Ammonium formate → HCID 58172333, compound

HRID 2190069Notes

Reaction equation

HRID 2190069 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-a355c52bd8a4442aa9ea1219117b36c7
Source dataset
uspto-grants-2012_12
Patent number
US08324221B2

Reaction notes

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