Diisopropylethylamine → HCID 67075958, compound

HRID 1676773Notes

Reaction equation

HRID 1676773 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]([OH:28])=O)=[C:24]([F:31])[C:23]=4[F:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(C(F)(F)[CH2:37][N:38]([CH:59]1[CH2:63]CCC1)[C:39]1[C:44](NC)=[CH:43][N:42]=C(NC2C=CC(C(O)=O)=C(F)C=2F)N=1)(O)=O.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.NC1CCN(C)CC1>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:42][CH:43]5[CH2:44][CH2:39][N:38]([CH3:37])[CH2:59][CH2:63]5)=[O:28])=[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 27375314-Amino-1-methylpiperidineHCID 67076159HCID 67076159, compoundHCID 67076488HCID 67076488, compoundHCID 178484293HCID 178484293, compound

Product 1

HCID 67075958HCID 67075958, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 0.0507 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 in 4 mL of dimethylformamide was treated with 0.0971 g (0.248 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate and 0.0742 g (0.574 mmole) of diisopropylethylamine. After 15 minutes, 0.0186 g (0.162 mmole) of 4-amino-1-methylpiperidine 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 0.0359 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)-2,3-difluoro-N-(1-methyl-piperidin-4-yl)-benzamide (I-243) 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-a462502884984115ba3902f8039ec7ba
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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