Ammonium Chloride → HCID 178458933, compound

HRID 2272668Notes

Reaction equation

HRID 2272668 reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11]3[N:16]=[C:15]([C:17]4[S:21][C:20]([C:22]([C@H:26]5[CH2:31][CH2:30][C@H:29]([C:32](O)=[O:33])[CH2:28][CH2:27]5)([OH:25])[CH2:23][CH3:24])=[N:19][CH:18]=4)[CH:14]=[C:13]([CH3:35])[CH:12]=3)[CH:5]=2)[CH2:3][CH2:2]1.C[N:37](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl-].[NH4+].C(N(CC)C(C)C)(C)C>CO.CN(C=O)C>[CH:1]1([C:4]2[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11]3[N:16]=[C:15]([C:17]4[S:21][C:20]([C:22]([C@H:26]5[CH2:27][CH2:28][C@H:29]([C:32]([NH2:37])=[O:33])[CH2:30][CH2:31]5)([OH:25])[CH2:23][CH3:24])=[N:19][CH:18]=4)[CH:14]=[C:13]([CH3:35])[CH:12]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178458934HCID 178458934, compound

Product 1

HCID 178458933HCID 178458933, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a flask containing racemic trans-4-[1-(5-{6-[(4-cyclopropylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1,3-thiazol-2-yl)-1-hydroxypropyl]cyclohexanecarboxylic acid (25 mg, 0.051 mmol) was added 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (25.1 mg, 0.066 mmol) and ammonium chloride (10.9 mg, 0.203 mmol). DMF (1 mL) and N,N-diisopropylethylamine (0.089 mL, 0.507 mmol) were added and the reaction was sealed and stirred for 2 hours. Methanol (0.1 mL) was then added to quench the reaction and the resulting solution was filtered. The filtrate was purified by reversed phase HPLC (10-100% acetonitrile/water with 0.1% TFA). The fractions containing desired product were pooled, frozen and concentrated to dryness on a lyophilizer to afford trans-4-[1-(5-{6-[(4-cyclopropylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1,3-thiazol-2-yl)-1-hydroxypropyl]cyclohexanecarboxamide. MS ESI calc'd. for C27H34N5O2S [M+H]+ 492. found 492. 1H NMR (500 MHz, DMSO-d6) δ 11.31 (s, 1H), 8.49 (s, 1H), 8.30 (d, J=6.4 Hz, 1H), 7.53 (s, 1H), 7.38 (s, 1H), 7.15 (s, 1H), 7.04 (d, J=6.4 Hz, 1H), 6.94 (s, 1H), 6.68 (s, 1H), 5.84-5.30 (m, 1H), 2.43 (s, 3H), 2.30-2.15 (m, 1H), 2.07-1.87 (m, 4H), 1.87-1.67 (m, 3H), 1.54-1.42 (m, 1H), 1.42-1.18 (m, 6H), 1.12-0.93 (m, 3H), 0.79 (t, J=7.3 Hz, 3H) ppm. rhSyk=+++.

Workup

  1. customthe reaction was sealed
  2. customto quench
  3. customthe reaction
  4. filtrationthe resulting solution was filtered
  5. customThe filtrate was purified by reversed phase HPLC (10-100% acetonitrile/water with 0.1% TFA)
  6. additionThe fractions containing desired product
  7. temperaturefrozen
  8. concentrationconcentrated to dryness on a lyophilizer

Sources & evidence

ORD record
ord-56c70d64e96443628ebb9da9e29cf998
Source dataset
uspto-grants-2015_09
Patent number
US09120785B2

Reaction notes

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