Acetic Acid → HCID 117872454, compound

HRID 525305Notes

Reaction equation

HRID 525305 reaction equation
[C:1]([O:5][C:6](=[O:31])[N:7]([C@H:9]([C:11](=[O:30])[NH:12][C@H:13]([C:17]([N:19]1[C:23]2=[N:24][CH:25]=[CH:26][CH:27]=[C:22]2[CH2:21][C@H:20]1[CH:28]=O)=[O:18])[CH:14]([CH3:16])[CH3:15])[CH3:10])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[CH:32]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]=[CH:34][C:33]=1[NH2:42].C(O)(=O)C.[BH3-]C#N.[Na+]>CO>[C:1]([O:5][C:6](=[O:31])[N:7]([CH3:8])[C@H:9]([C:11](=[O:30])[NH:12][C@H:13]([C:17]([N:19]1[C:23]2=[N:24][CH:25]=[CH:26][CH:27]=[C:22]2[CH2:21][C@H:20]1[CH2:28][NH:42][C:33]1[CH:34]=[CH:35][C:36]2[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:32]=1)=[O:18])[CH:14]([CH3:16])[CH3:15])[CH3:10])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 70572-NaphthylamineHCID 5003444Sodium cyanoborohydrideHCID 118354234HCID 118354234, compound

Product 1

HCID 117872454HCID 117872454, compoundYield 81.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of {(S)-1-[(S)-1-((S)-2-formyl-2,3-dihydro-pyrrolo[2,3-b]pyridine-1-carbonyl)-2-methyl-propylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester (30 mg, 0.07 mmol) in dry MeOH (1.0 mL) was added 2-napthylamine (20 mg, 0.14 mmol) was the reaction was stirred at rt for 18 h. Acetic acid was added to adjust to pH ˜4. NaCNBH3 (8.7 mg, 0.139 mmol) was added and the reaction was stirred at rt for 18 h. The reaction mixture was concentrated in vacuo. The residue was taken up in EtOAc (25 mL) and washed with saturated aqueous NaHCO3 (10 mL×2), water (10 mL×2) and brine (4 mL×2) and concentrated in vacuo. The crude material was purified by preparative HPLC (X Bridge Prep C18 (250×19 0 mm) 5μ, acetonitrile and 5 mM NH4OAc) to give methyl-((S)-1-{(S)-2-methyl-1-[(S)-2-(naphthalen-2-ylaminomethyl)-2,3-dihydro-pyrrolo[2,3-b]pyridine-1-carbonyl]-propylcarbamoyl}-ethyl)-carbamic acid tert-butyl ester (32 mg), m/z=560 (M+H).

Workup

  1. stirringthe reaction was stirred at rt for 18 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. washwashed with saturated aqueous NaHCO3 (10 mL×2), water (10 mL×2) and brine (4 mL×2)
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by preparative HPLC (X Bridge Prep C18 (250×19 0 mm) 5μ, acetonitrile and 5 mM NH4OAc)

Sources & evidence

ORD record
ord-bb8c9b2db60c4e49bb1068a2cbcb8bcf
Source dataset
uspto-grants-2016_05
Patent number
US09340573B2

Reaction notes

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