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)-N-(1-methyl-piperidin-4-yl)-benzamide

HRID 2234293Notes

Reaction equation

HRID 2234293 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][CH:47]=2)=[N:34][CH:35]=3)[CH2:29][CH2:28][CH2:27][CH2:26]1.CCN(C(C)C)C(C)C.[NH2:64][CH:65]1[CH2:70][CH2:69][N:68]([CH3:71])[CH2:67][CH2:66]1>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:64][CH:65]4[CH2:70][CH2:69][N:68]([CH3:71])[CH2:67][CH2:66]4)=[O:52])=[CH:48][CH:47]=2)=[N:34][CH:35]=3)[CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 27375314-Amino-1-methylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581539364-(9-cyclopentyl-5,7,7-trimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-benzoic acid

Product 1

HCID 250155384-(9-cyclopentyl-5,7,7-trimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzamide

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

A solution of HATU (126 mg, 0.33 mmol) in DMA (5 mL) was added to a mixture of 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]benzoic acid, (Intermediate 129; 123 mg, 0.3 mmol) DIPEA (261 uL, 1.5 mmol) and 4-amino N-methylpiperidine (43 mg, 0.375) in DMA (5 mL). The resulting mixture was stirred at room temperature for 2 hours, then partially purified by SCX. The compound was eluted 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 a pale yellow amorphous solid. (100 mg, 66%)

Workup

  1. custompartially purified by SCX
  2. washThe compound was eluted from the SCX column
  3. concentrationconcentrated in vacuo
  4. customfurther purified by column chromatography
  5. washeluting with 0-10% ammonia (7N in methanol) in DCM
  6. customThe pure material was recovered as an orange oil, which
  7. customTrituration under ether gave a pale yellow amorphous solid

Sources & evidence

ORD record
ord-a011c8bab1e4405ab188cb1ba7fb6127
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

Loading…