Ammonium formate → HCID 58172333, compound

HRID 529133Notes

Reaction equation

HRID 529133 reaction equation
C([O-])=O.[NH4+].C([N:12]1[CH2:16][CH2:15][C@:14]2([C:24]3[C:19](=[CH:20][CH:21]=[CH:22][C:23]=3[CH2:25][NH:26][CH:27]([CH3:29])[CH3:28])[N:18]([C:30]3[C:31]4[C@H:38]([CH3:39])[CH2:37][C@@H:36]([OH:40])[C:32]=4[N:33]=[CH:34][N:35]=3)[CH2:17]2)[CH2:13]1)C1C=CC=CC=1>CO.[Pd]>[CH:27]([NH:26][CH2:25][C:23]1[CH:22]=[CH:21][CH:20]=[C:19]2[N:18]([C:30]3[C:31]4[C@H:38]([CH3:39])[CH2:37][C@@H:36]([OH:40])[C:32]=4[N:33]=[CH:34][N:35]=3)[CH2:17][C@@:14]3([CH2:15][CH2:16][NH:12][CH2:13]3)[C:24]=12)([CH3:29])[CH3:28]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 68764711HCID 68764711, compound

Product 1

HCID 58172333HCID 58172333, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Pd/C (35.2 mg, 0.017 mmol) and ammonium formate (52.2 mg, 0.827 mmol) was added to a solution of (5R,7R)-4-((S)-1′-benzyl-4-((isopropylamino)methyl)spiro[indoline-3,3′-pyrrolidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol (40.0 mg, 0.083 mmol) in MeOH (3 mL). The resulting mixture was stirred at ambient temperature overnight. The reaction mixture was filtered, and the filtrate was concentrated and purified by Analogix chromatography (DCM/MeOH/1% NH4OH gradient) to give (5R,7R)-4-((S)-4-((isopropylamino)methyl)spiro[indoline-3,3′-pyrrolidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol. This material was converted to the bis-HCl salt by dissolving the material in DCM and adding HCl (4N in dioxane) and concentrating the mixture (9.0 mg, 0.022 mmol, 27%). 1H NMR (400 MHz, d6-DMSO) δ 10.05 (br s, 1H), 9.92 (br s, 1H), 9.58 (br s, 1H), 9.47 (br s, 1H), 8.89 (s, 1H), 8.10 (d, J=8.2 Hz, 1H), 7.66 (s, J=7.8 Hz, 1H), 7.46 (t, J=8.2 Hz, 1H), 5.30 (t, J=7.8 Hz, 1H), 4.83 (d, J=10.5 Hz, 1H), 4.35 (t, J=10.5 Hz, 1H), 4.20 (d, J=7.8 Hz, 1H), 4.14 (d, J=10.9 Hz, 1H), 3.96-3.85 (m, 1H), 3.71-3.67 (m, 4H), 3.43 (dd, J=10.9, 3.9 Hz, 2H), 3.41-3.31 (m, 2H), 2.63-2.58 (m, 1H), 2.35-2.33 (m, 1H), 2.18-2.13 (m, 2H), 1.41 (d, J=6.2 Hz, 6H), 1.18 (d, J=6.4 Hz, 2H), 1.12 (d, J=6.6 Hz, 3H). LCMS (APCI+) M+H+ 394 (100%); Rt=1.72 min. HPLC purity at 254 nm >99%, Rt=1.63 min.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated
  3. custompurified by Analogix chromatography (DCM/MeOH/1% NH4OH gradient)

Sources & evidence

ORD record
ord-973a0661f0bf468e8a8215d8b03ef4aa
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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