Dimethylamine → HCID 86731757, compound

HRID 1504884Notes

Reaction equation

HRID 1504884 reaction equation
[OH:1][C:2](C(F)(F)F)=[O:3].[NH2:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[CH:17]=[C:18]([NH:25][C:26]2[N:31]=[C:30]([CH3:32])[C:29]([C:33](O)=[O:34])=[CH:28][CH:27]=2)[C:19]([C:22](=[O:24])[NH2:23])=[N:20][CH:21]=1.[CH3:36][NH:37][CH3:38].CCN([CH:45]([CH3:47])[CH3:46])C(C)C.[CH3:48]CCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>CN(C=O)C>[C:22]([C:19]1[N:20]=[CH:21][C:16]([NH:15][C@@H:10]2[CH2:11][CH2:12][CH2:13][CH2:14][C@@H:9]2[NH:8][C:2](=[O:1])[O:3][C:45]([CH3:47])([CH3:48])[CH3:46])=[CH:17][C:18]=1[NH:25][C:26]1[CH:27]=[CH:28][C:29]([C:33](=[O:34])[N:37]([CH3:38])[CH3:36])=[C:30]([CH3:32])[N:31]=1)(=[O:24])[NH2:23]

Participants

6

Reactant 4

HCID 674DimethylamineHCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 131734336HCID 131734336, compound

Product 1

HCID 86731757HCID 86731757, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-{[5-({(1R,2S)-2-[(tert-butoxycarbonyl)amino]cyclohexyl}amino)-2-carbamoylpyridin-3-yl]amino}-2-methylpyridine-3-carboxylic acid (from Step 4 of Example 16) (45 mg, 0.093 mmol), dimethylamine (2.0 M in methanol, 0.093 mL, 0.19 mmol) and N,N′-diisopropylethylamine (0.032 mL, 0.19 mmol) in DMF (1 mL) was added dropwise 1-propanephosphonic acid cyclic anhydride (50% in ethyl acetate, 0.065 mL, 0.11 mmol) at 0° C. The reaction mixture was stirred for 2 hours while warming to room temperature. The reaction mixture was concentrated under reduced pressure. The residue was purified by reverse phase HPLC (0-100% acetonitrile/water with 0.1% TFA, linear gradient) to afford tert-butyl {(1S,2R)-2-[(6-carbamoyl-5-{[5-(dimethylcarbamoyl)-6-methylpyridin-2-yl]amino}pyridin-3-yl)amino]cyclohexyl}carbamate. MS ESI calc'd. for C26H38N7O4 [M+H]+ 512. found 512. 1H NMR (500 MHz, DMSO-d6) δ 11.95 (s, 1H), 8.51 (s, 1H), 7.88 (s, 1H), 7.62 (s, 1H), 7.42 (d, J=8.1 Hz, 1H), 7.29 (s, 1H), 6.65 (d, J=8.2 Hz, 1H), 6.61-6.51 (m, 1H), 6.21-6.03 (m, 1H), 3.87-3.74 (m, 1H), 3.69-3.56 (m, 1H), 2.97 (s, 3H), 2.81 (s, 3H), 2.33 (s, 3H), 1.87-1.74 (m, 1H), 1.74-1.63 (m, 1H), 1.64-1.42 (m, 4H), 1.33 (s, 2H), 1.27 (s, 9H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customThe residue was purified by reverse phase HPLC (0-100% acetonitrile/water with 0.1% TFA, linear gradient)

Sources & evidence

ORD record
ord-683666b15489435396e81fcc4d32eb49
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

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