Dimethylamine → HCID 66548110, compound

HRID 877772Notes

Reaction equation

HRID 877772 reaction equation
[C:1]([C:4]1[CH:9]=[N:8][N:7]2[CH:10]=[C:11]([C:13]3[CH:14]=[CH:15][C:16]([C:19]([OH:21])=O)=[N:17][CH:18]=3)[CH:12]=[C:6]2[C:5]=1[NH:22][C@H:23]1[C@@H:27]([CH3:28])[CH2:26][N:25]([C:29]([C:31]2([C:34]#[N:35])[CH2:33][CH2:32]2)=[O:30])[CH2:24]1)(=[O:3])[NH2:2].C[CH2:37][N:38](C(C)C)[CH:39](C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CNC.C1COCC1>CN(C=O)C>[C:34]([C:31]1([C:29]([N:25]2[CH2:26][C@H:27]([CH3:28])[C@H:23]([NH:22][C:5]3[C:6]4[N:7]([CH:10]=[C:11]([C:13]5[CH:18]=[N:17][C:16]([C:19](=[O:21])[N:38]([CH3:39])[CH3:37])=[CH:15][CH:14]=5)[CH:12]=4)[N:8]=[CH:9][C:4]=3[C:1]([NH2:2])=[O:3])[CH2:24]2)=[O:30])[CH2:32][CH2:33]1)#[N:35]

Participants

7

Reactant 5

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 68290870HCID 68290870, compound

Product 1

HCID 66548110HCID 66548110, compoundYield 55.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To solution of 5-(3-carbamoyl-4-((3S,4S)-1-(1-cyanocyclopropanecarbonyl)-4-methylpyrrolidin-3-ylamino)pyrrolo[1,2-b]pyridazin-6-yl)picolinic acid (15 mg, 0.026 mmol), DIPEA (0.018 mL, 0.102 mmol) and BOP (16.94 mg, 0.038 mmol) in DMF (0.3 mL) was added a 2 M solution of dimethylamine in THF (0.026 mL, 0.051 mmol) and the resulting mixture was stirred for 1 h. The mixture was concentrated to remove the THF and was purified by preparative LC/MS with the following conditions: column: Waters XBridge C18, 19×200 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 10-100% B over 15 minutes, then a 7-minute hold at 100% B; Flow: 25 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to afford 7.2 mg of the title compound. LCMS (method H) retention time=1.78 min. (MH+501.2). 1H NMR (500 MHz, METHANOL-d4, appeared as rotomers) δ 9.06 (dd, J=7.9, 1.5 Hz, 1H), 8.40-8.29 (m, 2H), 8.22 (dd, J=11.1, 1.7 Hz, 1H), 7.80 (d, J=7.9 Hz, 1H), 7.47-7.34 (m, 1H), 5.28-5.04 (m, 1H), 4.58-4.42 (m, 2H), 4.13-3.87 (m, 2H), 3.64-3.52 (m, 1H), 3.34-3.26 (m, 6H), 3.09-2.89 (m, 1H), 2.01-1.83 (m, 1H), 1.80-1.59 (m, 3H), 1.51-1.35 (m, 3H).

Workup

  1. concentrationThe mixture was concentrated
  2. customto remove the THF
  3. customwas purified by preparative LC/MS with the following conditions
  4. waitGradient: 10-100% B over 15 minutes
  5. customa 7-minute hold
  6. additionFractions containing the desired product
  7. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-c83c2df0ebd146b4a2ae8dac25203a75
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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