4-Methylmorpholine → Ammonium Hydroxide

HRID 1921222Notes

Reaction equation

HRID 1921222 reaction equation
[O:1]=[C:2]1[N:6]([CH2:7][C:8]([OH:10])=O)[C:5]2[CH:11]=[CH:12][CH:13]=[CH:14][C:4]=2[N:3]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1.[NH2:21][C:22]1[N:27]=[CH:26][C:25]2[CH2:28][C:29]3([CH2:39][C:24]=2[CH:23]=1)[C:37]1[C:32](=[N:33][CH:34]=[CH:35][CH:36]=1)[NH:31][C:30]3=[O:38].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CN(C=O)C>[NH4+:3].[OH-:1].[O:1]=[C:2]1[N:6]([CH2:7][C:8]([NH:21][C:22]2[N:27]=[CH:26][C:25]3[CH2:28][C:29]4([CH2:39][C:24]=3[CH:23]=2)[C:37]2[C:32](=[N:33][CH:34]=[CH:35][CH:36]=2)[NH:31][C:30]4=[O:38])=[O:10])[C:5]2[CH:11]=[CH:12][CH:13]=[CH:14][C:4]=2[N:3]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 18449368(2-Oxo-3-pyridin-2-yl-2,3-dihydro-1H-benzimidazol-1-yl)acetic acid2×HCID 57974077(+/-)-3-amino-5,7-dihydrospiro[cyclopenta[c]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one2×

Product 2

HCID 14923Ammonium HydroxideHCID 25022610(+/-)-2-(2-Oxo-3-pyridin-2-yl-2,3-dihydro-1H-benzimidazol-1-yl)-N-(2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[c]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-3-yl)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of (2-oxo-3-pyridin-2-yl-2,3-dihydro-1H-benzimidazol-1-yl)acetic acid (11 mg, 0.040 mmol, described in Intermediate 7), (±)-3-amino-5,7-dihydrospiro[cyclopenta[c]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (10 mg, 0.040 mmol, described in Intermediate 3), HATU (19 mg, 0.050 mmol), and N-methylmorpholine (0.018 mL, 0.16 mmol) in DMF (1 mL) was stirred at 50° C. for 18 h. Additional HATU (19 mg, 0.050 mmol), and N-methylmorpholine (0.018 mL, 0.16 mmol) was added and the mixture was stirred at 50° C. for a further 6 h. The reaction mixture was purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. Lyophilization provided a crude product, which was further purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:NH4OH—100:0:0 to 95:5:1, to give the title compound. MS: m/z=504 (M+1). HRMS: m/z=504.1809; calculated m/z=504.1779 for C28H22N7O3.

Workup

  1. stirringthe mixture was stirred at 50° C. for a further 6 h
  2. customThe reaction mixture was purified directly by HPLC
  3. washeluting with a gradient of H2O
  4. customLyophilization provided a crude product, which
  5. customwas further purified by silica gel chromatography
  6. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-8813838233d94fa68b358d9abe4e628c
Source dataset
uspto-grants-2012_05
Patent number
US08173655B2

Reaction notes

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