Diisopropylethylamine → HCID 67075977, compound

HRID 1676774Notes

Reaction equation

HRID 1676774 reaction equation
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9](C)[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[C:24]([F:31])[C:23]=4[F:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(N2CC(F)(F)C(=O)NC3C=NC(NC4C=CC(C(NC5CCN(C)CC5)=O)=C(F)C=4F)=NC2=3)CCCC1.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.C(N(C(C)C)CC)(C)C.[NH2:104][CH:105]1[CH2:110][CH2:109][N:108]([CH2:111][CH3:112])[CH2:107][CH2:106]1>CN(C)C=O.C(OCC)(=O)C.O>[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[NH:9][C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:104][CH:105]5[CH2:110][CH2:109][N:108]([CH2:111][CH3:112])[CH2:107][CH2:106]5)=[O:27])=[C:24]([F:31])[C:23]=4[F:32])=[N:20][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 37349901-Ethylpiperidin-4-amineHCID 67075958HCID 67075958, compoundHCID 67076488HCID 67076488, compoundHCID 178484293HCID 178484293, compound

Product 1

HCID 67075977HCID 67075977, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 0.0801 g of the 2:1 mixture 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)-2,3-difluoro-benzoic acid and 4-{4-[(2-carboxy-2,2-difluoro-ethyl)-cyclopentyl-amino]-5-methylamino-pyrimidin-2-ylamino}-2,3-difluoro-benzoic acid (from example 243) in 7 mL of dimethylformamide was treated with 0.154 g (0.393 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate and 0.1185 g (0.918 mmole) of diisopropylethylamine. After 15 minutes, 0.0328 g (0.256 mmole) of 4-amino-1-ethylpiperidine in 1 mL of dimethylformamide was added. The reaction mixture stirred for 30 minutes and then diluted with 150 mL of ethyl acetate and 25 mL of water. The mixture was then washed successively with 20 mL of ammonium chloride, 20 mL of saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 95:5-80:20) gave 0.0651 g of 4-(9-cyclopentyl-7,7-difluoro-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-ethyl-piperidin-4-yl)-2,3-difluoro-benzamide (I-244) as a white solid.

Workup

  1. washThe mixture was then washed successively with 20 mL of ammonium chloride, 20 mL of saturated aqueous sodium bicarbonate
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by silica gel chromatography
  6. washeluting with dichloromethane-methanol (gradient, 95:5-80:20)

Sources & evidence

ORD record
ord-41c2f1bb4bce4574a3150888f86fbc42
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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