Dimethylformamide → HCID 68350507, compound

HRID 877811Notes

Reaction equation

HRID 877811 reaction equation
I.[CH3:2][C:3]1([CH3:29])[CH2:7][NH:6][CH2:5][C@H:4]1[NH:8][C:9]1[C:10]2[N:11]([CH:18]=[C:19]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([O:27][CH3:28])[CH:22]=3)[CH:20]=2)[N:12]=[CH:13][C:14]=1[C:15]([NH2:17])=[O:16].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)[C:41]2[CH:42]=CC=C[C:40]=2[N:39]=N1.C(N(CC)C(C)C)(C)C.CN(C)C=[O:69]>>[C:40]([CH2:41][C:42]([N:6]1[CH2:7][C:3]([CH3:29])([CH3:2])[C@H:4]([NH:8][C:9]2[C:10]3[N:11]([CH:18]=[C:19]([C:21]4[CH:26]=[CH:25][N:24]=[C:23]([O:27][CH3:28])[CH:22]=4)[CH:20]=3)[N:12]=[CH:13][C:14]=2[C:15]([NH2:17])=[O:16])[CH2:5]1)=[O:69])#[N:39]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 68291252HCID 68291252, compound

Product 1

HCID 68350507HCID 68350507, compoundYield 52%

Procedure

A solution of (S)-4-((4,4-dimethylpyrrolidin-3-yl)amino)-6-(2-methoxypyridin-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide hydroiodide (12 mg, 0.024 mmol) in N,N-dimethylformamide (1 mL), was added BOP (10.2 mg, 0.024 mmol) and N,N-diisopropylethylamine (0.012 mL, 0.07 mmol). The mixture was stirred for 2 h. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 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: 25-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to give the title compound (7 mg, 52% yield). 1H NMR (400 MHz, METHANOL-d4, Rotamer) δ 8.36 (s, 1H), 8.27 (d, J=3.7 Hz, 1H), 8.20 (d, J=5.9 Hz, 1H), 7.67-7.62 (m, 1H), 7.57 (dd, J=16.5, 1.8 Hz, 1H), 7.53 (d, J=3.1 Hz, 1H), 4.73 (t, J=5.9 Hz, 1H), 4.28-4.17 (m, 1H), 4.15 (d, J=6.4 Hz, 3H), 3.89 (d, J=3.5 Hz, 1H), 3.86-3.83 (m, 1H), 3.65-3.46 (m, 4H), 1.36-1.25 (m, 6H). MS (ES+) m/z: 448.2, 448.2 (M+H); LC retention time: 2.86 min (analytical HPLC Method I).

Workup

  1. customThe crude material was purified via preparative LC/MS with the following conditions
  2. waitGradient: 25-100% B over 25 minutes
  3. customa 5-minute hold
  4. additionFractions containing the desired product
  5. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-7d0b48f4fa5a4dee93cd1ce622374877
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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