Water → HCID 178457295, compound

HRID 386691Notes

Reaction equation

HRID 386691 reaction equation
[Cl:1][C:2]1[CH:12]=[C:11]([CH2:13][CH2:14][C:15]([N:17]2[CH2:38][CH2:37][C:20]3([NH:24]/[C:23](=[N:25]/[C:26]([C:28]4[C:33]([NH2:34])=[N:32][C:31]([NH2:35])=[C:30]([Cl:36])[N:29]=4)=[O:27])/[NH:22][CH2:21]3)[CH2:19][CH2:18]2)=[O:16])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([OH:8])=[O:7].Cl[CH2:40][C:41]([N:43]([CH2:47][CH2:48][CH3:49])[CH2:44][CH2:45][CH3:46])=[O:42].C(=O)([O-])O.[Na+].O>CN(C=O)C>[CH2:44]([N:43]([CH2:47][CH2:48][CH3:49])[C:41]([CH2:40][O:7][C:6](=[O:8])[CH2:5][O:4][C:3]1[CH:9]=[CH:10][C:11]([CH2:13][CH2:14][C:15]([N:17]2[CH2:18][CH2:19][C:20]3([NH:24]/[C:23](=[N:25]/[C:26]([C:28]4[C:33]([NH2:34])=[N:32][C:31]([NH2:35])=[C:30]([Cl:36])[N:29]=4)=[O:27])/[NH:22][CH2:21]3)[CH2:37][CH2:38]2)=[O:16])=[CH:12][C:2]=1[Cl:1])=[O:42])[CH2:45][CH3:46]

Participants

6

Reactant 4

HCID 962WaterHCID 2196472-chloro-N,N-dipropylacetamideHCID 516892Sodium BicarbonateHCID 178508778HCID 178508778, compound

Product 1

HCID 178457295HCID 178457295, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of [2-Chloro-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 (step 2) (4.82 g, 8.52 mmol) in DMF (70 ml) was treated with 2-chloro-N,N-dipropyl-acetamide (3.18 g, 17.9 mmol) followed by sodium hydrogen carbonate (2.26 g, 26.9 mmol) and the resulting suspension heated to 60° C. overnight. Water (500 ml) was added to the reaction mixture and the product extracted with EtOAc (1000 ml). The organic extracts were washed with water (500 ml) and brine (500 ml), dried (MgSO4) and concentrated in vacuo. Purification by chromatography on silica eluting with 0-12% 2N ammonia in ethanol in DCM followed by further purification by C18 reverse phase chromatography eluting with MeCN/water afforded the title product; 1H NMR (400 MHz, DMSO-d6) δ 8.43 (1H, br s), 8.36 (1H, br s), 7.34 (1H, d), 7.14 (1H, dd), 7.02 (1H, s), 6.71 (2H, br s), 4.95 (2H, s), 4.89 (2H, s), 3.67-3.53 (2H, m), 3.39 (3H, br s), 3.19 (2H, t), 3.13 (2H, t), 2.75 (2H, t), 2.62 (2H, t), 1.65-1.41 (8H, m), 0.85 (3H, t), 0.80 (3H, t). LC-MS Rt 4.11 mins; 706.5 [M+H]+, Method 10minLC_v003.

Workup

  1. extractionthe product extracted with EtOAc (1000 ml)
  2. washThe organic extracts were washed with water (500 ml) and brine (500 ml)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification by chromatography on silica eluting with 0-12% 2N ammonia in ethanol in DCM
  6. customfollowed by further purification by C18 reverse phase chromatography
  7. washeluting with MeCN/water

Sources & evidence

ORD record
ord-1b9ead5ac0b744098026c059bb6f6a74
Source dataset
uspto-grants-2013_02
Patent number
US08372845B2

Reaction notes

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