Formic Acid → HCID 67253080, compound

HRID 1948092Notes

Reaction equation

HRID 1948092 reaction equation
N[C:2]1([C:27]([O-:29])=[O:28])[CH2:7][CH2:6][CH:5]([C:8]2[CH:16]=[CH:15][C:14]([NH:17]C(OC(C)(C)C)=O)=[C:13]3[C:9]=2[CH2:10][N:11]([CH3:26])[C:12]3=[O:25])[CH2:4][CH2:3]1.[Na+].CO.C=O.[CH:35](O)=O.[C:38]([BH3-])#[N:39].[Na+]>>[NH2:17][C:14]1[CH:15]=[CH:16][C:8]([CH:5]2[CH2:4][CH2:3][C:2]([N:39]([CH3:38])[CH3:35])([C:27]([OH:29])=[O:28])[CH2:7][CH2:6]2)=[C:9]2[C:13]=1[C:12](=[O:25])[N:11]([CH3:26])[CH2:10]2

Participants

6

Reactant 5

HCID 284Formic AcidHCID 712FormaldehydeHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 67256033HCID 67256033, compound2×

Product 1

HCID 67253080HCID 67253080, compound

Procedure

Sodium 1-amino-4-{7-[(tert-butoxycarbonyl)amino]-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl}cyclohexanecarboxylate (Compound 285B, 50.0 mg, 0.118 mmol) was taken up in MeOH (1.0 mL, 25 mmol) and over the course of about 5 days was treated repeatedly with formaldehyde (52.5 uL, 0.705 mmol) and Formic acid (26.6 uL, 0.705 mmol) followed by several hours of stirring and then sodium cyanoborohydride (73.8 mg, 1.18 mmol) addition. The reaction was eventually driven to completion after which, the reaction mixture became a suspension. This was filtered and the solid washed a little MeOH. The MeOH filtrate was concentrated to yield a waxy white material which was triturated with DCM and filtered. The DCM filtrate was concentrated to a clear oil and dried in vacuo. 1H NMR (400 MHz, CHLOROFORM-d) d 9.52 (s, 1H), 8.10-8.15 (m, 1H), 7.42 (d, J=8.59 Hz, 1H), 4.36 (s, 2H), 3.18 (s, 3H), 2.93 (s, 6H), 2.82 (dd, J=4.67, 8.72 Hz, 1H), 2.23 (t, J=4.55 Hz, 4H), 1.97-2.07 (m, 2H), 1.83-1.94 (m, 2H), 1.50 (s, 9H). MS (ES+): m/z=432.2303 [MH+]. HPLC: tR=1.12 min (UPLC TOF, polar—3 min). The crude product was taken up in DCM and treated with TFA, stirred for 15 min. The reaction mixture was concentrated to an oil and used without further purification and characterization.

Workup

  1. waitfollowed by several hours
  2. filtrationThis was filtered
  3. washthe solid washed a little MeOH
  4. concentrationThe MeOH filtrate was concentrated
  5. customto yield a waxy white material which
  6. customwas triturated with DCM
  7. filtrationfiltered
  8. concentrationThe DCM filtrate was concentrated to a clear oil
  9. customdried in vacuo
  10. customHPLC: tR=1.12 min (UPLC TOF, polar—3 min)
  11. additiontreated with TFA
  12. stirringstirred for 15 min
  13. concentrationThe reaction mixture was concentrated to an oil
  14. customused without further purification and characterization

Sources & evidence

ORD record
ord-633fd213c500483c88193825b891ec24
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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