Morpholine → HCID 131730332, compound

HRID 1948324Notes

Reaction equation

HRID 1948324 reaction equation
[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]2[S:19][C:20]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[C:21]([CH:23]=O)[N:22]=2)[CH2:14][CH:13]1[O:30][CH3:31])=[O:10].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1>C(Cl)Cl.Cl>[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][C@H:12]1[CH2:17][CH2:16][N:15]([C:18]2[S:19][C:20]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[C:21]([CH2:23][N:46]3[CH2:51][CH2:50][O:49][CH2:48][CH2:47]3)[N:22]=2)[CH2:14][C@H:13]1[O:30][CH3:31])=[O:10]

Participants

6

Reactant 3

HCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 87481864HCID 87481864, compound

Product 1

HCID 131730332HCID 131730332, compoundYield 52.4%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of ethyl 2-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-formyl-1,3-thiazole-5-carboxylate (0.15 g, 0.31 mmol, Example 252) in methylene chloride (20 mL) was added sodium triacetoxyborohydride (0.1 g, 0.47 mmol) and morpholine (0.03 mL, 0.34 mmol). Reaction was stirred at room temperature and monitored by LCMS. Upon completion, the reaction mixture was diluted with 1N HCl and then partitioned with EtOAc/sat. sodium bicarbonate. Washing with brine, drying with MgSO4 and concentrating yielded a solid. Purification by silica gel flash column (gradient elution 70-100% EtOAc/CH2Cl2) afforded pure product (0.091 g) MS (ES) M+H+: 560 for C23H31Cl2N5O5S; NMR: 1.24 (t, 3 H) 1.75 (s, 2 H) 2.18 (s, 3 H) 3.32 (s, 2 H) 3.36 (s, 3 H) 3.52 (s, 2 H) 3.54 (d, 4 H) 3.65-3.75 (m, 2 H) 3.76-3.86 (m, 2 H) 3.93 (s, 1 H) 4.18 (q, 2 H) 4.27 (s, 1 H) 7.16 (d, 1 H) 12.16 (s, 1 H).

Workup

  1. customReaction
  2. custompartitioned with EtOAc/
  3. washWashing with brine
  4. dry with materialdrying with MgSO4
  5. concentrationconcentrating
  6. customyielded a solid
  7. customPurification
  8. washby silica gel flash column (gradient elution 70-100% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-5018e5a7072e4714abbc4d3f4db220c7
Source dataset
uspto-grants-2013_03
Patent number
US08399489B2

Reaction notes

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