Tert-butyl 3-aminoazetidine-1-carboxylate → HCID 57955666, compound

HRID 1880977Notes

Reaction equation

HRID 1880977 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[C:30]([O:31][CH3:32])=[CH:29][C:25]([C:26]([OH:28])=O)=[C:24]([F:33])[CH:23]=4)=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=[N:49][C:44]2C=C[CH:47]=[N:48][C:43]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.NC1CN(C(OC(C)(C)C)=O)C1>>[NH:48]1[CH2:43][CH:44]([NH:49][C:26](=[O:28])[C:25]2[CH:29]=[C:30]([O:31][CH3:32])[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[CH2:2][CH2:3][CH2:4][CH2:5]5)[C:7]=4[N:20]=3)=[CH:23][C:24]=2[F:33])[CH2:47]1

Participants

4

Reactant 3

HCID 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 252536794-(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-fluoro-5-methoxybenzoic acid

Product 1

HCID 57955666HCID 57955666, compound

Procedure

The title compound was synthesized from 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-fluoro-5-methoxybenzoic acid as described in the general procedure for amide bond synthesis using HATU and 3-amino-N—Boc-azetidine. The Boc group was then removed by treatment with 1:1 trifluoroacetic acid and dichloromethane for 1 hour. At this time the solvent was removed and NaHCO3 (sat.) and EtOAc were added to the residue. The layers were separated, the organic layer was then dried over MgSO4, filtered, the solvent was removed and the final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.49-1.79 (m, 6 H) 1.93 (br. s., 2 H) 3.52-3.66 (m, 4 H) 3.94 (s, 3 H) 4.05 (t, J=14.02 Hz, 2 H) 4.56-4.84 (m, 2 H) 7.45-7.58 (m, 2 H) 7.98 (s, 1 H) 8.26 (s, 1 H) 8.28 (d, J=8.34 Hz, 1 H) 8.75 (d, J=7.07 Hz, 1 H). [M+H] calculated for C24H29F2N7O3, 502; found 502.

Workup

  1. customas described in the general procedure for amide bond synthesis
  2. customThe Boc group was then removed by treatment with 1:1 trifluoroacetic acid and dichloromethane for 1 hour
  3. customAt this time the solvent was removed
  4. additionNaHCO3 (sat.) and EtOAc were added to the residue
  5. customThe layers were separated
  6. dry with materialthe organic layer was then dried over MgSO4
  7. filtrationfiltered
  8. customthe solvent was removed
  9. customthe final compound was purified by reverse phase HPLC
  10. customto give the free base

Sources & evidence

ORD record
ord-41a2437fa66c47749432fa0006a536d5
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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