Diisopropylethylamine → HCID 57955587, compound

HRID 914239Notes

Reaction equation

HRID 914239 reaction equation
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[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)=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:33][CH:34]1[CH2:37][N:36](C(OC(C)(C)C)=O)[CH2:35]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[NH:36]1[CH2:37][CH:34]([NH:33][C:26](=[O:28])[C:25]2[CH:29]=[CH:30][C:22]([NH:21][C:19]3[N:18]=[CH:17][C:8]4[N:9]([CH3:16])[C:10](=[O:15])[C:11]([F:14])([F:13])[CH2:12][N:6]([CH:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)[C:7]=4[N:20]=3)=[C:23]([O:31][CH3:32])[CH:24]=2)[CH2:35]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1516507Tert-butyl 3-aminoazetidine-1-carboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 252529054-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid

Product 1

HCID 57955587HCID 57955587, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution 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)-3-methoxybenzoic acid (100 mg, 0.22 mmol) in DMF (1 mL) was added tert-butyl 3-aminoazetidine-1-carboxylate (41.3 mg, 0.24 mmol), HATU (125 mg, 0.33 mmol), and DIEA (80 μL, 0.44 mmol). The reaction mixture was stirred for 1 h. It was then poured into 100 mL of rapidly stirring water. A peach solid forms and was filtered, washed with water and dried. This solid was treated with TFA in DCM (3 mL 1:1) for 30 minutes. The solvent was then removed, and the product purified by reverse phase HPLC, free based and lyophilized to yield a white solid (37.4 mg, 34% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.49-1.79 (m, 6H) 1.93 (br. s., 2H) 3.52-3.66 (m, 4H) 3.94 (s, 3H) 4.05 (t, J=14.02 Hz, 2H) 4.56-4.84 (m, 2H) 7.45-7.58 (m, 2H) 7.98 (s, 1H) 8.26 (s, 1H) 8.28 (d, J=8.34 Hz, 1H) 8.75 (d, J=7.07 Hz, 1H). [M+H] calc'd for C24H29F2N7O3, 502. found 502.

Workup

  1. filtrationA peach solid forms and was filtered
  2. washwashed with water
  3. customdried
  4. additionThis solid was treated with TFA in DCM (3 mL 1:1) for 30 minutes
  5. customThe solvent was then removed
  6. customthe product purified by reverse phase HPLC

Sources & evidence

ORD record
ord-a6a7c198734f492786b394ead0ceba3c
Source dataset
uspto-grants-2011_09
Patent number
US08026234B2

Reaction notes

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