Hydrochloric Acid → 4-[4-(3-Methyl-3H-benzimidazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butylamide

HRID 2375919Notes

Reaction equation

HRID 2375919 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[NH:34][C:17]3[N:18]=[CH:19][N:20]=[C:21]([NH:22][C:23]4[CH:28]=[CH:27][CH:26]=[C:25](C5NC=CN=5)[CH:24]=4)[C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.Cl.[CH2:36]([N:38]([CH2:41]C)CC)C.[C:43]([N:47]=C=O)([CH3:46])([CH3:45])[CH3:44].[N:50]#N>CO>[C:43]([NH:47][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[NH:34][C:17]3[N:18]=[CH:19][N:20]=[C:21]([NH:22][C:23]4[CH:28]=[CH:27][C:26]5[N:50]=[CH:36][N:38]([CH3:41])[C:25]=5[CH:24]=4)[C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:44])([CH3:45])[CH3:46]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 947NitrogenHCID 8471TriethylamineHCID 62412tert-Butyl isocyanateHCID 587099384-{4-[3-(1H-Imidazol-2-yl)-phenylamino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Product 1

HCID 587099514-[4-(3-Methyl-3H-benzimidazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butylamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Into the solution of 4-{4-[3-(1H-imidazol-2-yl)-phenylamino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (EXAMPLE 279) (59.4 mg, 0.118 mmol) in methanol (1.0 mL) was added HCl in methanol (9 M, 1.0 mL). The above mixture was stirred at rt for 4 h. After that time, the mixture was concentrated in vacuo and suspended in DMF (2 mL). Into the above suspension were added triethylamine (159 μL, 1.18 mmol) and tert-butyl isocyanate (14.8 μL, 0.130 mmol). The above mixture was stirred at rt under of N2 for 1 h and concentrated in vacuo to obtain a brown oil that was purified using the mass-directed purification system to yield the title compound. 1H NMR (CD3OD, 400 MHz): δ=1.37 (s, 9H), 2.56 (brs, 2H), 3.61 (t, 2H, J=4.8 Hz), 3.90 (s, 3H), 4.07 (brs, 2H), 5.69 (s, 1H), 6.29 (brs, 1H), 6.62 (s, 1H), 7.43 (dd, 1H, J=2.0 & 8.8 Hz), 7.63 (d, 1H, J=8.8 Hz), 8.08 (s, 1H), 8.11 (d, 1H, J=2.0 Hz), 8.22 (s, 1H). MS (ES+): m/z 445.11 (100) [MH+]. HPLC: tR=2.00 min (ZQ2000, polar—5 min).

Workup

  1. concentrationAfter that time, the mixture was concentrated in vacuo
  2. concentrationconcentrated in vacuo
  3. customto obtain a brown oil that
  4. customwas purified

Sources & evidence

ORD record
ord-1c02c0cdeeb4457ca88216e3a5f62733
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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