Trifluoroacetic acid methylene chloride → HCID 67354535, compound

HRID 1676602Notes

Reaction equation

HRID 1676602 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:45])[C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]3[N:24]=[CH:25][C:26]4[N:32]([CH3:33])[C:31](=[O:34])[C:30]([F:36])([F:35])[CH2:29][N:28]([CH:37]5[CH2:41][CH2:40][CH2:39][CH2:38]5)[C:27]=4[N:42]=3)=[C:18]([O:43][CH3:44])[CH:17]=2)[CH:10]([O:46][CH3:47])[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.ClCCl>ClCCl>[CH:37]1([N:28]2[CH2:29][C:30]([F:35])([F:36])[C:31](=[O:34])[N:32]([CH3:33])[C:26]3[CH:25]=[N:24][C:23]([NH:22][C:19]4[CH:20]=[CH:21][C:16]([C:15]([NH:14][CH:11]5[CH2:12][CH2:13][NH:8][CH2:9][CH:10]5[O:46][CH3:47])=[O:45])=[CH:17][C:18]=4[O:43][CH3:44])=[N:42][C:27]2=3)[CH2:41][CH2:40][CH2:39][CH2:38]1

Participants

4

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 67354452HCID 67354452, compound

Product 1

HCID 67354535HCID 67354535, compoundYield 37.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 0.050 g (0.075 mmole) of rac-(3S,4R)-4-[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-benzoylamino]-3-methoxy-piperidine-1-carboxylic acid tert-butyl ester (I-56) and 1 mL of dichloromethane was added 1 mL of trifluoroacetic acid-dichloromethane (25:75). The mixture was stirred for 1.5 hours, and then concentrated under reduced pressure. The residue was dissolved in methanol, and the mixture neutralized by the addition of 1M sodium hydroxide at 0 degrees. The mixture was purified by reverse phase silica gel chromatography, eluting with acetonitrile-water (gradient, 1:99-90:10) to give 0.0156 g of rac-(3S,4R)-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-N-(3-methoxy-piperidin-4-yl)-benzamide (I-57).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in methanol
  3. additionthe mixture neutralized by the addition of 1M sodium hydroxide at 0 degrees
  4. customThe mixture was purified by reverse phase silica gel chromatography
  5. washeluting with acetonitrile-water (gradient, 1:99-90:10)

Sources & evidence

ORD record
ord-6fcb945a5d734769b5f20deef5dd51ab
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

Loading…