Diisopropylethylamine → 4-(9-cyclopentyl-5,7,7-trimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide

HRID 2234289Notes

Reaction equation

HRID 2234289 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:25]1([N:30]2[CH2:40][C:39]([CH3:42])([CH3:41])[C:38](=[O:43])[N:37]([CH3:44])[C:36]3[C:31]2=[N:32][C:33]([NH:45][C:46]2[CH:54]=[CH:53][C:49]([C:50]([OH:52])=O)=[CH:48][C:47]=2[O:55][CH3:56])=[N:34][CH:35]=3)[CH2:29][CH2:28][CH2:27][CH2:26]1.CCN(C(C)C)C(C)C.NC1C=CC(C([NH:73][CH:74]2[CH2:79][CH2:78][N:77]([CH3:80])[CH2:76][CH2:75]2)=O)=CC=1OC>CC(N(C)C)=O>[CH:25]1([N:30]2[CH2:40][C:39]([CH3:42])([CH3:41])[C:38](=[O:43])[N:37]([CH3:44])[C:36]3[C:31]2=[N:32][C:33]([NH:45][C:46]2[CH:54]=[CH:53][C:49]([C:50]([NH:73][CH:74]4[CH2:79][CH2:78][N:77]([CH3:80])[CH2:76][CH2:75]4)=[O:52])=[CH:48][C:47]=2[O:55][CH3:56])=[N:34][CH:35]=3)[CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 426107874-(9-cyclopentyl-5,7,7-trimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid

Product 1

HCID 250154654-(9-cyclopentyl-5,7,7-trimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

A solution of HATU (221 mg, 0.55 mmol) in DMA (10 mL) was added to a mixture of the 4-[(2-cyclopentyl-4,4,6-trimethyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-3-methoxy-benzoic acid (Example 242; 220 mg, 0.5 mmol), DIPEA (261 uL, 1.5 mmol) and 4-amino-3-methoxy-N-(1-methyl-4-piperidyl)benzamide (WO06/018220; 72 mg, 0.62 mmol) in DMA (10 mL). The resulting mixture was stirred at room temperature for 2 hours, then partially purified by SCX. The compound was retrieved from the SCX column using 7N ammonia in methanol, then concentrated in vacuo, and further purified by column chromatography, eluting with 0-10% ammonia (7N in methanol) in DCM. The pure material was recovered as an orange oil, which foamed and solidified under high vacuum. Trituration under ether gave the title compound as a pale yellow amorphous solid. (154 mg, 58%)

Workup

  1. custompartially purified by SCX
  2. concentrationconcentrated in vacuo
  3. customfurther purified by column chromatography
  4. washeluting with 0-10% ammonia (7N in methanol) in DCM
  5. customThe pure material was recovered as an orange oil, which

Sources & evidence

ORD record
ord-abc02a140647446a9d6f07146aaf8e94
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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