID 1676840 reaction equation
[F:1][C:2]1([F:30])[CH2:8][N:7]([CH:9]([CH3:11])[CH3:10])[C:6]2[N:12]=[C:13]([NH:16][C:17]3[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][C:18]=3[O:26][CH3:27])[N:14]=[CH:15][C:5]=2[N:4]([CH3:28])[C:3]1=[O:29].C(N(C(C)C)C(C)C)C.[CH:40]1([CH2:43][N:44]2[CH2:49][CH2:48][N:47]([CH:50]3[CH2:55][CH2:54][CH:53]([NH2:56])[CH2:52][CH2:51]3)[CH2:46][CH2:45]2)[CH2:42][CH2:41]1>CN(C)C=O>[CH:40]1([CH2:43][N:44]2[CH2:49][CH2:48][N:47]([C@@H:50]3[CH2:55][CH2:54][C@H:53]([NH:56][C:21](=[O:22])[C:20]4[CH:24]=[CH:25][C:17]([NH:16][C:13]5[N:14]=[CH:15][C:5]6[N:4]([CH3:28])[C:3](=[O:29])[C:2]([F:30])([F:1])[CH2:8][N:7]([CH:9]([CH3:10])[CH3:11])[C:6]=6[N:12]=5)=[C:18]([O:26][CH3:27])[CH:19]=4)[CH2:52][CH2:51]3)[CH2:46][CH2:45]2)[CH2:41][CH2:42]1.[CH:40]1([CH2:43][N:44]2[CH2:49][CH2:48][N:47]([C@H:50]3[CH2:55][CH2:54][C@H:53]([NH:56][C:21](=[O:22])[C:20]4[CH:24]=[CH:25][C:17]([NH:16][C:13]5[N:14]=[CH:15][C:5]6[N:4]([CH3:28])[C:3](=[O:29])[C:2]([F:30])([F:1])[CH2:8][N:7]([CH:9]([CH3:10])[CH3:11])[C:6]=6[N:12]=5)=[C:18]([O:26][CH3:27])[CH:19]=4)[CH2:52][CH2:51]3)[CH2:46][CH2:45]2)[CH2:41][CH2:42]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 11586738trans-4-(4-(Cyclopropylmethyl)piperazin-1-yl)cyclohexanamineHCID 445467354-(7,7-difluoro-9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid

Product 2

HCID 178492713HCID 178492713, compoundHCID 178492714HCID 178492714, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 0.08 g (0.19 mmole) of 4-(7,7-difluoro-9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-292), 0.20 mL (1.2 mmole) of ethyldiisopropyl amine and 0.072 mg (0.21 mmole) of a cis/trans mixture of 4-(4-cyclopropylmethyl-piperazin-1-yl)-cyclohexylamine with trihydrochloride in 2.0 mL of dimethylformamide was added 0.090 g (0.21 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 0.024 g of N-[cis-4-(4-cyclopropylmethyl-piperazin-1-yl)-cyclohexyl]-4-(7,7-difluoro-9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzamide (I-301) (Rf: 0.58 in dichloromethane:methanol 7:3) as a white solid and 0.061 g of N-[trans-4-(4-cyclopropylmethyl-piperazin-1-yl)-cyclohexyl]-4-(7,7-difluoro-9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzamide (I-302) (Rf: 0.46 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-23ba99b3deb248599a33c9f3fcebe755
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Linked notes

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