4-Methylmorpholine → HCID 178451331, compound

HRID 2170085Notes

Reaction equation

HRID 2170085 reaction equation
[C:1]([O:5][C:6]([CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][C:18]([OH:20])=O)=[CH:12][C:11]=1[Cl:21])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.C(OC(=O)COC1C=CC(CCC([N:71]2[CH2:92][CH2:91][C:74]3([NH:78]/[C:77](=[N:79]/[C:80]([C:82]4[C:87]([NH2:88])=[N:86][C:85]([NH2:89])=[C:84]([Cl:90])[N:83]=4)=[O:81])/[NH:76][CH2:75]3)[CH2:73][CH2:72]2)=O)=CC=1)(C)(C)C>CN(C=O)C.O>[C:1]([O:5][C:6](=[O:7])[CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][C:18]([N:71]2[CH2:92][CH2:91][C:74]3([NH:78]/[C:77](=[N:79]/[C:80]([C:82]4[C:87]([NH2:88])=[N:86][C:85]([NH2:89])=[C:84]([Cl:90])[N:83]=4)=[O:81])/[NH:76][CH2:75]3)[CH2:73][CH2:72]2)=[O:20])=[CH:12][C:11]=1[Cl:21])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 667975163-(4-Tert-butoxycarbonylmethoxy-3-chloro-phenyl)-propionic acid2×HCID 178451329[4-(3-{2-[(E)-3,5-Diamino-6-chloro-pyrazine-2-carbonylimino]-1,3,8-triaza-spiro[4.5]dec-8-yl}-3-oxo-propyl)-phenoxy]-acetic acid tert-butyl ester

Product 1

HCID 178451331HCID 178451331, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 3-(4-tert-butoxycarbonylmethoxy-3-chloro-phenyl)-propionic acid (Intermediate B) (4 g, 12.71 mol) in DMF (80 ml) at RT was treated with HATU (4.83 g, 12.71 mmol), N-methylmorpholine (5.73 ml, 52.1 mmol) followed by 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid [1,3,8-triaza-spiro[4.5]dec-(2E)-ylidene]-amide (WO09074575, Ex. 38, page 123) (5.31 g, 13.34 mmol). The resulting mixture was stirred at RT for 1 h and then diluted with water (500 ml). The resulting solid was collected by filtration and rinsed with water. Purification by chromatography on silica eluting with 0-7% 7N ammonia in MeOH/DCM afforded the title product; 1H NMR (400 MHz, DMSO-d6) δ 8.53 (2H, br hump), 7.34 (1H, d), 7.14 (1H, dd), 6.90 (1H, d), 6.87 (2H, br hump), 4.74 (2H, s), 3.65 (1H, m), 3.57 (1H, m), 3.43 (2H, s), 3.37 (2H, m), 2.75 (2H, t), 2.62 (2H, t), 1.62 (4H, m), 1.43 (9H, s).

Workup

  1. filtrationThe resulting solid was collected by filtration
  2. washrinsed with water
  3. customPurification by chromatography on silica eluting with 0-7% 7N ammonia in MeOH/DCM

Sources & evidence

ORD record
ord-66470175faa9497a800194606d338e50
Source dataset
uspto-grants-2015_06
Patent number
US09050339B2

Reaction notes

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